Tuberculous ventriculitis: A rare complication of central nervous system tuberculosis.

PubMed

Vaziri, Siavash; Soleiman-Meigooni, Saeed; Rajabi, Jalil; Asgari, Ali

2016-06-01

Tuberculous ventriculitis is an inflammatory infection of the ventricular system of the brain, and is caused by Mycobacterium tuberculosis. We herein present the case of an immunocompromised patient with brain tuberculomas who developed ventriculitis during treatment. The patient was successfully treated with a high dose of steroid, long-term antituberculosis drugs, and aggressive supportive care. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Infusion of adrenergic receptor agonists and antagonists into the locus coeruleus and ventricular system of the brain. Effects on swim-motivated and spontaneous motor activity.

PubMed

Weiss, J M; Simson, P G; Hoffman, L J; Ambrose, M J; Cooper, S; Webster, A

1986-04-01

These studies examined how pharmacological stimulation and blockade of alpha receptors would affect active motor behavior in rats. In experiment I, alpha-2 receptor antagonists (piperoxane, yohimbine) and agonists [clonidine, norepinephrine (NE)] were infused into various locations in the ventricular system of the brain, including the locus coeruleus region, and motor activity was measured. Activity was measured principally in a swim test but spontaneous (ambulatory) activity was also recorded while drugs were being infused. When infused into the locus coeruleus region, small doses of the antagonists piperoxane and yohimbine depressed activity in the swim test while infusion of the agonists clonidine and NE had the opposite effect of stimulating activity. These effects were highly specific to the region of the locus coeruleus, since infusions of these drugs into other nearby locations in the ventricular system or use of larger doses had different, often opposite effects. This was especially true of clonidine and NE which profoundly depressed activity when infused posterior to the locus coeruleus, particularly over the dorsal vagal complex. Infusion of small doses of these drugs into the lateral ventricle had effects similar to infusion into the locus coeruleus region, though less pronounced. Changes in spontaneous motor activity were also observed, but this measure differentiated the groups less well than did the swim test. In experiment II, the predominantly postsynaptic receptor agonists isoproterenol (beta agonist) and phenylephrine (alpha-1 agonist) were infused into the ventricular system. Since infusions of piperoxane and yohimbine into the locus coeruleus that decreased activity in experiment I increase the release of NE by blocking alpha-2 inhibitory receptors on cell bodies and dendrites of the locus coeruleus, experiment II tested whether ventricular infusion of predominantly postsynaptic receptor agonists would also decrease activity in the swim test. Both isoproterenol and phenylephrine produced this effect, but did so selectively with respect to dose and location of infusion in the ventricular system. These findings are consistent with recent results relating to the mechanism that underlies stress-induced depression of active behavior.

Rat strain differences in brain structure and neurochemistry in response to binge alcohol.

PubMed

Zahr, Natalie M; Mayer, Dirk; Rohlfing, Torsten; Hsu, Oliver; Vinco, Shara; Orduna, Juan; Luong, Richard; Bell, Richard L; Sullivan, Edith V; Pfefferbaum, Adolf

2014-01-01

Ventricular enlargement is a robust phenotype of the chronically dependent alcoholic human brain, yet the mechanism of ventriculomegaly is unestablished. Heterogeneous stock Wistar rats administered binge EtOH (3 g/kg intragastrically every 8 h for 4 days to average blood alcohol levels (BALs) of 250 mg/dL) demonstrate profound but reversible ventricular enlargement and changes in brain metabolites (e.g., N-acetylaspartate (NAA) and choline-containing compounds (Cho)). Here, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats systematically bred from heterogeneous stock Wistar rats for differential alcohol drinking behavior were compared with Wistar rats to determine whether genetic divergence and consequent morphological and neurochemical variation affect the brain's response to binge EtOH treatment. The three rat lines were dosed equivalently and approached similar BALs. Magnetic resonance imaging and spectroscopy evaluated the effects of binge EtOH on brain. As observed in Wistar rats, P and NP rats showed decreases in NAA. Neither P nor NP rats, however, responded to EtOH intoxication with ventricular expansion or increases in Cho levels as previously noted in Wistar rats. Increases in ventricular volume correlated with increases in Cho in Wistar rats. The latter finding suggests that ventricular volume expansion is related to adaptive changes in brain cell membranes in response to binge EtOH. That P and NP rats responded differently to EtOH argues for intrinsic differences in their brain cell membrane composition. Further, differential metabolite responses to EtOH administration by rat strain implicate selective genetic variation as underlying heterogeneous effects of chronic alcoholism in the human condition.

Regional pressure and temperature variations across the injured human brain: comparisons between paired intraparenchymal and ventricular measurements.

PubMed

Childs, Charmaine; Shen, Liang

2015-06-23

Intraparenchymal, multimodality sensors are commonly used in the management of patients with severe traumatic brain injury (TBI). The 'gold standard', based on accuracy, reliability and cost for intracranial pressure (ICP) monitoring is within the cerebral ventricle (external strain gauge). There are no standards yet for intracerebral temperature monitoring and little is known of temperature differences between brain tissue and ventricle. The aim of the study therefore was to determine pressure and temperature differences at intraparenchymal and ventricular sites during five days of continuous neuromonitoring. Patients with severe TBI requiring emergency surgery. patients who required ICP monitoring were eligible for recruitment. Two intracerebral probe types were used: a) intraventricular, dual parameter sensor (measuring pressure, temperature) with inbuilt catheter for CSF drainage: b) multiparameter intraparenchymal sensor measuring pressure, temperature and oxygen partial pressure. All sensors were inserted during surgery and under aseptic conditions. Seventeen patients, 12 undergoing neurosurgery (decompressive craniectomy n = 8, craniotomy n = 4) aged 21-78 years were studied. Agreement of measures for 9540 brain tissue-ventricular temperature 'pairs' and 10,291 brain tissue-ventricular pressure 'pairs' were determined using mixed model to compare mean temperature and pressure for longitudinal data. There was no significant overall difference for mean temperature (p = 0.92) or mean pressure readings (p = 0.379) between tissue and ventricular sites. With 95.8 % of paired temperature readings within 2SD (-0.4 to 0.4 °C) differences in temperature between brain tissue and ventricle were clinically insignificant. For pressure, 93.5 % of readings pairs fell within the 2SD range (-9.4756 to 7.8112 mmHg). However, for individual patients, agreement for mean tissue-ventricular pressure differences was poor on occasions. There is good overall agreement between paired temperature measurements obtained from deep white matter and brain ventricle in patients with and without early neurosurgery. For paired ICP measurements, 93.5 % of readings were within 2SD of mean difference. Whilst the majority of paired readings were comparable (within 10 mmHg) clinically relevant tissue-ventricular dissociations were noted. Further work is required to unravel the events responsible for short intervals of pressure dissociation before tissue pressure readings can be definitively accepted as a reliable surrogate for ventricular pressure.

Spatial distribution and cellular composition of adult brain proliferative zones in the teleost, Gymnotus omarorum

PubMed Central

Olivera-Pasilio, Valentina; Peterson, Daniel A.; Castelló, María E.

2014-01-01

Proliferation of stem/progenitor cells during development provides for the generation of mature cell types in the CNS. While adult brain proliferation is highly restricted in the mammals, it is widespread in teleosts. The extent of adult neural proliferation in the weakly electric fish, Gymnotus omarorum has not yet been described. To address this, we used double thymidine analog pulse-chase labeling of proliferating cells to identify brain proliferation zones, characterize their cellular composition, and analyze the fate of newborn cells in adult G. omarorum. Short thymidine analog chase periods revealed the ubiquitous distribution of adult brain proliferation, similar to other teleosts, particularly Apteronotus leptorhynchus. Proliferating cells were abundant at the ventricular-subventricular lining of the ventricular-cisternal system, adjacent to the telencephalic subpallium, the diencephalic preoptic region and hypothalamus, and the mesencephalic tectum opticum and torus semicircularis. Extraventricular proliferation zones, located distant from the ventricular-cisternal system surface, were found in all divisions of the rombencephalic cerebellum. We also report a new adult proliferation zone at the caudal-lateral border of the electrosensory lateral line lobe. All proliferation zones showed a heterogeneous cellular composition. The use of short (24 h) and long (30 day) chase periods revealed abundant fast cycling cells (potentially intermediate amplifiers), sparse slow cycling (potentially stem) cells, cells that appear to have entered a quiescent state, and cells that might correspond to migrating newborn neural cells. Their abundance and migration distance differed among proliferation zones: greater numbers and longer range and/or pace of migrating cells were associated with subpallial and cerebellar proliferation zones. PMID:25249943

Formation of fibroblastic reticular network in the brain after infection with neurovirulent murine coronavirus.

PubMed

Watanabe, Rihito; Kakizaki, Masatoshi; Ikehara, Yuzuru; Togayachi, Akira

2016-12-01

cl-2 virus is an extremely neurovirulent murine coronavirus. However, during the initial phase of infection between 12 and 24 h post-inoculation (hpi), the viral antigens are detected only in the meninges, followed by viral spread into the ventricular wall before invasion into the brain parenchyma, indicating that the viruses employ a passage between the meninges and ventricular wall as an entry route into the brain parenchyma. At 48 hpi, the passage was found to be constructed by ER-TR7 antigen (ERag)-positive fibers (ERfibs) associated with laminin and collagen III between the fourth ventricle and meninges at the cerebellopontine angle. The construct of the fibers mimics the reticular fibers of the fibroblastic reticular network, which comprises a conduit system in the lymphoid organs. In the meninges, ERfibs together with collagen fibers, lining in a striped pattern, made up a pile of thin sheets. In the brain parenchyma, mature ERfibs associated with laminin were found around blood vessels. Besides mature ERfibs, immature Erfibs without associations with other extracellular matrix components like laminin and collagen appeared after infection, suggesting that the CNS creates a unique conduit system for immune communication triggered by viral invasion. © 2016 Japanese Society of Neuropathology.

Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia.

PubMed

Horga, Guillermo; Bernacer, Javier; Dusi, Nicola; Entis, Jonathan; Chu, Kingwai; Hazlett, Erin A; Haznedar, M Mehmet; Kemether, Eileen; Byne, William; Buchsbaum, Monte S

2011-10-01

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.

Cerebroventricular Microinjection (CVMI) into Adult Zebrafish Brain Is an Efficient Misexpression Method for Forebrain Ventricular Cells

PubMed Central

Kizil, Caghan; Brand, Michael

2011-01-01

The teleost fish Danio rerio (zebrafish) has a remarkable ability to generate newborn neurons in its brain at adult stages of its lifespan-a process called adult neurogenesis. This ability relies on proliferating ventricular progenitors and is in striking contrast to mammalian brains that have rather restricted capacity for adult neurogenesis. Therefore, investigating the zebrafish brain can help not only to elucidate the molecular mechanisms of widespread adult neurogenesis in a vertebrate species, but also to design therapies in humans with what we learn from this teleost. Yet, understanding the cellular behavior and molecular programs underlying different biological processes in the adult zebrafish brain requires techniques that allow manipulation of gene function. As a complementary method to the currently used misexpression techniques in zebrafish, such as transgenic approaches or electroporation-based delivery of DNA, we devised a cerebroventricular microinjection (CVMI)-assisted knockdown protocol that relies on vivo morpholino oligonucleotides, which do not require electroporation for cellular uptake. This rapid method allows uniform and efficient knockdown of genes in the ventricular cells of the zebrafish brain, which contain the neurogenic progenitors. We also provide data on the use of CVMI for growth factor administration to the brain – in our case FGF8, which modulates the proliferation rate of the ventricular cells. In this paper, we describe the CVMI method and discuss its potential uses in zebrafish. PMID:22076157

Prevalence of lateral ventricle asymmetry in brain MRI studies of neurologically normal dogs and dogs with idiopathic epilepsy.

PubMed

Pivetta, Mauro; De Risio, Luisa; Newton, Richard; Dennis, Ruth

2013-01-01

Asymmetry of the cerebral lateral ventricles is a common finding in cross-sectional imaging of otherwise normal canine brains and has been assumed to be incidental. The purpose of this retrospective study was to compare the prevalence of ventricular asymmetry in brain MRI studies of normal dogs and dogs with idiopathic epilepsy. Brain MRI archives were searched for 100 neurologically normal dogs (Group 1) and 100 dogs with idiopathic epilepsy (Group 2). For each dog, asymmetry of the lateral ventricles was subjectively classified as absent, mild, moderate, and severe based on a consensus of two observers who were unaware of group status. Ventricular areas were measured from transverse T1W images at the level of the interthalamic adhesion. An asymmetry ratio was calculated as the ratio of the larger to smaller ventricular transverse area. There was excellent agreement between subjective assessments of ventricular asymmetry and quantitative assessments using asymmetry ratios (k = 0.995). The prevalence of asymmetry was 38% in Group 1 dogs and 44% in Group 2 dogs. Assymmetry was scored as mild in the majority of Group 2 dogs. There was no significant association between presence/absence and degree of ventricular asymmetry vs. dog group, age, gender, or skull conformation. Findings from the current study supported previously published assumptions that asymmetry of the lateral cerebral ventricles is an incidental finding in MRI studies of the canine brain. © 2013 Veterinary Radiology & Ultrasound.

Hollow mandrin facilitates external ventricular drainage placement.

PubMed

Heese, O; Regelsberger, J; Kehler, U; Westphal, M

2005-07-01

Placement of ventricular catheters is a routine procedure in neurosurgery. Ventricle puncture is done using a flexible ventricular catheter stabilised by a solid steel mandrin in order to improve stability during brain penetration. A correct catheter placement is confirmed after removing the solid steel mandrin by observation of cerebrospinal fluid (CSF) flow out of the flexible catheter. Incorrect placement makes further punctures necessary. The newly developed device allows CSF flow observation during the puncture procedure and in addition precise intracranial pressure (ICP) measurement. The developed mandrin is hollow with a blunt tip. On one side 4-5 small holes with a diameter of 0.8 mm are drilled corresponding exactly with the holes in the ventricular catheter, allowing CSF to pass into the hollow mandrin as soon as the ventricle is reached. By connecting a small translucent tube at the distal portion of the hollow mandrin ICP can be measured without loss of CSF. The system has been used in 15 patients with subarachnoid haemorrhage (SAH) or intraventricular haemeorrhage (IVH) and subsequent hydrocephalus. The new system improved the external ventricular drainage implantation procedure. In all 15 patients catheter placement was correct. ICP measurement was easy to perform immediately at ventricle puncture. In 4 patients at puncture no spontaneous CSF flow was observed, therefore by connecting a syringe and gentle aspiration of CSF correct placement was confirmed in this unexpected low pressure hydrocephalus. Otherwise by using the conventional technique further punctures would have been necessary. Advantages of the new technique are less puncture procedures with a lower risk of damage to neural structures and reduced risk of intracranial haemorrhages. Implantation of the ventricular catheter to far into the brain can be monitored and this complication can be overcome. Using the connected pressure monitoring tube an exact measurement of the opening intracranial pressure can be obtained performed without losing CSF.

Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex.

PubMed

Gaser, Christian; Nenadic, Igor; Buchsbaum, Bradley R; Hazlett, Erin A; Buchsbaum, Monte S

2004-01-01

Enlargement of the lateral ventricles is among the most frequently reported macroscopic brain structural changes in schizophrenia, although variable in extent and localization. The authors investigated whether ventricular enlargement is related to regionally specific volume loss. High-resolution magnetic resonance imaging scans from 39 patients with schizophrenia were analyzed with deformation-based morphometry, a voxel-wise whole brain morphometric technique. Significant negative correlations with the ventricle-brain ratio were found for voxels in the left and right thalamus and posterior putamen and in the left superior temporal gyrus and insula. Thalamic shrinkage, especially of medial nuclei and the adjacent striatum and insular cortex, appear to be important contributors to ventricular enlargement in schizophrenia.

Neuregulin 1 Type II-ErbB Signaling Promotes Cell Divisions Generating Neurons from Neural Progenitor Cells in the Developing Zebrafish Brain.

PubMed

Sato, Tomomi; Sato, Fuminori; Kamezaki, Aosa; Sakaguchi, Kazuya; Tanigome, Ryoma; Kawakami, Koichi; Sehara-Fujisawa, Atsuko

2015-01-01

Post-mitotic neurons are generated from neural progenitor cells (NPCs) at the expense of their proliferation. Molecular and cellular mechanisms that regulate neuron production temporally and spatially should impact on the size and shape of the brain. While transcription factors such as neurogenin1 (neurog1) and neurod govern progression of neurogenesis as cell-intrinsic mechanisms, recent studies show regulatory roles of several cell-extrinsic or intercellular signaling molecules including Notch, FGF and Wnt in production of neurons/neural progenitor cells from neural stem cells/radial glial cells (NSCs/RGCs) in the ventricular zone (VZ). However, it remains elusive how production of post-mitotic neurons from neural progenitor cells is regulated in the sub-ventricular zone (SVZ). Here we show that newborn neurons accumulate in the basal-to-apical direction in the optic tectum (OT) of zebrafish embryos. While neural progenitor cells are amplified by mitoses in the apical ventricular zone, neurons are exclusively produced through mitoses of neural progenitor cells in the sub-basal zone, later in the sub-ventricular zone, and accumulate apically onto older neurons. This neurogenesis depends on Neuregulin 1 type II (NRG1-II)-ErbB signaling. Treatment with an ErbB inhibitor, AG1478 impairs mitoses in the sub-ventricular zone of the optic tectum. Removal of AG1478 resumes sub-ventricular mitoses without precedent mitoses in the apical ventricular zone prior to basal-to-apical accumulation of neurons, suggesting critical roles of ErbB signaling in mitoses for post-mitotic neuron production. Knockdown of NRG1-II impairs both mitoses in the sub-basal/sub-ventricular zone and the ventricular zone. Injection of soluble human NRG1 into the developing brain ameliorates neurogenesis of NRG1-II-knockdown embryos, suggesting a conserved role of NRG1 as a cell-extrinsic signal. From these results, we propose that NRG1-ErbB signaling stimulates cell divisions generating neurons from neural progenitor cells in the developing vertebrate brain.

Cannabinoid receptor 2 activation restricts fibrosis and alleviates hydrocephalus after intraventricular hemorrhage.

PubMed

Tan, Qiang; Chen, Qianwei; Feng, Zhou; Shi, Xia; Tang, Jun; Tao, Yihao; Jiang, Bing; Tan, Liang; Feng, Hua; Zhu, Gang; Yang, Yunfeng; Chen, Zhi

2017-01-01

Fibrosis in ventricular system has a role in hydrocephalus following intraventricular hemorrhage (IVH). The cannabinoid receptor 2 (CB2) has been reported to participate in alleviating the fibrosis process of many diseases. However, its role in fibrosis after IVH was unclear so far, and we hypothesized that CB2 activation has potential to attenuate hydrocephalus after IVH via restricting fibrosis. So the present study was designed to investigate this hypothesis in a modified rat IVH model. Autologous non-anticoagulative blood injection model was induced to mimic ventricular extension of hemorrhage in adult Sprague-Dawley rats. Rats were randomized to receive JWH-133(CB2 agonist), SR144528 (CB2 antagonist) or saline. The lateral ventricular volumes, fibrosis in the subarachnoid space and ventricular wall, transforming growth factor-β 1(TGF-β1) in cerebrospinal fluid and brain tissue, and animal neurological scores were measured to evaluate the effects of CB2 in hydrocephalus following IVH. CB2 agonist JWH-133 significantly decreased the lateral ventricular volumes, improved the associated neurological deficits, down-regulated TGF-β1 expression, and alleviated fibrosis in the subarachnoid space and ventricular wall after IVH. All of these effects were reversed by SR144528. In conclusion, CB2 may have anti-fibrogenic effects after IVH. CB2 agonist suppressed fibrosis of ventricular system and alleviated hydrocephalus following IVH, which is partly mediated by inhibiting TGF-β1. Copyright © 2016 Elsevier B.V. All rights reserved.

Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

PubMed Central

Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

2016-01-01

Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied, the changes in mechanical properties were modest. Moreover, the effect of ventricular enlargement is not limited to the CC+PVWM and ventral internal capsule, the extent of microstructural changes vary between brain regions, and there is regional and temporal variation in brain tissue stiffness during hydrocephalus development. PMID:26848844

Innervation of Ventricular and Periventricular Brain Compartments

PubMed Central

Leak, Rehana K.; Moore, Robert Y.

2012-01-01

Synaptic transmission is divided into two broad categories on the basis of the distance over which neurotransmitters travel. Wiring transmission is the release of transmitter into synaptic clefts in close apposition to receptors. Volume transmission is the release of transmitters or modulators over varying distances before interacting with receptors. One case of volume transmission over potentially long distances involves release into cerebrospinal fluid (CSF). The CSF contains neuroactive substances that affect brain function and range in size from small molecule transmitters to peptides and large proteins. CSF-contacting neurons are a well-known and universal feature of non-mammalian vertebrates, but only supra- and subependymal serotonergic plexuses are a commonly studied feature in mammals. The origin of most other neuroactive substances in CSF is unknown. In order to determine which brain regions communicate with CSF, we describe the distribution of retrograde neuronal labeling in the rat brain following ventricular injection of Cholera toxin, β subunit (CTβ), a tracer frequently used in brain circuit analysis. Within 15 to 30 minutes following intraventricular injection, there is only diffuse, non-specific staining adjacent to the ventricular surface. Within 2 to 10 days, however, there is extensive labeling of neuronal perikarya in specific nuclear groups in the telencephalon, thalamus, hypothalamus and brainstem, many at a considerable distance from the ventricles. These observations support the view that ventricular CSF is a significant channel for volume transmission and identifies those brain regions most likely to be involved in this process. PMID:22575559

Prenatal assessment of ventriculomegaly: an anatomical study.

PubMed

Glonek, Michał; Kedzia, Alicja; Derkowski, Wojciech

2003-07-01

The aim of the study was to analyze the development of the lateral ventricles during the 1st and 2nd trimester of fetal life using computerized image processing, and to compare the findings with the results obtained by ultrasound imaging and MRI. The material consisted of 32 fetuses from spontaneous abortions, 54-235 mm crown-rump length. After detached craniotomy, the brains were cut into axial sections; the sections were filmed with a video camera and then analyzed using specialized software In 12 analyzed brains, no significant pathological changes were observed in the cerebral hemispheres, whereas the remaining 20 (63%) demonstrated visible pathology. In 10 cases there were areas of leukomalacia, in 5 intra- and periventricular hemorrhages, and in 2 fetuses ventriculomegaly with lateral ventricular triangles over 10 mm wide (in cases of active hydrocephalus and colpocephaly). In 1 case of an 18-week-old fetus, lateral ventricular morphology typical of hydrocephalus (generalized distension) was observed with ventricular triangles 8.5 mm wide. The other 2 fetuses demonstrated developmental defects. The frontal horns were the most markedly enlarged in both cases of hydrocephalus (100%) and were semicircular, whereas after intra- and periventricular hemorrhages they were less enlarged and triangular, with the base of the triangle directed to the front and frequent significant asymmetry. The shape of the ventricular system, including that of the frontal horns, is important in the diagnostics of fetal CNS.

Role of lipocalin 2 in intraventricular haemoglobin-induced brain injury

PubMed Central

Shishido, Hajime; Toyota, Yasunori; Hua, Ya; Keep, Richard F; Xi, Guohua

2016-01-01

Objective Our recent studies have shown that blood components, including haemoglobin and iron, contribute to hydrocephalus development and brain injury after intraventricular haemorrhage (IVH). The current study investigated the role of lipocalin 2 (LCN2), a protein involved in iron handling, in the ventricular dilation and neuroinflammation caused by brain injury in a mouse model of IVH. Design Female wild-type (WT) C57BL/6 mice and LCN2-deficient (LCN2−/−) mice had an intraventricular injection of haemoglobin, and control mice received an equivalent amount of saline. MRI was performed presurgery and postsurgery to measure ventricular volume and the brains were used for either immunohistochemistry or western blot. Results Ventricular dilation was observed in WT mice at 24 h after haemoglobin (25 mg/mL, 20 µL) injection (12.5±2.4 vs 8.6±1.5 mm3 in the control, p<0.01). Western blotting showed that LCN2 was significantly upregulated in the periventricular area (p<0.01). LCN2 was mainly expressed in astrocytes, whereas the LCN2 receptor was detected in astrocytes, microglia/macrophages and neurons. Haemoglobin-induced ventricle dilation and glia activation were less in LCN2−/− mice (p<0.01). Injection of high-dose haemoglobin (50 mg/mL) resulted in lower mortality in LCN2−/− mice (27% vs 86% in WT; p<0.05). Conclusions Intraventricular haemoglobin caused LCN2 upregulation and ventricular dilation. Haemoglobin resulted in lower mortality and less ventricular dilation in LCN2−/− mice. These results suggest that LCN2 has a role in haemoglobin-induced brain injury and may be a therapeutic target for IVH. PMID:28959462

Synergistic Utility of Brain Natriuretic Peptide and Left Ventricular Global Longitudinal Strain in Asymptomatic Patients With Significant Primary Mitral Regurgitation and Preserved Systolic Function Undergoing Mitral Valve Surgery.

PubMed

Alashi, Alaa; Mentias, Amgad; Patel, Krishna; Gillinov, A Marc; Sabik, Joseph F; Popović, Zoran B; Mihaljevic, Tomislav; Suri, Rakesh M; Rodriguez, L Leonardo; Svensson, Lars G; Griffin, Brian P; Desai, Milind Y

2016-07-01

In asymptomatic patients with ≥3+ mitral regurgitation and preserved left ventricular (LV) ejection fraction who underwent mitral valve surgery, we sought to discover whether baseline LV global longitudinal strain (LV-GLS) and brain natriuretic peptide provided incremental prognostic utility. Four hundred and forty-eight asymptomatic patients (61±12 years and 69% men) with ≥3+ primary mitral regurgitation and preserved left ventricular ejection fraction, who underwent mitral valve surgery (92% repair) at our center between 2005 and 2008, were studied. Baseline clinical and echocardiographic data (including LV-GLS using Velocity Vector Imaging, Siemens, PA) were recorded. The Society of Thoracic Surgeons score was calculated. The primary outcome was death. Mean Society of Thoracic Surgeons score, left ventricular ejection fraction, mitral effective regurgitant orifice, indexed LV end-diastolic volume, and right ventricular systolic pressure were 4±1%, 62±3%, 0.55±0.2 cm(2), 58±13 cc/m(2), and 37±15 mm Hg, respectively. Forty-five percent of patients had flail. Median log-transformed BNP and LV-GLS were 4.04 (absolute brain natriuretic peptide: 60 pg/dL) and -20.7%. At 7.7±2 years, death occurred in 41 patients (9%; 0% at 30 days). On Cox analysis, a higher Society of Thoracic Surgeons score (hazard ratio 1.55), higher baseline right ventricular systolic pressure (hazard ratio 1.11), more abnormal LV-GLS (hazard ratio 1.17), and higher median log-transformed BNP (hazard ratio 2.26) were associated with worse longer-term survival (all P<0.01). Addition of LV-GLS and median log-transformed BNP to a clinical model (Society of Thoracic Surgeons score and baseline right ventricular systolic pressure) provided incremental prognostic utility (χ(2) for longer-term mortality increased from 31-47 to 61; P<0.001). In asymptomatic patients with significant primary mitral regurgitation and preserved left ventricular ejection fraction who underwent mitral valve surgery, brain natriuretic peptide and LV-GLS provided synergistic risk stratification, independent of established factors. © 2016 American Heart Association, Inc.

Pressure-controlled drainage of cerebrospinal fluid: clinical experience with a new type of ventricular catheter (Ventcontrol MTC)and an integrated Piezo-resistive sensor at its tip: technical note.

PubMed

Piek, J; Raes, P

1996-01-01

We described a new ventricular catheter that is the combination of a "classic" ventricular catheter with a piezo-resistive transducer at its tip. The device allows parallel recordings of intraventricular fluid pressure via a chip and a fluid-filled external transducer, drainage of cerebrospinal fluid from the ventricle or injection of fluid into the ventricle with simultaneous monitoring of intracranial pressure, and recording of brain tissue pressure in cases of misplacement or dislocation of the ventricular catheter or in cases of progressively narrowing ventricles caused by brain edema. Clinical tests in various situations at different pressure ranges (total recording time, 1356 h in 13 patients) gave excellent correlations of both pressures. Application of the device is especially indicated in clinical situations in which pressure-controlled drainage is desirable, occlusion of ventricular bolts is likely, or pressure-volume tests are needed.

Metronidazole and hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration measurements in patients with external ventricular drain.

PubMed

Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William; Marchand, Sandrine

2014-01-01

This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0-τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0-τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF.

Can using a peel-away sheath in shunt implantation prevent ventricular catheter obstruction?

PubMed

Camlar, Mahmut; Ersahin, Yusuf; Ozer, Fusun Demirçivi; Sen, Fatih; Orman, Mehmet

2011-02-01

Shunt obstruction is the most common shunt complication. In 2003, Kehler et al. used peel-away sheath while implanting the ventricular catheter in 20 patients. They found less revision rate in the peel-away sheath group. We aimed to test the efficacy of this technique in cadavers. We used 100 fresh brains obtained from medicolegal autopsies. Posterior parietal and frontal approaches were used to puncture the lateral ventricle in each cerebral hemisphere. The ventricle is punctured with a peel-away sheath system. After the ventricle is reached, the mandarin is retracted and the ventricular catheter is introduced through the opening. The ventricular catheter was removed from the ventricle, the opening at the tip of the ventricular catheter was checked out for obstruction, and the number of patent and plugged openings was recorded. This procedure was repeated four times for each location with and without using peel-away sheath. The control group consisted of the procedures done without using peel-away sheath. The number of the plugged openings in the peel-away sheath group was significantly smaller than the control group. There was no significant difference between the two groups in terms of gender and left and right cerebral hemispheres. The obstruction rate was significantly lower in the posterior parietal approach. Pearson's correlation showed that increasing age was associated with less obstruction rate. Peel-away sheath decreases the number of plugged openings of the ventricular catheter. A clinical cooperative study is needed to prove that a peel-away sheath should be included in the ventricular shunt systems in the market.

Aneurysm in the brain

MedlinePlus

... ruptured: Clipping is done during open brain surgery (craniotomy) . Endovascular repair is most often done. It usually ... unit (ICU) Complete bed rest and activity restrictions Drainage of blood from the brain area (cerebral ventricular ...

Syringe Port: A Convenient, Safe, and Cost-Effective Tubular Retractor for Transportal Removal of Deep-Seated Lesions of the Brain.

PubMed

Singh, Harnarayan; Patir, Rana; Vaishya, Sandeep; Miglani, Rahul; Kaur, Amandeep

2018-06-01

Minimally invasive transportal resection of deep intracranial lesions has become a widely accepted surgical technique. Many disposable, mountable port systems are available in the market for this purpose, like the ViewSite Brain Access System. The objective of this study was to find a cost-effective substitute for these systems. Deep-seated brain lesions were treated with a port system made from disposable syringes. The syringe port could be inserted through minicraniotomies placed and planned with navigation. All deep-seated lesions like ventricular tumours, colloid cysts, deep-seated gliomas, and basal ganglia hemorrhages were treated with this syringe port system and evaluated for safety, operative site hematomas, and blood loss. 62 patients were operated on during the study period from January 2015 to July 2017, using this innovative syringe port system for deep-seated lesions of the brain. No operative site hematoma or contusions were seen along the port entry site and tract. Syringe port is a cost-effective and safe alternative to the costly disposable brain port systems, especially for neurosurgical setups in developing countries for minimally invasive transportal resection of deep brain lesions. Copyright © 2018 Elsevier Inc. All rights reserved.

Hydrocephalus secondary to obstruction of the lateral apertures in two dogs.

PubMed

Kent, M; Glass, E N; Haley, A C; Shaikh, L S; Sequel, M; Blas-Machado, U; Bishop, T M; Holmes, S P; Platt, S R

2016-11-01

Traditionally, hydrocephalus is divided into communicating or non-communicating (obstructive) based on the identification of a blockage of cerebrospinal fluid (CSF) flow through the ventricular system. Hydrocephalus ex vacuo refers to ventricular enlargement as a consequence of neuroparenchymal loss. Hydrocephalus related to obstruction of the lateral apertures of the fourth ventricles has rarely been described. The clinicopathologic findings in two dogs with hydrocephalus secondary to obstruction of the lateral apertures of the fourth ventricle are reported. Signs were associated with a caudal cervical spinal cord lesion in one dog and a caudal brain stem lesion in the other dog. Magnetic resonance imaging (MRI) disclosed dilation of the ventricular system, including the lateral recesses of the fourth ventricle. In one dog, postmortem ventriculography confirmed obstruction of the lateral apertures. Microscopic changes were identified in the choroid plexus in both dogs, yet a definitive cause of the obstructions was not identified. The MRI findings in both dogs are similar to membranous occlusion of the lateral and median apertures in human patients. MRI detection of dilation of the entire ventricular system in the absence of an identifiable cause should prompt consideration of an obstruction of the lateral apertures. In future cases, therapeutic interventions aimed at re-establishing CSF flow or ventriculoperitoneal catheterisation should be considered. © 2016 Australian Veterinary Association.

Automatic delineation and 3D visualization of the human ventricular system using probabilistic neural networks

NASA Astrophysics Data System (ADS)

Hatfield, Fraser N.; Dehmeshki, Jamshid

1998-09-01

Neurosurgery is an extremely specialized area of medical practice, requiring many years of training. It has been suggested that virtual reality models of the complex structures within the brain may aid in the training of neurosurgeons as well as playing an important role in the preparation for surgery. This paper focuses on the application of a probabilistic neural network to the automatic segmentation of the ventricles from magnetic resonance images of the brain, and their three dimensional visualization.

Automatically measuring brain ventricular volume within PACS using artificial intelligence.

PubMed

Yepes-Calderon, Fernando; Nelson, Marvin D; McComb, J Gordon

2018-01-01

The picture archiving and communications system (PACS) is currently the standard platform to manage medical images but lacks analytical capabilities. Staying within PACS, the authors have developed an automatic method to retrieve the medical data and access it at a voxel level, decrypted and uncompressed that allows analytical capabilities while not perturbing the system's daily operation. Additionally, the strategy is secure and vendor independent. Cerebral ventricular volume is important for the diagnosis and treatment of many neurological disorders. A significant change in ventricular volume is readily recognized, but subtle changes, especially over longer periods of time, may be difficult to discern. Clinical imaging protocols and parameters are often varied making it difficult to use a general solution with standard segmentation techniques. Presented is a segmentation strategy based on an algorithm that uses four features extracted from the medical images to create a statistical estimator capable of determining ventricular volume. When compared with manual segmentations, the correlation was 94% and holds promise for even better accuracy by incorporating the unlimited data available. The volume of any segmentable structure can be accurately determined utilizing the machine learning strategy presented and runs fully automatically within the PACS.

Gene Delivery to Postnatal Rat Brain by Non-ventricular Plasmid Injection and Electroporation

PubMed Central

Molotkov, Dmitry A.; Yukin, Alexey Y.; Afzalov, Ramil A.; Khiroug, Leonard S.

2010-01-01

Creation of transgenic animals is a standard approach in studying functions of a gene of interest in vivo. However, many knockout or transgenic animals are not viable in those cases where the modified gene is expressed or deleted in the whole organism. Moreover, a variety of compensatory mechanisms often make it difficult to interpret the results. The compensatory effects can be alleviated by either timing the gene expression or limiting the amount of transfected cells. The method of postnatal non-ventricular microinjection and in vivo electroporation allows targeted delivery of genes, siRNA or dye molecules directly to a small region of interest in the newborn rodent brain. In contrast to conventional ventricular injection technique, this method allows transfection of non-migratory cell types. Animals transfected by means of the method described here can be used, for example, for two-photon in vivo imaging or in electrophysiological experiments on acute brain slices. PMID:20972387

Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest.

PubMed

Li, Duan; Mabrouk, Omar S; Liu, Tiecheng; Tian, Fangyun; Xu, Gang; Rengifo, Santiago; Choi, Sarah J; Mathur, Abhay; Crooks, Charles P; Kennedy, Robert T; Wang, Michael M; Ghanbari, Hamid; Borjigin, Jimo

2015-04-21

The mechanism by which the healthy heart and brain die rapidly in the absence of oxygen is not well understood. We performed continuous electrocardiography and electroencephalography in rats undergoing experimental asphyxia and analyzed cortical release of core neurotransmitters, changes in brain and heart electrical activity, and brain-heart connectivity. Asphyxia stimulates a robust and sustained increase of functional and effective cortical connectivity, an immediate increase in cortical release of a large set of neurotransmitters, and a delayed activation of corticocardiac functional and effective connectivity that persists until the onset of ventricular fibrillation. Blocking the brain's autonomic outflow significantly delayed terminal ventricular fibrillation and lengthened the duration of detectable cortical activities despite the continued absence of oxygen. These results demonstrate that asphyxia activates a brainstorm, which accelerates premature death of the heart and the brain.

An evaluation and comparison of intraventricular, intraparenchymal, and fluid-coupled techniques for intracranial pressure monitoring in patients with severe traumatic brain injury.

PubMed

Vender, John; Waller, Jennifer; Dhandapani, Krishnan; McDonnell, Dennis

2011-08-01

Intracranial pressure measurements have become one of the mainstays of traumatic brain injury management. Various technologies exist to monitor intracranial pressure from a variety of locations. Transducers are usually placed to assess pressure in the brain parenchyma and the intra-ventricular fluid, which are the two most widely accepted compartmental monitoring sites. The individual reliability and inter-reliability of these devices with and without cerebrospinal fluid diversion is not clear. The predictive capability of monitors in both of these sites to local, regional, and global changes also needs further clarification. The technique of monitoring intraventricular pressure with a fluid-coupled transducer system is also reviewed. There has been little investigation into the relationship among pressure measurements obtained from these two sources using these three techniques. Eleven consecutive patients with severe, closed traumatic brain injury not requiring intracranial mass lesion evacuation were admitted into this prospective study. Each patient underwent placement of a parenchymal and intraventricular pressure monitor. The ventricular catheter tubing was also connected to a sensor for fluid-coupled measurement. Pressure from all three sources was measured hourly with and without ventricular drainage. Statistically significant correlation within each monitoring site was seen. No monitoring location was more predictive of global pressure changes or more responsive to pressure changes related to patient stimulation. However, the intraventricular pressure measurements were not reliable in the presence of cerebrospinal fluid drainage whereas the parenchymal measurements remained unaffected. Intraparenchymal pressure monitoring provides equivalent, statistically similar pressure measurements when compared to intraventricular monitors in all care and clinical settings. This is particularly valuable when uninterrupted cerebrospinal fluid drainage is desirable.

Development of Realistic Striatal Digital Brain (SDB) Phantom for 123I-FP-CIT SPECT and Effect on Ventricle in the Brain for Semi-quantitative Index of Specific Binding Ratio.

PubMed

Furuta, Akihiro; Onishi, Hideo; Nakamoto, Kenta

This study aimed at developing the realistic striatal digital brain (SDB) phantom and to assess specific binding ratio (SBR) for ventricular effect in the 123 I-FP-CIT SPECT imaging. SDB phantom was constructed in to four segments (striatum, ventricle, brain parenchyma, and skull bone) using Percentile method and other image processing in the T2-weighted MR images. The reference image was converted into 128×128 matrixes to align MR images with SPECT images. The process image was reconstructed with projection data sets generated from reference images additive blurring, attenuation, scatter, and statically noise. The SDB phantom was evaluated to find the accuracy of calculated SBR and to find the effect of SBR with/without ventricular counts with the reference and process images. We developed and investigated the utility of the SDB phantom in the 123 I-FP-CIT SPECT clinical study. The true value of SBR was just marched to calculate SBR from reference and process images. The SBR was underestimated 58.0% with ventricular counts in reference image, however, was underestimated 162% with ventricular counts in process images. The SDB phantom provides an extremely convenient tool for discovering basic properties of 123 I-FP-CIT SPECT clinical study image. It was suggested that the SBR was susceptible to ventricle.

Effects of hormone therapy on brain structure

PubMed Central

Tosakulwong, Nirubol; Lesnick, Timothy G.; Zuk, Samantha M.; Gunter, Jeffrey L.; Gleason, Carey E.; Wharton, Whitney; Dowling, N. Maritza; Vemuri, Prashanthi; Senjem, Matthew L.; Shuster, Lynne T.; Bailey, Kent R.; Rocca, Walter A.; Jack, Clifford R.; Asthana, Sanjay; Miller, Virginia M.

2016-01-01

Objective: To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Methods: Participants (aged 42–56 years, within 5–36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 μg/d transdermal 17β-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active treatment groups for 12 days each month. MRI and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization (n = 95). Changes in whole brain, ventricular, and white matter hyperintensity volumes, and in global cognitive function, were measured. Results: Higher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo; however, the difference was significant only in the CEE group (p = 0.01). Rates of ventricular expansion correlated with rates of decrease in brain volume (r = −0.58; p ≤ 0.001) and with rates of increase in white matter hyperintensity volume (r = 0.27; p = 0.01) after adjusting for age. The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures. The change in global cognitive function was not different across the groups. Conclusions: Ventricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance. Because the sample size was small and the follow-up limited to 4 years, the findings should be interpreted with caution and need confirmation. Classification of evidence: This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo. PMID:27473135

Effects of hormone therapy on brain structure: A randomized controlled trial.

PubMed

Kantarci, Kejal; Tosakulwong, Nirubol; Lesnick, Timothy G; Zuk, Samantha M; Gunter, Jeffrey L; Gleason, Carey E; Wharton, Whitney; Dowling, N Maritza; Vemuri, Prashanthi; Senjem, Matthew L; Shuster, Lynne T; Bailey, Kent R; Rocca, Walter A; Jack, Clifford R; Asthana, Sanjay; Miller, Virginia M

2016-08-30

To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Participants (aged 42-56 years, within 5-36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 μg/d transdermal 17β-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active treatment groups for 12 days each month. MRI and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization (n = 95). Changes in whole brain, ventricular, and white matter hyperintensity volumes, and in global cognitive function, were measured. Higher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo; however, the difference was significant only in the CEE group (p = 0.01). Rates of ventricular expansion correlated with rates of decrease in brain volume (r = -0.58; p ≤ 0.001) and with rates of increase in white matter hyperintensity volume (r = 0.27; p = 0.01) after adjusting for age. The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures. The change in global cognitive function was not different across the groups. Ventricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance. Because the sample size was small and the follow-up limited to 4 years, the findings should be interpreted with caution and need confirmation. This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo. © 2016 American Academy of Neurology.

A multiport MR-compatible neuroendoscope: spanning the gap between rigid and flexible scopes

PubMed Central

Manjila, Sunil; Mencattelli, Margherita; Rosa, Benoit; Price, Karl; Fagogenis, Georgios; Dupont, Pierre E.

2017-01-01

OBJECTIVE Rigid endoscopes enable minimally invasive access to the ventricular system; however, the operative field is limited to the instrument tip, necessitating rotation of the entire instrument and causing consequent tissue compression while reaching around corners. Although flexible endoscopes offer tip steerability to address this limitation, they are more difficult to control and provide fewer and smaller working channels. A middle ground between these instruments—a rigid endoscope that possesses multiple instrument ports (for example, one at the tip and one on the side)—is proposed in this article, and a prototype device is evaluated in the context of a third ventricular colloid cyst resection combined with septostomy. METHODS A prototype neuroendoscope was designed and fabricated to include 2 optical ports, one located at the instrument tip and one located laterally. Each optical port includes its own complementary metal-oxide semiconductor (CMOS) chip camera, light-emitting diode (LED) illumination, and working channels. The tip port incorporates a clear silicone optical window that provides 2 additional features. First, for enhanced safety during tool insertion, instruments can be initially seen inside the window before they extend from the scope tip. Second, the compliant tip can be pressed against tissue to enable visualization even in a blood-filled field. These capabilities were tested in fresh porcine brains. The image quality of the multiport endoscope was evaluated using test targets positioned at clinically relevant distances from each imaging port, comparing it with those of clinical rigid and flexible neuroendoscopes. Human cadaver testing was used to demonstrate third ventricular colloid cyst phantom resection through the tip port and a septostomy performed through the lateral port. To extend its utility in the treatment of periventricular tumors using MR-guided laser therapy, the device was designed to be MR compatible. Its functionality and compatibility inside a 3-T clinical scanner were also tested in a brain from a freshly euthanized female pig. RESULTS Testing in porcine brains confirmed the multiport endoscope’s ability to visualize tissue in a blood-filled field and to operate inside a 3-T MRI scanner. Cadaver testing confirmed the device’s utility in operating through both of its ports and performing combined third ventricular colloid cyst resection and septostomy with an endoscope rotation of less than 5°. CONCLUSIONS The proposed design provides freedom in selecting both the number and orientation of imaging and instrument ports, which can be customized for each ventricular pathological entity. The lightweight, easily manipulated device can provide added steerability while reducing the potential for the serious brain distortion that happens with rigid endoscope navigation. This capability would be particularly valuable in treating hydrocephalus, both primary and secondary (due to tumors, cysts, and so forth). Magnetic resonance compatibility can aid in endoscope-assisted ventricular aqueductal plasty and stenting, the management of multiloculated complex hydrocephalus, and postinflammatory hydrocephalus in which scarring obscures the ventricular anatomy. PMID:27581309

Ultrasonic evaluation of the neonatal brain.

PubMed

Johnson, M L; Rumack, C M

1980-04-01

Ultrasound examination of the infant brain has been performed in selected medical centers for many years. However, the equipment necessary for obtaining satisfactory visualization of the brain has only recently become commercially available. Currently, ultrasonography is an excellent, noninvasive, inexpensive, rapid, and safe imaging modality for the evaluation of hydrocephalus and other pathologic conditions of the neonatal brain. Ventricular size can often be evaluated in infants up to two or three years of age, but a detailed image of the brain parenchyma becomes more difficult to obtain in a term infant after the first two to three months of life. With the use of the water path and high resolution, real-time systems and with the delineation of structures by multiple projections, (axial, coronal, sagittal and occipital), complex abnormalities may be delineated.

Ventriculostomy Simulation Using Patient-Specific Ventricular Anatomy, 3D Printing, and Hydrogel Casting.

PubMed

Ryan, Justin R; Chen, Tsinsue; Nakaji, Peter; Frakes, David H; Gonzalez, L Fernando

2015-11-01

Educational simulators provide a means for students and experts to learn and refine surgical skills. Educators can leverage the strengths of medical simulators to effectively teach complex and high-risk surgical procedures, such as placement of an external ventricular drain. Our objective was to develop a cost-effective, patient-derived medical simulacrum for cerebral lateral ventriculostomy. A cost-effective, patient-derived medical simulacrum was developed for placement of an external lateral ventriculostomy. Elastomeric and gel casting techniques were used to achieve realistic brain geometry and material properties. 3D printing technology was leveraged to develop accurate cranial properties and dimensions. An economical, gravity-driven pump was developed to provide normal and abnormal ventricular pressures. A small pilot study was performed to gauge simulation efficacy using a technology acceptance model. An accurate geometric representation of the brain was developed with independent lateral cerebral ventricular chambers. A gravity-driven pump pressurized the ventricular cavities to physiologic values. A qualitative study illustrated that the simulation has potential as an educational tool to train medical professionals in the ventriculostomy procedure. The ventricular simulacrum can improve learning in a medical education environment. Rapid prototyping and multi-material casting techniques can produce patient-derived models for cost-effective and realistic surgical training scenarios. Copyright © 2015 Elsevier Inc. All rights reserved.

Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 2. Cerebrospinal Fluid Concentration Measurements in Patients with External Ventricular Drain

PubMed Central

Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William

2014-01-01

This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0–τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0–τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF. PMID:24277050

Three-dimensional mapping of the lateral ventricles in autism

PubMed Central

Vidal, Christine N.; Nicolsonln, Rob; Boire, Jean-Yves; Barra, Vincent; DeVito, Timothy J.; Hayashi, Kiralee M.; Geaga, Jennifer A.; Drost, Dick J.; Williamson, Peter C.; Rajakumar, Nagalingam; Toga, Arthur W.; Thompson, Paul M.

2009-01-01

In this study, a computational mapping technique was used to examine the three-dimensional profile of the lateral ventricles in autism. T1-weighted three-dimensional magnetic resonance images of the brain were acquired from 20 males with autism (age: 10.1 ± 3.5 years) and 22 male control subjects (age: 10.7 ± 2.5 years). The lateral ventricles were delineated manually and ventricular volumes were compared between the two groups. Ventricular traces were also converted into statistical three-dimensional maps, based on anatomical surface meshes. These maps were used to visualize regional morphological differences in the thickness of the lateral ventricles between patients and controls. Although ventricular volumes measured using traditional methods did not differ significantly between groups, statistical surface maps revealed subtle, highly localized reductions in ventricular size in patients with autism in the left frontal and occipital horns. These localized reductions in the lateral ventricles may result from exaggerated brain growth early in life. PMID:18502618

Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan.

PubMed

Brickman, Adam M; Schupf, Nicole; Manly, Jennifer J; Luchsinger, José A; Andrews, Howard; Tang, Ming X; Reitz, Christiane; Small, Scott A; Mayeux, Richard; DeCarli, Charles; Brown, Truman R

2008-08-01

Aging is accompanied by a decrease in brain volume and by an increase in cerebrovascular disease. To examine the effects of age, sex, race/ethnicity, and vascular disease history on measures of brain morphology, including relative brain volume, ventricular volume, hippocampus and entorhinal cortex volumes, and white matter hyperintensity (WMH) burden, in a large community-based cohort of racially/ethnically diverse older adults without dementia. The associations of age, sex, race/ethnicity, and self-reported vascular disease history with brain morphology were examined in a cross-sectional study using multiple linear regression analyses. Sex x race/ethnicity interactions were also considered. The Washington Heights-Inwood Columbia Aging Project, a community-based epidemiological study of older adults from 3 racial/ethnic groups (white, Hispanic, and African American) from northern Manhattan. Beginning in 2003, high-resolution quantitative magnetic resonance (MR) images were acquired in 769 participants without dementia. Relative brain volume (total brain volume/intracranial volume), ventricular volume, and hippocampus and entorhinal cortex volumes were derived manually on high-resolution MR images. White matter hyperintensities were quantified semiautomatically on fluid-attenuated inversion recovery-T2-weighted MR images. Older age was associated with decreased relative brain volume and with increased ventricular and WMH volumes. Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than white participants, but the associations of these variables with age were similar across racial/ethnic groups. Compared with men, women had larger relative brain volumes. Vascular disease was associated with smaller relative brain volume and with higher WMH burden, particularly among African Americans. Older age and vascular disease, particularly among African Americans, are associated with increased brain atrophy and WMH burden. African American and Hispanic subjects have larger relative brain volumes and more WMH than white subjects. Racial/ethnic group differences in WMH severity seem to be partially attributable to differences in vascular disease. Future work will focus on the determinants and cognitive correlates of these differences.

A recommended workflow methodology in the creation of an educational and training application incorporating a digital reconstruction of the cerebral ventricular system and cerebrospinal fluid circulation to aid anatomical understanding.

PubMed

Manson, Amy; Poyade, Matthieu; Rea, Paul

2015-10-19

The use of computer-aided learning in education can be advantageous, especially when interactive three-dimensional (3D) models are used to aid learning of complex 3D structures. The anatomy of the ventricular system of the brain is difficult to fully understand as it is seldom seen in 3D, as is the flow of cerebrospinal fluid (CSF). This article outlines a workflow for the creation of an interactive training tool for the cerebral ventricular system, an educationally challenging area of anatomy. This outline is based on the use of widely available computer software packages. Using MR images of the cerebral ventricular system and several widely available commercial and free software packages, the techniques of 3D modelling, texturing, sculpting, image editing and animations were combined to create a workflow in the creation of an interactive educational and training tool. This was focussed on cerebral ventricular system anatomy, and the flow of cerebrospinal fluid. We have successfully created a robust methodology by using key software packages in the creation of an interactive education and training tool. This has resulted in an application being developed which details the anatomy of the ventricular system, and flow of cerebrospinal fluid using an anatomically accurate 3D model. In addition to this, our established workflow pattern presented here also shows how tutorials, animations and self-assessment tools can also be embedded into the training application. Through our creation of an established workflow in the generation of educational and training material for demonstrating cerebral ventricular anatomy and flow of cerebrospinal fluid, it has enormous potential to be adopted into student training in this field. With the digital age advancing rapidly, this has the potential to be used as an innovative tool alongside other methodologies for the training of future healthcare practitioners and scientists. This workflow could be used in the creation of other tools, which could be developed for use not only on desktop and laptop computers but also smartphones, tablets and fully immersive stereoscopic environments. It also could form the basis on which to build surgical simulations enhanced with haptic interaction.

A hydroelastic model of hydrocephalus

NASA Astrophysics Data System (ADS)

Smillie, Alan; Sobey, Ian; Molnar, Zoltan

2005-09-01

We combine elements of poroelasticity and of fluid mechanics to construct a mathematical model of the human brain and ventricular system. The model is used to study hydrocephalus, a pathological condition in which the normal flow of the cerebrospinal fluid is disturbed, causing the brain to become deformed. Our model extends recent work in this area by including flow through the aqueduct, by incorporating boundary conditions that we believe accurately represent the anatomy of the brain and by including time dependence. This enables us to construct a quantitative model of the onset, development and treatment of this condition. We formulate and solve the governing equations and boundary conditions for this model and give results that are relevant to clinical observations.

Partially silencing brain toll-like receptor 4 prevents in part left ventricular remodeling with sympathoinhibition in rats with myocardial infarction-induced heart failure.

PubMed

Ogawa, Kiyohiro; Hirooka, Yoshitaka; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji

2013-01-01

Left ventricular (LV) remodeling and activation of sympathetic nervous system (SNS) are cardinal features of heart failure. We previously demonstrated that enhanced central sympathetic outflow is associated with brain toll-like receptor 4 (TLR4) probably mediated by brain angiotensin II type 1 receptor in mice with myocardial infarction (MI)-induced heart failure. The purpose of the present study was to examine whether silencing brain TLR4 could prevent LV remodeling with sympathoinhibition in MI-induced heart failure. MI-induced heart failure model rats were created by ligation of left coronary artery. The expression level of TLR4 in brainstem was significantly higher in MI-induced heart failure treated with intracerebroventricular (ICV) injection of hGAPDH-SiRNA than in sham. TLR4 in brainstem was significantly lower in MI-induced heart failure treated with ICV injection of TLR4-SiRNA than in that treated with ICV injection of hGAPDH-SiRNA. Lung weight, urinary norepinephrine excretion, and LV end-diastolic pressure were significantly lower and LV dimension was significantly smaller in MI-induced heart failure treated with TLR4-SiRNA than in that treated with hGAPDH-SiRNA for 2 weeks. Partially silencing brain TLR4 by ICV injection of TLR4-SiRNA for 2 weeks could in part prevent LV remodeling with sympathoinhibition in rats with MI-induced heart failure. Brain TLR4 has a potential to be a target of the treatment for MI-induced heart failure.

Late effects of whole brain irradiation within the therapeutic range

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caveness, W.F.; Carsten, A.L.

1978-01-01

Whole brain exposure with supervoltage x irradiation was carried out in three sets of Macaca mulatta. Two sets of 12 monkeys each, at puberty, received single and fractionated exposures, respectively. One set of 21 monkeys in adulthood received a fractionated exposure. Exposure to 1000 rads in a single dose, at puberty, caused no late effects. Exposure to 1500 rads caused small areas of necrosis in the forebrain white matter at 26 weeks, but a much more extensive involvement at and beyond 52 weeks that included confluent areas of necrosis in gray and white matter. Brain loss resulted in ventricular dilatation.more » Gliomas appeared in two out of three monkeys at or beyond 52 weeks. Exposure to 2000 rads caused such a wide scatter of focal areas of necrosis, including those in the brain stem, that survival beyond 20 to 26 weeks was not possible. All showed enlarged ventricular systems. Whole brain exposure, 200 rads a day, five days a week, for a course of 4000 rads, at puberty, resulted in no delayed effects. Whole brain exposure to 6000 rads in a six weeks course, in the adult, produced less effects than the same dose at puberty. The onset of the scattered necrotic lesions was later than expected, appearing in one out of three animals at 33 weeks, two out of three animals at 52 weeks, and two out of three at 104 weeks. The lesions at 104 weeks were predominantly mineralized, but were accompanied by a greater extent of telangiectasia than seen in the pubescent monkeys.« less

Mechanical Evaluation of Unobstructing Magnetic Microactuators for Implantable Ventricular Catheters

PubMed Central

Lee, Hyowon; Kolahi, Kameran; Bergsneider, Marvin; Judy, Jack W.

2017-01-01

Here, we report on the development and evaluation of novel unobstructing magnetic microactuators for maintaining the patency of implantable ventricular catheters used in hydrocephalus application. The treatment of hydrocephalus requires chronic implantation of a shunt system to divert excess cerebrospinal fluid from the brain. These shunt systems suffer from a high failure rate (>40%) within the first year of implantation, often due to biological accumulation. Previously, we have shown that magnetic microactuators can be used to remove biological blockage. The new cantilever-based magnetic microactuator presented in this paper improves upon the previous torsional design using a bimorph to induce a postrelease out-of-plane deflection that will prevent the device from occluding the pore at rest. The mechanical evaluations (i.e., postrelease deflection, static and dynamic responses) of fabricated devices are reported and compared with theoretical values. PMID:29151776

23.4% saline decreases brain tissue volume in severe hepatic encephalopathy as assessed by a quantitative computed tomography marker

PubMed Central

Liotta, Eric M; Lizza, Bryan D; Romanova, Anna L; Guth, James C; Berman, Michael D; Carroll, Timothy J; Francis, Brandon; Ganger, Daniel; Ladner, Daniela P; Maas, Matthew B; Naidech, Andrew M

2016-01-01

Objective Cerebral edema is common in severe hepatic encephalopathy and may be life-threatening. Bolus 23.4% hypertonic saline (HTS) improves surveillance neuromonitoring scores, although its mechanism of action is not clearly established. We investigated the hypothesis that bolus HTS decreases cerebral edema in severe hepatic encephalopathy utilizing a quantitative technique to measure brain and CSF volume changes. Design Retrospective analysis of serial computed tomography (CT) scans and clinical data for a case-control series was performed. Setting Intensive care units of a tertiary care hospital. Patients Patients with severe hepatic encephalopathy treated with 23.4% HTS and control patients who did not receive 23.4% HTS. Methods We used clinically obtained CT scans to measure volumes of the ventricles, intracranial CSF, and brain using a previously validated semi-automated technique (Analyze Direct; Overland Park, KS). Volumes before and after 23.4% HTS were compared with Wilcoxon signed-rank test. Associations between total CSF volume, ventricular volume, serum sodium, and Glasgow Coma Scale Scores were assessed using Spearman correlation. Results Eleven patients with 18 administrations of 23.4% HTS met inclusion criteria. Total CSF (median 47.6 [35.1–69.4] to 61.9 [47.7–87.0] mL, p<0.001) and ventricular volumes (median 8.0 [6.9–9.5] to 9.2 [7.8–11.9] mL, p=0.002) increased and Glasgow Coma Scale Scores improved (median 4 [3–6] to 7 [6–9], p=0.008) after 23.4% HTS. In contrast, total CSF and ventricular volumes decreased in untreated control patients. Serum sodium increase was associated with increase in total CSF volume (r=0.83, p<0.001) and change in total CSF volume was associated with ventricular volume change (r=0.86, p<0.001). Conclusions Total CSF and ventricular volumes increased after 23.4% HTS, consistent with a reduction in brain tissue volume. Total CSF and ventricular volume change may be useful quantitative measures to assess cerebral edema in severe hepatic encephalopathy. PMID:26308431

Preferential cephalic redistribution of left ventricular cardiac output during therapeutic hypothermia for perinatal hypoxic-ischemic encephalopathy

PubMed Central

Hochwald, Ori; Jabr, Mohammed; Osiovich, Horacio; Miller, Steven P.; McNamara, Patrick J.; Lavoie, Pascal M.

2015-01-01

Objective To determine the relationship between left ventricular cardiac output (LVCO), superior vena cava (SVC) flow, and brain injury during whole-body therapeutic hypothermia. Study design Sixteen newborns with moderate or severe hypoxic-ischemic encephalopathy were studied using echocardiography during and immediately after therapeutic hypothermia. Measures were also compared with 12 healthy newborns of similar postnatal age. Newborns undergoing therapeutic hypothermia also had a cerebral magnetic resonance imaging as part of routine clinical care on postnatal day 3–4. Results LVCO was markedly reduced (mean+/−SD: 126+/−38 mL/kg/min) during therapeutic hypothermia, whereas SVC flow was maintained within expected normal values (88+/− 27 mL/kg/min) such that it represented 70% of the LVCO. The reduction in LVCO during therapeutic hypothermia was mainly accounted by a reduction in heart rate (99 +/− 13 BPM versus 123 +/− 17 BPM; p<0.001) compared to immediately post-warming, in the context of myocardial dysfunction. Neonates with documented brain injury on MRI showed higher SVC flow pre-rewarming, compared to newborns without brain injury (p=0.013). Conclusion Newborns with perinatal hypoxic-ischemic encephalopathy showed a preferential systemic-to cerebral redistribution of cardiac blood flow during whole-body therapeutic hypothermia, which may reflect a lack of cerebral vascular adaptation in newborns with more severe brain injury. PMID:24582011

Preferential cephalic redistribution of left ventricular cardiac output during therapeutic hypothermia for perinatal hypoxic-ischemic encephalopathy.

PubMed

Hochwald, Ori; Jabr, Mohammad; Osiovich, Horacio; Miller, Steven P; McNamara, Patrick J; Lavoie, Pascal M

2014-05-01

To determine the relationship between left ventricular cardiac output (LVCO), superior vena cava (SVC) flow, and brain injury during whole-body therapeutic hypothermia. Sixteen newborns with moderate or severe hypoxic-ischemic encephalopathy were studied using echocardiography during and immediately after therapeutic hypothermia. Measures were also compared with 12 healthy newborns of similar postnatal age. Newborns undergoing therapeutic hypothermia also had cerebral magnetic resonance imaging as part of routine clinical care on postnatal day 3-4. LVCO was markedly reduced (mean ± SD 126 ± 38 mL/kg/min) during therapeutic hypothermia, whereas SVC flow was maintained within expected normal values (88 ± 27 mL/kg/min) such that SVC flow represented 70% of the LVCO. The reduction in LVCO during therapeutic hypothermia was mainly accounted by a reduction in heart rate (99 ± 13 vs 123 ± 17 beats/min; P < .001) compared with immediately postwarming in the context of myocardial dysfunction. Neonates with brain injury on magnetic resonance imaging had higher SVC flow prerewarming, compared with newborns without brain injury (P = .013). Newborns with perinatal hypoxic-ischemic encephalopathy showed a preferential systemic-to-cerebral redistribution of cardiac blood flow during whole-body therapeutic hypothermia, which may reflect a lack of cerebral vascular adaptation in newborns with more severe brain injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Conditional N-WASP knockout in mouse brain implicates actin cytoskeleton regulation in hydrocephalus pathology.

PubMed

Jain, Neeraj; Lim, Lee Wei; Tan, Wei Ting; George, Bhawana; Makeyev, Eugene; Thanabalu, Thirumaran

2014-04-01

Cerebrospinal fluid (CSF) is produced by the choroid plexus and moved by multi-ciliated ependymal cells through the ventricular system of the vertebrate brain. Defects in the ependymal layer functionality are a common cause of hydrocephalus. N-WASP (Neural-Wiskott Aldrich Syndrome Protein) is a brain-enriched regulator of actin cytoskeleton and N-WASP knockout caused embryonic lethality in mice with neural tube and cardiac abnormalities. To shed light on the role of N-WASP in mouse brain development, we generated N-WASP conditional knockout mouse model N-WASP(fl/fl); Nestin-Cre (NKO-Nes). NKO-Nes mice were born with Mendelian ratios but exhibited reduced growth characteristics compared to their littermates containing functional N-WASP alleles. Importantly, all NKO-Nes mice developed cranial deformities due to excessive CSF accumulation and did not survive past weaning. Coronal brain sections of these animals revealed dilated lateral ventricles, defects in ciliogenesis, loss of ependymal layer integrity, reduced thickness of cerebral cortex and aqueductal stenosis. Immunostaining for N-cadherin suggests that ependymal integrity in NKO-Nes mice is lost as compared to normal morphology in the wild-type controls. Moreover, scanning electron microscopy and immunofluorescence analyses of coronal brain sections with anti-acetylated tubulin antibodies revealed the absence of cilia in ventricular walls of NKO-Nes mice indicative of ciliogenesis defects. N-WASP deficiency does not lead to altered expression of N-WASP regulatory proteins, Fyn and Cdc42, which have been previously implicated in hydrocephalus pathology. Taken together, our results suggest that N-WASP plays a critical role in normal brain development and implicate actin cytoskeleton regulation as a vulnerable axis frequently deregulated in hydrocephalus. Copyright © 2014 Elsevier Inc. All rights reserved.

Normative biometry of the fetal brain using magnetic resonance imaging.

PubMed

Kyriakopoulou, Vanessa; Vatansever, Deniz; Davidson, Alice; Patkee, Prachi; Elkommos, Samia; Chew, Andrew; Martinez-Biarge, Miriam; Hagberg, Bibbi; Damodaram, Mellisa; Allsop, Joanna; Fox, Matt; Hajnal, Joseph V; Rutherford, Mary A

2017-07-01

The fetal brain shows accelerated growth in the latter half of gestation, and these changes can be captured by 2D and 3D biometry measurements. The aim of this study was to quantify brain growth in normal fetuses using Magnetic Resonance Imaging (MRI) and to produce reference biometry data and a freely available centile calculator ( https://www.developingbrain.co.uk/fetalcentiles/ ). A total of 127 MRI examinations (1.5 T) of fetuses with a normal brain appearance (21-38 gestational weeks) were included in this study. 2D and 3D biometric parameters were measured from slice-to-volume reconstructed images, including 3D measurements of supratentorial brain tissue, lateral ventricles, cortex, cerebellum and extra-cerebral CSF and 2D measurements of brain biparietal diameter and fronto-occipital length, skull biparietal diameter and occipitofrontal diameter, head circumference, transverse cerebellar diameter, extra-cerebral CSF, ventricular atrial diameter, and vermis height, width, and area. Centiles were constructed for each measurement. All participants were invited for developmental follow-up. All 2D and 3D measurements, except for atrial diameter, showed a significant positive correlation with gestational age. There was a sex effect on left and total lateral ventricular volumes and the degree of ventricular asymmetry. The 5th, 50th, and 95th centiles and a centile calculator were produced. Developmental follow-up was available for 73.1% of cases [mean chronological age 27.4 (±10.2) months]. We present normative reference charts for fetal brain MRI biometry at 21-38 gestational weeks. Developing growth trajectories will aid in the better understanding of normal fetal brain growth and subsequently of deviations from typical development in high-risk pregnancies or following premature delivery.

Using ventricular modeling to robustly probe significant deep gray matter pathologies: Application to cerebral palsy.

PubMed

Pagnozzi, Alex M; Shen, Kaikai; Doecke, James D; Boyd, Roslyn N; Bradley, Andrew P; Rose, Stephen; Dowson, Nicholas

2016-11-01

Understanding the relationships between the structure and function of the brain largely relies on the qualitative assessment of Magnetic Resonance Images (MRIs) by expert clinicians. Automated analysis systems can support these assessments by providing quantitative measures of brain injury. However, the assessment of deep gray matter structures, which are critical to motor and executive function, remains difficult as a result of large anatomical injuries commonly observed in children with Cerebral Palsy (CP). Hence, this article proposes a robust surrogate marker of the extent of deep gray matter injury based on impingement due to local ventricular enlargement on surrounding anatomy. Local enlargement was computed using a statistical shape model of the lateral ventricles constructed from 44 healthy subjects. Measures of injury on 95 age-matched CP patients were used to train a regression model to predict six clinical measures of function. The robustness of identifying ventricular enlargement was demonstrated by an area under the curve of 0.91 when tested against a dichotomised expert clinical assessment. The measures also showed strong and significant relationships for multiple clinical scores, including: motor function (r 2  = 0.62, P < 0.005), executive function (r 2  = 0.55, P < 0.005), and communication (r 2  = 0.50, P < 0.005), especially compared to using volumes obtained from standard anatomical segmentation approaches. The lack of reliance on accurate anatomical segmentations and its resulting robustness to large anatomical variations is a key feature of the proposed automated approach. This coupled with its strong correlation with clinically meaningful scores, signifies the potential utility to repeatedly assess MRIs for clinicians diagnosing children with CP. Hum Brain Mapp 37:3795-3809, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cerebral atrophy in elderly with subjective memory complaints.

PubMed

Palm, Walter M; Ferrarini, Luca; van der Flier, Wiesje M; Westendorp, Rudi G J; Bollen, Eduard L E M; Middelkoop, Huub A M; Milles, Julien R; van der Grond, Jeroen; van Buchem, Mark A

2013-08-01

To evaluate ventricular shape differences along the complete surface of the lateral and third ventricles of persons with subjective memory complaints (MC). We included 28 controls and 21 persons with MC. FLAIR, T2, and PD-weighted brain MRI scans were acquired at 1.5 Tesla, followed by semi-automated segmentation of the lateral and third ventricles, and local shape difference analysis based on growing and adaptive meshes. Ventricular meshes were used to highlight local areas with significant differences between controls and persons with MC, determined by permutation tests with a predefined threshold (P = 0.01). Compared with control subjects, relevant differences were found in the shape of the ventricular surface adjacent to the thalamus and corona radiata in persons with MC. Before correction for multiple comparisons, relevant differences were also found in the shape of the ventricular surface adjacent to the corpus callosum, hippocampus, and amydala. Our findings suggest the presence of localized structural brain differences in patients with subjective memory complaints in the thalamus and the corona radiata. Copyright © 2013 Wiley Periodicals, Inc.

Cardiac structure and function, and ventricular-arterial interaction 11 years following a pregnancy with preeclampsia.

PubMed

Al-Nashi, Maha; Eriksson, Maria J; Östlund, Eva; Bremme, Katarina; Kahan, Thomas

2016-04-01

Preeclampsia (PE) is associated with acute left ventricular dysfunction. Whether these changes eventually resolve remains unclear. This study assessed left and right ventricular structure and function, and ventricular-arterial interaction in 15 women 11 years after a pregnancy with PE and 16 matched control subjects with a normal pregnancy. We found normal left and right ventricular dimensions, systolic function, and global left ventricular strain, with no differences between the groups. In addition, indices of diastolic function, left and right atrial size, and amino-terminal pro-brain natriuretic peptide were normal and did not differ between the groups. Women with a previous PE had impaired night/day ratios for systolic and diastolic ambulatory blood pressure. However, indices of aortic stiffness or ventricular-arterial coupling did not differ between the groups. In conclusion, we could not demonstrate remaining alterations in systolic or diastolic left or right ventricular function, or in ventricular-arterial interaction in women 11 years after PE. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single-Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.

PubMed

Fukushima, Norihide; Tatsumi, Eisuke; Seguchi, Osamu; Takewa, Yoshiaki; Hamasaki, Toshimitsu; Onda, Kaori; Yamamoto, Haruko; Hayashi, Teruyuki; Fujita, Tomoyuki; Kobayashi, Junjiro

2018-06-08

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A total of nine patients will be enrolled in the study. The study was planned using Simon's minimax two-stage phase design. The primary endpoint is a composite of survival free of device-related serious adverse events and complications during device support. For left ventricular assistance, withdrawal of a trial device due to cardiac function recovery or exchange to other ventricular assist devices (VADs) for the purpose of bridge to transplantation (BTT) during 30 days after implantation will be considered study successes. For right ventricular assistance, withdrawal of tal device due to right ventricular function recovery within 30 days after implantation will be considered a study success. Secondary objectives include changes in brain natriuretic peptide levels (7 days after implantation of a trial device and the day of withdrawal of a trial device), period of mechanical ventricular support, changes in left ventricular ejection fraction (7 days after implantation of a trial device and the day of withdrawal of a trial device), and changes in left ventricular diastolic dimension (7 days after implantation of a trial device and the day of withdrawal of a trial device). We will disseminate the findings through regional, national, and international conferences and through peer-reviewed journals. UMIN Clinical Trials Registry (UMIN-CTR; R000033243) registered on 8 September 2017.

Successful treatment of Dandy-Walker syndrome by endoscopic third ventriculostomy in a 6-month-old girl with progressive hydrocephalus: a case report and literature review.

PubMed

Hu, Chih-Fen; Fan, Hueng-Chuen; Chang, Cheng-Fu; Wang, Chih-Chien; Chen, Shyi-Jou

2011-02-01

Dandy-Walker syndrome (DWS) is a congenital brain malformation involving the cerebellum and fourth ventricle. We report a 6-month-old girl with DWS presenting an initially normal ventricular system and mild cyst-like lesion over the posterior fossa as assessed by postnatal brain sonography. However, symptoms and signs of increased intracranial cerebral pressure in terms of frequent vomiting and tense anterior fontanel developed, and these were associated with mild hypotonia and poor neck support, and upward-gaze palsy at the age of 6 months. Magnetic resonance imaging revealed a huge cystic lesion of the fourth ventricle, which filled the posterior fossa and ventricular dilatation. The tentorium was progressively displaced upward by the cyst. A nearly complete agenesis of the cerebellar vermis was also confirmed. After a successful endoscopic third ventriculostomy, a series of brain magnetic resonance imaging scans, taken during a follow-up survey, showed normal lateral and third ventricles. Consequently, symptoms of intracranial cerebral pressure resolved, and a developmental milestone was achieved. In conclusion, DWS can be confirmed postpartum, and endoscopic third ventriculostomy was found to be a preferential operative procedure for DWS with hydrocephalus. It may be effective for patients younger than 1 year. Copyright © 2011. Published by Elsevier B.V.

Dandy-Walker malformation: analysis of 19 cases.

PubMed

Alexiou, George A; Sfakianos, George; Prodromou, Neofytos

2010-02-01

Dandy-Walker malformation is a congenital disorder that involves the cerebellum and fourth ventricle. Regarding treatment, there is still controversy over the optimum surgical management. In the current study, we present 19 consecutive cases of Dandy-Walker malformation diagnosed between January 1992 and January 2008 that were treated in our institute. All patients presented with hydrocephalus at the time of diagnosis and were treated surgically. Combined drainage of the ventricular system and posterior fossa cyst, using a 3-way connector was performed in 5 patients. Posterior fossa cyst drainage alone was performed in 10 patients and the remaining 4 patients were treated by ventricular drainage alone. All patients improved after treatment. Dandy-Walker malformation is a developmental abnormality of the central nervous system associated with various brain and extracranial abnormalities. Surgical treatment remains controversial, whereas prognosis varies greatly according to the severity of syndrome and associated comorbidities.

Phenotyping Cardiac Arrest: Bench and Bedside Characterization of Brain and Heart Injury Based on Etiology.

PubMed

Uray, Thomas; Lamade, Andrew; Elmer, Jonathan; Drabek, Tomas; Stezoski, Jason P; Missé, Amalea; Janesko-Feldman, Keri; Garman, Robert H; Chen, Niel; Kochanek, Patrick M; Dezfulian, Cameron; Callaway, Clifton W; Doshi, Ankur A; Frisch, Adam; Guyette, Francis X; Reynolds, Josh C; Rittenberger, Jon C

2018-06-01

Cardiac arrest etiology may be an important source of between-patient heterogeneity, but the impact of etiology on organ injury is unknown. We tested the hypothesis that asphyxial cardiac arrest results in greater neurologic injury than cardiac etiology cardiac arrest (ventricular fibrillation cardiac arrest), whereas ventricular fibrillation cardiac arrest results in greater cardiovascular dysfunction after return of spontaneous circulation. Prospective observational human and randomized animal study. University laboratory and ICUs. Five-hundred forty-three cardiac arrest patients admitted to ICU. Seventy-five male Sprague-Dawley rats. We examined neurologic and cardiovascular injury in Isoflurane-anesthetized rat cardiac arrest models matched by ischemic time. Hemodynamic and neurologic outcomes were assessed after 5 minutes no flow asphyxial cardiac arrest or ventricular fibrillation cardiac arrest. Comparison was made to injury patterns observed after human asphyxial cardiac arrest or ventricular fibrillation cardiac arrest. In rats, cardiac output (20 ± 10 vs 45 ± 9 mL/min) and pH were lower and lactate higher (9.5 ± 1.0 vs 6.4 ± 1.3 mmol/L) after return of spontaneous circulation from ventricular fibrillation cardiac arrest versus asphyxial cardiac arrest (all p < 0.01). Asphyxial cardiac arrest resulted in greater early neurologic deficits, 7-day neuronal loss, and reduced freezing time (memory) after conditioned fear (all p < 0.05). Brain antioxidant reserves were more depleted following asphyxial cardiac arrest. In adjusted analyses, human ventricular fibrillation cardiac arrest was associated with greater cardiovascular injury based on peak troponin (7.8 ng/mL [0.8-57 ng/mL] vs 0.3 ng/mL [0.0-1.5 ng/mL]) and ejection fraction by echocardiography (20% vs 55%; all p < 0.0001), whereas asphyxial cardiac arrest was associated with worse early neurologic injury and poor functional outcome at hospital discharge (n = 46 [18%] vs 102 [44%]; p < 0.0001). Most ventricular fibrillation cardiac arrest deaths (54%) were the result of cardiovascular instability, whereas most asphyxial cardiac arrest deaths (75%) resulted from neurologic injury (p < 0.0001). In transcending rat and human studies, we find a consistent phenotype of heart and brain injury after cardiac arrest based on etiology: ventricular fibrillation cardiac arrest produces worse cardiovascular dysfunction, whereas asphyxial cardiac arrest produces worsened neurologic injury associated with greater oxidative stress.

Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency.

PubMed

Yang, Xuejun; Zhou, Hua; Qu, Huiyan; Liu, Weifang; Huang, Xiaojin; Shun, Yating; He, Liqun

2014-01-01

To observe the efficacy of Shenxinning Decoction (SXND) in ventricular remodeling in AT1 receptor-knockout (AT1-KO) mice with chronic renal insufficiency (CRI). AT1-KO mice modeled with subtotal (5/6) nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN), serum creatinine (SCr), brain natriuretic peptide (BNP), echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF), collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1) of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice's BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. SXND may antagonize the renin-angiotensin system (RAS) and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1.

Reduction of ventricular size after shunting for normal pressure hydrocephalus related to CSF dynamics before shunting.

PubMed Central

Tans, J T; Poortvliet, D C

1988-01-01

Reduction of ventricular size was determined by repeated computed tomography in 30 adult patients shunted for normal pressure hydrocephalus (NPH) and related to the pressure-volume index (PVI) and resistance to outflow of cerebrospinal fluid (Rcsf) measured before shunting. Rapid and marked reduction of ventricular size (n = 10) was associated with a significantly lower PVI than slow and moderate to marked (n = 13) or minimal to mild reduction (n = 7). Otherwise no relationship could be found between the reduction of ventricular size and PVI or Rcsf. It is concluded that both rate and magnitude of reduction of ventricular size after shunting for NPH are extremely variable. High brain elasticity seems to be the best predictor of rapid and marked reduction. PMID:3379425

Donor Preconditioning After the Onset of Brain Death With Dopamine Derivate n-Octanoyl Dopamine Improves Early Posttransplant Graft Function in the Rat.

PubMed

Li, S; Korkmaz-Icöz, S; Radovits, T; Ruppert, M; Spindler, R; Loganathan, S; Hegedűs, P; Brlecic, P; Theisinger, B; Theisinger, S; Höger, S; Brune, M; Lasitschka, F; Karck, M; Yard, B; Szabó, G

2017-07-01

Heart transplantation is the therapy of choice for end-stage heart failure. However, hemodynamic instability, which has been demonstrated in brain-dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n-octanoyl-dopamine (NOD) improves donor cardiac and graft function after transplantation. Donor rats were given a continuous intravenous infusion of either NOD (0.882 mg/kg/h, BDD+NOD, n = 6) or a physiological saline vehicle (BDD, n = 9) for 5 h after the induction of brain death by inflation of a subdural balloon catheter. Controls were sham-operated (n = 9). In BDD, decreased left-ventricular contractility (ejection fraction; maximum rate of rise of left-ventricular pressure; preload recruitable stroke work), relaxation (maximum rate of fall of left-ventricular pressure; Tau), and increased end-diastolic stiffness were significantly improved after the NOD treatment. Following the transplantation, the NOD-treatment of BDD improved impaired systolic function and ventricular relaxation. Additionally, after transplantation increased interleukin-6, tumor necrosis factor TNF-α, NF-kappaB-p65, and nuclear factor (NF)-kappaB-p105 gene expression, and increased caspase-3, TNF-α and NF-kappaB protein expression could be significantly downregulated by the NOD treatment compared to BDD. BDD postconditioning with NOD through downregulation of the pro-apoptotic factor caspase-3, pro-inflammatory cytokines, and NF-kappaB may protect the heart against the myocardial injuries associated with brain death and ischemia/reperfusion. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Diagnostic Accuracy of Right Ventricular Dysfunction Markers in Normotensive Emergency Department Patients With Acute Pulmonary Embolism.

PubMed

Weekes, Anthony J; Thacker, Gregory; Troha, Daniel; Johnson, Angela K; Chanler-Berat, Jordan; Norton, H James; Runyon, Michael

2016-09-01

We determine the diagnostic accuracy of goal-directed echocardiography, cardiac biomarkers, and computed tomography (CT) in early identification of severe right ventricular dysfunction in normotensive emergency department patients with pulmonary embolism compared with comprehensive echocardiography. This was a prospective observational study of consecutive normotensive patients with confirmed pulmonary embolism. Investigators, blinded to clot burden and biomarkers, performed qualitative goal-directed echocardiography for right ventricular dysfunction: right ventricular enlargement (diameter greater than or equal to that of the left ventricle), severe right ventricular systolic dysfunction, and septal bowing. Brain natriuretic peptide and troponin cutoffs of greater than or equal to 90 pg/mL and greater than or equal to 0.07 ng/mL and CT right ventricular:left ventricular diameter ratio greater than or equal to 1.0 were also compared with comprehensive echocardiography. One hundred sixteen normotensive pulmonary embolism patients (111 confirmed by CT, 5 by ventilation-perfusion scan) were enrolled. Twenty-six of 116 patients (22%) had right ventricular dysfunction on comprehensive echocardiography. Goal-directed echocardiography had a sensitivity of 100% (95% confidence interval [CI] 87% to 100%), specificity of 99% (95% CI 94% to 100%), positive likelihood ratio (+LR) of 90.0 (95% CI 16.3 to 499.8), and negative likelihood ratio (-LR) of 0 (95% CI 0 to 0.13). Brain natriuretic peptide had a sensitivity of 88% (95% CI 70% to 98%), specificity of 68% (95% CI 57% to 78%), +LR of 2.8 (95% CI 2.0 to 3.9), and -LR of 0.17 (95% CI 0.06 to 0.43). Troponin had a sensitivity of 62% (95% CI 41% to 80%), specificity of 93% (95% CI 86% to 98%), +LR of 9.2 (95% CI 4.1 to 20.9), and -LR of 0.41 (95% CI 0.24 to 0.62). CT had a sensitivity of 91% (95% CI 72% to 99%), specificity of 79% (95% CI 69% to 87%), +LR of 4.3 (95% CI 2.8 to 6.7), and -LR of 0.11 (95% CI 0.03 to 0.34). Goal-directed echocardiography was highly accurate for early severe right ventricular dysfunction identification and pulmonary embolism risk-stratification. Brain natriuretic peptide was sensitive but less specific, whereas troponin had lower sensitivity but higher specificity. CT had good sensitivity and moderate specificity. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Ventricular Catheter Systems with Subcutaneous Reservoirs (Ommaya Reservoirs) in Pediatric Patients with Brain Tumors: Infections and Other Complications.

PubMed

Gerber, Nicolas U; Müller, Anna; Bellut, David; Bozinov, Oliver; Berger, Christoph; Grotzer, Michael A

2015-12-01

This study aims to describe complications related to ventricular catheter systems with subcutaneous reservoirs (VCSR) (such as Ommaya reservoirs) in pediatric patients with brain tumors. Retrospective analysis of consecutive patients with a total of 31 VCSR treated at the Children's University Hospital of Zurich, Switzerland. A total of 20 patients with a median age of 3.3 years at VCSR implantation received 31 VCSR. Overall, 19 complications in 11 patients were recorded: 7 patients had a VCSR-related infection with coagulase-negative staphylococci, 4 of these probably as a surgical complication and 3 probably related to VCSR use. Systemic perioperative prophylaxis was administered in 22 cases, and intraventricular vancomycin and gentamicin were given in 8 cases (none of which subsequently developed an infection). Other complications included wound dehiscence, catheter malplacement, and leakage of cerebrospinal fluid. Overall, 17 VCSR were explanted due to complications. Infections were the most frequent VCSR-related complication. In our own institution, the high rate of complications led to the definition of a bundle of measures as a standard operating procedure for VCSR placement and use. Prospective studies in larger patient collectives are warranted to better identify risk factors and evaluate preventive measures such as the administration of perioperative antibiotics and the use of antimicrobial coating of catheters. Georg Thieme Verlag KG Stuttgart · New York.

Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder.

PubMed

Palmen, Saskia J M C; Hulshoff Pol, Hilleke E; Kemner, Chantal; Schnack, Hugo G; Durston, Sarah; Lahuis, Bertine E; Kahn, René S; Van Engeland, Herman

2005-04-01

To establish whether high-functioning children with autism spectrum disorder (ASD) have enlarged brains in later childhood, and if so, whether this enlargement is confined to the gray and/or to the white matter and whether it is global or more prominent in specific brain regions. Brain MRI scans were acquired from 21 medication-naive, high-functioning children with ASD between 7 and 15 years of age and 21 comparison subjects matched for gender, age, IQ, height, weight, handedness, and parental education, but not pubertal status. Patients showed a significant increase of 6% in intracranium, total brain, cerebral gray matter, cerebellum, and of more than 40% in lateral and third ventricles compared to controls. The cortical gray-matter volume was evenly affected in all lobes. After correction for brain volume, ventricular volumes remained significantly larger in patients. High-functioning children with ASD showed a global increase in gray-matter, but not white-matter and cerebellar volume, proportional to the increase in brain volume, and a disproportional increase in ventricular volumes, still present after correction for brain volume. Advanced pubertal development in the patients compared to the age-matched controls may have contributed to the findings reported in the present study.

Mechanosensory Genes Pkd1 and Pkd2 Contribute to the Planar Polarization of Brain Ventricular Epithelium

PubMed Central

Herranz-Pérez, Vicente; Nakatani, Jin; Boletta, Alessandra; García-Verdugo, José Manuel

2015-01-01

Directional beating of ependymal (E) cells' cilia in the walls of the ventricles in the brain is essential for proper CSF flow. E cells display two forms of planar cell polarity (PCP): rotational polarity of individual cilium and translational polarity (asymmetric positioning of cilia in the apical area). The orientation of individual E cells varies according to their location in the ventricular wall (location-specific PCP). It has been hypothesized that hydrodynamic forces on the apical surface of radial glia cells (RGCs), the embryonic precursors of E cells, could guide location-specific PCP in the ventricular epithelium. However, the detection mechanisms for these hydrodynamic forces have not been identified. Here, we show that the mechanosensory proteins polycystic kidney disease 1 (Pkd1) and Pkd2 are present in primary cilia of RGCs. Ablation of Pkd1 or Pkd2 in Nestin-Cre;Pkd1flox/flox or Nestin-Cre;Pkd2flox/flox mice, affected PCP development in RGCs and E cells. Early shear forces on the ventricular epithelium may activate Pkd1 and Pkd2 in primary cilia of RGCs to properly polarize RGCs and E cells. Consistently, Pkd1, Pkd2, or primary cilia on RGCs were required for the proper asymmetric localization of the PCP protein Vangl2 in E cells' apical area. Analyses of single- and double-heterozygous mutants for Pkd1 and/or Vangl2 suggest that these genes function in the same pathway to establish E cells' PCP. We conclude that Pkd1 and Pkd2 mechanosensory proteins contribute to the development of brain PCP and prevention of hydrocephalus. SIGNIFICANCE STATEMENT This study identifies key molecules in the development of planar cell polarity (PCP) in the brain and prevention of hydrocephalus. Multiciliated ependymal (E) cells within the brain ventricular epithelium generate CSF flow through ciliary beating. E cells display location-specific PCP in the orientation and asymmetric positioning of their cilia. Defects in this PCP can result in hydrocephalus. Hydrodynamic forces on radial glial cells (RGCs), the embryonic progenitors of E cells, have been suggested to guide PCP. We show that the mechanosensory proteins Pkd1 and Pkd2 localize to primary cilia in RGCs, and their ablation disrupts the development of PCP in E cells. Early shear forces on RGCs may activate Pkd1 and Pkd2 in RGCs' primary cilia to properly orient E cells. This study identifies key molecules in the development of brain PCP and prevention of hydrocephalus. PMID:26245976

Independent effects of both right and left ventricular function on plasma brain natriuretic peptide.

PubMed

Vogelsang, Thomas Wiis; Jensen, Ruben J; Monrad, Astrid L; Russ, Kaspar; Olesen, Uffe H; Hesse, Birger; Kjaer, Andreas

2007-09-01

Brain natriuretic peptide (BNP) is increased in heart failure; however, the relative contribution of the right and left ventricles is largely unknown. To investigate if right ventricular function has an independent influence on plasma BNP concentration. Right (RVEF), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume index (LVEDVI) were determined in 105 consecutive patients by first-pass radionuclide ventriculography (FP-RNV) and multiple ECG-gated equilibrium radionuclide ventriculography (ERNV), respectively. BNP was analyzed by immunoassay. Mean LVEF was 0.51 (range 0.10-0.83) with 36% having a reduced LVEF (<0.50). Mean RVEF was 0.50 (range 0.26-0.78) with 43% having a reduced RVEF (<0.50). The mean LVEDVI was 92 ml/m2 with 22% above the upper normal limit (117 ml/m2). Mean BNP was 239 pg/ml range (0.63-2523). In univariate linear regression analysis LVEF, LVEDVI and RVEF all correlated significantly with log BNP (p<0.0001). In a multivariate analysis only RVEF and LVEF remained significant. The parameter estimates of the final adjusted model indicated that RVEF and LVEF influence on log BNP were of the same magnitude. BNP, which is a strong prognostic marker in heart failure, independently depends on both left and right ventricular systolic function. This might, at least in part, explain why BNP holds stronger prognostic value than LVEF alone.

Fourth ventricular thyrotropin induces satiety and increases body temperature in rats.

PubMed

Smedh, Ulrika; Scott, Karen A; Moran, Timothy H

2018-05-01

Besides its well-known action to stimulate thyroid hormone release, thyrotropin mRNA is expressed within the brain, and thyrotropin and its receptor have been shown to be present in brain areas that control feeding and gastrointestinal function. Here, the hypothesis that thyrotropin acts on receptors in the hindbrain to alter food intake and/or gastric function was tested. Fourth ventricular injections of thyrotropin (0.06, 0.60, and 6.00 µg) were given to rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle. Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In contrast, subcutaneous administration of corresponding thyrotropin doses had no effect on nutrient intake. The highest effective dose of fourth ventricular thyrotropin (6 µg) did not produce a conditioned flavor avoidance in a standardized two-bottle test, nor did it affect water intake or gastric emptying of glucose. Thyrotropin injected in the fourth ventricle produced a small but significant increase in rectal temperature and lowered plasma levels of tri-iodothyronin but did not affect plasma levels of thyroxine. In addition, there was a tendency toward a reduction in blood glucose 2 h after fourth ventricular thyrotropin injection ( P = 0.056). In conclusion, fourth ventricular thyrotropin specifically inhibits food intake, increases core temperature, and lowers plasma levels of tri-iodothyronin but does not affect gastromotor function.

QR in V1--an ECG sign associated with right ventricular strain and adverse clinical outcome in pulmonary embolism.

PubMed

Kucher, Nils; Walpoth, Nazan; Wustmann, Kerstin; Noveanu, Markus; Gertsch, Marc

2003-06-01

To test the hypothesis that Qr in V(1)is a predictor of pulmonary embolism, right ventricular strain, and adverse clinical outcome. ECG's from 151 patients with suspected pulmonary embolism were blindly interpreted by two observers. Echocardiography, troponin I, and pro-brain natriuretic peptide levels were obtained in 75 patients with pulmonary embolism. Qr in V(1)(14 vs 0 in controls; p<0.0001) and ST elevation in V(1)> or =1 mV (15 vs 1 in controls; p=0.0002) were more frequently present in patients with pulmonary embolism. Sensitivity and specificity of Qr in V(1)and T wave inversion in V(2)for predicting right ventricular dysfunction were 31/97% and 45/94%, respectively. Three of five patients who died in-hospital and 11 of 20 patients with a complicated course, presented with Qr in V(1). After adjustment for right ventricular strain including ECG, echocardiography, pro-brain natriuretic peptide and troponin I levels, Qr in V(1)(OR 8.7, 95%CI 1.4-56.7; p=0.02) remained an independent predictor of adverse outcome. Among the ECG signs seen in patients with acute pulmonary embolism, Qr in V(1)is closely related to the presence of right ventricular dysfunction, and is an independent predictor of adverse clinical outcome.

Robust space-time extraction of ventricular surface evolution using multiphase level sets

NASA Astrophysics Data System (ADS)

Drapaca, Corina S.; Cardenas, Valerie; Studholme, Colin

2004-05-01

This paper focuses on the problem of accurately extracting the CSF-tissue boundary, particularly around the ventricular surface, from serial structural MRI of the brain acquired in imaging studies of aging and dementia. This is a challenging problem because of the common occurrence of peri-ventricular lesions which locally alter the appearance of white matter. We examine a level set approach which evolves a four dimensional description of the ventricular surface over time. This has the advantage of allowing constraints on the contour in the temporal dimension, improving the consistency of the extracted object over time. We follow the approach proposed by Chan and Vese which is based on the Mumford and Shah model and implemented using the Osher and Sethian level set method. We have extended this to the 4 dimensional case to propagate a 4D contour toward the tissue boundaries through the evolution of a 5D implicit function. For convergence we use region-based information provided by the image rather than the gradient of the image. This is adapted to allow intensity contrast changes between time frames in the MRI sequence. Results on time sequences of 3D brain MR images are presented and discussed.

Does left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study.

PubMed

Patel, Sheila K; Restrepo, Carolina; Werden, Emilio; Churilov, Leonid; Ekinci, Elif I; Srivastava, Piyush M; Ramchand, Jay; Wai, Bryan; Chambers, Brian; O'Callaghan, Christopher J; Darby, David; Hachinski, Vladimir; Cumming, Toby; Donnan, Geoff; Burrell, Louise M; Brodtmann, Amy

2017-04-07

Cognitive impairment is common in type 2 diabetes mellitus, and there is a strong association between type 2 diabetes and Alzheimer's disease. However, we do not know which type 2 diabetes patients will dement or which biomarkers predict cognitive decline. Left ventricular hypertrophy (LVH) is potentially such a marker. LVH is highly prevalent in type 2 diabetes and is a strong, independent predictor of cardiovascular events. To date, no studies have investigated the association between LVH and cognitive decline in type 2 diabetes. The Diabetes and Dementia (D2) study is designed to establish whether patients with type 2 diabetes and LVH have increased rates of brain atrophy and cognitive decline. The D2 study is a single centre, observational, longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes: 50% with LVH (case) and 50% without LVH (control). It will assess change in cardiovascular risk, brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 24 months. The primary outcome is brain volume change at 24 months. The co-primary outcome is the presence of cognitive decline at 24 months. The secondary outcome is change in left ventricular mass associated with brain atrophy and cognitive decline at 24 months. The D2 study will test the hypothesis that patients with type 2 diabetes and LVH will exhibit greater brain atrophy than those without LVH. An understanding of whether LVH contributes to cognitive decline, and in which patients, will allow us to identify patients at particular risk. Australian New Zealand Clinical Trials Registry ( ACTRN12616000546459 ), date registered, 28/04/2016.

Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest

PubMed Central

Li, Duan; Mabrouk, Omar S.; Liu, Tiecheng; Tian, Fangyun; Xu, Gang; Rengifo, Santiago; Choi, Sarah J.; Mathur, Abhay; Crooks, Charles P.; Kennedy, Robert T.; Wang, Michael M.; Ghanbari, Hamid; Borjigin, Jimo

2015-01-01

The mechanism by which the healthy heart and brain die rapidly in the absence of oxygen is not well understood. We performed continuous electrocardiography and electroencephalography in rats undergoing experimental asphyxia and analyzed cortical release of core neurotransmitters, changes in brain and heart electrical activity, and brain–heart connectivity. Asphyxia stimulates a robust and sustained increase of functional and effective cortical connectivity, an immediate increase in cortical release of a large set of neurotransmitters, and a delayed activation of corticocardiac functional and effective connectivity that persists until the onset of ventricular fibrillation. Blocking the brain’s autonomic outflow significantly delayed terminal ventricular fibrillation and lengthened the duration of detectable cortical activities despite the continued absence of oxygen. These results demonstrate that asphyxia activates a brainstorm, which accelerates premature death of the heart and the brain. PMID:25848007

Primary Intraventricular Leiomyoma in an Immunocompetent Patient: First Case Report and Review of the Literature.

PubMed

Garces, Juanita; Mathkour, Mansour; Valle-Giler, Edison; Scullen, Tyler; Berry, J Franklin; Smith, Roger D

2016-06-01

Primary intracranial leiomyoma is an extremely rare occurrence of a low-grade mesenchymal tumor characterized by a proliferation of smooth muscle cells. When present, these lesions predominantly occur in immunocompromised patients in the setting of infection or transplant and have not been known to involve the ventricular system of the brain. In this report, we describe a case of primary leiomyoma of the lateral ventricle in an immunocompetent patient. A 30-year-old man with no medical history presented with progressive diplopia and occipital headaches. Magnetic resonance imaging of the brain revealed a homogenously enhancing mass of the left lateral ventricle with associated cerebral edema. The patient underwent interhemispheric transcallosal craniotomy for resection for symptom alleviation and surgical diagnosis. Histopathology and immunohistochemistry was subsequently consistent with that of leiomyoma. Genetic probing for Epstein-Barr virus was negative. Computed tomography of the chest and abdomen failed to uncover a primary tumor. The patient did well postoperatively and was discharged 3 days after resection. At a two-and-a-half year follow-up, there continued to be no radiologic or clinical evidence of recurrence. To date and to our knowledge, there are fewer than 25 reported cases of primary intracranial leiomyoma, with only 13 occurring in immunocompetent individuals. We believe this is the first report of this tumor type occurring within the ventricular system of the brain. As such, leiomyoma should be considered as a rare etiology in the differential diagnosis of intraventricular lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased radial glia quiescence, decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon.

PubMed

Edelmann, Kathrin; Glashauser, Lena; Sprungala, Susanne; Hesl, Birgit; Fritschle, Maike; Ninkovic, Jovica; Godinho, Leanne; Chapouton, Prisca

2013-09-01

The zebrafish has recently become a source of new data on the mechanisms of neural stem cell (NSC) maintenance and ongoing neurogenesis in adult brains. In this vertebrate, neurogenesis occurs at high levels in all ventricular regions of the brain, and brain injuries recover successfully, owing to the recruitment of radial glia, which function as NSCs. This new vertebrate model of adult neurogenesis is thus advancing our knowledge of the molecular cues in use for the activation of NSCs and fate of their progeny. Because the regenerative potential of somatic stem cells generally weakens with increasing age, it is important to assess the extent to which zebrafish NSC potential decreases or remains unaltered with age. We found that neurogenesis in the ventricular zone, in the olfactory bulb, and in a newly identified parenchymal zone of the telencephalon indeed declines as the fish ages and that oligodendrogenesis also declines. In the ventricular zone, the radial glial cell population remains largely unaltered morphologically but enters less frequently into the cell cycle and hence produces fewer neuroblasts. The neuroblasts themselves do not change their behavior with age and produce the same number of postmitotic neurons. Thus, decreased neurogenesis in the physiologically aging zebrafish brain is correlated with an increasing quiescence of radial glia. After injuries, radial glia in aged brains are reactivated, and the percentage of cell cycle entry is increased in the radial glia population. However, this reaction is far less pronounced than in younger animals, pointing to irreversible changes in aging zebrafish radial glia. Copyright © 2013 Wiley Periodicals, Inc.

Ablation and pacing: improving brain perfusion and cognitive function in patients with atrial fibrillation and uncontrolled ventricular rates.

PubMed

Efimova, Irina; Efimova, Nataliya; Chernov, Vladimir; Popov, Sergey; Lishmanov, Yuri

2012-03-01

The aim of our study was to determine if ablation and pacing improved brain perfusion (BP) and cognitive function (CF) in patients with medically refractory rapidly conducted atrial fibrillation (Med Refr RCAF). The study included 17 patients with Med Refr RCAF (average age 55.3 ± 4.5 years). All patients underwent brain single photon emission computed tomography scanning with (99m) Tc-hexamethylpropylene amine oxime and comprehensive neuropsychological testing before and after 3 months following pacemaker implantation. The BP was significantly lower in all regions in patients with Med Refr RCAF compared with the control group. The greatest BP decrease was revealed in the inferior frontal (P = 0.002) and posterior parietal (P = 0.024) brain regions. These patients showed cognitive deficit in 94%. There was a direct correlation between BP and CF parameters. Ablation followed by pacemaker implantation had a positive effect on BP and CF in all patients with Med Refr RCAF. Thus, BP increased in the right inferior frontal (P = 0.01), in the left superior frontal (P = 0.007), and in the left temporal (P = 0.005) cortex. These patients demonstrated improvements in immediate and delayed verbal memory, immediate and delayed visual memory, abstract mentation, attention, psychomotor speed, as well as in learning. Patients with atrial fibrillation and rapid ventricular rates refractory to medical treatment have marked signs of brain hypoperfusion and impaired CF. Ablation and pacing improve left ventricular systolic function, thereby increasing BP and improving CF. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

Exploring Deep Space - Uncovering the Anatomy of Periventricular Structures to Reveal the Lateral Ventricles of the Human Brain.

PubMed

Colibaba, Alexandru S; Calma, Aicee Dawn B; Webb, Alexandra L; Valter, Krisztina

2017-10-22

Anatomy students are typically provided with two-dimensional (2D) sections and images when studying cerebral ventricular anatomy and students find this challenging. Because the ventricles are negative spaces located deep within the brain, the only way to understand their anatomy is by appreciating their boundaries formed by related structures. Looking at a 2D representation of these spaces, in any of the cardinal planes, will not enable visualisation of all of the structures that form the boundaries of the ventricles. Thus, using 2D sections alone requires students to compute their own mental image of the 3D ventricular spaces. The aim of this study was to develop a reproducible method for dissecting the human brain to create an educational resource to enhance student understanding of the intricate relationships between the ventricles and periventricular structures. To achieve this, we created a video resource that features a step-by-step guide using a fiber dissection method to reveal the lateral and third ventricles together with the closely related limbic system and basal ganglia structures. One of the advantages of this method is that it enables delineation of the white matter tracts that are difficult to distinguish using other dissection techniques. This video is accompanied by a written protocol that provides a systematic description of the process to aid in the reproduction of the brain dissection. This package offers a valuable anatomy teaching resource for educators and students alike. By following these instructions educators can create teaching resources and students can be guided to produce their own brain dissection as a hands-on practical activity. We recommend that this video guide be incorporated into neuroanatomy teaching to enhance student understanding of the morphology and clinical relevance of the ventricles.

Brain and cord myelin water imaging: a progressive multiple sclerosis biomarker

PubMed Central

Kolind, Shannon; Seddigh, Arshia; Combes, Anna; Russell-Schulz, Bretta; Tam, Roger; Yogendrakumar, Vignan; Deoni, Sean; Sibtain, Naomi A.; Traboulsee, Anthony; Williams, Steven C.R.; Barker, Gareth J.; Brex, Peter A.

2015-01-01

Objectives Conventional magnetic resonance imaging (MRI) is used to diagnose and monitor inflammatory disease in relapsing remitting (RR) multiple sclerosis (MS). In the less common primary progressive (PP) form of MS, in which focal inflammation is less evident, biomarkers are still needed to enable evaluation of novel therapies in clinical trials. Our objective was to characterize the association — across the brain and cervical spinal cord — between clinical disability measures in PPMS and two potential biomarkers (one for myelin, and one for atrophy, both resulting from the same imaging technique). Methods Multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) MRI of the brain and cervical spinal cord were obtained for 15 PPMS patients and 11 matched controls. Data were analysed to estimate the signal related to myelin water (VFM), as well as volume measurements. MS disability was assessed using the Multiple Sclerosis Functional Composite score, which includes measures of cognitive processing (Paced Auditory Serial Addition Test), manual dexterity (9-Hole Peg Test) and ambulatory function (Timed 25-Foot Walk); and the Expanded Disability Status Scale. Results Brain and spinal cord volumes were different in PPMS compared to controls, particularly ventricular (+ 46%, p = 0.0006) and cervical spinal cord volume (− 16%, p = 0.0001). Brain and spinal cord myelin (VFM) were also reduced in PPMS (brain: − 11%, p = 0.01; spine: − 19%, p = 0.000004). Cognitive processing correlated with brain ventricular volume (p = 0.009). Manual dexterity correlated with brain ventricular volume (p = 0.007), and both brain and spinal cord VFM (p = 0.01 and 0.06, respectively). Ambulation correlated with spinal cord volume (p = 0.04) and spinal cord VFM (p = 0.04). Interpretation In this study we demonstrated that mcDESPOT can be used to measure myelin and atrophy in the brain and spinal cord. Results correlate well with clinical disability scores in PPMS representing cognitive, fine motor and ambulatory disability. PMID:26594633

Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency

PubMed Central

Yang, Xuejun; Zhou, Hua; Qu, Huiyan; Liu, Weifang; Huang, Xiaojin; Shun, Yating; He, Liqun

2014-01-01

Objective: To observe the efficacy of Shenxinning Decoction (SXND) in ventricular remodeling in AT1 receptor-knockout (AT1-KO) mice with chronic renal insufficiency (CRI). Materials and Methods: AT1-KO mice modeled with subtotal (5/6) nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN), serum creatinine (SCr), brain natriuretic peptide (BNP), echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF), collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1) of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. Results: AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice's BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. Conclusion: SXND may antagonize the renin–angiotensin system (RAS) and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1. PMID:25097276

Adolescents who were born very preterm have decreased brain volumes.

PubMed

Nosarti, Chiara; Al-Asady, Mazin H S; Frangou, Sophia; Stewart, Ann L; Rifkin, Larry; Murray, Robin M

2002-07-01

Infants born very preterm have an increased risk of brain injury. Given the great increase in the number of such infants that are surviving, it is important to establish whether any resultant brain abnormalities persist into adolescence and adult life. We therefore examined in vivo whole brain, grey matter, white matter and hippocampal volumes, ventricular size and grey/white matter ratios in a series of adolescents who had been born very preterm, and an age-matched full-term control group. Structural MRI was carried out on a cohort of 72 adolescents (mean age 15 years) who were born before 33 weeks, and 48 age-matched full-term controls. Brain measurements were made blind to group affiliation using stereological principles. After controlling for gender and height, the very preterm subjects showed a 6.0% decrease in whole brain volume, and an 11.8% decrease in cortical grey matter volume, as well as a 15.6% decrease in right and a 12.1% decrease in left hippocampal volumes; they also had a 42.0% increase in the size of the lateral ventricles. Therefore, individuals who were born very preterm continue to show noticeable decrements in brain volumes and striking increases in lateral ventricular volume into adolescence. The functional significance of these abnormalities merits further investigation.

Features of Brain MRI in Dogs with Treated and Untreated Mucopolysaccharidosis Type I

PubMed Central

Vite, Charles H; Nestrasil, Igor; Mlikotic, Anton; Jens, Jackie K; Snella, Elizabeth M; Gross, William; Shapiro, Elsa G; Kovac, Victor; Provenzale, James M; Chen, Steven; Le, Steven Q; Kan, Shih-hsin; Banakar, Shida; Wang, Raymond Y; Haskins, Mark E; Ellinwood, N Matthew; Dickson, Patricia I

2013-01-01

The mucopolysaccharidosis type I (MPS I) dog model has been important in the development of therapies for human patients. We treated dogs with enzyme replacement therapy (ERT) by various approaches. Dogs assessed included untreated MPS I dogs, heterozygous carrier dogs, and MPS I dogs treated with intravenous ERT as adults (beginning at age 13 to 16 mo), intrathecal and intravenous ERT as adults (beginning at age 13 to 16 mo), or intrathecal ERT as juveniles (beginning at age 4 mo). We then characterized the neuroimaging findings of 32 of these dogs (age, 12 to 30 mo). Whole and midsagittal volumes of the corpus callosum, measured from brain MRI, were significantly smaller in affected dogs compared with unaffected heterozygotes. Corpus callosum volumes in dogs that were treated with intrathecal ERT from 4 mo until 21 mo of age were indistinguishable from those of age-matched carrier controls. Dogs with MPS I showed cerebral ventricular enlargement and cortical atrophy as early as 12 mo of age. Ventricular enlargement was greater in untreated MPS I dogs than in age-matched dogs treated with intrathecal ERT as juveniles or adults. However, treated dogs still showed some ventricular enlargement or cortical atrophy (or both). Understanding the progression of neuroimaging findings in dogs with MPS I and their response to brain-directed therapy may improve preclinical studies for new human-directed therapies. In particular, corpus callosum volumes may be useful quantitative neuroimaging markers for MPS-related brain disease and its response to therapy. PMID:23582423

Right ventricular function and N-terminal pro-brain natriuretic peptide levels in adult patients with simple dextro-transposition of the great arteries.

PubMed

Martínez-Quintana, Efrén; Marrero-Negrín, Natalia; Gopar-Gopar, Silvia; Rodríguez-González, Fayna

2017-06-01

Dextro-transposition of the great arteries (d-TGA) patients is at high risk of developing right ventricular dysfunction and tricuspid regurgitation in adulthood. Determining the relation between echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the New York Heart Association (NYHA) functional class may help determining the best time to operate them. Patients with simple d-TGA operated in infancy with an atrial switch procedure (Mustard or Senning operation) were followed up in our Adult Congenital Heart Disease Unit. Analytical, echocardiographic, and clinical parameters were determined to evaluate the correlation between right echocardiographic ventricular function, NT-pro-BNP levels, and NYHA functional class. Twenty-four patients with d-TGA were operated in infancy of whom 17 alive patients had simple d-TGA. Nine patients had NT-pro-BNP levels lower than 200 pg/mL and eight patients were above 200 pg/mL. Patients with lower hemoglobin concentration, higher right ventricular diameter or under diuretic treatment showed significant higher NT-pro-BNP levels (above 200 pg/dL). The Spearman test showed a positive correlation between basal right ventricular diameter and tricuspid regurgitation with pro NT BNP levels (correlation coefficient of .624; P=.017 and .490; P=.046, respectively) and a negative correlation with the right ventricle fractional area change (-.508, P=.045). No correlation was seen between NT-pro-BNP levels and the rest of echocardiographic parameters or the NYHA functional class. NT-pro-BNP levels showed a positive correlation with basal right ventricular diameter and tricuspid regurgitation but not with NYHA association functional class in d-TGA patients. © 2017, Wiley Periodicals, Inc.

Mapping correlations between ventricular expansion and CSF amyloid and tau biomarkers in 240 subjects with Alzheimer’s disease, mild cognitive impairment and elderly controls

PubMed Central

Chou, Yi-Yu; Leporé, Natasha; Avedissian, Christina; Madsen, Sarah K.; Parikshak, Neelroop; Hua, Xue; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Toga, Arthur W.; Thompson, Paul M.

2009-01-01

Automated ventricular mapping with multi-atlas fluid image alignment reveals genetic effects in Alzheimer’s disease, NeuroImage 40(2): 615–630); with this method, we calculated minimal numbers of subjects needed to detect correlations between clinical scores and ventricular maps. We also assessed correlations between emerging CSF biomarkers of Alzheimer’s disease pathology and localizable deficits in the brain, in 80 AD, 80 mild cognitive impairment (MCI), and 80 healthy controls from the Alzheimer’s Disease Neuroimaging Initiative. Six expertly segmented images and their embedded parametric mesh surfaces were fluidly registered to each brain; segmentations were averaged within subjects to reduce errors. Surface-based statistical maps revealed powerful correlations between surface morphology and 4 variables: (1) diagnosis, (2) depression severity, (3) cognitive function at baseline, and (4) future cognitive decline over the following year. Cognitive function was assessed using the mini-mental state exam (MMSE), global and sum-of-boxes clinical dementia rating (CDR) scores, at baseline and 1-year follow-up. Lower CSF Aβ1–42 protein levels, a biomarker of AD pathology assessed in 138 of the 240 subjects, were correlated with lateral ventricular expansion. Using false discovery rate (FDR) methods, 40 and 120 subjects, respectively, were needed to discriminate AD and MCI from normal groups. 120 subjects were required to detect correlations between ventricular enlargement and MMSE, global CDR, sum-of-boxes CDR and clinical depression scores. Ventricular expansion maps correlate with pathological and cognitive measures in AD, and may be useful in future imaging-based clinical trials. PMID:19236926

Echocardiographic assessment and N-terminal pro-brain natriuretic peptide in hypertensives with metabolic syndrome.

PubMed

Krzesiński, Paweł; Uziebło-Życzkowska, Beata; Gielerak, Grzegorz; Stańczyk, Adam; Piotrowicz, Katarzyna; Piechota, Wiesław; Smurzyński, Paweł; Skrobowski, Andrzej

2017-01-01

N-terminal pro-brain natriuretic peptide (NT-proBNP) release is associated with left ventricular expansion and pressure overload. Elevation of serum levels of natriuretic peptides is observed in patients with impaired as well as preserved left ventricular systolic function. High NT-proBNP has been shown to be related not only to preload but also to increased afterload, especially blood pressure and arterial stiffness. The aim of the study was to evaluate the association of NT-proBNP and echocardiographic parameters in hypertensives with metabolic syndrome. The study group comprised 133 patients (99 men; mean age 45.9 ± 9.4 years) with at least a 3-month history of arterial hypertension (stages 1 and 2) and fulfilling the diagnostic criteria for metabolic syndrome. Following initial clinical assessment, which included NT-proBNP levels, they underwent two-dimensional echocardiography. Echocardiographic abnormalities were observed in 60 subjects (45.1%), including left ventricular diastolic dysfunction (LVDdf) in 41 (30.8%) and left ventricular hypertrophy (LVH) in 35 (26.3%). Higher NT-proBNP concentrations were observed in patients with LVH, especially in the presence of LVDdf. Further analysis demonstrated that NT-proBNP correlated negatively with septal E' (r = -0.38; p = 0.015) and heart rate (r = -0.42; p = 0.006) in patients with LVDdf, and positively with left ventricular end diastolic diameter (r = 0.46; p = 0.006) and left ventricular mass index (r = 0.49; p = 0.005) in subjects with LVH. However, the analysis of ROC curves revealed no NT-proBNP level of good sensitivity and specificity in diagnosing LVDdf/LVH (maximal area under the curve 0.571). Even a relatively low NT-proBNP concentration can be a useful marker of left ventricular hypertrophy and end-diastolic wall stretch. However, in the present study there was no NT-proBNP level of satisfactory predictive value to diagnose LV abnormalities.

Characterization of multiciliated ependymal cells that emerge in the neurogenic niche of the aged zebrafish brain.

PubMed

Ogino, Takashi; Sawada, Masato; Takase, Hiroshi; Nakai, Chiemi; Herranz-Pérez, Vicente; Cebrián-Silla, Arantxa; Kaneko, Naoko; García-Verdugo, José Manuel; Sawamoto, Kazunobu

2016-10-15

In mammals, ventricular walls of the developing brain maintain a neurogenic niche, in which radial glial cells act as neural stem cells (NSCs) and generate new neurons in the embryo. In the adult brain, the neurogenic niche is maintained in the ventricular-subventricular zone (V-SVZ) of the lateral wall of lateral ventricles and the hippocampal dentate gyrus. In the neonatal V-SVZ, radial glial cells transform into astrocytic postnatal NSCs and multiciliated ependymal cells. On the other hand, in zebrafish, radial glial cells continue to cover the surface of the adult telencephalic ventricle and maintain a higher neurogenic potential in the adult brain. However, the cell composition of the neurogenic niche of the aged zebrafish brain has not been investigated. Here we show that multiciliated ependymal cells emerge in the neurogenic niche of the aged zebrafish telencephalon. These multiciliated cells appear predominantly in the dorsal part of the ventral telencephalic ventricular zone, which also contains clusters of migrating new neurons. Scanning electron microscopy and live imaging analyses indicated that these multiple cilia beat coordinately and generate constant fluid flow within the ventral telencephalic ventricle. Analysis of the cell composition by transmission electron microscopy revealed that the neurogenic niche in the aged zebrafish contains different types of cells, with ultrastructures similar to those of ependymal cells, transit-amplifying cells, and migrating new neurons in postnatal mice. These data suggest that the transformation capacity of radial glial cells is conserved but that its timing is different between fish and mice. J. Comp. Neurol. 524:2982-2992, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Support with intra-aortic balloon pump vs. Impella2.5® and blood flow to the heart, brain and kidneys - an experimental porcine model of ischaemic heart failure.

PubMed

Møller-Helgestad, Ole K; Poulsen, Christian B; Christiansen, Evald H; Lassen, Jens F; Ravn, Hanne B

2015-01-15

Cardiogenic shock as a complication to an acute myocardial infarction has an unacceptably high death rate that has not changed for the last 15years. Mortality is partly related to organ hypoperfusion and mechanical assist devices are used for the most severe cases but we do not know which assist device is the best option. Therefore, we have investigated how an IABP and an Impella®-pump influenced blood flow to the brain, heart and kidneys, in a closed-chest porcine model of severe left ventricular failure. 13 pigs were anesthetised and left ventricular failure was induced by occluding the proximal LAD for 45min followed by 30min of reperfusion. Blood flow was measured in the carotid artery, the LAD, and the renal artery. The Impella® and IABP were inserted via the femoral arteries, and the two devices were tested individually and combined after induction of heart failure. Carotid- (p=0.01) and renal blood flow (p=0.045) were higher on Impella®-support, compared to no support. None of the devices altered the blood flow in the LAD. Cardiac power output (p<0.005) and left ventricular work (p<0.00) were also higher on Impella®-support compared to no support. Haemodynamics and blood flow to the brain and kidneys were significantly better on Impella®-support, suggesting that the Impella® is superior to the IABP in a state of ischaemia induced left ventricular failure. These data, however, needs to be confirmed in a proper clinical trial with patients in cardiogenic shock. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Quantitation of specific binding ratio in 123I-FP-CIT SPECT: accurate processing strategy for cerebral ventricular enlargement with use of 3D-striatal digital brain phantom.

PubMed

Furuta, Akihiro; Onishi, Hideo; Amijima, Hizuru

2018-06-01

This study aimed to evaluate the effect of ventricular enlargement on the specific binding ratio (SBR) and to validate the cerebrospinal fluid (CSF)-Mask algorithm for quantitative SBR assessment of 123 I-FP-CIT single-photon emission computed tomography (SPECT) images with the use of a 3D-striatum digital brain (SDB) phantom. Ventricular enlargement was simulated by three-dimensional extensions in a 3D-SDB phantom comprising segments representing the striatum, ventricle, brain parenchyma, and skull bone. The Evans Index (EI) was measured in 3D-SDB phantom images of an enlarged ventricle. Projection data sets were generated from the 3D-SDB phantoms with blurring, scatter, and attenuation. Images were reconstructed using the ordered subset expectation maximization (OSEM) algorithm and corrected for attenuation, scatter, and resolution recovery. We bundled DaTView (Southampton method) with the CSF-Mask processing software for SBR. We assessed SBR with the use of various coefficients (f factor) of the CSF-Mask. Specific binding ratios of 1, 2, 3, 4, and 5 corresponded to SDB phantom simulations with true values. Measured SBRs > 50% that were underestimated with EI increased compared with the true SBR and this trend was outstanding at low SBR. The CSF-Mask improved 20% underestimates and brought the measured SBR closer to the true values at an f factor of 1.0 despite an increase in EI. We connected the linear regression function (y = - 3.53x + 1.95; r = 0.95) with the EI and f factor using root-mean-square error. Processing with CSF-Mask generates accurate quantitative SBR from dopamine transporter SPECT images of patients with ventricular enlargement.

Automated segmentation of neuroanatomical structures in multispectral MR microscopy of the mouse brain.

PubMed

Ali, Anjum A; Dale, Anders M; Badea, Alexandra; Johnson, G Allan

2005-08-15

We present the automated segmentation of magnetic resonance microscopy (MRM) images of the C57BL/6J mouse brain into 21 neuroanatomical structures, including the ventricular system, corpus callosum, hippocampus, caudate putamen, inferior colliculus, internal capsule, globus pallidus, and substantia nigra. The segmentation algorithm operates on multispectral, three-dimensional (3D) MR data acquired at 90-microm isotropic resolution. Probabilistic information used in the segmentation is extracted from training datasets of T2-weighted, proton density-weighted, and diffusion-weighted acquisitions. Spatial information is employed in the form of prior probabilities of occurrence of a structure at a location (location priors) and the pairwise probabilities between structures (contextual priors). Validation using standard morphometry indices shows good consistency between automatically segmented and manually traced data. Results achieved in the mouse brain are comparable with those achieved in human brain studies using similar techniques. The segmentation algorithm shows excellent potential for routine morphological phenotyping of mouse models.

A Pilot Study of Quantitative MRI Measurements of Ventricular Volume and Cortical Atrophy for the Differential Diagnosis of Normal Pressure Hydrocephalus

PubMed Central

Moore, Dana W.; Kovanlikaya, Ilhami; Heier, Linda A.; Raj, Ashish; Huang, Chaorui; Chu, King-Wai; Relkin, Norman R.

2012-01-01

Current radiologic diagnosis of normal pressure hydrocephalus (NPH) requires a subjective judgment of whether lateral ventricular enlargement is disproportionate to cerebral atrophy based on visual inspection of brain images. We investigated whether quantitative measurements of lateral ventricular volume and total cortical thickness (a correlate of cerebral atrophy) could be used to more objectively distinguish NPH from normal controls (NC), Alzheimer's (AD), and Parkinson's disease (PD). Volumetric MRIs were obtained prospectively from patients with NPH (n = 5), PD (n = 5), and NC (5). Additional NC (n = 5) and AD patients (n = 10) from the ADNI cohort were examined. Although mean ventricular volume was significantly greater in the NPH group than all others, the range of values overlapped those of the AD group. Individuals with NPH could be better distinguished when ventricular volume and total cortical thickness were considered in combination. This pilot study suggests that volumetric MRI measurements hold promise for improving NPH differential diagnosis. PMID:21860791

Vertebrate brains and evolutionary connectomics: on the origins of the mammalian ‘neocortex’

PubMed Central

Karten, Harvey J.

2015-01-01

The organization of the non-mammalian forebrain had long puzzled neurobiologists. Unlike typical mammalian brains, the telencephalon is not organized in a laminated ‘cortical’ manner, with distinct cortical areas dedicated to individual sensory modalities or motor functions. The two major regions of the telencephalon, the basal ventricular ridge (BVR) and the dorsal ventricular ridge (DVR), were loosely referred to as being akin to the mammalian basal ganglia. The telencephalon of non-mammalian vertebrates appears to consist of multiple ‘subcortical’ groups of cells. Analysis of the nuclear organization of the avian brain, its connections, molecular properties and physiology, and organization of its pattern of circuitry and function relative to that of mammals, collectively referred to as ‘evolutionary connectomics’, revealed that only a restricted portion of the BVR is homologous to the basal ganglia of mammals. The remaining dorsal regions of the DVR, wulst and arcopallium of the avian brain contain telencephalic inputs and outputs remarkably similar to those of the individual layers of the mammalian ‘neocortex’, hippocampus and amygdala, with instances of internuclear connections strikingly similar to those found between cortical layers and within radial ‘columns’ in the mammalian sensory and motor cortices. The molecular properties of these ‘nuclei’ in birds and reptiles are similar to those of the corresponding layers of the mammalian neocortex. The fundamental pathways and cell groups of the auditory, visual and somatosensory systems of the thalamus and telencephalon are homologous at the cellular, circuit, network and gene levels, and are of great antiquity. A proposed altered migration of these homologous neurons and circuits during development is offered as a mechanism that may account for the altered configuration of mammalian telencephalae. PMID:26554047

Improvement in hemodynamic performance, exercise capacity, inflammatory profile, and left ventricular reverse remodeling after intracoronary delivery of mesenchymal stem cells in an experimental model of pressure overload hypertrophy.

PubMed

Molina, Ezequiel J; Palma, Jon; Gupta, Dipin; Torres, Denise; Gaughan, John P; Houser, Steven; Macha, Mahender

2008-02-01

In a rat model of pressure overload hypertrophy, we studied the effects of intracoronary delivery of mesenchymal stem cells on hemodynamic performance, exercise capacity, systemic inflammation, and left ventricular reverse remodeling. Sprague-Dawley rats underwent aortic banding and were followed up by echocardiographic scanning. After a decrease in fractional shortening of 25% from baseline, animals were randomized to intracoronary injection of mesenchymal stem cells (MSC group; n = 28) or phosphate-buffered saline solution (control group; n = 20). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of inflammatory markers were performed before the rats were humanely killed on postoperative day 7, 14, 21, or 28. Injection of mesenchymal stem cells improved systolic function in the MSC group compared with the control group (mean +/- standard deviation: maximum dP/dt 3048 +/- 230 mm Hg/s vs 2169 +/- 97 mm Hg/s at 21 days and 3573 +/- 741 mm Hg/s vs 1363 +/- 322 mm Hg/s at 28 days: P < .001). Time to exhaustion was similarly increased in the MSC group compared with controls (487 +/- 35 seconds vs 306 +/- 27 seconds at 28 days; P < .01). Serum levels of interleukins 1 and 6, tumor necrosis factor-alpha, and brain natriuretic peptide-32 were significantly decreased in animals treated with mesenchymal stem cells. Stem cell transplantation improved left ventricular fractional shortening at 21 and 28 days. Left ventricular end-systolic and end-diastolic diameters were also improved at 28 days. In this model of pressure overload hypertrophy, intracoronary delivery of mesenchymal stem cells during heart failure was associated with an improvement in hemodynamic performance, maximal exercise tolerance, systemic inflammation, and left ventricular reverse remodeling. This study suggests a potential role of this treatment strategy for the management of hypertrophic heart failure resulting from pressure overload.

Cilia driven flow networks in the brain

NASA Astrophysics Data System (ADS)

Wang, Yong; Faubel, Regina; Westendorf, Chrsitian; Eichele, Gregor; Bodenschatz, Eberhard

Neurons exchange soluble substances via the cerebrospinal fluid (CSF) that fills the ventricular system. The walls of the ventricular cavities are covered with motile cilia that constantly beat and thereby induce a directional flow. We recently discovered that cilia in the third ventricle generate a complex flow pattern leading to partitioning of the ventricular volume and site-directed transport paths along the walls. Transient and daily recurrent alterations in the cilia beating direction lead to changes in the flow pattern. This has consequences for delivery of CSF components along the near wall flow. The contribution of this cilia-induced flow to overall CSF flow remains to be investigated. The state-of-art lattice Boltzmann method is adapted for studying the CFS flow. The 3D geometry of the third ventricle at high resolution was reconstructed. Simulation of CSF flow without cilia in this geometry confirmed that the previous idea about unidirectional flow does not explain how different components of CSF can be delivered to their various target sites. We study the contribution of the cilia-induced flow pattern to overall CSF flow and identify target areas for site-specific delivery of CSF-constituents with respect to the temporal changes.

Late stage infection in sleeping sickness.

PubMed

Wolburg, Hartwig; Mogk, Stefan; Acker, Sven; Frey, Claudia; Meinert, Monika; Schönfeld, Caroline; Lazarus, Michael; Urade, Yoshihiro; Kubata, Bruno Kilunga; Duszenko, Michael

2012-01-01

At the turn of the 19(th) century, trypanosomes were identified as the causative agent of sleeping sickness and their presence within the cerebrospinal fluid of late stage sleeping sickness patients was described. However, no definitive proof of how the parasites reach the brain has been presented so far. Analyzing electron micrographs prepared from rodent brains more than 20 days after infection, we present here conclusive evidence that the parasites first enter the brain via the choroid plexus from where they penetrate the epithelial cell layer to reach the ventricular system. Adversely, no trypanosomes were observed within the parenchyma outside blood vessels. We also show that brain infection depends on the formation of long slender trypanosomes and that the cerebrospinal fluid as well as the stroma of the choroid plexus is a hostile environment for the survival of trypanosomes, which enter the pial space including the Virchow-Robin space via the subarachnoid space to escape degradation. Our data suggest that trypanosomes do not intend to colonize the brain but reside near or within the glia limitans, from where they can re-populate blood vessels and disrupt the sleep wake cycles.

A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion.

PubMed

Shelton, Laura M; Mukherjee, Purna; Huysentruyt, Leanne C; Urits, Ivan; Rosenberg, Joshua A; Seyfried, Thomas N

2010-09-01

Glioblastoma multiforme (GBM) is a rapidly progressive disease of morbidity and mortality and is the most common form of primary brain cancer in adults. Lack of appropriate in vivo models has been a major roadblock to developing effective therapies for GBM. A new highly invasive in vivo GBM model is described that was derived from a spontaneous brain tumor (VM-M3) in the VM mouse strain. Highly invasive tumor cells could be identified histologically on the hemisphere contralateral to the hemisphere implanted with tumor cells or tissue. Tumor cells were highly expressive for the chemokine receptor CXCR4 and the proliferation marker Ki-67 and could be identified invading through the pia mater, the vascular system, the ventricular system, around neurons, and over white matter tracts including the corpus callosum. In addition, the brain tumor cells were labeled with the firefly luciferase gene, allowing for non-invasive detection and quantitation through bioluminescent imaging. The VM-M3 tumor has a short incubation time with mortality occurring in 100% of the animals within approximately 15 days. The VM-M3 brain tumor model therefore can be used in a pre-clinical setting for the rapid evaluation of novel anti-invasive therapies.

Multivariate Tensor-based Morphometry on Surfaces: Application to Mapping Ventricular Abnormalities in HIV/AIDS

PubMed Central

Wang, Yalin; Zhang, Jie; Gutman, Boris; Chan, Tony F.; Becker, James T.; Aizenstein, Howard J.; Lopez, Oscar L.; Tamburo, Robert J.; Toga, Arthur W.; Thompson, Paul M.

2010-01-01

Here we developed a new method, called multivariate tensor-based surface morphometry (TBM), and applied it to study lateral ventricular surface differences associated with HIV/AIDS. Using concepts from differential geometry and the theory of differential forms, we created mathematical structures known as holomorphic one-forms, to obtain an efficient and accurate conformal parameterization of the lateral ventricular surfaces in the brain. The new meshing approach also provides a natural way to register anatomical surfaces across subjects, and improves on prior methods as it handles surfaces that branch and join at complex 3D junctions. To analyze anatomical differences, we computed new statistics from the Riemannian surface metrics - these retain multivariate information on local surface geometry. We applied this framework to analyze lateral ventricular surface morphometry in 3D MRI data from 11 subjects with HIV/AIDS and 8 healthy controls. Our method detected a 3D profile of surface abnormalities even in this small sample. Multivariate statistics on the local tensors gave better effect sizes for detecting group differences, relative to other TBM-based methods including analysis of the Jacobian determinant, the largest and smallest eigenvalues of the surface metric, and the pair of eigenvalues of the Jacobian matrix. The resulting analysis pipeline may improve the power of surface-based morphometry studies of the brain. PMID:19900560

Biventricular non-compaction with predominant right ventricular involvement, reduced left ventricular systolic and diastolic function, and pulmonary hypertension in a Hispanic male.

PubMed

Said, Sarmad; Cooper, Chad J; Quevedo, Karla; Rodriguez, Emmanuel; Hernandez, German T

2013-01-01

Male, 22 FINAL DIAGNOSIS: Cardiomyopathy Symptoms: Shortness of breath • dispnoea • chest discomfort - Clinical Procedure: Echocardiogram • cardiac MRI Specialty: Cardiology. Challenging differential diagnosis. Non-compaction cardiomyopathy (NCM) is a rare congenital cardiomyopathy characterized by increased trabeculation in one or more segments of the ventricle. The left ventricle is most commonly affected. However, biventricular involvement or right ventricle predominance has also been described. Clinical features of NCM are non-specific and can range from being asymptomatic to symptoms of congestive heart failure, arrhythmia, and systemic thromboembolism. 22-year-old Hispanic male presented with two month history of chest discomfort. Laboratory workup revealed an elevated brain-natriuretic-peptide of 1768 pg/ml. ECG and chest x-ray was nonspecific. Transthoracic echocardiogram revealed prominent trabeculae and spongiform appearance of the left ventricle (LV) with an ejection-fraction of 15-20%; 5 of 9 segments of the LV were trabeculated with deep intertrabecular recesses also involving the right ventricle (RV) with demonstrated blood flow in these recesses on color-doppler. The biventricular spongiform appearance was morphologically suggestive for NCM with involvement of the RV. Confirmatory cardiac MRI was performed, demonstrating excessive trabeculation of the left-ventricular apex and mid-ventricular segments. Hypertrabecularion was exhibited at the apical and lateral wall of the RV. Cardiac catheterization showed an intact cardiac vessel system. The patient was discharged on heart failure treatment and was placed on the heart transplantation list. NCM is a unique disorder resulting in serious and severe complications. The majority of the reported cases describe the involvement of the left ventricle. However, the right ventricle should be taken into careful consideration. The early diagnosis may help to increase the event-free survival.

Regional growth and atlasing of the developing human brain

PubMed Central

Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V.; Edwards, A. David; Counsell, Serena J.; Rueckert, Daniel

2016-01-01

Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45 weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. PMID:26499811

Regional growth and atlasing of the developing human brain.

PubMed

Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V; Edwards, A David; Counsell, Serena J; Rueckert, Daniel

2016-01-15

Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Right and Left Ventricular Function and Mass in Male Elite Master Athletes: A Controlled Contrast-Enhanced Cardiovascular Magnetic Resonance Study.

PubMed

Bohm, Philipp; Schneider, Günther; Linneweber, Lutz; Rentzsch, Axel; Krämer, Nadine; Abdul-Khaliq, Hashim; Kindermann, Wilfried; Meyer, Tim; Scharhag, Jürgen

2016-05-17

It is under debate whether the cumulative effects of intensive endurance exercise induce chronic cardiac damage, mainly involving the right heart. The aim of this study was to examine the cardiac structure and function in long-term elite master endurance athletes with special focus on the right ventricle by contrast-enhanced cardiovascular magnetic resonance. Thirty-three healthy white competitive elite male master endurance athletes (age range, 30-60 years) with a training history of 29±8 years, and 33 white control subjects pair-matched for age, height, and weight underwent cardiopulmonary exercise testing, echocardiography including tissue-Doppler imaging and speckle tracking, and cardiovascular magnetic resonance. Indexed left ventricular mass and right ventricular mass (left ventricular mass/body surface area, 96±13 and 62±10 g/m(2); P<0.001; right ventricular mass/body surface area, 36±7 and 24±5 g/m(2); P<0.001) and indexed left ventricular end-diastolic volume and right ventricular end-diastolic volume (left ventricular end-diastolic volume/body surface area, 104±13 and 69±18 mL/m(2); P<0.001; right ventricular end-diastolic volume/body surface area, 110±22 and 66±16 mL/m(2); P<0.001) were significantly increased in athletes in comparison with control subjects. Right ventricular ejection fraction did not differ between athletes and control subjects (52±8 and 54±6%; P=0.26). Pathological late enhancement was detected in 1 athlete. No correlations were found for left ventricular and right ventricular volumes and ejection fraction with N-terminal pro-brain natriuretic peptide, and high-sensitive troponin was negative in all subjects. Based on our results, chronic right ventricular damage in elite endurance master athletes with lifelong high training volumes seems to be unlikely. Thus, the hypothesis of an exercise-induced arrhythmogenic right ventricular cardiomyopathy has to be questioned. © 2016 American Heart Association, Inc.

A proposed role for efflux transporters in the pathogenesis of hydrocephalus

PubMed Central

Krishnamurthy, Satish; Tichenor, Michael D.; Satish, Akhila G.; Lehmann, David B.

2014-01-01

Hydrocephalus is a common brain disorder that is treated only with surgery. The basis for surgical treatment rests on the circulation theory. However, clinical and experimental data to substantiate circulation theory have remained inconclusive. In brain tissue and in the ventricles, we see that osmotic gradients drive water diffusion in water-permeable tissue. As the osmolarity of ventricular CSF increases within the cerebral ventricles, water movement into the ventricles increases and causes hydrocephalus. Macromolecular clearance from the ventricles is a mechanism to establish the normal CSF osmolarity, and therefore ventricular volume. Efflux transporters, (p-glycoprotein), are located along the blood brain barrier and play an important role in the clearance of macromolecules (endobiotics and xenobiotics) from the brain to the blood. There is clinical and experimental data to show that macromolecules are cleared out of the brain in normal and hydrocephalic brains. This article summarizes the existing evidence to support the role of efflux transporters in the pathogenesis of hydrocephalus. The location of p-gp along the pathways of macromolecular clearance and the broad substrate specificity of this abundant transporter to a variety of different macromolecules are reviewed. Involvement of p-gp in the transport of amyloid beta in Alzheimer disease and its relation to normal pressure hydrocephalus is reviewed. Finally, individual variability of p-gp expression might explain the variability in the development of hydrocephalus following intraventricular hemorrhage. PMID:25165050

Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET.

PubMed

de Leon, Mony J; Li, Yi; Okamura, Nobuyuki; Tsui, Wai H; Saint-Louis, Les A; Glodzik, Lidia; Osorio, Ricardo S; Fortea, Juan; Butler, Tracy; Pirraglia, Elizabeth; Fossati, Silvia; Kim, Hee-Jin; Carare, Roxana O; Nedergaard, Maiken; Benveniste, Helene; Rusinek, Henry

2017-09-01

Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Dynamic PET with 18 F-THK5117, a tracer for tau pathology, was used to estimate the ventricular CSF time-activity as a biomarker for CSF clearance. We tested 3 hypotheses: extracranial CSF is detected at the superior turbinates; CSF clearance is reduced in AD; and CSF clearance is inversely associated with amyloid deposition. Methods: Fifteen subjects, 8 with AD and 7 normal control volunteers, were examined with 18 F-THK5117. Ten subjects additionally underwent 11 C-Pittsburgh compound B ( 11 C-PiB) PET scanning, and 8 were 11 C-PiB-positive. Ventricular time-activity curves of 18 F-THK5117 were used to identify highly correlated time-activity curves from extracranial voxels. Results: For all subjects, the greatest density of CSF-positive extracranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinate CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET-measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Long-term follow-up of successful treatment for dandy-walker syndrome (DWS).

PubMed

Lin, Jun; Liang, Guobiao; Liang, Yong; Kou, Yun

2015-01-01

Various managements of Dandy-Walker syndrome (DWS) from open excision of the cysts to CSF diversion have been reported. However, optimal treatment for DWS remains elusive. Cyst fenestration was employed firstly, but failed 15 days after the surgery. Then a ventriculoperitoneal (VP) shunt was inserted and the patient discharged from hospital 13 days after the second surgery. During the 12-year follow-up, CT scanning, MRI, and X-radiation were performed. CT scanning showed that the size of ventricular system gradually returned to normal. MRI revealed similar changes of the ventricular system, and further revealed the development of supratentorial brain. The results of X-radiation during the follow-up years showed that the peritoneal end of the shunt might be already out of the abdominal cavity. Slow refilling of the shunt valve may suggest that the shunt could be probably not functional. The treatment of the patient was successfully, and the abnormal cerebral ventricle system gradually recovered during the 12-year follow-up. Because the patient might be probably independent on the shunt, further choice of the shunt removal should be thinking thoroughly, considering both safety and quality of life for the patient.

Long-term follow-up of successful treatment for dandy-walker syndrome (DWS)

PubMed Central

Lin, Jun; Liang, Guobiao; Liang, Yong; Kou, Yun

2015-01-01

Background: Various managements of Dandy-Walker syndrome (DWS) from open excision of the cysts to CSF diversion have been reported. However, optimal treatment for DWS remains elusive. Methods: Cyst fenestration was employed firstly, but failed 15 days after the surgery. Then a ventriculoperitoneal (VP) shunt was inserted and the patient discharged from hospital 13 days after the second surgery. During the 12-year follow-up, CT scanning, MRI, and X-radiation were performed. Results: CT scanning showed that the size of ventricular system gradually returned to normal. MRI revealed similar changes of the ventricular system, and further revealed the development of supratentorial brain. The results of X-radiation during the follow-up years showed that the peritoneal end of the shunt might be already out of the abdominal cavity. Slow refilling of the shunt valve may suggest that the shunt could be probably not functional. Conclusion: The treatment of the patient was successfully, and the abnormal cerebral ventricle system gradually recovered during the 12-year follow-up. Because the patient might be probably independent on the shunt, further choice of the shunt removal should be thinking thoroughly, considering both safety and quality of life for the patient. PMID:26770421

Morphogenesis underlying the development of the everted teleost telencephalon.

PubMed

Folgueira, Mónica; Bayley, Philippa; Navratilova, Pavla; Becker, Thomas S; Wilson, Stephen W; Clarke, Jonathan D W

2012-09-18

Although the mechanisms underlying brain patterning and regionalization are very much conserved, the morphology of different brain regions is extraordinarily variable across vertebrate phylogeny. This is especially manifest in the telencephalon, where the most dramatic variation is seen between ray-finned fish, which have an everted telencephalon, and all other vertebrates, which have an evaginated telencephalon. The mechanisms that generate these distinct morphologies are not well understood. Here we study the morphogenesis of the zebrafish telencephalon from 12 hours post fertilization (hpf) to 5 days post fertilization (dpf) by analyzing forebrain ventricle formation, evolving patterns of gene and transgene expression, neuronal organization, and fate mapping. Our results highlight two key events in telencephalon morphogenesis. First, the formation of a deep ventricular recess between telencephalon and diencephalon, the anterior intraencephalic sulcus (AIS), effectively creates a posterior ventricular wall to the telencephalic lobes. This process displaces the most posterior neuroepithelial territory of the telencephalon laterally. Second, as telencephalic growth and neurogenesis proceed between days 2 and 5 of development, the pallial region of the posterior ventricular wall of the telencephalon bulges into the dorsal aspect of the AIS. This brings the ventricular zone (VZ) into close apposition with the roof of the AIS to generate a narrow ventricular space and the thin tela choroidea (tc). As the pallial VZ expands, the tc also expands over the upper surface of the telencephalon. During this period, the major axis of growth and extension of the pallial VZ is along the anteroposterior axis. This second step effectively generates an everted telencephalon by 5 dpf. Our description of telencephalic morphogenesis challenges the conventional model that eversion is simply due to a laterally directed outfolding of the telencephalic neuroepithelium. This may have significant bearing on understanding the eventual organization of the adult fish telencephalon.

Morphogenesis underlying the development of the everted teleost telencephalon

PubMed Central

2012-01-01

Background Although the mechanisms underlying brain patterning and regionalization are very much conserved, the morphology of different brain regions is extraordinarily variable across vertebrate phylogeny. This is especially manifest in the telencephalon, where the most dramatic variation is seen between ray-finned fish, which have an everted telencephalon, and all other vertebrates, which have an evaginated telencephalon. The mechanisms that generate these distinct morphologies are not well understood. Results Here we study the morphogenesis of the zebrafish telencephalon from 12 hours post fertilization (hpf) to 5 days post fertilization (dpf) by analyzing forebrain ventricle formation, evolving patterns of gene and transgene expression, neuronal organization, and fate mapping. Our results highlight two key events in telencephalon morphogenesis. First, the formation of a deep ventricular recess between telencephalon and diencephalon, the anterior intraencephalic sulcus (AIS), effectively creates a posterior ventricular wall to the telencephalic lobes. This process displaces the most posterior neuroepithelial territory of the telencephalon laterally. Second, as telencephalic growth and neurogenesis proceed between days 2 and 5 of development, the pallial region of the posterior ventricular wall of the telencephalon bulges into the dorsal aspect of the AIS. This brings the ventricular zone (VZ) into close apposition with the roof of the AIS to generate a narrow ventricular space and the thin tela choroidea (tc). As the pallial VZ expands, the tc also expands over the upper surface of the telencephalon. During this period, the major axis of growth and extension of the pallial VZ is along the anteroposterior axis. This second step effectively generates an everted telencephalon by 5 dpf. Conclusion Our description of telencephalic morphogenesis challenges the conventional model that eversion is simply due to a laterally directed outfolding of the telencephalic neuroepithelium. This may have significant bearing on understanding the eventual organization of the adult fish telencephalon. PMID:22989074

Influence of the hole geometry on the flow distribution in ventricular catheters for hydrocephalus.

PubMed

Giménez, Ángel; Galarza, Marcelo; Pellicer, Olga; Valero, José; Amigó, José M

2016-07-15

Hydrocephalus is a medical condition consisting of an abnormal accumulation of cerebrospinal fluid within the brain. A catheter is inserted in one of the brain ventricles and then connected to an external valve to drain the excess of cerebrospinal fluid. The main drawback of this technique is that, over time, the ventricular catheter ends up getting blocked by the cells and macromolecules present in the cerebrospinal fluid. A crucial factor influencing this obstruction is a non-uniform flow pattern through the catheter, since it facilitates adhesion of suspended particles to the walls. In this paper we focus on the effects that tilted holes as well as conical holes have on the flow distribution and shear stress. We have carried out 3D computational simulations to study the effect of the hole geometry on the cerebrospinal fluid flow through ventricular catheters. All the simulations were done with the OpenFOAM® toolbox. In particular, three different groups of models were investigated by varying (i) the tilt angles of the holes, (ii) the inner and outer diameters of the holes, and (iii) the distances between the so-called hole segments. The replacement of cylindrical holes by conical holes was found to have a strong influence on the flow distribution and to lower slightly the shear stress. Tilted holes did not involve flow distribution changes when the hole segments are sufficiently separated, but the mean shear stress was certainly reduced. The authors present new results about the behavior of the fluid flow through ventricular catheters. These results complete earlier work on this topic by adding the influence of the hole geometry. The overall objective pursued by this research is to provide guidelines to improve existing commercially available ventricular catheters.

Cerebrovascular Manifestations of Neurosarcoidosis: An Underrecognized Aspect of the Imaging Spectrum.

PubMed

Bathla, G; Watal, P; Gupta, S; Nagpal, P; Mohan, S; Moritani, T

2017-12-28

Involvement of the central nervous system by sarcoidosis, also referred to as neurosarcoidosis, is seen clinically in about 5% of patients with systemic disease. CNS involvement most frequently affects the leptomeninges and cranial nerves, though the ventricular system, brain parenchyma, and pachymeninges may also be involved. Even though the involvement of the intracranial vascular structures is well-known on postmortem studies, there is scant literature on imaging manifestations secondary to the vessel wall involvement, being confined mostly to isolated case reports and small series. The authors present a review of various cerebrovascular manifestations of neurosarcoidosis, along with a brief synopsis of the existing literature. © 2018 by American Journal of Neuroradiology.

STUDIES IN THE PATHOGENESIS OF EXPERIMENTAL DYSENTERY INTOXICATION

PubMed Central

Penner, Abraham; Bernheim, Alice Ida

1960-01-01

The introduction of Shiga toxin into the ventricular system of the brain with major location in the third ventricle resulted in a response similar to that following the administration of the toxin either intravenously or by cross-circulation. The intravenous administration at the dosage level employed would have elicited no response. These observations lend support to the hypothesis that Shiga toxin activates some mechanisms in the central nervous system which are capable of producing visceral lesions. These mechanisms are those which control the vasomotor components of homeostasis. This hypothesis permits an explanation of the proximo-distal and intramural features of the lesion. PMID:13734126

Prevention of salt induced hypertension and fibrosis by angiotensin converting enzyme inhibitors in Dahl S rats

PubMed Central

Liang, B; Leenen, F H H

2007-01-01

Background and purpose: In Dahl S rats, high salt increases activity of the tissue renin-angiotensin-aldosterone system (RAAS) in the CNS, heart and kidneys. Here, we assessed the effects of chronic angiotensin converting enzyme (ACE) inhibition on salt-induced hypertension and cardiovascular and renal hypertrophy and fibrosis, relative to the extent of ACE blockade. Experimental approach: From 4.5 weeks of age, Dahl S rats received either the lipophilic ACE inhibitor trandolapril (1 or 5 mg kg-1 day-1) or the hydrophilic ACE inhibitor lisinopril (10 or 50 mg kg-1 day-1) and a high salt diet was started 0.5 week later. Treatments ended at 9 weeks of age. Key results: High salt diet markedly increased blood pressure (BP), decreased plasma angiotensin II and increased ACE binding densities in brain, heart, aorta and kidneys. Trandolapril and lisinopril prevented 50% of the increase in BP in light and dark period of the day. After the last doses, trandolapril decreased ACE densities by ∼80% in brain nuclei and heart and lisinopril by ∼60% in the brain and by ∼70% in the heart. The two ACE inhibitors prevented right ventricular hypertrophy and attenuated left ventricular hypertrophy but did not affect renal hypertrophy caused by high salt. Both drugs prevented high salt-induced fibrosis in heart, kidney and aorta. Conclusion and implication: As the ACE inhibitors could completely prevent tissue fibrosis and partially prevent tissue hypertrophy and hypertension, the tissue RAAS may play a critical role in salt-induced fibrosis, but a lesser role in the hypertrophy. PMID:17906684

The Superior Frontal Transsulcal Approach to the Anterior Ventricular System: Exploring the Sulcal and Subcortical Anatomy Using Anatomic Dissections and Diffusion Tensor Imaging Tractography.

PubMed

Koutsarnakis, Christos; Liakos, Faidon; Kalyvas, Aristotelis V; Skandalakis, Georgios P; Komaitis, Spyros; Christidi, Fotini; Karavasilis, Efstratios; Liouta, Evangelia; Stranjalis, George

2017-10-01

To explore the superior frontal sulcus (SFS) morphology, trajectory of the applied surgical corridor, and white matter bundles that are traversed during the superior frontal transsulcal transventricular approach. Twenty normal, adult, formalin-fixed cerebral hemispheres and 2 cadaveric heads were included in the study. The topography, morphology, and dimensions of the SFS were recorded in all specimens. Fourteen hemispheres were investigated through the fiber dissection technique whereas the remaining 6 were explored using coronal cuts. The cadaveric heads were used to perform the superior frontal transsulcal transventricular approach. In addition, 2 healthy volunteers underwent diffusion tensor imaging and tractography reconstruction studies. The SFS was interrupted in 40% of the specimens studied and was always parallel to the interhemispheric fissure. The proximal 5 cm of the SFS (starting from the SFS precentral sulcus meeting point) were found to overlie the anterior ventricular system in all hemispheres. Five discrete white matter layers were identified en route to the anterior ventricular system (i.e., the arcuate fibers, the frontal aslant tract, the external capsule, internal capsule, and the callosal radiations). Diffusion tensor imaging studies confirmed the fiber tract architecture. When feasible, the superior frontal transsulcal transventricular approach offers a safe and effective corridor to the anterior part of the lateral ventricle because it minimizes brain retraction and transgression and offers a wide and straightforward working corridor. Meticulous preoperative planning coupled with a sound microneurosurgical technique are prerequisites to perform the approach successfully. Copyright © 2017 Elsevier Inc. All rights reserved.

Engineering human ventricular heart muscles based on a highly efficient system for purification of human pluripotent stem cell-derived ventricular cardiomyocytes.

PubMed

Li, Bin; Yang, Hui; Wang, Xiaochen; Zhan, Yongkun; Sheng, Wei; Cai, Huanhuan; Xin, Haoyang; Liang, Qianqian; Zhou, Ping; Lu, Chao; Qian, Ruizhe; Chen, Sifeng; Yang, Pengyuan; Zhang, Jianyi; Shou, Weinian; Huang, Guoying; Liang, Ping; Sun, Ning

2017-09-29

Most infarctions occur in the left anterior descending coronary artery and cause myocardium damage of the left ventricle. Although current pluripotent stem cells (PSCs) and directed cardiac differentiation techniques are able to generate fetal-like human cardiomyocytes, isolation of pure ventricular cardiomyocytes has been challenging. For repairing ventricular damage, we aimed to establish a highly efficient purification system to obtain homogeneous ventricular cardiomyocytes and prepare engineered human ventricular heart muscles in a dish. The purification system used TALEN-mediated genomic editing techniques to insert the neomycin or EGFP selection marker directly after the myosin light chain 2 (MYL2) locus in human pluripotent stem cells. Purified early ventricular cardiomyocytes were estimated by immunofluorescence, fluorescence-activated cell sorting, quantitative PCR, microelectrode array, and patch clamp. In subsequent experiments, the mixture of mature MYL2-positive ventricular cardiomyocytes and mesenchymal cells were cocultured with decellularized natural heart matrix. Histological and electrophysiology analyses of the formed tissues were performed 2 weeks later. Human ventricular cardiomyocytes were efficiently isolated based on the purification system using G418 or flow cytometry selection. When combined with the decellularized natural heart matrix as the scaffold, functional human ventricular heart muscles were prepared in a dish. These engineered human ventricular muscles can be great tools for regenerative therapy of human ventricular damage as well as drug screening and ventricular-specific disease modeling in the future.

On old and new comparative neurological sinners: the evolutionary importance of the membranous parts of the actinopterygian forebrain and their sites of attachment.

PubMed

Nieuwenhuys, Rudolf

2009-09-10

The forebrain of actinopterygian fishes differs from that of other vertebrates in that it consists of a pair of solid lobes. Lateral ventricles surrounded by nervous tissue are entirely lacking. This peculiar configuration of the actinopterygian forebrain results from an outward bending or eversion of its lateral walls during ontogenesis. Due to this eversion, the telencephalic roof plate is transformed into a wide, membranous structure that surrounds the dorsal and lateral parts of the solid lobes and is attached to their lateral or ventrolateral aspects. Another effect of the eversion is that the ventricular surface of the telencephalic lobes is very extensive, whereas their meningeal surface is small. In many recent publications on the forebrain of actinopterygian fishes, these structures are presented as solid lobes, without any reference to the fact that they are the product of an eversion process, and without any indication concerning the location and extent of their ventricular and meningeal surfaces. It is explained here that, in light of current concepts concerning the histogenesis of the brain, these omissions are intolerable. It is also strongly recommended that the location and extent of these surfaces should always be clearly indicated in brain sections in general, because the simple notion that in the brain of vertebrates the ventricular surface is on the inside and the meningeal surface on the outside has numerous and notable exceptions. Copyright 2009 Wiley-Liss, Inc.

Computational and Organotypic Modeling of Microcephaly ...

EPA Pesticide Factsheets

Microcephaly is associated with reduced cortical surface area and ventricular dilations. Many genetic and environmental factors precipitate this malformation, including prenatal alcohol exposure and maternal Zika infection. This complexity motivates the engineering of computational and experimental models to probe the underlying molecular targets, cellular consequences, and biological processes. We describe an Adverse Outcome Pathway (AOP) framework for microcephaly derived from literature on all gene-, chemical-, or viral- effects and brain development. Overlap with NTDs is likely, although the AOP connections identified here focused on microcephaly as the adverse outcome. A query of the Mammalian Phenotype Browser database for ‘microcephaly’ (MP:0000433) returned 85 gene associations; several function in microtubule assembly and centrosome cycle regulated by (microcephalin, MCPH1), a gene for primary microcephaly in humans. The developing ventricular zone is the likely target. In this zone, neuroprogenitor cells (NPCs) self-replicate during the 1st trimester setting brain size, followed by neural differentiation of the neocortex. Recent studies with human NPCs confirmed infectivity with Zika virions invoking critical cell loss (apoptosis) of precursor NPCs; similar findings have been shown with fetal alcohol or methylmercury exposure in rodent studies, leading to mathematical models of NPC dynamics in size determination of the ventricular zone. A key event

[Value of computer tomography in the managment of brain injuries].

PubMed

Keita, A D; Toure, M; Sissako, A; Doumbia, S; Coulibaly, Y; Doumbia, D; Kane, M; Diallo, A K; Toure, A A; Traore, I

2005-11-01

The purpose of this prospective study conducted from January 2001 to December 2001 was to ascertain the value of computer tomography for evaluation of brain injuries. Computer tomography was performed using a Toshiba X VID system with contiguous 5 mm axial sections through the posterior fossa and 10 mm contiguous axial sections through the subtentorial region without contrast injection. A total of 107 patients with brain injuries were enrolled over the one-year study period. These patients accounted for 0.8% of all admissions to surgical emergency unit of Gabriel Toure Hospital in Bamako, Mali. The predominant age group for brain injuries was the 20- to 29-year-old group (35 cases). The male-to-female sex ratio was 5:1. Vehicular accident was the most frequent cause of brain injury (76 cases). Trauma was severe in 48 patients with a Glasgow score less than 8. Coma occurred immediately after injury in 90 cases. Ventricular hemorrhage led to coma in 100% of cases whereas brain hemorrhage and hematoma led to coma in 93.3% and 83.3% of cases respectively. Treatment was medical in 99 cases and neurosurgical in 8. The mortality rate was 34% and the morbidity rate (permanent sequels) was 36%. Computer tomography is a valuable tool for therapeutic decision-making in medico-surgical emergencies involving brain injuries.

Neuroanatomy: The added value of the Klingler method.

PubMed

Silva, Susana M; Andrade, José Paulo

2016-11-01

Undergraduate neuroanatomy students are usually not able to achieve a clear comprehension of the spatial relationships existing between the white matter fiber tracts in spite of numerous neuroanatomy textbooks, atlases and multimedia tools. The objective of this paper is to show the educational value of the application of the Klingler fiber dissection technique and the use of these dissections in the understanding of the three-dimensional intrinsic anatomy of the brain white matter for medical students. Four formalin-fixed brains were dissected using the Klingler methodology in order to reveal the inner anatomical organization of the brain white matter. The most important fiber systems were dissected and their relationships to the cerebral and cerebellar gray matter structures visualized. These dissections were used as a learning tool in teaching the brain white matter structural and topographical connectivity. The white matter fiber systems were presented to undergraduate medical students during a neuroanatomy course. They observed and manipulated the dissected specimens leading to a thorough understanding of the configuration and location of the white matter fiber tracts, and their relationships to the ventricular system and gray matter structures. Subsequently, students were asked to answer a survey concerning the importance of the utilization of this material in their understanding of the three-dimensional intrinsic anatomy of the brain white matter. The knowledge acquired with this technique, complemented by conventional formalin-fixed sections may improve the neuroanatomical knowledge and future retention of medical students. Copyright © 2016 Elsevier GmbH. All rights reserved.

Inflammatory biomarkers are not predictive of intermediate-term risk of ventricular tachyarrhythmias in stable CHF patients.

PubMed

Konstantino, Yuval; Kusniec, Jairo; Reshef, Tamar; David-Zadeh, Ofer; Mazur, Alexander; Strasberg, Boris; Battler, Alexander; Haim, Moti

2007-08-01

Elevated levels of inflammatory biomarkers and brain natriuretic peptide (BNP) are associated with increased mortality in patients with heart failure (HF). : The aim of the current study was to assess the correlation between circulating biomarkers and ventricular tachyarrhythmias among patients with HF. Blood samples from 50 stable ambulatory HF patients with moderate to severe systolic left ventricular (LV) dysfunction and an implantable cardioverter defibrillator (ICD) were analyzed for interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), high-sensitivity C-reactive protein (hsCRP) and BNP. Thereafter, the patients were followed for a mean period of 152 +/- 44 days, during which ventricular tachyarrhythmias were recorded by the ICDs. Follow-up data were obtained from 47 patients. Of them, 45 (96%) had ischemic cardiomyopathy, 38 (81%) had New York Heart Association class I-II, 43 (91%) were males, and the mean age was 68.6 +/- 11.1 years. During follow-up, 5 patients (11%) had nonsustained ventricular tachycardia (NSVT), 6 patients (13%) had sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and 36 patients (76%) had no events. The circulating biomarkers' levels upon enrollment were not significantly different between patients who subsequently had NSVT or VT/VF and patients who were free of events. No correlation was found between plasma levels of IL-6, TNF-alpha, hsCRP and BNP and ventricular arrhythmic events among stable HF patients during an intermediate term follow-up of 5.1 months. Further studies are still required to assess the association between these biomarkers and long-term risk of ventricular tachyarrhythmia. (c) 2007 Wiley Periodicals, Inc.

Postnatal brain development of the pulse type, weakly electric gymnotid fish Gymnotus omarorum.

PubMed

Iribarne, Leticia; Castelló, María E

2014-01-01

Teleosts are a numerous and diverse group of fish showing great variation in body shape, ecological niches and behaviors, and a correspondent diversity in brain morphology, usually associated with their functional specialization. Weakly electric fish are a paradigmatic example of functional specialization, as these teleosts use self-generated electric fields to sense the nearby environment and communicate with conspecifics, enabling fish to better exploit particular ecological niches. We analyzed the development of the brain of the pulse type gymnotid Gymnotus omarorum, focusing on the brain regions involved directly or indirectly in electrosensory information processing. A morphometric analysis has been made of the whole brain and of brain regions of interest, based on volumetric data obtained from 3-D reconstructions to study the growth of the whole brain and the relative growth of brain regions, from late larvae to adulthood. In the smallest studied larvae some components of the electrosensory pathway appeared to be already organized and functional, as evidenced by tract-tracing and in vivo field potential recordings of electrosensory-evoked activity. From late larval to adult stages, rombencephalic brain regions (cerebellum and electrosensory lateral line lobe) showed a positive allometric growth, mesencephalic brain regions showed a negative allometric growth, and the telencephalon showed an isometric growth. In a first step towards elucidating the role of cell proliferation in the relative growth of the analyzed brain regions, we also studied the spatial distribution of proliferation zones by means of pulse type BrdU labeling revealed by immunohistochemistry. The brain of G. omarorum late larvae showed a widespread distribution of proliferating zones, most of which were located at the ventricular-cisternal lining. Interestingly, we also found extra ventricular-cisternal proliferation zones at in the rombencephalic cerebellum and electrosensory lateral line lobe. We discuss the role of extraventricular-cisternal proliferation in the relative growth of the latter brain regions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus

PubMed Central

Pyykkö, Okko T.; Lumela, Miikka; Rummukainen, Jaana; Nerg, Ossi; Seppälä, Toni T.; Herukka, Sanna-Kaisa; Koivisto, Anne M.; Alafuzoff, Irina; Puli, Lakshman; Savolainen, Sakari; Soininen, Hilkka; Jääskeläinen, Juha E.; Hiltunen, Mikko; Zetterberg, Henrik; Leinonen, Ville

2014-01-01

Background The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) is unknown. Objective To investigate the role of soluble APP (sAPP) and amyloid beta (Aβ) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Aβ and hyperphosphorylated tau (HPτ) findings. Methods The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Aβ and HPτ. CSF levels of AD-related biomarkers (Aβ42, p-tau, total tau), non-AD-related Aβ isoforms (Aβ38, Aβ40), sAPP isoforms (sAPPα, sAPPβ), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results Lumbar CSF levels of sAPPα were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPβ showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Aβ or HPτ in the brain biopsy. Quantified Aβ load in the brain biopsy showed a negative correlation with CSF levels of Aβ42 in ventricular (r = −0.295, p = 0.003) and lumbar (r = −0.356, p = 0.01) samples, while the levels of Aβ38 and Aβ40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD. PMID:24638077

Changes in motor function, cognition, and emotion-related behavior after right hemispheric intracerebral hemorrhage in various brain regions of mouse.

PubMed

Zhu, Wei; Gao, Yufeng; Wan, Jieru; Lan, Xi; Han, Xiaoning; Zhu, Shanshan; Zang, Weidong; Chen, Xuemei; Ziai, Wendy; Hanley, Daniel F; Russo, Scott J; Jorge, Ricardo E; Wang, Jian

2018-03-01

Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Efficient Multi-Atlas Registration using an Intermediate Template Image

PubMed Central

Dewey, Blake E.; Carass, Aaron; Blitz, Ari M.; Prince, Jerry L.

2017-01-01

Multi-atlas label fusion is an accurate but time-consuming method of labeling the human brain. Using an intermediate image as a registration target can allow researchers to reduce time constraints by storing the deformations required of the atlas images. In this paper, we investigate the effect of registration through an intermediate template image on multi-atlas label fusion and propose a novel registration technique to counteract the negative effects of through-template registration. We show that overall computation time can be decreased dramatically with minimal impact on final label accuracy and time can be exchanged for improved results in a predictable manner. We see almost complete recovery of Dice similarity over a simple through-template registration using the corrected method and still maintain a 3–4 times speed increase. Further, we evaluate the effectiveness of this method on brains of patients with normal-pressure hydrocephalus, where abnormal brain shape presents labeling difficulties, specifically the ventricular labels. Our correction method creates substantially better ventricular labeling than traditional methods and maintains the speed increase seen in healthy subjects. PMID:28943702

Efficient multi-atlas registration using an intermediate template image

NASA Astrophysics Data System (ADS)

Dewey, Blake E.; Carass, Aaron; Blitz, Ari M.; Prince, Jerry L.

2017-03-01

Multi-atlas label fusion is an accurate but time-consuming method of labeling the human brain. Using an intermediate image as a registration target can allow researchers to reduce time constraints by storing the deformations required of the atlas images. In this paper, we investigate the effect of registration through an intermediate template image on multi-atlas label fusion and propose a novel registration technique to counteract the negative effects of through-template registration. We show that overall computation time can be decreased dramatically with minimal impact on final label accuracy and time can be exchanged for improved results in a predictable manner. We see almost complete recovery of Dice similarity over a simple through-template registration using the corrected method and still maintain a 3-4 times speed increase. Further, we evaluate the effectiveness of this method on brains of patients with normal-pressure hydrocephalus, where abnormal brain shape presents labeling difficulties, specifically the ventricular labels. Our correction method creates substantially better ventricular labeling than traditional methods and maintains the speed increase seen in healthy subjects.

Detecting occlusion inside a ventricular catheter using photoacoustic imaging through skull

NASA Astrophysics Data System (ADS)

Tavakoli, Behnoosh; Guo, Xiaoyu; Taylor, Russell H.; Kang, Jin U.; Boctor, Emad M.

2014-03-01

Ventricular catheters are used to treat hydrocephalus by diverting the excess of the cerebrospinal fluid (CSF) to the reabsorption site so as to regulate the intracranial pressure. The failure rate of these shunts is extremely high due to the ingrown tissue that blocks the CSF flow. We have studied a method to image the occlusion inside the shunt through the skull. In this approach the pulsed laser light coupled to the optical fiber illuminate the occluding tissue inside the catheter and an external ultrasound transducer is applied to detect the generated photoacoustic signal. The feasibility of this method is investigated using a phantom made of ovis aries brain tissue and adult human skull. We were able to image the target inside the shunt located 20mm deep inside the brain through about 4mm thick skull bone. This study could lead to the development of a simple, safe and non-invasive device for percutaneous restoration of patency to occluded shunts. This will eliminate the need of the surgical replacement of the occluded catheters which expose the patients to risks including hemorrhage and brain injury.

Blood borne hormones in a cross-talk between peripheral and brain mechanisms regulating blood pressure, the role of circumventricular organs.

PubMed

Ufnal, Marcin; Skrzypecki, Janusz

2014-04-01

Accumulating evidence suggests that blood borne hormones modulate brain mechanisms regulating blood pressure. This appears to be mediated by the circumventricular organs which are located in the walls of the brain ventricular system and lack the blood-brain barrier. Recent evidence shows that neurons of the circumventricular organs express receptors for the majority of cardiovascular hormones. Intracerebroventricular infusions of hormones and their antagonists is one approach to evaluate the influence of blood borne hormones on the neural mechanisms regulating arterial blood pressure. Interestingly, there is no clear correlation between peripheral and central effects of cardiovascular hormones. For example, angiotensin II increases blood pressure acting peripherally and centrally, whereas peripherally acting pressor catecholamines decrease blood pressure when infused intracerebroventricularly. The physiological role of such dual hemodynamic responses has not yet been clarified. In the paper we review studies on hemodynamic effects of catecholamines, neuropeptide Y, angiotensin II, aldosterone, natriuretic peptides, endothelins, histamine and bradykinin in the context of their role in a cross-talk between peripheral and brain mechanisms involved in the regulation of arterial blood pressure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging

NASA Astrophysics Data System (ADS)

Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

2013-02-01

The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

Predicting the risk of sudden cardiac death.

PubMed

Lerma, Claudia; Glass, Leon

2016-05-01

Sudden cardiac death (SCD) is the result of a change of cardiac activity from normal (typically sinus) rhythm to a rhythm that does not pump adequate blood to the brain. The most common rhythms leading to SCD are ventricular tachycardia (VT) or ventricular fibrillation (VF). These result from an accelerated ventricular pacemaker or ventricular reentrant waves. Despite significant efforts to develop accurate predictors for the risk of SCD, current methods for risk stratification still need to be improved. In this article we briefly review current approaches to risk stratification. Then we discuss the mathematical basis for dynamical transitions (called bifurcations) that may lead to VT and VF. One mechanism for transition to VT or VF involves a perturbation by a premature ventricular complex (PVC) during sinus rhythm. We describe the main mechanisms of PVCs (reentry, independent pacemakers and abnormal depolarizations). An emerging approach to risk stratification for SCD involves the development of individualized dynamical models of a patient based on measured anatomy and physiology. Careful analysis and modelling of dynamics of ventricular arrhythmia on an individual basis will be essential in order to improve risk stratification for SCD and to lay a foundation for personalized (precision) medicine in cardiology. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Brain CT scan indexes in the normal pressure hydrocephalus: predictive value in the outcome of patients and correlation to the clinical symptoms.

PubMed

Chatzidakis, Emmanuel M; Barlas, George; Condilis, Nicolas; Bouramas, Dimos; Anagnostopoulos, Demetrios; Volikas, Zacharias; Simopoulos, Konstantinos

2008-01-01

The aim of this study is to find out the correlation of the ventricular size of the brain, as it is estimated using brain computed tomography (CT) scan indexes in patients with normal pressure hydrocephalus (NPH), to: a) the clinical symptoms, and b) the results of cerebrospinal fluid (CSF) shunting procedures. We looked for any predictive value in the estimation of brain CT scan indexes, in patients as above, in whom a shunt is going to be placed. It is well known that it is very difficult to decide who is going to improve after shunting. We studied 40 cases of patients with the diagnosis "NPH" in whom the ventricular shunts were placed. Every symptom (motor disturbance, deficit of memory, incontinence) was separately evaluated preoperatively. The outcome of shunting was also evaluated and the patients were graded. The following CT scan indexes were estimated from the preoperative CT scans of the brain in every case: the ventricle-brain ratio (VBR), the bi-caudate and bi-frontal ratios, the third ventricle-Sylvian fissure (3V-SF) ratio, and the four largest cortical gyri. The method we have used for statistics is "one way analysis of variance", correlating the CT scan indexes to the symptoms of the patients preoperatively, and the outcome of them postoperatively. The main conclusion is that the size of the lateral ventricles of the brain preoperatively is not correlated to the outcome after CSF shunting surgery, but it is correlated to the symptoms of NPH preoperatively.

Neuroprotective Effects of Drug-Induced Therapeutic Hypothermia in Central Nervous System Diseases.

PubMed

Ma, Junwei; Wang, Yibin; Wang, Zhong; Li, Haiying; Wang, Zhimin; Chen, Gang

2017-01-01

This review article focuses on the neuroprotective effect of drug-induced hypothermia in cerebrovascular diseases and discusses its related side effects. A systematic literature search was performed using Pubmed and Embase electronic databases for a retrospective analysis. Experimental studies have shown that drug-induced hypothermia alleviates brain damage and plays a neuroprotective role, thereby reducing mortality and ameliorating neurological deficits. Therefore, drug-induced hypothermia has an important research value and is worth further consideration in the clinical setting. However, drug-induced hypothermia is also associated with side effects, such as ventricular tachycardia, ventricular fibrillation, suppressed immune function, infection, electrolyte imbalance, glucose metabolism disorders, and skeletal muscle tremor. Existing drugs with cooling effects belong to the following categories: (1) dopamine receptor agonists; (2) cannabis; (3) opioid receptors; (4) vanilloid receptors; (5) vasopressins (potent neurotensin receptor agonists); (6) thyroid drugs; (7) adenosine drugs; and (8) purine drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Feasibility Study for Perioperative Ventricular Tachycardia Prognosis and Detection and Noise Detection Using a Neural Network and Predictive Linear Operators

NASA Technical Reports Server (NTRS)

Moebes, T. A.

1994-01-01

To locate the accessory pathway(s) in preexicitation syndromes, epicardial and endocardial ventricular mapping is performed during anterograde ventricular activation via accessory pathway(s) from data originally received in signal form. As the number of channels increases, it is pertinent that more automated detection of coherent/incoherent signals is achieved as well as the prediction and prognosis of ventricular tachywardia (VT). Today's computers and computer program algorithms are not good in simple perceptual tasks such as recognizing a pattern or identifying a sound. This discrepancy, among other things, has been a major motivating factor in developing brain-based, massively parallel computing architectures. Neural net paradigms have proven to be effective at pattern recognition tasks. In signal processing, the picking of coherent/incoherent signals represents a pattern recognition task for computer systems. The picking of signals representing the onset ot VT also represents such a computer task. We attacked this problem by defining four signal attributes for each potential first maximal arrival peak and one signal attribute over the entire signal as input to a back propagation neural network. One attribute was the predicted amplitude value after the maximum amplitude over a data window. Then, by using a set of known (user selected) coherent/incoherent signals, and signals representing the onset of VT, we trained the back propagation network to recognize coherent/incoherent signals, and signals indicating the onset of VT. Since our output scheme involves a true or false decision, and since the output unit computes values between 0 and 1, we used a Fuzzy Arithmetic approach to classify data as coherent/incoherent signals. Furthermore, a Mean-Square Error Analysis was used to determine system stability. The neural net based picking coherent/incoherent signal system achieved high accuracy on picking coherent/incoherent signals on different patients. The system also achieved a high accuracy of picking signals which represent the onset of VT, that is, VT immediately followed these signals. A special binary representation of the input and output data allowed the neural network to train very rapidly as compared to another standard decimal or normalized representations of the data.

Mitral valve prolapse and electrolyte abnormality: a dangerous combination for ventricular arrhythmias

PubMed Central

Rajani, Ali Raza; Murugesan, Vagishwari; Baslaib, Fahad Omar; Rafiq, Muhammad Anwer

2014-01-01

A 27-year-old woman with a history of bileaflet mitral valve prolapse and moderate mitral regurgitation presented to our emergency with untractable polymorphic wide complex tachycardia and unstable haemodynamics. After cardiopulmonary resuscitation, return of spontaneous circulation was achieved 30 min later. Her post-resuscitation ECG showed a prolonged QT interval which progressively normalised over the same day. Her laboratory investigations revealed hypocalcaemia while other electrolytes were within normal limits. A diagnosis of ventricular arrhythmia secondary to structural heart disease further precipitated by hypocalcaemia was made. Further hospital stay did not reveal a recurrence of prolonged QT interval or other arrhythmias except for an episode of non-sustained ventricular tachycardia. However, the patient suffered diffuse hypoxic brain encephalopathy secondary to prolonged cardiopulmonary resuscitation. PMID:24827670

Spontaneous haemorrhage and rupture of third ventricular colloid cyst

PubMed Central

Ogbodo, Elisha; Kaliaperumal, Chandrasekaran; Bermingham, Niamh; O'Sullivan, Michael

2012-01-01

Acute bleeding within a colloid cyst of the third ventricle represents a rare event causing sudden increase in the cyst volume that may lead to acute hydrocephalus and rapid neurological deterioration. We report a case of spontaneous rupture of haemorrhagic third ventricular colloid cyst and its management. A 77-year-old ex-smoker presented with unsteady gait, incontinence and gradually worsening confusion over a 3-week period. Brain CT scan findings were highly suggestive of a third ventricular colloid cyst with intraventricular rupture. He underwent cyst excision and histopathology, which confirmed the radiological diagnosis with evidence of haemorrhage within the cyst. A ventriculo peritoneal shunt was performed for delayed hydrocephalus. Surgical management of these patients must include emergency ventriculostomy followed by prompt surgical removal of the haemorrhagic cyst. PMID:22949002

The proliferative ventricular zone in adult vertebrates: a comparative study using reptiles, birds, and mammals.

PubMed

García-Verdugo, Jose Manuel; Ferrón, Sacri; Flames, Nuria; Collado, Lucía; Desfilis, Ester; Font, Enrique

2002-04-01

Although evidence accumulated during the last decades has advanced our understanding of adult neurogenesis in the vertebrate brain, many aspects of this intriguing phenomenon remain controversial. Here we review the organization and cellular composition of the ventricular wall of reptiles, birds, and mammals in an effort to identify differences and commonalities among these vertebrate classes. Three major cell types have been identified in the ventricular zone of reptiles and birds: migrating (Type A) cells, radial glial (Type B) cells, and ependymal (Type E) cells. Cells similar anatomically and functionally to Types A, B, and E have also been described in the ventricular wall of mammals, which contains an additional cell type (Type C) not found in reptiles or birds. The bulk of the evidence points to a role of Type B cells as primary neural precursors (stem cells) in the three classes of living amniotic vertebrates. This finding may have implications for the development of strategies for the possible treatment of human neurological disorders.

Progenitor cell dynamics in the Newt Telencephalon during homeostasis and neuronal regeneration.

PubMed

Kirkham, Matthew; Hameed, L Shahul; Berg, Daniel A; Wang, Heng; Simon, András

2014-04-08

The adult newt brain has a marked neurogenic potential and is highly regenerative. Ventricular, radial glia-like ependymoglia cells give rise to neurons both during normal homeostasis and after injury, but subpopulations among ependymoglia cells have not been defined. We show here that a substantial portion of GFAP(+) ependymoglia cells in the proliferative hot spots of the telencephalon has transit-amplifying characteristics. In contrast, proliferating ependymoglia cells, which are scattered along the ventricular wall, have stem cell features in terms of label retention and insensitivity to AraC treatment. Ablation of neurons remodels the proliferation dynamics and leads to de novo formation of regions displaying features of neurogenic niches, such as the appearance of cells with transit-amplifying features and proliferating neuroblasts. The results have implication both for our understanding of the evolutionary diversification of radial glia cells as well as the processes regulating neurogenesis and regeneration in the adult vertebrate brain.

Is right ventricular mid-septal pacing superior to apical pacing in patients with high degree atrio-ventricular block and moderately depressed left ventricular function?

PubMed

Chen, Kang; Mao, Ye; Liu, Shao-hua; Wu, Qiong; Luo, Qing-zhi; Pan, Wen-qi; Jin, Qi; Zhang, Ning; Ling, Tian-you; Chen, Ying; Gu, Gang; Shen, Wei-feng; Wu, Li-qun

2014-06-01

We are aimed to investigate whether right ventricular mid-septal pacing (RVMSP) is superior to conventional right ventricular apical pacing (RVAP) in improving clinical functional capacity and left ventricular ejection fraction (LVEF) for patients with high-degree atrio-ventricular block and moderately depressed left ventricle (LV) function. Ninety-two patients with high-degree atrio-ventricular block and moderately reduced LVEF (ranging from 35% to 50%) were randomly allocated to RVMSP (n=45) and RVAP (n=47). New York Heart Association (NYHA) functional class, echocardiographic LVEF, and distance during a 6-min walk test (6MWT) were determined at 18 months after pacemaker implantation. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Compared with baseline, NYHA functional class remained unchanged at 18 months, distance during 6MWT (485 m vs. 517 m) and LVEF (36.7% vs. 41.8%) were increased, but BNP levels were reduced (2352 pg/ml vs. 710 pg/ml) in the RVMSP group compared with those in the RVAP group, especially in patients with LVEF 35%-40% (for all comparisons, P<0.05). However, clinical function capacity and LV function measurements were not significantly changed in patients with RVAP, despite the pacing measurements being similar in both groups, such as R-wave amplitude and capture threshold. RVMSP provides a better clinical utility, compared with RVAP, in patients with high-degree atrioventricular block and moderately depressed LV function whose LVEF levels ranged from 35% to 40%.

Reduction of N terminal-pro-brain (B-type) natriuretic peptide levels with exercise-based cardiac rehabilitation in patients with left ventricular dysfunction after myocardial infarction.

PubMed

Giallauria, Francesco; De Lorenzo, Anna; Pilerci, Francesco; Manakos, Athanasio; Lucci, Rosa; Psaroudaki, Marianna; D'Agostino, Mariantonietta; Del Forno, Domenico; Vigorito, Carlo

2006-08-01

N-terminal-pro-brain (B-type) natriuretic peptide (NT-pro-BNP) is a peptide hormone released from ventricles in response to myocyte stretch. The aim of the study was to investigate the influence of exercise training on plasma NT-pro-BNP to verify if this parameter could be used as a biological marker of left ventricular remodelling in myocardial infarction patients undergoing an exercise training programme. Forty-four patients after myocardial infarction were enrolled into a cardiac rehabilitation programme, and were randomized in two groups of 22 patients each. Group A patients followed a 3-month exercise training programme, while group B patients received only routine recommendations. All patients underwent NT-pro-BNP assay, and cardiopulmonary exercise test before hospital discharge and after 3 months. In Group A, exercise training reduced NT-pro-BNP levels (from 1498+/-438 to 470+/-375 pg/ml, P=0.0026), increased maximal (VO2peak+4.3+/-2.9 ml/kg per min, P<0.001; Powermax+38+/-7, P<0.001) exercise parameters and work efficiency (Powermax/VO2peak+1.3+/-0.4 Power/ml per kg per min, P<0.001); there was also an inverse correlation between changes in NT-pro-BNP levels and in VO2peak (r=-0.72, P<0.001), E-wave (r=-0.51, P<0.001) and E/A ratio (r=0.59, P<0.001). In group B, at 3 months, no changes were observed in NT-pro-BNP levels, exercise and echocardiographic parameters. Three months exercise training in patients with moderate left ventricular systolic dysfunction after myocardial infarction induced a reduction in NT-pro-BNP levels, an improvement of exercise capacity and early left ventricular diastolic filling, without negative left ventricular remodelling. Whether the reduction of NT-pro-BNP levels could be useful as a surrogate marker of favourable left ventricular remodelling at a later follow-up remains to be further explored.

Effects of carvedilol on structural and functional outcomes and plasma biomarkers in the mouse transverse aortic constriction heart failure model

PubMed Central

Hampton, Caryn; Rosa, Raymond; Szeto, Daphne; Forrest, Gail; Campbell, Barry; Kennan, Richard; Wang, Shubing; Huang, Chin-Hu; Gichuru, Loise; Ping, Xiaoli; Shen, Xiaolan; Small, Kersten; Madwed, Jeffrey; Lynch, Joseph J

2017-01-01

Introduction: Despite the widespread use of the mouse transverse aortic constriction heart failure model, there are no reports on the characterization of the standard-of-care agent carvedilol in this model. Methods: Left ventricular pressure overload was produced in mice by transverse aortic constriction between the innominate and left common carotid arteries. Carvedilol was administered at multiple dose levels (3, 10 and 30 mg/kg/day per os; yielding end-study mean plasma concentrations of 0.002, 0.015 and 0.044 µM, respectively) in a therapeutic design protocol with treatment initiated after the manifestation of left ventricular remodeling at 3 weeks post transverse aortic constriction and continued for 10 weeks. Results: Carvedilol treatment in transverse aortic constriction mice significantly decreased heart rate and left ventricular dP/dt (max) at all dose levels consistent with β-adrenoceptor blockade. The middle dose of carvedilol significantly decreased left ventricular weight, whereas the higher dose decreased total heart, left and right ventricular weight and wet lung weight compared to untreated transverse aortic constriction mice. The higher dose of carvedilol significantly increased cardiac performance as measured by ejection fraction and fractional shortening and decreased left ventricular end systolic volume consistent with the beneficial effect on cardiac function. End-study plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic constriction control and transverse aortic constriction carvedilol groups. Plasma brain natriuretic peptide concentrations were elevated significantly in transverse aortic constriction control animals (~150%) compared to shams in association with changes in ejection fraction and heart weight and tended to decrease (~30%, p = 0.10–0.12) with the mid- and high-dose carvedilol treatment. Conclusion: A comparison of carvedilol hemodynamic and structural effects in the mouse transverse aortic constriction model versus clinical use indicates a strong agreement in effect profiles preclinical versus clinical, providing important translational validation for this widely used animal model. The present plasma brain natriuretic peptide biomarker findings support the measurement of plasma natriuretic peptides in the mouse transverse aortic constriction model to extend the translational utility of the model. PMID:28491305

[The effect of atrial pacing on left ventricular diastolic function and BNP levels in patients with DDD pacemaker].

PubMed

Apali, Zeynep; Bayata, Serdar; Yeşil, Murat; Arikan, Erdinç; Postaci, Nursen

2010-08-01

We aimed to investigate the effect of atrial pacing on left ventricular diastolic function and brain natriuretic peptide (BNP) levels in patients with DDD pacemaker. Thirty patients with complete atrio-ventricular (AV) block and DDD pacemaker were included. All patients had normal left ventricular systolic function. Echocardiographic diastolic function parameters (transmitral and tissue Doppler velocities during early (E and E') and late (A and A') filling) and NT-pro-BNP levels were evaluated prospectively during atrial sensing and pacing periods. Echocardiographic data were compared with paired sample t test and NT-pro-BNP levels were compared with Wilcoxon test. Echocardiographic E/A, E'/A', E/E' ratios were calculated as 0.72+/-0.34, 0.61+/-0.21 and 8.76+/-2.58 during atrial sensing period. Same parameters were found as 0.71+/-0.23, 0.64+/-0.16 and 8.93+/-3.16 respectively during atrial pacing period. Echocardiographic left ventricular diastolic function parameters were not significantly different during atrial pacing and atrial sensing periods. Median plasma NT-pro-BNP levels were measured as 142 pg/ml (min-max 47-563 pg/ml) and 147 pg/ml (min-max 33-1035 pg/ml) during atrial sensing and pacing periods respectively. These levels were not significantly different (p=0.86). The result of this study has shown that, atrial pacing has not any additional detrimental effect on left ventricular diastolic function parameters in paced patients with normal left ventricular systolic function.

In vivo evaluation of radiotracers targeting the melanin-concentrating hormone receptor 1: [11C]SNAP-7941 and [18F]FE@SNAP reveal specific uptake in the ventricular system.

PubMed

Zeilinger, Markus; Dumanic, Monika; Pichler, Florian; Budinsky, Lubos; Wadsak, Wolfgang; Pallitsch, Katharina; Spreitzer, Helmut; Lanzenberger, Rupert; Hacker, Marcus; Mitterhauser, Markus; Philippe, Cécile

2017-08-14

The MCHR1 is involved in the regulation of energy homeostasis and changes of the expression are linked to a variety of associated diseases, such as diabetes and adiposity. The study aimed at the in vitro and in vivo evaluation of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP as potential PET-tracers for the MCHR1. Competitive binding studies with non-radioactive derivatives and small-animal PET/CT and MRI brain studies were performed under baseline conditions and tracer displacement with the unlabelled MCHR1 antagonist (±)-SNAP-7941. Binding studies evinced high binding affinity of the non-radioactive derivatives. Small-animal imaging of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP evinced high tracer uptake in MCHR1-rich regions of the ventricular system. Quantitative analysis depicted a significant tracer reduction after displacement with (±)-SNAP-7941. Due to the high binding affinity of the non-labelled derivatives and the high specific tracer uptake of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP, there is strong evidence that both radiotracers may serve as highly suitable agents for specific MCHR1 imaging.

Development of representative magnetic resonance imaging-based atlases of the canine brain and evaluation of three methods for atlas-based segmentation.

PubMed

Milne, Marjorie E; Steward, Christopher; Firestone, Simon M; Long, Sam N; O'Brien, Terrence J; Moffat, Bradford A

2016-04-01

To develop representative MRI atlases of the canine brain and to evaluate 3 methods of atlas-based segmentation (ABS). 62 dogs without clinical signs of epilepsy and without MRI evidence of structural brain disease. The MRI scans from 44 dogs were used to develop 4 templates on the basis of brain shape (brachycephalic, mesaticephalic, dolichocephalic, and combined mesaticephalic and dolichocephalic). Atlas labels were generated by segmenting the brain, ventricular system, hippocampal formation, and caudate nuclei. The MRI scans from the remaining 18 dogs were used to evaluate 3 methods of ABS (manual brain extraction and application of a brain shape-specific template [A], automatic brain extraction and application of a brain shape-specific template [B], and manual brain extraction and application of a combined template [C]). The performance of each ABS method was compared by calculation of the Dice and Jaccard coefficients, with manual segmentation used as the gold standard. Method A had the highest mean Jaccard coefficient and was the most accurate ABS method assessed. Measures of overlap for ABS methods that used manual brain extraction (A and C) ranged from 0.75 to 0.95 and compared favorably with repeated measures of overlap for manual extraction, which ranged from 0.88 to 0.97. Atlas-based segmentation was an accurate and repeatable method for segmentation of canine brain structures. It could be performed more rapidly than manual segmentation, which should allow the application of computer-assisted volumetry to large data sets and clinical cases and facilitate neuroimaging research and disease diagnosis.

Developmental and Regional Patterns of GAP-43 Immunoreactivity in a Metamorphosing Brain

PubMed Central

Simmons, Andrea Megela; Tanyu, Leslie H.; Horowitz, Seth S.; Chapman, Judith A.; Brown, Rebecca A.

2012-01-01

Growth-associated protein-43 is typically expressed at high levels in the nervous system during development. In adult animals, its expression is lower, but still observable in brain areas showing structural or functional plasticity. We examined patterns of GAP-43 immunoreactivity in the brain of the bullfrog, an animal whose nervous system undergoes considerable reorganization across metamorphic development and retains a strong capacity for plasticity in adulthood. Immunolabeling was mostly diffuse in hatchling tadpoles, but became progressively more discrete as larval development proceeded. In many brain areas, intensity of immunolabel peaked at metamorphic climax, the time of final transition from aquatic to semi-terrestrial life. Changes in intensity of GAP-43 expression in the medial vestibular nucleus, superior olivary nucleus, and torus semicircularis appeared correlated with stage-dependent functional changes in processing auditory stimuli. Immunolabeling in the Purkinje cell layer of the cerebellum and in the cerebellar nucleus was detectable at most developmental time points. Heavy immunolabel was present from early larval stages through the end of climax in the thalamus (ventromedial, anterior, posterior, central nuclei). Immunolabel in the tadpole telencephalon was observed around the lateral ventricles, and in the medial septum and ventral striatum. In postmetamorphic animals, immunoreactivity was confined mainly to the ventricular zones and immediately adjacent cell layers. GAP-43 expression was present in olfactory, auditory and optic cranial nerves throughout larval and postmetamorphic life. The continued expression of GAP-43 in brain nuclei and in cranial nerves throughout development and into adulthood reflects the high regenerative potential of the bullfrog’s central nervous system. PMID:18431052

Cardiac index is associated with brain aging: the Framingham Heart Study.

PubMed

Jefferson, Angela L; Himali, Jayandra J; Beiser, Alexa S; Au, Rhoda; Massaro, Joseph M; Seshadri, Sudha; Gona, Philimon; Salton, Carol J; DeCarli, Charles; O'Donnell, Christopher J; Benjamin, Emelia J; Wolf, Philip A; Manning, Warren J

2010-08-17

Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community. Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, or dementia (age, 61+/-9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent cardiovascular disease were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post hoc comparisons revealed that participants in the bottom cardiac index tertile (values <2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values >2.92). Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.

Cardiac index is associated with brain aging: The Framingham Heart Study

PubMed Central

Jefferson, Angela L.; Himali, Jayandra J.; Beiser, Alexa S.; Au, Rhoda; Massaro, Joseph M.; Seshadri, Sudha; Gona, Philimon; Salton, Carol J.; DeCarli, Charles; O’Donnell, Christopher J.; Benjamin, Emelia J.; Wolf, Philip A.; Manning, Warren J.

2010-01-01

Background Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease (CVD), theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with pre-clinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer’s disease in the community. Methods and Results Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free from clinical stroke, transient ischemic attack, or dementia (61±9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent CVD were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post-hoc comparisons revealed that participants in the bottom cardiac index tertile (values<2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values>2.92). Conclusions Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging. PMID:20679552

Genetic and environmental influences on the size of specific brain regions in midlife: the VETSA MRI study.

PubMed

Kremen, William S; Prom-Wormley, Elizabeth; Panizzon, Matthew S; Eyler, Lisa T; Fischl, Bruce; Neale, Michael C; Franz, Carol E; Lyons, Michael J; Pacheco, Jennifer; Perry, Michele E; Stevens, Allison; Schmitt, J Eric; Grant, Michael D; Seidman, Larry J; Thermenos, Heidi W; Tsuang, Ming T; Eisen, Seth A; Dale, Anders M; Fennema-Notestine, Christine

2010-01-15

The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, most studies of genetic and environmental influences on human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs). Participants were 474 middle-aged male twins (202 pairs; 70 unpaired) in the Vietnam Era Twin Study of Aging (VETSA). They were 51-59 years old, and were similar to U.S. men in their age range in terms of sociodemographic and health characteristics. We measured thickness of cortical ROIs and volume of other ROIs. On average, genetic influences accounted for approximately 70% of the variance in the volume of global, subcortical, and ventricular ROIs and approximately 45% of the variance in the thickness of cortical ROIs. There was greater variability in the heritability of cortical ROIs (0.00-0.75) as compared with subcortical and ventricular ROIs (0.48-0.85). The results did not indicate lateralized heritability differences or greater genetic influences on the size of regions underlying higher cognitive functions. The findings provide key information for imaging genetic studies and other studies of brain phenotypes and endophenotypes. Longitudinal analysis will be needed to determine whether the degree of genetic and environmental influences changes for different ROIs from midlife to later life.

Longitudinal relaxographic imaging of white matter hyperintensities in the elderly

PubMed Central

2014-01-01

Background Incidental white matter hyperintensities (WMHs) are common findings on T2-weighted magnetic resonance images of the aged brain and have been associated with cognitive decline. While a variety of pathogenic mechanisms have been proposed, the origin of WMHs and the extent to which lesions in the deep and periventricular white matter reflect distinct etiologies remains unclear. Our aim was to quantify the fractional blood volume (vb) of small WMHs in vivo using a novel magnetic resonance imaging (MRI) approach and examine the contribution of blood–brain barrier disturbances to WMH formation in the deep and periventricular white matter. Methods Twenty-three elderly volunteers (aged 59–82 years) underwent 7 Tesla relaxographic imaging and fluid-attenuated inversion recovery (FLAIR) MRI. Maps of longitudinal relaxation rate constant (R1) were prepared before contrast reagent (CR) injection and throughout CR washout. Voxelwise estimates of vb were determined by fitting temporal changes in R1 values to a two-site model that incorporates the effects of transendothelial water exchange. Average vb values in deep and periventricular WMHs were determined after semi-automated segmentation of FLAIR images. Ventricular permeability was estimated from the change in CSF R1 values during CR washout. Results In the absence of CR, the total water fraction in both deep and periventricular WMHs was increased compared to normal appearing white matter (NAWM). The vb of deep WMHs was 1.8 ± 0.6 mL/100 g and was significantly reduced compared to NAWM (2.4 ± 0.8 mL/100 g). In contrast, the vb of periventricular WMHs was unchanged compared to NAWM, decreased with ventricular volume and showed a positive association with ventricular permeability. Conclusions Hyperintensities in the deep WM appear to be driven by vascular compromise, while those in the periventricular WM are most likely the result of a compromised ependyma in which the small vessels remain relatively intact. These findings support varying contributions of blood–brain barrier and brain-CSF interface disturbances in the pathophysiology of deep and periventricular WMHs in the aged human brain. PMID:25379172

Localisation of atrial natriuretic peptide immunoreactivity in the ventricular myocardium and conduction system of the human fetal and adult heart.

PubMed Central

Wharton, J; Anderson, R H; Springall, D; Power, R F; Rose, M; Smith, A; Espejo, R; Khaghani, A; Wallwork, J; Yacoub, M H

1988-01-01

Atrial natriuretic peptide immunoreactivity was found in ventricular and atrial tissues with specific antisera raised to the amino and carboxy terminal regions of the precursor molecule. In 13 developing human hearts (7-24 weeks' gestation) the immunoreactivity was concentrated in the atrial myocardium and ventricular conduction system but it was also detected in the early fetal ventricular myocardium. Immunoreactivity in five normal adults was largely confined to the atrial myocardium although it was also found in the ventricular conduction tissues of hearts removed from 10 patients who were undergoing cardiac transplantation. The ventricular conduction system is an extra-atrial site for the synthesis of atrial natriuretic peptide. In the failing heart this synthesis may be further supplemented by expression of the gene in the ventricular myocardium. It is possible that ventricular production of the peptide contributes to the raised circulating concentrations of atrial natriuretic peptide immunoreactivity found in severe congestive heart disease, particularly in patients with dilated cardiomyopathy. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 PMID:2973340

The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output.

PubMed

Smerup, Morten; Damkjær, Mads; Brøndum, Emil; Baandrup, Ulrik T; Kristiansen, Steen Buus; Nygaard, Hans; Funder, Jonas; Aalkjær, Christian; Sauer, Cathrine; Buchanan, Rasmus; Bertelsen, Mads Frost; Østergaard, Kristine; Grøndahl, Carsten; Candy, Geoffrey; Hasenkam, J Michael; Secher, Niels H; Bie, Peter; Wang, Tobias

2016-02-01

Giraffes--the tallest extant animals on Earth--are renowned for their high central arterial blood pressure, which is necessary to secure brain perfusion. Arterial pressure may exceed 300 mmHg and has historically been attributed to an exceptionally large heart. Recently, this has been refuted by several studies demonstrating that the mass of giraffe heart is similar to that of other mammals when expressed relative to body mass. It thus remains unexplained how the normal-sized giraffe heart generates such massive arterial pressures. We hypothesized that giraffe hearts have a small intraventricular cavity and a relatively thick ventricular wall, allowing for generation of high arterial pressures at normal left ventricular wall tension. In nine anaesthetized giraffes (495±38 kg), we determined in vivo ventricular dimensions using echocardiography along with intraventricular and aortic pressures to calculate left ventricular wall stress. Cardiac output was also determined by inert gas rebreathing to provide an additional and independent estimate of stroke volume. Echocardiography and inert gas-rebreathing yielded similar cardiac outputs of 16.1±2.5 and 16.4±1.4 l min(-1), respectively. End-diastolic and end-systolic volumes were 521±61 ml and 228±42 ml, respectively, yielding an ejection fraction of 56±4% and a stroke volume of 0.59 ml kg(-1). Left ventricular circumferential wall stress was 7.83±1.76 kPa. We conclude that, relative to body mass, a small left ventricular cavity and a low stroke volume characterizes the giraffe heart. The adaptations result in typical mammalian left ventricular wall tensions, but produce a lowered cardiac output. © 2016. Published by The Company of Biologists Ltd.

Extraction of the human cerebral ventricular system from MRI: inclusion of anatomical knowledge and clinical perspective

NASA Astrophysics Data System (ADS)

Aziz, Aamer; Hu, Qingmao; Nowinski, Wieslaw L.

2004-04-01

The human cerebral ventricular system is a complex structure that is essential for the well being and changes in which reflect disease. It is clinically imperative that the ventricular system be studied in details. For this reason computer assisted algorithms are essential to be developed. We have developed a novel (patent pending) and robust anatomical knowledge-driven algorithm for automatic extraction of the cerebral ventricular system from MRI. The algorithm is not only unique in its image processing aspect but also incorporates knowledge of neuroanatomy, radiological properties, and variability of the ventricular system. The ventricular system is divided into six 3D regions based on the anatomy and its variability. Within each ventricular region a 2D region of interest (ROI) is defined and is then further subdivided into sub-regions. Various strict conditions that detect and prevent leakage into the extra-ventricular space are specified for each sub-region based on anatomical knowledge. Each ROI is processed to calculate its local statistics, local intensity ranges of cerebrospinal fluid and grey and white matters, set a seed point within the ROI, grow region directionally in 3D, check anti-leakage conditions and correct growing if leakage occurs and connects all unconnected regions grown by relaxing growing conditions. The algorithm was tested qualitatively and quantitatively on normal and pathological MRI cases and worked well. In this paper we discuss in more detail inclusion of anatomical knowledge in the algorithm and usefulness of our approach from clinical perspective.

Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

PubMed

Kizil, Caghan; Iltzsche, Anne; Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

2015-01-01

Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

Ultrasound-guided microinjection into the mouse forebrain in utero at E9.5.

PubMed

Pierfelice, Tarran J; Gaiano, Nicholas

2010-11-13

In utero survival surgery in mice permits the molecular manipulation of gene expression during development. However, because the uterine wall is opaque during early embryogenesis, the ability to target specific parts of the embryo for microinjection is greatly limited. Fortunately, high-frequency ultrasound imaging permits the generation of images that can be used in real time to guide a microinjection needle into the embryonic region of interest. Here we describe the use of such imaging to guide the injection of retroviral vectors into the ventricular system of the mouse forebrain at embryonic day (E) 9.5. This method uses a laparotomy to permit access to the uterine horns, and a specially designed plate that permits host embryos to be bathed in saline while they are imaged and injected. Successful surgeries often result in most or all of the injected embryos surviving to any subsequent time point of interest (embryonically or postnatally). The principles described here can be used with slight modifications to perform injections into the amnionic fluid of E8.5 embryos (thereby permitting infection along the anterior posterior extent of the neural tube, which has not yet closed), or into the ventricular system of the brain at E10.5/11.5. Furthermore, at mid-neurogenic ages (~E13.5), ultrasound imaging can be used direct injection into specific brain regions for viral infection or cell transplantation. The use of ultrasound imaging to guide in utero injections in mice is a very powerful technique that permits the molecular and cellular manipulation of mouse embryos in ways that would otherwise be exceptionally difficult if not impossible.

Neural basis of exertional fatigue in the heat: A review of magnetic resonance imaging methods.

PubMed

Tan, X R; Low, I C C; Stephenson, M C; Soong, T W; Lee, J K W

2018-03-01

The central nervous system, specifically the brain, is implicated in the development of exertional fatigue under a hot environment. Diverse neuroimaging techniques have been used to visualize the brain activity during or after exercise. Notably, the use of magnetic resonance imaging (MRI) has become prevalent due to its excellent spatial resolution and versatility. This review evaluates the significance and limitations of various brain MRI techniques in exercise studies-brain volumetric analysis, functional MRI, functional connectivity MRI, and arterial spin labeling. The review aims to provide a summary on the neural basis of exertional fatigue and proposes future directions for brain MRI studies. A systematic literature search was performed where a total of thirty-seven brain MRI studies associated with exercise, fatigue, or related physiological factors were reviewed. The findings suggest that with moderate dehydration, there is a decrease in total brain volume accompanied with expansion of ventricular volume. With exercise fatigue, there is increased activation of sensorimotor and cognitive brain areas, increased thalamo-insular activation and decreased interhemispheric connectivity in motor cortex. Under passive hyperthermia, there are regional changes in cerebral perfusion, a reduction in local connectivity in functional brain networks and an impairment to executive function. Current literature suggests that the brain structure and function are influenced by exercise, fatigue, and related physiological perturbations. However, there is still a dearth of knowledge and it is hoped that through understanding of MRI advantages and limitations, future studies will shed light on the central origin of exertional fatigue in the heat. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intraoperative Tumoral Bleeding of Hypervascular Medulloblastoma after Ventricular Drainage: A Case Report.

PubMed

Ryu, Han-Seung; Jung, Tae-Young; Han, Moon-Soo; Kim, Seul-Ki; Lee, Kyung-Hwa

2017-01-01

We report a rare case of intraoperative tumoral bleeding of a hypervascular medulloblastoma. A 12-year-old girl presented with dizziness and nausea. Brain magnetic resonance (MR) images revealed an approximately 4.2-cm enhanced mass on the cerebellar vermis associated with mild perilesional edema and increased cerebral blood volume. Angiography showed tumoral staining and developed occipital and circular dural sinuses in the venous phase. A suboccipital craniotomy was performed. To relieve the intracranial pressure, cerebrospinal fluid (CSF) was drained via a lateral ventricular catheter in the occipital horn. During the opening of the dura, the brain swelling had progressed, and brain computed tomography revealed an intratumoral hemorrhage with brainstem compression. The patient was in a stuporous mental state. A reoperation was performed, and the mass was totally removed. The pathologic findings revealed a medulloblastoma with abnormal enlarged arterial vascular structures. Postoperatively, the patient recovered to an alert mental state. She underwent chemotherapy and radiotherapy. There was no recurrence after 1 year. Pre-resectional CSF drainage should not be routinely performed in posterior fossa tumors, especially with increased cerebral blood volume on MR perfusion images. Complete removal should be performed quickly while CSF drainage should be performed slowly. An intratumoral hemorrhage should be considered in posterior fossa tumors when severe brain swelling suddenly develops after CSF drainage. © 2016 S. Karger AG, Basel.

Seed-competent HMW tau species accumulates in the cerebrospinal fluid of Alzheimer's disease mouse model and human patients

PubMed Central

Takeda, Shuko; Commins, Caitlin; DeVos, Sarah L.; Nobuhara, Chloe K.; Wegmann, Susanne; Roe, Allyson D.; Costantino, Isabel; Fan, Zhanyun; Nicholls, Samantha B.; Sherman, Alexis E.; Trisini Lipsanopoulos, Ana T.; Scherzer, Clemens R.; Carlson, George A.; Pitstick, Rose; Peskind, Elaine R.; Raskind, Murray A.; Li, Ge; Montine, Thomas J.; Frosch, Matthew P.; Hyman, Bradley T.

2016-01-01

Objective Cerebrospinal fluid (CSF) tau is an excellent surrogate marker for assessing neuropathological changes that occur in Alzheimer's disease (AD) patients. However, whether the elevated tau in AD CSF is just a marker of neurodegeneration or in fact a part of the disease process is uncertain. Moreover, it is unknown how CSF tau relates to the recently described soluble high-molecular-weight (HMW) species that is found in postmortem AD brain and can be taken up by neurons and seed aggregates. Methods We have examined seeding and uptake properties of brain extracellular tau from various sources including: interstitial fluid (ISF) and CSF from an AD transgenic mouse model, and postmortem ventricular and antemortem lumbar CSF from AD patients. Results We found that brain ISF and CSF tau from the AD mouse model can be taken up by cells and induce intracellular aggregates. Ventricular CSF from AD patients contained a rare HMW tau species that exerted a higher seeding activity. Notably, the HMW tau species was also detected in lumbar CSF from AD patients and its levels were significantly elevated compared with control subjects. HMW tau derived from CSF of AD patients was seed-competent in vitro. Interpretation These findings suggest that CSF from an AD brain contains potentially bioactive HMW tau species giving new insights into the role of CSF tau and biomarker development for AD. PMID:27351289

Automatic segmentation of brain MRIs and mapping neuroanatomy across the human lifespan

NASA Astrophysics Data System (ADS)

Keihaninejad, Shiva; Heckemann, Rolf A.; Gousias, Ioannis S.; Rueckert, Daniel; Aljabar, Paul; Hajnal, Joseph V.; Hammers, Alexander

2009-02-01

A robust model for the automatic segmentation of human brain images into anatomically defined regions across the human lifespan would be highly desirable, but such structural segmentations of brain MRI are challenging due to age-related changes. We have developed a new method, based on established algorithms for automatic segmentation of young adults' brains. We used prior information from 30 anatomical atlases, which had been manually segmented into 83 anatomical structures. Target MRIs came from 80 subjects (~12 individuals/decade) from 20 to 90 years, with equal numbers of men, women; data from two different scanners (1.5T, 3T), using the IXI database. Each of the adult atlases was registered to each target MR image. By using additional information from segmentation into tissue classes (GM, WM and CSF) to initialise the warping based on label consistency similarity before feeding this into the previous normalised mutual information non-rigid registration, the registration became robust enough to accommodate atrophy and ventricular enlargement with age. The final segmentation was obtained by combination of the 30 propagated atlases using decision fusion. Kernel smoothing was used for modelling the structural volume changes with aging. Example linear correlation coefficients with age were, for lateral ventricular volume, rmale=0.76, rfemale=0.58 and, for hippocampal volume, rmale=-0.6, rfemale=-0.4 (allρ<0.01).

Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure.

PubMed

Honda, Nobuhiro; Hirooka, Yoshitaka; Ito, Koji; Matsukawa, Ryuichi; Shinohara, Keisuke; Kishi, Takuya; Yasukawa, Keiji; Utsumi, Hideo; Sunagawa, Kenji

2013-11-01

Enhanced central sympathetic outflow is an indicator of the prognosis of heart failure. Although the central sympatholytic drug moxonidine is an established therapeutic strategy for hypertension, its benefits for hypertensive heart failure are poorly understood. In the present study, we investigated the effects of central sympathoinhibition by intracerebral infusion of moxonidine on survival in a rat model of hypertensive heart failure and the possible mechanisms involved. As a model of hypertensive heart failure, we fed Dahl salt-sensitive rats an 8% NaCl diet from 7 weeks of age. Intracerebroventricular (ICV) infusion of moxonidine (moxonidine-ICV-treated group [Mox-ICV]) or vehicle (vehicle-ICV-treated group [Veh-ICV]) was performed at 14-20 weeks of age, during the increased heart failure phase. Survival rates were examined, and sympathetic activity, left ventricular function and remodelling, and brain oxidative stress were measured. Hypertension and left ventricular hypertrophy were established by 13 weeks of age. At around 20 weeks of age, Veh-ICV rats exhibited overt heart failure concomitant with increased urinary norepinephrine (uNE) excretion as an index of sympathetic activity, dilated left ventricle, decreased percentage fractional shortening, and myocardial fibrosis. Survival rates at 21 weeks of age (n = 28) were only 23% in Veh-ICV rats, and 76% (n = 17) in Mox-ICV rats with concomitant decreases in uNE, myocardial fibrosis, collagen type I/III ratio, brain oxidative stress, and suppressed left ventricular dysfunction. Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodelling, and improved the prognosis in rats with hypertensive heart failure. Central sympathoinhibition can be effective for the treatment of hypertensive heart failure.

Demonstration of uneven distribution of intracranial pulsatility in hydrocephalus patients.

PubMed

Eide, Per K

2008-11-01

Data from intracranial pressure (ICP) recordings in patients with hydrocephalus were reviewed to determine whether intracranial pulsatility within the cerebrospinal fluid (CSF) of cerebral ventricles (ICP(LV)) may differ from that within the brain parenchyma (ICP(PAR)), and whether pulsatility may differ between noncommunicating ventricles. The authors retrieved data from recordings previously obtained in 7 patients with hydrocephalus (noncommunicating in 4 and communicating in 3) and shunt failure who received both an external ventricular drainage (EVD) and an ICP sensor as part of surveillance during intensive care. Simultaneous ICP(LV) and ICP(PAR) signals were available in 6 cases, and simultaneous signals from the lateral and fourth ventricles (ICP(LV) and ICP4V, respectively) were recorded in 1 case. The recordings with both signals were parsed into 6-second time windows. Pulsatility was characterized by the wave amplitude and rise time coefficient, and differences in pulsatility between the ICP(LV) and ICP(PAR) signals (6 cases) or ICP(LV) and ICP4V signals (1 case) were determined. There was uneven distribution of intracranial pulsatility in all 7 patients, shown as significantly elevated pulsatility (that is, higher wave amplitudes and rise time coefficients) within the ventricles (ICP(LV)) than within brain parenchyma (ICP(PAR)) in 6 patients, and significantly higher pulsatility in the fourth (ICP4V) than in the lateral (ICP(LV)) ventricles in 1 patient. Differences > or = 1 mm Hg in ICP wave amplitude were found in 0.5-100% (median 9.4%) of observations in the 7 patients (total number of 6-second time windows, 68,242). The present observations demonstrate uneven distribution of intracranial pulsatility in patients with hydrocephalus, higher pulse pressure amplitudes within the ventricular CSF (ICP(LV)) than within the brain parenchyma (ICP(PAR)). This may be one mechanism behind ventricular enlargement in hydrocephalus.

Spaceflight-induced changes in white matter hyperintensity burden in astronauts.

PubMed

Alperin, Noam; Bagci, Ahmet M; Lee, Sang H

2017-11-21

To assess the effect of weightlessness and the respective roles of CSF and vascular fluid on changes in white matter hyperintensity (WMH) burden in astronauts. We analyzed prespaceflight and postspaceflight brain MRI scans from 17 astronauts, 10 who flew a long-duration mission on the International Space Station (ISS) and 7 who flew a short-duration mission on the Space Shuttle. Automated analysis methods were used to determine preflight to postflight changes in periventricular and deep WMH, CSF, and brain tissue volumes in fluid-attenuated inversion recovery and high-resolution 3-dimensional T1-weighted imaging. Differences between cohorts and associations between individual measures were assessed. The short-term reversibility of the identified preflight to postflight changes was tested in a subcohort of 5 long-duration astronauts who had a second postflight MRI scan 1 month after the first postflight scan. Significant preflight to postflight changes were measured only in the long-duration cohort and included only the periventricular WMH and ventricular CSF volumes. Changes in deep WMH and brain tissue volumes were not significant in either cohort. The increase in periventricular WMH volume was significantly associated with an increase in ventricular CSF volume (ρ = 0.63, p = 0.008). A partial reversal of these increases was observed in the long-duration subcohort with a 1-month follow-up scan. Long-duration exposure to microgravity is associated with an increase in periventricular WMH in astronauts. This increase was linked to an increase in ventricular CSF volume documented in ISS astronauts. There was no associated change in or abnormal levels of WMH volumes in deep white matter as reported in U-2 high-altitude pilots. © 2017 American Academy of Neurology.

The importance of the cortical subarachnoid space in understanding hydrocephalus.

PubMed

Rekate, Harold L; Nadkarni, Trimurti D; Wallace, Donna

2008-07-01

In this paper the authors define the role of the cortical subarachnoid space (CSAS) in poorly understood forms of hydrocephalus to cerebrospinal fluid (CSF) dynamics to improve understanding of the importance of the CSAS and its role in selecting patients for endoscopic third ventriculostomy (ETV). The secondary purpose of this work was to define testable hypotheses to explain enigmatic disorders of CSF dynamics and to suggest how these concepts could be tested. The magnitude of the contribution of the CSAS is explored using the solid geometry of concentric spheres. With this starting point, clinical conditions in which CSF dynamics are not easily understood are explored regarding the potential role of the CSAS. Overall, problems of CSF dynamics are easily understood. Insights may be gained when the results of a pathological process or its treatment vary from what has been expected. Acute changes in ventricular volume at the time that hydrocephalus develops, the failure of shunts, and the changes in ventricular volume with shunt repair may occur very rapidly. Changes in the volume of water in the brain, especially in the brain substance itself, are unlikely to occur at this rapid rate and may be interpreted as a simple redistribution of the CSF between the ventricle and CSAS with no initial change in the actual volume of brain parenchyma. Problems such as pseudotumor cerebri, shunt failure with nonresponsive ventricles, and negative-pressure hydrocephalus can be explained by assessing the ability of ventricular CSF to flow to the CSAS and the ability of this fluid to exit this compartment. Ventricular enlargement at the time of shunt failure implies a failure of flow between the ventricles and CSAS, implying that all patients who show this phenomenon are potential candidates for ETV. The important role of the CSAS in the pathophysiology of various forms of hydrocephalus has been largely ignored. Attention to the dynamics of the CSF in this compartment will improve understanding of enigmatic conditions of hydrocephalus and improve selection criteria for treatment paradigms such as ETV. These concepts lead to clearly defined problems that may be solved by the creation of a central database to address these issues.

Intra-aortic balloon pumping in acute mitral regurgitation reduces aortic impedance and regurgitant fraction.

PubMed

Dekker, André L A J; Reesink, Koen D; van der Veen, Frederik H; van Ommen, G Vincent A; Geskes, Gijs G; Soemers, A Cecilia M; Maessen, Jos G

2003-04-01

Acute mitral regurgitation (MR) is present in 10% of patients presenting with cardiogenic shock. To stabilize these patients, intra-aortic balloon pumping (IABP) is recommended, but the mechanism of IABP support in these patients is unknown. This animal study was designed to describe the hemodynamic effect of intra-aortic balloon pumping during cardiogenic shock induced by acute MR. In eight calves, left ventricular pressure-volume loops, aortic and left atrial pressure, and aortic, carotid artery, and coronary blood flow were recorded. Acute MR (range 36%-79%) was created by placing a metal cage in the mitral valve. Hemodynamic data was obtained at control, during acute MR, and during acute MR with 1:1 IABP support. Acute MR caused a decrease in cardiac output (-32%, P = 0.018), blood pressure, and carotid artery flow, whereas left ventricular output (+127%, P = 0.018), end-diastolic volume, and left atrial pressure all significantly increased. Stroke work, ejection fraction, and coronary blood flow were not significantly changed, and no signs of ischemia were seen on the ECG. The IABP raised average cardiac output by 31% (P = 0.012) and significantly raised blood pressure and flow to the brain while decreasing systemic vascular resistance. Left ventricular function and mean coronary blood flow did not change, but diastolic coronary flow became more important as shown by the increase in diastolic fraction from 64% to 95%. (P = 0.028). Average MR dropped by 7.5% (P = 0.025). In conclusion, application of the IABP during acute MR lowers aortic impedance, resulting in less MR and more output toward the aorta without changing left ventricular function.

Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early- and late-onset pre-eclampsia.

PubMed

Borges, V T M; Zanati, S G; Peraçoli, M T S; Poiati, J R; Romão-Veiga, M; Peraçoli, J C; Thilaganathan, B

2018-04-01

Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P < 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Aquaporin-4 in brain and spinal cord oedema.

PubMed

Saadoun, S; Papadopoulos, M C

2010-07-28

Brain oedema is a major clinical problem produced by CNS diseases (e.g. stroke, brain tumour, brain abscess) and systemic diseases that secondarily affect the CNS (e.g. hyponatraemia, liver failure). The swollen brain is compressed against the surrounding dura and skull, which causes the intracranial pressure to rise, leading to brain ischaemia, herniation, and ultimately death. A water channel protein, aquaporin-4 (AQP4), is found in astrocyte foot processes (blood-brain border), the glia limitans (subarachnoid cerebrospinal fluid-brain border) and ependyma (ventricular cerebrospinal fluid-brain border). Experiments using mice lacking AQP4 or alpha syntrophin (which secondarily downregulate AQP4) showed that AQP4 facilitates oedema formation in diseases causing cytotoxic (cell swelling) oedema such as cerebral ischaemia, hyponatraemia and meningitis. In contrast, AQP4 facilitates oedema elimination in diseases causing vasogenic (vessel leak) oedema and therefore AQP4 deletion aggravates brain oedema produced by brain tumour and brain abscess. AQP4 is also important in spinal cord oedema. AQP4 deletion was associated with less cord oedema and improved outcome after compression spinal cord injury in mice. Here we consider the possible routes of oedema formation and elimination in the injured cord and speculate about the role of AQP4. Finally we discuss the role of AQP4 in neuromyelitis optica (NMO), an inflammatory demyelinating disease that produces oedema in the spinal cord and optic nerves. NMO patients have circulating AQP4 IgG autoantibody, which is now used for diagnosing NMO. We speculate how NMO-IgG might produce CNS inflammation, demyelination and oedema. Since AQP4 plays a key role in the pathogenesis of CNS oedema, we conclude that AQP4 inhibitors and activators may reduce CNS oedema in many diseases. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Radionuclide evaluation of left ventricular function with nonimaging probes.

PubMed

Wexler, J P; Blaufox, M D

1979-10-01

Portable nonimaging probes have been developed that can evaluate left ventricular function using radionuclide techniques. Two modes of data acquisition are possible with these probe systems, first-pass and gated. Precordial radiocardiograms obtained after a bolus injection can be used to determine cardiac output, pulmonary transit time, pulmonary blood volume, left ventricle ejection fraction, and left-to-right shunts. Gated techniques can be used to determine left ventricular ejection fraction and sytolic time intervals. Probe-determined indices of left ventricular function agree excellently with comparable measurements determined by conventional camera-computer methods as well as by invasive techniques. These have begun to be used in a preliminary manner in a variety of clinical problems associated with left ventricular dysfunction. This review discusses the types of probe systems available, the methods used in positioning them, and details the specifics of their data acquisition and processing capacity. The major criticisms of probe methods are that they are nonimaging and that they measure global rather than regional left ventricular function. In spite of these criticisms, probe systems, because of their portability, high sensitivity, and relatively low cost are useful supplements to conventional camera-computer systems for the measurement of parameters of left ventricular performance using radionuclide techniques.

Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat

NASA Technical Reports Server (NTRS)

Lehnert, Hendrik; Lombardi, Federico; Raeder, Ernst A.; Lorenzo, Antonio V.; Verrier, Richard L.; Lown, Bernard; Wurtman, Richard J.

1987-01-01

The effect of administering the serotonin precursor 5-l-hydroxytryptophan, in conjunction with a monamine oxidase inhibitor phenelzine and a l-amino acid decarboxylase inhibitor carbidopa, on neurochemical changes in the concentrations of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid of the cat were investigated. Results showed that this drug regimen led to increases of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid by 330 and 830 percent, respectively. Concomitantly, the threshold of ventricular fibrillation was found to be elevated by 42 percent and the effective refractory period was prolonged by 7 percent; the efferent sympathetic neural activity was suppressed in the normal heart. The results indicate that the enhancement of central serotoninergic neurotransmission can reduce the susceptibility of the heart to ventricular fibrillation mediated through a decline in sympathetic neural traffic to the heart.

Abnormal ventricular development in preterm neonates with visually normal MRIs

NASA Astrophysics Data System (ADS)

Shi, Jie; Wang, Yalin; Lao, Yi; Ceschin, Rafael; Mi, Liang; Nelson, Marvin D.; Panigrahy, Ashok; Leporé, Natasha

2015-12-01

Children born preterm are at risk for a wide range of neurocognitive and neurobehavioral disorders. Some of these may stem from early brain abnormalities at the neonatal age. Hence, a precise characterization of neonatal neuroanatomy may help inform treatment strategies. In particular, the ventricles are often enlarged in neurocognitive disorders, due to atrophy of surrounding tissues. Here we present a new pipeline for the detection of morphological and relative pose differences in the ventricles of premature neonates compared to controls. To this end, we use a new hyperbolic Ricci flow based mapping of the ventricular surfaces of each subjects to the Poincaré disk. Resulting surfaces are then registered to a template, and a between group comparison is performed using multivariate tensor-based morphometry. We also statistically compare the relative pose of the ventricles within the brain between the two groups, by performing a Procrustes alignment between each subject's ventricles and an average shape. For both types of analyses, differences were found in the left ventricles between the two groups.

Importance of the atrial channel for ventricular arrhythmia therapy in the dual chamber implantable cardioverter defibrillator.

PubMed

Dijkman, B; Wellens, H J

2000-12-01

Performance of dual chamber implantable cardioverter defibrillator (ICD) systems has been judged based on functioning of the ventricular tachycardia:supraventricular tachycardia (VT:SVT) discrimination criteria and DDD pacing. The purpose of this study was to evaluate the use of dual chamber diagnostics to improve the electrical and antiarrhythmic therapy of ventricular arrhythmias. Information about atrial and ventricular rhythm in relation to ventricular arrhythmia occurrence and therapy was evaluated in 724 spontaneous arrhythmia episodes detected and treated by three types of dual chamber ICDs in 41 patients with structural heart disease. Device programming was based on clinically documented and induced ventricular arrhythmias. In ambulatory patients, sinus tachycardia preceded ventricular arrhythmias more often than in the hospital during exercise testing. The incidence of these VTs could be reduced by increasing the dose of a beta-blocking agent in only two patients. In five patients in whom sinus tachycardia developed after onset of hemodynamic stable VT, propranolol was more effective than Class III antiarrhythmics combined with another beta-blocking agent with regard to the incidence of VT and pace termination. In all but three cases, atrial arrhythmias were present for a longer time before the onset of ventricular arrhythmias. During atrial arrhythmias, fast ventricular rates before the onset of ventricular rate were observed more often than RR irregularities and short-long RR sequences. Dual chamber diagnostics allowed proper interpretation of detection and therapy outcome in patients with different types of ventricular arrhythmia. The advantages of the dual chamber ICD system go further than avoiding the shortcomings of the single chamber system. Information from the atrial chamber allows better device programming and individualization of drug therapy for ventricular arrhythmia.

Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function.

PubMed

Shah, Prajay T; Stratton, Jo A; Stykel, Morgan Gail; Abbasi, Sepideh; Sharma, Sandeep; Mayr, Kyle A; Koblinger, Kathrin; Whelan, Patrick J; Biernaskie, Jeff

2018-05-03

Ependymal cells are multi-ciliated cells that form the brain's ventricular epithelium and a niche for neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ). In addition, ependymal cells are suggested to be latent NSCs with a capacity to acquire neurogenic function. This remains highly controversial due to a lack of prospective in vivo labeling techniques that can effectively distinguish ependymal cells from neighboring V-SVZ NSCs. We describe a transgenic system that allows for targeted labeling of ependymal cells within the V-SVZ. Single-cell RNA-seq revealed that ependymal cells are enriched for cilia-related genes and share several stem-cell-associated genes with neural stem or progenitors. Under in vivo and in vitro neural-stem- or progenitor-stimulating environments, ependymal cells failed to demonstrate any suggestion of latent neural-stem-cell function. These findings suggest remarkable stability of ependymal cell function and provide fundamental insights into the molecular signature of the V-SVZ niche. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of irregular cerebrospinal fluid production rate in human brain ventricular system

NASA Astrophysics Data System (ADS)

Hadzri, Edi Azali; Shamsudin, Amir Hamzah; Osman, Kahar; Abdul Kadir, Mohammed Rafiq; Aziz, Azian Abd

2012-06-01

Hydrocephalus is an abnormal accumulation of fluid in the ventricles and cavities in the brain. It occurs when the cerebrospinal fluid (CSF) flow or absorption is blocked or when excessive CSF is secreted. The excessive accumulation of CSF results in an abnormal widening of the ventricles. This widening creates potentially harmful pressure on the tissues of the brain. In this study, flow analysis of CSF was conducted on a three-dimensional model of the third ventricle and aqueduct of Sylvius, derived from MRI scans. CSF was modeled as Newtonian Fluid and its flow through the region of interest (ROI) was done using EFD. Lab software. Different steady flow rates through the Foramen of Monro, classified by normal and hydrocephalus cases, were modeled to investigate its effects. The results show that, for normal and hydrocephalus cases, the pressure drop of CSF flow across the third ventricle was observed to be linearly proportionally to the production rate increment. In conclusion, flow rates that cause pressure drop of 5 Pa was found to be the threshold for the initial sign of hydrocephalus.

Subcortical hyperintensity volumetrics in Alzheimer's disease and normal elderly in the Sunnybrook Dementia Study: correlations with atrophy, executive function, mental processing speed, and verbal memory.

PubMed

Ramirez, Joel; McNeely, Alicia A; Scott, Christopher Jm; Stuss, Donald T; Black, Sandra E

2014-01-01

Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer's disease (AD) and normal elderly controls. Although the presence of SH is believed to indicate some form of subcortical vasculopathy, pathological heterogeneity, methodological differences, and the contribution of brain atrophy associated with AD pathology have yielded inconsistent results in the literature. Using the Lesion Explorer (LE) MRI processing pipeline for SH quantification and brain atrophy, this study examined SH volumes of interest and cognitive function in a sample of patients with AD (n = 265) and normal elderly controls (n = 100) from the Sunnybrook Dementia Study. Compared with healthy controls, patients with AD were found to have less gray matter, less white matter, and more sulcal and ventricular cerebrospinal fluid (all significant, P <0.0001). Additionally, patients with AD had greater volumes of whole-brain SH (P <0.01), periventricular SH (pvSH) (P <0.01), deep white SH (dwSH) (P <0.05), and lacunar lesions (P <0.0001). In patients with AD, regression analyses revealed a significant association between global atrophy and pvSH (P = 0.02) and ventricular atrophy with whole-brain SH (P <0.0001). Regional volumes of interest revealed significant correlations with medial middle frontal SH volume and executive function (P <0.001) in normal controls but not in patients with AD, global pvSH volume and mental processing speed (P <0.01) in patients with AD, and left temporal SH volume and memory (P <0.01) in patients with AD. These brain-behavior relationships and correlations with brain atrophy suggest that subtle, yet measurable, signs of small vessel disease may have potential clinical relevance as targets for treatment in Alzheimer's dementia.

Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction.

PubMed

Xiong, Liang; Liu, Yu; Zhou, Mingmin; Wang, Guangji; Quan, Dajun; Shen, Caijie; Shuai, Wei; Kong, Bin; Huang, Congxin; Huang, He

2018-05-31

The purpose of this study was to evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI). Thirty-eight anaesthetized dogs were randomly assigned into the sham-operated, MI, and MI-TACSN groups, respectively. Myocardial infarction-targeted ablation of cardiac sympathetic neuron was induced by injecting cholera toxin B subunit-saporin compound in the left stellate ganglion (LSG). Five weeks after surgery, the cardiac function, heart rate variability (HRV), ventricular electrophysiological parameters, LSG function and neural activity, serum norepinephrine (NE), nerve growth factor (NGF), and brain natriuretic peptide (BNP) levels were measured. Cardiac sympathetic innervation was determined with immunofluorescence staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Compared with MI group, TACSN significantly improved HRV, attenuated LSG function and activity, prolonged corrected QT interval, decreased Tpeak-Tend interval, prolonged ventricular effective refractory period (ERP), and action potential duration (APD), decreased the slopes of APD restitution curves, suppressed the APD alternans, increased ventricular fibrillation threshold, and reduced serum NE, NGF, and BNP levels. Moreover, the densities of GAP43 and TH-positive nerve fibres in the infarcted border zone in the MI-TACSN group were lower than those in the MI group. Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.

Magnetic resonance imaging during untreated ventricular fibrillation reveals prompt right ventricular overdistention without left ventricular volume loss.

PubMed

Berg, Robert A; Sorrell, Vincent L; Kern, Karl B; Hilwig, Ronald W; Altbach, Maria I; Hayes, Melinda M; Bates, Kathryn A; Ewy, Gordon A

2005-03-08

Most out-of-hospital ventricular fibrillation (VF) is prolonged (>5 minutes), and defibrillation from prolonged VF typically results in asystole or pulseless electrical activity. Recent visual epicardial observations in an open-chest, open-pericardium model of swine VF indicate that blood flows from the high-pressure arterial system to the lower-pressure venous system during untreated VF, thereby overdistending the right ventricle and apparently decreasing left ventricular size. Therefore, inadequate left ventricular stroke volume after defibrillation from prolonged VF has been postulated as a major contributor to the development of pulseless rhythms. Ventricular dimensions were determined by MRI for 30 minutes of untreated VF in a closed-chest, closed-pericardium model in 6 swine. Within 1 minute of untreated VF, mean right ventricular volume increased by 29% but did not increase thereafter. During the first 5 minutes of untreated VF, mean left ventricular volume increased by 34%. Between 20 and 30 minutes of VF, stone heart occurred as manifested by dramatic thickening of the myocardium and concomitant substantial decreases in left ventricular volume. In this closed-chest swine model of VF, substantial right ventricular volume changes occurred early and did not result in smaller left ventricular volumes. The changes in ventricular volumes before the late development of stone heart do not explain why defibrillation from brief duration VF (<5 minutes) typically results in a pulsatile rhythm with return of spontaneous circulation, whereas defibrillation from prolonged VF (5 to 15 minutes) does not.

An Unusual Association of Microcephalic Osteodysplastic Primordial Dwarfism Type I with Cardiac and Brain Anomalies

PubMed Central

Bhutia, Euden; Verma, Arushi; Gupta, Amit Kumar; Maria, Arti

2014-01-01

Less than 100 cases of primordial dwarfism have been reported worldwide out of which Microcephalic osteodysplastic primordial dwarfism type I comprise about <30 cases. We report a rare case of extreme growth failure in a neonate with primordial dwarfism of antenatal onset due to Microcephalic osteodysplastic primordial dwarfism type I. Our case is also unique in being associated with hitertho unreported association of subpulmonic ventricular septal defect and a dorsal interhemispheric cyst in the brain. PMID:24741545

The impact of substance use on brain structure in people at high risk of developing schizophrenia.

PubMed

Welch, Killian A; McIntosh, Andrew M; Job, Dominic E; Whalley, Heather C; Moorhead, Thomas W; Hall, Jeremy; Owens, David G C; Lawrie, Stephen M; Johnstone, Eve C

2011-09-01

Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances.

Organotypic distribution of stem cell markers in formalin-fixed brain harboring glioblastoma multiforme.

PubMed

Schrot, Rudolph J; Ma, Joyce H; Greco, Claudia M; Arias, Angelo D; Angelastro, James M

2007-11-01

The role of stem cells in the origin, growth patterns, and infiltration of glioblastoma multiforme is a subject of intense investigation. One possibility is that glioblastoma may arise from transformed stem cells in the ventricular zone. To explore this hypothesis, we examined the distribution of two stem cell markers, activating transcription factor 5 (ATF5) and CD133, in an autopsy brain specimen from an individual with glioblastoma multiforme. A 41-year-old male with a right posterior temporal glioblastoma had undergone surgery, radiation, and chemotherapy. The brain was harvested within several hours after death. After formalin fixation, sectioning, and mapping of tumor location in the gross specimen, histologic specimens were prepared from tumor-bearing and grossly normal hemispheres. Fluorescence immunohistochemistry and colorimetric staining were performed for ATF5 and CD133. Both markers co-localized to the ependymal and subependymal zones on the side of the tumor, but not in the normal hemisphere or more rostrally in the affected hemisphere. ATF5 staining was especially robust within the diseased hemisphere in histologically normal ependyma. To our knowledge, this is the first in situ demonstration of stem cell markers in whole human brain. These preliminary results support the hypothesis that some glioblastomas may arise from the neurogenic zone of the lateral ventricle. The robust staining for ATF5 and CD133 in histologically normal ventricular zone suggests that an increase in periventricular stem cell activity occurred in this patient on the side of the tumor, either as a localized response to brain injury or as an integral component of oncogenesis and tumor recurrence.

83. Ventricular Enlargement and Progressive Reduction in Cortical Gray Matter Are Linked in Prodromal Youth Who Develop Psychosis

PubMed Central

Chung, Yoonho; Haut, Kristen; He, George; Van Erp, Theo; McEwen, Sarah; Addington, Jean; Bearden, Carrie; Cadenhead, Kristin; Cornblatt, Barbara; Mathalon, Daniel; McGlashan, Thomas; Perkins, Diana; Seidman, Larry; Tsuang, Ming; Walker, Elaine; Woods, Scott; Cannon, Tyrone

2017-01-01

Abstract Background: In a recent prospective longitudinal neuroimaging study, clinical high-risk (CHR) individuals who later developed full-blown psychosis showed an accelerated rate of gray matter thinning in superior and medial prefrontal cortex (PFC) and expansion of the ventricular system after applying a stringent correction for multiple comparisons. Although cortical and subcortical volume loss and enlarged ventricles are well characterized structural brain abnormalities among patients with schizophrenia, no prior study has evaluated whether these progressive changes of neuroanatomical indicators are linked in time prior to onset of psychosis. Therefore, we investigated the relationship between the changes in cortical gray matter thickness and ventricular volume using the longitudinal neuroimaging data from the North American Prodrome Longitudinal Study (NAPLS) at the whole-brain level. Methods: MRI structural data were acquired at baseline and 12-month follow-up, and follow-up scans for those who developed fully psychotic symptoms were assessed at the point of conversion. In total, 37 CHR cases who converted to psychosis, 230 CHR cases who did not convert (nonconverters), and 132 healthy comparison subjects had usable baseline and second time point scans. Imaging measures were first transformed to annualized rates of percent change (ARCH) in each cortical vertex. Interval is the time between BL and FU scans in years. Relationships between ARCH of total ventricle volume and ARCH of cortical gray matter values were tested vertex-wise using the general linear model. Among the subjects with BL and 12-FU data available, 125 CHR cases and 66 controls were followed to an additional third time point for a 24-month MRI assessment. For the purpose of testing the replicability of our main hypotheses, neuroanatomical ARCH measures between the 12 and 24 month follow-ups were also computed with a parallel set of statistical tests as described earlier. Results: The results showed that ventricular expansion is linked in time to progressive reduction of gray matter, rather than to structural changes in proximal subcortical regions, in a broadly distributed set of cortical regions among CHR youth, including superior, medial, lateral, and inferior PFC, superior temporal gyrus, and parietal cortices. In contrast, the healthy controls did not show the same pattern of associations. The main findings were further replicated using a third assessment wave of MRI scans in a subset of study participants who were followed for an additional year. Conclusion: In summary, expansion of the ventricular spaces is linked in time with an accelerated rate of widespread cortical thinning prior to psychosis onset. The cortical regions experiencing altered maturation during the psychosis prodrome may be more widespread than the regionally specific clusters that have been identified in previous case–control studies

Intensity-Modulated and 3D-Conformal Radiotherapy for Whole-Ventricular Irradiation as Compared With Conventional Whole-Brain Irradiation in the Management of Localized Central Nervous System Germ Cell Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Michael Jenwei, E-mail: michaelchen@einstein.b; Silva Santos, Adriana da; Sakuraba, Roberto Kenji

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a 'boost' to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluatedmore » at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy, respectively, compared with 3D-CRT. Intensity-modulated radiotherapy provided statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment.« less

Resuscitation after prolonged cardiac arrest: role of cardiopulmonary bypass and systemic hyperkalemia.

PubMed

Liakopoulos, Oliver J; Allen, Bradley S; Buckberg, Gerald D; Hristov, Nikola; Tan, Zhongtuo; Villablanca, J Pablo; Trummer, Georg

2010-06-01

The purpose of this study was to determine (1) the role of emergency cardiopulmonary bypass (CPB) after prolonged cardiac arrest and failed cardiopulmonary resuscitation, and (2) the use of systemic hyperkalemia during CPB to convert intractable ventricular fibrillation (VF). Thirty-one pigs (34 +/- 2 kg) underwent 15 minutes of cardiac arrest after induced VF, followed by 10 minutes of cardiopulmonary resuscitation-advanced life support. Peripheral CPB was used if cardiopulmonary resuscitation failed to restore stable circulation. Damage was assessed by evaluating hemodynamics, biochemical variables (creatine kinase-MB, neuron-specific enolase), neurologic deficit score, and brain magnetic resonance imaging. Cardiopulmonary resuscitation alone was successful in only 19% (6 of 31 pigs). Cardiopulmonary bypass was initiated in 81% of animals (25 of 31 pigs) either for hypotension (5 of 25 pigs) or intractable VF (20 of 25 pigs). Defibrillation was successful in 7 of 20 animals during the first 10 minutes after initiating CPB. Ventricular fibrillation persisted more than 10 minutes in 13 of 20 pigs, and animals were treated either with repeated defibrillation (6 of 13 pigs) or with a potassium bolus (7 of 13 pigs) to induce transient cardiac arrest. Overall survival at 24 hours was 84% with cardiopulmonary resuscitation (100% of pigs with hypotension; 71% in CPB-VF < 10 minutes). Despite CPB, fatal myocardial failure occurred after VF duration of more than 10 minutes in all pigs treated with electrical defibrillation, whereas hyperkalemia allowed 100% cardioversion and 86% survival. Biochemical variables remained elevated in all groups. Similarly, severe brain injury was present in all animals as confirmed by neurologic deficit score (197 +/- 10) and magnetic resonance imaging. Emergency CPB after prolonged cardiac arrest improves survival and allows systemic hyperkalemia to convert intractable VF, but fails to reduce neurologic damage. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device.

PubMed

Gohean, Jeffrey R; George, Mitchell J; Pate, Thomas D; Kurusz, Mark; Longoria, Raul G; Smalling, Richard W

2013-01-01

The purpose of this investigation is to use a computational model to compare a synchronized valveless pulsatile left ventricular assist device with continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate the support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous pulsatile valveless dual-piston positive displacement pump. These results were compared with measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared with the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device.

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device

PubMed Central

Gohean, Jeffrey R.; George, Mitchell J.; Pate, Thomas D.; Kurusz, Mark; Longoria, Raul G.; Smalling, Richard W.

2012-01-01

The purpose of this investigation is to utilize a computational model to compare a synchronized valveless pulsatile left ventricular assist device to continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous, pulsatile, valveless, dual piston positive displacement pump. These results were compared to measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared to the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device. PMID:23438771

Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain

PubMed Central

Murlidharan, Giridhar; Crowther, Andrew; Reardon, Rebecca A.; Song, Juan

2016-01-01

Adeno-associated viruses (AAV) are currently being evaluated in clinical trials for gene therapy of CNS disorders. However, host factors that influence the spread, clearance, and transduction efficiency of AAV vectors in the brain are not well understood. Recent studies have demonstrated that fluid flow mediated by aquaporin-4 (AQP4) channels located on astroglial end feet is essential for exchange of solutes between interstitial and cerebrospinal fluid. This phenomenon, which is essential for interstitial clearance of solutes from the CNS, has been termed glial-associated lymphatic transport or glymphatic transport. In the current study, we demonstrate that glymphatic transport profoundly affects various aspects of AAV gene transfer in the CNS. Altered localization of AQP4 in aged mouse brains correlated with significantly increased retention of AAV vectors in the parenchyma and reduced systemic leakage following ventricular administration. We observed a similar increase in AAV retention and transgene expression upon i.c.v. administration in AQP4–/– mice. Consistent with this observation, fluorophore-labeled AAV vectors showed markedly reduced flux from the ventricles of AQP4–/– mice compared with WT mice. These results were further corroborated by reduced AAV clearance from the AQP4-null brain, as demonstrated by reduced transgene expression and vector genome accumulation in systemic organs. We postulate that deregulation of glymphatic transport in aged and diseased brains could markedly affect the parenchymal spread, clearance, and gene transfer efficiency of AAV vectors. Assessment of biomarkers that report the kinetics of CSF flux in prospective gene therapy patients might inform variable treatment outcomes and guide future clinical trial design. PMID:27699236

How I Cool Children in Neurocritical Care

PubMed Central

Fink, Ericka L.; Kochanek, Patrick M.; Clark, Robert S. B.; Bell, Michael J.

2010-01-01

Brain injury is the leading cause of death in our pediatric ICU 1. Clinical care for brain injury remains largely supportive. Therapeutic hypothermia has been shown to be effective in improving neurological outcome after adult ventricular-arrhythmia induced cardiac arrest and neonatal asphyxia, and is under investigation as a neuroprotectant after cardiac arrest and traumatic brain injury in children in our ICU and other centers. We routinely induce hypothermia in children comatose after cardiac arrest targeting 32–34°C using cooling blankets and intravenous iced saline as primary methods for induction, for 24–72 hours duration and vigilant re-warming. The objective of this article is to share our hypothermia protocol for cooling children with acute brain injury. PMID:20146026

Comparison of usefulness of N-terminal pro-brain natriuretic peptide as an independent predictor of cardiac function among admission cardiac serum biomarkers in patients with anterior wall versus nonanterior wall ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PubMed

Haeck, Joost D E; Verouden, Niels J W; Kuijt, Wichert J; Koch, Karel T; Van Straalen, Jan P; Fischer, Johan; Groenink, Maarten; Bilodeau, Luc; Tijssen, Jan G P; Krucoff, Mitchell W; De Winter, Robbert J

2010-04-15

The purpose of the present study was to determine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), among other serum biomarkers, on cardiac magnetic resonance (CMR) imaging parameters of cardiac function and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We measured NT-pro-BNP, cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and creatinine on the patients' arrival at the catheterization laboratory in 206 patients with ST-segment elevation myocardial infarction. The NT-pro-BNP levels were divided into quartiles and correlated with left ventricular function and infarct size measured by CMR imaging at 4 to 6 months. Compared to the lower quartiles, patients with nonanterior wall myocardial infarction in the highest quartile of NT-pro-BNP (> or = 260 pg/ml) more often had a greater left ventricular end-systolic volume (68 vs 39 ml/m(2), p <0.001), a lower left ventricular ejection fraction (42% vs 54%, p <0.001), a larger infarct size (9 vs 4 g/m(2), p = 0.002), and a larger number of transmural segments (11% of segments vs 3% of segments, p <0.001). Multivariate analysis revealed that a NT-pro-BNP level of > or = 260 pg/ml was the strongest independent predictor of left ventricular ejection fraction in patients with nonanterior wall myocardial infarction compared to the other serum biomarkers (beta = -5.8; p = 0.019). In conclusion, in patients with nonanterior wall myocardial infarction undergoing primary percutaneous coronary intervention, an admission NT-pro-BNP level of > or = 260 pg/ml was a strong, independent predictor of left ventricular function assessed by CMR imaging at follow-up. Our findings suggest that NT-pro-BNP, a widely available biomarker, might be helpful in the early risk stratification of patients with nonanterior wall myocardial infarction. Copyright 2010 Elsevier Inc. All rights reserved.

The role of cerebral hyperperfusion in postoperative neurologic dysfunction after left ventricular assist device implantation for end-stage heart failure.

PubMed

Lietz, Katherine; Brown, Kevin; Ali, Syed S; Colvin-Adams, Monica; Boyle, Andrew J; Anderson, David; Weinberg, Alan D; Miller, Leslie W; Park, Soon; John, Ranjit; Lazar, Ronald M

2009-04-01

Cerebral hyperperfusion is a life-threatening syndrome that can occur in patients with chronically hypoperfused cerebral vasculature whose normal cerebral circulation was re-established after carotid endarterectomy or angioplasty. We sought to determine whether the abrupt restoration of perfusion to the brain after left ventricular assist device (LVAD) implantation produced similar syndromes. We studied the role of increased systemic flow after LVAD implantation on neurologic dysfunction in 69 consecutive HeartMate XVE LVAD (Thoratec, Pleasanton, Calif) recipients from October 2001 through June 2006. Neurologic dysfunction was defined as postoperative permanent or transient central change in neurologic status, including confusion, focal neurologic deficits, visual changes, seizures, or coma for more than 24 hours within 30 days after LVAD implantation. We found that 19 (27.5%) patients had neurologic dysfunction, including encephalopathy (n = 11), coma (n = 3), and other complications (n = 5). The multivariate analysis showed that an increase in cardiac index from the preoperative baseline value (relative risk, 1.33 per 25% cardiac index increase; P = .01) and a previous coronary bypass operation (relative risk, 4.53; P = .02) were the only independent predictors of neurologic dysfunction. Reduction of left ventricular assist device flow in 16 of the 19 symptomatic patients led to improvement of symptoms in 14 (87%) patients. Our findings showed that normal flow might overwhelm cerebral autoregulation in patients with severe heart failure, suggesting that cerebral hyperperfusion is possible in recipients of mechanical circulatory support with neurologic dysfunction.

Embryonic Cerebrospinal Fluid Increases Neurogenic Activity in the Brain Ventricular-Subventricular Zone of Adult Mice.

PubMed

Alonso, Maria I; Lamus, Francisco; Carnicero, Estela; Moro, Jose A; de la Mano, Anibal; Fernández, Jose M F; Desmond, Mary E; Gato, Angel

2017-01-01

Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies.

Embryonic Cerebrospinal Fluid Increases Neurogenic Activity in the Brain Ventricular-Subventricular Zone of Adult Mice

PubMed Central

Alonso, Maria I.; Lamus, Francisco; Carnicero, Estela; Moro, Jose A.; de la Mano, Anibal; Fernández, Jose M. F.; Desmond, Mary E.; Gato, Angel

2017-01-01

Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies. PMID:29311854

Association of IQ Changes and Progressive Brain Changes in Patients With Schizophrenia.

PubMed

Kubota, Manabu; van Haren, Neeltje E M; Haijma, Sander V; Schnack, Hugo G; Cahn, Wiepke; Hulshoff Pol, Hilleke E; Kahn, René S

2015-08-01

Although schizophrenia is characterized by impairments in intelligence and the loss of brain volume, the relationship between changes in IQ and brain measures is not clear. To investigate the association between IQ and brain measures in patients with schizophrenia across time. Case-control longitudinal study at the Department of Psychiatry at the University Medical Center Utrecht, Utrecht, the Netherlands, comparing patients with schizophrenia and healthy control participants between September 22, 2004, and April 17, 2008. Magnetic resonance imaging of the brain and IQ scores were obtained at baseline and the 3-year follow-up. Participants included 84 patients with schizophrenia (mean illness duration, 4.35 years) and 116 age-matched healthy control participants. Associations between changes in IQ and the total brain, cerebral gray matter, cerebral white matter, lateral ventricular, third ventricles, cortical, and subcortical volumes; cortical thickness; and cortical surface area. Cerebral gray matter volume (P = .006) and cortical volume (P = .03) and thickness (P = .02) decreased more in patients with schizophrenia across time compared with control participants. Patients showed additional loss in cortical volume and thickness of the right supramarginal, posterior superior temporal, left supramarginal, left postcentral, and occipital regions (P values were between <.001 and .03 after clusterwise correction). Although IQ increased similarly in patients with schizophrenia and control participants, changes in IQ were negatively correlated with changes in lateral ventricular volume (P = .05) and positively correlated with changes in cortical volume (P = .007) and thickness (P = .004) only in patients with schizophrenia. Positive correlations between changes in IQ and cortical volume and thickness were found globally and in widespread regions across frontal, temporal, and parietal cortices (P values were between <.001 and .03 after clusterwise correction). These findings were independent of symptom severity at follow-up, cannabis use, and the use of cumulative antipsychotic medications during the 3 years of follow-up. Progressive brain tissue loss in schizophrenia is related to relative cognitive decline during the early course of illness.

[Long-term effects of hydroxychloroquine on metabolism of serum lipids and left ventricular structure and function in patients of systemic lupus erythematosus].

PubMed

Meng, Juan; Lu, Yuewu; Dong, Xin; Liu, Hongyan

2014-04-08

To observe the long-term effects of hydroxychloroquine treatment on blood lipids and left ventricular function of systemic lupus erythematosus (SLE) patients. A total of 72 SLE patients were randomly divided into 2 groups of hydroxychloroquine treatment (n = 36) and non-hydroxychloroquine (n = 36). The serum level of lipids, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), fractional shortening rate (FS), left ventricular ejection fraction (LVEF) and E/A ratio were measured before, 6 month, 12 month and 2 years after treatment. After long-term use of hydroxychloroquine, there were statistically differences in the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). And LVEDD, LVWPT and E/A were statistically different (P < 0.05) before and after hydroxychloroquine dosing. The long-term use of hydroxychloroquine may improve lipid metabolism and left ventricular function in SLE patients.

Neurogenesis in the aging brain.

PubMed

Apple, Deana M; Solano-Fonseca, Rene; Kokovay, Erzsebet

2017-10-01

Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair. In this review, we describe NSCs and their niches during tissue homeostasis and how they undergo age-associated remodeling and dysfunction. We also discuss some of the functional ramifications in the brain from NSC aging. Finally, we discuss some recent insights from interventions in NSC aging that could eventually translate into therapies for healthy brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Adams-Oliver Syndrome with Unusual Central Nervous System Findings and an Extrahepatic Portosystemic Shunt

PubMed Central

Pérez-García, Carlos; Martín, Yolanda Ruíz; del Hoyo, Alejandra Aguado; Rodríguez, Carlos Marín; Domínguez, Minia Campos

2017-01-01

We report a case of a premature neonate girl with scalp and skull defects and brachydactyly of the feet consistent with an Adams-Oliver syndrome (AOS). The patient had central nervous system abnormalities, such as periventricular calcifications, hypoplastic corpus callosum, and bilateral hemispheric corticosubcortical hemorrhagic lesions. A muscular ventricular septal defect and a portosystemic shunt were diagnosed. To our knowledge, this is the first report of congenital supratentorial grey-white matter junction lesions without dural sinus thrombosis in association with AOS. Some of these lesions may be secondary to birth trauma (given the skull defect) whilst others have a watershed location, perhaps as further evidence of vascular disruption and decreased perfusion during critical periods of fetal brain development as the previously proposed pathogenesis of this syndrome. PMID:28706620

Physiologic underpinnings of negative BOLD cerebrovascular reactivity in brain ventricles.

PubMed

Thomas, Binu P; Liu, Peiying; Aslan, Sina; King, Kevin S; van Osch, Matthias J P; Lu, Hanzhang

2013-12-01

With a growing need for specific biomarkers in vascular diseases, there has been a surging interest in mapping cerebrovascular reactivity (CVR) of the brain. This index can be measured by conducting a hypercapnia challenge while acquiring blood-oxygenation-level-dependent (BOLD) signals. A BOLD signal increase with hypercapnia is the expected outcome and represents the majority of literature reports; in this work we report an intriguing observation of an apparently negative BOLD CVR response at 3T, during inhalation of 5% CO2 with balance medical air. These "negative-CVR" clusters were specifically located in the ventricular regions of the brain, where CSF is abundant and results in an intense baseline signal. The amplitude of the CVR response was -0.51±0.44% (N=14, age 26±4 years). We hypothesized that this observation might not be due to a decrease in oxygenation but rather a volume effect in which bright CSF signal is replaced by a less intensive blood signal as a result of vasodilation. To test this, we performed an inversion-recovery (IR) experiment to suppress the CSF signal (N=10, age 27±5 years). This maneuver in imaging sequence reversed the sign of the signal response (to 0.66±0.25%), suggesting that the volume change was the predominant reason for the apparently negative CVR in the BOLD experiment. Further support of this hypothesis was provided by a BOLD hyperoxia experiment, in which no voxels showed a negative response, presumably because vasodilation is not usually associated with this challenge. Absolute CBF response to hypercapnia was measured in a new group of subjects (N=8, age 29±7 years) and it was found that CBF in ventricular regions increased by 48% upon CO2 inhalation, suggesting that blood oxygenation most likely increased rather than decreased. The findings from this study suggest that CO2 inhalation results in the dilation of ventricular vessels accompanied by shrinkage in CSF space, which is responsible for the apparently negative CVR in brain ventricles. © 2013.

Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.

PubMed

Kyrtsos, Christina Rose; Baras, John S

2015-01-01

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.

Exploring energy loss by vector flow mapping in children with ventricular septal defect: Pathophysiologic significance.

PubMed

Honda, Takashi; Itatani, Keiichi; Takanashi, Manabu; Kitagawa, Atsushi; Ando, Hisashi; Kimura, Sumito; Oka, Norihiko; Miyaji, Kagami; Ishii, Masahiro

2017-10-01

Vector flow mapping is a novel echocardiographic flow visualization method, and it has enabled us to quantitatively evaluate the energy loss in the left ventricle (intraventricular energy loss). Although intraventricular energy loss is assumed to be a part of left ventricular workload itself, it is unclear what this parameter actually represents. The aim of the present study was to elucidate the characteristics of intraventricular energy loss. We enrolled 26 consecutive children with ventricular septal defect (VSD). On echocardiography vector flow mapping, intraventricular energy loss was measured in the apical 3-chamber view. We measured peak energy loss and averaged energy loss in the diastolic and systolic phases, and subsequently compared these parameters with catheterization parameters and serum brain natrium peptide (BNP) level. Diastolic, peak, and systolic energy loss were strongly and positively correlated with right ventricular systolic pressure (r=0.76, 0.68, and 0.56, p<0.0001, = 0.0001, and 0.0029, respectively) and right ventricular end diastolic pressure (r=0.55, 0.49, and 0.49, p=0.0038, 0.0120, and 0.0111, respectively). In addition, diastolic, peak, and systolic energy loss were significantly correlated with BNP (r=0.75, 0.69 and 0.49, p<0.0001, < 0.0001, and=0.0116, respectively). In children with VSD, elevated right ventricular pressure is one of the factors that increase energy loss in the left ventricle. The results of the present study encourage further studies in other study populations to elucidate the characteristics of intraventricular energy loss for its possible clinical application. Copyright © 2017 Elsevier B.V. All rights reserved.

Coupling of a 3D Finite Element Model of Cardiac Ventricular Mechanics to Lumped Systems Models of the Systemic and Pulmonic Circulation

PubMed Central

Kerckhoffs, Roy C. P.; Neal, Maxwell L.; Gu, Quan; Bassingthwaighte, James B.; Omens, Jeff H.; McCulloch, Andrew D.

2010-01-01

In this study we present a novel, robust method to couple finite element (FE) models of cardiac mechanics to systems models of the circulation (CIRC), independent of cardiac phase. For each time step through a cardiac cycle, left and right ventricular pressures were calculated using ventricular compliances from the FE and CIRC models. These pressures served as boundary conditions in the FE and CIRC models. In succeeding steps, pressures were updated to minimize cavity volume error (FE minus CIRC volume) using Newton iterations. Coupling was achieved when a predefined criterion for the volume error was satisfied. Initial conditions for the multi-scale model were obtained by replacing the FE model with a varying elastance model, which takes into account direct ventricular interactions. Applying the coupling, a novel multi-scale model of the canine cardiovascular system was developed. Global hemodynamics and regional mechanics were calculated for multiple beats in two separate simulations with a left ventricular ischemic region and pulmonary artery constriction, respectively. After the interventions, global hemodynamics changed due to direct and indirect ventricular interactions, in agreement with previously published experimental results. The coupling method allows for simulations of multiple cardiac cycles for normal and pathophysiology, encompassing levels from cell to system. PMID:17111210

Seasonal variation in cell proliferation and cell migration in the brain of adult red-sided garter snakes (Thamnophis sirtalis parietalis).

PubMed

Maine, Ashley R; Powers, Sean D; Lutterschmidt, Deborah I

2014-01-01

Plasticity in the adult central nervous system has been described in all vertebrate classes as well as in some invertebrate groups. However, the limited taxonomic diversity represented in the current neurogenesis literature limits our ability to assess the functional significance of adult neurogenesis for natural behaviors as well as the evolution of its regulatory mechanisms. In the present study, we used free-ranging red-sided garter snakes (Thamnophis sirtalis parietalis) to test the hypothesis that seasonal shifts in physiology and behavior are associated with seasonal variation in postembryonic neurogenesis. Specifically, we used the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to determine if the rates of cell proliferation in the adult brain vary between male snakes collected during spring and fall at 1, 5, and 10 days post-BrdU treatment. To assess rates of cell migration within the brain, we further categorized BrdU-labeled cells according to their location within the ventricular zone or parenchymal region. BrdU-labeled cells were localized mainly within the lateral, dorsal, and medial cortex, septal nucleus, nucleus sphericus, preoptic area, and hypothalamus. In all regions, the number of BrdU-labeled cells in the ventricular zone was higher in the fall compared to spring. In the parenchymal region, a significantly higher number of labeled cells was also observed during the fall, but only within the nucleus sphericus and the combined preoptic area/hypothalamus. The immunoreactive cell number did not vary significantly with days post-BrdU treatment in either season or in any brain region. While it is possible that the higher rates of cell proliferation in the fall simply reflect increased growth of all body tissues, including the brain, our data show that seasonal changes in cell migration into the parenchyma are region specific. In red-sided garter snakes and other reptiles, the dorsal and medial cortex is important for spatial navigation and memory, whereas the nucleus sphericus, septal nucleus, and preoptic area/hypothalamus are central to reproductive regulation. Thus, our results provide support for the hypothesis that adult neurogenesis plays a role in mediating seasonal rhythms in migratory and reproductive behaviors. © 2014 S. Karger AG, Basel.

Left ventricular diastolic dysfunction and increased left ventricular mass index related to pulmonary hypertension in patients with systemic autoimmune disease without pericardial effusion.

PubMed

Sugiura, Atsushi; Funabashi, Nobusada; Ozawa, Koya; Kobayashi, Yoshio

2016-10-01

We investigated the relationship of left ventricular (LV) diastolic dysfunction and LV mass index (LVMI) against pulmonary hypertension (PH) in systemic autoimmune disease (SAD). A total of 84 SAD patients (68 females; 53±17years; systemic lupus erythematosus, 27%; scleroderma, 17%; vasculitis, 16%; mixed connective tissue disease, 13% and polymyositis/dermatomyositis complex, 10%) without significant pericardial effusion (PE) on TTE (Vivid E9, GE) were analyzed. On TTE, PH was defined as peak tricuspid regurgitation velocity (TRV) of ≥2.9m/s based upon 2015 ESC guideline. Left atrial volume index (LAVI) and E/E' were measured as indicators of LV diastolic dysfunction. LVMI was also measured. Seven patients (8%) had PH. PH patients had greater LAVI (p<0.001), E/E' (p=0.004), LVMI (p=0.009) than non-PH patients. LAVI (R=0.458), E/E' (R=0.337), and LVMI (R=0.313) significantly and positively correlated with TRV (all p<0.05). Multiple regression analysis was performed to explore determinants of TRV. Age, female sex, and brain natriuretic peptide (BNP) were included in all the models. Three multiple regression models were generated using 1) LAVI, 2) E/E', and 3) LVMI and included LAVI, E/E', LVMI, and BNP as significant variables influencing TRV. Multi logistic regression analysis for predicting TRV of ≥2.9m/s showed that LAVI, and E/E' were significant predictors (Odds ratio, 1.296, and 1.370, respectively). In SAD patients without PE, LV diastolic dysfunction and increment of LVMI was closely associated with PH based upon TRV. LAVI and E/E' were independent predictors for PH. Measuring LAVI and E/E' may be a key to determine the mechanism of PH in these patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Specialized impulse conduction pathway in the alligator heart

PubMed Central

Crossley, Dane A; Conner, Justin; Mohan, Rajiv A; van Duijvenboden, Karel; Postma, Alex V; Gloschat, Christopher R; Elsey, Ruth M; Sedmera, David; Efimov, Igor R

2018-01-01

Mammals and birds have a specialized cardiac atrioventricular conduction system enabling rapid activation of both ventricles. This system may have evolved together with high heart rates to support their endothermic state (warm-bloodedness) and is seemingly lacking in ectothermic vertebrates from which first mammals then birds independently evolved. Here, we studied the conduction system in crocodiles (Alligator mississippiensis), the only ectothermic vertebrates with a full ventricular septum. We identified homologues of mammalian conduction system markers (Tbx3-Tbx5, Scn5a, Gja5, Nppa-Nppb) and show the presence of a functional atrioventricular bundle. The ventricular Purkinje network, however, was absent and slow ventricular conduction relied on trabecular myocardium, as it does in other ectothermic vertebrates. We propose the evolution of the atrioventricular bundle followed full ventricular septum formation prior to the development of high heart rates and endothermy. In contrast, the evolution of the ventricular Purkinje network is strongly associated with high heart rates and endothermy. PMID:29565246

Patterns of contrast enhancement in the brain and meninges.

PubMed

Smirniotopoulos, James G; Murphy, Frances M; Rushing, Elizabeth J; Rees, John H; Schroeder, Jason W

2007-01-01

Contrast material enhancement for cross-sectional imaging has been used since the mid 1970s for computed tomography and the mid 1980s for magnetic resonance imaging. Knowledge of the patterns and mechanisms of contrast enhancement facilitate radiologic differential diagnosis. Brain and spinal cord enhancement is related to both intravascular and extravascular contrast material. Extraaxial enhancing lesions include primary neoplasms (meningioma), granulomatous disease (sarcoid), and metastases (which often manifest as mass lesions). Linear pachymeningeal (dura-arachnoid) enhancement occurs after surgery and with spontaneous intracranial hypotension. Leptomeningeal (pia-arachnoid) enhancement is present in meningitis and meningoencephalitis. Superficial gyral enhancement is seen after reperfusion in cerebral ischemia, during the healing phase of cerebral infarction, and with encephalitis. Nodular subcortical lesions are typical for hematogenous dissemination and may be neoplastic (metastases) or infectious (septic emboli). Deeper lesions may form rings or affect the ventricular margins. Ring enhancement that is smooth and thin is typical of an organizing abscess, whereas thick irregular rings suggest a necrotic neoplasm. Some low-grade neoplasms are "fluid-secreting," and they may form heterogeneously enhancing lesions with an incomplete ring sign as well as the classic "cyst-with-nodule" morphology. Demyelinating lesions, including both classic multiple sclerosis and tumefactive demyelination, may also create an open ring or incomplete ring sign. Thick and irregular periventricular enhancement is typical for primary central nervous system lymphoma. Thin enhancement of the ventricular margin occurs with infectious ependymitis. Understanding the classic patterns of lesion enhancement--and the radiologic-pathologic mechanisms that produce them--can improve image assessment and differential diagnosis.

Early trends in N-terminal pro-brain natriuretic peptide values after left ventricular assist device implantation for chronic heart failure.

PubMed

Hasin, Tal; Kushwaha, Sudhir S; Lesnick, Timothy G; Kremers, Walter; Boilson, Barry A; Schirger, John A; Clavell, Alfredo L; Rodeheffer, Richard J; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Stulak, John M; Joyce, Lyle; Daly, Richard; Park, Soon J; Jaffe, Allan S

2014-10-15

Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading. Copyright © 2014 Elsevier Inc. All rights reserved.

Cardiovascular response to exercise training in the systemic right ventricle of adults with transposition of the great arteries

PubMed Central

Shafer, K M; Janssen, L; Carrick-Ranson, G; Rahmani, S; Palmer, D; Fujimoto, N; Livingston, S; Matulevicius, S A; Forbess, L W; Brickner, B; Levine, B D

2015-01-01

We aimed to assess the haemodynamic effects of exercise training in transposition of the great arteries (TGA) patients with systemic right ventricles (SRVs). TGA patients have limited exercise tolerance and early mortality due to systemic (right) ventricular failure. Whether exercise training enhances or injures the SRV is unclear. Fourteen asymptomatic patients (34 ± 10 years) with TGA and SRV were enrolled in a 12 week exercise training programme (moderate and high-intensity workouts). Controls were matched on age, gender, BMI and physical activity. Exercise testing pre- and post- training included: (a) submaximal and peak; (b) prolonged (60 min) submaximal endurance and (c) high-intensity intervals. Oxygen uptake (; Douglas bag technique), cardiac output (, foreign-gas rebreathing), ventricular function (echocardiography and cardiac MRI) and serum biomarkers were assessed. TGA patients had lower peak , , and stroke volume (SV), a blunted / slope, and diminished SV response to exercise (SV increase from rest: TGA = 15.2%, controls = 68.9%, P < 0.001) compared with controls. After training, TGA patients increased peak by 6 ± 8.5%, similar to controls (interaction P = 0.24). The magnitude of SV reserve on initial testing correlated with training response (r = 0.58, P = 0.047), though overall, no change in peak was observed. High-sensitivity troponin T (hs-TnT) and N-terminal prohormone of brain naturetic peptide (NT pro-BNP) were low and did not change with acute exercise or after training. Our data show that TGA patients with SRVs in this study safely participated in exercise training and improved peak . Neither prolonged submaximal exercise, nor high-intensity intervals, nor short-term exercise training seem to injure the systemic right ventricle. Key Points Patients with transposition of the great arteries (TGA) and systemic right ventricles have premature congestive heart failure; there is also a growing concern that athletes who perform extraordinary endurance exercise may injure the right ventricle. Therefore we felt it essential to determine whether exercise training might injure a systemic right ventricle which is loaded with every heartbeat. Previous studies have shown that short term exercise training is feasible in TGA patients, but its effect on ventricular function is unclear. We demonstrate that systemic right ventricular function is preserved (and may be improved) in TGA patients with exercise training programmes that are typical of recreational and sports participation, with no evidence of injury on biomarker assessment. Stroke volume reserve during exercise correlates with exercise training response in our TGA patients, identifying this as a marker of a systemic right ventricle (SRV) that may most tolerate (and possibly even be improved by) exercise training. PMID:25809342

MR elastography of hydrocephalus

NASA Astrophysics Data System (ADS)

Pattison, Adam J.; Lollis, S. Scott; Perrinez, Phillip R.; Weaver, John B.; Paulsen, Keith D.

2009-02-01

Hydrocephalus occurs due to a blockage in the transmission of cerebrospinal fluid (CSF) in either the ventricles or subarachnoid space. Characteristics of this condition include increased intracranial pressure, which can result in neurologic deterioration [1]. Magnetic resonance elastography (MRE) is an imaging technique that estimates the mechanical properties of tissue in vivo. While some investigations of brain tissue have been performed using MRE [2,3,4,5], the effects due to changes in interstitial pressure and fluid content on the mechanical properties of the brain remain unknown. The purpose of this work is to assess the potential of MRE to differentiate between the reconstructed properties of normal and hydrocephalic brains. MRE data was acquired in 18 female feline subjects, 12 of which received kaolin injections resulting in an acute form of hydrocephalus. In each animal, four MRE scans were performed during the process including one pre-injection and three post-injection scans. The elastic parameters were obtained using a subzone-based reconstruction algorithm that solves Navier's equations for linearly elastic materials [6]. The remaining cats were used as controls, injected with saline instead of kaolin. To determine the state of hydrocephalus, ventricular volume was estimated from segmenting anatomical images. The mean ventricular volume of hydrocephalic cats significantly increased (P <~ 0.0001) between the first and second scans. The mean volume was not observed to increase (P >~ 0.5) for the control cats. Also, there was an observable increase in the recorded elastic shear modulus of brain tissue in the normal and hydrocephalic acquisitions. Results suggest that MRE is able to detect changes in the mechanical properties of brain tissue resulting from kaolin-induced hydrocephalus, indicating the need for further study.

Brain Trauma Foundation Guideline Compliance: Results of a Multidisciplinary, International Survey.

PubMed

Hirschi, Ryan; Rommel, Casey; Letsinger, Joshua; Nirula, Raminder; Hawryluk, Gregory W J

2018-05-09

Brain Trauma Foundation (BTF) guidelines reflect evidence-based best practices in management of traumatic brain injury. The aim of this study was to examine self-reported physician compliance and predictors of compliance related to BTF guidelines. We conducted an international, multidisciplinary survey examining self-reported adherence to BTF guidelines and multiple factors potentially affecting adherence. We also surveyed intracranial pressure monitoring practices. Of 154 physician respondents, 15.9% reported their institutions "always" follow BTF guidelines and 72.2% reported that they follow them "most of the time." Personal volume of traumatic brain injury cases and years in practice were not significantly related to adherence. Reported adherence varied significantly in association with respondent's institutional trauma level (P = 0.0010): 17.3% of practitioners at level I, 13.0% at level II, and 0% at level III trauma centers reported "always" following guidelines. Reported adherence to guidelines also varied significantly in association with provider specialty (P = 0.015) and institutional volume of severe traumatic brain injury cases (P = 0.008). Regarding intracranial pressure monitoring practices, 52% of respondents used external ventricular drains, 21% used intraparenchymal monitors, and 27% had no preference (P < 0.001). Of respondents not routinely using external ventricular drains, 36% claimed to "always" follow guidelines. There was no apparent association between type of intracranial pressure monitoring used and reported guideline adherence. Few respondents reported their institutions "always" follow BTF guidelines. General surgeons and providers at high-volume level I trauma centers were more likely to comply with guidelines. Differences in survey responses based on provider and institutional characteristics may help target educational efforts. Copyright © 2018 Elsevier Inc. All rights reserved.

Congenital left ventricular aneurysms and diverticula: an entity in search of an identity

PubMed Central

Ohlow, Marc-Alexander

2017-01-01

Congenital left ventricular aneurysm or diverticulum are rare cardiac malformations described in 809 cases since the first description in 1816, being associated with other cardiac, vascular or thoraco-abdominal abnormalities in about 70%. It appears to be a developmental anomaly, starting in the 4th embryonic week. In an experimental study, targeted knockdown of cardiac troponin T in the chick was performed at day 3, after the heart tube has formed. Morpholino treatment of gene TNNT2 at this stage led to the development of left ventricular diverticula (LVD) in the primitive left ventricular wall. Diagnosis of left ventricular aneurysms (LVA)/LVD can be made after exclusion of coronary artery disease, local or systemic inflammation or traumatic causes as well as cardiomyopathies. Clinically, most of LVA and LVD are asymptomatic or may cause systemic embolization, congestive heart failure, valvular regurgitation, ventricular wall rupture, ventricular tachycardia or sudden cardiac death. Diagnosis is established by imaging studies (echocardiography, magnetic resonance imaging or left ventricular angiography) visualizing the structural changes and accompanying abnormalities. Mode of treatment has to be individually tailored and depends on clinical presentation, accompanying abnormalities and possible complications, options include surgical resection (especially in symptomatic patients), anticoagulation after systemic embolization, radiofrequency ablation or implantation of an implantable cardioverter defibrillator (ICD) in case of symptomatic ventricular tachycardias, and occasionally combined with class I- or III-antiarrhythmic drugs. Cardiac death occurs usually in childhood, is significantly more frequent in LVA patients and caused by congestive heart failure in most of the cases, whereas patients diagnosed with LVD died more frequently from rupture of the LVD. PMID:29581714

Congenital left ventricular aneurysms and diverticula: an entity in search of an identity.

PubMed

Ohlow, Marc-Alexander

2017-12-01

Congenital left ventricular aneurysm or diverticulum are rare cardiac malformations described in 809 cases since the first description in 1816, being associated with other cardiac, vascular or thoraco-abdominal abnormalities in about 70%. It appears to be a developmental anomaly, starting in the 4 th embryonic week. In an experimental study, targeted knockdown of cardiac troponin T in the chick was performed at day 3, after the heart tube has formed. Morpholino treatment of gene TNNT2 at this stage led to the development of left ventricular diverticula (LVD) in the primitive left ventricular wall. Diagnosis of left ventricular aneurysms (LVA)/LVD can be made after exclusion of coronary artery disease, local or systemic inflammation or traumatic causes as well as cardiomyopathies. Clinically, most of LVA and LVD are asymptomatic or may cause systemic embolization, congestive heart failure, valvular regurgitation, ventricular wall rupture, ventricular tachycardia or sudden cardiac death. Diagnosis is established by imaging studies (echocardiography, magnetic resonance imaging or left ventricular angiography) visualizing the structural changes and accompanying abnormalities. Mode of treatment has to be individually tailored and depends on clinical presentation, accompanying abnormalities and possible complications, options include surgical resection (especially in symptomatic patients), anticoagulation after systemic embolization, radiofrequency ablation or implantation of an implantable cardioverter defibrillator (ICD) in case of symptomatic ventricular tachycardias, and occasionally combined with class I- or III-antiarrhythmic drugs. Cardiac death occurs usually in childhood, is significantly more frequent in LVA patients and caused by congestive heart failure in most of the cases, whereas patients diagnosed with LVD died more frequently from rupture of the LVD.

Postoperative epidural haematomas associated with hydrocephalus caused by intraoperative overdrainage of cerebrospinal fluid: two case reports with a literature review of 19 cases

PubMed Central

Niimura, Manabu; Takai, Keisuke; Taniguchi, Makoto

2015-01-01

We report two cases with postoperative epidural haematomas (EDHs) associated with hydrocephalus and discuss the cause of haematoma development on the basis of a literature review. A 13-year-old boy presented with obstructive hydrocephalus caused by a sellar mass lesion. Multifocal EDHs occurred after partial resection of the lesion via a transcallosal approach following ventricular drainage. In the second case, a 26-year-old man who had a history of ventriculoperitoneal shunting for congenital hydrocephalus presented with hydrocephalus caused by ventricular catheter obstruction. An EDH occurred after replacement of the ventricular catheter with a new burr hole opening. On the basis of a review of 19 cases including our two cases, the authors concluded that postoperative EDH development associated with hydrocephalus was mostly caused by intraoperative overdrainage of cerebrospinal fluid, resulting in rapid shrinkage of the brain with dilation of the epidural space, a situation that may have caused dural venous bleeding. PMID:25666241

Remote magnetic navigation to map and ablate left coronary cusp ventricular tachycardia.

PubMed

Burkhardt, J David; Saliba, Walid I; Schweikert, Robert A; Cummings, Jennifer; Natale, Andrea

2006-10-01

Premature ventricular contractions (PVCs) and ventricular tachycardia may arise from the coronary cusps. Navigation, mapping, and ablation in the coronary cusps can be challenging. Remote magnetic navigation may offer an alternative to conventional manually operated catheters. We report a case of left coronary cusp ventricular tachycardia ablation using remote magnetic navigation. Right ventricular outflow tract and coronary cusp mapping, and ablation of the left coronary cusp using a remote magnetic navigation and three-dimensional (3-D) mapping system was performed in a 28-year-old male with frequent, symptomatic PVCs and ventricular tachycardia. Successful ablation of left coronary cusp ventricular tachycardia was performed using remote magnetic navigation. Remote magnetic navigation may be used to map and ablate PVCs and ventricular tachycardia originating from the coronary cusps.

Brain 'imaging' in the Renaissance.

PubMed

Paluzzi, Alessandro; Belli, Antonio; Bain, Peter; Viva, Laura

2007-12-01

During the Renaissance, a period of 'rebirth' for humanities and science, new knowledge and speculation began to emerge about the function of the human body, replacing ancient religious and philosophical dogma. The brain must have been a fascinating mystery to a Renaissance artist, but some speculation existed at that time on the function of its parts. Here we show how revived interest in anatomy and life sciences may have influenced the figurative work of Italian and Flemish masters, such as Rafael, Michelangelo and David. We present a historical perspective on the artists and the period in which they lived, their fascination for human anatomy and its symbolic use in their art. Prior to the 16th century, knowledge of the brain was limited and influenced in a dogmatic way by the teachings of Galen(1) who, as we now know, conducted his anatomical studies not on humans but on animals.(2) Nemesus, Bishop of Emesa, in around the year 400 was one of the first to attribute mental faculties to the brain, specifically to the ventricles. He identified two anterior (lateral) ventricles, to which he assigned perception, a middle ventricle responsible for cognition and a posterior ventricle for memory.(2,3) After a long period of stasis in the Middle Ages, Renaissance scholars realized the importance of making direct observations on dissected cadavers. Between 1504 and 1507, Leonardo da Vinci conducted experiments to reveal the anatomy of the ventricular system in the brain. He injected hot wax through a tube thrust into the ventricular cavities of an ox and then scraped the overlying brain off, thus obtaining, in a simple but ingenious way, an accurate cast of the ventricles.(2,4) Leonardo shared the belief promoted by scholarly Christians that the ventricles were the abode of rational soul. We have several examples of hidden symbolism in Renaissance paintings, but the influence of phrenology and this rudimentary knowledge of neuroanatomy on artists of that period is under-recognized. In the absence of documentary or scientific evidence as to the real intentions of these painters, the notion of such commixture of sacred and profane remains speculative and probably controversial, but at the same time fascinating and provocative. Here we present three examples of Renaissance masterpieces where such symbolism may have been used, although probably many more exist. Conducting an artistic, philosophical and anatomical analysis of the paintings can be an intriguing exercise, but the interpretation will inevitably be conjectural.

Brain ‘imaging’ in the Renaissance

PubMed Central

Paluzzi, Alessandro; Belli, Antonio; Bain, Peter; Viva, Laura

2007-01-01

During the Renaissance, a period of ‘rebirth’ for humanities and science, new knowledge and speculation began to emerge about the function of the human body, replacing ancient religious and philosophical dogma. The brain must have been a fascinating mystery to a Renaissance artist, but some speculation existed at that time on the function of its parts. Here we show how revived interest in anatomy and life sciences may have influenced the figurative work of Italian and Flemish masters, such as Rafael, Michelangelo and David. We present a historical perspective on the artists and the period in which they lived, their fascination for human anatomy and its symbolic use in their art. Prior to the 16th century, knowledge of the brain was limited and influenced in a dogmatic way by the teachings of Galen1 who, as we now know, conducted his anatomical studies not on humans but on animals.2 Nemesus, Bishop of Emesa, in around the year 400 was one of the first to attribute mental faculties to the brain, specifically to the ventricles. He identified two anterior (lateral) ventricles, to which he assigned perception, a middle ventricle responsible for cognition and a posterior ventricle for memory.2,3 After a long period of stasis in the Middle Ages, Renaissance scholars realized the importance of making direct observations on dissected cadavers. Between 1504 and 1507, Leonardo da Vinci conducted experiments to reveal the anatomy of the ventricular system in the brain. He injected hot wax through a tube thrust into the ventricular cavities of an ox and then scraped the overlying brain off, thus obtaining, in a simple but ingenious way, an accurate cast of the ventricles.2,4 Leonardo shared the belief promoted by scholarly Christians that the ventricles were the abode of rational soul. We have several examples of hidden symbolism in Renaissance paintings, but the influence of phrenology and this rudimentary knowledge of neuroanatomy on artists of that period is under-recognized. In the absence of documentary or scientific evidence as to the real intentions of these painters, the notion of such commixture of sacred and profane remains speculative and probably controversial, but at the same time fascinating and provocative. Here we present three examples of Renaissance masterpieces where such symbolism may have been used, although probably many more exist. Conducting an artistic, philosophical and anatomical analysis of the paintings can be an intriguing exercise, but the interpretation will inevitably be conjectural. PMID:18065703

Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

PubMed Central

Bigini, Paolo; Diana, Valentina; Barbera, Sara; Fumagalli, Elena; Micotti, Edoardo; Sitia, Leopoldo; Paladini, Alessandra; Bisighini, Cinzia; De Grada, Laura; Coloca, Laura; Colombo, Laura; Manca, Pina; Bossolasco, Patrizia; Malvestiti, Francesca; Fiordaliso, Fabio; Forloni, Gianluigi; Morbidelli, Massimo; Salmona, Mario; Giardino, Daniela; Mennini, Tiziana; Moscatelli, Davide; Silani, Vincenzo; Cova, Lidia

2012-01-01

Stem Cell (SC) therapy is one of the most promising approaches for the treatment of Amyotrophic Lateral Sclerosis (ALS). Here we employed Super Paramagnetic Iron Oxide nanoparticles (SPIOn) and Hoechst 33258 to track human Amniotic Fluid Cells (hAFCs) after transplantation in the lateral ventricles of wobbler (a murine model of ALS) and healthy mice. By in vitro, in vivo and ex vivo approaches we found that: 1) the main physical parameters of SPIOn were maintained over time; 2) hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258 labeled nuclei; 3) SPIOn internalization did not alter survival, cell cycle, proliferation, metabolism and phenotype of hAFCs; 4) after transplantation hAFCs rapidly spread to the whole ventricular system, but did not migrate into the brain parenchyma; 5) hAFCs survived for a long time in the ventricles of both wobbler and healthy mice; 6) the transplantation of double-labeled hAFCs did not influence mice survival. PMID:22384217

Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease.

PubMed

Li, Rui; Sun, Le; Fang, Ai; Li, Peng; Wu, Qian; Wang, Xiaoqun

2017-11-01

The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.

Hydrocephalus: the role of cerebral aquaporin-4 channels and computational modeling considerations of cerebrospinal fluid.

PubMed

Desai, Bhargav; Hsu, Ying; Schneller, Benjamin; Hobbs, Jonathan G; Mehta, Ankit I; Linninger, Andreas

2016-09-01

Aquaporin-4 (AQP4) channels play an important role in brain water homeostasis. Water transport across plasma membranes has a critical role in brain water exchange of the normal and the diseased brain. AQP4 channels are implicated in the pathophysiology of hydrocephalus, a disease of water imbalance that leads to CSF accumulation in the ventricular system. Many molecular aspects of fluid exchange during hydrocephalus have yet to be firmly elucidated, but review of the literature suggests that modulation of AQP4 channel activity is a potentially attractive future pharmaceutical therapy. Drug therapy targeting AQP channels may enable control over water exchange to remove excess CSF through a molecular intervention instead of by mechanical shunting. This article is a review of a vast body of literature on the current understanding of AQP4 channels in relation to hydrocephalus, details regarding molecular aspects of AQP4 channels, possible drug development strategies, and limitations. Advances in medical imaging and computational modeling of CSF dynamics in the setting of hydrocephalus are summarized. Algorithmic developments in computational modeling continue to deepen the understanding of the hydrocephalus disease process and display promising potential benefit as a tool for physicians to evaluate patients with hydrocephalus.

Identification of the Upward Movement of Human CSF In Vivo and its Relation to the Brain Venous System.

PubMed

Dreha-Kulaczewski, Steffi; Joseph, Arun A; Merboldt, Klaus-Dietmar; Ludwig, Hans-Christoph; Gärtner, Jutta; Frahm, Jens

2017-03-01

CSF flux is involved in the pathophysiology of neurodegenerative diseases and cognitive impairment after traumatic brain injury, all hallmarked by the accumulation of cellular metabolic waste. Its effective disposal via various CSF routes has been demonstrated in animal models. In contrast, the CSF dynamics in humans are still poorly understood. Using novel real-time MRI, forced inspiration has been identified recently as a main driving force of CSF flow in the human brain. Exploiting technical advances toward real-time phase-contrast MRI, the current work analyzed directions, velocities, and volumes of human CSF flow within the brain aqueduct as part of the internal ventricular system and in the spinal canal during respiratory cycles. A consistent upward CSF movement toward the brain in response to forced inspiration was seen in all subjects at the aqueduct, in 11/12 subjects at thoracic level 2, and in 4/12 subjects at thoracic level 5. Concomitant analyses of CSF dynamics and cerebral venous blood flow, that is, in epidural veins at cervical level 3, uniquely demonstrated CSF and venous flow to be closely communicating cerebral fluid systems in which inspiration-induced downward flow of venous blood due to reduced intrathoracic pressure is counterbalanced by an upward movement of CSF. The results extend our understanding of human CSF flux and open important clinical implications, including concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and idiopathic intracranial hypertension. SIGNIFICANCE STATEMENT Effective disposal of brain cellular waste products via CSF has been demonstrated repeatedly in animal models. However, CSF dynamics in humans are still poorly understood. A novel quantitative real-time MRI technique yielded in vivo CSF flow directions, velocities, and volumes in the human brain and upper spinal canal. CSF moved upward toward the head in response to forced inspiration. Concomitant analysis of brain venous blood flow indicated that CSF and venous flux act as closely communicating systems. The finding of a human CSF-venous network with upward CSF net movement opens new clinical concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and ideopathic intracranial hypertension. Copyright © 2017 the authors 0270-6474/17/372395-08$15.00/0.

Modeling Laterality of the Globus Pallidus Internus in Patients With Parkinson's Disease.

PubMed

Sharim, Justin; Yazdi, Daniel; Baohan, Amy; Behnke, Eric; Pouratian, Nader

2017-04-01

Neurosurgical interventions such as deep brain stimulation surgery of the globus pallidus internus (GPi) play an important role in the treatment of medically refractory Parkinson's disease (PD), and require high targeting accuracy. Variability in the laterality of the GPi across patients with PD has not been well characterized. The aim of this report is to identify factors that may contribute to differences in position of the motor region of GPi. The charts and operative reports of 101 PD patients following deep brain stimulation surgery (70 males, aged 11-78 years) representing 201 GPi were retrospectively reviewed. Data extracted for each subject include age, gender, anterior and posterior commissures (AC-PC) distance, and third ventricular width. Multiple linear regression, stepwise regression, and relative importance of regressors analysis were performed to assess the predictive ability of these variables on GPi laterality. Multiple linear regression for target vs. third ventricular width, gender, AC-PC distance, and age were significant for normalized linear regression coefficients of 0.333 (p < 0.0001), 0.206 (p = 0.00219), 0.168 (p = 0.0119), and 0.159 (p = 0.0136), respectively. Third ventricular width, gender, AC-PC distance, and age each account for 44.06% (21.38-65.69%, 95% CI), 20.82% (10.51-35.88%), 21.46% (8.28-37.05%), and 13.66% (2.62-28.64%) of the R 2 value, respectively. Effect size calculation was significant for a change in the GPi laterality of 0.19 mm per mm of ventricular width, 0.11 mm per mm of AC-PC distance, 0.017 mm per year in age, and 0.54 mm increase for male gender. This variability highlights the limitations of indirect targeting alone, and argues for the continued use of MRI as well as intraoperative physiological testing to account for such factors that contribute to patient-specific variability in GPi localization. © 2016 International Neuromodulation Society.

Ventricular-subcutaneous shunt for the treatment of experimental hydrocephalus in young rats: technical note.

PubMed

Santos, Marcelo Volpon; Garcia, Camila Araujo Bernardino; Jardini, Evelise Oliveira; Romeiro, Thais Helena; da Silva Lopes, Luiza; Machado, Hélio Rubens; de Oliveira, Ricardo Santos

2016-08-01

Hydrocephalus is a complex disease that affects cerebrospinal fluid (CSF) dynamics and is very common in children. To this date, CSF shunting is still the standard treatment for childhood hydrocephalus, but, nevertheless, the effects of such an operation on the developing brain are widely unknown. To help overcome this, experimental models of CSF shunts are surely very useful tools. The objective of this study was to describe a feasible and reliable technique of an adapted ventricular-subcutaneous shunt for the treatment of kaolin-induced hydrocephalus in young rats. We developed a ventricular-subcutaneous shunt (VSCS) technique which was used in 31 Wistar young rats with kaolin-induced hydrocephalus. Hydrocephalus was induced at 7 days of age, and shunt implantation was performed 7 days later. Our technique used a 0.7-mm gauge polypropylene catheter tunneled to a subcutaneous pocket created over the animal's back and inserted into the right lateral ventricle. All animals were sacrificed 14 days after shunt insertion. Twenty-four rats survived and remained well until the study was ended. No major complications were seen. Their weight gain went back to normal. They all underwent ambulatory behavioral testing prior and after VSCS, which showed improvement in their motor skills. We have also obtained magnetic resonance (MR) scans of 16 pups confirming reduction of ventricular size after shunting and indicating effective treatment. Histopathological analysis of brain samples before and after shunting showed reversion of ependymal and corpus callosum disruption, as well as fewer reactive astrocytes in shunted animals. An experimental CSF shunt technique was devised. Excessive CSF of hydrocephalic rats is diverted into the subcutaneous space where it can be resorbed. This technique has a low complication rate and is effective. It might be applied to various types of experimental studies involving induction and treatment of hydrocephalus.

A description of model 3B of the multipurpose ventricular actuating system. [providing controlled driving pressures

NASA Technical Reports Server (NTRS)

Webb, J. A., Jr.

1974-01-01

The multipurpose ventricular actuating system is a pneumatic signal generating device that provides controlled driving pressures for actuating pulsatile blood pumps. Overall system capabilities, the timing circuitry, and calibration instruction are included.

MRI, volumetry, 1H spectroscopy, and cerebropetal blood flowmetry in childhood idiopathic anatomic megalencephaly.

PubMed

Koudijs, Suzanne M; van der Grond, Jeroen; Hoogendoorn, Mechteld L C; Hulshoff Pol, Hilleke E; Schnack, Hugo G; Witkamp, Theo D; Gooskens, Rob H J M; van Nieuwenhuizen, Onno; Braun, Kees P J

2006-08-01

To evaluate cerebral abnormalities in childhood idiopathic anatomic megalencephaly (MC) by means of different magnetic resonance (MR) modalities. MRI, volumetry, spectroscopy, and cerebropetal blood flowmetry were performed in six children with idiopathic anatomic MC, and seven volunteers. MRI revealed an increased ventricular system in five of six patients. A thalamic hamartoma was found in one patient and a Chiari I malformation was found in two. Volumetric analysis showed a disproportional increase of ventricular volume but normal subarachnoid cerebrospinal fluid (CSF) volume. Supratentorial volume was disproportionally increased compared to cerebellar volume. Intracranial volume correlated significantly with skull circumference. MR spectroscopy (MRS) N-acetyl aspartate/choline (NAA/Cho) peak ratios in WM were significantly higher in patients than in controls. Choline/creatine (Cho/Cr) peak ratios in WM were significantly lower in patients. Cortical gray matter (GM) MRS ratios were unaltered. Cerebropetal flow was increased in MC, possibly related to increased brain volume. This study reveals associated developmental anomalies for idiopathic anatomic MC. A relative ventriculomegaly was found, which should not be misinterpreted as true hydrocephalus. In contrast to metabolic MC, MRS showed no severe disturbances. Total intracranial volume is correlated to skull circumference and cerebropetal blood flow.

Cerebrospinal fluid circulation and hydrocephalus.

PubMed

Leinonen, Ville; Vanninen, Ritva; Rauramaa, Tuomas

2017-01-01

Hydrocephalus (HC) is classically defined as dynamic imbalance between the production and absorption of cerebrospinal fluid (CSF) leading to enlarged ventricles. Potential causative factors include various brain disorders like tumors causing obstruction of CSF flow within the ventricular system or the subarachnoid space. Classification of HC is based on the site of CSF flow obstruction guiding optimal treatment, with endoscopic third ventriculostomy in intraventricular obstruction and CSF shunt in communicating HC. Another clinically relevant classification is acute and chronic; the most frequent chronic form is idiopathic normal-pressure hydrocephalus (iNPH). The reported incidence of HC varies according to the study population and classification used. The incidence of congenital HC is approximately 0.4-0.6/1,000 newborns and the annual incidence of iNPH varies from 0.5/100,000 to 5.5/100,000. Radiologically, ventricular dilatation may be nonspecific, and differentiation of iNPH from other neurodegenerative diseases may be ambiguous. There are no known specific microscopic findings of HC but a systematic neuropathologic examination is needed to detect comorbid diseases and possible etiologic factors of HC. Depending on the etiology of HC, there are several nonspecific signs potentially to be seen. Copyright © 2017 Elsevier B.V. All rights reserved.

Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

PubMed

Anselmi, L; Toti, L; Bove, C; Travagli, R A

2017-11-01

Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

Brain perfusion evaluated by regional tissue oxygenation as a possible quality indicator of ongoing cardiopulmonary resuscitation. An experimental porcine cardiac arrest study.

PubMed

Bouček, Tomáš; Mlček, Mikuláš; Krupičková, Petra; Huptych, Michal; Belza, Tomáš; Kittnar, Otomar; Linhart, Aleš; Bělohlávek, Jan

2018-05-01

Relationship between regional tissue oxygenation (rSO 2 ) and microcirculatory changes during cardiac arrest (CA) are still unclear. Therefore, we designed an experimental study to correlate rSO 2 , microcirculation and systemic hemodynamic parameters in a porcine model of CA. Ventricular fibrillation was induced in 24 female pigs (50±3kg) and left for three minutes untreated followed by five minutes of mechanical CPR. Regional and peripheral saturations were assessed by near-infrared spectroscopy, sublingual microcirculation by Sidestream Dark Field technology and continuous hemodynamic parameters, including systemic blood pressure (MAP) and carotid blood flow (CF), during baseline, CA and CPR periods. The Wilcoxon Signed-Rank test, the Friedman test and the partial correlation method were used to compare these parameters. Brain and peripheral rSO 2 showed a gradual decrease during CA and only an increase of brain rSO 2 during mechanical CPR (34.5 to 42.5; p=0.0001), reflected by a rapid decrease of microcirculatory and hemodynamic parameters during CA and a slight increase during CPR. Peripheral rSO 2 was not changed significantly during CPR (38 to 38.5; p=0.09). We only found a moderate correlation of cerebral/peripheral rSO 2 to microcirculatory parameters (PVD: r=0.53/0.46; PPV: r=0.6/0.5 and MFI: r=0.64/0.52) and hemodynamic parameters (MAP: r=0.64/0.71 and CF: 0.71/0.67). Our experimental study confirmed that monitoring brain and peripheral rSO 2 is an easy-to-use method, well reflecting the hemodynamics during CA. However, only brain rSO 2 reflects the CPR efforts and might be used as a potential quality indicator for CPR.

Anatomy and histology of the brain and sense organs of the antarctic plunderfish Dolloidraco longedorsalis (Perciformes: Notothenioidei: Artedidraconidae), with comments on the brain morphology of other artedidraconids and closely related harpagiferids.

PubMed

Eastman, Joseph T; Lannoo, Michael J

2003-03-01

In the high-latitude shelf waters of Antarctica, fishes in the perciform suborder Notothenioidei dominate the fish fauna and constitute an adaptive radiation and a species flock. The 25 species of notothenioid plunderfishes, comprising four genera of the family Artedidraconidae, contribute substantially to fish species diversity on the high Antarctic shelf. A mental barbel is an autapomorphy for the family. Dolloidraco longedorsalis is the most abundant artedidraconid at depths over 400 m in these waters. In this article we present the anatomy and histology of the brain and special sense organs of Dolloidraco and compare it to the brains of other artedidraconids, closely related harpagiferids, and more generally to other notothenioids. We provide a detailed drawing of the brain and cranial nerves. The brain of Dolloidraco is simple, without external hypertrophy of sensory or motor regions, but contains several unusual features associated with the ventricular system and CSF, including well-developed circumventricular organs, subependymal expansions, and subarachnoid cisterns; and a ventricle in the corpus cerebellum. The brain of Dolloidraco also contains a lobed chief sensory nucleus of the trigeminal nerve that is correlated across species with barbel length. The eyes are large and contain a small choroid rete, a structure previously thought to be absent from members of this family. We document the histology of the duplex retina, olfactory apparatus, cutaneous taste buds, and barbel musculature and innervation. We discuss the role of pedomorphy in producing simplified brain morphologies. We consider the possibility that Dolloidraco is a somatosensory specialist-an unusual feature among vertebrates-and decide that this is unlikely. Copyright 2003 Wiley-Liss, Inc.

Arterial Ventricular Uncoupling with Age and Disease and Recoupling with Exercise

PubMed Central

Chantler, Paul D

2017-01-01

The deterioration in arterial and cardiac function with aging impairs arterial ventricular coupling, an important determinant of cardiovascular performance. However, exercise training improves arterial ventricular coupling especially during exercise during the age and disease process. This review examines the concept of arterial-ventricular coupling, and how age, and disease uncouples but exercise training recouples the heart and arterial system. PMID:28072585

The Role of NT-proBNP in the Diagnosis of Ventricular Arrhythmias in Patients with Systemic Sclerosis

PubMed Central

MURESAN, Lucian; PETCU, Ana; MURESAN, Crina; RINZIS, Mirela; GUSETU, Gabriel; POP, Dana; ZDRENGHEA, Dumitru; REDNIC, Simona

2017-01-01

Background: In patients with systemic sclerosis, NT-proBNP is a useful diagnostic marker for pulmonary hypertension and ventricular dysfunction, with important prognostic significance. The aim of this study was to assess the relationship between the NT-proBNP levels and the presence and severity of ventricular arrhythmias in patients with scleroderma. Methods: Forty consecutive patients with a diagnostic of systemic sclerosis according to the EULAR criteria admitted at the Rheumatology Clinic of Cluj-Napoca, Romania, from Jan 2014 to Apr 2014 were enrolled. Patients underwent a 12-lead ECG and a 24-hour Holter ECG monitoring for ventricular arrhythmias evaluation. Blood sample testing (including NT-proBNP level measurements), echocardiography, spirometry, chest X-ray and, when considered appropriate, high-resolution chest CT were performed. Results: Sixty percent of patients (n=24) had abnormal NT-proBNP serum levels (>125 pg/ml) and 10 patients had >100 PVC/24 h. There was a statistically significant correlation between the NT-proBNP levels and the total number of premature ventricular contractions (PVC) (r=0.445, P=0.006), total number of isolated PVC (r=0,493, P=0.002), total number of ventricular couplets (r=0.379, P=0.021) and the number of PVC morphologies (r=0.501, P=0.002). The presence of an NT-proBNP serum level >287 pg/ml had a sensitivity of 55% and a specificity of 93% in predicting the presence of complex ventricular arrhythmias on 24-hour Holter ECG monitoring. Conclusion: NT-proBNP levels could become a useful ventricular arrhythmia marker for assessing the arrhythmic risk in patients with systemic sclerosis. PMID:28845401

Dynamic radionuclide determination of regional left ventricular wall motion using a new digital imaging device

NASA Technical Reports Server (NTRS)

Steele, P.; Kirch, D.

1975-01-01

In 47 men with arteriographically defined coronary artery disease comparative studies of left ventricular ejection fraction and segmental wall motion were made with radionuclide data obtained from the image intensifier camera computer system and with contrast cineventriculography. The radionuclide data was digitized and the images corresponding to left ventricular end-diastole and end-systole were identified from the left ventricular time-activity curve. The left ventricular end-diastolic and end-systolic images were subtracted to form a silhouette difference image which described wall motion of the anterior and inferior left ventricular segments. The image intensifier camera allows manipulation of dynamically acquired radionuclide data because of the high count rate and consequently improved resolution of the left ventricular image.

Choline Availability During Embryonic Development Alters Progenitor Cell Mitosis in Developing Mouse Hippocampus1,2

PubMed Central

Craciunescu, Corneliu N.; Albright, Craig D.; Mar, Mei-Heng; Song, Jiannan; Zeisel, Steven H.

2006-01-01

Previously, we reported that dietary choline influences development of the hippocampus in fetal rat brain. It is important to know whether similar effects of choline occur in developing fetal mouse brain because interesting new experimental approaches are now available using several transgenic mouse models. Timed-pregnant mice were fed choline-supplemented (CS), control (CT) or choline-deficient (CD) AIN-76 diet from embryonic day 12 to 17 (E12–17). Fetuses from CD dams had diminished concentrations of phosphocholine and phosphatidylcholine in their brains compared with CT or CS fetuses (P < 0.05). When we analyzed fetal hippocampus on day E17 for cells with mitotic phase–specific expression of phosphorylated histone H3, we detected fewer labeled cells at the ventricular surface of the ventricular zone in the CD group (14.8 ± 1.9) compared with the CT (30.7 ± 1.9) or CS (36.6 ± 2.6) group (P < 0.05). At the same time, we detected more apoptotic cells in E17 hippocampus using morphology in the CD group (11.8 ± 1.4) than in CT (5.6 ± 0.6) or CS (4.2 ± 0.7) group (P < 0.05). This was confirmed using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin anti-digoxigenin fluorescein conjugate antibody nick end-labeling (TUNEL) and activated caspase-3 immunoreactivity. We conclude that the dietary availability of choline to the mouse dam influences progenitor cell proliferation and apoptosis in the fetal brain. J. Nutr. 133: 3614–3618, 2003. PMID:14608083

Studying ventricular abnormalities in mild cognitive impairment with hyperbolic Ricci flow and tensor-based morphometry.

PubMed

Shi, Jie; Stonnington, Cynthia M; Thompson, Paul M; Chen, Kewei; Gutman, Boris; Reschke, Cole; Baxter, Leslie C; Reiman, Eric M; Caselli, Richard J; Wang, Yalin

2015-01-01

Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and dementia and people with MCI are at high risk of progression to dementia. MCI is attracting increasing attention, as it offers an opportunity to target the disease process during an early symptomatic stage. Structural magnetic resonance imaging (MRI) measures have been the mainstay of Alzheimer's disease (AD) imaging research, however, ventricular morphometry analysis remains challenging because of its complicated topological structure. Here we describe a novel ventricular morphometry system based on the hyperbolic Ricci flow method and tensor-based morphometry (TBM) statistics. Unlike prior ventricular surface parameterization methods, hyperbolic conformal parameterization is angle-preserving and does not have any singularities. Our system generates a one-to-one diffeomorphic mapping between ventricular surfaces with consistent boundary matching conditions. The TBM statistics encode a great deal of surface deformation information that could be inaccessible or overlooked by other methods. We applied our system to the baseline MRI scans of a set of MCI subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI: 71 MCI converters vs. 62 MCI stable). Although the combined ventricular area and volume features did not differ between the two groups, our fine-grained surface analysis revealed significant differences in the ventricular regions close to the temporal lobe and posterior cingulate, structures that are affected early in AD. Significant correlations were also detected between ventricular morphometry, neuropsychological measures, and a previously described imaging index based on fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This novel ventricular morphometry method may offer a new and more sensitive approach to study preclinical and early symptomatic stage AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Synergic effects of renin and aldosterone on right ventricular function in hypertension: a tissue Doppler study.

PubMed

Gregori, Mario; Giammarioli, Benedetta; Tocci, Giuliano; Befani, Alberto; Ciavarella, Giuseppino Massimo; Ferrucci, Andrea; Paneni, Francesco

2015-12-01

Right ventricular dysfunction (RVD) is associated with poor cardiovascular outcome. The renin-angiotensin-aldosterone system is involved in alterations of the left ventricular geometry and function. Detrimental effects of the renin-angiotensin-aldosterone system on the right ventricular function are being postulated, but data supporting this assumption are still lacking. The aim of the study was to assess the impact of hyperreninemia, hyperaldosteronism or their combination on right ventricular function in hypertensive individuals. Plasma renin activity (PRA) and plasma aldosterone concentrations (PACs) were measured in 116 hypertensive patients, divided as follows: normal PRA and PAC (n = 38); high PRA and normal PAC (hypereninemia) (n = 26); normal PRA and high PAC (hyperaldosternism) (n = 27); high PRA and PAC (HRA) (n = 25). Echocardiographic evaluation of the left and right ventricles (RV), including tissue Doppler imaging, was performed. RVD was identified by tissue Doppler Imaging-derived Myocardial Performance Index, calculated with a multisegmental approach. Indices of the right ventricular structure and function, as well as the prevalence of RVD, were higher in hyperreninemia and hyperaldosternism groups as compared with the normal group, and a further increase was observed in the HRA patients. Regression models showed a similar risk of RVD in the hyperreninemia and hyperaldosternism patients, regardless of systemic and pulmonary pressure, as well as left ventricular dysfunction. Notably, patients with both hyperreninemia and hyperaldosternism exhibited the strongest association with RVD as compared with patients with only hyperreninemia or hyperaldosternism. Isolated hyperreninemia or hyperaldosternism determines a similar impairment of the right ventricular function, whereas their combination is further detrimental. Renin and aldosterone may represent early biomarkers of right ventricular dysfunction in hypertension.

STUDYING VENTRICULAR ABNORMALITIES IN MILD COGNITIVE IMPAIRMENT WITH HYPERBOLIC RICCI FLOW AND TENSOR-BASED MORPHOMETRY

PubMed Central

Shi, Jie; Stonnington, Cynthia M.; Thompson, Paul M.; Chen, Kewei; Gutman, Boris; Reschke, Cole; Baxter, Leslie C.; Reiman, Eric M.; Caselli, Richard J.; Wang, Yalin

2014-01-01

Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and dementia and people with MCI are at high risk of progression to dementia. MCI is attracting increasing attention, as it offers an opportunity to target the disease process during an early symptomatic stage. Structural magnetic resonance imaging (MRI) measures have been the mainstay of Alzheimer’s disease (AD) imaging research, however, ventricular morphometry analysis remains challenging because of its complicated topological structure. Here we describe a novel ventricular morphometry system based on the hyperbolic Ricci flow method and tensor-based morphometry (TBM) statistics. Unlike prior ventricular surface parameterization methods, hyperbolic conformal parameterization is angle-preserving and does not have any singularities. Our system generates a one-to-one diffeomorphic mapping between ventricular surfaces with consistent boundary matching conditions. The TBM statistics encode a great deal of surface deformation information that could be inaccessible or overlooked by other methods. We applied our system to the baseline MRI scans of a set of MCI subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI: 71 MCI converters vs. 62 MCI stable). Although the combined ventricular area and volume features did not differ between the two groups, our fine-grained surface analysis revealed significant differences in the ventricular regions close to the temporal lobe and posterior cingulate, structures that are affected early in AD. Significant correlations were also detected between ventricular morphometry, neuropsychological measures, and a previously described imaging index based on fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This novel ventricular morphometry method may offer a new and more sensitive approach to study preclinical and early symptomatic stage AD. PMID:25285374

Reduction of shunt obstructions by using a peel-away sheath technique? A multicenter prospective randomized trial.

PubMed

Kehler, Uwe; Langer, Niels; Gliemroth, Jan; Meier, Ullrich; Lemcke, Johannes; Sprung, Christian; Schlosser, Hans-Georg; Kiefer, Michael; Eymann, Regina; Heese, Oliver

2012-05-01

Shunt obstructions may partly be caused by brain debris, which intrude into the ventricular catheter during ventricle puncture. Avoiding contact between the catheter and brain tissue, by using a peel-away sheath, should reduce the number of shunt failures caused by obstruction. To test this hypothesis, we conducted a randomized, prospective multicenter study. 201 patients from 6 different neurosurgical centers in Germany receiving a ventriculo-peritoneal shunt were included in this study. Of these, 177 patients completed a 1-year follow-up period. Surgery was randomized in a 1 to 1 fashion, such that out of 177 procedures, 91 were performed using a peel-away sheath and 86 were performed without. The rate of surgical re-interventions and shunt obstructions within a 12-month period was recorded. Within 1 year post-surgery, 17 shunt obstructions (9.6%) leading to shunt revisions were recorded. However, no difference was found between surgeries performed using a peel-away sheath (9.9%) or not (9.3%). The overall shunt infection rate was 2.8% and the shunt revision rate for overdrainage was 3.9%. The theoretical advantages attributed to the use of a peel-away sheath to introduce a ventricular catheter could not be confirmed in this randomized study, suggesting that the proposed role of brain debris in shunt obstructions may be overestimated. Copyright © 2011 Elsevier B.V. All rights reserved.

Migration Pathways of Thalamic Neurons and Development of Thalamocortical Connections in Humans Revealed by Diffusion MR Tractography.

PubMed

Wilkinson, Molly; Kane, Tara; Wang, Rongpin; Takahashi, Emi

2017-12-01

The thalamus plays an important role in signal relays in the brain, with thalamocortical (TC) neuronal pathways linked to various sensory/cognitive functions. In this study, we aimed to see fetal and postnatal development of the thalamus including neuronal migration to the thalamus and the emergence/maturation of the TC pathways. Pathways from/to the thalami of human postmortem fetuses and in vivo subjects ranging from newborns to adults with no neurological histories were studied using high angular resolution diffusion MR imaging (HARDI) tractography. Pathways likely linked to neuronal migration from the ventricular zone and ganglionic eminence (GE) to the thalami were both successfully detected. Between the ventricular zone and thalami, more tractography pathways were found in anterior compared with posterior regions, which was well in agreement with postnatal observations that the anterior TC segment had more tract count and volume than the posterior segment. Three different pathways likely linked to neuronal migration from the GE to the thalami were detected. No hemispheric asymmetry of the TC pathways was quantitatively observed during development. These results suggest that HARDI tractography is useful to identify multiple differential neuronal migration pathways in human brains, and regional differences in brain development in fetal ages persisted in postnatal development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Roles of inflammation and apoptosis in experimental brain death-induced right ventricular failure.

PubMed

Belhaj, Asmae; Dewachter, Laurence; Rorive, Sandrine; Remmelink, Myriam; Weynand, Birgit; Melot, Christian; Galanti, Laurence; Hupkens, Emeline; Sprockeels, Thomas; Dewachter, Céline; Creteur, Jacques; McEntee, Kathleen; Naeije, Robert; Rondelet, Benoît

2016-12-01

Right ventricular (RV) dysfunction remains the leading cause of early death after cardiac transplantation. Methylprednisolone is used to improve graft quality; however, evidence for that remains empirical. We sought to determine whether methylprednisolone, acting on inflammation and apoptosis, might prevent brain death-induced RV dysfunction. After randomization to placebo (n = 11) or to methylprednisolone (n = 8; 15 mg/kg), 19 pigs were assigned to a brain-death procedure. The animals underwent hemodynamic evaluation at 1 and 5 hours after Cushing reflex (i.e., hypertension and bradycardia). The animals euthanized, and myocardial tissue was sampled. This was repeated in a control group (n = 8). At 5 hours after the Cushing reflex, brain death resulted in increased pulmonary artery pressure (27 ± 2 vs 18 ± 1 mm Hg) and in a 30% decreased ratio of end-systolic to pulmonary arterial elastances (Ees/Ea). Cardiac output and right atrial pressure did not change. This was prevented by methylprednisolone. Brain death-induced RV dysfunction was associated with increased RV expression of heme oxygenase-1, interleukin (IL)-6, IL-10, IL-1β, tumor necrosis factor (TNF)-α, IL-1 receptor-like (ST)-2, signal transducer and activator of transcription-3, intercellular adhesion molecules-1 and -2, vascular cell adhesion molecule-1, and neutrophil infiltration, whereas IL-33 expression decreased. RV apoptosis was confirmed by terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling staining. Methylprednisolone pre-treatment prevented RV-arterial uncoupling and decreased RV expression of TNF-α, IL-1 receptor-like-2, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and neutrophil infiltration. RV Ees/Ea was inversely correlated to RV TNF-α and IL-6 expression. Brain death-induced RV dysfunction is associated with RV activation of inflammation and apoptosis and is partly limited by methylprednisolone. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The overloaded right heart and ventricular interdependence.

PubMed

Naeije, Robert; Badagliacca, Roberto

2017-10-01

The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Thulium fiber laser recanalization of occluded ventricular catheters in an ex vivo tissue model

NASA Astrophysics Data System (ADS)

Hutchens, Thomas C.; Gonzalez, David A.; Hardy, Luke A.; McLanahan, C. Scott; Fried, Nathaniel M.

2017-04-01

Hydrocephalus is a chronic medical condition that occurs in individuals who are unable to reabsorb cerebrospinal fluid (CSF) created within the ventricles of the brain. Treatment requires excess CSF to be diverted from the ventricles to another part of the body, where it can be returned to the vascular system via a shunt system beginning with a catheter within the ventricle. Catheter failures due to occlusion by brain tissues commonly occur and require surgical replacement of the catheter. In this preliminary study, minimally invasive clearance of occlusions is explored using an experimental thulium fiber laser (TFL), with comparison to a conventional holmium: yttrium aluminium garnet (YAG) laser. The TFL utilizes smaller optical fibers (<200-μm OD) compared with holmium laser (>450-μm OD), providing critical extra cross-sectional space within the 1.2-mm-inner-diameter ventricular catheter for simultaneous application of an endoscope for image guidance and a saline irrigation tube for visibility and safety. TFL ablation rates using 100-μm core fiber, 33-mJ pulse energy, 500-μs pulse duration, and 20- to 200-Hz pulse rates were compared to holmium laser using a 270-μm core fiber, 325-mJ, 300-μs, and 10 Hz. A tissue occluded catheter model was prepared using coagulated egg white within clear silicone tubing. An optimal TFL pulse rate of 50 Hz was determined, with an ablation rate of 150 μm/s and temperature rise outside the catheter of ˜10°C. High-speed camera images were used to explore the mechanism for removal of occlusions. Image guidance using a miniature, 0.7-mm outer diameter, 10,000 pixel endoscope was explored to improve procedure safety. With further development, simultaneous application of TFL with small fibers, miniature endoscope for image guidance, and irrigation tube for removal of tissue debris may provide a safe, efficient, and minimally invasive method of clearing occluded catheters in the treatment of hydrocephalus.

Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance.

PubMed

Cao, Jia-Li; Yang, Yu-Qing; Nabeel, Dookhun Muhammad; Sun, Ya-Li; Zou, Hua-Yi-Yang; Kong, Xiang-Qing; Lu, Xin-Zheng

The aim of this study is to investigate the correlation between calcineurin (CaN) and hypertension with left ventricular hypertrophy (HLVH) and to evaluate its potential clinical significance. The study involved 160 patients diagnosed with hypertension and 42 controls. Based on the exclusion criteria, 42 were not eligible for this study. The remaining 118 hypertensive patients were categorized into 2 subgroups based on left ventricular mass index and relative ventricular wall thickness: a normal model subgroup with hypertension (HNM) and an HLVH subgroup. Serum CaN levels were determined by enzyme-linked immunosorbent assay, while serum CaN activity was determined by malachite green colorimetric assay. Among the HNM and HLVH subgroups, a positive correlation was demonstrated between serum CaN activity, but not serum CaN level, and HLVH. Moreover, the HLVH subgroup displayed a remarkable increase in the levels of brain natriuretic peptide, cystatin C, urinary albumin/creatinine ratio, and left atrium diameter compared to the HNM subgroup and controls. There was a positive correlation between serum CaN activity and LVH in hypertensive patients. Activated CaN could play an important role in the pathophysiologic mechanism of HLVH. Serum CaN activity could be a clinically useful diagnostic and prognostic biomarker for LVH. © 2018 S. Karger AG, Basel.

Left Ventricular Myocardial Function in Children With Pulmonary Hypertension: Relation to Right Ventricular Performance and Hemodynamics.

PubMed

Burkett, Dale A; Slorach, Cameron; Patel, Sonali S; Redington, Andrew N; Ivy, D Dunbar; Mertens, Luc; Younoszai, Adel K; Friedberg, Mark K

2015-08-01

Through ventricular interdependence, pulmonary hypertension (PH) induces left ventricular (LV) dysfunction. We hypothesized that LV strain/strain rate, surrogate measures of myocardial contractility, are reduced in pediatric PH and relate to invasive hemodynamics, right ventricular strain, and functional measures of PH. At 2 institutions, echocardiography was prospectively performed in 54 pediatric PH patients during cardiac catheterization, and in 54 matched controls. Patients with PH had reduced LV global longitudinal strain (LS; -18.8 [-17.3 to -20.4]% versus -20.2 [-19.0 to -20.9]%; P=0.0046) predominantly because of reduced basal (-12.9 [-10.8 to -16.3]% versus -17.9 [-14.5 to -20.7]%; P<0.0001) and mid (-17.5 [-15.5 to -19.0]% versus -21.1 [-19.1 to -23.0]%; P<0.0001) septal strain. Basal global circumferential strain was reduced (-18.7 [-15.7 to -22.1]% versus -20.6 [-19.0 to -22.5]%; P=0.0098), as were septal and free-wall segments. Mid circumferential strain was reduced within the free-wall. Strain rates were reduced in similar patterns. Basal septum LS, the combined average LS of basal and mid interventricular septal segments, correlated strongly with degree of PH (r=0.66; P<0.0001), pulmonary vascular resistance (r=0.60; P<0.0001), and right ventricular free-wall LS (r=0.64; P<0.0001). Brain natriuretic peptide levels correlated moderately with septal LS (r=0.48; P=0.0038). PH functional class correlated moderately with LV free-wall LS (r=-0.48; P=0.0051). The septum, shared between ventricles and affected by septal shift, was the most affected LV region in PH. Pediatric PH patients demonstrate reduced LV strain/strain rate, predominantly within the septum, with relationships to invasive hemodynamics, right ventricular strain, and functional PH measures. © 2015 American Heart Association, Inc.

Extraventricular Neurocytoma in the Left Frontal Lobe: A Case Report and Literature Review.

PubMed

Chen, Fan; Jin, Rihua; Wu, Xinmin; Dong, Zengping; Chen, Dawei

2018-04-01

Neurocytoma is a rare brain neoplasm of neuroepithelial origin that occurs predominantly in the ventricular system adjacent to the interventricular foramen and septum pellucidum. However, extraventricular neurocytoma is an extremely rare entity, with poor clinical, radiologic, and histopathological characterization. Here we report a case of an extraventricular parafalcine neurocytoma in the left frontal lobe. We also examine previously reported cases of extraventricular neurocytoma in an attempt to provide an up-to-date summary of the condition. A literature search was performed using PubMed with specific key terms, inclusion criteria, and exclusion criteria. Selected case studies and case series were then compared, and statistical analyses were performed where appropriate. We report a 59-year-old woman presenting with weakness in her right leg and urinary incontinence. Physical examination revealed muscle strength of grade 3/5 in the right lower extremity. Brain magnetic resonance imaging showed a parafalcine mass in the left frontal lobe, with perilesional edema; the cerebral falx and lateral ventricle were shifted due to the compression. Gross total resection was performed. Histopathological examination revealed a neurocytoma. Immunohistochemical staining showed diffuse positivity for synaptophysin. MIB-1 staining for Ki-67 antibody showed a labeling index of 20%. No adjuvant radiation or chemotherapy was administered. Brain computed tomography performed at a 3-month follow-up showed no signs of recurrence. Extraventricular neurocytoma occurring in the brain parenchyma is a very rare central nervous system tumor. Its clinical and radiologic manifestations are nonspecific. The diagnosis depends on histopathological and immunohistochemical examination. Surgical resection should be the first-choice treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

An electrocardiographic scoring system for distinguishing right ventricular outflow tract arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy from idiopathic ventricular tachycardia.

PubMed

Hoffmayer, Kurt S; Bhave, Prashant D; Marcus, Gregory M; James, Cynthia A; Tichnell, Crystal; Chopra, Nagesh; Moxey, Laura; Krahn, Andrew D; Dixit, Sanjay; Stevenson, William; Calkins, Hugh; Badhwar, Nitish; Gerstenfeld, Edward P; Scheinman, Melvin M

2013-04-01

Ventricular arrhythmias in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and idiopathic ventricular tachycardia (VT) can share a left bundle branch block/inferior axis morphology. We previously reported electrocardiogram characteristics during outflow tract ventricular arrhythmias that helped distinguish VT related to ARVD/C from idiopathic VT. To prospectively validate these criteria. We created a risk score by using a derivation cohort. Two experienced electrophysiologists blinded to the diagnosis prospectively scored patients with VT/premature ventricular contractions (PVCs) with left bundle branch block/inferior axis pattern in a validation cohort of 37 ARVD/C tracings and 49 idiopathic VT tracings. All patients with ARVD/C had their diagnosis confirmed based on the revised task force criteria. Patients with idiopathic VT were selected based on structurally normal hearts with documented right ventricular outflow tract VT successfully treated with ablation. The scoring system provides 3 points for sinus rhythm anterior T-wave inversions in leads V1-V3 and during ventricular arrhythmia: 2 points for QRS duration in lead I≥120 ms, 2 points for QRS notching, and 1 point for precordial transition at lead V5 or later. A score of 5 or greater was able to correctly distinguish ARVD/C from idiopathic VT 93% of the time, with a sensitivity of 84%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 91%. We describe a simple scoring algorithm that uses 12-lead electrocardiogram characteristics to effectively distinguish right ventricular outflow tract arrhythmias originating from patients with ARVD/C versus patients with idiopathic VT. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Quest for the basic plan of nervous system circuitry

PubMed Central

Swanson, Larry W.

2007-01-01

The basic plan of nervous system organization has been investigated since classical antiquity. The first model centered on pneumas pumped from sensory nerves through the ventricular system and out motor nerves to muscles. It was popular well into the seventeenth century and diverted attention from the organization of brain parenchyma itself. Willis focused on gray matter production and white matter conduction of pneumas in 1664, and by the late nineteenth century a clear cellular model of nervous system organization based on sensory, motor, and association neuron classes transmitting nerve impulses was elaborated by Cajal and his contemporaries. Today, revolutionary advances in experimental pathway tracing methods, molecular genetics, and computer science inspire systems neuroscience. Seven minimal requirements are outlined for knowledge management systems capable of describing, analyzing, and modeling the basic plan of nervous system circuitry in general, and the plan evolved for vertebrates, for mammals, and ultimately for humans in particular. The goal remains a relatively simple, easy to understand model analogous to the one Harvey elaborated in 1628 for circulation in the cardiovascular system. As Cajal wrote in 1909, “To extend our understanding of neural function to the most complex human physiological and psychological activities, it is essential that we first generate a clear and accurate view of the structure of the relevant centers, and of the human brain itself, so that the basic plan—the overview—can be grasped in the blink of an eye.” PMID:17267046

Characterization of angiotensin-binding sites in the bovine adrenal and the rat brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rogulja, I.

1989-01-01

The first study was designed to determine whether systemically administered MSG affects neurons in the CVOs that are potentially important in mediating angiotensin-dependent responses. Rats were pretreated with MSG and the receptors for angiotensin II were assayed by radioligand binding in brain homogenates from the septum anteroventral third ventricular region (AV3V) and the thalamus/hypothalamus region using {sup 125}I-angiotensin II as the radioligand. The results of this experiment indicate that systematically administered MSG in the rat significantly reduced the number (Bmax) of Ang II receptors in a tissue sample which contained both extra blood-brain barrier organs as well as tissue withinmore » the blood-brain barrier with no change in the affinity (Kd) of the binding sites. The second chapter reports the successful solubilization of bovine adrenal {sup 125}I Ang II and {sup 125}I Sar{sup 1},Ile{sup 8}-Ang II binding sites with the detergent CHAPS. The results of our studies indicate the presence of two angiotensin binding sites. The one site is specific for naturally occurring angiotensins as well as sarcosine-1 substituted angiotensin analogues. The other site which can be optimally stabilized be re-addition of 0.3% CHAPS into the incubation assay binds sarcosine-1 substituted angiotensins exclusively. Hydrophobic interaction chromatography experiments suggest that these sites, possibly, represent distinct proteins. The third chapter discusses the successful solubilization and partial characterization of the rat brain angiotensin receptor.« less

[The reasonable use of right ventricular protection strategy in right ventricular outflow tract reconstruction].

PubMed

Zhang, Y; Yuan, H Y; Liu, X B; Wen, S S; Xu, G; Cui, H J; Zhuang, J; Chen, J M

2018-06-01

As a result of right ventricular outflow tract reconstruction, which is the important and basic step of complex cardiac surgery, the blood flow of right ventricular outflow tract is unobstructed, while pulmonary valve regurgitation and right heart dysfunction could be happened. These problems are often ignored in early days, more and more cases of right heart dysfunction need clinical intervention, which is quite difficult and less effective. How to protect effectively the right ventricular function is the focus. At present main methods to protect the right ventricular function include trying to avoid or reduce length of right ventricular incision, reserving or rebuilding the function of the pulmonary valve, using growth potential material for surgery. The protection of the right ventricular function is a systemic project, it involves many aspects, single measures is difficult to provide complete protection, only the comprehensive use of various protection strategy, can help to improve the long-term prognosis.

Mössbauer and X-ray study of biodegradation of 57Fe3 O 4 magnetic nanoparticles in rat brain

NASA Astrophysics Data System (ADS)

Gabbasov, R. R.; Cherepanov, V. M.; Chuev, M. A.; Lomov, A. A.; Mischenko, I. N.; Nikitin, M. P.; Polikarpov, M. A.; Panchenko, V. Y.

2016-12-01

Biodegradation of a 57Fe3 O 4 - based dextran - stabilized ferrofluid in the ventricular cavities of the rat brain was studied by X-ray diffraction and Mössbauer spectroscopy. A two-step process of biodegradation, consisting of fast disintegration of the initial composite magnetic beads into separate superparamagnetic nanoparticles and subsequent slow dissolution of the nanoparticles has been found. Joint fitting of the couples of Mössbauer spectra measured at different temperatures in the formalism of multi-level relaxation model with one set of fitting parameters, allowed us to measure concentration of exogenous iron in the rat brain as a function of time after the injection of nanoparticles.

Brain tissue water content in patients with idiopathic normal pressure hydrocephalus.

PubMed

Aygok, G; Marmarou, A; Fatouros, P; Young, H

2006-01-01

Relatively little is known regarding the water content of brain tissue in idiopathic normal-pressure hydrocephalus (NPH) patients. The objective of our study was to determine absolute water content non-invasively in hydrocephalic patients, particularly in the anterior and posterior ventricular horns and in the periventricular white matter. Ten patients who were diagnosed and treated for idiopathic NPH in our clinic were selected for study. Magnetic resonance imaging (MRI) techniques were used to obtain anatomical image slices for quantitative brain water measurements. Apparent diffusion coefficient measures were also extracted from regions of interest. To our knowledge, this is the first study to confirm that periventricular lucency seen on MRI represents increased water content in the extracellular space that is markedly elevated prior to shunting.

Dorsal spinal cord stimulation obtunds the capacity of intrathoracic extracardiac neurons to transduce myocardial ischemia

PubMed Central

Ardell, Jeffrey L.; Cardinal, René; Vermeulen, Michel; Armour, J. Andrew

2009-01-01

Populations of intrathoracic extracardiac neurons transduce myocardial ischemia, thereby contributing to sympathetic control of regional cardiac indices during such pathology. Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) modulates such local reflex control. In 10 anesthetized canines, middle cervical ganglion neurons were identified that transduce the ventricular milieu. Their capacity to transduce a global (rapid ventricular pacing) vs. regional (transient regional ischemia) ventricular stress was tested before and during SCS (50 Hz, 0.2 ms duration at 90% MT) applied to the dorsal aspect of the T1 to T4 spinal cord. Rapid ventricular pacing and transient myocardial ischemia both activated cardiac-related middle cervical ganglion neurons. SCS obtunded their capacity to reflexly respond to the regional ventricular ischemia, but not rapid ventricular pacing. In conclusion, spinal cord inputs to the intrathoracic extracardiac nervous system obtund the latter's capacity to transduce regional ventricular ischemia, but not global cardiac stress. Given the substantial body of literature indicating the adverse consequences of excessive adrenergic neuronal excitation on cardiac function, these data delineate the intrathoracic extracardiac nervous system as a potential target for neuromodulation therapy in minimizing such effects. PMID:19515981

Adult onset of the Dandy-Walker syndrome.

PubMed

Lipton, H L; Preziosi, T J; Moses, H

1978-10-01

Two patients with the Dandy-Walker malformation first developed neurologic symptoms in adult life. In both patients there was normal motor and intellectual development during childhood, but as adults they had gradual evolution of brain stem and cerebellar signs and obstructive hydrocephalus. Following resection of the fourth ventricular cyst, both patients recovered. A review of the literature disclosed seven additional patients in whom the Dandy-Walker syndrome was first diagnosed in adult life. These cases illustrate that this congenital brain malformation may not only first become symptomatic later in life, but that it is possible for patients to remain asymptomatic.

Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer’s Disease Pathogenesis

PubMed Central

Kyrtsos, Christina Rose; Baras, John S.

2015-01-01

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain. PMID:26448331

Cardiac remodeling in the mouse model of Marfan syndrome develops into two distinctive phenotypes

PubMed Central

Tae, Hyun-Jin; Marshall, Shannon; Krawczyk, Melissa; Talan, Mark

2015-01-01

Marfan syndrome (MFS) is a systemic disorder of connective tissue caused by mutations in fibrillin-1. Cardiac dysfunction in MFS has not been characterized halting the development of therapies of cardiac complication in MFS. We aimed to study the age-dependent cardiac remodeling in the mouse model of MFS FbnC1039G+/− mouse [Marfan heterozygous (HT) mouse] and its association with valvular regurgitation. Marfan HT mice of 2–4 mo demonstrated a mild hypertrophic cardiac remodeling with predominant decline of diastolic function and increased transforming growth factor-β canonical (p-SMAD2/3) and noncanonical (p-ERK1/2 and p-p38 MAPK) signaling and upregulation of hypertrophic markers natriuretic peptides atrium natriuretic peptide and brain natriuretic peptide. Among older HT mice (6–14 mo), cardiac remodeling was associated with two distinct phenotypes, manifesting either dilated or constricted left ventricular chamber. Dilatation of left ventricular chamber was accompanied by biochemical evidence of greater mechanical stress, including elevated ERK1/2 and p38 MAPK phosphorylation and higher brain natriuretic peptide expression. The aortic valve regurgitation was registered in 20% of the constricted group and 60% of the dilated group, whereas mitral insufficiency was observed in 40% of the constricted group and 100% of the dilated group. Cardiac dysfunction was not associated with the increase of interstitial fibrosis and nonmyocyte proliferation. In the mouse model fibrillin-1, haploinsufficiency results in the early onset of nonfibrotic hypertrophic cardiac remodeling and dysfunction, independently from valvular abnormalities. MFS heart is vulnerable to stress-induced cardiac dilatation in the face of valvular regurgitation, and stress-activated MAPK signals represent a potential target for cardiac management in MFS. PMID:26566724

Cardiac remodeling in the mouse model of Marfan syndrome develops into two distinctive phenotypes.

PubMed

Tae, Hyun-Jin; Petrashevskaya, Natalia; Marshall, Shannon; Krawczyk, Melissa; Talan, Mark

2016-01-15

Marfan syndrome (MFS) is a systemic disorder of connective tissue caused by mutations in fibrillin-1. Cardiac dysfunction in MFS has not been characterized halting the development of therapies of cardiac complication in MFS. We aimed to study the age-dependent cardiac remodeling in the mouse model of MFS FbnC1039G+/- mouse [Marfan heterozygous (HT) mouse] and its association with valvular regurgitation. Marfan HT mice of 2-4 mo demonstrated a mild hypertrophic cardiac remodeling with predominant decline of diastolic function and increased transforming growth factor-β canonical (p-SMAD2/3) and noncanonical (p-ERK1/2 and p-p38 MAPK) signaling and upregulation of hypertrophic markers natriuretic peptides atrium natriuretic peptide and brain natriuretic peptide. Among older HT mice (6-14 mo), cardiac remodeling was associated with two distinct phenotypes, manifesting either dilated or constricted left ventricular chamber. Dilatation of left ventricular chamber was accompanied by biochemical evidence of greater mechanical stress, including elevated ERK1/2 and p38 MAPK phosphorylation and higher brain natriuretic peptide expression. The aortic valve regurgitation was registered in 20% of the constricted group and 60% of the dilated group, whereas mitral insufficiency was observed in 40% of the constricted group and 100% of the dilated group. Cardiac dysfunction was not associated with the increase of interstitial fibrosis and nonmyocyte proliferation. In the mouse model fibrillin-1, haploinsufficiency results in the early onset of nonfibrotic hypertrophic cardiac remodeling and dysfunction, independently from valvular abnormalities. MFS heart is vulnerable to stress-induced cardiac dilatation in the face of valvular regurgitation, and stress-activated MAPK signals represent a potential target for cardiac management in MFS.

Real-time detection and data acquisition system for the left ventricular outline. Ph.D. Thesis - Stanford Univ.

NASA Technical Reports Server (NTRS)

Reiber, J. H. C.

1976-01-01

To automate the data acquisition procedure, a real-time contour detection and data acquisition system for the left ventricular outline was developed using video techniques. The X-ray image of the contrast-filled left ventricle is stored for subsequent processing on film (cineangiogram), video tape or disc. The cineangiogram is converted into video format using a television camera. The video signal from either the TV camera, video tape or disc is the input signal to the system. The contour detection is based on a dynamic thresholding technique. Since the left ventricular outline is a smooth continuous function, for each contour side a narrow expectation window is defined in which the next borderpoint will be detected. A computer interface was designed and built for the online acquisition of the coordinates using a PDP-12 computer. The advantage of this system over other available systems is its potential for online, real-time acquisition of the left ventricular size and shape during angiocardiography.

Effects of Spaceflight on Astronaut Brain Structure as Indicated on MRI.

PubMed

Roberts, Donna R; Albrecht, Moritz H; Collins, Heather R; Asemani, Davud; Chatterjee, A Rano; Spampinato, M Vittoria; Zhu, Xun; Chimowitz, Marc I; Antonucci, Michael U

2017-11-02

There is limited information regarding the effects of spaceflight on the anatomical configuration of the brain and on cerebrospinal fluid (CSF) spaces. We used magnetic resonance imaging (MRI) to compare images of 18 astronauts' brains before and after missions of long duration, involving stays on the International Space Station, and of 16 astronauts' brains before and after missions of short duration, involving participation in the Space Shuttle Program. Images were interpreted by readers who were unaware of the flight duration. We also generated paired preflight and postflight MRI cine clips derived from high-resolution, three-dimensional imaging of 12 astronauts after long-duration flights and from 6 astronauts after short-duration flights in order to assess the extent of narrowing of CSF spaces and the displacement of brain structures. We also compared preflight ventricular volumes with postflight ventricular volumes by means of an automated analysis of T 1 -weighted MRIs. The main prespecified analyses focused on the change in the volume of the central sulcus, the change in the volume of CSF spaces at the vertex, and vertical displacement of the brain. Narrowing of the central sulcus occurred in 17 of 18 astronauts after long-duration flights (mean flight time, 164.8 days) and in 3 of 16 astronauts after short-duration flights (mean flight time, 13.6 days) (P<0.001). Cine clips from a subgroup of astronauts showed an upward shift of the brain after all long-duration flights (12 astronauts) but not after short-duration flights (6 astronauts) and narrowing of CSF spaces at the vertex after all long-duration flights (12 astronauts) and in 1 of 6 astronauts after short-duration flights. Three astronauts in the long-duration group had optic-disk edema, and all 3 had narrowing of the central sulcus. A cine clip was available for 1 of these 3 astronauts, and the cine clip showed upward shift of the brain. Narrowing of the central sulcus, upward shift of the brain, and narrowing of CSF spaces at the vertex occurred frequently and predominantly in astronauts after long-duration flights. Further investigation, including repeated postflight imaging conducted after some time on Earth, is required to determine the duration and clinical significance of these changes. (Funded by the National Aeronautics and Space Administration.).

Clinical application of a light-pen computer system for quantitative angiography

NASA Technical Reports Server (NTRS)

Alderman, E. L.

1975-01-01

The paper describes an angiographic analysis system which uses a video disk for recording and playback, a light-pen for data input, minicomputer processing, and an electrostatic printer/plotter for hardcopy output. The method is applied to quantitative analysis of ventricular volumes, sequential ventriculography for assessment of physiologic and pharmacologic interventions, analysis of instantaneous time sequence of ventricular systolic and diastolic events, and quantitation of segmental abnormalities. The system is shown to provide the capability for computation of ventricular volumes and other measurements from operator-defined margins by greatly reducing the tedium and errors associated with manual planimetry.

A Neonate with Susceptibility to Long QT Syndrome Type 6 who Presented with Ventricular Fibrillation and Sudden Unexpected Infant Death.

PubMed

Sauer, Charles W; Marc-Aurele, Krishelle L

2016-07-28

BACKGROUND This is a case of a neonate with susceptibility to long QT syndrome (LQTS) who presented with a sudden unexpected infant death. Experts continue to debate whether universal electrocardiogram (ECG) screening of all newborns is feasible, practical, and cost-effective. CASE REPORT A 19-day-old neonate was found unresponsive by her mother. ECG showed ventricular fibrillation and a combination of a lidocaine drip plus multiple defibrillations converted the rhythm to normal sinus. Unfortunately, MRI brain imaging showed multiple infarcts and EEG showed burst suppression pattern with frequent seizures; life supportive treatment was stopped and the infant died. Genetic testing revealed two mutations in the KCNE2 gene consistent with susceptibility to LQTS type 6. CONCLUSIONS We believe this case is the first to demonstrate both a precipitating electrocardiographic and genetic cause of death for an infant with LQTS, showing a cause-and-effect relationship between LQTS mutation, ventricular arrhythmia, and death. We wonder whether universal ECG newborn screening to prevent LQTS death could have saved this baby.

Periodic oscillation of intracranial pressure in ventricular dilation: a preliminary report.

PubMed

Kuchiwaki, H; Misu, N; Kageyama, N; Ishiguri, H; Takada, S

1987-12-01

Artificial pressure waves (PWs) were generated by manual inflation of a balloon in the trigonum of the lateral ventricle in seven adult mongrel dogs with normal cerebrospinal fluid (CSF) circulation. In 14 of 16 series of continuous appearances of artificial PWs, local shifts of the brain were successfully monitored using small strain-gauge sensors at the periventricular structures in these animals. Of the 14 series, 13 showed displacements of the periventricular structures, suggesting ventricular dilation. These results did not always correlate with macroscopic findings. They are thought to be due largely to periventricular oedemas and, in part, non-uniform dilations of the ventricles during PWs. We conclude that a water hammer formed by reflection of an increased pulse pressure of PWs at the site of CSF absorption causes a shift of CSF from the ventricle to the periventricular structures through the wall of the ventricle. This phenomenon appears amplified in patients with impaired CSF absorption. Thus, PWs have a pathological role in the progress of ventricular dilation in patients with normal pressure hydrocephalus.

Cerebral lactic acidosis correlates with neurological impairment in MELAS.

PubMed

Kaufmann, P; Shungu, D C; Sano, M C; Jhung, S; Engelstad, K; Mitsis, E; Mao, X; Shanske, S; Hirano, M; DiMauro, S; De Vivo, D C

2004-04-27

To evaluate the role of chronic cerebral lactic acidosis in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). The authors studied 91 individuals from 34 families with MELAS and the A3243G point mutation and 15 individuals from two families with myoclonus epilepsy and ragged red fibers (MERRF) and the A8344G mutation. Subjects were divided into four groups. Paternal relatives were studied as controls (Group 1). The maternally related subjects were divided clinically into three groups: asymptomatic (no clinical evidence of neurologic disease) (Group 2), oligosymptomatic (neurologic symptoms but without the full clinical picture of MELAS or MERRF) (Group 3), and symptomatic (fulfilling MELAS or MERRF criteria) (Group 4). The authors performed a standardized neurologic examination, neuropsychological testing, MRS, and leukocyte DNA analysis in all subjects. The symptomatic and oligosymptomatic MELAS subjects had significantly higher ventricular lactate than the other groups. There was a significant correlation between degree of neuropsychological and neurologic impairment and cerebral lactic acidosis as estimated by ventricular MRS lactate levels. High levels of ventricular lactate, the brain spectroscopic signature of MELAS, are associated with more severe neurologic impairment.

The double switch for atrioventricular discordance.

PubMed

Brawn, William J

2005-01-01

Conventional surgery for atrioventricular discordance usually associated with ventricular arterial discordance leaves the morphologic right ventricle in the systemic circulation. Long-term follow-up results with this approach reveal a high incidence of right ventricular failure. The double switch procedure was introduced to restore the morphologic left ventricle to the systemic circulation. This operation is performed in two main ways: the atrial-arterial switch and the atrial switch plus Rastelli procedure. This double switch approach has been successful at least in the medium term in abolishing morphologic right ventricular failure and its associated tricuspid valve regurgitation. In the atrial-arterial switch group, there is an incidence of morphologic left ventricular dysfunction, sometimes associated with neoaortic valve regurgitation, and the minority of cases need aortic valve replacement. The long-term function of the morphologic left ventricle and the aortic valve need careful surveillance in the future. The atrial-Rastelli group of patients has not in the medium term shown evidence of ventricular dysfunction but will require change on a regular basis of their ventricular to pulmonary artery valved conduits.

Effects of 4 month exercise on left ventricular remodeling and autonomic nervous system in hypertensive patients.

PubMed

Zheng, Huan; Xie, Nanzi; Xu, Huifeng; Huang, Junling; Xie, Xiaoyun; Luo, Ming

2016-03-01

We sought to investigate effects of supervised exercise training on left ventricular remodeling, left ventricular function and autonomic nervous system of hypertensive patients without medication. Fifty borderline and mildly hypertensive patients were enrolled and randomly divided into 2 groups (25 in each). Exercise group received a 4 months' exercise program, prescribed according to their first cardiopulmonary exercise tests, while the control group received routine dietary recommendation. All patients underwent noradrenalin assay, cardiopulmonary exercise tests and echocardiographic studies at enrollment and 4 month follow-up. At baseline no statistically difference between the two groups were observed in clinical characteristics, echographic variants or cardiopulmonary test index. Four months later, exercise group showed higher values of VO2peak, Powermax (max workload), AT (anaerobic threshold), VO2AT (VO2 at anaerobic threshold), tAT (time from beginning to anaerobic threshold) and heart rate recovery compared to the control group (P<0.05). Additionally, systolic/diastolic blood pressure decreased significantly in the exercise group compared to the control group (P<0.05). Moreover, there was significant reduction in left ventricular mass index in the exercise group (P<0.01), and there was also an inverse correlation between changes in left ventricular mass index and heart rate recovery (r=-0.52, P<0.01). Four-month exercise training in borderline and mildly hypertensive patients not only decreased their blood pressure levels, but also induced an improvement of exercise capability, left ventricular remodeling and heart rate recovery. Heart rate recovery improvement was significantly associated with decrease of left ventricular mass index, which indicated that favorable adjustment in autonomic nervous system of exercise training might be an important pathway to reverse left ventricular remodeling.

Simultaneous total cavopulmonary connection and cardiac re-synchronisation therapy.

PubMed

Nakanishi, Keisuke; Kawasaki, Shiori; Amano, Atsushi

2017-08-01

We report the simultaneous use of cardiac re-synchronisation therapy and total cavopulmonary connection in a patient with dyssynchrony, wide QRS, and cardiac failure. To our knowledge, this simultaneous approach has not been reported previously. On follow-up, we noted that QRS width and brain natriuretic peptide levels improved. In addition, speckle tracking revealed improved synchronisation of ventricular wall motion.

[Continuous registration of micropotentials of the human heart. Initial experiences with a new high resolution ECG amplifier system].

PubMed

Hombach, V; Kebbel, U; Höpp, H W; Winter, U J; Braun, V; Deutsch, H; Hirche, H; Hilger, H H

1982-12-24

A new ECG-amplifier system for recording cardiac microvolt potentials from the body surface is described. The improvement in signal-to-noise ratio was achieved by using specially designed suction electrodes, which were isolated from each other; by applying parallel signal averaging from four electrode pairs via four low-noise amplifiers; and by conducting the registration in Faraday cage. in 14 normal subjects, 12 patients with coronary heart disease and one patient with surgically corrected ventricular septal defect and pulmonary stenosis, pre-P-potentials (possible sinus node activity), His bundle potentials and ventricular late potentials were recorded with differing degrees of success. Variations of the time intervals to the preceding QRS complex were observed within the S-T segment in six of nine patients with demonstrable ventricular late ventricular late potentials. The advantage of such continuously recording ECG system lies in the highly accurate registration of cardiac micropotentials, particularly with ventricular late potentials that are changing in time, whereas the signal-averaging technique does not provide such possibilities.

The Molecular Pathway Regulating Bergmann Glia and Folia Generation in the Cerebellum.

PubMed

Leung, Alan W; Li, James Y H

2018-02-01

Evolution of complex behaviors in higher vertebrates and primates require the development of sophisticated neuronal circuitry and the expansion of brain surface area to accommodate the vast number of neuronal and glial populations. To achieve these goals, the neocortex in primates and the cerebellum in amniotes have developed specialized types of basal progenitors to aid the folding of their cortices. In the cerebellum, Bergmann glia constitute such a basal progenitor population, having a distinctive morphology and playing a critical role in cerebellar corticogenesis. Here, we review recent studies on the induction of Bergmann glia and their crucial role in mediating folding of the cerebellar cortex. These studies uncover a key function of FGF-ERK-ETV signaling cascade in the transformation of Bergmann glia from radial glia in the ventricular zone. Remarkably, in the neocortex, the same signaling axis operates to facilitate the transformation of ventricular radial glia into basal radial glia, a Bergmann glia-like basal progenitor population, which have been implicated in the establishment of neocortical gyri. These new findings draw a striking similarity in the function and ontogeny of the two basal progenitor populations born in distinct brain compartments.

The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice

PubMed Central

Ju, Xiang-Chun; Hou, Qiong-Qiong; Sheng, Ai-Li; Wu, Kong-Yan; Zhou, Yang; Jin, Ying; Wen, Tieqiao; Yang, Zhengang; Wang, Xiaoqun; Luo, Zhen-Ge

2016-01-01

Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding. DOI: http://dx.doi.org/10.7554/eLife.18197.001 PMID:27504805

First report on an inotropic peptide activating tetrodotoxin-sensitive, "neuronal" sodium currents in the heart.

PubMed

Kirchhof, Paulus; Tal, Tzachy; Fabritz, Larissa; Klimas, Jan; Nesher, Nir; Schulte, Jan S; Ehling, Petra; Kanyshkova, Tatayana; Budde, Thomas; Nikol, Sigrid; Fortmueller, Lisa; Stallmeyer, Birgit; Müller, Frank U; Schulze-Bahr, Eric; Schmitz, Wilhelm; Zlotkin, Eliahu; Kirchhefer, Uwe

2015-01-01

New therapeutic approaches to improve cardiac contractility without severe risk would improve the management of acute heart failure. Increasing systolic sodium influx can increase cardiac contractility, but most sodium channel activators have proarrhythmic effects that limit their clinical use. Here, we report the cardiac effects of a novel positive inotropic peptide isolated from the toxin of the Black Judean scorpion that activates neuronal tetrodotoxin-sensitive sodium channels. All venoms and peptides were isolated from Black Judean Scorpions (Buthotus Hottentotta) caught in the Judean Desert. The full scorpion venom increased left ventricular function in sedated mice in vivo, prolonged ventricular repolarization, and provoked ventricular arrhythmias. An inotropic peptide (BjIP) isolated from the full venom by chromatography increased cardiac contractility but did neither provoke ventricular arrhythmias nor prolong cardiac repolarization. BjIP increased intracellular calcium in ventricular cardiomyocytes and prolonged inactivation of the cardiac sodium current. Low concentrations of tetrodotoxin (200 nmol/L) abolished the effect of BjIP on calcium transients and sodium current. BjIP did not alter the function of Nav1.5, but selectively activated the brain-type sodium channels Nav1.6 or Nav1.3 in cellular electrophysiological recordings obtained from rodent thalamic slices. Nav1.3 (SCN3A) mRNA was detected in human and mouse heart tissue. Our pilot experiments suggest that selective activation of tetrodotoxin-sensitive neuronal sodium channels can safely increase cardiac contractility. As such, the peptide described here may become a lead compound for a new class of positive inotropic agents. © 2014 American Heart Association, Inc.

Implantable physiologic controller for left ventricular assist devices with telemetry capability.

PubMed

Asgari, Siavash S; Bonde, Pramod

2014-01-01

Rotary type left ventricular assist devices have mitigated the problem of durability associated with earlier pulsatile pumps and demonstrated improved survival. However, the compromise is the loss of pulsatility due to continuous flow and retained percutaneous driveline leading to increased mortality and morbidity. Lack of pulsatility is implicated in increased gastrointestinal bleeding, aortic incompetence, and diastolic hypertension. We present a novel, wirelessly powered, ultra-compact, implantable physiologic controller capable of running a left ventricular assist device in a pulsatile mode with wireless power delivery. The schematic of our system was laid out on a circuit board to wirelessly receive power and run a left ventricular assist device with required safety and backup measures. We have embedded an antenna and wireless network for telemetry. Multiple signal processing steps and controlling algorithm were incorporated. The controller was tested in in vitro and in vivo experiments. The controller drove left ventricular assist devices continuously for 2 weeks in an in vitro setup and in vivo without any failure. Our controller is more power efficient than the current Food and Drug Administration-approved left ventricular assist device controllers. When used with electrocardiography synchronization, the controller allowed on-demand customization of operation with instantaneous flow and revolutions per minute changes, resulting in a pulsatile flow with adjustable pulse pressure. Our test results prove the system to be remarkably safe, accurate, and efficient. The unique combination of wireless powering and small footprint makes this system an ideal totally implantable physiologic left ventricular assist device system. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial.

PubMed

van der Bom, Teun; Winter, Michiel M; Bouma, Berto J; Groenink, Maarten; Vliegen, Hubert W; Pieper, Petronella G; van Dijk, Arie P J; Sieswerda, Gertjan T; Roos-Hesselink, Jolien W; Zwinderman, Aeilko H; Mulder, Barbara J M

2013-01-22

The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, Vo(2)peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, -1.3% to 3.9%; P=0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3-28 mL; P<0.01) and mass (8 g; 95% confidence interval, 2-14 g; P=0.01) in the placebo group than in the valsartan group. There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN52352170.

Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis.

PubMed

Pardini, Matteo; Sudre, Carole H; Prados, Ferran; Yaldizli, Özgür; Sethi, Varun; Muhlert, Nils; Samson, Rebecca S; van de Pavert, Steven H; Cardoso, M Jorge; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

2016-11-01

To assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS). 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm 3 ) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured. Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces. In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

PubMed

El Chehadeh, Salima; Faivre, Laurence; Mosca-Boidron, Anne-Laure; Malan, Valérie; Amiel, Jeanne; Nizon, Mathilde; Touraine, Renaud; Prieur, Fabienne; Pasquier, Laurent; Callier, Patrick; Lefebvre, Mathilde; Marle, Nathalie; Dubourg, Christèle; Julia, Sophie; Sarret, Catherine; Francannet, Christine; Laffargue, Fanny; Boespflug-Tanguy, Odile; David, Albert; Isidor, Bertrand; Le Caignec, Cédric; Vigneron, Jacqueline; Leheup, Bruno; Lambert, Laetitia; Philippe, Christophe; Cuisset, Jean-Marie; Andrieux, Joris; Plessis, Ghislaine; Toutain, Annick; Goldenberg, Alice; Cormier-Daire, Valérie; Rio, Marlène; Bonnefont, Jean-Paul; Thevenon, Julien; Echenne, Bernard; Journel, Hubert; Afenjar, Alexandra; Burglen, Lydie; Bienvenu, Thierry; Addor, Marie-Claude; Lebon, Sébastien; Martinet, Danièle; Baumann, Clarisse; Perrin, Laurence; Drunat, Séverine; Jouk, Pierre-Simon; Devillard, Françoise; Coutton, Charles; Lacombe, Didier; Delrue, Marie-Ange; Philip, Nicole; Moncla, Anne; Badens, Catherine; Perreton, Nathalie; Masurel, Alice; Thauvin-Robinet, Christel; Des Portes, Vincent; Guibaud, Laurent

2016-01-01

Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment. © 2015 Wiley Periodicals, Inc.

Dyskalaemia following diffuse axonal injury: case report and review of the literature

PubMed Central

Cronin, David; Kaliaperumal, Chandrasekaran; Kumar, Ramanathan; Kaar, George

2012-01-01

Traumatic brain injury, and its management, commonly causes derangements in potassium balance. There are a number of recognised causative factors including head trauma, hypothermia and iatrogenic factors such as pharmacological agents and permissive cooling. We describe a case of a 19-year-old man with a severe traumatic brain injury. In a 36-h period, his intracranial pressure increased despite maximal medical therapy and he developed refractory hypokalaemia. Immediately following a decompressive craniectomy, the patient was noted to be profoundly hyperkalaemic; this led to the development of ventricular tachycardia and cardiac arrest, from which the patient did not recover. The effects of brain injury on potassium balance are not well appreciated; the effect of decompressive craniectomy on potassium (K+) balance has not been described previously. We would like to emphasise the potential effect of diffuse axonal injury, a severe form of brain injury and decompressive craniectomy on potassium balance. PMID:23060370

Aerobic training in adults after atrial switch procedure for transposition of the great arteries improves exercise capacity without impairing systemic right ventricular function.

PubMed

Westhoff-Bleck, Mechthild; Schieffer, Bernhard; Tegtbur, Uwe; Meyer, Gerd Peter; Hoy, Ludwig; Schaefer, Arnd; Tallone, Ezequiel Marcello; Tutarel, Oktay; Mertins, Ramona; Wilmink, Lena Mara; Anker, Stefan D; Bauersachs, Johann; Roentgen, Philipp

2013-12-05

Exercise training safely and efficiently improves symptoms in patients with heart failure due to left ventricular dysfunction. However, studies in congenital heart disease with systemic right ventricle are scarce and results are controversial. In a randomised controlled study we investigated the effect of aerobic exercise training on exercise capacity and systemic right ventricular function in adults with d-transposition of the great arteries after atrial redirection surgery (28.2 ± 3.0 years after Mustard procedure). 48 patients (31 male, age 29.3 ± 3.4 years) were randomly allocated to 24 weeks of structured exercise training or usual care. Primary endpoint was the change in maximum oxygen uptake (peak VO2). Secondary endpoints were systemic right ventricular diameters determined by cardiac magnetic resonance imaging (CMR). Data were analysed per intention to treat analysis. At baseline peak VO2 was 25.5 ± 4.7 ml/kg/min in control and 24.0 ± 5 ml/kg/min in the training group (p=0.3). Training significantly improved exercise capacity (treatment effect for peak VO2 3.8 ml/kg/min, 95% CI: 1.8 to 5.7; p=0.001), work load (p=0.002), maximum exercise time (p=0.002), and NYHA class (p=0.046). Systemic ventricular function and volumes determined by CMR remained unchanged. None of the patients developed signs of cardiac decompensation or arrhythmias while on exercise training. Aerobic exercise training did not detrimentally affect systemic right ventricular function, but significantly improved exercise capacity and heart failure symptoms. Aerobic exercise training can be recommended for patients following atrial redirection surgery to improve exercise capacity and to lessen or prevent heart failure symptoms. ( ClinicalTrials.gov #NCT00837603). © 2013.

Outcome of infants shunted for post-haemorrhagic ventricular dilatation.

PubMed

Hislop, J E; Dubowitz, L M; Kaiser, A M; Singh, M P; Whitelaw, A G

1988-08-01

Between April 1980 and March 1986, 19 infants underwent cerebrospinal fluid (CSF) shunting procedures for post-haemorrhagic ventricular dilatation at the Hammersmith Hospital, London. A total of 58 shunt-related procedures have been performed on these children. The major perioperative complication was seizure activity (eight children). Postoperative complications included infection (12 shunts) and blockage (29 shunts). Prophylactic antibiotics failed to prevent shunt infection. The likelihood of the first shunt failing was significantly reduced by greater weight of the infant and lower CSF protein at surgery. Long-term outcome was poor: three have died and another four are quadriplegic with severe mental retardation. Only four children are developmentally normal. These outcomes cannot be related to the shunt surgery or its complications, but correlate best with pre-operative parenchymal brain-lesions, as shown on ultrasound scans.

Evidence of an application of a variable MEMS capacitive sensor for detecting shunt occlusions

NASA Astrophysics Data System (ADS)

Apigo, David J.; Bartholomew, Philip L.; Russell, Thomas; Kanwal, Alokik; Farrow, Reginald C.; Thomas, Gordon A.

2017-04-01

A sensor was tested subdural and in vitro, simulating a supine infant with a ventricular-peritoneal shunt and controlled occlusions. The variable MEMS capacitive device is able to detect and forecast blockages, similar to early detection procedures in cancer patients. For example, with gradual occlusion development over a year, the method forecasts a danger over one month ahead of blockage. The method also distinguishes between ventricular and peritoneal occlusions. Because the sensor provides quantitative data on the dynamics of the cerebrospinal fluid, it can help test new therapies and work toward understanding hydrocephalus as well as idiopathic normal pressure hydrocephalus. The sensor appears to be a substantial advance in treating brain injuries treated with shunts and has the potential to bring significant impact in a clinical setting.

Cortical magnetic resonance imaging findings in familial pediatric bipolar disorder.

PubMed

Chang, Kiki; Barnea-Goraly, Naama; Karchemskiy, Asya; Simeonova, Diana Iorgova; Barnes, Patrick; Ketter, Terence; Reiss, Allan L

2005-08-01

Morphometric magnetic resonance imaging (MRI) studies of pediatric bipolar disorder (BD) have not reported on gray matter volumes but have reported increased lateral ventricular size and presence of white matter hyperintensities (WMH). We studied gray matter volume, ventricular-to-brain ratios (VBR), and number of WMH in patients with familial, pediatric BD compared with control subjects. Twenty subjects with BD (aged 14.6 +/- 2.8 years; 4 female) according to the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, each with a parent with BD, and 20 age-, gender-, and intelligence quotient-matched healthy control subjects (aged 14.1 +/- 2.8 years; 4 female) were scanned at 3 T. Most subjects were taking psychotropic medications. A high-resolution T1-weighted spoiled gradient echo three-dimensional MRI sequence was analyzed by BrainImage for volumetric measurements, and T2-weighted images were read by a neuroradiologist to determine presence of WMH. After covarying for age and total brain volume, there were no significant differences between subjects with BD and control subjects in volume of cerebral (p = .09) or prefrontal gray matter (p = .34). Subjects with BD did not have elevated numbers of WMH or greater VBR when compared with control subjects. Children and adolescents with familial BD do not seem to have decreased cerebral grey matter or increased numbers of WMH, dissimilar to findings in adults with BD. Gray matter decreases and development of WMH might be later sequelae of BD or unique to adult-onset BD.

Cognitive correlates of white matter lesion load and brain atrophy

PubMed Central

Dong, Chuanhui; Nabizadeh, Nooshin; Caunca, Michelle; Cheung, Ying Kuen; Rundek, Tatjana; Elkind, Mitchell S.V.; DeCarli, Charles; Sacco, Ralph L.; Stern, Yaakov

2015-01-01

Objective: We investigated white matter lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population. Methods: We quantified white matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates. Results: MRI and cognitive data were available for 1,163 participants (mean age 70 ± 9 years; 60% women; 66% Hispanic, 17% black, 15% white). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE ε4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function. Conclusions: In this racially/ethnically diverse, community-based sample, white matter lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance. PMID:26156514

Remote and chronic access to the third cerebral ventricle of the unrestrained prepubertal rhesus monkey.

PubMed

Gay, V L; Mikuma, N; Plant, T M

1993-03-01

One channel of a commercially available standard-size three-channel fluid swivel was modified to permit continuous access to the brain of unrestrained prepubertal rhesus monkeys via a continuous length of small-bore Teflon tube originating from a swivel device on top of the animal's cage and terminating in the third cerebral ventricle. This system was employed to achieve continuous access to the third cerebroventricle in four monkeys for periods of up to 12 mo. The value of the system for studies of the neurochemical control of hypothalamic-releasing factor secretion was established by monitoring adenohypophysial responses to neurotransmitter receptor agonists infused into the third ventricle. Specifically, repetitive infusions of morphine (30 micrograms/infusion) elicited a robust train of prolactin discharges, and third ventricular administration of N-methyl-DL-aspartic acid (NMA; 20 micrograms) resulted in striking discharges of LH.

[Primary central nervous system lymphoma mimicking ventriculitis].

PubMed

Yamamoto, Shiro; Nagano, Seiji; Shibata, Sumiya; Kunieda, Takeharu; Imai, Yukihiro; Kohara, Nobuo

2013-01-01

A 66-year-old man presented with deteriorated bradykinesia, gait disturbance, disorientation, and urinary incontinence for three weeks. Magnetic resonance imaging (MRI) showed dilatation of the ventricles. Cerebrospinal fluid (CSF) examination demonstrated lymphocytic pleocytosis, elevation of protein levels, and decreased of glucose levels. A gadolinium-enhanced MRI revealed lesions in the ventricular wall and choroid plexus, mimicking ventriculitis. No evidence of bacterial, fungal, mycobacterial, or viral infections were observed in the CSF. Flow cytometry of CSF showed predominance of CD20+, λ+ cells. PCR examination of CSF revealed positive IgH gene rearrangement, suggesting B cell lymphoma. Endoscopic brain biopsy showed diffuse large B cell lymphoma. As the patient had no evidence of lymphoma in the other organs, we made a diagnosed of primary central nervous system lymphoma (PCNSL). A limited intraventricular spread of PCNSL is rare but important as one of differential diagnosis of ventriculitis.

[Corrected transposition of the great arteries].

PubMed

Alva-Espinosa, Carlos

2016-01-01

Corrected transposition of the great arteries is one of the most fascinating entities in congenital heart disease. The apparent corrected condition is only temporal. Over time, most patients develop systemic heart failure, even in the absence of associated lesions. With current imaging studies, precise visualization is achieved in each case though the treatment strategy remains unresolved. In asymptomatic patients or cases without associated lesions, focalized follow-up to assess systemic ventricular function and the degree of tricuspid valve regurgitation is important. In cases with normal ventricular function and mild tricuspid failure, it seems unreasonable to intervene surgically. In patients with significant associated lesions, surgery is indicated. In the long term, the traditional approach may not help tricuspid regurgitation and systemic ventricular failure. Anatomical correction is the proposed alternative to ease the right ventricle overload and to restore the systemic left ventricular function. However, this is a prolonged operation and not without risks and long-term complications. In this review the clinical, diagnostic, and therapeutic aspects are overviewed in the light of the most significant and recent literature.

Association of Blood Pressure Control Level With Left Ventricular Morphology and Function and With Subclinical Cerebrovascular Disease.

PubMed

Nakanishi, Koki; Jin, Zhezhen; Homma, Shunichi; Elkind, Mitchell S V; Rundek, Tatjana; Tugcu, Aylin; Sacco, Ralph L; Di Tullio, Marco R

2017-07-30

Left ventricular (LV) hypertrophy and subclinical cerebrovascular disease are early manifestations of cardiac and brain target organ damage caused by hypertension. This study aimed to investigate whether intensive office systolic blood pressure (SBP) control has beneficial effects on LV morphology and function and subclinical cerebrovascular disease in elderly patients with hypertension. We examined 420 patients treated for hypertension without history of heart failure and stroke from the CABL (Cardiovascular Abnormalities and Brain Lesions) study. All patients underwent 2-dimensional echocardiographic examination and brain magnetic resonance imaging. Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume. Patients were divided into 3 groups: SBP <120 mm Hg (intensive control); SBP 120 to 139 mm Hg (less intensive control); and SBP ≥140 mm Hg (uncontrolled). Prevalence of LV hypertrophy and diastolic dysfunction were lowest in the intensive control, intermediate in the less intensive control, and highest in the uncontrolled groups (12.8%, 31.8%, and 44.7%, respectively [ P <0.001], for LV hypertrophy; 46.8%, 61.7%, and 72.6%, respectively [ P =0.003], for diastolic dysfunction). Patients with less intensive SBP control had greater risk of LV hypertrophy than those with intensive control (adjusted odds ratio, 3.26; P =0.013). A similar trend was observed for LV diastolic dysfunction but did not reach statistical significance (adjusted odds ratio, 1.65; P =0.144). Conversely, intensive SBP control was not significantly associated with reduced risk of silent brain infarcts and white matter hyperintensity volume compared with less intensive control. Compared with less intensive control, intensive SBP control may have a stronger beneficial effect on cardiac than cerebral subclinical disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

SU-E-QI-12: Morphometry Based Measurements of the Structural Response to Whole Brain Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fuentes, D; Castillo, R; Castillo, E

2014-06-15

Purpose: Although state of the art radiation therapy techniques for treating intracranial malignancies have eliminated acute brain injury, cognitive impairment occurs in 50–90% of patients who survive >6mo post irradiation. Quantitative characterization of therapy response is needed to facilitate therapeutic strategies to minimize radiation induced cognitive impairment [1]. Deformation based morphometry techniques [2, 3] are presented as a quantitative imaging biomarker of therapy response in patients receiving whole brain radiation for treating medulloblastoma. Methods: Post-irradiation magnetic resonance imaging (MRI) data sets were retrospectively analyzed in N=15 patients, >60 MR image datasets. As seen in Fig 1(a), volume changes at multiplemore » time points post-irradiation were quantitatively measured in the cerebrum and ventricles with respect to pre-irradiation MRI. A high resolution image Template, was registered to the pre-irradiation MRI of each patient to create a brain atlas for the cerebrum, cerebellum, and ventricles. Skull stripped images for each patient were registered to the initial pre-treatment scan. Average volume changes in the labeled regions were measured using the determinant of the displacement field Jacobian. Results: Longitudinal measurements, Fig 1(b-c), show a negative correlation p=.06, of the cerebral volume change with the time interval from irradiation. A corresponding positive correlation, p=.01, between ventricular volume change and time interval from irradiation is seen. One sample t-test for correlations were computed using a Spearman method. An average decrease in cerebral volume, p=.08, and increase in ventricular volume, p<.001, was observed. The radiation dose was seen directly proportional to the induced volume changes in the cerebrum, r=−.44, p<.001, Fig 1(d). Conclusion: Results indicate that morphometric monitoring of brain tissue volume changes may potentially be used to quantitatively assess toxicity and response to radiation and may provide insight in developing new therapeutic approaches and monitoring efficacy.« less

Left ventricular hypertrophy does not prevent heart failure in experimental hypertension.

PubMed

Hernán Gómez Llambí, H; Cao, G; Donato, M; Suárez, D; Ottaviano, G; Müller, A; Buchholz, B; Gelpi, R; Otero-Losada, M; Milei, J

2017-07-01

Left ventricular hypertrophy (LVH) secondary to hypertension has been accepted to prevent heart failure (HF) while paradoxically increasing cardiovascular morbi-mortality. To evaluate whether antihypertensive treatment inhibits LVH, restores beta-adrenergic response and affects myocardial oxidative metabolism. Ninety spontaneously hypertensive rats (SHR) were distributed into groups and treated (mg/kg, p.o.) with: losartan 30 (L), hydralazine 11 (H), rosuvastatin 10 (R), carvedilol 20 (C). Hypertension control group comprised 18 normotensive rats (Wistar-Kyoto, WKY). Following euthanasia at 16months, contractility was measured in 50% of rats (Langendorff system) before and after isoproterenol (Iso) 10 -9 M, 10 -7 M and 10 -5 M stimulation. Left ventricular weight (LVW) was measured in the remaining hearts, and normalized by BW. Expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2), glutaredoxin 3 (Grx-3), caspase-3 and brain natriuretic peptide (BNP) was determined. Systolic blood pressure (mmHg): 154±3 (L), 137±1 (H), 190±3 (R)*, 206±3 (SHR)*, 183±1 (C)**, and 141±1 (WKY) (*p<0.05 vs. L, H, WKY, **p<0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p<0.05). Groups SHR, R and C evidenced baseline contractile depression. Response to Iso 10 -5 M was similar in WKY and L. Expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (p<0.01). Present findings argue against the traditional idea and support that LVH might not be required to prevent HF. Increased expression of thioredoxins by antihypertensive treatment might be involved in protection from HF. Copyright © 2017 Elsevier B.V. All rights reserved.

The impact of sub-clinical over-hydration on left ventricular mass in peritoneal dialysis patients.

PubMed

Hassan, Kamal; Hassan, Dunia; Shturman, Alexander; Rubinchik, Irina; Fadi, Hassan; Shadi, Hassan; Atar, Shaul

2015-01-01

Left ventricular hypertrophy (LVH) represents a major predictor of the development of cardiovascular (CV) complications. Over-hydration (OH) is an important uremic risk factor associated with LVH and increased CV morbidity and mortality in peritoneal dialysis (PD) patients. In the present study we evaluated the prevalence of sub-clinical OH (SCOH) among PD patients and its effects on left ventricular mass (LVM). In this cross sectional study hydration status, blood pressure, glucose load, systemic inflammation and LVM were evaluated in 43 clinically stable patients on maintenance PD for 24-76 months. The hydration status was assessed by whole-body bio-impedance spectroscopy (BIS). Peripheral edema and any evidence of pulmonary congestion were considered clinical signs of OH. OH ≥ 1.5 L was detected in 26 (60.5%) of the study participants; the OH in 19 (73.1%) of them was sub-clinical. Only 23.5% (4/17) of patients with OH < 1.5 L had LVH compared to 68.4% (13/19) of those with SCOH ≥ 1.5 L (P = 0.007). Compared to patients with OH < 1.5 L, patients with SCOH ≥ 1.5 L had higher levels of blood pressure, peritoneal glucose load, plasma brain natriuretic peptide, high sensitive C-reactive protein, interleukin-6 and LVMI; and lower levels of serum albumin (P < 0.001). No significant differences were found between patients with clinical OH or SCOH with OH ≥ 1.5 L. SCOH is highly prevalent among PD patients and may contribute to the development of LVH. Considering the poor prognosis associated with over-hydrated PD patients, periodic assessment of hydration status using accurate BIS is suggested.

Electronic circuit detects left ventricular ejection events in cardiovascular system

NASA Technical Reports Server (NTRS)

Gebben, V. D.; Webb, J. A., Jr.

1972-01-01

Electronic circuit processes arterial blood pressure waveform to produce discrete signals that coincide with beginning and end of left ventricular ejection. Output signals provide timing signals for computers that monitor cardiovascular systems. Circuit operates reliably for heart rates between 50 and 200 beats per minute.

Pineal and ectopic pineal tumors: the role of radiation therapy. [X ray; /sup 60/Co

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, Y.T.R.; Medini, E.; Haselow, R.E.

Seventeen patients with pineal tumors and one ectopic (suprasellar) germinoma were treated with radiation therapy. Surgery was restricted to decompression in 16 patients, and only two patients had resection of the tumor. Thirteen of 18 patients are alive without evidence for disease with a ten-year surrvival rate of 88%. The tumor dose ranged from 4000 rads to 6000 rads. No age or dose dependence in survival was noted, but patients with whole brain irradiation or generous volume to include ventricular system had better survival. No case of spinal metastasis was noted. The possibility of increased incidence of meningeal seeding followingmore » surgical intervention is considered. From their data, the authors feel that radiation therapy with or without surgical decompression should be the primary treatment for pinealoma. Surgery can be used for diagnosis and/or treatment of patients who show delayed response to radiation. Recommendation is made for the use of whole brain irradiation to 4000 rads followed by a boost to the tumor area to 5000 rads.« less

Development and evaluation of totally implantable ventricular assist system using a vibrating flow pump and transcutaneous energy transmission system with amorphous fibers.

PubMed

Yambe, T; Hashimoto, H; Kobayashi, S; Sonobe, T; Naganuma, S; Nanka, S S; Matsuki, H; Yoshizawa, M; Tabayashi, K; Takayasu, H; Takeda, H; Nitta, S

1997-01-01

We have developed a vibrating flow pump (VFP) that can generate oscillated blood flow with a relatively high frequency (10-50 Hz) for a totally implantable ventricular assist system (VAS). To evaluate the newly developed VAS, left heart bypasses, using the VFP, were performed in chronic animal experiments. Hemodynamic parameters were recorded in a data recorder in healthy adult goats during an awake condition and analyzed in a personal computer system through an alternating-direct current converter. Basic performance of the total system with a transcutaneous energy transmission system were satisfactory. During left ventricular assistance with the VFP, Mayer wave fluctuations of hemodynamics were decreased in the power spectrum, the fractal dimensions of the hemodynamics were significantly decreased, and peripheral vascular resistance was significantly decreased. These results suggest that cardiovascular regulatory nonlinear dynamics, which mediate the hemodynamics, may be affected by left ventricular bypass with oscillated flow. The decreased power of the Mayer wave in the spectrum caused the limit cycle attractor of the hemodynamics and decreased peripheral resistance. These results suggest that this newly developed VAS is useful for the totally implantable system with unique characteristics that can control hemodynamic properties.

Urinary type IV collagen is related to left ventricular diastolic function and brain natriuretic peptide in hypertensive patients with prediabetes.

PubMed

Iida, Masato; Yamamoto, Mitsuru; Ishiguro, Yuko S; Yamazaki, Masatoshi; Ueda, Norihiro; Honjo, Haruo; Kamiya, Kaichirou

2014-01-01

Urinary type IV collagen is an early biomarker of diabetic nephropathy. Concomitant prediabetes (the early stage of diabetes) was associated with left ventricular (LV) diastolic dysfunction and increased brain natriuretic peptide (BNP) in hypertensive patients. We hypothesized that urinary type IV collagen may be related to these cardiac dysfunctions. We studied hypertensive patients with early prediabetes (HbA1c <5.7% and fasting glucose >110, n=18), those with prediabetes (HbA1c 5.7-6.4, n=98), and those with diabetes (HbA1c>6.5 or on diabetes medications, n=92). The participants underwent echocardiography to assess left atrial volume/body surface area (BSA) and the ratio of early mitral flow velocity to mitral annular velocity (E/e'). Left ventricular diastolic dysfunction (LVDD) was defined if patients had E/e'≥15, or E/e'=9-14 accompanied by left atrial volume/BSA≥32ml/mm(2). Urinary samples were collected for type IV collagen and albumin, and blood samples were taken for BNP and HbA1c. Urinary type IV collagen and albumin increased in parallel with the deterioration of glycemic status. In hypertensive patients with prediabetes, subjects with LVDD had higher levels of BNP and urinary type IV collagen than those without LVDD. In contrast, in hypertensive patients with diabetes, subjects with LVDD had higher urinary albumin and BNP than those without LVDD. Urinary type IV collagen correlated positively with BNP in hypertensive patients with prediabetes, whereas it correlated with HbA1c in those with diabetes. In hypertensive patients with prediabetes, urinary type IV collagen was associated with LV diastolic dysfunction and BNP. Copyright © 2014 Elsevier Inc. All rights reserved.

Case report: paradoxical ventricular septal motion in the setting of primary right ventricular myocardial failure.

PubMed

Maslow, Andrew; Schwartz, Carl; Mahmood, Feroze; Singh, Arun; Heerdt, Paul M

2009-07-01

In this report, a case of right ventricular (RV) failure, hemodynamic instability, and systemic organ failure is described to highlight how paradoxical ventricular systolic septal motion (PVSM), or a rightward systolic displacement of the interventricular septum, may contribute to RV ejection. Multiple inotropic medications and vasopressors were administered to treat right heart failure and systemic hypotension in a patient following combined aortic and mitral valve replacement. In the early postoperative period, echocardiographic evaluation revealed adequate left ventricular systolic function, akinesis of the RV myocardial tissues, and PVSM. In the presence of PVSM, RV fractional area of contraction was > or =35% despite akinesis of the primary RV myocardial walls. The PVSM appeared to contribute toward RV ejection. As a result, the need for multiple inotropes was re-evaluated, in considering that end-organ dysfunction was the result of systemic hypotension and prolonged vasopressor administration. After discontinuation of phosphodiesterase inhibitors, native vascular tone returned and the need for vasopressors declined. This was followed by recovery of systemic organ function. Echocardiographic re-evaluation two years later, revealed persistent akinesis of the RV myocardial tissues and PVSM, the latter appearing to contribute toward RV ejection. This case highlights the importance of left to RV interactions, and how PVSM may mediate these hemodynamic interactions.

Role of brain-derived neurotrophic factor during the regenerative response after traumatic brain injury in adult zebrafish.

PubMed

Cacialli, Pietro; Palladino, Antonio; Lucini, Carla

2018-06-01

Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The brain of adult zebrafish, a teleost fish widely used as vertebrate model, possesses high regenerative properties after injury due to the presence of numerous stem cells niches. The ventricular lining of the zebrafish dorsal telencephalon is the most studied neuronal stem cell niche because its dorso-lateral zone is considered the equivalent to the hippocampus of mammals which contains one of the two constitutive neurogenic niches of mammals. To mimic TBI, stab wound in the dorso-lateral telencephalon of zebrafish was used in studies devoted to fish regenerative properties. Brain-derived neurotrophic factor, which is known to play key roles in the repair process after traumatic brain lesions, persists around the lesioned area of injured telencephalon of adult zebrafish. These results are extensively compared to reparative processes in rodent brain. Considering the complete repair of the damaged area in fish, it could be tempting to consider brain-derived neurotrophic factor as a factor contributing to create a permissive environment that enables the establishment of new neuronal population in damaged brain.

High-resolution synchrotron radiation-based phase tomography of the healthy and epileptic brain

NASA Astrophysics Data System (ADS)

Bikis, Christos; Janz, Philipp; Schulz, Georg; Schweighauser, Gabriel; Hench, Jürgen; Thalmann, Peter; Deyhle, Hans; Chicherova, Natalia; Rack, Alexander; Khimchenko, Anna; Hieber, Simone E.; Mariani, Luigi; Haas, Carola A.; Müller, Bert

2016-10-01

Phase-contrast micro-tomography using synchrotron radiation has yielded superior soft tissue visualization down to the sub-cellular level. The isotropic spatial resolution down to about one micron is comparable to the one of histology. The methods, however, provide different physical quantities and are thus complementary, also allowing for the extension of histology into the third dimension. To prepare for cross-sectional animal studies on epilepsy, we have standardized the specimen's preparation and scanning procedure for mouse brains, so that subsequent histology remains entirely unaffected and scanning of all samples (n = 28) is possible in a realistic time frame. For that, we have scanned five healthy and epileptic mouse brains at the ID19 beamline, ESRF, Grenoble, France, using grating- and propagation-based phase contrast micro-tomography. The resulting datasets clearly show the cortex, ventricular system, thalamus, hypothalamus, and hippocampus. Our focus is on the latter, having planned kainate-induced epilepsy experiments. The cell density and organization in the dentate gyrus and Ammon's horn region were clearly visualized in control animals. This proof of principle was required to initiate experiment. The resulting three-dimensional data have been correlated to histology. The goal is a brain-wide quantification of cell death or structural reorganization associated with epilepsy as opposed to histology alone that represents small volumes of the total brain only. Thus, the proposed technique bears the potential to correlate the gold standard in analysis with independently obtained data sets. Such an achievement also fuels interest for other groups in neuroscience research to closely collaborate with experts in phase micro-tomography.

Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy.

PubMed

Stockburger, Martin; de Teresa, Eduardo; Lamas, Gervasio; Desaga, Martin; Koenig, Carsten; Habedank, Dirk; Cobo, Erik; Navarro, Xavier; Wiegand, Uwe

2014-01-01

Previous studies showed unfavourable effects of right ventricular (RV) pacing. Ventricular pacing (VP), however, is required in many patients with atrioventricular (AV) block. The PREVENT-HF study explored left ventricular (LV) remodelling during RV vs. biventricular (BIV) pacing in AV block without advanced heart failure. The pre-specified PREVENT-HF German Substudy examined exercise capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP). Patients with expected VP ≥80% were randomized to RV or BIV pacing. Endpoints were peak oxygen uptake (pVO2), oxygen uptake at the anaerobic threshold (VO2AT), ventilatory efficiency (VE/VCO2), and logNT-proBNP. Considering crossover, intention to treat (ITT), and on-treatment (OT) analyses of covariance (ANCOVA) were performed. For exercise testing 44 (RV: 25, BIV: 19), and for NT-proBNP 53 patients (RV: 29, BIV: 24) were included. The ITT analysis revealed significant differences in pVO2 [ANCOVA effect 2.83 mL/kg/min, confidence interval (CI) 0.83-4.91, P = 0.007], VO2AT (ANCOVA effect 2.14 mL/min/k, CI 0.14-4.15, P = 0.03), and VE/VCO2 (ANCOVA effect -5.46, CI -10.79 to -0.13, P = 0.04) favouring BIV randomization. The significant advantage in pVO2 persisted in OT analysis, while VO2AT and VE/VCO2 showed trends favouring BIV pacing. LogNT-proBNP did not differ between groups. (ITT: ANCOVA effect 0.008, CI -0.40 to +0.41, P = 0.97; OT: ANCOVA effect -0.03, CI -0.44 to 0.30, P = 0.90). Our study suggests that BIV pacing produces better exercise capacity over 1 year compared with RV pacing in patients without advanced heart failure and AV block. In contrast, we observed no significant changes of NT-proBNP. Larger trials will allow appraising the clinical usefulness of BIV pacing in AV block. ClinicalTrials.gov Identifier: NCT00170326.

The effect of heart failure and left ventricular assist device treatment on right ventricular mechanics: a computational study.

PubMed

Park, Jun I K; Heikhmakhtiar, Aulia Khamas; Kim, Chang Hyun; Kim, Yoo Seok; Choi, Seong Wook; Song, Kwang Soup; Lim, Ki Moo

2018-05-22

Although it is important to analyze the hemodynamic factors related to the right ventricle (RV) after left ventricular assist device (LVAD) implantation, previous studies have focused only on the alteration of the ventricular shape and lack quantitative analysis of the various hemodynamic parameters. Therefore, we quantitatively analyzed various hemodynamic parameters related to the RV under normal, heart failure (HF), and HF incorporated with continuous flow LVAD therapy by using a computational model. In this study, we combined a three-dimensional finite element electromechanical model of ventricles, which is based on human ventricular morphology captured by magnetic resonance imaging (MRI) with a lumped model of the circulatory system and continuous flow LVAD function in order to construct an integrated model of an LVAD implanted-cardiovascular system. To induce systolic dysfunction, the magnitude of the calcium transient function under HF condition was reduced to 70% of the normal value, and the time constant was reduced by 30% of the normal value. Under the HF condition, the left ventricular end systolic pressure decreased, the left ventricular end diastolic pressure increased, and the pressure in the right atrium (RA), RV, and pulmonary artery (PA) increased compared with the normal condition. The LVAD therapy decreased the end-systolic pressure of the LV by 41%, RA by 29%, RV by 53%, and PA by 71%, but increased the right ventricular ejection fraction by 52% and cardiac output by 40%, while the stroke work was reduced by 67% compared with the HF condition without LVAD. The end-systolic ventricular tension and strain decreased with the LVAD treatment. LVAD enhances CO and mechanical unloading of the LV as well as those of the RV and prevents pulmonary hypertension which can be induced by HF.

Atrial fibrillation and sudden cardiac death: catheter-based sensor and mapping system of the heart

NASA Astrophysics Data System (ADS)

Ramasamy, Mouli; Kumar, Prashanth S.; Varadan, Vijay K.

2017-04-01

Ventricular arrhythmias in the heart and the rapid heartbeat of ventricular tachycardia can lead to sudden cardiac death. This is a major health issue worldwide. What is needed is to develop a catheter based sensor and mapping approach which will provide the mechanisms of ventricular arrhythmia, and effectively prevent and treat the same, potentially save life.

Successful ablation of a right atrium-axillary ventricular accessory pathway associated with Wolff-Parkinson-White syndrome.

PubMed

Yuan, Yuan; Long, Deyong; Dong, Jianzeng; Tao, Ling; Ma, Changsheng

2017-12-01

We report a case of a patient with right axillary ventricular. Similar congenital anomaly of the right atrium was reported as "right appendage diverticulum or right atrial diverticulum." However, this independent chamber has its own annulus, synchronizes with the right ventricular, and generates large ventricular potential. Under the guidance of the CARTO mapping system (Biosense Webster, Diamond Bar, CA, USA), a right atrioventricular accessory pathway associated with type B Wolff-Parkinson-White syndrome was ablated successfully. This pathway was close to the annulus of the axillary ventricular. The patient remained free of arrhythmia at 1-year follow-up. © 2017 Wiley Periodicals, Inc.

Novel temporary left ventricular assist system with hydrodynamically levitated bearing pump for bridge to decision: initial preclinical assessment in a goat model.

PubMed

Kishimoto, Satoru; Takewa, Yoshiaki; Tsukiya, Tomonori; Mizuno, Toshihide; Date, Kazuma; Sumikura, Hirohito; Fujii, Yutaka; Ohnuma, Kentaro; Togo, Konomi; Katagiri, Nobumasa; Naito, Noritsugu; Kishimoto, Yuichiro; Nakamura, Yoshinobu; Nishimura, Motonobu; Tatsumi, Eisuke

2018-03-01

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. We developed a new temporary left ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing. We used three adult goats (body weight, 58-68 kg) to investigate the 30-day performance and hemocompatibility of the newly developed left ventricular assist system, which included the pump, inflow and outflow cannulas, the extracorporeal circuit, and connectors. Hemodynamic, hematologic, and blood chemistry measurements were investigated as well as end-organ effect on necropsy. All goats survived for 30 days in good general condition. The blood pump was operated at a rotational speed of 3000-4500 rpm and a mean pump flow of 3.2 ± 0.6 L min. Excess hemolysis, observed in one goat, was due to the inadequate increase in pump rotational speed in response to drainage insufficiency caused by continuous contact of the inflow cannula tip with the left ventricular septal wall in the early days after surgery. At necropsy, no thrombus was noted in the pump, and no damage caused by mechanical contact was found on the bearing. The newly developed temporary left ventricular assist system using a disposable centrifugal pump with hydrodynamic bearing demonstrated consistent and satisfactory hemodynamic performance and hemocompatibility in the goat model.

Paeoniflorin improves cardiac function and decreases adverse postinfarction left ventricular remodeling in a rat model of acute myocardial infarction.

PubMed

Chen, Hengwen; Dong, Yan; He, Xuanhui; Li, Jun; Wang, Jie

2018-01-01

Paeoniflorin (PF) is the active component of Paeonia lactiflora Pall. or Paeonia veitchii Lynch. This study was, therefore, aimed to evaluate the improvement and mechanism of the PF on ventricular remodeling in rats with acute myocardial infarction (AMI). In this study, AMI model was established by ligating the anterior descending coronary artery in Wistar rats. After 4 weeks gavage of PF, the apparent signs and the left ventricle weight index of Wistar rats were observed. The left ventricular ejection fraction (LVEF) was evaluated by Doppler ultrasonography. Changes in cardiac morphology were observed by pathologic examination, and apoptosis was observed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, enzyme-linked immunosorbent assay was used to detect the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) interleukin-10 (IL-10) and brain natriuretic peptide (BNP). Immunohistochemistry and Western blot method were applied to detect Caspase-3 and Caspase-9. Compared with the model control, the survival conditions of rats in all treatment groups were generally improved after PF treatment. LVEF was significantly increased, and both left ventricular end-diastolic inner diameter and left ventricular end-systolic inner diameter were significantly reduced. Moreover, pathologic examination showed that the myocardium degeneration of the rats treated with PF was decreased, including neater arrangement, more complete myofilament, more uniform gap and less interstitial collagen fibers. Furthermore, the mitochondrial structure of cardiomyocytes was significantly improved. The ultrastructure was clear, and the arrangement of myofilament was more regular. Also, the expression of Caspase-3 and Caspase-9 was inhibited, and apoptosis was obviously reduced in the PF treatment groups. BNP, TNF-α and IL-6 were also decreased and IL-10 was increased in the treated rats. PF could significantly improve the LVEF of rats. It decreased adverse left ventricular remodeling after myocardial infarction in rat models. The potential mechanism could be that PF decreased and inhibited BNP, TNF-α and IL-6, increased IL-10 and further inhibited the expression of Caspase-3 and Caspase-9, thus promoting ventricular remodeling.

Effect of right ventricular pacing lead site on left ventricular function in patients with high-grade atrioventricular block: results of the Protect-Pace study.

PubMed

Kaye, Gerald C; Linker, Nicholas J; Marwick, Thomas H; Pollock, Lucy; Graham, Laura; Pouliot, Erika; Poloniecki, Jan; Gammage, Michael

2015-04-07

Chronic right ventricle (RV) apical (RVA) pacing is standard treatment for an atrioventricular (AV) block but may be deleterious to left ventricle (LV) systolic function. Previous clinical studies of non-apical pacing have produced conflicting results. The aim of this randomized, prospective, international, multicentre trial was to compare change in LV ejection fraction (LVEF) between right ventricular apical and high septal (RVHS) pacing over a 2-year study period. We randomized 240 patients (age 74 ± 11 years, 67% male) with a high-grade AV block requiring >90% ventricular pacing and preserved baseline LVEF >50%, to receive pacing at the RVA (n = 120) or RVHS (n = 120). At 2 years, LVEF decreased in both the RVA (57 ± 9 to 55 ± 9%, P = 0.047) and the RVHS groups (56 ± 10 to 54 ± 10%, P = 0.0003). However, there was no significant difference in intra-patient change in LVEF between confirmed RVA (n = 85) and RVHS (n = 83) lead position (P = 0.43). There were no significant differences in heart failure hospitalization, mortality, the burden of atrial fibrillation, or plasma brain natriutetic peptide levels between the two groups. A significantly greater time was required to place the lead in the RVHS position (70 ± 25 vs. 56 ± 24 min, P < 0.0001) with longer fluoroscopy times (11 ± 7 vs. 5 ± 4 min, P < 0.0001). In patients with a high-grade AV block and preserved LV function requiring a high percentage of ventricular pacing, RVHS pacing does not provide a protective effect on left ventricular function over RVA pacing in the first 2 years. ClinicalTrials.gov number NCT00461734. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Interdependence of right ventricular systolic function and left ventricular filling and its association with outcome for patients with pulmonary hypertension.

PubMed

Motoji, Yoshiki; Tanaka, Hidekazu; Fukuda, Yuko; Sano, Hiroyuki; Ryo, Keiko; Imanishi, Junichi; Miyoshi, Tatsuya; Sawa, Takuma; Mochizuki, Yasuhide; Matsumoto, Kensuke; Emoto, Noriaki; Hirata, Ken-ichi

2015-04-01

Although impaired right ventricular (RV) performance has been associated with adverse outcomes for pulmonary hypertension (PH) patients, the relationship between bi-ventricular interdependence and outcomes is not yet fully understood. We studied 96 PH patients. RV systolic function was assessed by means of RV free-wall longitudinal speckle-tracking strain (RV-free), and left ventricular (LV) filling as early diastolic transmitral flow velocity (TMF-E). RV-free ≤19 % and TMF-E <60 cm/s were adopted as pre-defined cut-offs for RV systolic dysfunction and LV under-filling, respectively, associated with worse outcomes. Long-term outcome was tracked over 2.2 years. RV-free correlated significantly with TMF-E (r = 0.57, p < 0.001).TMF-E and RV-free were significantly lower in patients with than in those without cardiac events. RV systolic dysfunction and LV under-filling was observed in 35 patients. These features were associated with worse long-term survival compared to other sub-groups (log-rank p = 0.012). A sequential Cox model based on clinical variables including world health organization functional class IV and brain natriuretic peptide >150 pg/dl (χ(2) = 1.2) was improved by the addition of RV-free (χ(2) = 5.5, p = 0.04) as well as of TMF-E (χ(2) = 11.5, p = 0.01). In conclusions, RV systolic function was shown to correlate significantly with LV filling in PH patients. In addition, not only assessment of RV systolic function, but also of a combined bi-ventricular parameter comprising RV systolic function and LV filling may well have clinical implications for more successful management of PH patients.

[SIMULTANEOUS MEASUREMENT OF INTRAVENTRICULAR AND PARENCHYMAL INTRACRANIAL PRESSURE IN PATIENTS WITH SEVERE TRAUMA BRAIN INJURY].

PubMed

Oshorov, A V; Popugaev, K A; Savin, I A; Potapov, A A

2016-01-01

"Standard" assessment of ICP by measuring liquor ventricular pressure recently questioned. THE OBJECTIVE OF THE STUDY: Compare the values of ventricular and parenchymal ICP against the closure of open liquor drainage and during active CSF drainage. Examined 7 patients with TBI and intracranial hypertension syndrome, GCS 5.6 ± 1.2 points, 4.2 ± age 33 years. Compared parenchymal and ventricular ICP in three time periods: 1--during closure of ventricular drainage, 2--during of the open drains and drainage at the level of 14-15 mmHg, 3--during the period of active drainage. When comparing two methods of measurement used Bland-Altman method. 1. During time period of the closed drainage correlation coefficient was r = 0.83, p < 0.001. Bland-Altman method: the difference of the two measurements is equal to the minimum and 0.7 mm Hg, the standard deviation of 2.02 mm Hg 2. During time period of the open drainage was reduction of the correlation coefficient to r = 0.46, p < 0.01. Bland-Altman method: an increase in the difference of the two measurements to -0.84 mmHg, standard deviation 2.8 mm Hg 3. During time period of the active drainage of cerebrospinal fluid was marked difference between methods of measurement. Bland-Altman method: the difference was 8.64 mm Hg, and a standard deviation of 2.6 mm Hg. 1. During the closure of the ventricular drainage were good correlation between ventricular and parenchymal ICR 2. During open the liquor drainage correlation between the two methods of measuring the intracranial pressure is reduced. 3. During the active CSF drainage correlation between the two methods of measuring intracranial pressure can be completely lost. Under these conditions, CSF pressure is not correctly reflect the ICP 4. For an accurate and continuous measurement of intracranial pressure on the background of the active CSF drainage should be carried out simultaneous parenchymal ICP measurement.

Analysis of transthoracic echocardiographic data in major vascular surgery from a prospective randomised trial comparing sevoflurane and fentanyl with propofol and remifentanil anaesthesia.

PubMed

Lindholm, E E; Aune, E; Frøland, G; Kirkebøen, K A; Otterstad, J E

2014-06-01

The aim of this study was to define pre-operative echocardiographic data and explore if postoperative indices of cardiac function after open abdominal aortic surgery were affected by the anaesthetic regimen. We hypothesised that volatile anaesthesia would improve indices of cardiac function compared with total intravenous anaesthesia. Transthoracic echocardiography was performed pre-operatively in 78 patients randomly assigned to volatile anaesthesia and 76 to total intravenous anaesthesia, and compared with postoperative data. Pre-operatively, 16 patients (10%) had left ventricular ejection fraction < 46%. In 138 patients with normal left ventricular ejection fraction, 5/8 (62%) with left ventricular dilatation and 41/130 (33%) without left ventricular dilatation had evidence of left ventricular diastolic dysfunction (p < 0.001). Compared with pre-operative findings, significant increases in left ventricular end-diastolic volume, left atrial maximal volume, cardiac output, velocity of early mitral flow and early myocardial relaxation occurred postoperatively (all p < 0.001). The ratio of the velocity of early mitral flow to early myocardial relaxation remained unchanged. There were no significant differences in postoperative echocardiographic findings between patients anaesthetised with volatile anaesthesia or total intravenous anaesthesia. Patients had an iatrogenic surplus of approximately 4.1 l of fluid volume by the first postoperative day. N-terminal prohormone of brain natriuretic peptide increased on the first postoperative day (p < 0.001) and remained elevated after 30 days (p < 0.001) in both groups. Although postoperative echocardiographic alterations were most likely to be related to increased preload due to a substantial iatrogenic surplus of fluid, a component of peri-operative myocardial ischaemia cannot be excluded. Our hypothesis that volatile anaesthesia improved indices of cardiac function compared with total intravenous anaesthesia could not be verified. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Ischemic Ventricular Tachycardia Presenting as a Narrow Complex Tachycardia

PubMed Central

Page, Stephen P; Watts, Troy; Yeo, Wee Tiong; Mehul, Dhinoja

2014-01-01

This report describes a patient presenting with a narrow complex tachycardia in the context of prior myocardial infarction and impaired ventricular function. Electrophysiological studies confirmed ventricular tachycardia and activation and entrainment mapping demonstrated a critical isthmus within an area of scar involving the His-Purkinje system accounting for the narrow QRS morphology. This very rare case shares some similarities with upper septal ventricular tachycardia seen in patients with structurally normal hearts, but to our knowledge has not been seen previously in patients with ischemic heart disease. PMID:25057222

Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study.

PubMed

Park, Chloe M; Williams, Emily D; Chaturvedi, Nish; Tillin, Therese; Stewart, Robert J; Richards, Marcus; Shibata, Dean; Mayet, Jamil; Hughes, Alun D

2017-04-18

Subclinical left ventricular (LV) dysfunction has been inconsistently associated with early cognitive impairment, and mechanistic pathways have been poorly considered. We investigated the cross-sectional relationship between LV dysfunction and structural/functional measures of the brain and explored the role of potential mechanisms. A total of 1338 individuals (69±6 years) from the Southall and Brent Revisited study underwent echocardiography for systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial diameter) assessment. Cognitive function was assessed and total and hippocampal brain volumes were measured by magnetic resonance imaging. Global LV function was assessed by circulating N-terminal pro-brain natriuretic peptide. The role of potential mechanistic pathways of arterial stiffness, atherosclerosis, microvascular disease, and inflammation were explored. After adjusting for age, sex, and ethnicity, lower systolic function was associated with lower total brain (beta±standard error, 14.9±3.2 cm 3 ; P <0.0001) and hippocampal volumes (0.05±0.02 cm 3 , P =0.01). Reduced diastolic function was associated with poorer working memory (-0.21±0.07, P =0.004) and fluency scores (-0.18±0.08, P =0.02). Reduced global LV function was associated with smaller hippocampal volume (-0.10±0.03 cm 3 , P =0.004) and adverse visual memory (-0.076±0.03, P =0.02) and processing speed (0.063±0.02, P =0.006) scores. Separate adjustment for concomitant cardiovascular risk factors attenuated associations with hippocampal volume and fluency only. Further adjustment for the alternative pathways of microvascular disease or arterial stiffness attenuated the relationship between global LV function and visual memory. In a community-based sample of older people, measures of LV function were associated with structural/functional measures of the brain. These associations were not wholly explained by concomitant risk factors or potential mechanistic pathways. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Volumetric-modulated arc therapy vs conventional fixed-field intensity-modulated radiotherapy in a whole-ventricular irradiation: A planning comparison study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakanaka, Katsuyuki; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Sato, Sayaka

This study evaluated the dosimetric difference between volumetric-modulated arc therapy (VMAT) and conventional fixed-field intensity-modulated radiotherapy (cIMRT) in whole-ventricular irradiation. Computed tomography simulation data for 13 patients were acquired to create plans for VMAT and cIMRT. In both plans, the same median dose (100% = 24 Gy) was prescribed to the planning target volume (PTV), which comprised a tumor bed and whole ventricles. During optimization, doses to the normal brain and body were reduced, provided that the dose constraints of the target coverage were satisfied. The dose-volume indices of the PTV, normal brain, and body as well as monitor unitsmore » were compared between the 2 techniques by using paired t-tests. The results showed no significant difference in the homogeneity index (0.064 vs 0.065; p = 0.824) of the PTV and conformation number (0.78 vs 0.77; p = 0.065) between the 2 techniques. In the normal brain and body, the dose-volume indices showed no significant difference between the 2 techniques, except for an increase in the volume receiving a low dose in VMAT; the absolute volume of the normal brain and body receiving 1 Gy of radiation significantly increased in VMAT by 1.6% and 8.3%, respectively, compared with that in cIMRT (1044 vs 1028 mL for the normal brain and 3079.2 vs 2823.3 mL for the body; p<0.001). The number of monitor units to deliver a 2.0-Gy fraction was significantly reduced in VMAT compared with that in cIMRT (354 vs 873, respectively; p<0.001). In conclusion, VMAT delivers IMRT to complex target volumes such as whole ventricles with fewer monitor units, while maintaining target coverage and conformal isodose distribution comparable to cIMRT; however, in addition to those characteristics, the fact that the volume of the normal brain and body receiving a low dose would increase in VMAT should be considered.« less

Percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder.

PubMed

Xi, Er-Ping; Zhu, Jian; Zhu, Shui-Bo; Yin, Gui-Lin; Liu, Yong; Dong, Yong-Qiang; Zhang, Yu; Xia, Feng

2012-11-01

Ventricular septal defects resulting from post-traumatic cardiac injury are very rare. Percutaneous closure has emerged as a method for treating this disorder. We wish to report our experience in three patients who underwent percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder. We treated three patients with post-traumatic ventricular septal defects caused by stab wounds with knives. After the heart wound was repaired, patient examinations revealed ventricular septal defects with pulmonary/systemic flow ratios (Qp/Qs) of over 1.7. The post-traumatic ventricular septal defects were closed percutaneously with a patent ductus arteriosus occluder (Lifetech Scientific (Shenzhen) Co., LTD, Guangdong, China) utilizing standard techniques. Post-operative transthoracic echocardiography revealed no residual left-to-right shunt and indicated normal ventricular function. In addition, 320-slice computerized tomography showed that the occluder was well placed and exhibited normal morphology. Our experiences indicate that closure of a post-traumatic ventricular septal defect using a patent ductus arteriosus occluder is feasible, safe, and effective.

Percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder

PubMed Central

Xi, Er-Ping; Zhu, Jian; Zhu, Shui-Bo; Yin, Gui-Lin; Liu, Yong; Dong, Yong-Qiang; Zhang, Yu; Xia, Feng

2012-01-01

OBJECTIVE: Ventricular septal defects resulting from post-traumatic cardiac injury are very rare. Percutaneous closure has emerged as a method for treating this disorder. We wish to report our experience in three patients who underwent percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder. METHODS: We treated three patients with post-traumatic ventricular septal defects caused by stab wounds with knives. After the heart wound was repaired, patient examinations revealed ventricular septal defects with pulmonary/systemic flow ratios (Qp/Qs) of over 1.7. The post-traumatic ventricular septal defects were closed percutaneously with a patent ductus arteriosus occluder (Lifetech Scientific (Shenzhen) Co., LTD, Guangdong, China) utilizing standard techniques. RESULTS: Post-operative transthoracic echocardiography revealed no residual left-to-right shunt and indicated normal ventricular function. In addition, 320-slice computerized tomography showed that the occluder was well placed and exhibited normal morphology. CONCLUSION: Our experiences indicate that closure of a post-traumatic ventricular septal defect using a patent ductus arteriosus occluder is feasible, safe, and effective. PMID:23184204

Hemodynamics on abrupt stoppage of centrifugal pumps during left ventricular assist.

PubMed

Kono, S; Nishimura, K; Nishina, T; Akamatsu, T; Komeda, M

2000-01-01

A magnetically suspended centrifugal pump (MSCP), developed for long-term ventricular assist, is reliable and durable because it has no shaft or seal. However, with nonvalve pumps such as a MSCP, regurgitation occurs when they accidentally stop without cannula clamping. We investigated the hemodynamics during temporary stoppage of a MSCP being used as a left ventricular assist system (LVAS), comparing two inflow cannulation sites. In four sheep (weight, 35-45 kg), microspheres were injected into the left main coronary artery to induce heart failure. An outflow cannula was sutured onto the descending aorta, and two inflow cannulae were inserted into the left atrium and the left ventricle. The MSCP was stopped with both the left ventricular cannula and left atrial cannula clamped, and the hemodynamics and P-V loops were recorded. Each cannula was then unclamped in order, and similar parameters were recorded. LVEDP increased at unclamping of the left ventricular cannula (ULVC), and rose further at unclamping of the left atrial cannula (ULAC). Aortic pressure did not change at ULVC, but decreased at ULAC. The effective systemic flow that subtracted the regurgitant flow through the MSCP from left ventricular output was half at ULVC and almost 0 at ULAC. When stopping centrifugal pumps without circuit clamping, hemodynamic deterioration is less at ULVC than at ULAC. This finding suggests that left ventricular inflow cannulation is recommended to allow more time in emergency situations.

Early results of MitraClip system implantation by real-time three-dimensional speckle-tracking left ventricle analysis.

PubMed

Scandura, Salvatore; Dipasqua, Fabio; Gargiulo, Giuseppe; Capodanno, Davide; Caggegi, Anna; Grasso, Carmelo; Mangiafico, Sarah; Pistritto, Anna Maria; Immè, Sebastiano; Chiarandà, Marta; Ministeri, Margherita; Ronsivalle, Giuseppe; Cannata, Stefano; Arcidiacono, Antonio Andrea; Capranzano, Piera; Tamburino, Corrado

2016-11-01

To appraise the early effect of percutaneous mitral valve repair with the MitraClip system on myocardial function using real-time three-dimensional speckle-tracking echocardiography (3D-STE). Consecutive patients with moderate-to-severe or severe mitral regurgitation, undergoing mitral valve repair with the MitraClip system, were prospectively evaluated during the peri-procedural workout and follow-up. Left ventricular deformation was evaluated by a two-dimensional and 3D speckle-tracking analysis. 3D-STE acquisitions were elaborated obtaining real-time 3D global longitudinal strain evaluation, and by appraising both volumetric and hemodynamic parameters (i.e. left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, cardiac output, and stroke volume). In all, 30 patients were included. At 1-month follow-up, 3D-STE analysis revealed no changes in left ventricular end-diastolic volume (162.6 ± 73.7 ml at baseline vs. 159.8 ± 64.5 ml at 1-month follow-up; P = 0.63) and a downward trend in left ventricular end-systolic volume (104.7 ± 52.0 vs. 100.1 ± 50.4 ml, respectively; P = 0.06). Left ventricular ejection fraction did not significantly increase (38.1 ± 11.3% at baseline vs. 39.4 ± 11.0% at 1-month follow-up; P = 0.20). No significant changes were reported in cardiac output (4.3 ± 2.0 l/min at baseline vs. 4.0 ± 1.5 l/min at follow-up; P = 0.377) and in stroke volume (59.5 ± 25.5 ml at baseline vs. 59.9 ± 20.7 ml at follow-up; P = 0.867). On the contrary, left ventricular deformation capability significantly improved, with the real-time 3D global longitudinal strain value changing from -9.8 ± 4.1% at baseline to -11.0 ± 4.4% at follow-up (P = 0.018). Accurately assessing myocardial function by the use of 3D-STE, this study reported irrelevant early changes in left ventricular size, but a positive effect on left ventricular deformation capability following mitral valve repair with the MitraClip system. These preliminary results need to be confirmed in larger series and extended to long-term follow-up.

Addressing the need for biomarker liquid chromatography/mass spectrometry assays: a protocol for effective method development for the bioanalysis of endogenous compounds in cerebrospinal fluid.

PubMed

Benitex, Yulia; McNaney, Colleen A; Luchetti, David; Schaeffer, Eric; Olah, Timothy V; Morgan, Daniel G; Drexler, Dieter M

2013-08-30

Research on disorders of the central nervous system (CNS) has shown that an imbalance in the levels of specific endogenous neurotransmitters may underlie certain CNS diseases. These alterations in neurotransmitter levels may provide insight into pathophysiology, but can also serve as disease and pharmacodynamic biomarkers. To measure these potential biomarkers in vivo, the relevant sample matrix is cerebrospinal fluid (CSF), which is in equilibrium with the brain's interstitial fluid and circulates through the ventricular system of the brain and spinal cord. Accurate analysis of these potential biomarkers can be challenging due to low CSF sample volume, low analyte levels, and potential interferences from other endogenous compounds. A protocol has been established for effective method development of bioanalytical assays for endogenous compounds in CSF. Database searches and standard-addition experiments are employed to qualify sample preparation and specificity of the detection thus evaluating accuracy and precision. This protocol was applied to the study of the histaminergic neurotransmitter system and the analysis of histamine and its metabolite 1-methylhistamine in rat CSF. The protocol resulted in a specific and sensitive novel method utilizing pre-column derivatization ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS), which is also capable of separating an endogenous interfering compound, identified as taurine, from the analytes of interest. Copyright © 2013 John Wiley & Sons, Ltd.

Canine spontaneous glioma: A translational model system for convection-enhanced delivery

PubMed Central

Dickinson, Peter J.; LeCouteur, Richard A.; Higgins, Robert J.; Bringas, John R.; Larson, Richard F.; Yamashita, Yoji; Krauze, Michal T.; Forsayeth, John; Noble, Charles O.; Drummond, Daryl C.; Kirpotin, Dmitri B.; Park, John W.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2010-01-01

Canine spontaneous intracranial tumors bear striking similarities to their human tumor counterparts and have the potential to provide a large animal model system for more realistic validation of novel therapies typically developed in small rodent models. We used spontaneously occurring canine gliomas to investigate the use of convection-enhanced delivery (CED) of liposomal nanoparticles, containing topoisomerase inhibitor CPT-11. To facilitate visualization of intratumoral infusions by real-time magnetic resonance imaging (MRI), we included identically formulated liposomes loaded with Gadoteridol. Real-time MRI defined distribution of infusate within both tumor and normal brain tissues. The most important limiting factor for volume of distribution within tumor tissue was the leakage of infusate into ventricular or subarachnoid spaces. Decreased tumor volume, tumor necrosis, and modulation of tumor phenotype correlated with volume of distribution of infusate (Vd), infusion location, and leakage as determined by real-time MRI and histopathology. This study demonstrates the potential for canine spontaneous gliomas as a model system for the validation and development of novel therapeutic strategies for human brain tumors. Data obtained from infusions monitored in real time in a large, spontaneous tumor may provide information, allowing more accurate prediction and optimization of infusion parameters. Variability in Vd between tumors strongly suggests that real-time imaging should be an essential component of CED therapeutic trials to allow minimization of inappropriate infusions and accurate assessment of clinical outcomes. PMID:20488958

Fornix Under Water? Ventricular Enlargement Biases Forniceal Diffusion Magnetic Resonance Imaging Indices in Anorexia Nervosa.

PubMed

Kaufmann, Lisa-Katrin; Baur, Volker; Hänggi, Jürgen; Jäncke, Lutz; Piccirelli, Marco; Kollias, Spyros; Schnyder, Ulrich; Pasternak, Ofer; Martin-Soelch, Chantal; Milos, Gabriella

2017-07-01

Acute anorexia nervosa (AN) is characterized by reduced brain mass and corresponding increased sulcal and ventricular cerebrospinal fluid. Recent studies of white matter using diffusion tensor imaging consistently identified alterations in the fornix, such as reduced fractional anisotropy (FA). However, because the fornix penetrates the ventricles, it is prone to cerebrospinal fluid-induced partial volume effects that interfere with a valid assessment of FA. We investigated the hypothesis that in the acute stage of AN, FA of the fornix is markedly affected by ventricular volumes. First, using diffusion tensor imaging data we established the inverse associations between forniceal FA and volumes of the third and lateral ventricles in a prestudy with 32 healthy subjects to demonstrate the strength of ventricular influence on forniceal FA independent of AN. Second, we investigated a sample of 25 acute AN patients and 25 healthy control subjects. Using ventricular volumes as covariates markedly reduced the group effect of forniceal FA, even with tract-based spatial statistics focusing only on the center of the fornix. In addition, after correcting for free water on voxel level, the group differences in forniceal FA between AN patients and controls disappeared completely. It is unlikely that microstructural changes affecting FA occurred in the fornix of AN patients. Previously identified alterations in acute AN may have been biased by partial volume effects and the proposed central role of this structure in the pathophysiology may need to be reconsidered. Future studies on white matter alterations in AN should carefully deal with partial volume effects. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Sulforaphane, a Natural Isothiocyanate Compound, Improves Cardiac Function and Remodeling by Inhibiting Oxidative Stress and Inflammation in a Rabbit Model of Chronic Heart Failure.

PubMed

Ma, Tongliang; Zhu, Decai; Chen, Duoxue; Zhang, Qiaoyun; Dong, Huifang; Wu, Wenwu; Lu, Huihe; Wu, Guangfu

2018-03-12

BACKGROUND The aim of this study was to investigate the effects of sulforaphane (SFN), a natural isothiocyanate compound, in a rabbit ascending aortic cerclage model of chronic heart failure (CHF). MATERIAL AND METHODS Thirty New Zealand White rabbits were divided into the sham operation group (n=10), the CHF group (n=10), and the CHF + SFN group (n=10) treated with subcutaneous SFN (0.5 mg/kg) for five days per week for 12 weeks. After 12 weeks, echocardiography and biometric analysis were performed, followed by the examination of the rabbit hearts. Enzyme-linked immunosorbent assay (ELISA) and Western blot were used to detect levels of inflammatory cytokines, superoxide dismutase (SOD), and malondialdehyde (MDA). RESULTS In the CHF group, compared with the sham operation group, there was an increase in the heart weight to body weight ratio (HW/BW), the left ventricular weight to body weight ratio (LVW/BW), the left ventricular end diastolic diameter (LVEDD), the left ventricular end systolic diameter (LVESD), plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) levels, the cardiac collagen volume fraction (CVF), apoptotic index, expression levels of collagen I, collagen III, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) in the myocardial tissue, and a decrease in the left ventricular shortening fraction (LVFS) and left ventricular ejection fraction (LVEF), and cardiac superoxide dismutase (SOD) activity. These changes were corrected in the SFN-treated group. CONCLUSIONS In a rabbit model of CHF, treatment with SFN improved cardiac function and remodeling by inhibiting oxidative stress and inflammation.

Late deterioration of left ventricular function after right ventricular pacemaker implantation.

PubMed

Bellmann, Barbara; Muntean, Bogdan G; Lin, Tina; Gemein, Christopher; Schmitz, Kathrin; Schauerte, Patrick

2016-09-01

Right ventricular (RV) pacing induces a left bundle branch block pattern on ECG and may promote heart failure. Patients with dual chamber pacemakers (DCPs) who present with progressive reduction in left ventricular ejection fraction (LVEF) secondary to RV pacing are candidates for cardiac resynchronization therapy (CRT). This study analyzes whether upgrading DCP to CRT with the additional implantation of a left ventricular (LV) lead improves LV function in patients with reduced LVEF following DCP implantation. Twenty-two patients (13 males) implanted with DCPs and a high RV pacing percentage (>90%) were evaluated in term of new-onset heart failure symptoms. The patients were enrolled in this retrospective single-center study after obvious causes for a reduced LVEF were excluded with echocardiography and coronary angiography. In all patients, DCPs were then upgraded to biventricular devices. LVEF was analyzed with a two-sided t-test. QRS duration and brain natriuretic peptide (BNP) levels were analyzed with the unpaired t-test. LVEF declined after DCP implantation from 54±10% to 31±7%, and the mean QRS duration was 161±20 ms during RV pacing. NT-pro BNP levels were elevated (3365±11436 pmol/L). After upgrading to a biventricular device, a biventricular pacing percentage of 98.1±2% was achieved. QRS duration decreased to 108±16 ms and 106±20 ms after 1 and 6 months, respectively. There was a significant increase in LVEF to 38±8% and 41±11% and a decrease in NT-pro BNP levels to 3088±2326 pmol/L and 1860±1838 pmol/L at 1 and 6 months, respectively. Upgrading to CRT may be beneficial in patients with DCPs and heart failure induced by a high RV pacing percentage.

Pathogenesis of developmental anomalies of the central nervous system induced by congenital cytomegalovirus infection.

PubMed

Kawasaki, Hideya; Kosugi, Isao; Meguro, Shiori; Iwashita, Toshihide

2017-02-01

In humans, the herpes virus family member cytomegalovirus (CMV) is the most prevalent mediator of intrauterine infection-induced congenital defect. Central nervous system (CNS) dysfunction is a distinguishing symptom of CMV infection, and characterized by ventriculoencephalitis and microglial nodular encephalitis. Reports on the initial distribution of CMV particles and its receptors on the blood brain barrier (BBB) are rare. Nevertheless, several factors are suggested to affect CMV etiology. Viral particle size is the primary factor in determining the pattern of CNS infections, followed by the expression of integrin β1 in endothelial cells, pericytes, meninges, choroid plexus, and neural stem progenitor cells (NSPCs), which are the primary targets of CMV infection. After initial infection, CMV disrupts BBB structural integrity to facilitate the spread of viral particles into parenchyma. Then, the initial meningitis and vasculitis eventually reaches NSPC-dense areas such as ventricular zone and subventricular zone, where viral infection inhibits NSPC proliferation and differentiation and results in neuronal cell loss. These cellular events clinically manifest as brain malformations such as a microcephaly. The purpose of this review is to clearly delineate the pathophysiological basis of congenital CNS anomalies caused by CMV. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Frameless robotically targeted stereotactic brain biopsy: feasibility, diagnostic yield, and safety.

PubMed

Bekelis, Kimon; Radwan, Tarek A; Desai, Atman; Roberts, David W

2012-05-01

Frameless stereotactic brain biopsy has become an established procedure in many neurosurgical centers worldwide. Robotic modifications of image-guided frameless stereotaxy hold promise for making these procedures safer, more effective, and more efficient. The authors hypothesized that robotic brain biopsy is a safe, accurate procedure, with a high diagnostic yield and a safety profile comparable to other stereotactic biopsy methods. This retrospective study included 41 patients undergoing frameless stereotactic brain biopsy of lesions (mean size 2.9 cm) for diagnostic purposes. All patients underwent image-guided, robotic biopsy in which the SurgiScope system was used in conjunction with scalp fiducial markers and a preoperatively selected target and trajectory. Forty-five procedures, with 50 supratentorial targets selected, were performed. The mean operative time was 44.6 minutes for the robotic biopsy procedures. This decreased over the second half of the study by 37%, from 54.7 to 34.5 minutes (p < 0.025). The diagnostic yield was 97.8% per procedure, with a second procedure being diagnostic in the single nondiagnostic case. Complications included one transient worsening of a preexisting deficit (2%) and another deficit that was permanent (2%). There were no infections. Robotic biopsy involving a preselected target and trajectory is safe, accurate, efficient, and comparable to other procedures employing either frame-based stereotaxy or frameless, nonrobotic stereotaxy. It permits biopsy in all patients, including those with small target lesions. Robotic biopsy planning facilitates careful preoperative study and optimization of needle trajectory to avoid sulcal vessels, bridging veins, and ventricular penetration.

Relationships among neuroscore, magnetic resonance imaging features, and intracranial pressure in sheep affected by slow-growing brain lesions.

PubMed

Evangelisti, Maria A; Deiana, Roberta; Melosu, Valentino; Burrai, Giovanni P; Ballocco, Isabella; Varcasia, Antonio; Scala, Antonio; Manunta, Maria L

2018-05-01

Diagnosing high intracranial pressure by clinical and diagnostic imaging is particularly challenging for chronic or slow-growing lesions. The aim of this prospective case-control study is to determine whether the neuroscore and brain magnetic resonance imaging (MRI) are related to the direct measurement of intracranial pressure in sheep affected by intracranial slow-growing lesions due to chronic cerebral coenurosis (Coenurus cerebralis). Seventeen affected and 10 control sheep were included. All animals underwent a neurological examination, MRI of the brain, and direct measurement of intracranial pressure. The severity of clinical signs and MRI findings were scored. Data were statistically analyzed. The invasive intracranial pressure value was higher in affected animals. A severely altered neuroscore is related to an increased intracranial pressure beyond the normal threshold (P < 0.05). The volume of the calvarium was larger in affected animals than in control animals (P = 0.0001) and was positively influenced by the presence and volume of the parasitic cyst (r = 0.7881, P < 0.01). Several degrees of deviation and deformation of both the ventricular system and brain parenchyma were detected by MRI. Subjective MRI findings were not associated with intracranial hypertension. In conclusion, this study shows that in sheep affected by slow-growing lesions, severe alterations in the neuroscore and the results of objective MRI are related to an increased intracranial pressure beyond the normal threshold. © 2017 American College of Veterinary Radiology.

Contribution of serum FGF21 level to the identification of left ventricular systolic dysfunction and cardiac death.

PubMed

Shen, Yun; Zhang, Xueli; Pan, Xiaoping; Xu, Yiting; Xiong, Qin; Lu, Zhigang; Ma, Xiaojing; Bao, Yuqian; Jia, Weiping

2017-08-18

The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death. Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan-Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay. A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037-9.500], P = 0.043, OR 9.207 [2.036-41.643], P = 0.004, separately). Further Kaplan-Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years [RR 5.000 (1.326-18.861), P = 0.026; RR 9.643 (2.596-35.825), P = 0.009, respectively]. Serum FGF21 level was significantly correlated with left ventricular systolic dysfunction at baseline. Patients with higher serum levels of FGF21 tended to suffer greater risks of cardiac death than patients with lower serum levels of FGF21. The identification of FGF21 and its relationship with left ventricular systolic function and cardiac death were non-inferior to NT-pro-BNP.

Are there differences in brain morphometry between twins and unrelated singletons? A pediatric MRI study.

PubMed

Ordaz, S J; Lenroot, R K; Wallace, G L; Clasen, L S; Blumenthal, J D; Schmitt, J E; Giedd, J N

2010-04-01

Twins provide a unique capacity to explore relative genetic and environmental contributions to brain development, but results are applicable to non-twin populations only to the extent that twin and singleton brains are alike. A reason to suspect differences is that as a group twins are more likely than singletons to experience adverse prenatal and perinatal events that may affect brain development. We sought to assess whether this increased risk leads to differences in child or adolescent brain anatomy in twins who do not experience behavioral or neurological sequelae during the perinatal period. Brain MRI scans of 185 healthy pediatric twins (mean age = 11.0, SD = 3.6) were compared to scans of 167 age- and sex-matched unrelated singletons on brain structures measured, which included gray and white matter lobar volumes, ventricular volume, and area of the corpus callosum. There were no significant differences between groups for any structure, despite sufficient power for low type II (i.e. false negative) error. The implications of these results are twofold: (1) within this age range and for these measures, it is appropriate to include healthy twins in studies of typical brain development, and (2) findings regarding heritability of brain structures obtained from twin studies can be generalized to non-twin populations.

An Unusual Presentation of Neurocysticercosis: A Space-Occupying Lesion in the Fourth Ventricle Associated with Progressive Cognitive Decline.

PubMed

Kurz, Carolin; Schmidt, Veronika; Poppert, Holger; Wilkins, Patricia; Noh, John; Poppert, Sven; Schlegel, Jürgen; Delbridge, Claire; da Costa, Clarissa Prazeres; Winkler, Andrea S

2016-01-01

We communicate a case of a middle-aged Brazilian patient with an unusual presentation of fourth ventricular neurocysticercosis: occurrence of two intraventricular cysts at different locations in the brain within 2 years and cognitive decline as the only neurological symptom. Neurocysticercosis was confirmed by magnetic resonance imaging, serology, histology, and genetic analysis. Neurocysticercosis should be considered as a differential diagnosis in cases with atypical neurologic or psychiatric symptoms, atypical neuroimaging and travel history. Especially, fourth ventricular cysts carry the risk of obstructive hydrocephalus and brainstem compression and therefore should be extirpated completely. If complete removal of the cystic structures cannot be proven in cases with surgically treated neurocysticercosis, anthelminthic therapy and thorough follow-up examinations should be conducted. © The American Society of Tropical Medicine and Hygiene.

Ventricular efficiency in pregnant women with congenital heart disease.

PubMed

Muneuchi, Jun; Yamasaki, Keiko; Watanabe, Mamie; Fukumitsu, Azusa; Kawakami, Takeshi; Nakahara, Hiromasa; Joo, Kunitaka

2018-06-15

Pregnant women with congenital heart disease (CHD) are at risk of cardiovascular events during pregnancy as well as postpartum. The aim of our study is to address the feasibility of echocardiography-derived ventricular-arterial coupling during pregnancy and postpartum among women with CHD. In 31 pregnant women with CHD, we performed serial echocardiography at the first and third trimesters, early and late postpartum. The indices of contractility (single-beat determined end-systolic elastance, Ees ab ) and afterload (effective arterial elastance, Ea) were approximated on the basis of the systemic blood pressure and systemic ventricular volume. The ratio of stroke work and pressure-volume area (SW/PVA) representing ventricular efficiency was also calculated. Age at the delivery was 28 (24-31) years. ZAHARA score was 0.75 (0.75-1.50). Gestational age and birth weight of newborns were 38 (37-39) weeks and 2.73 (2.42-2.92) kg, respectively. Heart rate, systemic ventricular end-diastolic volume and stroke volume significantly increased from the first trimester to the third trimester and reversed postpartum to the values of the first trimester. Ees ab and Ea significantly decreased from the first trimester to the third trimester (Ees ab ; 4.90 [2.86-7.14] vs 3.41 [2.53-4.61] mm Hg/ml, p = 0.0001, Ea; 2.83 [1.74-3.30] vs 2.18 [1.67-2.68] mm Hg/ml, p = 0.0012), and reversed early postpartum parallelly. Ejection fraction and SW/PVA remained unchanged throughout pregnancy and postpartum. Echocardiography-derived ventricular-arterial coupling is feasible to understand ventricular function in pregnant women with CHD. Copyright © 2018 Elsevier B.V. All rights reserved.

Expression profiles of inka2 in the murine nervous system.

PubMed

Iwasaki, Yumi; Yumoto, Takahito; Sakakibara, Shin-Ichi

2015-01-01

Dynamic rearrangement of the actin cytoskeleton impacts many cellular characteristics in both the developing and adult central nervous systems (CNS), including the migration and adhesion of highly motile neural progenitor cells, axon guidance of immature neurons, and reconstruction of synaptic structures in the adult brain. Inka1, a known regulator of actin cytoskeleton reconstruction, is predominantly expressed by the neural crest cell lineage and regulates the migration and differentiation of these cells. In the present study, we identified a novel gene, designated as inka2, which is related to inka1. Inka2/fam212b is an evolutionarily conserved gene found in different vertebrate species and constitutes a novel gene family together with inka1. Northern blot analysis showed that inka2 mRNA was highly enriched in the nervous system. The spatiotemporal propagation cell profiles of those cells that expressed inka2 transcripts were compatible with those of Olig2-positive oligodendrocyte progenitor cells, which originate in the ventral ventricular zone during embryogenesis. Intense expression of inka2 was also noted in the proliferative neuronal progenitors in the developing cerebellum. On the other hand, immature newborn neurons in the embryonic brain showed no expression of inka2, except for the cells residing in the marginal zone of the embryonic telencephalon, which is known to contain transient cells including the non-subplate pioneer neurons and Cajal-Retzius cells. As brain development proceeds during the postnatal stage, inka2 expression emerged in some populations of immature neurons, including the neocortical pyramidal neurons, hippocampal pyramidal neurons, and granule cells migrating in the cerebellar cortex. In the adult brain, the expression of inka2 was interestingly confined in terminally differentiated neurons in the restricted forebrain regions. Taken together, as a novel regulator of actin cytoskeletons in the CNS, inka2 may be involved in multiple actin-driven processes, including cell migration and establishment of neuronal polarity. Copyright © 2015 Elsevier B.V. All rights reserved.

Synchronous ventricular pacing with direct capture of the atrioventricular conduction system: Functional anatomy, terminology, and challenges.

PubMed

Mulpuru, Siva K; Cha, Yong-Mei; Asirvatham, Samuel J

2016-11-01

Right ventricular apical pacing is associated with an increased incidence of heart failure, atrial fibrillation, and overall mortality. As a result, pacing the ventricles in a manner that closely mimics normal AV conduction with an intact His-Purkinje system has been explored. Recently, the sustainable benefits of selective His-bundle stimulation have been demonstrated and proposed as the preferred method of ventricular stimulation for appropriate patients. Ideally, conduction system pacing should be selective without myocardial capture, overcome distal bundle branch block when present, and not compromise tricuspid valve function. Contemporary literature on conduction system pacing is confusing largely because of inconsistent terminology and, at times, anatomically inaccurate terms used interchangeably for nonsynonymous anatomic sites. In this review, we discuss the functional anatomy of AV conduction access with specific emphasis on terminology, relationship to the membranous septum, tricuspid valve tissue, and proximity to atrial or ventricular myocardium. The potential benefits of each specific site as well as associated unique difficulties with those sites are described. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Longitudinal Regional Brain Development and Clinical Risk Factors in Extremely Preterm Infants.

PubMed

Kersbergen, Karina J; Makropoulos, Antonios; Aljabar, Paul; Groenendaal, Floris; de Vries, Linda S; Counsell, Serena J; Benders, Manon J N L

2016-11-01

To investigate third-trimester extrauterine brain growth and correlate this with clinical risk factors in the neonatal period, using serially acquired brain tissue volumes in a large, unselected cohort of extremely preterm born infants. Preterm infants (gestational age <28 weeks) underwent brain magnetic resonance imaging (MRI) at around 30 weeks postmenstrual age and again around term equivalent age. MRIs were segmented in 50 different regions covering the entire brain. Multivariable regression analysis was used to determine the influence of clinical variables on volumes at both scans, as well as on volumetric growth. MRIs at term equivalent age were available for 210 infants and serial data were available for 131 infants. Growth over these 10 weeks was greatest for the cerebellum, with an increase of 258%. Sex, birth weight z-score, and prolonged mechanical ventilation showed global effects on brain volumes on both scans. The effect of brain injury on ventricular size was already visible at 30 weeks, whereas growth data and volumes at term-equivalent age revealed the effect of brain injury on the cerebellum. This study provides data about third-trimester extrauterine volumetric brain growth in preterm infants. Both global and local effects of several common clinical risk factors were found to influence serial volumetric measurements, highlighting the vulnerability of the human brain, especially in the presence of brain injury, during this period. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiovascular studies using the chimpanzee (Pan troglodytes)

NASA Technical Reports Server (NTRS)

Hinds, J. E.; Cothran, L. N.; Hawthorne, E. W.

1977-01-01

Despite the phylogenetic similarities between chimpanzees and man, there exists a paucity of reliable data on normal cardiovascular function and the physiological responses of the system to standard interventions. Totally implanted biotelemetry systems or hardwire analog techniques were used to examine the maximum number of cardiovascular variables which could be simultaneously monitored without significantly altering the system's performance. This was performed in order to acquire base-line data not previously obtained in this species, to determine cardiovascular response to specific forcing functions such as ventricular pacing, drug infusions, and lower body negative pressure. A cardiovascular function profile protocol was developed in order to adjust independently the three major factors which modify ventricular performance, namely, left ventricular performance, left ventricular preload, afterload, and contractility. Cardiac pacing at three levels above the ambient rate was used to adjust end diastolic volume (preload). Three concentrations of angiotensin were infused continuously to evaluate afterload in a stepwide fashion. A continuous infusion of dobutamine was administered to raise the manifest contractile state of the heart.

A novel technique for ventriculoperitoneal shunting by flat panel detector CT-guided real-time fluoroscopy

PubMed Central

Kobayashi, Shinya; Ishikawa, Tatsuya; Mutoh, Tatsushi; Hikichi, Kentaro; Suzuki, Akifumi

2012-01-01

Background: Surgical placement of a ventriculoperitoneal shunt (VPS) is the main strategy to manage hydrocephalus. However, the failure rate associated with placement of ventricular catheters remains high. Methods: A hybrid operating room, equipped with a flat-panel detector digital subtraction angiography system containing C-arm cone-beam computed tomography (CB-CT) imaging, has recently been developed and utilized to assist neurosurgical procedures. We have developed a novel technique using intraoperative fluoroscopy and a C-arm CB-CT system to facilitate accurate placement of a VPS. Results: Using this novel technique, 39 consecutive ventricular catheters were placed accurately, and no ventricular catheter failures were experienced during the follow-up period. Only two patients experienced obstruction of the VPS, both of which occurred in the extracranial portion of the shunt system. Conclusion: Surgical placement of a VPS assisted by flat panel detector CT-guided real-time fluoroscopy enabled accurate placement of ventricular catheters and was associated with a decreased need for shunt revision. PMID:23226605

Right ventricular exclusion and univentricular palliation for failed one and a half ventricle repair for Ebstein's anomaly.

PubMed

Sasikumar, Navaneetha; Krishna Manohar, Soman R; Philip, Saji; Cherian, Kottoorathu Mammen; Suresh Kumar, Raghavannair

2013-08-01

A 20 year-old male was diagnosed to have Ebstein's anomaly with severe right ventricular dysfunction. He was taken up for 1.5 ventricle repair. Post procedure, there was difficulty in weaning from cardiopulmonary bypass due to progressive right ventricular dilatation compromising the systemic output. An atrial septectomy did not help. Progressive right ventricular dilatation compressing the left ventricle, demonstrated on transoesophageal echocardiogram, prompted us to perform a right ventricular exclusion and univentricular palliation. The patient was successfully weaned off cardiopulmonary bypass and had a smooth postoperative recovery. Judicious use of right ventricular exclusion and univentricular palliation could be an effective bailout strategy in difficult surgical scenarios in Ebstein's anomaly. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Initial experience with remote magnetic navigation for left ventricular lead placement.

PubMed

Mischke, Karl; Knackstedt, Christian; Schmid, Michael; Hatam, Nima; Becker, Michael; Spillner, Jan; Fache, Kerstin; Kelm, Malte; Schauerte, Patrick

2009-08-01

A novel magnetic navigation system allows remote steering of guidewires and catheters. This system may be used for left ventricular lead placement for cardiac resynchronization therapy (CRT). We sought to evaluate the feasibility and safety of magnetic guidewire navigation for CRT procedures. 123 consecutive patients underwent CRT implantation/revision procedures (including pacemaker upgrades in n=22 and left ventricular lead placement after dislocation in n=4 patients). Left ventricular lead placement in a coronary sinus side branch was performed either conventionally or using magnetic navigation. The magnetic navigation system (Niobe) consists of two permanent magnets creating a steerable magnetic field. Guidewires with integrated magnets align to the magnetic field and were used for over-the-wire implantation of pacemaker leads in the coronary sinus. Patients were assigned to conventional (n=93) or magnetic (n=30) navigation according to room availability. Venography of the coronary venous system was performed to select a target vessel for lead implantation. Guidewire access to the target vessel was achieved in 100% using magnetic navigation compared to 87% with the conventional approach (P < 0.05). Implantation success rates, total procedure and fluoroscopy times did not differ significantly between groups. No periprocedural death and no intraoperative device dysfunction occurred in either group.The magnetic guidewire ruptured in one patient. Left ventricular lead placement using magnetic guidewire navigation to engage the desired coronary sinus side branch can be successfully performed for CRT.

Comparison of Quantitative Characteristics of Early Post-resuscitation EEG Between Asphyxial and Ventricular Fibrillation Cardiac Arrest in Rats.

PubMed

Chen, Bihua; Chen, Gang; Dai, Chenxi; Wang, Pei; Zhang, Lei; Huang, Yuanyuan; Li, Yongqin

2018-04-01

Quantitative electroencephalogram (EEG) analysis has shown promising results in studying brain injury and functional recovery after cardiac arrest (CA). However, whether the quantitative characteristics of EEG, as potential indicators of neurological prognosis, are influenced by CA causes is unknown. The purpose of this study was designed to compare the quantitative characteristics of early post-resuscitation EEG between asphyxial CA (ACA) and ventricular fibrillation CA (VFCA) in rats. Thirty-two Sprague-Dawley rats of both sexes were randomized into either ACA or VFCA group. Cardiopulmonary resuscitation was initiated after 5-min untreated CA. Characteristics of early post-resuscitation EEG were compared, and the relationships between quantitative EEG features and neurological outcomes were investigated. Compared with VFCA, serum level of S100B, neurological deficit score and brain histopathologic damage score were dramatically higher in the ACA group. Quantitative measures of EEG, including onset time of EEG burst, time to normal trace, burst suppression ratio, and information quantity, were significantly lower for CA caused by asphyxia and correlated with the 96-h neurological outcome and survival. Characteristics of earlier post-resuscitation EEG differed between cardiac and respiratory causes. Quantitative measures of EEG not only predicted neurological outcome and survival, but also have the potential to stratify CA with different causes.

Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage.

PubMed

McAllister, James P; Guerra, Maria Montserrat; Ruiz, Leandro Castaneyra; Jimenez, Antonio J; Dominguez-Pinos, Dolores; Sival, Deborah; den Dunnen, Wilfred; Morales, Diego M; Schmidt, Robert E; Rodriguez, Esteban M; Limbrick, David D

2017-05-01

To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls without hemorrhages or ventriculomegaly. Birth and expiration estimated gestational ages were 23.0-39.1 and 23.7-44.1 weeks, respectively; survival ranges were 0-42 days (median, 2.0 days). Routine histology and immunohistochemistry for neural stem cells (NSCs), neural progenitors (NPs), multiciliated ependymal cells (ECs), astrocytes (AS), and cell adhesion molecules were performed. Controls exhibited monociliated NSCs and multiciliated ECs lining the ventricles, abundant NPs in the SVZ, and medial vs. lateral wall differences with a complex mosaic organization in the latter. In IVH cases, normal VZ/SVZ areas were mixed with foci of NSC and EC loss, eruption of cells into the ventricle, cytoplasmic transposition of N-cadherin, subependymal rosettes, and periventricular heterotopia. Mature AS populated areas believed to be sites of VZ disruption. The cytopathology and extension of the VZ disruption correlated with developmental age but not with brain hemorrhage grade or location. These results corroborate similar findings in congenital hydrocephalus in animals and humans and indicate that VZ disruption occurs consistently in premature neonates with IVH. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Neoadjuvant chemotherapy for atypical teratoid rhabdoid tumors: case report.

PubMed

Thatikunta, Meena; Mutchnick, Ian; Elster, Jennifer; Thompson, Matthew P; Huang, Michael A; Spalding, Aaron C; Moriarty, Thomas

2017-05-01

Atypical teratoid rhabdoid tumors (ATRTs) are a rare pediatric brain tumor with high mortality rate. Several large series have reported achieving gross-total resection (GTR) in less than 50% of patients due to the lesions' large size, vascularity, and limited blood volume in young patients. While neoadjuvant chemotherapy for choroid plexus carcinomas in pediatric patients has become widely accepted, it has not been used as widely for other pediatric brain tumors. To the best of the authors' knowledge, there are only 3 published cases of neoadjuvant chemotherapy for ATRTs. In the present report, the authors present a fourth case of neoadjuvant chemotherapy for ATRT and review the available literature on this strategy. A 17-month-old child presented with a left ventricular ATRT for which imaging raised concern for a highly vascularized tumor. The authors undertook neoadjuvant chemotherapy with 2 cycles of Head Start II therapy, which reduced the size of the ventricular tumor by 35% and decreased the vascularity of the lesion on imaging. The estimated blood loss during resection was 425 ml and GTR was achieved. The patient continued with postoperative chemotherapy but suffered an on-therapy recurrence. While higher-quality data are necessary, available evidence suggests that neoadjuvant chemotherapy can reduce the size and vascularity of ATRTs and facilitate a surgical avenue for large or "inoperable" tumors.

Regional TNFα mapping in the brain reveals the striatum as a neuroinflammatory target after ventricular fibrillation cardiac arrest in rats☆

PubMed Central

Janata, Andreas; Magnet, Ingrid A.M.; Uray, Thomas; Stezoski, Jason P.; Janesko-Feldman, Keri; Tisherman, Samuel A.; Kochanek, Patrick M.; Drabek, Tomas

2014-01-01

Cardiac arrest (CA) triggers neuroinflammation that could play a role in a delayed neuronal death. In our previously established rat model of ventricular fibrillation (VF) CA characterized by extensive neuronal death, we tested the hypothesis that individual brain regions have specific neuroinflammatory responses, as reflected by regional brain tissue levels of tumor necrosis factor (TNF)α and other cytokines. In a prospective study, rats were randomized to 6 min (CA6), 8 min (CA8) or 10 min (CA10) of VF CA, or sham group. Cortex, striatum, hippocampus and cerebellum were evaluated for TNFα and interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 and interferon gamma at 3 h, 6 h or 14 d after CA by ELISA and Luminex. Immunohistochemistry was used to determine the cell source of TNFα. CA resulted in a selective TNFα response with significant regional and temporal differences. At 3 h after CA, TNFα-levels increased in all regions depending on the duration of the insult. The most pronounced increase was observed in striatum that showed 20-fold increase in CA10 vs. sham, and 3-fold increase vs. CA6 or CA8 group, respectively (p < 0.01). TNFα levels in striatum decreased between 3 h and 6 h, but increased in other regions between 3 h and 14 d. TNFα levels remained twofold higher in CA6 vs. shams across brain regions at 14 d (p < 0.01). In contrast to pronounced TNFα response, other cytokines showed only a minimal increase in CA6 and CA8 groups vs. sham in all brain regions with the exception that IL-1β increased twofold in cerebellum and striatum (p < 0.01). TNFα colocalized with neurons. In conclusion, CA produced a duration-dependent acute TNFα response, with dramatic increase in the striatum where TNFα colocalized with neurons. Increased TNFα levels persist for at least two weeks. This TNFα surge contrasts the lack of an acute increase in other cytokines in brain after CA. Given that striatum is a selectively vulnerable brain region, our data suggest possible role of neuronal TNFα in striatum after CA and identify therapeutic targets for future experiments. PMID:24530249

Prenatal Immune Challenge Is an Environmental Risk Factor for Brain and Behavior Change Relevant to Schizophrenia: Evidence from MRI in a Mouse Model

PubMed Central

Wei, Ran; Hui, Edward S.; Feldon, Joram; Meyer, Urs; Chung, Sookja; Chua, Siew E.; Sham, Pak C.; Wu, Ed X.; McAlonan, Grainne M.

2009-01-01

Objectives Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. Method We used an established mouse model of maternal immune activation (MIA) by the viral mimic PolyI:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. Results PolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4th ventricle volume but did not disrupt sensorimotor gating. Conclusions Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life. PMID:19629183

Quantification of cerebral ventricle volume change of preterm neonates using 3D ultrasound images

NASA Astrophysics Data System (ADS)

Chen, Yimin; Kishimoto, Jessica; Qiu, Wu; de Ribaupierre, Sandrine; Fenster, Aaron; Chiu, Bernard

2015-03-01

Intraventricular hemorrhage (IVH) is a major cause of brain injury in preterm neonates. Quantitative measurement of ventricular dilation or shrinkage is important for monitoring patients and in evaluation of treatment options. 3D ultrasound (US) has been used to monitor the ventricle volume as a biomarker for ventricular dilation. However, volumetric quantification does not provide information as to where dilation occurs. The location where dilation occurs may be related to specific neurological problems later in life. For example, posterior horn enlargement, with thinning of the corpus callosum and parietal white matter fibres, could be linked to poor visuo-spatial abilities seen in hydrocephalic children. In this work, we report on the development and application of a method used to analyze local surface change of the ventricles of preterm neonates with IVH from 3D US images. The technique is evaluated using manual segmentations from 3D US images acquired in two imaging sessions. The surfaces from baseline and follow-up were registered and then matched on a point-by-point basis. The distance between each pair of corresponding points served as an estimate of local surface change of the brain ventricle at each vertex. The measurements of local surface change were then superimposed on the ventricle surface to produce the 3D local surface change map that provide information on the spatio-temporal dilation pattern of brain ventricles following IVH. This tool can be used to monitor responses to different treatment options, and may provide important information for elucidating the deficiencies a patient will have later in life.

Evolving targeted therapies for right ventricular failure.

PubMed

Di Salvo, Thomas G

2015-01-01

Although right and left ventricular embryological origins, morphology and cardiodynamics differ, the notion of selectively targeted right ventricular therapies remains controversial. This review focuses on both the currently evolving pharmacologic agents targeting right ventricular failure (metabolic modulators, phosphodiesterase type V inhibitors) and future therapeutic approaches including epigenetic modulation by miRNAs, chromatin binding complexes, long non-coding RNAs, genomic editing, adoptive gene transfer and gene therapy, cell regeneration via cell transplantation and cell reprogramming and cardiac tissue engineering. Strategies for adult right ventricular regeneration will require a more holistic approach than strategies for adult left ventricular failure. Instances of right ventricular failure requiring global reconstitution of right ventricular myocardium, attractive approaches include: i) myocardial patches seeded with cardiac fibroblasts reprogrammed into cardiomyocytes in vivo by small molecules, miRNAs or other epigenetic modifiers; and ii) administration of miRNAs, lncRNAs or small molecules by non-viral vector delivery systems targeted to fibroblasts (e.g., episomes) to stimulate in vivo reprogramming of fibroblasts into cardiomyocytes. For selected heritable genetic myocardial diseases, genomic editing affords exciting opportunities for allele-specific silencing by site-specific directed silencing, mutagenesis or gene excision. Genomic editing by adoptive gene transfer affords similarly exciting opportunities for restoration of myocardial gene expression.

Bivariate Heritability of Total and Regional Brain Volumes: the Framingham Study

PubMed Central

DeStefano, Anita L.; Seshadri, Sudha; Beiser, Alexa; Atwood, Larry D.; Massaro, Joe M.; Au, Rhoda; Wolf, Philip A.; DeCarli, Charles

2009-01-01

Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging (MRI) who were free of stroke and other neurological disorders that might influence brain volumes and who were members of families with at least two Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile. Genetic and environmental correlations between traits were obtained from bivariate analysis. Heritability estimates ranging from 0.46 to 0.60, were observed for total brain, white matter hyperintensity, hippocampal, temporal lobe, and lateral ventricular volumes. Moderate, yet significant, heritability was observed for the other measures. Bivariate analyses demonstrated that relationships between brain volume measures, except for white matter hyperintensity, reflected both moderate to strong shared genetic and shared environmental influences. This study confirms strong genetic effects on brain and white matter hyperintensity volumes. These data extend current knowledge by showing that these two different types of MRI measures do not share underlying genetic or environmental influences. PMID:19812462

Novel Micropatterned Cardiac Cell Cultures with Realistic Ventricular Microstructure

PubMed Central

Badie, Nima; Bursac, Nenad

2009-01-01

Systematic studies of cardiac structure-function relationships to date have been hindered by the intrinsic complexity and variability of in vivo and ex vivo model systems. Thus, we set out to develop a reproducible cell culture system that can accurately replicate the realistic microstructure of native cardiac tissues. Using cell micropatterning techniques, we aligned cultured cardiomyocytes at micro- and macroscopic spatial scales to follow local directions of cardiac fibers in murine ventricular cross sections, as measured by high-resolution diffusion tensor magnetic resonance imaging. To elucidate the roles of ventricular tissue microstructure in macroscopic impulse conduction, we optically mapped membrane potentials in micropatterned cardiac cultures with realistic tissue boundaries and natural cell orientation, cardiac cultures with realistic tissue boundaries but random cell orientation, and standard isotropic monolayers. At 2 Hz pacing, both microscopic changes in cell orientation and ventricular tissue boundaries independently and synergistically increased the spatial dispersion of conduction velocity, but not the action potential duration. The realistic variations in intramural microstructure created unique spatial signatures in micro- and macroscopic impulse propagation within ventricular cross-section cultures. This novel in vitro model system is expected to help bridge the existing gap between experimental structure-function studies in standard cardiac monolayers and intact heart tissues. PMID:19413993

Segmentation and texture analysis of structural biomarkers using neighborhood-clustering-based level set in MRI of the schizophrenic brain.

PubMed

Latha, Manohar; Kavitha, Ganesan

2018-02-03

Schizophrenia (SZ) is a psychiatric disorder that especially affects individuals during their adolescence. There is a need to study the subanatomical regions of SZ brain on magnetic resonance images (MRI) based on morphometry. In this work, an attempt was made to analyze alterations in structure and texture patterns in images of the SZ brain using the level-set method and Laws texture features. T1-weighted MRI of the brain from Center of Biomedical Research Excellence (COBRE) database were considered for analysis. Segmentation was carried out using the level-set method. Geometrical and Laws texture features were extracted from the segmented brain stem, corpus callosum, cerebellum, and ventricle regions to analyze pattern changes in SZ. The level-set method segmented multiple brain regions, with higher similarity and correlation values compared with an optimized method. The geometric features obtained from regions of the corpus callosum and ventricle showed significant variation (p < 0.00001) between normal and SZ brain. Laws texture feature identified a heterogeneous appearance in the brain stem, corpus callosum and ventricular regions, and features from the brain stem were correlated with Positive and Negative Syndrome Scale (PANSS) score (p < 0.005). A framework of geometric and Laws texture features obtained from brain subregions can be used as a supplement for diagnosis of psychiatric disorders.

A physical multifield model predicts the development of volume and structure in the human brain

NASA Astrophysics Data System (ADS)

Rooij, Rijk de; Kuhl, Ellen

2018-03-01

The prenatal development of the human brain is characterized by a rapid increase in brain volume and a development of a highly folded cortex. At the cellular level, these events are enabled by symmetric and asymmetric cell division in the ventricular regions of the brain followed by an outwards cell migration towards the peripheral regions. The role of mechanics during brain development has been suggested and acknowledged in past decades, but remains insufficiently understood. Here we propose a mechanistic model that couples cell division, cell migration, and brain volume growth to accurately model the developing brain between weeks 10 and 29 of gestation. Our model accurately predicts a 160-fold volume increase from 1.5 cm3 at week 10 to 235 cm3 at week 29 of gestation. In agreement with human brain development, the cortex begins to form around week 22 and accounts for about 30% of the total brain volume at week 29. Our results show that cell division and coupling between cell density and volume growth are essential to accurately model brain volume development, whereas cell migration and diffusion contribute mainly to the development of the cortex. We demonstrate that complex folding patterns, including sinusoidal folds and creases, emerge naturally as the cortex develops, even for low stiffness contrasts between the cortex and subcortex.

Hydrocephalus as a rare compilation of vertebrobasilar dolichoectasia: A case report and review of the literature.

PubMed

Ebrahimzadeh, Keveh; Bakhtevari, Mehrdad H; Shafizad, Misagh; Rezaei, Omidvar

2017-01-01

Vertebrobasilar dolichoectasia (VBD) is a rare disease characterized by significant expansion, elongation, and tortuosity of the vertebrobasilar arteries. Hydrocephalus is a rare compilation of VBD. In this study, we report a 68-year-old male presenting with headache, progressive decreased visual acuity, memory loss, imbalance while walking, and episodes of urinary incontinency. The patient was diagnosed with dolichoectasia of basilar artery causing compression of the third ventricular outflow and thus, presenting with hydrocephalus documented with brain computed tomography scan and brain magnetic resonance imaging. The patient underwent surgical operation and ventriculoperitoneal shunt placement. In the case of hydrocephalus or normal pressure hydrocephalous, VBD should be considered as a differential diagnosis.

Flow Visualization Studies in the Novacor Left Ventricular Assist System CRADA PC91-002, Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borovetz, H.S.; Shaffer, F.; Schaub, R.

This paper discusses a series of experiments to visualize and measure flow fields in the Novacor left ventricular assist system (LVAS). The experiments utilize a multiple exposure, optical imaging technique called fluorescent image tracking velocimetry (FITV) to hack the motion of small, neutrally-buoyant particles in a flowing fluid.

Spatial ability and training in virtual neuroanatomy.

PubMed

Plumley, Leah; Armstrong, Ryan; De Ribaupierre, Sandrine; Eagleson, Roy

2013-01-01

Neuroanatomy is one of the most challenging sections of anatomy to learn, partially related to the intricate relation of multiple 3D structures. As part of the medical student curriculum, it is usually taught in 2D using illustrations and plastinated brain section, since the number of hours devoted to anatomy have dropped in the curriculum, making the dissection of brain too time-consuming to be done. In this study we are analyzing the role of innate spatial ability of novices in learning some basic structures and placing them back in a 3D volumetric brain. Two tasks are performed after a short training session: the first one is to localize the ventricular tip as would be required during a temporal lobectomy, and the second task requires that the subject 'reconstruct' 3D anatomical structures within the context of our 3D brain model. We report our findings on the performance scores obtained from a population of subjects of differing backgrounds and spatial abilities.

Longitudinal brain MRI study in a mouse model of Rett Syndrome and the effects of choline.

PubMed

Ward, B C; Agarwal, S; Wang, K; Berger-Sweeney, J; Kolodny, N H

2008-07-01

Rett Syndrome (RTT), the second most common cause of mental retardation in girls, is associated with mutations of an X-linked gene encoding the transcriptional repressor protein MeCP2. Mecp2(1lox) mutant mice express no functional MeCP2 protein and exhibit behavioral abnormalities similar to those seen in RTT patients. Here we monitor the development of both whole brain and regional volumes between 21 and 42 days of age in this model of RTT using MRI. We see decreases in whole brain volumes in both male and female mutant mice. Cerebellar and ventricular volumes are also decreased in RTT males. Previous work has suggested that perinatal choline supplementation alleviates some of the behavioral deficits in both male and female Mecp2(1lox) mutant mice. Here we show that perinatal choline supplementation also positively affects whole brain volume in heterozygous females, and cerebellar volume in male RTT mice.

An architecture for rapid prototyping of control schemes for artificial ventricles.

PubMed

Ficola, Antonio; Pagnottelli, Stefano; Valigi, Paolo; Zoppitelli, Maurizio

2004-01-01

This paper presents an experimental system aimed at rapid prototyping of feedback control schemes for ventricular assist devices, and artificial ventricles in general. The system comprises a classical mock circulatory system, an actuated bellow-based ventricle chamber, and a software architecture for control schemes implementation and experimental data acquisition, visualization and storing. Several experiments have been carried out, showing good performance of ventricular pressure tracking control schemes.

A servo-controlled canine model of stable severe ischemic left ventricular failure.

PubMed

Wagner, Richard L; Hood, William B; Howland, Peter A

2009-12-01

Reversible left ventricular failure was produced in conscious dogs by compromise of the coronary circulation. In animals with prior left anterior descending coronary artery occlusion, mean left atrial pressure (LAP) was incorporated into an automatic feedback control system used to inflate a balloon cuff on the circumflex (Cfx) coronary artery. The system could produce stable increases in LAP to 15-20 mm Hg. The dominating system transfer function was the ratio of LAP to balloon volume (BV), which was characterized by a fixed delay (5 s), with LAP/BV = (8e(-jomegatau ))/(0.02 + jomega). The system was stabilized by a phase lead network to reduce oscillations of LAP. A total of seven experiments were conducted in three dogs, and testing of inotropic agents was possible in three experiments under stable conditions with the pump off after an hour or more of operation. Problems encountered were 0.003-0.008 Hz oscillations in LAP in three experiments, which could usually be controlled by reducing the system gain. Late stage ventricular fibrillation occurred in all three animals, but defibrillation was easily accomplished after deflating the Cfx balloon. This system produces reversible left ventricular failure solely due to ischemia, thus closely simulating clinical heart failure due to coronary insufficiency.

Thoracic Epidural Anesthesia Reduces Right Ventricular Systolic Function With Maintained Ventricular-Pulmonary Coupling.

PubMed

Wink, Jeroen; de Wilde, Rob B P; Wouters, Patrick F; van Dorp, Eveline L A; Veering, Bernadette Th; Versteegh, Michel I M; Aarts, Leon P H J; Steendijk, Paul

2016-10-18

Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia may affect right ventricular function and interfere with the coupling between right ventricular function and right ventricular afterload. Our main objectives were to study the effects of thoracic epidural anesthesia on right ventricular function and ventricular-pulmonary coupling. In 10 patients scheduled for lung resection, right ventricular function and its response to increased afterload, induced by temporary, unilateral clamping of the pulmonary artery, was tested before and after induction of thoracic epidural anesthesia using combined pressure-conductance catheters. Thoracic epidural anesthesia resulted in a significant decrease in right ventricular contractility (ΔESV 25 : +25.5 mL, P=0.0003; ΔEes: -0.025 mm Hg/mL, P=0.04). Stroke work, dP/dt MAX , and ejection fraction showed a similar decrease in systolic function (all P<0.05). A concomitant decrease in effective arterial elastance (ΔEa: -0.094 mm Hg/mL, P=0.004) yielded unchanged ventricular-pulmonary coupling. Cardiac output, systemic vascular resistance, and mean arterial blood pressure were unchanged. Clamping of the pulmonary artery significantly increased afterload (ΔEa: +0.226 mm Hg/mL, P<0.001). In response, right ventricular contractility increased (ΔESV 25 : -26.6 mL, P=0.0002; ΔEes: +0.034 mm Hg/mL, P=0.008), but ventricular-pulmonary coupling decreased (Δ(Ees/Ea) = -0.153, P<0.0001). None of the measured indices showed significant interactive effects, indicating that the effects of increased afterload were the same before and after thoracic epidural anesthesia. Thoracic epidural anesthesia impairs right ventricular contractility but does not inhibit the native positive inotropic response of the right ventricle to increased afterload. Right ventricular-pulmonary arterial coupling was decreased with increased afterload but not affected by the induction of thoracic epidural anesthesia. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2844. Unique identifier: NTR2844. © 2016 American Heart Association, Inc.

Monitoring ventricular function at rest and during exercise with a nonimaging nuclear detector.

PubMed

Wagner, H N; Rigo, P; Baxter, R H; Alderson, P O; Douglass, K H; Housholder, D F

1979-05-01

A portable nonimaging device, the nuclear stethoscope, for measuring beat to beat ventricular time-activity curves in normal people and patients with heart disease, both at rest and during exercise, is being developed and evaluated. The latest device has several operating modes that facilitate left ventricular and background localization, measurement of transit times and automatic calculation and display of left ventricular ejection fraction. The correlation coefficient of left ventricular ejection fraction obtained with the device and with a camera-computer system was 0.92 in 35 subjects. During bicycle exercise the ejection fraction in 15 normal persons increased from 44 to 64 percent (P less than 0.001), whereas among 12 patients with heart disease it was unchanged in 5 and decreased in 7.

Human FGF1 promoter is active in ependymal cells and dopaminergic neurons in the brains of F1B-GFP transgenic mice.

PubMed

Chen, Mei-Shu; Lin, Hua-Kuo; Chiu, Hsun; Lee, Don-Ching; Chung, Yu-Fen; Chiu, Ing-Ming

2015-03-01

FGF1 is involved in multiple biological functions and exhibits the importance in neuroprotective effects. Our previous studies indicated that, in human brain and retina, the FGF1B promoter controlled the expression of FGF1. However, the exact function and regulation of FGF1 in brain is still unclear. Here, we generated F1B-GFP transgenic mice that expressed the GFP reporter gene under the control of human FGF1B promoter (-540 to +31). Using the fresh brain sections of F1B-GFP transgenic mice, we found that the F1B-GFP cells expressed strong fluorescent signals in the ventricular system throughout the brain. The results of immunohistochemistry further showed that two distinct populations of F1B-GFP(+) cells existed in the brains of F1B-GFP transgenic mice. We demonstrated that one population of F1B-GFP(+) cells was ependymal cells, which distributed along the entire ventricles, and the second population of F1B-GFP(+) cells was neuronal cells that projected their long processes into multiple directions in specific areas of the brain. The double labeling of F1B-GFP(+) cells and tyrosine hydroxylase indicated that a subpopulation of F1B-GFP(+) -neuronal cells was dopaminergic neurons. Importantly, these F1B-GFP(+) /TH(+) cells were distributed in the main dopaminergic neuronal groups including hypothalamus, ventral tegmental area, and raphe nuclei. These results suggested that human FGF1B promoter was active in ependymal cells, neurons, and a portion of dopaminergic neurons. Thus, the F1B-GFP transgenic mice provide an animal model not only for studying FGF1 gene expression in vivo but also for understanding the role of FGF1 contribution in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. © 2014 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc.

[Extracorporeal ventriculoatrial shunt with the use of one-way ball valve].

PubMed

Kubo, Shigeki; Takimoto, Hiroshi; Hosoi, Kazuki; Toyota, Shingo; Takakura, Shuji; Hayashi, Yasuhiro; Ueno, Masato; Morisako, Toshitaka; Karasawa, Jun; Ninaga, Hideo; Yoshimine, Toshiki

2002-04-01

We developed a simple system of an "extracorporeal" ventriculoatrial (VA) shunt using a one-way ball valve (Acty valve II, Kaneka Medix) to release the patient from postoperative constraint during the ventricular drainage. The system is constructed in such a way that the ventricular drainage tube is connected to the central venous catheter via a one-way valve. The CSF is regulated by using the valve and is diverted into the systemic circulation as in the conventional ventriculoatrial shunt. After 2 or 3 weeks of CSF diversion through the extracorporeal VA shunt, a ventriculoperitoneal shunt is placed if hydrocephalus is apparent by temporary occlusion of the system. We applied this system to 4 patients with hydrocephalus, and we found it useful and free from adverse effects. The patient was freed from physical constraint involved in conventional ventricular drainage and an effective program of early rehabilitation was able to be started.

Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing

NASA Technical Reports Server (NTRS)

Taylor, J. A.; Morillo, C. A.; Eckberg, D. L.; Ellenbogen, K. A.

1996-01-01

OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p < 0.05). Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9% vs. -48 +/- 10%; p < 0.05). Although most patients showed a strong inverse relation between arterial pressure and muscle sympathetic nerve activity, three patients with severe left ventricular dysfunction (ejection fraction < or = 30%) showed no relation between arterial pressure and sympathetic activity. CONCLUSIONS: Short-term AV pacing results in lower sympathetic nerve activity and higher arterial pressure than does ventricular pacing, indicating that cardiac pacing mode may influence sympathetic outflow simply through arterial baroreflex mechanisms. We speculate that the greater incidence of adverse outcomes in patients treated with single-chamber ventricular rather than dual-chamber pacing may be due in part to increased sympathetic nervous outflow.

[Complex ventricular arrhythmias and carvedilol: efficacy in hemodialyzed uremic patients].

PubMed

Cice, G; Tagliamonte, E; Ferrara, L; Di Benedetto, A; Iacono, A

1998-06-01

Carvedilol has been shown to be effective in systemic hypertension and coronary artery disease in patients with end-stage renal disease, on maintenance hemodialysis. The aim of our study was to assess the effects of carvedilol on ventricular arrhythmias in these patients. Ninety-eight uremic patients maintained on hemodialysis, with complex ventricular arrhythmias (class III, IV and V of Lown's classification), not only during dialysis, were included in the study. They were divided into two groups, with mild-to-moderate hypertension or coronary artery disease. The efficacy and safety of carvedilol (50 mg/day) was compared to placebo in a 6-week randomized, double-blind study. Carvedilol significantly reduced, in both hypertensive and ischemic patients, total ventricular premature contractions (82.7 +/- 11.3 vs 358.1 +/- 73.9, p < 0.001; 88.3 +/- 24.4 vs 369.9 +/- 77.8, p < 0.001), repetitive ventricular premature contractions (1.3 +/- 1.3 vs 6.3 +/- 3.5, p < 0.001; 1.2 +/- 0.7 vs 6.9 +/- 2.6, p < 0.001) and episodes of ventricular tachycardia (1.1 +/- 1.2 vs 11.8 +/- 7.5, p < 0.001; 1.4 +/- 1.2 vs 14.0 +/- 8.3, p < 0.001). In placebo-treated patients, instead, these parameters were not significantly changed (329.1 +/- 76.5 vs 361.7 +/- 71.7, NS, and 324.6 +/- 79.7 vs 359.3 +/- 58.1, NS; 6.2 +/- 3.7 vs 7.3 +/- 3.7, NS, and 4.9 +/- 2.2 vs 6.1 +/- 3.2, NS; 9.8 +/- 6.3 vs 13.3 +/- 8.0, NS, and 9.0 +/- 6.2 vs 12.4 +/- 7.8, NS). Carvedilol confirmed a significant effect on myocardial ischemia and systemic hypertension. No significant side effects were reported. Ventricular arrhythmias are frequent in patients with end-stage renal disease maintained on hemodialysis. They are often due to an underlying cardiac disease, namely systemic hypertension with left ventricular hypertrophy and coronary artery disease. The results of our study show that the antiarrhythmic effect of carvedilol is linked, at least partly, to an improvement of the underlying cardiac disease. Uremic patients have a chronic increase in adrenergic tone, with a direct correlation between norepinephrine plasmatic concentration and frequence of premature ventricular contractions. Beta-blockers are very important in these patients because of their modulation on the adrenergic system. They also reduce potassium flow, from extracellular to intracellular fluid. Therefore carvedilol can affect the sudden hypokalemia occurring in the first phase of hemodialysis treatment, that may be an important cause of intradialytic arrhythmias.

[Wearable Automatic External Defibrillators].

PubMed

Luo, Huajie; Luo, Zhangyuan; Jin, Xun; Zhang, Leilei; Wang, Changjin; Zhang, Wenzan; Tu, Quan

2015-11-01

Defibrillation is the most effective method of treating ventricular fibrillation(VF), this paper introduces wearable automatic external defibrillators based on embedded system which includes EGG measurements, bioelectrical impedance measurement, discharge defibrillation module, which can automatic identify VF signal, biphasic exponential waveform defibrillation discharge. After verified by animal tests, the device can realize EGG acquisition and automatic identification. After identifying the ventricular fibrillation signal, it can automatic defibrillate to abort ventricular fibrillation and to realize the cardiac electrical cardioversion.

A porcine model for acute ischaemic right ventricular dysfunction.

PubMed

Haraldsen, Pernille; Lindstedt, Sandra; Metzsch, Carsten; Algotsson, Lars; Ingemansson, Richard

2014-01-01

To establish an experimental model for acute ischaemic isolated right ventricular dysfunction and the subsequent haemodynamic changes. An open-chest porcine model with ischaemic dysfunction of the right ventricle induced by ligation of the three main branches supporting the right ventricular free wall. Invasive monitoring of mean arterial blood pressure (MAP), central venous pressure (CVP), left atrial pressure (LAP) and right ventricular pressure (RVP); ultrasonic measurement of cardiac output (CO) and calculation of haemodynamic parameters such as stroke volume (SV), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and right ventricular stroke work (RVSW) using standard formulae. The ischaemic challenge to the right ventricle resulted in a significant (≥30%) reduction in RVSW associated with an increase (6-25%) in CVP and reduction (8-18%) in pulmonary artery pressure (PAP) despite unchanged PVR, all reflecting the failing right ventricle. There was also a significant drop in CO (14-22%) despite unchanged LAP indicating lessened transpulmonary delivery of left ventricular preload due to the failing right ventricle causing the haemodynamic compromise rather than left ventricular failure. Supraventricular and ventricular arrhythmias occurred in three and two out of seven pigs, respectively-all of which except one were successfully resuscitated with cardioversion and/or defibrillation. This novel open-chest porcine model of induced ischaemia of the right ventricular free wall resulted in significant haemodynamic compromise confirmed using standard haemodynamic measurements making it useful for further research on acute, ischaemic isolated right ventricular failure.

The effects of beta-endorphin: state change modification.

PubMed

Veening, Jan G; Barendregt, Henk P

2015-01-29

Beta-endorphin (β-END) is an opioid neuropeptide which has an important role in the development of hypotheses concerning the non-synaptic or paracrine communication of brain messages. This kind of communication between neurons has been designated volume transmission (VT) to differentiate it clearly from synaptic communication. VT occurs over short as well as long distances via the extracellular space in the brain, as well as via the cerebrospinal fluid (CSF) flowing through the ventricular spaces inside the brain and the arachnoid space surrounding the central nervous system (CNS). To understand how β-END can have specific behavioral effects, we use the notion behavioral state, inspired by the concept of machine state, coming from Turing (Proc London Math Soc, Series 2,42:230-265, 1937). In section 1.4 the sequential organization of male rat behavior is explained showing that an animal is not free to switch into another state at any given moment. Funneling-constraints restrict the number of possible behavioral transitions in specific phases while at other moments in the sequence the transition to other behavioral states is almost completely open. The effects of β-END on behaviors like food intake and sexual behavior, and the mechanisms involved in reward, meditation and pain control are discussed in detail. The effects on the sequential organization of behavior and on state transitions dominate the description of these effects.

Chlamydophila pneumoniae myopericarditis in a child.

PubMed

Suesaowalak, Monnipa; Cheung, Michele M; Tucker, Dawn; Chang, Anthony C; Chu, James; Arrieta, Antonio

2009-04-01

An 11-year-old boy with serologically confirmed Chlamydophila pneumoniae infection presented with clinical, laboratory, and echocardiographic changes consistent with myopericarditis. No reports on C. pneumoniae myopericarditis in children are found in the medical literature. The boy, previously healthy, presented with fever, rash, constitutional symptoms, elevated acute phase reactants, elevated cardiac enzymes, and high brain natriuretic peptide levels. Hemodynamic instabilities, including hypotension and mild hypoxia, were noted. Two-dimensional echocardiographic findings showed mildly depressed left ventricular systolic function and small pericardial effusion. Requiring inotropic support, the boy was treated with azithromycin 10 mg/kg once daily for 7 days and a single dose of intravenous immunoglobulin 2 g/kg. He recovered fully with improved left ventricular systolic function before hospital discharge. An early definitive diagnosis is essential to knowing the etiology of pediatric myocarditis. Specific therapy may play role in the management and prognosis of this disorder.

Dangers of collapsible ventricular drainage systems. Technical note.

PubMed

Kaye, A H; Wallace, D

1982-02-01

Ventricular drainage systems employing a collapsible plastic bag for fluid collection were postulated to cause an increasing back-pressure produced in part by the elasticity of the bag. This postulate was shown to be correct in an experimental situation. There was a logarithmic rise in cerebrospinal fluid pressure as the bag filled. By increasing the size of the bag, the problem was overcome.

Morphological and Behavioral Changes in the Pathogenesis of a Novel Mouse Model of Communicating Hydrocephalus

PubMed Central

McMullen, Allison B.; Baidwan, Gurlal S.; McCarthy, Ken D.

2012-01-01

The Ro1 model of hydrocephalus represents an excellent model for studying the pathogenesis of hydrocephalus due to its complete penetrance and inducibility, enabling the investigation of the earliest cellular and histological changes in hydrocephalus prior to overt pathology. Hematoxylin and eosin staining, immunofluorescence and electron microscopy were used to characterize the histopathological events of hydrocephalus in this model. Additionally, a broad battery of behavioral tests was used to investigate behavioral changes in the Ro1 model of hydrocephalus. The earliest histological changes observed in this model were ventriculomegaly and disorganization of the ependymal lining of the aqueduct of Sylvius, which occurred concomitantly. Ventriculomegaly led to thinning of the ependyma, which was associated with periventricular edema and areas of the ventricular wall void of cilia and microvilli. Ependymal denudation was subsequent to severe ventriculomegaly, suggesting that it is an effect, rather than a cause, of hydrocephalus in the Ro1 model. Additionally, there was no closure of the aqueduct of Sylvius or any blockages within the ventricular system, even with severe ventriculomegaly, suggesting that the Ro1 model represents a model of communicating hydrocephalus. Interestingly, even with severe ventriculomegaly, there were no behavioral changes, suggesting that the brain is able to compensate for the structural changes that occur in the pathogenesis of hydrocephalus if the disorder progresses at a sufficiently slow rate. PMID:22291910

Current Perspectives on Systemic Hypertension in Heart Failure with Preserved Ejection Fraction.

PubMed

Tam, Marty C; Lee, Ran; Cascino, Thomas M; Konerman, Matthew C; Hummel, Scott L

2017-02-01

Heart failure with preserved ejection fraction (HFpEF) is a prevalent but incompletely understood syndrome. Traditional models of HFpEF pathophysiology revolve around systemic HTN and other causes of increased left ventricular afterload leading to left ventricular hypertrophy (LVH) and diastolic dysfunction. However, emerging models attribute the development of HFpEF to systemic proinflammatory changes secondary to common comorbidities which include HTN. Alterations in passive ventricular stiffness, ventricular-arterial coupling, peripheral microvascular function, systolic reserve, and chronotropic response occur. As a result, HFpEF is heterogeneous in nature, making it difficult to prescribe uniform therapies to all patients. Nonetheless, treating systemic HTN remains a cornerstone of HFpEF management. Antihypertensive therapies have been linked to LVH regression and improvement in diastolic dysfunction. However, to date, no therapies have definitive mortality benefit in HFpEF. Non-pharmacologic management for HTN, including dietary modification, exercise, and treating sleep disordered breathing, may provide some morbidity benefit in the HFpEF population. Future research is need to identify effective treatments, perhaps in more specific subgroups, and focus may need to shift from reducing mortality to improving exercise capacity and symptoms. Tailoring antihypertensive therapies to specific phenotypes of HFpEF may be an important component of this strategy.

Slow waves, sharp waves, ripples, and REM in sleeping dragons.

PubMed

Shein-Idelson, Mark; Ondracek, Janie M; Liaw, Hua-Peng; Reiter, Sam; Laurent, Gilles

2016-04-29

Sleep has been described in animals ranging from worms to humans. Yet the electrophysiological characteristics of brain sleep, such as slow-wave (SW) and rapid eye movement (REM) activities, are thought to be restricted to mammals and birds. Recording from the brain of a lizard, the Australian dragon Pogona vitticeps, we identified SW and REM sleep patterns, thus pushing back the probable evolution of these dynamics at least to the emergence of amniotes. The SW and REM sleep patterns that we observed in lizards oscillated continuously for 6 to 10 hours with a period of ~80 seconds. The networks controlling SW-REM antagonism in amniotes may thus originate from a common, ancient oscillator circuit. Lizard SW dynamics closely resemble those observed in rodent hippocampal CA1, yet they originate from a brain area, the dorsal ventricular ridge, that has no obvious hodological similarity with the mammalian hippocampus. Copyright © 2016, American Association for the Advancement of Science.

Structural magnetic resonance imaging in patients with first-episode schizophrenia, psychotic and severe non-psychotic depression and healthy controls. Results of the schizophrenia and affective psychoses (SAP) project.

PubMed

Salokangas, R K R; Cannon, T; Van Erp, T; Ilonen, T; Taiminen, T; Karlsson, H; Lauerma, H; Leinonen, K M; Wallenius, E; Kaljonen, A; Syvälahti, E; Vilkman, H; Alanen, A; Hietala, J

2002-09-01

Structural brain abnormalities are prevalent in patients with schizophrenia and affective disorders. To study how regional brain volumes and their ratios differ between patients with schizophrenia, psychotic depression, severe non-psychotic depression and healthy controls. Magnetic resonance imaging scans of the brain on first-episode patients and on healthy controls. Patients with schizophrenia had a smaller left frontal grey matter volume than the other three groups. Patients with psychotic depression had larger ventricular and posterior sulcal cerebrospinal fluid (CSF) volumes than controls. Patients with depression had larger white matter volumes than the other patients. Left frontal lobe, especially its grey matter volume, seems to be specifically reduced in first-episode schizophrenia. Enlarged cerebral ventricles and sulcal CSF volumes are prevalent in psychotic depression. Preserved or expanded white matter is typical of non-psychotic depression.

Cognitive disorders in children's hydrocephalus.

PubMed

Zielińska, Dorota; Rajtar-Zembaty, Anna; Starowicz-Filip, Anna

Hydrocephalus is defined as an increase of volume of cerebrospinal fluid in the ventricular system of the brain. It develops as a result of cerebrospinal fluid flow disorder due to dysfunctions of absorption or, less frequently, as a result of the increase of its production. Hydrocephalus may lead to various cognitive dysfunctions in children. In order to determine cognitive functioning in children with hydrocephalus, the authors reviewed available literature while investigating this subject. The profile of cognitive disorders in children with hydrocephalus may include a wide spectrum of dysfunctions and the process of neuropsychological assessment may be very demanding. The most frequently described cognitive disorders within children's hydrocephalus include attention, executive, memory, visual, spatial or linguistic dysfunctions, as well as behavioral problems. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Usefulness of N-terminal pro-brain natriuretic Peptide and brain natriuretic peptide to predict cardiovascular outcomes in patients with heart failure and preserved left ventricular ejection fraction.

PubMed

Grewal, Jasmine; McKelvie, Robert S; Persson, Hans; Tait, Peter; Carlsson, Jonas; Swedberg, Karl; Ostergren, Jan; Lonn, Eva

2008-09-15

More than 40% of patients hospitalized with heart failure have preserved left ventricular ejection fraction (HF-PLVEF) and are at high risk for cardiovascular (CV) events. The purpose of this study was to determine the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in predicting CV outcomes in patients with HF-PLVEF. Participants with an ejection fraction >40% in the prospective CHARM Echocardiographic Substudy were included in this analysis. Plasma NT-proBNP levels were measured, and 2 cut-offs were selected prospectively at 300 pg/ml and 600 pg/ml. BNP cut-off was set at 100 pg/ml. Clinical characteristics were recorded, and systolic and diastolic function were evaluated by echocardiography. The primary substudy outcome was the composite of CV mortality, hospitalization for heart failure, and myocardial infarction or stroke. A total of 181 patients were included, and there were 17 primary CV events (9.4%) during a median follow-up time of 524 days. In a model including clinical characteristics, echocardiographic measures, and BNP or NT-proBNP, the composite CV event outcome was best predicted by NT-proBNP >300 pg/ml (hazard ratio 5.8, 95% confidence intervals [CI] 1.3 to 26.4, p = 0.02) and moderate or severe diastolic dysfunction on echocardiography. When NT-proBNP >600 pg/ml was used in the model, it was the sole independent predictor of primary CV events (hazard ratio 8.0, 95% CI 2.6 to 24.8, p = 0.0003) as was BNP >100 pg/ml (hazard ratio 3.1, 95% CI 1.2 to 8.2, p = 0.02) in the BNP model. In conclusion, both elevated NT-proBNP and BNP are strong independent predictors of clinical events in patients with HF-PLVEF.

Biomarker pattern of ARIA-E participants in phase 3 randomized clinical trials with bapineuzumab.

PubMed

Liu, Enchi; Wang, Dai; Sperling, Reisa; Salloway, Stephen; Fox, Nick C; Blennow, Kaj; Scheltens, Philip; Schmidt, Mark E; Streffer, Johannes; Novak, Gerald; Einstein, Steve; Booth, Kevin; Ketter, Nzeera; Brashear, H Robert

2018-03-06

To evaluate whether amyloid-related imaging abnormalities with edema/effusion (ARIA-E) observed in bapineuzumab clinical trials was associated with specific biomarker patterns. Bapineuzumab, an anti-β-amyloid monoclonal antibody, was evaluated in patients with mild to moderate Alzheimer disease. Amyloid PET imaging, CSF biomarkers, or volumetric MRI (vMRI) were assessed. A total of 1,512 participants underwent one or more biomarker assessments; 154 developed incident ARIA-E. No differences were observed at baseline between ARIA-E and non-ARIA-E participants in brain amyloid burden by PET, the majority of vMRI measures, or CSF biomarkers, with the exception of lower baseline CSF Aβ 42 in APOE ε4 noncarrier ARIA-E vs non-ARIA-E groups (bapineuzumab non-ARIA-E p = 0.027; placebo non-ARIA-E p = 0.012). At week 71, bapineuzumab-treated participants with ARIA-E vs non-ARIA-E showed greater reduction in brain amyloid PET, greater reductions in CSF phosphorylated tau (p-tau) (all comparisons p < 0.01), and total tau (t-tau) (all comparisons p < 0.025), and greater hippocampal volume reduction and ventricular enlargement (all p < 0.05). Greater reduction in CSF Aβ 40 concentrations was observed for ARIA-E versus both non-ARIA-E groups (bapineuzumab/placebo non-ARIA-E p = 0.015/0.049). No group differences were observed at week 71 for changes in whole brain volume or CSF Aβ 42 . Baseline biomarkers largely do not predict risk for developing ARIA-E. ARIA-E was associated with significant longitudinal changes in several biomarkers, with larger reductions in amyloid PET and CSF p-tau and t-tau concentrations, and paradoxically greater hippocampal volume reduction and ventricular enlargement, suggesting that ARIA-E in bapineuzumab-treated cases may be related to increased Aβ efflux from the brain and affecting downstream pathogenic processes. © 2018 American Academy of Neurology.

Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.

1984-01-19

To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thalliummore » defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent, and 36 +/- 12 per cent vs. 47 +/- 7 per cent, respectively). The authors conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury.« less

GFAP-immunopositive structures in spiny dogfish, Squalus acanthias, and little skate, Raia erinacea, brains: differences have evolutionary implications.

PubMed

Kálmán, M; Gould, R M

2001-07-01

GFAP expression patterns were compared between the brains of a spiny dogfish (Squalus acanthias) and a little skate (Raia erinacea). After anesthesia, the animals were perfused with paraformaldehyde. Serial vibratome sections were immunostained against GFAP using the avidin-biotin method. Spiny dogfish brain contained mainly uniformly-distributed, radially arranged ependymoglia. From GFAP distribution, the layered organization in both the telencephalon and the tectum were visible. In the cerebellum, the molecular and granular layers displayed conspicuously different glial structures; in the former a Bergmann glia-like population was found. No true astrocytes (i.e., stellate-shaped cells) were found. Radial glial endfeet lined all meningeal surfaces. Radial fibers also seemed to form endfeet and en passant contacts on the vessels. Plexuses of fine perivascular glial fibers also contributed to the perivascular glia. Compared with spiny dogfish brain, GFAP expression in the little skate brain was confined. Radial glia were limited to a few areas, e.g., segments of the ventricular surface of the telencephalon, and the midline of the diencephalon and mesencephalon. Scarce astrocytes occurred in every brain part, but only the optic chiasm, and the junction of the tegmentum and optic tectum contained large numbers of astrocytes. Astrocytes formed the meningeal glia limitans and the perivascular glia. No GFAP-immunopositive Bergmann glia-like structure was found. Astrocytes seen in the little skate were clearly different from the mammalian and avian ones; they had a different process system - extra large forms were frequently seen, and the meningeal and perivascular cells were spread along the surface instead of forming endfeet by processes. The differences between Squalus and Raia astroglia were much like those found between reptiles versus mammals and birds. It suggests independent and parallel glial evolutionary processes in amniotes and chondrichthyans, seemingly correlated with the thickening of the brain wall, and the growing complexity of the brain. There is no strict correlation, however, between the replacement of radial ependymoglia with astrocytes, and the local thickness of the brain wall.

Evaluation of left ventricular performance during supine exercise by transoesophageal M-mode echocardiography in normal subjects.

PubMed Central

Matsumoto, M; Hanrath, P; Kremer, P; Tams, C; Langenstein, B A; Schlüter, M; Weiter, R; Bleifeld, W

1982-01-01

In order to evaluate left ventricular function during dynamic exercise transoesophageal M-mode recordings of the left ventricle were carried out with a newly developed transducer gastroscope system. Twelve healthy subjects performed a graded supine bicycle exercise test. Stable and good quality images of the left ventricle at rest and during exercise at different steps up to a maximum workload of 100 watts were obtained in all patients. Isotonic maximum exercise resulted in a significant increase in fractional shortening of the left ventricle, peak shortening rate, and peak lengthening rate of the left ventricular minor axis. Left ventricular end-diastolic dimension decreased significantly. With increasing workload the pressure rate product increased significantly. It is concluded that transoesophageal M-mode echocardiography is a useful method of evaluating left ventricular performance during dynamic exercise. Images PMID:7082515

Kawasaki syndrome in an adult: endomyocardial histology and ventricular function during acute and recovery phases of illness.

PubMed

Marcella, J J; Ursell, P C; Goldberger, M; Lovejoy, W; Fenoglio, J J; Weiss, M B

1983-08-01

Kawasaki syndrome, an acute systemic inflammatory illness of unknown origin usually affecting children, may develop into a serious illness complicated by coronary artery aneurysms or myocarditis. This report describes an adult with Kawasaki syndrome studied by right ventricular endomyocardial biopsy and cardiac catheterization during the acute and recovery phases of illness. The initial biopsy specimen showed acute myocarditis and was associated with hemodynamic evidence of biventricular dysfunction, a severely depressed left ventricular ejection fraction and global hypokinesia. With time, there was spontaneous and rapid resolution of the inflammatory cell infiltrate with concurrent return to normal myocardial function. Right ventricular endomyocardial biopsy studies early in the course of the cardiac disease associated with Kawasaki syndrome may correlate with ventricular function and may be useful for monitoring immunosuppressive therapy in patients with this syndrome.

38 CFR 4.97 - Schedule of ratings-respiratory system.

Code of Federal Regulations, 2013 CFR

2013-07-01

... pulmonale (right heart failure), or; right ventricular hypertrophy, or; pulmonary hypertension (shown by... hypertension (shown by Echo or cardiac catheterization), or; episode(s) of acute respiratory failure, or...; cor pulmonale (right heart failure), or; right ventricular hypertrophy, or; pulmonary hypertension...

38 CFR 4.97 - Schedule of ratings-respiratory system.

Code of Federal Regulations, 2012 CFR

2012-07-01

... pulmonale (right heart failure), or; right ventricular hypertrophy, or; pulmonary hypertension (shown by... hypertension (shown by Echo or cardiac catheterization), or; episode(s) of acute respiratory failure, or...; cor pulmonale (right heart failure), or; right ventricular hypertrophy, or; pulmonary hypertension...

38 CFR 4.97 - Schedule of ratings-respiratory system.

Code of Federal Regulations, 2011 CFR

2011-07-01

... pulmonale (right heart failure), or; right ventricular hypertrophy, or; pulmonary hypertension (shown by... hypertension (shown by Echo or cardiac catheterization), or; episode(s) of acute respiratory failure, or...; cor pulmonale (right heart failure), or; right ventricular hypertrophy, or; pulmonary hypertension...

38 CFR 4.97 - Schedule of ratings-respiratory system.

Code of Federal Regulations, 2010 CFR

2010-07-01

... pulmonale (right heart failure), or; right ventricular hypertrophy, or; pulmonary hypertension (shown by... hypertension (shown by Echo or cardiac catheterization), or; episode(s) of acute respiratory failure, or...; cor pulmonale (right heart failure), or; right ventricular hypertrophy, or; pulmonary hypertension...

38 CFR 4.97 - Schedule of ratings-respiratory system.

Code of Federal Regulations, 2014 CFR

2014-07-01

... pulmonale (right heart failure), or; right ventricular hypertrophy, or; pulmonary hypertension (shown by... hypertension (shown by Echo or cardiac catheterization), or; episode(s) of acute respiratory failure, or...; cor pulmonale (right heart failure), or; right ventricular hypertrophy, or; pulmonary hypertension...

Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis.

PubMed

Saito, Kanako; Dubreuil, Veronique; Arai, Yoko; Wilsch-Bräuninger, Michaela; Schwudke, Dominik; Saher, Gesine; Miyata, Takaki; Breier, Georg; Thiele, Christoph; Shevchenko, Andrej; Nave, Klaus-Armin; Huttner, Wieland B

2009-05-19

Although sufficient cholesterol supply is known to be crucial for neurons in the developing mammalian brain, the cholesterol requirement of neural stem and progenitor cells in the embryonic central nervous system has not been addressed. Here we have conditionally ablated the activity of squalene synthase (SQS), a key enzyme for endogenous cholesterol production, in the neural stem and progenitor cells of the ventricular zone (VZ) of the embryonic mouse brain. Mutant embryos exhibited a reduced brain size due to the atrophy of the neuronal layers, and died at birth. Analyses of the E11.5-E15.5 dorsal telencephalon and diencephalon revealed that this atrophy was due to massive apoptosis of newborn neurons, implying that this progeny of the SQS-ablated neural stem and progenitor cells was dependent on endogenous cholesterol biosynthesis for survival. Interestingly, the neural stem and progenitor cells of the VZ, the primary target of SQS inactivation, did not undergo significant apoptosis. Instead, vascular endothelial growth factor (VEGF) expression in these cells was strongly upregulated via a hypoxia-inducible factor-1-independent pathway, and angiogenesis in the VZ was increased. Consistent with an increased supply of lipoproteins to these cells, the level of lipid droplets containing triacylglycerides with unsaturated fatty acyl chains was found to be elevated. Our study establishes a direct link between intracellular cholesterol levels, VEGF expression, and angiogenesis. Moreover, our data reveal a hitherto unknown compensatory process by which the neural stem and progenitor cells of the developing mammalian brain evade the detrimental consequences of impaired endogenous cholesterol biosynthesis.

Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis

PubMed Central

Saito, Kanako; Dubreuil, Veronique; Arai, Yoko; Wilsch-Bräuninger, Michaela; Schwudke, Dominik; Saher, Gesine; Miyata, Takaki; Breier, Georg; Thiele, Christoph; Shevchenko, Andrej; Nave, Klaus-Armin; Huttner, Wieland B.

2009-01-01

Although sufficient cholesterol supply is known to be crucial for neurons in the developing mammalian brain, the cholesterol requirement of neural stem and progenitor cells in the embryonic central nervous system has not been addressed. Here we have conditionally ablated the activity of squalene synthase (SQS), a key enzyme for endogenous cholesterol production, in the neural stem and progenitor cells of the ventricular zone (VZ) of the embryonic mouse brain. Mutant embryos exhibited a reduced brain size due to the atrophy of the neuronal layers, and died at birth. Analyses of the E11.5–E15.5 dorsal telencephalon and diencephalon revealed that this atrophy was due to massive apoptosis of newborn neurons, implying that this progeny of the SQS-ablated neural stem and progenitor cells was dependent on endogenous cholesterol biosynthesis for survival. Interestingly, the neural stem and progenitor cells of the VZ, the primary target of SQS inactivation, did not undergo significant apoptosis. Instead, vascular endothelial growth factor (VEGF) expression in these cells was strongly upregulated via a hypoxia-inducible factor-1–independent pathway, and angiogenesis in the VZ was increased. Consistent with an increased supply of lipoproteins to these cells, the level of lipid droplets containing triacylglycerides with unsaturated fatty acyl chains was found to be elevated. Our study establishes a direct link between intracellular cholesterol levels, VEGF expression, and angiogenesis. Moreover, our data reveal a hitherto unknown compensatory process by which the neural stem and progenitor cells of the developing mammalian brain evade the detrimental consequences of impaired endogenous cholesterol biosynthesis. PMID:19416849

Choroid plexus glutathione peroxidases are instrumental in protecting the brain fluid environment from hydroperoxides during postnatal development.

PubMed

Saudrais, Elodie; Strazielle, Nathalie; Ghersi-Egea, Jean-Francois

2018-06-27

Hydrogen peroxide, released at low physiological concentration, is involved in different cell signaling pathways during brain development. When released at supraphysiological concentrations in brain fluids following an inflammatory, hypoxic or toxic stress, it can initiate lipid peroxidation, protein and nucleic acid damage and contribute to long-term neurological impairment associated with perinatal diseases. We found high glutathione peroxidase and glutathione reductase enzymatic activities in both lateral and fourth ventricle choroid plexus tissue isolated from developing rats, in comparison to the cerebral cortex and liver. Consistent with these, a high protein expression of glutathione peroxidases 1 and 4 was observed in choroid plexus epithelial cells, which form the blood-cerebrospinal fluid barrier. Live choroid plexuses isolated from newborn rats were highly efficient in detoxifying H2O2 from mock cerebrospinal fluid, illustrating the capacity of the choroid plexuses to control H2O2 concentration in the ventricular system of the brain. We used a differentiated cellular model of the blood-cerebrospinal fluid barrier coupled to kinetic and inhibition analyses to show that glutathione peroxidases are more potent than catalase to detoxify extracellular H2O2 at concentrations up to 250 µM. The choroidal cells also formed an enzymatic barrier preventing blood-borne hydroperoxides to reach the cerebrospinal fluid. These data point out the choroid plexuses as key structures in the control of hydroperoxide levels in the cerebral fluid environment during development, at a time when the protective glial cell network is still immature. Glutathione peroxidases are the main effectors of this choroidal hydroperoxide inactivation.

Angiotensin-converting enzyme in epithelial and neuroepithelial cells.

PubMed

Defendini, R; Zimmerman, E A; Weare, J A; Alhenc-Gelas, F; Erdös, E G

1983-07-01

Angiotensin-converting enzyme (CE) occurs in three types of cell: endothelial, epithelial, and neuroepithelial. In all three, it appears to be bound to plasma membrane. With antisera to the human enzyme, CE is demonstrated in paraffin sections on the apical surface of epithelial cells in the proximal tubule of the kidney, the mucosa of the small intestine, the syncytial trophoblast of the placenta, and the choroid plexus. Epithelial CE is characteristically found on microvillous surfaces in contact with an effluent, well placed to act on substrate in flux. In the brain, CE occurs in nerve fibers and terminals, mainly mesiobasally and in basal ganglia. Mesiobasal CE coincides with other components of the renin-angiotensin system (RAS) in the choroid/ventricular fluid, the subfornical organ, and the magnocellular neurosecretory system of the hypothalamus. Extrapyramidal CE, however, may not be related to the RAS. In the substantia nigra and the globus pallidus, the enzyme has the same cellular distribution as two putative neuromodulators, substance P and enkephalin, the latter a known substrate of CE.

Distinct roles of neuroepithelial-like and radial glia-like progenitor cells in cerebellar regeneration.

PubMed

Kaslin, Jan; Kroehne, Volker; Ganz, Julia; Hans, Stefan; Brand, Michael

2017-04-15

Zebrafish can regenerate after brain injury, and the regenerative process is driven by resident stem cells. Stem cells are heterogeneous in the vertebrate brain, but the significance of having heterogeneous stem cells in regeneration is not understood. Limited availability of specific stem cells might impair the regeneration of particular cell lineages. We studied regeneration of the adult zebrafish cerebellum, which contains two major stem and progenitor cell types: ventricular zone and neuroepithelial cells. Using conditional lineage tracing we demonstrate that cerebellar regeneration depends on the availability of specific stem cells. Radial glia-like cells are thought to be the predominant stem cell type in homeostasis and after injury. However, we find that radial glia-like cells play a minor role in adult cerebellar neurogenesis and in recovery after injury. Instead, we find that neuroepithelial cells are the predominant stem cell type supporting cerebellar regeneration after injury. Zebrafish are able to regenerate many, but not all, cell types in the cerebellum, which emphasizes the need to understand the contribution of different adult neural stem and progenitor cell subtypes in the vertebrate central nervous system. © 2017. Published by The Company of Biologists Ltd.

Brain natriuretic peptide and right heart dysfunction after heart transplantation.

PubMed

Talha, Samy; Charloux, Anne; Piquard, François; Geny, Bernard

2017-06-01

Heart transplantation (HT) should normalize cardiac endocrine function, but brain natriuretic peptide (BNP) levels remain elevated after HT, even in the absence of left ventricular hemodynamic disturbance or allograft rejection. Right ventricle (RV) abnormalities are common in HT recipients (HTx), as a result of engraftment process, tricuspid insufficiency, and/or repeated inflammation due to iterative endomyocardial biopsies. RV function follow-up is vital for patient management as RV dysfunction is a recognized cause of in-hospital death and is responsible for a worse prognosis. Interestingly, few and controversial data are available concerning the relationship between plasma BNP levels and RV functional impairment in HTx. This suggests that infra-clinical modifications, such as subtle immune system disorders or hypoxic conditions, might influence BNP expression. Nevertheless, due to other altered circulating molecular forms of BNP, a lack of specificity of BNP assays is described in heart failure patients. This phenomenon could exist in HT population and could explain elevated BNP plasmatic levels despite a normal RV function. In clinical practice, intra-individual change in BNP over time, rather than absolute BNP values, might be more helpful in detecting right cardiac dysfunction in HTx. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spontaneous third ventriculostomy 8 years after diagnosis of obstructive hydrocephalus.

PubMed

Öğrenci, Ahmet; Ekşi, Murat Şakir; Koban, Orkun

2016-09-01

Spontaneous ventriculostomy is spontaneous rupture of membranes separating the ventricular system from the subarachnoid space in patients with chronic obstructive hydrocephalus that ends with resolution of symptoms. We present a case of spontaneous third ventriculostomy occurred in a 19-year-old girl 8 years after the initial diagnosis of hydrocephalus. An 11-year-old girl applied to the clinic with intermittent headaches. She was neurologically stable with no visual problems. On her brain MRI, obstructive hydrocephalus was observed. Cerebrospinal fluid diversion procedures were recommended, yet the family denied any interventional procedure. She had routine follow-ups with occasional clinical admissions because of ongoing intermittent headaches. On her last clinical visit, 8 years after the first one, she was in well condition with improvement in her headache in the last 4 months. Her new brain MRI showed an active CSF flow between the basal cistern and the third ventricle. In patients with aqueductal stenosis and without any other mass lesion, wait and see protocol might be conveyed in case of mild symptoms of hydrocephalus. However, there is need for large-scaled studies to make a more comprehensive statement for benign obstructive hydrocephalus cases.

Impact of remote monitoring on the management of arrhythmias in patients with implantable cardioverter-defibrillator.

PubMed

Marcantoni, Lina; Toselli, Tiziano; Urso, Giulia; Pratola, Claudio; Ceconi, Claudio; Bertini, Matteo

2015-11-01

In the last decade, there has been an exponential increase in cardioverter-defibrillator (ICD) implants. Remote monitoring systems, allow daily follow-ups of patients with ICD. To evaluate the impact of remote monitoring on the management of cardiovascular events associated with supraventricular and ventricular arrhythmias during long-term follow-up. A total of 207 patients undergoing ICD implantation/replacement were enrolled: 79 patients received remote monitoring systems and were followed up every 12 months, and 128 patients were followed up conventionally every 6 months. All patients were followed up and monitored for the occurrence of supraventricular and ventricular arrhythmia-related cardiovascular events (ICD shocks and/or hospitalizations). During a median follow-up of 842 days (interquartile range 476-1288 days), 32 (15.5%) patients experienced supraventricular arrhythmia-related events and 51 (24.6%) patients experienced ventricular arrhythmia-related events. Remote monitoring had a significant role in the reduction of supraventricular arrhythmia-related events, but it had no effect on ventricular arrhythmia-related events. In multivariable analysis, remote monitoring remained as an independent protective factor, reducing the risk of supraventricular arrhythmia-related events of 67% [hazard ratio, 0.33; 95% confidence interval (CI), 0.13-0.82; P = 0.017]. Remote monitoring systems improved outcomes in patients with supraventricular arrhythmias by reducing the risk of cardiovascular events, but no benefits were observed in patients with ventricular arrhythmias.

Temporary epicardial cardiac resynchronisation versus conventional right ventricular pacing after cardiac surgery: study protocol for a randomised control trial.

PubMed

Russell, Stuart J; Tan, Christine; O'Keefe, Peter; Ashraf, Saeed; Zaidi, Afzal; Fraser, Alan G; Yousef, Zaheer R

2012-02-20

Heart failure patients with stable angina, acute coronary syndromes and valvular heart disease may benefit from revascularisation and/or valve surgery. However, the mortality rate is increased- 5-30%. Biventricular pacing using temporary epicardial wires after surgery is a potential mechanism to improve cardiac function and clinical endpoints. A multi-centred, prospective, randomised, single-blinded, intervention-control trial of temporary biventricular pacing versus standard pacing. Patients with ischaemic cardiomyopathy, valvular heart disease or both, an ejection fraction ≤ 35% and a conventional indication for cardiac surgery will be recruited from 2 cardiac centres. Baseline investigations will include: an electrocardiogram to confirm sinus rhythm and measure QRS duration; echocardiogram to evaluate left ventricular function and markers of mechanical dyssynchrony; dobutamine echocardiogram for viability and blood tests for renal function and biomarkers of myocardial injury- troponin T and brain naturetic peptide. Blood tests will be repeated at 18, 48 and 72 hours. The principal exclusions will be subjects with permanent atrial arrhythmias, permanent pacemakers, infective endocarditis or end-stage renal disease.After surgery, temporary pacing wires will be attached to the postero-lateral wall of the left ventricle, the right atrium and right ventricle and connected to a triple chamber temporary pacemaker. Subjects will be randomised to receive either temporary biventricular pacing or standard pacing (atrial inhibited pacing or atrial-synchronous right ventricular pacing) for 48 hours.The primary endpoint will be the duration of level 3 care. In brief, this is the requirement for invasive ventilation, multi-organ support or more than one inotrope/vasoconstrictor. Haemodynamic studies will be performed at baseline, 6, 18 and 24 hours after surgery using a pulmonary arterial catheter. Measurements will be taken in the following pacing modes: atrial inhibited; right ventricular only; atrial synchronous-right ventricular; atrial synchronous-left ventricular and biventricular pacing. Optimisation of the atrioventricular and interventricular delay will be performed in the biventricular pacing group at 18 hours. The effect of biventricular pacing on myocardial injury, post operative arrhythmias and renal function will also be quantified. ClinicalTrials.gov: NCT01027299.

Effects of carvedilol on structural and functional outcomes and plasma biomarkers in the mouse transverse aortic constriction heart failure model.

PubMed

Hampton, Caryn; Rosa, Raymond; Szeto, Daphne; Forrest, Gail; Campbell, Barry; Kennan, Richard; Wang, Shubing; Huang, Chin-Hu; Gichuru, Loise; Ping, Xiaoli; Shen, Xiaolan; Small, Kersten; Madwed, Jeffrey; Lynch, Joseph J

2017-01-01

Despite the widespread use of the mouse transverse aortic constriction heart failure model, there are no reports on the characterization of the standard-of-care agent carvedilol in this model. Left ventricular pressure overload was produced in mice by transverse aortic constriction between the innominate and left common carotid arteries. Carvedilol was administered at multiple dose levels (3, 10 and 30 mg/kg/day per os ; yielding end-study mean plasma concentrations of 0.002, 0.015 and 0.044 µM, respectively) in a therapeutic design protocol with treatment initiated after the manifestation of left ventricular remodeling at 3 weeks post transverse aortic constriction and continued for 10 weeks. Carvedilol treatment in transverse aortic constriction mice significantly decreased heart rate and left ventricular dP/dt (max) at all dose levels consistent with β-adrenoceptor blockade. The middle dose of carvedilol significantly decreased left ventricular weight, whereas the higher dose decreased total heart, left and right ventricular weight and wet lung weight compared to untreated transverse aortic constriction mice. The higher dose of carvedilol significantly increased cardiac performance as measured by ejection fraction and fractional shortening and decreased left ventricular end systolic volume consistent with the beneficial effect on cardiac function. End-study plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic constriction control and transverse aortic constriction carvedilol groups. Plasma b rain natriuretic peptide concentrations were elevated significantly in transverse aortic constriction control animals (~150%) compared to shams in association with changes in ejection fraction and heart weight and tended to decrease (~30%, p = 0.10-0.12) with the mid- and high-dose carvedilol treatment. A comparison of carvedilol hemodynamic and structural effects in the mouse transverse aortic constriction model versus clinical use indicates a strong agreement in effect profiles preclinical versus clinical, providing important translational validation for this widely used animal model. The present plasma brain natriuretic peptide biomarker findings support the measurement of plasma natriuretic peptides in the mouse transverse aortic constriction model to extend the translational utility of the model.

Evaluation of wireless stimulation of the endocardium, WiSE, technology for treatment heart failure.

PubMed

Seifert, M; Butter, C

2016-06-01

There are several unsolved limitations in delivering cardiac resynchronization therapy. 30-40% of patients fail to have any clinical benefit after 6 months caused by different reasons. Endocardial stimulation rather than conventional epicardial pacing has been shown to: be more physiologically, improve electrical stimulation of the left ventricular, give less dispersion of repolarisation and result in better resynchronization. The Wireless Cardiac Stimulation in Left Ventricle, WiCS-LV, system provides an option for wireless, left ventricular endocardial pacing triggered from a conventional right ventricular pacing spike from a co-implant. Expert commentary: The feasibility of the WiCS-LV system has been successfully demonstrated in a population of failed cardiac resynchronization patients, either failed implantation procedure of a conventional system, non-responder to conventional therapy or upgrade from pacemaker or defibrillator, where a conventional system was not an option. WiCS-LV is innovative technology with promising safety, performance and preliminary efficacy.

Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart.

PubMed

Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Ardell, Jeffrey L; Armour, J Andrew

2009-01-28

Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.

No Electromagnetic Interference Occurred in a Patient with a HeartMate II Left Ventricular Assist System and a Subcutaneous Implantable Cardioverter-Defibrillator.

PubMed

Raman, Ajay Sundara; Shabari, Farshad Raissi; Kar, Biswajit; Loyalka, Pranav; Hariharan, Ramesh

2016-04-01

The use of subcutaneous implantable cardioverter-defibrillators is a novel option for preventing arrhythmia-mediated cardiac death in patients who are at risk of endovascular-device infection or in whom venous access is difficult. However, the potential for electromagnetic interference between subcutaneous defibrillators and left ventricular assist devices is largely unknown. We report the case of a 24-year-old man in whom we observed no electromagnetic interference between a subcutaneous implanted cardioverter-defibrillator and a HeartMate II Left Ventricular Assist System, at 3 different pump speeds. To our knowledge, this is the first report of such findings in this circumstance.

No Electromagnetic Interference Occurred in a Patient with a HeartMate II Left Ventricular Assist System and a Subcutaneous Implantable Cardioverter-Defibrillator

PubMed Central

Raman, Ajay Sundara; Kar, Biswajit; Loyalka, Pranav; Hariharan, Ramesh

2016-01-01

The use of subcutaneous implantable cardioverter-defibrillators is a novel option for preventing arrhythmia-mediated cardiac death in patients who are at risk of endovascular-device infection or in whom venous access is difficult. However, the potential for electromagnetic interference between subcutaneous defibrillators and left ventricular assist devices is largely unknown. We report the case of a 24-year-old man in whom we observed no electromagnetic interference between a subcutaneous implanted cardioverter-defibrillator and a HeartMate II Left Ventricular Assist System, at 3 different pump speeds. To our knowledge, this is the first report of such findings in this circumstance. PMID:27127441

Patent foramen ovale increases the risk of acute ischemic stroke in patients with acute pulmonary embolism leading to right ventricular dysfunction.

PubMed

Goliszek, Sylwia; Wiśniewska, Małgorzata; Kurnicka, Katarzyna; Lichodziejewska, Barbara; Ciurzyński, Michał; Kostrubiec, Maciej; Gołębiowski, Marek; Babiuch, Marek; Paczynska, Marzanna; Koć, Marcin; Palczewski, Piotr; Wyzgał, Anna; Pruszczyk, Piotr

2014-11-01

Patent foramen ovale (PFO) is an established risk factor for ischemic stroke. Since acute right ventricular dysfunction (RVD) observed in patients with PE can lead to right-to-left inter-atrial shunt via PFO, we hypothesized that PFO is a risk factor for ischemic stroke in PE with significant right ventricular dysfunction. 55 patients (31 F, 24M), median age 49 years (range 19-83 years) with confirmed PE underwent echocardiography for RVD and PFO assessment. High risk acute PE was diagnosed in 3 (5.5%) patients, while 16 (29%) hemodynamically stable with RVD patients formed a group with intermediate-risk PE. PFO was diagnosed in 19 patients (34.5%). Diffusion-weighted MRI of the brain for acute ischemic stroke (AIS) was performed in all patients 4.91 ± 4.1 days after admission. AIS was detected by MRI in 4 patients (7.3%). Only one stroke was clinically overt and resulted in hemiplegia. All 4 AIS occurred in the PFO positive group (4 of 19 patients), and none in subjects without PFO (21.0% vs 0%, p=0.02). Moreover, all AIS occurred in patients with RVD and PFO, and none in patients with PFO without RVD (50% vs 0%, p=0.038). Our data suggest that acute pulmonary embolism resulting in right ventricular dysfunction may lead to acute ischemic stroke in patients with patent foramen ovale. However, the clinical significance of such lesions remains to be determined. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

PubMed

Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

2015-10-01

Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

A very rare case of coexistence of ventricular noncompaction cardiomyopathy, myocardial bridging and atherosclerosis

PubMed Central

Akkaya, Mehmet; Bacaksiz, Ahmet; Tasal, Abdurrahman; Sevgili, Emrah

2013-01-01

Noncompaction of the ventricular myocardium is a rare congenital heart disease, presumably caused by the intrauterine arrest of the myocardial compaction process at the beginning of fetal development. It could remain asymptomatic or manifest with congestive heart failure, arrhythmias, and systemic thromboemboli. Here we report a 55-year-old man who was admitted to hospital with chest pain and dyspnea, whose further evaluation revealed left ventricular noncompaction cardiomyopathy accompanying myocardial bridging and stenosis of the right coronary artery. PMID:24570713

Left ventricular, systemic arterial, and baroreflex responses to ketamine and TEE in chronically instrumented monkeys

NASA Technical Reports Server (NTRS)

Koenig, S. C.; Ludwig, D. A.; Reister, C.; Fanton, J. W.; Ewert, D.; Convertino, V. A.

2001-01-01

Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.

Measurement of left ventricular mass in vivo using gated nuclear magnetic resonance imaging.

PubMed

Florentine, M S; Grosskreutz, C L; Chang, W; Hartnett, J A; Dunn, V D; Ehrhardt, J C; Fleagle, S R; Collins, S M; Marcus, M L; Skorton, D J

1986-07-01

Alterations of left ventricular mass occur in a variety of congenital and acquired heart diseases. In vivo determination of left ventricular mass, using several different techniques, has been previously reported. Problems inherent in some previous methods include the use of ionizing radiation, complicated geometric assumptions and invasive techniques. We tested the ability of gated nuclear magnetic resonance imaging to determine in vivo left ventricular mass in animals. By studying both dogs (n = 9) and cats (n = 2) of various sizes, a broad range of left ventricular mass (7 to 133 g) was examined. With a 0.5 tesla superconducting nuclear magnetic resonance imaging system the left ventricle was imaged in the transaxial plane and multiple adjacent 10 mm thick slices were obtained. Endocardial and epicardial edges were manually traced in each computer-displayed image. The wall area of each image was determined by computer and the areas were summed and multiplied by the slice thickness and the specific gravity of muscle, providing calculated left ventricular mass. Calculated left ventricular mass was compared with actual postmortem left ventricular mass using linear regression analysis. An excellent relation between calculated and actual mass was found (r = 0.95; SEE = 13.1 g; regression equation: magnetic resonance mass = 0.95 X actual mass + 14.8 g). Intraobserver and interobserver reproducibility were also excellent (r = 0.99). Thus, gated nuclear magnetic resonance imaging can accurately determine in vivo left ventricular mass in anesthetized animals.

Levitronix bilateral ventricular assist device, a bridge to recovery in a patient with acute fulminant myocarditis and concomitant cerebellar infarction.

PubMed

Huang, Yi-Fan; Hsu, Po-Shun; Tsai, Chien-Sung; Tsai, Yi-Ting; Lin, Chih-Yuan; Ke, Hong-Yan; Lin, Yi-Chang; Yang, Hsiang-Yu

2018-02-07

We report on the case of a 27-year-old male who presented to our emergency room with chest tightness, dyspnoea and cold sweats. The 12-lead electrocardiogram showed diffuse ventricular tachycardia with wide QRS complexes. Troponin-I level was elevated to 100 ng/ml. The coronary angiogram showed good patency of all three coronary vessels, and acute fulminant myocarditis was suspected. The patient underwent cardiopulmonary resuscitation in the catheter room and high-dose inotropic support was initiated to stabilise his haemodynamic status. After resuscitation, the patient was in a coma and acute stroke was highly suspected. In addition, deteriorating cardiogenic shock with acute renal failure and pulmonary oedema were also detected. Due to haemodynamic compromise despite high-dose inotropic support, a Levitronix ® bilateral ventricular assist device (Bi-VAD) was implanted on an emergency basis for circulatory support. Postoperative brain computed tomography revealed acute left cerebellar infarction. Because the patient had left cerebellar infarction with right hemiplegia, heart transplantation was contraindicated. Eventually, cardiac systolic function recovered well and the patient underwent successful Bi-VAD removal after a total of 18 days on Levitronix ® haemodynamic support. He was weaned from the ventilator two weeks later and was discharged 10 days later.

Efferent projections of the dorsal ventricular ridge and the striatum in the Tegu lizard. Tupinambis nigropunctatus.

PubMed

Voneida, T J; Sligar, C M

1979-07-01

A H3 proline-leucine mixture was injected into the dorsal ventricular ridge (DVR) and striatum of the Tegu lizard in order to determine their efferent projections. The brains were processed according to standard radioautographic technique, and counterstained with cresyl violet. DVR projections were generally restricted to the telencephalon, while striatal projections were limited to diencephalic and mesencephalic structures. Thus the anterior DVR projects ipsilaterally to nuclei sphericus and lateralis amygdalae, striatum (ipsilateral and contralateral) ventromedial nucleus of the hypothalamus, nucleus accumbens, anterior olfactory nucleus, nucleus of the lateral olfactory tract and lateral pallium. Posterior DVR projections enter ipsilateral anterior olfactory nucleus, lateral and interstitial amygdalar nuclei, olfactory tubercle and bulb, nucleus of the lateral olfactory tract and a zone surrounding the ventromedial hypothalamic nucleus. Labeled axons from striatal injections pass caudally in the lateral forebrain bundle to enter (via dorsal peduncle) nuclei dorsomedialis, medialis posterior, entopeduncularis anterior, and a zone surrounding nucleus rotundus. Others join the ventral peduncle of LFB and enter ventromedial nucleus (thalami), while the remaining fibers continue caudally in the ventral peduncle to the mesencephalic prerubral field, central gray, substantia nigra, nucleus intercollicularis, reticular formation and pretectal nucleus posterodorsalis. These results are discussed in relation to the changing notions regarding terminology, classification and functions of dorsl ventricular ridge and striatum.

Intermittent levosimendan infusions in advanced heart failure: favourable effects on left ventricular function, neurohormonal balance, and one-year survival.

PubMed

Malfatto, Gabriella; Della Rosa, Francesco; Villani, Alessandra; Rella, Valeria; Branzi, Giovanna; Facchini, Mario; Parati, Gianfranco

2012-11-01

The role of repeated infusions of Levosimendan (LEVO) in patients with chronic advanced heart failure is still unclear. Thirty-three patients with chronic heart failure presenting clinical deterioration were randomized 2:1 to receive monthly infusions of LEVO (n = 22) or Furosemide (Controls, n = 11). At the first drug's administration, noninvasive hemodynamic evaluation was performed; before and after each infusion, we assessed NYHA class, systolic and diastolic function, functional mitral regurgitation, and brain natriuretic peptide (BNP) levels. Noninvasive hemodynamic in the LEVO group showed vasodilation and decrease in thoracic conductance (index of pulmonary congestion), whereas in Controls, only a reduced thoracic conductance was observed. In the LEVO group, systolic and diastolic function, ventricular volumes, severity of mitral regurgitation, and BNP levels improved over time from baseline and persisted 4 weeks after the last infusion (P < 0.01). In Controls, no change developed over time in cardiac function and BNP levels. In LEVO-treated patients, 1-year mortality tended to be lower than in those treated with Furosemide. In conclusion, serial LEVO infusions in advanced heart failure improved ventricular performance and favorably modulated neurohormonal activation. Multicenter randomized studies are warranted to test the effect of LEVO on long-term outcome.

Electrophysiological correlates of word recognition memory process in patients with ischemic left ventricular dysfunction.

PubMed

Giovannelli, Fabio; Simoni, David; Gavazzi, Gioele; Giganti, Fiorenza; Olivotto, Iacopo; Cincotta, Massimo; Pratesi, Alessandra; Baldasseroni, Samuele; Viggiano, Maria Pia

2016-09-01

The relationship between left ventricular ejection fraction (LVEF) and cognitive performance in patients with coronary artery disease without overt heart failure is still under debate. In this study we combine behavioral measures and event-related potentials (ERPs) to verify whether electrophysiological correlates of recognition memory (old/new effect) are modulated differently as a function of LVEF. Twenty-three male patients (12 without [LVEF>55%] and 11 with [LVEF<40%] left ventricular dysfunction), and a Mini Mental State Examination score >25 were enrolled. ERPs were recorded while participants performed an old/new visual word recognition task. A late positive ERP component between 350 and 550ms was differentially modulated in the two groups: a clear old/new effect (enhanced mean amplitude for old respect to new items) was observed in patients without LVEF dysfunction; whereas patients with overt LVEF dysfunction did not show such effect. In contrast, no significant differences emerged for behavioral performance and neuropsychological evaluations. These data suggest that ERPs may reveal functional brain abnormalities that are not observed at behavioral level. Detecting sub-clinical measures of cognitive decline may contribute to set appropriate treatments and to monitor asymptomatic or mildly symptomatic patients with LVEF dysfunction. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Hydrocephalus as a rare compilation of vertebrobasilar dolichoectasia: A case report and review of the literature

PubMed Central

Ebrahimzadeh, Keveh; Bakhtevari, Mehrdad H.; Shafizad, Misagh; Rezaei, Omidvar

2017-01-01

Background: Vertebrobasilar dolichoectasia (VBD) is a rare disease characterized by significant expansion, elongation, and tortuosity of the vertebrobasilar arteries. Hydrocephalus is a rare compilation of VBD. Case Description: In this study, we report a 68-year-old male presenting with headache, progressive decreased visual acuity, memory loss, imbalance while walking, and episodes of urinary incontinency. The patient was diagnosed with dolichoectasia of basilar artery causing compression of the third ventricular outflow and thus, presenting with hydrocephalus documented with brain computed tomography scan and brain magnetic resonance imaging. The patient underwent surgical operation and ventriculoperitoneal shunt placement. Conclusion: In the case of hydrocephalus or normal pressure hydrocephalous, VBD should be considered as a differential diagnosis. PMID:29184707

Diagnostic potential of serum N-terminal pro-B-type brain natriuretic peptide level in detection of cardiac wall stress in women with polycystic ovary syndrome: a cross-sectional comparison study.

PubMed

Celik, Onder; Sahin, Ibrahim; Celik, Nilufer; Hascalik, Seyma; Keskin, Lezzan; Ozcan, Hamdi; Uckan, Ahmet; Kosar, Feridun

2007-11-01

In addition to the negative effect on fertility, polycystic ovary syndrome (PCOS) has been associated with cardiac pathology. Brain natriuretic peptide (BNP) is a possible marker for cardiac risk, therefore we investigated whether N-terminal pro-B-type BNP (NT-proBNP) increases in women with PCOS compared with healthy women of comparable age and body mass index. Thirty women with PCOS and 30 healthy women not suffering from overt cardiac disease were involved in the study. Fasting insulin and serum NT-proBNP levels were measured, and M-Mode echocardiography was performed. Insulin resistance was calculated using the homeostasis model assessment insulin resistance index (HOMA-IR). PCOS subjects had higher NT-proBNP levels than the control subjects (P < 0.001). Abnormal echocardiography indices were detected in 14 of the PCOS subjects (but none of the controls), including valvular heart disease in nine, diastolic dysfunction in two, right ventricular enlargement in one, right atrial enlargement in one and pulmonary hypertension in one. PCOS subjects (n = 30) showed an increased left ventricular mass (LVM) (P < 0.001) and left ventricular posterior wall thickness (LVPWT) (P = 0.006). In addition, NT-proBNP concentration was positively correlated with LVM (r = 0.587, P = 0.001) and negatively correlated with sex-hormone-binding globulin (r = -0.528, P = 0.003). There was a positive correlation between LVM and HOMA-IR (r = 0.295, P = 0.03) while LVPWT was positively correlated with fasting insulin and HOMA-IR (r = 0.335, P = 0.031 and r = 0.346, P = 0.045, respectively) in PCOS subjects (n = 30). The present study demonstrated that the level of NT-proBNP was increased in PCOS subjects with asymptomatic heart disease.

Aortic valve bypass surgery in severe aortic valve stenosis: Insights from cardiac and brain magnetic resonance imaging.

PubMed

Mantini, Cesare; Caulo, Massimo; Marinelli, Daniele; Chiacchiaretta, Piero; Tartaro, Armando; Cotroneo, Antonio Raffaele; Di Giammarco, Gabriele

2018-04-13

To investigate and describe the distribution of aortic and cerebral blood flow (CBF) in patients with severe valvular aortic stenosis (AS) before and after aortic valve bypass (AVB) surgery. We enrolled 10 consecutive patients who underwent AVB surgery for severe AS. Cardiovascular magnetic resonance imaging (CMR) and brain magnetic resonance imaging were performed as baseline before surgery and twice after surgery. Quantitative flow measurements were obtained using 1.5-T magnetic resonance imaging (MRI) scanner phase-contrast images of the ascending aorta, descending thoracic aorta (3 cm proximally and distally from the conduit-to-aorta anastomosis), and ventricular outflow portion of the conduit. The evaluation of CBF was performed using 3.0-T MRI scanner arterial spin labeling (ASL) through sequences acquired at the gray matter, dorsal default-mode network, and sensorimotor levels. Conduit flow, expressed as the percentage of total antegrade flow through the conduit, was 63.5 ± 8% and 67.8 ± 7% on early and mid-term postoperative CMR, respectively (P < .05). Retrograde perfusion from the level of the conduit insertion in the descending thoracic aorta toward the aortic arch accounted for 6.9% of total cardiac output and 11% of total conduit flow. We did not observe any significant reduction in left ventricular stroke volume at postoperative evaluation compared with preoperative evaluation (P = .435). No differences were observed between preoperative and postoperative CBF at the gray matter, dorsal default-mode network, and sensorimotor levels (P = .394). After AVB surgery in patients with severe AS, cardiac output is split between the native left ventricular outflow tract and the apico-aortic bypass, with two-thirds of the total antegrade flow passing through the latter and one-third passing through the former. In our experience, CBF assessment confirms that the flow redistribution does not jeopardize cerebral blood supply. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study.

PubMed

Gidding, Samuel S; Bacha, Fida; Bjornstad, Petter; Levitt Katz, Lorraine E; Levitsky, Lynne L; Lynch, Jane; Tryggestad, Jeanie B; Weinstock, Ruth S; El Ghormli, Laure; Lima, Joao A C

2018-01-01

To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function. TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 treatments including 521 participants with type 2 diabetes, aged 10-17 years, and with 2-6 years of follow-up. Participants were 36% male, obese, and ethnically diverse. Annual serum concentrations of brain natriuretic peptide, troponin, tumor necrosis factor (TNF)-α, receptors 1 and 2 were related to blood pressure, body mass index, hemoglobin A1c, and left ventricular ejection fraction, diastolic function, relative wall thickness, and mass. Elevated concentrations of brain natriuretic peptide (≥100 pg/mL), TNF-α (≥5.6 pg/mL) and troponin (≥0.01 ng/mL), were present in 17.8%, 18.3%, and 34.2% of the cohort, respectively, at baseline, and in 15.4%, 17.1%, and 31.1% at the end of the study, with wide variability over time, without persistence in individuals or clear relationship to glycemia or cardiovascular structure/function. TNF receptors concentrations were increased at baseline and not significantly different from end-of-study concentrations. Adverse echocardiographic measures were more likely in the highest TNF receptor tertile (all P < .05): higher left ventricular mass (39.3 ± 9.0 g/m 2.7 ), left atrial internal dimension (3.7 ± 0.4 cm) and E/Em ratio, a measure of diastolic dysfunction (6.2 ± 1.9). After adjustment for body mass index, these relationships were no longer significant. Elevated serum concentrations of cardiac biomarkers were common in youth with type 2 diabetes, but their clinical significance is unclear and will require further long-term study. ClinicalTrials.govNCT00081328. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone.

PubMed

Rushing, Gabrielle; Ihrie, Rebecca A

2016-08-01

The origin and classification of neural stem cells (NSCs) has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate. This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone (V-SVZ). A literature search was conducted using Pubmed including the keywords "ventricular-subventricular zone," "neural stem cell," "heterogeneity," "identity" and/or "single cell" to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche(s). This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including flow cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type. Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including how these cells may be redirected after injury or genetic manipulation.

Relation between N-terminal pro-brain natriuretic peptide and cardiac remodeling and function assessed by cardiovascular magnetic resonance imaging in patients with arrhythmogenic right ventricular cardiomyopathy.

PubMed

Cheng, Huaibing; Lu, Minjie; Hou, Cuihong; Chen, Xuhua; Wang, Jing; Yin, Gang; Chu, Jianmin; Zhang, Shu; Prasad, Sanjay K; Pu, Jielin; Zhao, Shihua

2015-02-01

Although N-terminal pro-brain natriuretic peptide (NT-proBNP) is a useful screening test of impaired right ventricular (RV) function in conditions affecting the right-sided cardiac muscle, the role of NT-proBNP remains unclear in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study was designed to clarify the relation between the plasma NT-proBNP level and the RV function evaluated by cardiovascular magnetic resonance (CMR) imaging. We selected 56 patients with confirmed ARVC only when their blood specimens for NT-proBNP measurements were collected within 48 hours of a CMR scan. The NT-proBNP level was significantly higher in patients with RV dysfunction than in patients without RV dysfunction (median of 655.3 [interquartile range 556.4 to 870.0] vs 347.0 [interquartile range 308.0 to 456.2] pmol/L, p <0.001). The NT-proBNP levels were positively correlated with RV end-diastolic and end-systolic volume indices (r = 0.49 and 0.70, respectively) and negatively correlated with RV ejection fraction (r = -0.76, all p <0.001), which remained significant after adjustment for age, gender, and body mass index. The area under the receiver-operating characteristic curve for NT-proBNP was 0.91 (95% confidence interval 0.80 to 0.97, p <0.001). The cut-off value of NT-proBNP (458 pmol/L) was associated with sensitivity, specificity, and positive and negative predictive values of 91%, 89%, 67%, and 98%, respectively. In conclusion, NT-proBNP is a useful marker for the detection of RV dysfunction and associated with extent of RV dilatation and dysfunction determined by CMR in patients with ARVC. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

PubMed

Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E

2015-07-01

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A conformal, bio-interfaced class of silicon electronics for mapping cardiac electrophysiology.

PubMed

Viventi, Jonathan; Kim, Dae-Hyeong; Moss, Joshua D; Kim, Yun-Soung; Blanco, Justin A; Annetta, Nicholas; Hicks, Andrew; Xiao, Jianliang; Huang, Younggang; Callans, David J; Rogers, John A; Litt, Brian

2010-03-24

In all current implantable medical devices such as pacemakers, deep brain stimulators, and epilepsy treatment devices, each electrode is independently connected to separate control systems. The ability of these devices to sample and stimulate tissues is hindered by this configuration and by the rigid, planar nature of the electronics and the electrode-tissue interfaces. Here, we report the development of a class of mechanically flexible silicon electronics for multiplexed measurement of signals in an intimate, conformal integrated mode on the dynamic, three-dimensional surfaces of soft tissues in the human body. We demonstrate this technology in sensor systems composed of 2016 silicon nanomembrane transistors configured to record electrical activity directly from the curved, wet surface of a beating porcine heart in vivo. The devices sample with simultaneous submillimeter and submillisecond resolution through 288 amplified and multiplexed channels. We use this system to map the spread of spontaneous and paced ventricular depolarization in real time, at high resolution, on the epicardial surface in a porcine animal model. This demonstration is one example of many possible uses of this technology in minimally invasive medical devices.

Use of a Minimally Invasive Retractor System for Retrieval of Intracranial Fragments in Wartime Trauma.

PubMed

Rymarczuk, George N; Davidson, Laurence; Severson, Meryl A; Armonda, Rocco A

2015-10-01

Wartime penetrating brain injury can result in deep-seated parenchymal and intraventicular shrapnel, bullets, and bone. Large fragments pose a risk of secondary injury from migration, infection, and metal toxicity. It has been recommended that aggressive removal of fragments be avoided. The goal of this study is to report our technique of minimally invasive removal of select deep-seated fragments using a tubular retractor system. A retrospective review of our database of service members presenting with penetrating traumatic brain injuries incurred during Operations Iraqi Freedom and Enduring Freedom and treated at the Walter Reed Army Medical Center and the National Naval Medical Center was performed. Six individuals were identified in which the Vycor ViewSite retractor system (Vycor Medical, Boca Raton, Florida, USA) was used to remove a ventricular or deep intraparenchymal fragment. All patients were male and ranged in age from 21 to 29 years. Fragment location included the foramen of Monro; the atrium of the right lateral ventricle; parasagittally within the right occipital lobe; the occipital horn of the right lateral ventricle; the deep white matter of the dominant temporal lobe; and within the posterior right temporal lobe deep to the junction of the transverse and sigmoid dural venous sinuses. Fragments included in-driven bone, shrapnel from improvised explosive devices, and bullets. In all cases the fragment was successfully removed. No patient had worsening of their neurologic condition following surgery. Deep parenchymal and intraventricular fragments can be safely removed using a tubular retractor system. Published by Elsevier Inc.

Side effects of cocaine abuse: multiorgan toxicity and pathological consequences.

PubMed

Riezzo, I; Fiore, C; De Carlo, D; Pascale, N; Neri, M; Turillazzi, E; Fineschi, V

2012-01-01

Cocaine is a powerful stimulant of the sympathetic nervous system by inhibiting catecholamine reuptake, stimulating central sympathetic outflow, and increasing the sensitivity of adrenergic nerve endings to norepinephrine (NE). It is known, from numerous studies, that cocaine causes irreversible structural changes on the brain, heart, lung and other organs such as liver and kidney and there are many mechanisms involved in the genesis of these damages. Some effects are determined by the overstimulation of the adrenergic system. Most of the direct toxic effects are mediated by oxidative stress and by mitochondrial dysfunction produced during the metabolism of noradrenaline or during the metabolism of norcocaina, as in cocaine-induced hepathotoxicity. Cocaine is responsible for the coronary arteries vasoconstriction, atherosclerotic phenomena and thrombus formation. In this way, cocaine favors the myocardial infarction. While the arrhythmogenic effect of cocaine is mediated by the action on potassium channel (blocking), calcium channels (enhances the function) and inhibiting the flow of sodium during depolarization. Moreover chronic cocaine use is associated with myocarditis, ventricular hypertrophy, dilated cardiomyopathy and heart failure. A variety of respiratory problems temporally associated with crack inhalation have been reported. Cocaine may cause changes in the respiratory tract as a result of its pharmacologic effects exerted either locally or systemically, its method of administration (smoking, sniffing, injecting), or its alteration of central nervous system neuroregulation of pulmonary function. Renal failure resulting from cocaine abuse has been also well documented. A lot of studies demonstrated a high incidence of congenital cardiovascular and brain malformations in offspring born to mothers with a history of cocaine abuse.

Brain natriuretic peptide is not predictive of dilated cardiomyopathy in Becker and Duchenne muscular dystrophy patients and carriers.

PubMed

Schade van Westrum, Steven; Dekker, Lukas; de Haan, Rob; Endert, Erik; Ginjaar, Ieke; de Visser, Marianne; van der Kooi, Anneke

2013-07-16

Cardiomyopathy is reported in Duchenne and Becker muscle dystrophy patients and female carriers. Brain Natriuretic peptide (BNP) is a hormone produced mainly by ventricular cardiomyocytes and its production is up regulated in reaction to increased wall stretching. N-terminal-proBNP (NT-proBNP) has been shown to be a robust laboratory parameter to diagnose and monitor cardiac failure, and it may be helpful to screen for asymptomatic left ventricular dysfunction. Therefore we tested whether NT-proBNP can distinguish patients with Duchenne or Becker muscular dystrophy patients and carriers of a dystrophin mutation with a dilated cardiomyopathy from those without. In a cohort of Duchenne and Becker muscle dystrophy patients (n = 143) and carriers (n = 219) NT-proBNP was measured, and echocardiography was performed to diagnose dilated cardiomyopathy (DCM). In total sixty-one patients (17%) fulfilled the criteria for DCM, whereas 283 patients (78%) had an elevated NT-pro BNP. The sensitivity of NT-proBNP for DCM in patients or carriers was 85%, the specificity 23%, area under the ROC-curve = 0.56. In the specified subgroups there was also no association. Measurement of NT-pro BNP in patients suffering from Duchenne or Becker muscular dystrophy and carriers does not distinguish between those with and without dilated cardiomyopathy.

Post-hemorrhagic hydrocephalus: Recent advances and new therapeutic insights.

PubMed

Chen, Qianwei; Feng, Zhou; Tan, Qiang; Guo, Jing; Tang, Jun; Tan, Liang; Feng, Hua; Chen, Zhi

2017-04-15

Post-hemorrhagic hydrocephalus (PHH), also referred to as progressive ventricular dilatation, is caused by disturbances in cerebrospinal fluid (CSF) flow or absorption following hemorrhage in the brain. As one of the most serious complications of neonatal/adult intraventricular hemorrhage (IVH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI), PHH is associated with increased morbidity and disability of these events. Common sequelae of PHH include neurocognitive impairment, motor dysfunction, and growth impairment. Non-surgical measures to reduce increased intracranial pressure (ICP) in PHH have shown little success and most patients will ultimately require surgical management, such as external ventricular drainage and shunting which mostly by inserting a CSF drainage shunt. Unfortunately, shunt complications are common and the optimum time for intervention is unclear. To date, there remains no comprehensive strategy for PHH management and it becomes imperative that to explore new therapeutic targets and methods for PHH. Over past decades, increasing evidence have indicated that hemorrhage-derived blood and subsequent metabolic products may play a key role in the development of IVH-, SAH- and TBI-associated PHH. Several intervention strategies have recently been evaluated and cross-referenced. In this review, we summarized and discussed the common aspects of hydrocephalus following IVH, SAH and TBI, relevant experimental animal models, clinical translation of in vivo experiments, and potential preventive and therapeutic targets for PHH. Copyright © 2017 Elsevier B.V. All rights reserved.

The pathophysiology of heart failure.

PubMed

Kemp, Clinton D; Conte, John V

2012-01-01

Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

Left Ventricular Function in Patients with Pulmonary Arterial Hypertension: The Role of Two-Dimensional Speckle Tracking Strain.

PubMed

de Amorim Corrêa, Ricardo; de Oliveira, Fernanda Brito; Barbosa, Marcia M; Barbosa, Jose Augusto A; Carvalho, Taís Soares; Barreto, Michele Campos; Campos, Frederico Thadeu A F; Nunes, Maria Carmo Pereira

2016-09-01

Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary arterial pressure with abnormal right ventricular (RV) pressure overload that may alter left ventricular (LV) function. The aim of this study was to assess the impact of RV pressure overload on LV function in PAH patients using two-dimensional (2D) speckle tracking strain. The study enrolled 37 group 1 PAH patients and 38 age- and gender-matched healthy controls. LV longitudinal and radial 2D strains were measured with and without including the ventricular septum. Six-minute walk test (6MWT) and brain natriuretic peptide (BNP) levels were also obtained in patients with PAH. The mean age of patients was 46.4 ± 14.8 years, 76% women, and 16 patients (43%) had schistosomiasis. Sixteen patients (43%) were in WHO class III or IV under specific treatment for PAH. The overall 6MWT distance was 441 meters, and the BNP levels were 80 pg/mL. Patients with PAH more commonly presented with LV diastolic dysfunction and impairment of RV function when compared to controls. LV global longitudinal and radial strains were lower in patients than in controls (-17.9 ± 2.8 vs. -20.5 ± 1.9; P < 0.001 and 30.8 ± 10.5 vs. 49.8 ± 15.4; P < 0.001, respectively). After excluding septal values, LV longitudinal and radial strains remained lower in patients than in controls. The independent factors associated with global LV longitudinal strain were LV ejection fraction, RV fractional area change, and tricuspid annular systolic motion. This study showed impaired LV contractility in patients with PAH assessed by speckle tracking strain, irrespective of ventricular septal involvement. Global LV longitudinal strain was associated independently with RV fractional area change and tricuspid annular systolic motion, after adjustment for LV ejection fraction. © 2016, Wiley Periodicals, Inc.

Development of a patch type embedded cardiac function monitoring system using dual microprocessor for arrhythmia detection in heart disease patient.

PubMed

Jang, Yongwon; Noh, Hyung Wook; Lee, I B; Jung, Ji-Wook; Song, Yoonseon; Lee, Sooyeul; Kim, Seunghwan

2012-01-01

A patch type embedded cardiac function monitoring system was developed to detect arrhythmias such as PVC (Premature Ventricular Contraction), pause, ventricular fibrillation, and tachy/bradycardia. The overall system is composed of a main module including a dual processor and a Bluetooth telecommunication module. The dual microprocessor strategy minimizes power consumption and size, and guarantees the resources of embedded software programs. The developed software was verified with standard DB, and showed good performance.

Transient prehypertensive treatment in spontaneously hypertensive rats: a comparison of losartan and amlodipine regarding long-term blood pressure, cardiac and renal protection.

PubMed

Peng, Feng; Lin, Jinxiu; Lin, Liming; Tang, Hong

2012-12-01

The aim of this study was to compare the effectiveness of transient prehypertensive treatment with losartan compared with amlodipine in spontaneously hypertensive rats (SHRs) on long-term blood pressure (BP), cardiac and renal protection. SHRs were prehypertensively treated with losartan, amlodipine or saline. Rats were followed up until 46 weeks of age. The left ventricular (LV) geometry and function were assessed by echocardiography. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassay. Ang II type 1 (AT1R) and type 2 (AT2R) receptor protein expression was determined by western blotting. The systolic blood pressure (SBP) in losartan-treated SHRs (SHR-Los) was persistently reduced until 46 weeks of age, but returned to untreated SHR levels in amlodipine-treated SHRs (SHR-Aml) from 30 weeks onwards. Compared to untreated SHRs, the albuminuria excretion in SHR-Los at week 46 was markedly decreased, the plasma, myocardium and renal tissue Ang II and Aldo levels in SHR-Los at week 46 were markedly decreased; AT1R and TGF-β1 protein expression was downregulated and AT2R protein was upregulated. Compared to untreated SHRs, the left ventricular mass index (LVMI) and collagen volume fraction (CVF) in SHR-Los were markedly decreased until week 46, and the left ventricular ejection fraction (LVEF) and cardiac brain natriuretic peptide mRNA expression were improved, whereas similar LVMI and elevated CVF were observed in SHR-Aml, and the LVEF decreased significantly below that of untreated SHRs at week 46, with cardiac BNP mRNA expression increasing slightly. Prehypertensive treatment with losartan was more effective than amlodipine on delaying long-term BP increase and ameliorating cardiac, renal structure and function, which may be related to the permanent attenuation of the circulating and local renin-angiotensin systems.

Lung function and left ventricular hypertrophy in morbidly obese candidates for bariatric surgery

PubMed Central

Müller, Paulo de Tarso; Domingos, Hamilton; Patusco, Luiz Armando Pereira; Rapello, Gabriel Victor Guimarães

2015-01-01

Objective: To look for correlations between lung function and cardiac dimension variables in morbidly obese patients, in order to test the hypothesis that the relative size of the small airways is independently correlated with left ventricular hypertrophy. Methods: This was a retrospective study involving 192 medical records containing a clinical protocol employed in candidates for bariatric surgery between January of 2006 and December of 2010. Results: Of the 192 patients evaluated, 39 (10 males and 29 females) met the inclusion criteria. The mean BMI of the patients was 49.2 ± 7.6 kg/m2, and the mean age was 35.5 ± 7.7 years. The FEF25-75/FVC, % correlated significantly with left ventricular posterior wall thickness and relative left ventricular posterior wall thickness, those correlations remaining statistically significant (r = −0.355 and r = −0.349, respectively) after adjustment for weight, gender, and history of systemic arterial hypertension. Stepwise multivariate linear regression analysis showed that FVC and FEV1 were the major determinants of left ventricular mass (in grams or indexed to body surface area). Conclusions: A reduction in the relative size of the small airways appears to be independently correlated with obesity-related cardiac hypertrophy, regardless of factors affecting respiratory mechanics (BMI and weight), gender, or history of systemic arterial hypertension. However, FEV1 and FVC might be important predictors of left ventricular mass in morbidly obese individuals. PMID:26578134

Regional TNFα mapping in the brain reveals the striatum as a neuroinflammatory target after ventricular fibrillation cardiac arrest in rats.

PubMed

Janata, Andreas; Magnet, Ingrid A M; Uray, Thomas; Stezoski, Jason P; Janesko-Feldman, Keri; Tisherman, Samuel A; Kochanek, Patrick M; Drabek, Tomas

2014-05-01

Cardiac arrest (CA) triggers neuroinflammation that could play a role in a delayed neuronal death. In our previously established rat model of ventricular fibrillation (VF) CA characterized by extensive neuronal death, we tested the hypothesis that individual brain regions have specific neuroinflammatory responses, as reflected by regional brain tissue levels of tumor necrosis factor (TNF)α and other cytokines. In a prospective study, rats were randomized to 6min (CA6), 8min (CA8) or 10min (CA10) of VF CA, or sham group. Cortex, striatum, hippocampus and cerebellum were evaluated for TNFα and interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 and interferon gamma at 3h, 6h or 14 d after CA by ELISA and Luminex. Immunohistochemistry was used to determine the cell source of TNFα. CA resulted in a selective TNFα response with significant regional and temporal differences. At 3h after CA, TNFα-levels increased in all regions depending on the duration of the insult. The most pronounced increase was observed in striatum that showed 20-fold increase in CA10 vs. sham, and 3-fold increase vs. CA6 or CA8 group, respectively (p<0.01). TNFα levels in striatum decreased between 3h and 6h, but increased in other regions between 3h and 14 d. TNFα levels remained twofold higher in CA6 vs. shams across brain regions at 14 d (p<0.01). In contrast to pronounced TNFα response, other cytokines showed only a minimal increase in CA6 and CA8 groups vs. sham in all brain regions with the exception that IL-1β increased twofold in cerebellum and striatum (p<0.01). TNFα colocalized with neurons. In conclusion, CA produced a duration-dependent acute TNFα response, with dramatic increase in the striatum where TNFα colocalized with neurons. Increased TNFα levels persist for at least two weeks. This TNFα surge contrasts the lack of an acute increase in other cytokines in brain after CA. Given that striatum is a selectively vulnerable brain region, our data suggest possible role of neuronal TNFα in striatum after CA and identify therapeutic targets for future experiments. This study was approved by the University of Pittsburgh IACUC 1002340A-3. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A hemodynamics model to study the collective behavior of the ventricular-arterial system

NASA Astrophysics Data System (ADS)

Lin Wang, Yuh-Ying; Wang, Wei-Kung

2013-01-01

Applying principles from complex systems to study the efficacy of integrative therapies has become a new interest in medical research. We aimed to construct a concise model for the ventricular-arterial (VA) system and to provide a systematic method for exploring its overall behavior. The transportation of blood from the heart to the peripheral arterioles via hydraulic pressure forces was described by a multi-rank model. Parts of the VA system that have strong mutual interactions were combined into a single sub system. Sub systems of four different ranks were characterized. We then applied the multi-rank model to analyze the aortic pressure wave generated by the periodic ventricular blood ejection, the renal pressure in response to the input from the VA system, and the blood flowing from the renal artery to its arterioles. Maintaining the pressure distribution along the main arteries and in all of the organs with the lowest possible ventricular input turned out to be the first principle for the operation of an efficient VA system. By this principle, we pointed out the benefit of some arterial structures in mammals, derived specific regulation rules and deduced some fundamental concepts for healing. The justification of the biomechanics in our model that differed greatly from those in the prevailing models was given. We concluded that the oscillatory motion and the pressure pulse of the arterial system can be analyzed as steady states with resonance behaviors and suggested utilizing this model to construct integrative therapies for diseases correlated with abnormality in blood circulation.

Neuroinflammation Induced by Intracerebroventricular Injection of Microbial Neuraminidase

PubMed Central

Granados-Durán, Pablo; López-Ávalos, María D.; Grondona, Jesús M.; Gómez-Roldán, María del Carmen; Cifuentes, Manuel; Pérez-Martín, Margarita; Alvarez, Martina; Rodríguez de Fonseca, Fernando; Fernández-Llebrez, Pedro

2015-01-01

In the present paper, we describe the facts that took place in the rat brain after a single injection of the enzyme neuraminidase from Clostridium perfringens into the right lateral ventricle. After injection, it diffused through the cerebrospinal fluid of the ipsilateral ventricle and the third ventricle, and about 400 μm into the periventricular brain parenchyma. The expression of ICAM1 in the endothelial cells of the periventricular vessels, IBA1 in microglia, and GFAP in astrocytes notably increased in the regions reached by the injected neuraminidase. The subependymal microglia and the ventricular macrophages begun to express IL1β and some appeared to cross the ependymal layer. After about 4 h of the injection, leukocytes migrated from large venules of the affected choroid plexus, the meninges and the local subependyma, and infiltrated the brain. The invading cells arrived orderly: first neutrophils, then macrophage-monocytes, and last CD8α-positive T-lymphocytes and B-lymphocytes. Leukocytes in the ventricles and the perivascular zones penetrated the brain parenchyma passing through the ependyma and the glia limitans. Thus, it is likely that a great part of the damage produced by microorganism invading the brain may be due to their neuraminidase content. PMID:25853134

Neuroinflammation induced by intracerebroventricular injection of microbial neuraminidase.

PubMed

Granados-Durán, Pablo; López-Ávalos, María D; Grondona, Jesús M; Gómez-Roldán, María Del Carmen; Cifuentes, Manuel; Pérez-Martín, Margarita; Alvarez, Martina; Rodríguez de Fonseca, Fernando; Fernández-Llebrez, Pedro

2015-01-01

In the present paper, we describe the facts that took place in the rat brain after a single injection of the enzyme neuraminidase from Clostridium perfringens into the right lateral ventricle. After injection, it diffused through the cerebrospinal fluid of the ipsilateral ventricle and the third ventricle, and about 400 μm into the periventricular brain parenchyma. The expression of ICAM1 in the endothelial cells of the periventricular vessels, IBA1 in microglia, and GFAP in astrocytes notably increased in the regions reached by the injected neuraminidase. The subependymal microglia and the ventricular macrophages begun to express IL1β and some appeared to cross the ependymal layer. After about 4 h of the injection, leukocytes migrated from large venules of the affected choroid plexus, the meninges and the local subependyma, and infiltrated the brain. The invading cells arrived orderly: first neutrophils, then macrophage-monocytes, and last CD8α-positive T-lymphocytes and B-lymphocytes. Leukocytes in the ventricles and the perivascular zones penetrated the brain parenchyma passing through the ependyma and the glia limitans. Thus, it is likely that a great part of the damage produced by microorganism invading the brain may be due to their neuraminidase content.

Brain structure characteristics in intellectually superior schizophrenia.

PubMed

Vaskinn, Anja; Hartberg, Cecilie B; Sundet, Kjetil; Westlye, Lars T; Andreassen, Ole A; Melle, Ingrid; Agartz, Ingrid

2015-04-30

The current study aims to fill a gap in the knowledge base by investigating the structural brain characteristics of individuals with schizophrenia and superior intellectual abilities. Subcortical volumes, cortical thickness and cortical surface area were examined in intellectually normal and intellectually superior participants with schizophrenia and their IQ-matched healthy controls, as well as in intellectually low schizophrenia participants. We replicated significant diagnostic group effects on hippocampal and ventricular size after correction for multiple comparisons. There were no statistically significant effects of intellectual level or of the interaction between diagnostic group and intellectual level. Effect sizes indicated that differences between schizophrenia and healthy control participants were of similar magnitude at both intellectual levels for all three types of morphological data. A secondary analysis within the schizophrenia group, including participants with low intellectual abilities, yielded numerical, but no statistically significant differences on any structural brain measure. The present findings indicate that the brain structure abnormalities in schizophrenia are present at all intellectual levels, and individuals with schizophrenia and superior intellectual abilities have brain structure abnormalities of the same magnitude as individuals with schizophrenia and normal intellectual abilities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Atherosclerosis in epilepsy: its causes and implications.

PubMed

Hamed, Sherifa A

2014-12-01

Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and β-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

Hybrid model analysis of intra-aortic balloon pump performance as a function of ventricular and circulatory parameters.

PubMed

Ferrari, Gianfranco; Khir, Ashraf W; Fresiello, Libera; Di Molfetta, Arianna; Kozarski, Maciej

2011-09-01

We investigated the effects of the intra-aortic balloon pump (IABP) on endocardial viability ratio (EVR), cardiac output (CO), end-systolic (V(es)) and end-diastolic (V(ed)) ventricular volumes, total coronary blood flow (TCBF), and ventricular energetics (external work [EW], pressure-volume area [PVA]) under different ventricular (E(max) and diastolic stiffness) and circulatory (arterial compliance) parameters. We derived a hybrid model from a computational model, which is based on merging computational and hydraulic submodels. The lumped parameter computational submodel consists of left and right hearts and systemic, pulmonary, and coronary circulations. The hydraulic submodel includes part of the systemic arterial circulation, essentially a silicone rubber tube representing the aorta, which contains a 40-mL IAB. EVR, CO, V(es), and V(ed), TCBF and ventricular energetics (EW, PVA) were analyzed against the ranges of left ventricular E(max) (0.3-0.5-1 mm Hg/cm(3)) and diastolic stiffness V(stiffness) (≈0.08 and ≈0.3 mm Hg/cm(3), obtained by changing diastolic stiffness constant) and systemic arterial compliance (1.8-2.5 cm(3)/mm Hg). All experiments were performed comparing the selected variables before and during IABP assistance. Increasing E(maxl) from 0.5 to 2 mm Hg/cm(3) resulted in IABP assistance producing lower percentage changes in the selected variables. The changes in ventricular diastolic stiffness strongly influence both absolute value of EVR and its variations during IABP (71 and 65% for lower and higher arterial compliance, respectively). V(ed) and V(es) changes are rather small but higher for lower E(max) and higher V(stiffness). Lower E(max) and higher V(stiffness) resulted in higher TCBF and CO during IABP assistance (∼35 and 10%, respectively). The use of this hybrid model allows for testing real devices in realistic, stable, and repeatable circulatory conditions. Specifically, the presented results show that IABP performance is dependent, at least in part, on left ventricular filling, ejection characteristics, and arterial compliance. It is possible in this way to simulate patient-specific conditions and predict the IABP performance at different values of the circulatory or ventricular parameters. Further work is required to study the conditions for heart recovery modeling, baroreceptor controls, and physiological feedbacks. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Determination of Serotonin and Dopamine Metabolites in Human Brain Microdialysis and Cerebrospinal Fluid Samples by UPLC-MS/MS: Discovery of Intact Glucuronide and Sulfate Conjugates

PubMed Central

Suominen, Tina; Uutela, Päivi; Ketola, Raimo A.; Bergquist, Jonas; Hillered, Lars; Finel, Moshe; Zhang, Hongbo; Laakso, Aki; Kostiainen, Risto

2013-01-01

An UPLC-MS/MS method was developed for the determination of serotonin (5-HT), dopamine (DA), their phase I metabolites 5-HIAA, DOPAC and HVA, and their sulfate and glucuronide conjugates in human brain microdialysis samples obtained from two patients with acute brain injuries, ventricular cerebrospinal fluid (CSF) samples obtained from four patients with obstructive hydrocephalus, and a lumbar CSF sample pooled mainly from patients undergoing spinal anesthesia in preparation for orthopedic surgery. The method was validated by determining the limits of detection and quantification, linearity, repeatability and specificity. The direct method enabled the analysis of the intact phase II metabolites of 5-HT and DA, without hydrolysis of the conjugates. The method also enabled the analysis of the regioisomers of the conjugates, and several intact glucuronide and sulfate conjugates were identified and quantified for the first time in the human brain microdialysis and CSF samples. We were able to show the presence of 5-HIAA sulfate, and that dopamine-3-O-sulfate predominates over dopamine-4-O-sulfate in the human brain. The quantitative results suggest that sulfonation is a more important phase II metabolism pathway than glucuronidation in the human brain. PMID:23826355

Is there evidence for neurodegenerative change following traumatic brain injury in children and youth? A scoping review.

PubMed

Keightley, Michelle L; Sinopoli, Katia J; Davis, Karen D; Mikulis, David J; Wennberg, Richard; Tartaglia, Maria C; Chen, Jen-Kai; Tator, Charles H

2014-01-01

While generalized cerebral atrophy and neurodegenerative change following traumatic brain injury (TBI) is well recognized in adults, it remains comparatively understudied in the pediatric population, suggesting that research should address the potential for neurodegenerative change in children and youth following TBI. This focused review examines original research findings documenting evidence for neurodegenerative change following TBI of all severities in children and youth. Our relevant inclusion and exclusion criteria identified a total of 16 articles for review. Taken together, the studies reviewed suggest there is evidence for long-term neurodegenerative change following TBI in children and youth. In particular both cross-sectional and longitudinal studies revealed volume loss in selected brain regions including the hippocampus, amygdala, globus pallidus, thalamus, periventricular white matter, cerebellum, and brain stem as well as overall decreased whole brain volume and increased CSF and ventricular space. Diffusion Tensor Imaging (DTI) studies also report evidence for decreased cellular integrity, particularly in the corpus callosum. Sensitivity of the hippocampus and deep limbic structures in pediatric populations are similar to findings in the adult literature and we consider the data supporting these changes as well as the need to investigate the possibility of neurodegenerative onset in childhood associated with mild traumatic brain injury (mTBI).

Dynamical relations for left ventricular ejection - Flow rate, momentum, force and impulse

NASA Technical Reports Server (NTRS)

Back, L. H.; Selzer, R. H.; Gordon, D. G.; Ledbetter, D. C.; Crawford, D. W.

1984-01-01

An investigation was carried out to quantitatively evaluate left ventricular volume flow rate, momentum, force and impulse derived from application of conservation principles for mass and momentum of blood within the ventricle during the ejection phase. An automated digital image processing system was developed and applied to left ventricular angiograms which are computer processed and analyzed frame by frame to determine the dynamical relations by numerical methods. The initial experience with force and impulse has indicated that neither quantity seemed to be a sensitive indicator of coronary artery disease as evaluated by qualitative angiography for the particular patient group studied. Utilization of the dynamical relations in evaluating human left ventricular performance requires improved means of measurement and interpretation of clinical studies.

Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium

PubMed Central

Hoover, Donald B.; Shepherd, Angela V.; Southerland, E. Marie; Armour, J. Andrew; Ardell, Jeffrey L.

2008-01-01

While much is known about the influence of ventricular afferent neurons on cardiovascular function in the dog, identification of the neurochemicals transmitting cardiac afferent signals to central neurons is lacking. Accordingly, we identified ventricular afferent neurons in canine dorsal root ganglia (DRG) and nodose ganglia by retrograde labeling after injecting horseradish peroxidase (HRP) into the anterior right and left ventricles. Primary antibodies from three host species were used in immunohistochemical experiments to simultaneously evaluate afferent somata for the presence of HRP and markers for two neurotransmitters. Only a small percentage (2%) of afferent somata were labeled with HRP. About half of the HRP-identified ventricular afferent neurons in T3 DRG also stained for substance P (SP), calcitonin gene-related peptide (CGRP), or neuronal nitric oxide synthase (nNOS), either alone or with two markers colocalized. Ventricular afferent neurons and the general population of T3 DRG neurons showed the same labeling profiles; CGRP (alone or colocalized with SP) being the most common (30–40% of ventricular afferent somata in T3 DRG). About 30% of the ventricular afferent neurons in T2 DRG displayed CGRP immunoreactivity and binding of the putative nociceptive marker IB4. Ventricular afferent neurons of the nodose ganglia were distinct from those in the DRG by having smaller size and lacking immunoreactivity for SP, CGRP, and nNOS. These findings suggest that ventricular sensory information is transferred to the central nervous system by relatively small populations of vagal and spinal afferent neurons and that spinal afferents use a variety of neurotransmitters. PMID:18558516

Change of heart dimensions and function during pregnancy in goats.

PubMed

Szaluś-Jordanow, Olga; Czopowicz, Michał; Witkowski, Lucjan; Moroz, Agata; Mickiewicz, Marcin; Frymus, Tadeusz; Markowska-Daniel, Iwona; Bagnicka, Emilia; Kaba, Jarosław

2018-03-08

The study aimed to evaluate the effect of pregnancy on heart diameters and function in goats. Transthoracic echocardiography of 12 female dairy goats of two Polish regional breeds was performed. A Mindray M7 diagnostic ultrasound system with Phased Array transducer was used. Simultaneously, electrocardiography was recorded. All animals were examined four times - at mating season, at the end of the first trimester, at the end of the second trimester and just before kidding. Eleven measurements were taken each time: aortic and left atrial diameter (AoD and LAD), right and left ventricular internal diameter in diastole (RVIDd and LVIDd), left ventricular internal diameter in systole (LVIDs), inter-ventricular septum thickness in diastole and systole (IVSd and IVSd) and left ventricular posterior wall in diastole and systole (LVPWd and LVPWs), maximum left and right ventricular outflow tract velocity (RVOT Vmax and LVOT Vmax). Nine consecutive measurements were derived: the ratio of the left atrial diameter to the aortic diameter (AoD/LAD), left ventricular fractional shortening (FS%), left ventricular ejection fraction (EF%), maximum outflow tract pressure gradients (RVOT PGmax and LVOT PGmax), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV), stroke volume (SV) and cardiac output (CO). HR, LAD, LVPWs, IVSs increased significantly in the first trimester. AoD and RVIDd were significantly higher around parturition. LVIDd, FS%, EF%, SV and CO rose both in the first and third trimester. No measurement decreased during pregnancy. The study confirms that pregnancy causes changes in the heart size and functioning. Copyright © 2018. Published by Elsevier Ltd.

Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium.

PubMed

Hoover, Donald B; Shepherd, Angela V; Southerland, E Marie; Armour, J Andrew; Ardell, Jeffrey L

2008-08-18

While much is known about the influence of ventricular afferent neurons on cardiovascular function in the dog, identification of the neurochemicals transmitting cardiac afferent signals to central neurons is lacking. Accordingly, we identified ventricular afferent neurons in canine dorsal root ganglia (DRG) and nodose ganglia by retrograde labeling after injecting horseradish peroxidase (HRP) into the anterior right and left ventricles. Primary antibodies from three host species were used in immunohistochemical experiments to simultaneously evaluate afferent somata for the presence of HRP and markers for two neurotransmitters. Only a small percentage (2%) of afferent somata were labeled with HRP. About half of the HRP-identified ventricular afferent neurons in T(3) DRG also stained for substance P (SP), calcitonin gene-related peptide (CGRP), or neuronal nitric oxide synthase (nNOS), either alone or with two markers colocalized. Ventricular afferent neurons and the general population of T(3) DRG neurons showed the same labeling profiles; CGRP (alone or colocalized with SP) being the most common (30-40% of ventricular afferent somata in T(3) DRG). About 30% of the ventricular afferent neurons in T(2) DRG displayed CGRP immunoreactivity and binding of the putative nociceptive marker IB(4). Ventricular afferent neurons of the nodose ganglia were distinct from those in the DRG by having smaller size and lacking immunoreactivity for SP, CGRP, and nNOS. These findings suggest that ventricular sensory information is transferred to the central nervous system by relatively small populations of vagal and spinal afferent neurons and that spinal afferents use a variety of neurotransmitters.

Right Ventricular Failure Post LVAD Implantation Corrected with Biventricular Support: An In Vitro Model.

PubMed

Shehab, Sajad; Allida, Sabine M; Davidson, Patricia M; Newton, Phillip J; Robson, Desiree; Jansz, Paul C; Hayward, Christopher S

Right ventricular failure after left ventricular assist device (LVAD) implantation is associated with high mortality. Management remains limited to pharmacologic therapy and temporary mechanical support. Delayed right ventricular assist device (RVAD) support after LVAD implantation is associated with poorer outcomes. With the advent of miniaturized, durable, continuous flow ventricular assist device systems, chronic RVAD and biventricular assist device (BiVAD) support has been used with some success. The purpose of this study was to assess combined BiVAD and LVAD with delayed RVAD support within a four-elemental mock circulatory loop (MCL) simulating the human cardiovascular system. Our hypothesis was that delayed continuous flow RVAD (RVAD) would produce similar hemodynamic and flow parameters to those of initial BiVAD support. Using the MCL, baseline biventricular heart failure with elevated right and left filling pressures with low cardiac output was simulated. The addition of LVAD within a biventricular configuration improved cardiac output somewhat, but was associated with persistent right heart failure with elevated right-sided filling pressures. The addition of an RVAD significantly improved LVAD outputs and returned filling pressures to normal throughout the circulation. In conclusion, RVAD support successfully restored hemodynamics and flow parameters of biventricular failure supported with isolated LVAD with persistent elevated right atrial pressure.

Neurodevelopmental origin and adult neurogenesis of the neuroendocrine hypothalamus

PubMed Central

Maggi, Roberto; Zasso, Jacopo; Conti, Luciano

2015-01-01

The adult hypothalamus regulates many physiological functions and homeostatic loops, including growth, feeding and reproduction. In mammals, the hypothalamus derives from the ventral diencephalon where two distinct ventricular proliferative zones have been described. Although a set of transcription factors regulating the hypothalamic development has been identified, the exact molecular mechanisms that drive the differentiation of hypothalamic neural precursor cells (NPCs) toward specific neuroendocrine neuronal subtypes is yet not fully disclosed. Neurogenesis has been also reported in the adult hypothalamus at the level of specific niches located in the ventrolateral region of ventricle wall, where NPCs have been identified as radial glia-like tanycytes. Here we review the molecular and cellular systems proposed to support the neurogenic potential of developing and adult hypothalamic NPCs. We also report new insights on the mechanisms by which adult hypothalamic neurogenesis modulates key functions of this brain region. Finally, we discuss how environmental factors may modulate the adult hypothalamic neurogenic cascade. PMID:25610370

Radiological Characterization of Cerebral Phenotype in Newborn Microcephaly Cases from 2015 Outbreak in Brazil

PubMed Central

Ramalho Rocha, Yuri Raoni; Cavalcanti Costa, José Ricardo; Almeida Costa, Pericles; Maia, Gessica; Vasconcelos, Rafael de Medeiros; Ramos Tejo, Cynthia; Martins Batista, Rafaella; Lima Neto, Manoel; Martins de Lima, Gustavo Graco; Negromonte, Francisco; Borba, Marcelle; Bezerra Jeronimo, Selma Maria; Sequerra, Eduardo Bouth; Moreira Neto, Manuel

2016-01-01

Introduction: Brazil is facing, since October of 2015, an outbreak of microcephalic fetuses. This outbreak is correlated with the beginning of circulation of Zika virus (ZIKV) in the country. Although it is clear that the size of the head is diminished in these fetuses, the brain phenotype associated with these malformations is unknown. Methods: We collected computed tomography images of the microcephaly cases from the region of Natal, Rio Grande do Norte, from September 2015 to February 2016. Findings: The microcephalies derived from the current outbreak are associated with intracerebral calcifications, malformation of the ventricular system, migratory disorders in the telencephalon and, in a lower frequency, malformation of the cerebellum and brainstem. Discussion: The characteristics described herein are not usually found in other types of microcephaly. We suggest that this work can be used as a guideline to identify microcephaly cases associated to the current outbreak. PMID:27617166

Mechanisms of decreased left ventricular preload during continuous positive pressure ventilation in ARDS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhainaut, J.F.; Devaux, J.Y.; Monsallier, J.F.

1986-07-01

Continuous positive pressure ventilation is associated with a reduction in left ventricular preload and cardiac output, but the mechanisms responsible are controversial. The decrease in left ventricular preload may result exclusively from a decreased systemic venous return due to increased pleural pressure, or from an additional effect such as decreased left ventricular compliance. To determine the mechanisms responsible, we studied the changes in cardiac output induced by continuous positive pressure ventilation in eight patients with the adult respiratory distress syndrome. We measured cardiac output by thermodilution, and biventricular ejection fraction by equilibrium gated blood pool scintigraphy. Biventricular end-diastolic volumes weremore » then calculated by dividing stroke volume by ejection fraction. As positive end-expiratory pressure increased from 0 to 20 cm H/sub 2/O, stroke volume and biventricular end-diastolic volumes fell about 25 percent, and biventricular ejection fraction remained unchanged. At 20 cm H/sub 2/O positive end-expiratory pressure, volume expansion for normalizing cardiac output restored biventricular end-diastolic volumes without markedly changing biventricular end-diastolic transmural pressures. The primary cause of the reduction in left ventricular preload with continuous positive pressure ventilation appears to be a fall in venous return and hence in right ventricular stroke volume, without evidence of change in left ventricular diastolic compliance.« less

Development of an implantable ventricular assist system.

PubMed

Macris, M P; Parnis, S M; Frazier, O H; Fuqua, J M; Jarvik, R K

1997-02-01

This study describes the present state of progress in the development of the Jarvik 2000 ventricular assist system. Designed for implantation in the human thorax, the system consists of a small (25 cm3, 90 g) intraventricular axial-flow blood pump that transmits power and data via internal electronics and a transcutaneous energy transfer system. The pump is powered by portable internal and external polymer lithium ion batteries. The only moving part, the pump rotor, contains a permanent magnet of a brushless direct-current motor that mounts an axial-flow impeller and partial magnetic thrust support, with blood-immersed radial and thrust bearings. The motor uses a redundant coil and electric lead design, which permits continued operation in case of wire breakage. Seven calves have been supported for an average of 107 days (range, 40 to 162 days) with prototypes of the Jarvik 2000 ventricular assist system. No physiologic complications have occurred. When its user is at rest, the pump produces flows of 5 to 6 L/min with a decreased arterial pulse contour. Renal and hepatic functions have remained normal throughout the duration of all studies. Mean plasma free hemoglobin levels ranged from 4.3 to 11.4 mg/dL (mean, 6.3 mg/dL) for each study. Pathologic analyses of the heart and kidneys revealed no damage related to the device. These studies indicate that the Jarvik 2000 ventricular assist system is feasible in animals and holds promise for long-term support of patients.

Three-dimensional visual guidance improves the accuracy of calculating right ventricular volume with two-dimensional echocardiography

NASA Technical Reports Server (NTRS)

Dorosz, Jennifer L.; Bolson, Edward L.; Waiss, Mary S.; Sheehan, Florence H.

2003-01-01

Three-dimensional guidance programs have been shown to increase the reproducibility of 2-dimensional (2D) left ventricular volume calculations, but these systems have not been tested in 2D measurements of the right ventricle. Using magnetic fields to identify the probe location, we developed a new 3-dimensional guidance system that displays the line of intersection, the plane of intersection, and the numeric angle of intersection between the current image plane and previously saved scout views. When used by both an experienced and an inexperienced sonographer, this guidance system increases the accuracy of the 2D right ventricular volume measurements using a monoplane pyramidal model. Furthermore, a reconstruction of the right ventricle, with a computed volume similar to the calculated 2D volume, can be displayed quickly by tracing a few anatomic structures on 2D scans.

Brain Structural Effects of Psychopharmacological Treatment in Bipolar Disorder

PubMed Central

McDonald, Colm

2015-01-01

Bipolar disorder is associated with subtle neuroanatomical deficits including lateral ventricular enlargement, grey matter deficits incorporating limbic system structures, and distributed white matter pathophysiology. Substantial heterogeneity has been identified by structural neuroimaging studies to date and differential psychotropic medication use is potentially a substantial contributor to this. This selective review of structural neuroimaging and diffusion tensor imaging studies considers evidence that lithium, mood stabilisers, antipsychotic medication and antidepressant medications are associated with neuroanatomical variation. Most studies are negative and suffer from methodological weaknesses in terms of directly assessing medication effects on neuroanatomy, since they commonly comprise posthoc assessments of medication associations with neuroimaging metrics in small heterogenous patient groups. However the studies which report positive findings tend to form a relatively consistent picture whereby lithium and antiepileptic mood stabiliser use is associated with increased regional grey matter volume, especially in limbic structures. These findings are further supported by the more methodologically robust studies which include large numbers of patients or repeated intra-individual scanning in longitudinal designs. Some similar findings of an apparently ameliorative effect of lithium on white matter microstructure are also emerging. There is less support for an effect of antipsychotic or antidepressant medication on brain structure in bipolar disorder, but these studies are further limited by methodological difficulties. In general the literature to date supports a normalising effect of lithium and mood stabilisers on brain structure in bipolar disorder, which is consistent with the neuroprotective characteristics of these medications identified by preclinical studies. PMID:26412064

Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation

PubMed Central

Ashton, Jesse L.; Burton, Rebecca A. B.; Bub, Gil; Smaill, Bruce H.; Montgomery, Johanna M.

2018-01-01

Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart. The atria receive rich innervation from the autonomic branch of the peripheral nervous system. Sympathetic neurons are clustered in stellate and cervical ganglia alongside the spinal cord and extend fibers to the heart directly innervating the myocardium. These neurons are major drivers of hyperactive sympathetic activity observed in heart disease, ventricular arrhythmias, and sudden cardiac death. Both pre- and postsynaptic changes have been observed to occur at synapses formed by sympathetic ganglion neurons, suggesting that plasticity at sympathetic neuro-cardiac synapses is a major contributor to arrhythmias. Less is known about the plasticity in parasympathetic neurons located in clusters on the heart surface. These neuronal clusters, termed ganglionated plexi, or “little brains,” can independently modulate neural control of the heart and stimulation that enhances their excitability can induce arrhythmia such as atrial fibrillation. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by ganglionated plexi neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation. PMID:29615932

Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lins, Brittney R.; Pushie, Jake M.; Jones, Michael

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K +, Cl -, and Ca + distributions unreliable. In the present study, we directly examined themore » distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl - and Fe while K + levels increase further from the ventricle as Cl - levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl - surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. Furthermore, this study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models.« less

Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging

PubMed Central

Lins, Brittney R.; Pushie, Jake M.; Jones, Michael; Howard, Daryl L.; Howland, John G.; Hackett, Mark J.

2016-01-01

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K+, Cl−, and Ca+ distributions unreliable. In the present study, we directly examined the distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl− and Fe while K+ levels increase further from the ventricle as Cl− levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl− surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. This study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models. PMID:27351594

Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging

DOE PAGES

Lins, Brittney R.; Pushie, Jake M.; Jones, Michael; ...

2016-06-28

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K +, Cl -, and Ca + distributions unreliable. In the present study, we directly examined themore » distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl - and Fe while K + levels increase further from the ventricle as Cl - levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl - surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. Furthermore, this study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models.« less

Brain Structural Effects of Psychopharmacological Treatment in Bipolar Disorder.

PubMed

McDonald, Colm

2015-01-01

Bipolar disorder is associated with subtle neuroanatomical deficits including lateral ventricular enlargement, grey matter deficits incorporating limbic system structures, and distributed white matter pathophysiology. Substantial heterogeneity has been identified by structural neuroimaging studies to date and differential psychotropic medication use is potentially a substantial contributor to this. This selective review of structural neuroimaging and diffusion tensor imaging studies considers evidence that lithium, mood stabilisers, antipsychotic medication and antidepressant medications are associated with neuroanatomical variation. Most studies are negative and suffer from methodological weaknesses in terms of directly assessing medication effects on neuroanatomy, since they commonly comprise posthoc assessments of medication associations with neuroimaging metrics in small heterogenous patient groups. However the studies which report positive findings tend to form a relatively consistent picture whereby lithium and antiepileptic mood stabiliser use is associated with increased regional grey matter volume, especially in limbic structures. These findings are further supported by the more methodologically robust studies which include large numbers of patients or repeated intra-individual scanning in longitudinal designs. Some similar findings of an apparently ameliorative effect of lithium on white matter microstructure are also emerging. There is less support for an effect of antipsychotic or antidepressant medication on brain structure in bipolar disorder, but these studies are further limited by methodological difficulties. In general the literature to date supports a normalising effect of lithium and mood stabilisers on brain structure in bipolar disorder, which is consistent with the neuroprotective characteristics of these medications identified by preclinical studies.

Myocardial effective transverse relaxation time T2* Correlates with left ventricular wall thickness: A 7.0 T MRI study.

PubMed

Huelnhagen, Till; Hezel, Fabian; Serradas Duarte, Teresa; Pohlmann, Andreas; Oezerdem, Celal; Flemming, Bert; Seeliger, Erdmann; Prothmann, Marcel; Schulz-Menger, Jeanette; Niendorf, Thoralf

2017-06-01

Myocardial effective relaxation time T2* is commonly regarded as a surrogate for myocardial tissue oxygenation. However, it is legitimate to assume that there are multiple factors that influence T2*. To this end, this study investigates the relationship between T2* and cardiac macromorphology given by left ventricular (LV) wall thickness and left ventricular radius, and provides interpretation of the results in the physiological context. High spatio-temporally resolved myocardial CINE T2* mapping was performed in 10 healthy volunteers using a 7.0 Tesla (T) full-body MRI system. Ventricular septal wall thickness, left ventricular inner radius, and T2* were analyzed. Macroscopic magnetic field changes were elucidated using cardiac phase-resolved magnetic field maps. Ventricular septal T2* changes periodically over the cardiac cycle, increasing in systole and decreasing in diastole. Ventricular septal wall thickness and T2* showed a significant positive correlation, whereas the inner LV radius and T2* were negatively correlated. The effect of macroscopic magnetic field gradients on T2* can be considered minor in the ventricular septum. Our findings suggest that myocardial T2* is related to tissue blood volume fraction. Temporally resolved T2* mapping could be beneficial for myocardial tissue characterization and for understanding cardiac (patho)physiology in vivo. Magn Reson Med 77:2381-2389, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals.

PubMed

Zubiaurre-Elorza, Leire; Junque, Carme; Gómez-Gil, Esther; Guillamon, Antonio

2014-05-01

Untreated transsexuals have a brain cortical phenotype. Cross-sex hormone treatments are used to masculinize or feminize the bodies of female-to-male (FtMs) or male-to-female (MtFs) transsexuals, respectively. A longitudinal design was conducted to investigate the effects of treatments on brain cortical thickness (CTh) of FtMs and MtFs. This study investigated 15 female-to-male (FtMs) and 14 male-to-female (MtFs) transsexuals prior and during at least six months of cross-sex hormone therapy treatment. Brain MRI imaging was performed in a 3-Tesla TIM-TRIO Siemens scanner. T1-weighted images were analyzed with FreeSurfer software to obtain CTh as well as subcortical volumetric values. Changes in brain CTh thickness and volumetry associated to changes in hormonal levels due to cross-sex hormone therapy. After testosterone treatment, FtMs showed increases of CTh bilaterally in the postcentral gyrus and unilaterally in the inferior parietal, lingual, pericalcarine, and supramarginal areas of the left hemisphere and the rostral middle frontal and the cuneus region of the right hemisphere. There was a significant positive correlation between the serum testosterone and free testosterone index changes and CTh changes in parieto-temporo-occipital regions. In contrast, MtFs, after estrogens and antiandrogens treatment, showed a general decrease in CTh and subcortical volumetric measures and an increase in the volume of the ventricles. Testosterone therapy increases CTh in FtMs. Thickening in cortical regions is associated to changes in testosterone levels. Estrogens and antiandrogens therapy in MtFs is associated to a decrease in the CTh that consequently induces an enlargement of the ventricular system. © 2014 International Society for Sexual Medicine.

Minimally Invasive Transsulcal Resection of Intraventricular and Periventricular Lesions Through a Tubular Retractor System: Multicentric Experience and Results.

PubMed

Eliyas, Javed Khader; Glynn, Ryan; Kulwin, Charles G; Rovin, Richard; Young, Ronald; Alzate, Juan; Pradilla, Gustavo; Shah, Mitesh V; Kassam, Amin; Ciric, Ivan; Bailes, Julian

2016-06-01

Conventional approaches to deep-seated cerebral lesions range from biopsy to transcortical or transcallosal resection. Although the former does not reduce tumor burden, the latter are more invasive and associated with greater potential for irreparable injury to normal brain. Disconnection syndrome, hemiparesis, hemianesthesia, or aphasia is not uncommon after such surgery, especially when lesion is large. By contrast, the transsulcal parafascicular approach uses naturally existing corridors and a tubular retractor to minimize brain injury. A retrospective review of patients undergoing minimally invasive transsulcal parafascicular resection of ventricular and periventricular lesions, across 5 independent centers, was conducted. Twenty patients with lesions located in the lateral ventricle (n = 9), the third ventricle (n = 6) and periventricular region (n = 4) are described in this report. Average age was 64 years (8 male/12 female). The average depth from cortical surface was 4.37 cm. A 13.5-mm-diameter tubular retractor (BrainPath [NICO Corporation, Indianapolis, Indiana, USA]) of differing lengths was used, aided by neuronavigation. Gross total resection was obtained in 17 patients. Pathologies included colloid cyst, subependymoma, glioma, meningioma, central neurocytoma, lymphoma, and metastasis. Three patients experienced transient morbidity: memory loss (2), hemiparesis (1). One patient died 3 months postoperatively as a result of unrelated pulmonary illness. Follow-up ranged from 6 to 27 months (average, 12 months). This technique is safe and effective for the treatment of intraventricular and periventricular lesions. Surgery-related morbidity is minimal and often transient. Lesions are satisfactorily resected and residuum occurs only when the neoplasm involves vital structures. The tubular retractor minimizes trauma to brain incident in the surgeon's path. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Fragmented QRS complex is a prognostic marker of microvascular reperfusion and changes in LV function occur in patients with ST elevation myocardial infarction who underwent primary percutaneous coronary intervention.

PubMed

Zhang, Ruoxi; Chen, Shuyuan; Zhao, Qi; Sun, Meng; Yu, Bo; Hou, Jingbo

2017-06-01

The present study aimed to investigate the in-hospital and long-term prognostic value of fragmented QRS complex (fQRS) for microvascular reperfusion and changes in left ventricular (LV) function in patients with ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). A total of 216 patients with STEMI undergoing primary PCI were included in the current study. Patients were divided into two groups based on the presence (n=126) or absence (n=90) of fQRS following electrocardiograms (ECGs) on admission. Following primary PCI and follow up, patients were divided into four groups based on new onset, resolution, persistence and absence of fQRS. Major adverse cardiac events were defined to include cardiovascular death, arrhythmia, heart failure, reinfarction and target vessel revascularization. The percentage of patients with heart failure and microvascular reperfusion differed significantly between the fQRS(+) and fQRS(-) groups. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), Peak creatine kinase-MB (CK-MB) and Troponin I levels were observed to be significantly higher in the fQRS(+) group compared with the fQRS(-) group. In univariate logistic regression analysis, left ventricular ejection fraction (LVEF), NT-proBNP, Troponin I, Peak CK-MB and microvascular reperfusion were found to be associated with fQRS. Multivariate analysis identified that LVEF, NT-proBNP, Troponin I and microvascular reperfusion may be independent predictors of fQRS. The presence of fQRS was demonstrated to be associated with left ventricular dysfunction at follow up assessments. The presence of fQRS was not only significantly associated with myocardial microvascular reperfusion and left ventricular function, but was also a prognostic marker in STEMI.

Sex hormones affect outcome in arrhythmogenic right ventricular cardiomyopathy/dysplasia: from a stem cell derived cardiomyocyte-based model to clinical biomarkers of disease outcome.

PubMed

Akdis, Deniz; Saguner, Ardan M; Shah, Khooshbu; Wei, Chuanyu; Medeiros-Domingo, Argelia; von Eckardstein, Arnold; Lüscher, Thomas F; Brunckhorst, Corinna; Chen, H S Vincent; Duru, Firat

2017-05-14

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by fibrofatty infiltration of the myocardium and ventricular arrhythmias that may lead to sudden cardiac death. It has been observed that male patients develop the disease earlier and present with more severe phenotypes as compared to females. Thus, we hypothesized that serum levels of sex hormones may contribute to major arrhythmic cardiovascular events (MACE) in patients with ARVC/D. The serum levels of five sex hormones, sex hormone-binding globulin, high sensitivity troponin T, pro-brain natriuretic peptide, cholesterol, triglycerides, insulin, and glucose were measured in 54 ARVC/D patients (72% male). Twenty-six patients (48%) experienced MACE. Total and free testosterone levels were significantly increased in males with MACE as compared to males with a favourable outcome, whereas estradiol was significantly lower in females with MACE as compared to females with a favourable outcome. Increased testosterone levels remained independently associated with MACE in males after adjusting for age, body mass index, Task Force criteria, ventricular function, and desmosomal mutation status. Furthermore, an induced pluripotent stem cell-derived ARVC/D cardiomyocyte model was used to investigate the effects of sex hormones. In this model, testosterone worsened and estradiol improved ARVC/D-related pathologies such as cardiomyocyte apoptosis and lipogenesis, strongly supporting our clinical findings. Elevated serum testosterone levels in males and decreased estradiol levels in females are independently associated with MACE in ARVC/D, and directly influence disease pathology. Therefore, determining the levels of sex hormones may be useful for risk stratification and may open a new window for preventive interventions. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Idiopathic normal pressure hydrocephalus: theoretical concept of a spinal etiology.

PubMed

Hamlat, Abderrahmane; Abderrahmane, Hamlat; Sid-Ahmed, Seddik; Seddik, Sid-Ahmed; Adn, Mahmoudreza; Mahmoudreza, Adn; Askar, Brahim; Brahim, Askar; Pasqualini, Edouardo; Edouardo, Pasqualini

2006-01-01

Normal pressure hydrocephalus (NPH) is an adult syndrome characterised by a combination of gait disturbance, varying degrees of cognitive decline, urinary incontinence, ventricular enlargement and normal mean intracranial pressure. Since this syndrome was first described, its pathophysiology has been a matter of great debate, although it is now considered that NPH could be divided into two groups: cases with unknown etiology (idiopathic normal pressure hydrocephalus, or INPH) and those which develop from several known causes (such as trauma, meningitis or subarachnoid haemorrhage). The pathophysiology of INPH is still unclear and a matter of debate. In this manuscript, the current pathophysiological conditions of INPH are analysed and the authors put forward the theory that the disease is a dynamic syndrome which occurs in patients who have suffered a significant loss of spinal compliance over time. Consequently, intracranial pressure increases more during systole in INPH patients because it cannot be compensated for by the escape of CSF into the spinal canal as effectively, due to the reduced volume or lack of distension of the spinal canal. This leads to an increase in ventricular size and causes cumulative brain damage over a long period of time and accounts for the slow, progressive nature of NPH. The loss of spinal compliance with age is fundamental to the proposed theory which provides a theoretical justification for studying the spinal canal in INPH and investigating the relationship between the progressive narrowing of the spinal canal and the compensating ability of the craniospinal system.

Hydrocephalus due to multiple ependymal malformations is caused by mutations in the MPDZ gene.

PubMed

Saugier-Veber, Pascale; Marguet, Florent; Lecoquierre, François; Adle-Biassette, Homa; Guimiot, Fabien; Cipriani, Sara; Patrier, Sophie; Brasseur-Daudruy, Marie; Goldenberg, Alice; Layet, Valérie; Capri, Yline; Gérard, Marion; Frébourg, Thierry; Laquerrière, Annie

2017-05-01

Congenital hydrocephalus is considered as either acquired due to haemorrhage, infection or neoplasia or as of developmental nature and is divided into two subgroups, communicating and obstructive. Congenital hydrocephalus is either syndromic or non-syndromic, and in the latter no cause is found in more than half of the patients. In patients with isolated hydrocephalus, L1CAM mutations represent the most common aetiology. More recently, a founder mutation has also been reported in the MPDZ gene in foetuses presenting massive hydrocephalus, but the neuropathology remains unknown. We describe here three novel homozygous null mutations in the MPDZ gene in foetuses whose post-mortem examination has revealed a homogeneous phenotype characterized by multiple ependymal malformations along the aqueduct of Sylvius, the third and fourth ventricles as well as the central canal of the medulla, consisting in multifocal rosettes with immature cell accumulation in the vicinity of ependymal lining early detached from the ventricular zone. MPDZ also named MUPP1 is an essential component of tight junctions which are expressed from early brain development in the choroid plexuses and ependyma. Alterations in the formation of tight junctions within the ependyma very likely account for the lesions observed and highlight for the first time that primary multifocal ependymal malformations of the ventricular system is genetically determined in humans. Therefore, MPDZ sequencing should be performed when neuropathological examination reveals multifocal ependymal rosette formation within the aqueduct of Sylvius, of the third and fourth ventricles and of the central canal of the medulla.

Biochemical changes related to hypoxia during cerebral aneurysm surgery: combined microdialysis and tissue oxygen monitoring: case report.

PubMed

Hutchinson, P J; Al-Rawi, P G; O'Connell, M T; Gupta, A K; Pickard, J D; Kirkpatrick, P J

2000-01-01

The objective of this study was to monitor brain metabolism on-line during aneurysm surgery, by combining the use of a multiparameter (brain tissue oxygen, brain carbon dioxide, pH, and temperature) sensor with microdialysis (extracellular glucose, lactate, pyruvate, and glutamate). The case illustrates the potential value of these techniques by demonstrating the effects of adverse physiological events on brain metabolism and the ability to assist in both intraoperative and postoperative decision-making. A 41-year-old woman presented with a World Federation of Neurological Surgeons Grade I subarachnoid hemorrhage. Angiography revealed a basilar artery aneurysm that was not amenable to coiling, so the aneurysm was clipped. Before the craniotomy was performed, a multiparameter sensor and a microdialysis catheter were inserted to monitor brain metabolism. During the operation, the brain oxygen level decreased, in relation to biochemical changes, including the reduction of extracellular glucose and pyruvate and the elevation of lactate and glutamate. These changes were reversible. However, when the craniotomy was closed, a second decrease in brain oxygen occurred in association with brain swelling, which immediately prompted a postoperative computed tomographic scan. The scan demonstrated acute hydrocephalus, requiring external ventricular drainage. The patient made a full recovery. The monitoring techniques influenced clinical decision-making in the treatment of this patient. On-line measurement of brain tissue gases and extracellular chemistry has the potential to assist in the perioperative and postoperative management of patients undergoing complex cerebrovascular surgery and to establish the effects of intervention on brain homeostasis.

Effects of morphologic left ventricular pressure on right ventricular geometry and tricuspid valve regurgitation in patients with congenitally corrected transposition of the great arteries.

PubMed

Kral Kollars, Catharine A; Gelehrter, Sarah; Bove, Edward L; Ensing, Gregory

2010-03-01

Congenitally corrected transposition of the great arteries (CCTGA) is associated with tricuspid regurgitation (TR), which has been postulated to arise from the effect of ventricular septal position on the attachments of the tricuspid valve. This study was performed to determine the effect of left ventricular (LV) pressure on right ventricular (RV) and LV geometry and the degree of TR. Serial echocardiograms were reviewed from, 30 patients with CCTGA who underwent pulmonary artery banding to train the morphologic left ventricle (n = 14) or left ventricle-to-pulmonary artery conduit placement and ventricular septal defect closure in conjunction with physiologic repair (n = 16). The degree of TR, the LV/RV pressure ratio, RV and LV sphericity indexes, and tricuspid valve tethering distance and coaptation length were analyzed. After pulmonary artery banding, an increase in LV systolic pressure to > or =2/3 systemic resulted in a decrease in TR from severe to moderate (p = 0.02). The percentage of patients with severe TR decreased from 64% to 18% (p = 0.06). The RV sphericity index decreased (p = 0.05), and the LV sphericity index increased (p = 0.02). After left ventricle-to-pulmonary artery conduit placement, a decrease in LV pressure to < or =1/2 systemic resulted in an increase in TR from none to mild (p = 0.003). In conclusion, these data indicate that LV pressure in patients with CCTGA affects the degree of TR and that septal shift caused by changes in LV and RV pressure is an important mechanism. Copyright 2010. Published by Elsevier Inc.

How best to assess right ventricular function by echocardiography*

PubMed Central

DiLorenzo, Michael P.; Bhatt, Shivani M.; Mercer-Rosa, Laura

2016-01-01

Right ventricular function is a crucial determinant of long-term outcomes of children with heart disease. Quantification of right ventricular systolic and diastolic performance by echocardiography is of paramount importance, given the prevalence of children with heart disease, particularly those with involvement of the right heart, such as single or systemic right ventricles, tetralogy of Fallot, and pulmonary arterial hypertension. Identification of poor right ventricular performance can provide an opportunity to intervene. In this review, we will go through the different systolic and diastolic indices, as well as their application in practice. Quantification of right ventricular function is possible and should be routinely performed using a combination of different measures, taking into account each disease state. Quantification is extremely useful for individual patient follow-up. Laboratories should continue to strive to optimise reproducibility through quality improvement and quality assurance efforts in addition to investing in technology and training for new, promising techniques, such as three-dimensional echocardiography. PMID:26675593

The circumventricular organs: an atlas of comparative anatomy and vascularization.

PubMed

Duvernoy, Henri M; Risold, Pierre-Yves

2007-11-01

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.

Axonal Control of the Adult Neural Stem Cell Niche

PubMed Central

Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D.; Tecott, Laurence H.; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

2014-01-01

SUMMARY The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

Peripheral and central interactions between the renin-angiotensin system and the renal sympathetic nerves in control of renal function.

PubMed

DiBona, G F

2001-06-01

Increases in renal sympathetic nerve activity (RSNA) regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. As increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between RSNA and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, that is, the direct (via specific innervation) and indirect (via angiotensin II) contributions of increased RSNA to the regulation of renal function. The effects of increased RSNA on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with angiotensin-converting enzyme inhibitors or angiotensin II-type AT1 receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated following renal denervation. These interactions can also be extrarenal, that is, in the central nervous system, wherein RSNA and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, the permeable blood-brain barrier of which permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II type AT1 receptor antagonists, into the ventricular system or microinjected into the rostral ventrolateral medulla, are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (e.g., congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and RSNA are involved in influencing the neural control of renal function.

Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function.

PubMed

DiBona, G F

2000-12-01

Increases in renal sympathetic nerve activity regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. Because increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between the renal sympathetic nerves and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, for example, the direct (by specific innervation) and indirect (by angiotensin II) contributions of increased renal sympathetic nerve activity to the regulation of renal function. The effects of increased renal sympathetic nerve activity on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with ACE inhibitors or angiotensin II-type AT(1)-receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated after renal denervation. These interactions can also be extrarenal, for example, in the central nervous system, wherein renal sympathetic nerve activity and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, whose permeable blood-brain barrier permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II-type AT(1)-receptor antagonists into the ventricular system or microinjected into the rostral ventrolateral medulla are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (eg, congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and renal sympathetic nerve activity are involved in influencing the neural control of renal function.

Increased CSF aquaporin-4, and interleukin-6 levels in dogs with idiopathic communicating internal hydrocephalus and a decrease after ventriculo-peritoneal shunting.

PubMed

Schmidt, Martin J; Rummel, Christoph; Hauer, Jessica; Kolecka, Malgorzata; Ondreka, Nele; McClure, Vanessa; Roth, Joachim

2016-06-29

Studies in animal models, in which internal hydrocephalus has been induced by obstructing the cerebrospinal fluid pathways, have documented an up-regulation of the concentrations of aquaporin-4 (AQP4) in the brain. In this study, the concentrations of aquaporin-1 (AQP1), AQP1, AQP4 and interleukin-6 (IL-6) were determined in the CSF of dogs with idiopathic communicating hydrocephalus before and after the reduction of intraventricular volume following ventriculo-peritoneal shunt (VP-shunt) treatment. The concentrations of AQP4 and IL-6 were increased in the cerebrospinal fluid of dogs with hydrocephalus compared to controls. Both parameters significantly decreased after surgical treatment, accompanied by decrease of ventricular size and the clinical recovery of the dogs. AQP1 was not detectable in CSF. Brain AQP4 up-regulation might be a compensatory response in dogs with hydrocephalus. Future determination of AQP4 at the mRNA and protein level in brain tissue is warranted to substantiate this hypothesis.

Left ventricular outflow obstruction and necrotizing enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen, H.A.; Haney, P.J.

1984-02-01

Two neonates had unusually rapid development of necrotizing enterocolitis within 24 hours of birth. Both patients had decreased systemic perfusion secondary to aortic atresia. Onset of either clinical or radiographic manifestations of necrotizing enterocolitis in the first day of life should alert one to the possible presence of severe left ventricular outflow obstruction.

Left-to-right shunt reduction with intra-aortic balloon pump in postmyocardial infarction ventricular septal defect.

PubMed

Testuz, Ariane; Roffi, Marco; Bonvini, Robert Francis

2013-03-01

This case aims to describe the hemodynamic effects of intra-aortic balloon pump (IABP) in patients with ventricular septal defect (VSD) complicating myocardial infarction (MI). A 79-year-old man with no previous cardiovascular history presented to the emergency department with subacute inferior myocardial infarction associated with mild signs of systemic hypoperfusion. A transthoracic echocardiography revealed a large akinesia of the left ventricular inferior wall with preserved global left ventricular ejection fraction, as well as a large VSD in the midinferior portion of the interventricular septum. Coronary angiography showed an occlusion of the mid portion of a dominant circumflex coronary artery. The invasive hemodynamic evaluation showed a sizable left-to-right shunt (Q(p)/Q(s) = 3.1). Activation of the IABP led to an immediate reduction of the shunt (Q(p)/Q(s) = 2.4 = 22% reduction), an increase in systemic cardiac output (from 2.1 L/min to 2.4 L/min = +12%) and a decrease in the systemic vascular resistances (from 2240 to 1920 dyne-sec/cm(5) = 15% reduction). In patients with post-MI VSD, placement of IABP leads to an immediate reduction in left-to-right shunt and as a consequence to an increase in systemic cardiac output, which may allow hemodynamic stabilization of the patient prior to surgical VSD closure. Copyright © 2012 Wiley Periodicals, Inc.

Orthostatic effects on echocardiographic measures of ventricular function.

PubMed

Rowland, Thomas; Unnithan, Viswanath; Barker, Piers; Guerra, Miriam; Roche, Denise; Lindley, Martin

2012-05-01

Orthostatic-induced alterations in Doppler echocardiographic measures of ventricular function have not been well-defined. Identifying such changes may provide useful insights regarding the responses of these measures to variations in ventricular loading conditions. Standard assessment of mitral inflow velocity and tissue Doppler imaging (TDI) of left ventricular longitudinal myocardial velocities was performed on 14 young males (mean age 17.9 ± 0.7 years) in the supine position and then 5 minutes after assuming a sitting position with legs dependent. Upon sitting, average values of stroke volume and cardiac output fell by 28% and 18%, respectively, while heart rate increased from 64 ± 10 to 73 ± 12 beats/min (+14%) and calculated systemic vascular resistance rose from 12.9 ± 2.2 to 16.4 ± 3.1 units (+27%). Mitral E peak velocity declined from 87 ± 16 to 64 ± 16 cm/sec, and average TDI-E' and TDI-S both decreased (by -44% and -20%, respectively). When adjusted for orthostatic decreases in left ventricular end-diastolic volume, the mean decrease in TDI-E' was reduced to -29 (P < 0.01), but no significant decline was observed in adjusted TDI-S. Average E/E' rose with sitting by 40% (P = 0.02). These findings suggest that (a) decreases in TDI measures when assuming the upright position reflect the reduction of left ventricular size; (b) orthostatic fall in TDI-E' is also related to smaller ventricular size but, in addition, to a nonspecified reduction in ventricular relaxation; and (c) values of E/E' do not reflect alterations in ventricular preload, which occur during an orthostatic challenge. © 2012, Wiley Periodicals, Inc.

Muscular anatomy of the human ventricular folds.

PubMed

Moon, Jerald; Alipour, Fariborz

2013-09-01

Our purpose in this study was to better understand the muscular anatomy of the ventricular folds in order to help improve biomechanical modeling of phonation and to better understand the role of these muscles during phonatory and nonphonatory tasks. Four human larynges were decalcified, sectioned coronally from posterior to anterior by a CryoJane tape transfer system, and stained with Masson's trichrome. The total and relative areas of muscles observed in each section were calculated and used for characterizing the muscle distribution within the ventricular folds. The ventricular folds contained anteriorly coursing thyroarytenoid and ventricularis muscle fibers that were in the lower half of the ventricular fold posteriorly, and some ventricularis muscle was evident in the upper and lateral portions of the fold more anteriorly. Very little muscle tissue was observed in the medial half of the fold, and the anterior half of the ventricular fold was largely devoid of any muscle tissue. All 4 larynges contained muscle bundles that coursed superiorly and medially through the upper half of the fold, toward the lateral margin of the epiglottis. Although variability of expression was evident, a well-defined thyroarytenoid muscle was readily apparent lateral to the arytenoid cartilage in all specimens.

Effects of NOS inhibition on the cardiopulmonary system and brain microvascular markers after intermittent hypoxia in rats.

PubMed

Barer, G R; Fairlie, J; Slade, J Y; Ahmed, S; Laude, E A; Emery, C J; Thwaites-Bee, D; Oakley, A E; Barer, D H; Kalaria, R N

2006-07-07

We previously demonstrated that rats subjected to intermittent hypoxia (IH) by exposure to 10% O(2) for 4 h daily for 56 days in a normobaric chamber, developed pulmonary hypertension, right ventricular hypertrophy and wall-thickening in pulmonary arterioles, compared with normoxic (N) controls. These changes were greater in rats subjected to continuous hypoxia (CH breathing 10% O(2) for 56 days). Cerebral angiogenesis was demonstrated by immunostaining with glucose transporter 1 (GLUT1) antibody, in viable vessels, in CH and to a lesser degree in IH. In this study, adult Wistar rats were subjected to the same hypoxic regimes and given the nitric oxide synthase (NOS) inhibitor N(6)-nitro-L-arginine methyl ester (L-NAME) in drinking water (NLN, IHLN and CHLN regimes) to induce hypertension. There was significant systemic hypertension in NLN and IHLN rats, compared with N and IH, but surprisingly not in CHLN compared with CH. Hematocrit rose in all hypoxic groups (up to 79% in CHLN). There was no significant pulmonary hypertension in IHLN versus NLN rats, although there was asymmetric wall thickening in pulmonary arterioles. Cerebral GLUT1 immunoreactivity increased with L-NAME, with or without hypoxia, especially in CHLN rats, but conspicuously there was no evidence of angiogenesis in brains of IHLN compared with NLN rats. NOS blockade may attenuate the cerebral and pulmonary vascular changes of IH while augmenting cerebral angiogenesis in continuous hypoxia. However, whether cerebral effects are due to systemic hypertension or changes in cerebral nitric oxide production needs to be evaluated.

Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.

1984-09-01

Myocardial function and perfusion were evaluated in 22 patients with progressive systemic sclerosis with the CREST syndrome using exercise and radionuclide techniques, pulmonary function testing, and chest roentgenography. The results were compared with a similar study of 26 patients with progressive systemic sclerosis with diffuse scleroderma. The prevalence of thallium perfusion abnormalities was similar in the groups with CREST syndrome and diffuse scleroderma, (64 percent versus 77 percent), but the defects were significantly smaller in the CREST syndrome (p less than 0.01). Reperfusion thallium defects in the absence of extramural coronary artery disease were seen in 38 percent of patientsmore » with diffuse scleroderma. This finding was not seen in any of the patients with the CREST syndrome. In diffuse scleroderma, abnormalities of both right and left ventricular function were related to larger thallium perfusion defects. In the CREST syndrome, abnormalities of left ventricular function were minor, were seen only during exercise, and were unrelated to thallium perfusion defects. Abnormal resting right ventricular function was seen in 36 percent of the patients with the CREST syndrome and was associated with an isolated decrease in diffusing capacity of carbon monoxide. It is concluded that the cardiac manifestations of the CREST syndrome are distinct from those found in diffuse scleroderma. Unlike diffuse scleroderma, abnormalities of left ventricular function in the CREST syndrome are minor and are unrelated to abnormalities of coronary perfusion. Right ventricular dysfunction in the CREST syndrome appears to be primarily related to pulmonary vascular disease.« less

Spatial resolution of pace mapping of idiopathic ventricular tachycardia/ectopy originating in the right ventricular outflow tract.

PubMed

Bogun, Frank; Taj, Majid; Ting, Michael; Kim, Hyungjin Myra; Reich, Stephen; Good, Eric; Jongnarangsin, Krit; Chugh, Aman; Pelosi, Frank; Oral, Hakan; Morady, Fred

2008-03-01

Pace mapping has been used to identify the site of origin of focal ventricular arrhythmias. The spatial resolution of pace mapping has not been adequately quantified using currently available three-dimensional mapping systems. The purpose of this study was to determine the spatial resolution of pace mapping in patients with idiopathic ventricular tachycardia or premature ventricular contractions originating in the right ventricular outflow tract. In 16 patients with idiopathic ventricular tachycardia/ectopy from the right ventricular outflow tract, comparisons and classifications of pace maps were performed by two observers (good pace map: match >10/12 leads; inadequate pace map: match < or =10/12 leads) and a customized MATLAB 6.0 program (assessing correlation coefficient and normalized root mean square of the difference (nRMSd) between test and template signals). With an electroanatomic mapping system, the correlation coefficient of each pace map was correlated with the distance between the pacing site and the effective ablation site. The endocardial area within the 10-ms activation isochrone was measured. The ablation procedure was effective in all patients. Sites with good pace maps had a higher correlation coefficient and lower nRMSd than sites with inadequate pace maps (correlation coefficient: 0.96 +/- 0.03 vs 0.76 +/- 0.18, P <.0001; nRMSd: 0.41 +/- 0.16 vs 0.89 +/- 0.39, P <.0001). Using receiver operating characteristic curves, appropriate cutoff values were >0.94 for correlation coefficient (sensitivity 81%, specificity 89%) and < or =0.54 for nRMSd (sensitivity 76%, specificity 80%). Good pace maps were located a mean of 7.3 +/- 5.0 mm from the effective ablation site and had a mean activation time of -24 +/- 7 ms. However, in 3 (18%) of 16 patients, the best pace map was inadequate at the effective ablation site, with an endocardial activation time at these sites of -25 +/- 12 ms. Pace maps with correlation coefficient > or =0.94 were confined to an area of 1.8 +/- 0.6 cm2. The 10-ms isochrone measured 1.2 +/- 0.7 cm2. The spatial resolution of a good pace map for targeting ventricular tachycardia/ectopy is 1.8 cm2 in the right ventricular outflow tract and therefore is inferior to the spatial resolution of activation mapping as assessed by isochronal activation. In approximately 20% of patients, pace mapping is unreliable in identifying the site of origin, possibly due a deeper site of origin and preferential conduction via fibers connecting the focus to the endocardial surface.

A computational fluid dynamics simulation framework for ventricular catheter design optimization.

PubMed

Weisenberg, Sofy H; TerMaath, Stephanie C; Barbier, Charlotte N; Hill, Judith C; Killeffer, James A

2017-11-10

OBJECTIVE Cerebrospinal fluid (CSF) shunts are the primary treatment for patients suffering from hydrocephalus. While proven effective in symptom relief, these shunt systems are plagued by high failure rates and often require repeated revision surgeries to replace malfunctioning components. One of the leading causes of CSF shunt failure is obstruction of the ventricular catheter by aggregations of cells, proteins, blood clots, or fronds of choroid plexus that occlude the catheter's small inlet holes or even the full internal catheter lumen. Such obstructions can disrupt CSF diversion out of the ventricular system or impede it entirely. Previous studies have suggested that altering the catheter's fluid dynamics may help to reduce the likelihood of complete ventricular catheter failure caused by obstruction. However, systematic correlation between a ventricular catheter's design parameters and its performance, specifically its likelihood to become occluded, still remains unknown. Therefore, an automated, open-source computational fluid dynamics (CFD) simulation framework was developed for use in the medical community to determine optimized ventricular catheter designs and to rapidly explore parameter influence for a given flow objective. METHODS The computational framework was developed by coupling a 3D CFD solver and an iterative optimization algorithm and was implemented in a high-performance computing environment. The capabilities of the framework were demonstrated by computing an optimized ventricular catheter design that provides uniform flow rates through the catheter's inlet holes, a common design objective in the literature. The baseline computational model was validated using 3D nuclear imaging to provide flow velocities at the inlet holes and through the catheter. RESULTS The optimized catheter design achieved through use of the automated simulation framework improved significantly on previous attempts to reach a uniform inlet flow rate distribution using the standard catheter hole configuration as a baseline. While the standard ventricular catheter design featuring uniform inlet hole diameters and hole spacing has a standard deviation of 14.27% for the inlet flow rates, the optimized design has a standard deviation of 0.30%. CONCLUSIONS This customizable framework, paired with high-performance computing, provides a rapid method of design testing to solve complex flow problems. While a relatively simplified ventricular catheter model was used to demonstrate the framework, the computational approach is applicable to any baseline catheter model, and it is easily adapted to optimize catheters for the unique needs of different patients as well as for other fluid-based medical devices.

18-FDG-PET in a patient cohort suspected for cardiac sarcoidosis: Right ventricular uptake is associated with pathological uptake in mediastinal lymph nodes.

PubMed

Tuominen, Heikki; Haarala, Atte; Tikkakoski, Antti; Kähönen, Mika; Nikus, Kjell; Sipilä, Kalle

2018-05-02

In up to 65% of cardiac sarcoidosis patients, the disease is confined to the heart. Diagnosing isolated cardiac sarcoidosis is challenging due to the low sensitivity of endomyocardial biopsy. If cardiac sarcoidosis is part of biopsy-confirmed systemic sarcoidosis, the diagnosis can be based on cardiac imaging studies. We compared the imaging features of patients with isolated cardiac FDG uptake on positron emission tomography with those who had findings indicative of systemic sarcoidosis. 137 consecutive cardiac FDG-PET/CT studies performed on subjects suspected of having cardiac sarcoidosis were retrospectively analyzed. 33 patients had pathological left ventricular FDG uptake, and 12 of these also had pathological right ventricular uptake. 16/33 patients with pathological cardiac uptake had pathological extracardiac uptake. 10/12 patients with both LV- and RV-uptake patterns had extracardiac uptake compared to 6/21 of those with pathological LV uptake without RV uptake. SUVmax values in the myocardium were higher among patients with abnormal extracardiac uptake. The presence of extracardiac uptake was the only imaging-related factor that could predict a biopsy indicative of sarcoidosis. Right ventricular involvement seems to be more common in patients who also have findings suggestive of suspected systemic sarcoidosis, compared with patients with PET findings indicative of isolated cardiac disease.

Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial

PubMed Central

Tosakulwong, Nirubol; Lesnick, Timothy G.; Zuk, Samantha M.; Lowe, Val J.; Fields, Julie A.; Gunter, Jeffrey L.; Senjem, Matthew L.; Settell, Megan L.; Gleason, Carey E.; Shuster, Lynne T.; Bailey, Kent R.; Dowling, N. Maritza; Asthana, Sanjay; Jack, Clifford R.; Rocca, Walter A.; Miller, Virginia M.

2018-01-01

Objective The effects of 2 frequently used formulations of menopausal hormone therapy (mHT) on brain structure and cognition were investigated 3 years after the end of a randomized, placebo-controlled trial in recently menopausal women with good cardiovascular health. Methods Participants (aged 42–56 years; 5–36 months past menopause) were randomized to one of the following: 0.45 mg/d oral conjugated equine estrogen (oCEE); 50 μg/d transdermal 17β-estradiol (tE2); or placebo pills and patch for 4 years. Oral progesterone (200 mg/d) was given to mHT groups for 12 days each month. MRIs were performed at baseline, at the end of 4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of participants also underwent Pittsburgh compound B–PET (n = 68). Results Ventricular volumes increased more in the oCEE group compared to placebo during the 4 years of mHT, but the increase in ventricular volumes was not different from placebo 3 years after the discontinuation of mHT. Increase in white matter hyperintensity volume was similar in the oCEE and tE2 groups, but it was statistically significantly greater than placebo only in the oCEE group. The longitudinal decline in dorsolateral prefrontal cortex volumes was less in the tE2 group compared to placebo, which correlated with lower cortical Pittsburgh compound B uptake. Rates of global cognitive change in mHT groups were not different from placebo. Conclusions The effects of oCEE on global brain structure during mHT subside after oCEE discontinuation but white matter hyperintensities continue to increase. The relative preservation of dorsolateral prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may have long-term effects on the brain. Classification of evidence This study provides Class III evidence that the rates of change in global brain volumes and cognitive function in recently menopausal women receiving mHT (tE2 or oCEE) were not significantly different from women receiving placebo, as measured 3 years after exposure to mHT. PMID:29661902

Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial.

PubMed

Kantarci, Kejal; Tosakulwong, Nirubol; Lesnick, Timothy G; Zuk, Samantha M; Lowe, Val J; Fields, Julie A; Gunter, Jeffrey L; Senjem, Matthew L; Settell, Megan L; Gleason, Carey E; Shuster, Lynne T; Bailey, Kent R; Dowling, N Maritza; Asthana, Sanjay; Jack, Clifford R; Rocca, Walter A; Miller, Virginia M

2018-04-17

The effects of 2 frequently used formulations of menopausal hormone therapy (mHT) on brain structure and cognition were investigated 3 years after the end of a randomized, placebo-controlled trial in recently menopausal women with good cardiovascular health. Participants (aged 42-56 years; 5-36 months past menopause) were randomized to one of the following: 0.45 mg/d oral conjugated equine estrogen (oCEE); 50 μg/d transdermal 17β-estradiol (tE2); or placebo pills and patch for 4 years. Oral progesterone (200 mg/d) was given to mHT groups for 12 days each month. MRIs were performed at baseline, at the end of 4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of participants also underwent Pittsburgh compound B-PET (n = 68). Ventricular volumes increased more in the oCEE group compared to placebo during the 4 years of mHT, but the increase in ventricular volumes was not different from placebo 3 years after the discontinuation of mHT. Increase in white matter hyperintensity volume was similar in the oCEE and tE2 groups, but it was statistically significantly greater than placebo only in the oCEE group. The longitudinal decline in dorsolateral prefrontal cortex volumes was less in the tE2 group compared to placebo, which correlated with lower cortical Pittsburgh compound B uptake. Rates of global cognitive change in mHT groups were not different from placebo. The effects of oCEE on global brain structure during mHT subside after oCEE discontinuation but white matter hyperintensities continue to increase. The relative preservation of dorsolateral prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may have long-term effects on the brain. This study provides Class III evidence that the rates of change in global brain volumes and cognitive function in recently menopausal women receiving mHT (tE2 or oCEE) were not significantly different from women receiving placebo, as measured 3 years after exposure to mHT. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Outcomes of HeartWare Ventricular Assist System support in 141 patients: a single-centre experience.

PubMed

Wu, Long; Weng, Yu-Guo; Dong, Nian-Guo; Krabatsch, Thomas; Stepanenko, Alexander; Hennig, Ewald; Hetzer, Roland

2013-07-01

A third-generation ventricular assist device, the HeartWare Ventricular Assist System, has demonstrated its reliability and durability in animal models and clinical experience. However, studies of a large series of applications are still lacking. We evaluate the safety and efficacy of the HeartWare pump in 141 patients with end-stage heart failure at a single centre. A total of 141 patients (116 men and 25 women with a mean age of 52 years) in New York Heart Association (NYHA) Class IV received implantation of the HeartWare Ventricular Assist System between August 2009 and April 2011 at the Deutsches Herzzentrum Berlin. The outcomes were measured in terms of laboratory data, adverse events, NYHA functional class and survival during device support. The HeartWare system provided an adequate haemodynamic support for patients both inside and outside the hospital. NYHA class improved to I-II. Organ function and pulmonary vascular resistance improved significantly. In this cohort of patients, 14 patients underwent heart transplantation, one had had the device explanted following myocardial recovery, one had changed to another assist device, 81 were on ongoing support and 44 died. The overall actuarial survival rates at 6 and 12 months were 70 and 67%, respectively, and the 3-, 6- and 12-month survival rates on a left ventricular assist device (LVAD) support for bridge to transplantation patients were 82, 81 and 79%, respectively. Infection and bleeding were the main adverse events. Four patients underwent an LVAD exchange for pump thrombosis. The HeartWare system provides a safe and effective circulatory support in a population with a wide range of body surface areas, with a satisfactory actuarial survival time and an improved quality of life. It can be used for univentricular or biventricular support, being implanted into the pericardial space with simplified surgical techniques.

Catecholaminergic and serotoninergic fibres innervate the ventricular system of the hedgehog CNS.

PubMed Central

Michaloudi, H C; Papadopoulos, G C

1996-01-01

Immunocytochemistry with antisera against serotonin (5-HT), dopamine (DA) and noradrenaline (NA) was used to detect monoaminergic (MA) fibres in the ventricular system of the hedgehog Erinaceus europaeus. Light microscopic examination of immunocytochemically stained sections revealed that the ventricular system of the hedgehog is unique among mammals in that the choroid plexuses receive CA axons and that the supraependyma and subependyma of the cerebral ventricles and the spinal central canal are innervated both by serotoninergic and catecholaminergic (CA) fibres. Supraependymal 5-HT axons were generally more abundant and created at places a large number of interconnected basket-like structures, whereas CA fibres were usually directed towards the ventricular lumen. In the lateral ventricles, CA fibres were more numerous in the ependyma lining grey matter, whereas a higher 5-HT innervation density was observed in the area between the corpus callosum and the caudate nucleus or the septum. In the 3rd ventricle, the ependyma of its dorsal part exhibited a higher 5-HT and NA innervation density, whereas DA fibres were preferentially distributed in the ventral half of the basal region. The ependyma lining the cerebral aqueduct displayed a higher MA innervation density in its ventral part. The ependymal wall of the 4th ventricle exhibited an extremely dense 5-HT innervation, mainly in the floor of the ventricle, relatively fewer NA fibres and only sparse DA ones. Few NA and relatively more 5-HT fibres were detected in the ependyma of the central canal. Finally, the circumventricular organs were unevenly innervated by the 3 types of MA fibres. The extensive monoaminergic innervation of the hedgehog ventricular system described here probably reflects a transitory evolutionary stage in the phylogeny of the MA systems with presently unknown functional implications. Images Fig. 1 Fig. 2 Figs 3-8 Figs 9-14 Figs 15-20 PMID:8886949

Longitudinal analysis of head and somatic growth in fetuses with congenital heart defects.

PubMed

Turan, Sifa; Rosenbloom, Joshua I; Hussein, Mostafa; Berg, Christoph; Gembruch, Ulrich; Baschat, Ahmet A; Turan, Ozhan M

2017-02-01

Fetal head and somatic growth dynamics differs in fetuses with congenital heart defects (CHD). We longitudinally characterized fetal head and somatic growth in relation to the type of CHD. Four hundred eleven exams from isolated CHD were compared with 1,219 controls. Head and somatic growth was assessed using head circumference (HC), brain volume (BrV = 1/6 × π × (HC/π)3)/2), fetal cephalization index (FCI = BrV/[estimated fetal weight]), and growth percentile. Umbilical and middle cerebral artery Doppler indices were obtained. CHD were grouped as: (1) d-transposition of great arteries (n = 11); (2) left ventricular outflow tract obstruction with retrograde isthmic flow (n = 18); (3) left ventricular outflow tract obstruction with antegrade isthmic flow (n = 16); (4) pulmonary outflow tract obstructions (n = 22). The smallest head size was seen in group 1. Growth asymmetry was diagnosed in group 2. Brain sparing was seen in groups 2 and 4 (p < 0.0001). HC and BrV percentiles decreased with advancing gestational age (p < 0.001) in group 2, and a significant drop was observed around 28 weeks. d-Transposition of great arteries and left-sided CHD leading to isthmic blood flow reversal are associated with delayed head growth. Prenatal evaluation of central hemodynamics in CHD may be contributive for predicting neurodevelopmental risks in CHD and help directing prenatal interventions. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:96-104, 2017. © 2016 Wiley Periodicals, Inc.

Utility of N-terminal pro-brain natriuretic peptide for assessing hemodynamic significance of patent ductus arteriosus in dogs undergoing ductal repair.

PubMed

Hariu, Crystal D; Saunders, Ashley B; Gordon, Sonya G; Norby, Bo; Miller, Matthew W

2013-09-01

Determine if plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) correlates with markers of hemodynamically significant patent ductus arteriosus (PDA) in dogs. Ten dogs with PDA and 30 healthy dogs of similar ages. Prospective case series with control population. Dogs with PDA were initially evaluated with thoracic radiographs, transthoracic echocardiography, pulmonary capillary wedge pressure (PCWP) and NT-proBNP. Following ductal occlusion, NT-proBNP and echocardiography were repeated within 24 h and at day 90. PCWP was repeated at day 90. Correlation between NT-proBNP and hemodynamic measurements was assessed, and accuracy of NT-proBNP for identifying PDA severity was estimated. NT-proBNP was significantly higher (median; absolute range) in dogs with PDA (895; 490-7118 pmol/L) than controls (663; 50-1318 pmol/L) (p = 0.025). NT-proBNP decreased significantly 90 days post-ductal closure (597; 154-1858 pmol/L) (p = 0.013). Left atrial and ventricular size decreased significantly within 24 h and at day 90 as did PCWP (day 90 only). NT-proBNP correlated with vertebral heart size (VHS) and indexed left ventricular systolic diameter (iLVIDs); concentrations ≥ 1224 pmol/L distinguished dogs with elevated VHS and iLVIDs. NT-proBNP is elevated in dogs with PDA, decreases following PDA closure and correlates with select radiographic and echocardiographic markers of cardiac remodeling. Copyright © 2013 Elsevier B.V. All rights reserved.

[An autopsy case of neonatal lactic acidosis].

PubMed

Giordano, G; Corradi, D; D'Adda, T; Melissari, M

2001-02-01

Defects in mitochondrial enzymes, such as pyruvate dehydrogenase and cytochrome oxidase, cause hereditary disorders which lead to modifications in cellular pH due to the accumulation of pyruvate and lactic acid. Mitochondrial diseases include severe neonatal diseases and less severe forms of adult diseases. We report the case of lactic acidosis in a newborn girl who was delivered at 36 weeks of gestation and who died 3 months after birth. Her family history revealed a relative with tetraparesis and mental retardation. Her clinical findings, such as tonic-clonic convulsions and accumulation of pyruvate and lactic acid in blood, urine and cerebrospinal fluid, were refractory to treatment and developed soon after birth. Ultrasound scans of the brain some days before death revealed cerebral atrophy with ventricular dilatation and thinning of the corpus callosum and septum pellucidum. The clinical diagnosis of metabolic lactic acidosis was confirmed by macroscopic, microscopic and ultrastructural findings seen at autopsy. On macroscopic examination, the heart was hypertrophic, and the brain was atrophic with ventricular dilatation and thinning of corpus callosum. Small cystic lesions were present in the basal ganglia. On microscopic examination, the latter were characterized by loss of neurons, gliosis and capillary proliferation. Ultrastructural examination of the heart and skeletal muscle showed lysis of myofibrils, mitochondrial pleomorphism and hyperplasia, and crystalline inclusion in mitochondria and in the matrix compartment. In reporting this case, we emphasize the importance of accurate postmortem examination and clinical data for the diagnosis of metabolic lactic acidosis.

In vitro characterization of a magnetically suspended continuous flow ventricular assist device.

PubMed

Kim, H C; Bearnson, G B; Khanwilkar, P S; Olsen, D B; Maslen, E H; Allaire, P E

1995-01-01

A magnetically suspended continuous flow ventricular assist device using magnetic bearings was developed aiming at an implantable ventricular assist device. The main advantage of this device includes no mechanical wear and minimal chance of blood trauma such, as thrombosis and hemolysis, because there is no mechanical contact between the stationary and rotating parts. The total system consists of two subsystems: the centrifugal pump and the magnetic bearing. The centrifugal pump is comprised of a 4 vane logarithmic spiral radial flow impeller and a brushless DC motor with slotless stator, driven by the back emf commutation scheme. Two radial and one thrust magnetic bearing that dynamically controls the position of the rotor in a radial and axial direction, respectively, contains magnetic coils, the rotor's position sensors, and feedback electronic control system. The magnetic bearing system was able to successfully suspend a 365.5g rotating part in space and sustain it for up to 5000 rpm of rotation. Average force-current square factor of the magnetic bearing was measured as 0.48 and 0.44 (kg-f/Amp2) for radial and thrust bearing, respectively. The integrated system demonstrated adequate performance in mock circulation tests by providing a 6 L/min flow rate against 100 mmHg differential pressure at 2300 rpm. Based on these in vitro performance test results, long-term clinical application of the magnetically suspended continuous flow ventricular assist device is very promising after system optimization with a hybrid system using both active (electromagnet) and passive (permanent magnets) magnet bearings.

PTB deficiency causes the loss of adherens junctions in the dorsal telencephalon and leads to lethal hydrocephalus.

PubMed

Shibasaki, Takayuki; Tokunaga, Akinori; Sakamoto, Reiko; Sagara, Hiroshi; Noguchi, Shigeru; Sasaoka, Toshikuni; Yoshida, Nobuaki

2013-08-01

Polypyrimidine tract-binding protein (PTB) is a well-characterized RNA-binding protein and known to be preferentially expressed in neural stem cells (NSCs) in the central nervous system; however, its role in NSCs in the developing brain remains unclear. To explore the role of PTB in embryonic NSCs in vivo, Nestin-Cre-mediated conditional Ptb knockout mice were generated for this study. In the mutant forebrain, despite the depletion of PTB protein, neither abnormal neurogenesis nor flagrant morphological abnormalities were observed at embryonic day 14.5 (E14.5). Nevertheless, by 10 weeks, nearly all mutant mice succumbed to hydrocephalus (HC), which was caused by a lack of the ependymal cell layer in the dorsal cortex. Upon further analysis, a gradual loss of adherens junctions (AJs) was observed in the ventricular zone (VZ) of the dorsal telencephalon in the mutant brains, beginning at E14.5. In the AJs-deficient VZ, impaired interkinetic nuclear migration and precocious differentiation of NSCs were observed after E14.5. These findings demonstrated that PTB depletion in the dorsal telencephalon is causally involved in the development of HC and that PTB is important for the maintenance of AJs in the NSCs of the dorsal telencephalon.

Cerebral changes in SLE with or without antiphospholipid syndrome. a case-control MRI study.

PubMed

Valdés-Ferrer, Sergio I; Vega, Felipe; Cantú-Brito, Carlos; Ceballos-Ceballos, Joel; Estañol, Bruno; García-Ramos, Gullermo; Cabral, Antonio R

2008-01-01

To determine and characterize the prevalence of cerebral changes on MRI in patients with antiphospholipid syndrome (APLS) within systemic lupus erythematosus (SLE). Seventy-one patients with SLE were prospectively studied with brain MRI: 32 with definite APLS and 39 without. Atrophy, ventricular enlargement, leukoaraiosis, interuncal distance, Evans' index, infarcts, and white matter hyperintensities (WMH) were analyzed. Demographic data, treatment, and SLE activity were analyzed. Groups were similar in age (32.4 vs. 32.8 years old; P= non-significant [NS]), and gender. Duration of disease was longer in patients with APLS (87.3 vs. 55.4 months; P= .064). Cortical atrophy was common in both groups (68.7% vs. 89.7%; P= NS). Leukoaraiosis was present in only 3 patients (9.4%; P= .08), all in the APLS group. WMH were found in more than 40% of the patients from both groups. Infarcts (21.9% vs. 2.6%; P= .019) and infarcts plus WHM (12.5% vs. 0; P= .037) were more common in patients with APLS. Although a higher prevalence of neurological involvement in SLE has been reported in APLS patients, we found gross brain changes to be similar between groups. Strokes and leukoaraiosis were more common in the APLS group, consistent with the idea of an APLS-induced prothrombotic state.

Distribution of glycogen phosphorylase and cytochrome oxidase in the central nervous system of the turtle Trachemys dorbigni.

PubMed

Partata, W A; Krepsky, A M; Xavier, L L; Marques, M; Achaval, M

1999-10-01

Glycogen phosphorylase (GP) and cytochrome oxidase (CO) activities were mapped histochemically in the brain of the turtle Trachemys dorbigni. In the telencephalon, both activities occurred in the olfactory bulb, in all cortical areas, in the dorsal ventricular ridge, striatum, primordium hippocampi and olfactory tubercle. In the diencephalon, they were identified in some areas of the hypothalamus, and in rotundus and geniculate nuclei. Both reactions were detected in the oculomotor, trochlear, mesencephalic trigeminal nuclei, the nucleus of the posterior commissure, torus semicircularis, substantia nigra and ruber and isthmic nuclei of the mesencephalon. In all layers of the optic tectum GP activity was found, but CO only labelled the stratum griseum centrale. In the medulla oblonga both enzymes appear in the reticular, raphe and vestibular nuclei, locus coeruleus and nuclei of cranial nerves. In the cerebellum, the granular and molecular layers, and the deep cerebellar nuclei were positive for both enzymes. The Purkinje cells were only reactive for CO. In the spinal cord, motor and commissural neurones exhibited a positive reaction for the two enzymes. However, CO also occurred in the marginal nucleus and in the lateral funiculus. These results may be useful as a basis for subsequent studies on turtle brain metabolism.

Posttraumatic hydrocephalus: a clinical, neuroradiologic, and neuropsychologic assessment of long-term outcome.

PubMed

Mazzini, Letizia; Campini, Riccardo; Angelino, Elisabetta; Rognone, Felice; Pastore, Ilaria; Oliveri, Giuseppe

2003-11-01

To detect the clinical and radiologic characteristics of posttraumatic hydrocephalus (PTH), to define its prognostic value, and to assess the effects of shunt surgery. Correlational study on a prospective cohort. Brain injury rehabilitation center. One hundred forty patients with severe traumatic brain injury (TBI) referred to an inpatient intensive rehabilitation unit of primary care in a university-based system. Not applicable. The Glasgow Outcome Scale (GOS), Disability Rating Scale (DRS), FIM instrument, and Neurobehavioural Rating Scale (NRS), as well as single-photon emission computed tomography (SPECT) and magnetic resonance imaging. PTH was found in 45% of patients. Risk factors for PTH were as follows: age (P<.04), duration of coma (P<.0001), and decompressive craniectomy (P<.0001). PTH correlated with the degree of hypoperfusion in the temporal lobes (P<.001). Patients who showed clinical deterioration improved after surgery. PTH correlated significantly with GOS, DRS, FIM, and NRS (P<.0001) 1 year after the trauma, and it influenced the appearance of posttraumatic epilepsy (P<.02). PTH concerns about 50% of patients with severe TBI. It influences functional and behavioral outcome and the appearance of posttraumatic epilepsy. The selection of patients for surgery can be defined principally on a clinical basis. SPECT may be helpful for differentiating ventricular enlargement due to cortical atrophy and hydrocephalus.

White matter injury detection in neonatal MRI

NASA Astrophysics Data System (ADS)

Cheng, Irene; Hajari, Nasim; Firouzmanesh, Amirhossein; Shen, Rui; Miller, Steven; Poskitt, Ken; Basu, Anup

2013-02-01

Early detection of white matter injury in premature newborns can facilitate timely clinical treatments reducing the potential risk of later developmental deficits. It was reported that there were more than 5% premature newborns in British Columbia, Canada, among which 5-10% exhibited major motor deficits and 25-50% exhibited significant developmental and visual deficits. With the advancement of computer assisted detection systems, it is possible to automatically identify white matter injuries, which are found inside the grey matter region of the brain. Atlas registration has been suggested in the literature to distinguish grey matter from the soft tissues inside the skull. However, our subjects are premature newborns delivered at 24 to 32 weeks of gestation. During this period, the grey matter undergoes rapid changes and differs significantly from one to another. Besides, not all detected white spots represent injuries. Additional neighborhood information and expert input are required for verification. In this paper, we propose a white matter feature identification system for premature newborns, which is composed of several steps: (1) Candidate white matter segmentation; (2) Feature extraction from candidates; (3) Validation with data obtained at a later stage on the children; and (4) Feature confirmation for automated detection. The main challenge of this work lies in segmenting white matter injuries from noisy and low resolution data. Our approach integrates image fusion and contrast enhancement together with a fuzzy segmentation technique to achieve promising results. Other applications, such as brain tumor and intra-ventricular haemorrhage detection can also benefit from our approach.

Does hydration status affect MRI measures of brain volume or water content?

PubMed

Meyers, Sandra M; Tam, Roger; Lee, Jimmy S; Kolind, Shannon H; Vavasour, Irene M; Mackie, Emilie; Zhao, Yinshan; Laule, Cornelia; Mädler, Burkhard; Li, David K B; MacKay, Alex L; Traboulsee, Anthony L

2016-08-01

To determine whether differences in hydration state, which could arise from routine clinical procedures such as overnight fasting, affect brain total water content (TWC) and brain volume measured with magnetic resonance imaging (MRI). Twenty healthy volunteers were scanned with a 3T MR scanner four times: day 1, baseline scan; day 2, hydrated scan after consuming 3L of water over 12 hours; day 3, dehydrated scan after overnight fasting of 9 hours, followed by another scan 1 hour later for reproducibility. The following MRI data were collected: T2 relaxation (for TWC measurement), inversion recovery (for T1 measurement), and 3D T1 -weighted (for brain volumes). Body weight and urine specific gravity were also measured. TWC was calculated by fitting the T2 relaxation data with a nonnegative least-squares algorithm, with corrections for T1 relaxation and image signal inhomogeneity and normalization to ventricular cerebrospinal fluid. Brain volume changes were measured using SIENA. TWC means were calculated within 14 tissue regions. Despite indications of dehydration as demonstrated by increases in urine specific gravity (P = 0.03) and decreases in body weight (P = 0.001) between hydrated and dehydrated scans, there was no measurable change in TWC (within any brain region) or brain volume between hydration states. We demonstrate that within a range of physiologic conditions commonly encountered in routine clinical scans (no pretreatment with hydration, well hydrated before MRI, and overnight fasting), brain TWC and brain volumes are not substantially affected in a healthy control cohort. J. Magn. Reson. Imaging 2016;44:296-304. © 2016 Wiley Periodicals, Inc.

Assessing cell cycle progression of neural stem and progenitor cells in the mouse developing brain after genotoxic stress.

PubMed

Etienne, Olivier; Bery, Amandine; Roque, Telma; Desmaze, Chantal; Boussin, François D

2014-05-07

Neurons of the cerebral cortex are generated during brain development from different types of neural stem and progenitor cells (NSPC), which form a pseudostratified epithelium lining the lateral ventricles of the embryonic brain. Genotoxic stresses, such as ionizing radiation, have highly deleterious effects on the developing brain related to the high sensitivity of NSPC. Elucidation of the cellular and molecular mechanisms involved depends on the characterization of the DNA damage response of these particular types of cells, which requires an accurate method to determine NSPC progression through the cell cycle in the damaged tissue. Here is shown a method based on successive intraperitoneal injections of EdU and BrdU in pregnant mice and further detection of these two thymidine analogues in coronal sections of the embryonic brain. EdU and BrdU are both incorporated in DNA of replicating cells during S phase and are detected by two different techniques (azide or a specific antibody, respectively), which facilitate their simultaneous detection. EdU and BrdU staining are then determined for each NSPC nucleus in function of its distance from the ventricular margin in a standard region of the dorsal telencephalon. Thus this dual labeling technique allows distinguishing cells that progressed through the cell cycle from those that have activated a cell cycle checkpoint leading to cell cycle arrest in response to DNA damage. An example of experiment is presented, in which EdU was injected before irradiation and BrdU immediately after and analyzes performed within the 4 hr following irradiation. This protocol provides an accurate analysis of the acute DNA damage response of NSPC in function of the phase of the cell cycle at which they have been irradiated. This method is easily transposable to many other systems in order to determine the impact of a particular treatment on cell cycle progression in living tissues.

Longitudinal characterization of two siblings with frontotemporal dementia and parkinsonism linked to chromosome 17 associated with the S305N tau mutation.

PubMed

Boeve, Bradley F; Tremont-Lukats, Ivo W; Waclawik, Andrew J; Murrell, Jill R; Hermann, Bruce; Jack, Clifford R; Shiung, Maria M; Smith, Glenn E; Nair, Anil R; Lindor, Noralane; Koppikar, Vinaya; Ghetti, Bernardino

2005-04-01

The background to this study began with the reporting of two Japanese kindreds with the S305N tau mutation. Although the pathological findings in the autopsied cases were well characterized, only limited ante-mortem data were presented. In this study, longitudinal characterization was carried out in two siblings of European ancestry found to have frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) through comprehensive neurobehavioural examinations and other scales at approximate 6-month intervals. Scales included the Mini-Mental State Examination, Short Test of Mental Status, modified motor subtest of the Unified Parkinson's Disease Rating Scale, detailed neuropsychological testing, and the Neuropsychiatric Inventory. Changes in whole-brain volume and ventricular volume were measured from serial MRI studies. All members of the kindred underwent molecular genetic analyses to elucidate the mechanism of inheritance. The missense mutation in tau, S305N, was detected in the proband (onset age 30), who has undergone serial evaluations for almost 4 years. Her older sister (onset age 36) was subsequently found to have the same mutation, and has undergone serial evaluations for 2 years. This mutation is absent in both parents and the only other sibling, and non-paternity was excluded by additional analyses. The siblings have exhibited cognitive and behavioural features typical of FTDP-17, which have proved challenging to manage despite aggressive pharmacological and behavioural therapies. The proband's sister has demonstrated an atypical profile of impairment on neuropsychological testing. Both siblings have developed striking atrophy of the anterior part of temporal lobes and moderate atrophy of the dorsolateral and orbitofrontal cortical regions, which in both cases is relatively symmetrical. The annualized changes in whole-brain volume and ventricular volume, respectively, were -35.2 ml/year (3.23% decrease per year) and +20.75 ml/year (16.93% increase per year) for the proband, and -30.75 ml/year (2.77% decrease per year) and +5.01 ml/year (3.11% increase per year) for the proband's sister. In conclusion, the mutation in these siblings may have arisen during oogenesis in the mother and probably represents germline mosaicism. Although both patients have exhibited the typical cognitive and behavioural features of FTDP-17, one patient is exhibiting an atypical neuropsychological profile. Also, despite a similar topographic pattern of progressive atrophy on MRI, the rates of change in whole-brain volume and ventricular volume between the two patients are quite different. These findings have implications for future drug trial development in FTDP-17 and the sporadic tauopathies.

A Successful Anticoagulation Protocol for the First HeartMate® II Implantation in the United States

PubMed Central

Amir, Offer; Bracey, Arthur W.; Smart, Frank W.; Delgado, Reynolds M.; Shah, Nyma; Kar, Biswajit; Gregoric, Igor D.

2005-01-01

Bleeding and thrombus formation are common problems with life-threatening implications in patients receiving a left ventricular assist device. We describe the anticoagulation protocol for the 1st patient in the United States to undergo successful implantation of the HeartMate® II left ventricular assist system. PMID:16392229

Response of the Cardiovascular System to Vibration and Combined Stresses

DTIC Science & Technology

1975-08-31

Canines were chronically instrumented for continuous measurements of ascending aortic flow ( Zepeda ), left ventricular pressure (Konigsberg), circum- flex...different animals. Each dog was chronically instrumented for continuous measuremernt of ascending aortic flow ( Zepeda ), left ventricular pressure...vibration protocol as those animals restrained vertically. METHODS Canines (16 to 22 kg) were chronically instrumented with electromagnetic flow cuffs ( Zepeda

Research and Development of Advanced Life Support Equipment.

DTIC Science & Technology

1999-02-01

kg.) were catheterized f or measurement of left ventricular pressure (LVP), right ventricular pressure (RVP), mean aortic pressure (MAP), central ...Orientation Laboratory Venous Gas Emboli Variable Profile Breathing Simulator Wingate Anaerobic Test Weapons System Trainer World Wide Web... history screening of the potential subjects was conducted to eliminate those individuals who have known health conditions/ histories which would

Constitutional rho-kinase regulates atrioventricular nodal conduction and ventricular repolarization of the canine heart.

PubMed

Sugiyama, Atsushi; Takahara, Akira; Yatomi, Yutaka; Satoh, Yoshioki; Nakamura, Yuji; Hashimoto, Keitaro

2003-06-01

Given the limited information, physiological roles of Rho-kinase in the cardiac conduction system and ventricular repolarization process were assessed in comparison with those in the coronary vascular tone. A specific Rho-kinase inhibitor Y-27632 was administered to the nutrient coronary artery of the canine isolated, blood-perfused atrioventricular node preparation under the monitoring of the ventricular monophasic action potentials. Administration of Y-27632 moderately suppressed the atrioventricular nodal conduction, slightly but significantly accelerated the repolarization process, and potently increased the coronary blood flow, whereas it hardly affected the intraventricular conduction. The estimated concentrations of Y-27632 causing the currently observed effects were enough to inhibit Rho-kinase. These results suggest that constitutional Rho-kinase functions to moderately facilitate the atrioventricular nodal conduction, slightly delay ventricular repolarization process, and significantly increase the coronary vascular tone.

Brain MRI abnormalities in the adult form of myotonic dystrophy type 1: A longitudinal case series study.

PubMed

Conforti, Renata; de Cristofaro, Mario; Cristofano, Adriana; Brogna, Barbara; Sardaro, Angela; Tedeschi, Gioacchino; Cirillo, Sossio; Di Costanzo, Alfonso

2016-02-01

This study aimed to verify whether brain abnormalities, previously described in patients with myotonic dystrophy type 1 (DM1) by magnetic resonance imaging (MRI), progressed over time and, if so, to characterize their progression. Thirteen DM1 patients, who had at least two MRI examinations, were retrospectively evaluated and included in the study. The mean duration (± standard deviation) of follow-up was 13.4 (±3.8) years, over a range of 7-20 years. White matter lesions (WMLs) were rated by semi-quantitative method, the signal intensity of white matter poster-superior to trigones (WMPST) by reference to standard images and brain atrophy by ventricular/brain ratio (VBR). At the end of MRI follow-up, the scores relative to lobar, temporal and periventricular WMLs, to WMPST signal intensity and to VBR were significantly increased compared to baseline, and MRI changes were more evident in some families than in others. No correlation was found between the MRI changes and age, onset, disease duration, muscular involvement, CTG repetition and follow-up duration. These results demonstrated that white matter involvement and brain atrophy were progressive in DM1 and suggested that progression rate varied from patient to patient, regardless of age, disease duration and genetic defect. © The Author(s) 2016.

DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates.

PubMed

Keeney, J G; Davis, J M; Siegenthaler, J; Post, M D; Nielsen, B S; Hopkins, W D; Sikela, J M

2015-09-01

Genome sequences encoding DUF1220 protein domains show a burst in copy number among anthropoid species and especially humans, where they have undergone the greatest human lineage-specific copy number expansion of any protein coding sequence in the genome. While DUF1220 copy number shows a dosage-related association with brain size in both normal populations and in 1q21.1-associated microcephaly and macrocephaly, a function for these domains has not yet been described. Here we provide multiple lines of evidence supporting the view that DUF1220 domains function as drivers of neural stem cell proliferation among anthropoid species including humans. First, we show that brain MRI data from 131 individuals across 7 anthropoid species shows a strong correlation between DUF1220 copy number and multiple brain size-related measures. Using in situ hybridization analyses of human fetal brain, we also show that DUF1220 domains are expressed in the ventricular zone and primarily during human cortical neurogenesis, and are therefore expressed at the right time and place to be affecting cortical brain development. Finally, we demonstrate that in vitro expression of DUF1220 sequences in neural stem cells strongly promotes proliferation. Taken together, these data provide the strongest evidence so far reported implicating DUF1220 dosage in anthropoid and human brain expansion through mechanisms involving increasing neural stem cell proliferation.

Red and NIR light dosimetry in the human deep brain

NASA Astrophysics Data System (ADS)

Pitzschke, A.; Lovisa, B.; Seydoux, O.; Zellweger, M.; Pfleiderer, M.; Tardy, Y.; Wagnières, G.

2015-04-01

Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson’s Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 × 201 × 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated μeff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.

The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia.

PubMed

Matsumoto, Mitsuyuki; Straub, Richard E; Marenco, Stefano; Nicodemus, Kristin K; Matsumoto, Shun-Ichiro; Fujikawa, Akihiko; Miyoshi, Sosuke; Shobo, Miwako; Takahashi, Shinji; Yarimizu, Junko; Yuri, Masatoshi; Hiramoto, Masashi; Morita, Shuji; Yokota, Hiroyuki; Sasayama, Takeshi; Terai, Kazuhiro; Yoshino, Masayasu; Miyake, Akira; Callicott, Joseph H; Egan, Michael F; Meyer-Lindenberg, Andreas; Kempf, Lucas; Honea, Robyn; Vakkalanka, Radha Krishna; Takasaki, Jun; Kamohara, Masazumi; Soga, Takatoshi; Hiyama, Hideki; Ishii, Hiroyuki; Matsuo, Ayako; Nishimura, Shintaro; Matsuoka, Nobuya; Kobori, Masato; Matsushime, Hitoshi; Katoh, Masao; Furuichi, Kiyoshi; Weinberger, Daniel R

2008-04-22

The G protein-coupled receptor (GPCR) family is highly diversified and involved in many forms of information processing. SREB2 (GPR85) is the most conserved GPCR throughout vertebrate evolution and is expressed abundantly in brain structures exhibiting high levels of plasticity, e.g., the hippocampal dentate gyrus. Here, we show that SREB2 is involved in determining brain size, modulating diverse behaviors, and potentially in vulnerability to schizophrenia. Mild overexpression of SREB2 caused significant brain weight reduction and ventricular enlargement in transgenic (Tg) mice as well as behavioral abnormalities mirroring psychiatric disorders, e.g., decreased social interaction, abnormal sensorimotor gating, and impaired memory. SREB2 KO mice showed a reciprocal phenotype, a significant increase in brain weight accompanying a trend toward enhanced memory without apparent other behavioral abnormalities. In both Tg and KO mice, no gross malformation of brain structures was observed. Because of phenotypic overlap between SREB2 Tg mice and schizophrenia, we sought a possible link between the two. Minor alleles of two SREB2 SNPs, located in intron 2 and in the 3' UTR, were overtransmitted to schizophrenia patients in a family-based sample and showed an allele load association with reduced hippocampal gray matter volume in patients. Our data implicate SREB2 as a potential risk factor for psychiatric disorders and its pathway as a target for psychiatric therapy.

The construction of tridimensional representation of body and external reality in man. The greatest achievement of evolution to date implications for virtual reality.

PubMed

Woodbury, M A; Woodbury, M F

1998-01-01

Our 3-D Body Representation constructed during development by our Central Nervous System under the direction of our DNA, consists of a holographic representation arising from sensory input in the cerebellum and projected extraneurally in the brain ventricular fluid which has the chemical structure of liquid crystal. The structure of 3-D holographic Body Representation is then extrapolated by such cognitive instruments as boundarization, geometrization and gestalt organization upon the external environment which is perceived consequently as three dimensional. When the Body Representation collapses as in psychotic panic states. patients become terrified as they suddenly lose the perception of themselves and the world around them as three dimensional, solid in a reliably solid environment but feel suddenly that they are no longer a person but a disorganized blob. In our clinical practice we found serendipitously that the structure of three dimensionality can be restored even without medication by techniques involving stimulation of the body sensory system in the presence of a benevolent psychotherapist. Implications for Virtual Reality will be discussed.

[Patterns of brain ageing].

PubMed

Fernández Viadero, Carlos; Verduga Vélez, Rosario; Crespo Santiago, Dámaso

2017-06-01

Neuroplasticity lends the brain a strong ability to adapt to changes in the environment that occur during ageing. Animal models have shown alterations in neurotransmission and imbalances in the expression of neural growth factor. Changes at the morphometric level are not constant. Volume loss is related to alterations in neuroplasticity and involvement of the cerebral neuropil. Although there are no conclusive data, physical exercise improves the molecular, biological, functional and behavioural-cognitive changes associated with brain ageing. The aged human brain has been described as showing weight and volume loss and increased ventricular size. However, neuroimaging shows significant variation and many healthy elderly individuals show no significant macroscopic changes. In most brain regions, the number of neurons remains stable throughout life. Neuroplasticity does not disappear with ageing, and changes in dendritic arborization and the density of spines and synapses are more closely related to brain activity than to age. At the molecular level, although the presence of altered Tau and β-amyloid proteins is used as a biomarker of neurodegenerative disease, postmortem studies show that these abnormal proteins are common in the brains of elderly people without dementia. Finally, due to the relationship between neurodegenerative diseases and metabolic alterations, this article analyses the influence of insulin-like growth factor and ageing, both in animal models and in humans, and the possible neuroprotective effect of insulin. Copyright © 2017 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

Biomarkers of brain injury in the premature infant.

PubMed

Douglas-Escobar, Martha; Weiss, Michael D

2012-01-01

The term "encephalopathy of prematurity" encompasses not only the acute brain injury [such as intraventricular hemorrhage (IVH)] but also complex disturbance on the infant's subsequent brain development. In premature infants, the most frequent recognized source of brain injury is IVH and periventricular leukomalacia (PVL). Furthermore 20-25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500-750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury, and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD), and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP, and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9, and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after PHVD. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

Effects of coordinate system choice on measured regional myocardial function in short-axis cine electron-beam tomography

NASA Astrophysics Data System (ADS)

Reed, Judd E.; Rumberger, John A.; Buithieu, Jean; Behrenbeck, Thomas; Breen, Jerome F.; Sheedy, Patrick F., II

1995-05-01

Following myocardial infarction, the size of the infarcted region and the systolic functioning of the noninfarcted region are commonly assessed by various cross- sectional imaging techniques. A series of images representing successive phases of the cardiac cycle can be acquired by several imaging modalities including electron beam computed tomography, magnetic resonance imaging, and echocardiography. For the assessment of patterns of ventricular contraction, images are commonly acquired of ventricular cross-sections normal to the 'long' axis of the heart and parallel to the mitral valve plane. The endocardial and epicardial surfaces of the myocardium are identified. Then the ventricle is divided into sectors and the volumes of blood and myocardium within each sector at multiple phases of the cardiac cycle are measured. Regional function parameters are derived from these measurements. This generally mandates the use of a polar or cylindrical coordinate system. Various algorithms have been used to select the origin of this coordinate system. These include the centroid of the endocardial surface, the epicardial surface, or of a polygon whose vertices lie midway between the epicardial and endocardial surfaces of the myocardium (centerline method). Another algorithm has been developed in our laboratory. This uses the centroid (or center of mass) of the myocardium exclusive of the ventricular cavity. Each of these choices for origin of coordinate system can be derived from the end- diastolic image or from the end-systolic image. Alternately, new coordinate systems can be selected for each phase of the cardiac cycle. These are referred to as 'floating' coordinate systems. A series of computer models have been developed in our laboratory to study the effects of each of these choices on the regional function parameters of normal ventricles and how these choices effect the quantification of regional abnormalities after myocardial infarction. The most sophisticated of these is an interactive program with a graphical user interface which facilitates the simulation of a wide variety of dynamic ventricular cross sections. Analysis of these simulations has led to a better understanding of how polar coordinate system placement influences the results of quantitative regional ventricular function assessment. It has also created new insight into how the appropriateness of the placement of such a polar coordinate systems can be objectively assessed. The validity of the conclusions drawn from the analysis of simulated ventricular shapes was validated through the analysis of outlines extracted from cine electron beam computed tomographic images. This was done using another interactive software tool developed specifically for this purpose. With this tool, the effects on regional function parameters of various choices for origin placement can be directly observed. This has proven to reinforce the conclusions drawn from the simulations and has led to the modification of the procedures used in our laboratory. Conclusions: The so-called floating coordinate systems are superior to fixed ones for quantification of regional left ventricular contraction in almost every respect. The use of regional ejection fractions with a coordinate system origin located at the centroid of the endocardial surface can lead to 180 degree errors in identifying the location of a myocardial infarction. This problem is less pronounced with midline and epicardium- based centroids and does not occur when the centroid of the myocardium is used. The quantified migration of myocardial mass across sector boundaries is a useful indicator of an inappropriate choice of coordinate system origin. When the centroid of the myocardium falls well within the ventricular cavity, as it usually does, it is a better location for the origin for regional analysis than any of the other centroids analyzed.

Investigating the Role of Interventricular Interdependence in Development of Right Heart Dysfunction During LVAD Support: A Patient-Specific Methods-Based Approach.

PubMed

Sack, Kevin L; Dabiri, Yaghoub; Franz, Thomas; Solomon, Scott D; Burkhoff, Daniel; Guccione, Julius M

2018-01-01

Predictive computation models offer the potential to uncover the mechanisms of treatments whose actions cannot be easily determined by experimental or imaging techniques. This is particularly relevant for investigating left ventricular mechanical assistance, a therapy for end-stage heart failure, which is increasingly used as more than just a bridge-to-transplant therapy. The high incidence of right ventricular failure following left ventricular assistance reflects an undesired consequence of treatment, which has been hypothesized to be related to the mechanical interdependence between the two ventricles. To investigate the implication of this interdependence specifically in the setting of left ventricular assistance device (LVAD) support, we introduce a patient-specific finite-element model of dilated chronic heart failure. The model geometry and material parameters were calibrated using patient-specific clinical data, producing a mechanical surrogate of the failing in vivo heart that models its dynamic strain and stress throughout the cardiac cycle. The model of the heart was coupled to lumped-parameter circulatory systems to simulate realistic ventricular loading conditions. Finally, the impact of ventricular assistance was investigated by incorporating a pump with pressure-flow characteristics of an LVAD (HeartMate II™ operating between 8 and 12 k RPM) in parallel to the left ventricle. This allowed us to investigate the mechanical impact of acute left ventricular assistance at multiple operating-speeds on right ventricular mechanics and septal wall motion. Our findings show that left ventricular assistance reduces myofiber stress in the left ventricle and, to a lesser extent, right ventricle free wall, while increasing leftward septal-shift with increased operating-speeds. These effects were achieved with secondary, potentially negative effects on the interventricular septum which showed that support from LVADs, introduces unnatural bending of the septum and with it, increased localized stress regions. Left ventricular assistance unloads the left ventricle significantly and shifts the right ventricular pressure-volume-loop toward larger volumes and higher pressures; a consequence of left-to-right ventricular interactions and a leftward septal shift. The methods and results described in the present study are a meaningful advancement of computational efforts to investigate heart-failure therapies in silico and illustrate the potential of computational models to aid understanding of complex mechanical and hemodynamic effects of new therapies.

A Complete System for Automatic Extraction of Left Ventricular Myocardium From CT Images Using Shape Segmentation and Contour Evolution

PubMed Central

Zhu, Liangjia; Gao, Yi; Appia, Vikram; Yezzi, Anthony; Arepalli, Chesnal; Faber, Tracy; Stillman, Arthur; Tannenbaum, Allen

2014-01-01

The left ventricular myocardium plays a key role in the entire circulation system and an automatic delineation of the myocardium is a prerequisite for most of the subsequent functional analysis. In this paper, we present a complete system for an automatic segmentation of the left ventricular myocardium from cardiac computed tomography (CT) images using the shape information from images to be segmented. The system follows a coarse-to-fine strategy by first localizing the left ventricle and then deforming the myocardial surfaces of the left ventricle to refine the segmentation. In particular, the blood pool of a CT image is extracted and represented as a triangulated surface. Then, the left ventricle is localized as a salient component on this surface using geometric and anatomical characteristics. After that, the myocardial surfaces are initialized from the localization result and evolved by applying forces from the image intensities with a constraint based on the initial myocardial surface locations. The proposed framework has been validated on 34-human and 12-pig CT images, and the robustness and accuracy are demonstrated. PMID:24723531

A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

PubMed

Abdelhamed, Zakia; Vuong, Shawn M; Hill, Lauren; Shula, Crystal; Timms, Andrew; Beier, David; Campbell, Kenneth; Mangano, Francesco T; Stottmann, Rolf W; Goto, June

2018-01-09

Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 ( Ccdc39 ) is responsible for early postnatal hydrocephalus in the progressive hydrocephal us ( prh ) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39 prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development. © 2018. Published by The Company of Biologists Ltd.

Soluble Klotho and Brain Atrophy in Alcoholism.

PubMed

González-Reimers, Emilio; Romero-Acevedo, Lucía; Espelosín-Ortega, Elisa; Martín-González, M Candelaria; Quintero-Platt, Geraldine; Abreu-González, Pedro; José de-la-Vega-Prieto, María; Martínez-Martínez, Daniel; Santolaria-Fernández, Francisco

2018-05-26

Fibroblast growth factor (FGF-23) and α-Klotho (Klotho) levels may be altered in inflammatory conditions, possibly as compensatory mechanisms. Klotho exerts a protective effect on neurodegeneration and improves learning and cognition. No data exist about the association of Klotho and FGF-23 levels with brain atrophy observed in alcoholics. The aim of this study is to explore these relationships. FGF-23 and Klotho levels are altered in inflammation, possibly as compensatory mechanisms. Klotho enhances learning, but its role in ethanol-mediated brain atrophy is unknown. We found higher FGF-23 and lower Klotho levels in 131 alcoholics compared with 41 controls. Among cirrhotics, Klotho was higher and inversely related to brain atrophy. The study was performed on 131 alcoholic patients (54 cirrhotics) and 41 age- and sex-matched controls, in whom a brain computed tomography (CT) was performed and several indices were calculated. Marked brain atrophy was observed among patients when compared with controls. Patients also showed higher FGF-23 and lower Klotho values. However, among cirrhotics, Klotho values were higher. Klotho was inversely related to brain atrophy (for instance, ventricular index (ρ = -0.23, P = 0.008)), especially in cirrhotics. Klotho was also directly related to tumor necrosis factor (TNF) alpha (ρ = 0.22; P = 0.026) and inversely to transforming growth factor (TGF)-β (ρ = -0.34; P = 0.002), but not to C-reactive protein (CRP) or malondialdehyde levels. FGF-23 was also higher among cirrhotics but showed no association with CT indices. Klotho showed higher values among cirrhotics, and was inversely related to brain atrophy. FGF-23, although high among patients, especially cirrhotics, did not show any association with brain atrophy. Some inflammatory markers or cytokines, such as CRP or TGF-β were related to brain atrophy.

Postnatal Brain Growth Assessed by Sequential Cranial Ultrasonography in Infants Born <30 Weeks' Gestational Age.

PubMed

Cuzzilla, R; Spittle, A J; Lee, K J; Rogerson, S; Cowan, F M; Doyle, L W; Cheong, J L Y

2018-06-01

Brain growth in the early postnatal period following preterm birth has not been well described. This study of infants born at <30 weeks' gestational age and without major brain injury aimed to accomplish the following: 1) assess the reproducibility of linear measures made from cranial ultrasonography, 2) evaluate brain growth using sequential cranial ultrasonography linear measures from birth to term-equivalent age, and 3) explore perinatal predictors of postnatal brain growth. Participants comprised 144 infants born at <30 weeks' gestational age at a single center between January 2011 and December 2013. Infants with major brain injury seen on cranial ultrasonography or congenital or chromosomal abnormalities were excluded. Brain tissue and fluid spaces were measured from cranial ultrasonography performed as part of routine clinical care. Brain growth was assessed in 3 time intervals: <7, 7-27, and >27 days' postnatal age. Data were analyzed using intraclass correlation coefficients and mixed-effects regression. A total of 429 scans were assessed for 144 infants. Several linear measures showed excellent reproducibility. All measures of brain tissue increased with postnatal age, except for the biparietal diameter, which decreased within the first postnatal week and increased thereafter. Gestational age of ≥28 weeks at birth was associated with slower growth of the biparietal diameter and ventricular width compared with gestational age of <28 weeks. Postnatal corticosteroid administration was associated with slower growth of the corpus callosum length, transcerebellar diameter, and vermis height. Sepsis and necrotizing enterocolitis were associated with slower growth of the transcerebellar diameter. Postnatal brain growth in infants born at <30 weeks' gestational age can be evaluated using sequential linear measures made from routine cranial ultrasonography and is associated with perinatal predictors of long-term development. © 2018 by American Journal of Neuroradiology.

Relation of N-Terminal Pro-B-Type Natriuretic Peptide and Left Ventricular Diastolic Function to Exercise Tolerance in Patients With Significant Valvular Heart Disease and Normal Left Ventricular Systolic Function.

PubMed

Hwang, Ji-Won; Park, Sung-Ji; Cho, Eun Jeong; Kim, Eun Kyoung; Lee, Ga Yeon; Chang, Sung-A; Choi, Jin-Oh; Lee, Sang-Chol; Park, Seung Woo

2017-06-01

An association between N-terminal prohormone brain natriuretic peptide (NT-proBNP) and exercise tolerance in patients with valvular heart disease (VHD) has been suggested; however, there are few data available regarding this relation. The aim of this study is to evaluate the correlation between exercise tolerance and NT-proBNP in patients with asymptomatic or mildly symptomatic significant VHD and normal left ventricular ejection fraction (LV EF). A total of 96 patients with asymptomatic or mildly symptomatic VHD and normal LV EF (≥50%) underwent cardiopulmonary exercise echocardiography. NT-proBNP levels were determined at baseline and after exercise in 3 hours. Patients were divided in 2 groups based on lower (<26 ml/kg/min, n = 47) or higher (≥26 ml/kg/min, n = 49) peak oxygen consumption (VO 2 ) as a representation of exercise tolerance. In the 2 groups, after adjusting for age and gender, the NT-proBNP level after exercise in 3 hours, left atrial volume index before exercise, right ventricular systolic pressure before exercise, E velocity after exercise, and E/e' ratio after exercise varied significantly. In addition, peak VO 2 was inversely related to NT-proBNP before (r = -0.352, p <0.001) and after exercise (r = -0.351, p <0.001). The NT-proBNP level before exercise was directly related to the left atrial volume index, E/e' ratio, and right ventricular systolic pressure before and after exercise. NT-proBNP after exercise was also directly related to the same parameters. NT-proBNP levels both before and after exercise were higher in the group with lower exercise tolerance. In conclusion, through the correlation among exercise tolerance, NT-proBNP, and parameters of diastolic dysfunction, we demonstrated that diastolic dysfunction and NT-proBNP could predict exercise tolerance in patients with significant VHD and normal LV EF. Copyright © 2017 Elsevier Inc. All rights reserved.

Cortical and diencephalic lesions in Korsakoff's syndrome: a clinical and CT scan study.

PubMed

Jacobson, R R; Lishman, W A

1990-02-01

Twenty-five male alcoholic Korsakoff patients were compared with age and sex-matched non-Korsakoff chronic alcoholics and healthy volunteers on clinical and CT brain scan parameters. The scans were assessed by planimetry, visual grading procedures and computerized analysis. Reliable measures of third ventricular size were developed. The Korsakoff patients had wider third ventricles, larger lateral ventricles and wider interhemispheric fissures than the comparison groups; but sulcal and Sylvian fissure widths were equivalent in Korsakoff and non-Korsakoff alcoholics. The results suggest that, in addition to their well-established diencephalic lesions, many Korsakoff patients have sustained widespread cerebral damage. Shrinkage in the frontal brain regions appears to be especially pronounced. The implications for a dual aetiology of alcoholic Korsakoff's syndrome involving thiamine deficiency and features associated with alcoholism, probably direct alcohol neurotoxicity, are discussed.

Ecrg4 expression and its product augurin in the choroid plexus: impact on fetal brain development, cerebrospinal fluid homeostasis and neuroprogenitor cell response to CNS injury

PubMed Central

2011-01-01

Background The content and composition of cerebrospinal fluid (CSF) is determined in large part by the choroid plexus (CP) and specifically, a specialized epithelial cell (CPe) layer that responds to, synthesizes, and transports peptide hormones into and out of CSF. Together with ventricular ependymal cells, these CPe relay homeostatic signals throughout the central nervous system (CNS) and regulate CSF hydrodynamics. One new candidate signal is augurin, a newly recognized 14 kDa protein that is encoded by esophageal cancer related gene-4 (Ecrg4), a putative tumor suppressor gene whose presence and function in normal tissues remains unexplored and enigmatic. The aim of this study was to explore whether Ecrg4 and its product augurin, can be implicated in CNS development and the response to CNS injury. Methods Ecrg4 gene expression in CNS and peripheral tissues was studied by in situ hybridization and quantitative RT-PCR. Augurin, the protein encoded by Ecrg4, was detected by immunoblotting, immunohistochemistry and ELISA. The biological consequence of augurin over-expression was studied in a cortical stab model of rat CNS injury by intra-cerebro-ventricular injection of an adenovirus vector containing the Ecrg4 cDNA. The biological consequences of reduced augurin expression were evaluated by characterizing the CNS phenotype caused by Ecrg4 gene knockdown in developing zebrafish embryos. Results Gene expression and immunohistochemical analyses revealed that, the CP is a major source of Ecrg4 in the CNS and that Ecrg4 mRNA is predominantly localized to choroid plexus epithelial (CPe), ventricular and central canal cells of the spinal cord. After a stab injury into the brain however, both augurin staining and Ecrg4 gene expression decreased precipitously. If the loss of augurin was circumvented by over-expressing Ecrg4 in vivo, BrdU incorporation by cells in the subependymal zone decreased. Inversely, gene knockdown of Ecrg4 in developing zebrafish embryos caused increased proliferation of GFAP-positive cells and induced a dose-dependent hydrocephalus-like phenotype that could be rescued by co-injection of antisense morpholinos with Ecrg4 mRNA. Conclusion An unusually elevated expression of the Ecrg4 gene in the CP implies that its product, augurin, plays a role in CP-CSF-CNS function. The results are all consistent with a model whereby an injury-induced decrease in augurin dysinhibits target cells at the ependymal-subependymal interface. We speculate that the ability of CP and ependymal epithelium to alter the progenitor cell response to CNS injury may be mediated, in part by Ecrg4. If so, the canonic control of its promoter by DNA methylation may implicate epigenetic mechanisms in neuroprogenitor fate and function in the CNS. PMID:21349154

Emerging hemodynamic signatures of the right heart (Third International Right Heart Failure Summit, part 2).

PubMed

Maron, Bradley A

2014-12-01

Despite the importance of preserved right ventricular structure and function with respect to outcome across the spectrum of lung, cardiac, and pulmonary vascular diseases, only recently have organized efforts developed to consider the pulmonary vascular-right ventricular apparatus as a specific unit within the larger context of cardiopulmonary pathophysiology. The Third International Right Heart Failure Summit (Boston, MA) was a multidisciplinary event dedicated to promoting a dialogue about the scientific and clinical basis of right heart disease. The current review provides a synopsis of key discussions presented during the section of the summit titled "Emerging Hemodynamic Signatures of the Right Heart." Specifically, topics emphasized in this element of the symposium included (1) the effects of pulmonary vascular dysfunction at rest or provoked by exercise on the right ventricular pressure-volume relationship, (2) the role of pressure-volume loop analysis as a method to characterize right ventricular inefficiency and predict right heart failure, and (3) the importance of a systems biology approach to identifying novel factors that contribute to pathophenotypes associated with pulmonary arterial hypertension and/or right ventricular dysfunction. Collectively, these concepts frame a forward-thinking paradigm shift in the approach to right heart disease by emphasizing factors that regulate the transition from adaptive to maladaptive right ventricular-pulmonary vascular (patho)physiology.