Metabolic liver function measured in vivo by dynamic (18)F-FDGal PET/CT without arterial blood sampling.

PubMed

Horsager, Jacob; Munk, Ole Lajord; Sørensen, Michael

2015-01-01

Metabolic liver function can be measured by dynamic PET/CT with the radio-labelled galactose-analogue 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) in terms of hepatic systemic clearance of (18)F-FDGal (K, ml blood/ml liver tissue/min). The method requires arterial blood sampling from a radial artery (arterial input function), and the aim of this study was to develop a method for extracting an image-derived, non-invasive input function from a volume of interest (VOI). Dynamic (18)F-FDGal PET/CT data from 16 subjects without liver disease (healthy subjects) and 16 patients with liver cirrhosis were included in the study. Five different input VOIs were tested: four in the abdominal aorta and one in the left ventricle of the heart. Arterial input function from manual blood sampling was available for all subjects. K*-values were calculated using time-activity curves (TACs) from each VOI as input and compared to the K-value calculated using arterial blood samples as input. Each input VOI was tested on PET data reconstructed with and without resolution modelling. All five image-derived input VOIs yielded K*-values that correlated significantly with K calculated using arterial blood samples. Furthermore, TACs from two different VOIs yielded K*-values that did not statistically deviate from K calculated using arterial blood samples. A semicircle drawn in the posterior part of the abdominal aorta was the only VOI that was successful for both healthy subjects and patients as well as for PET data reconstructed with and without resolution modelling. Metabolic liver function using (18)F-FDGal PET/CT can be measured without arterial blood samples by using input data from a semicircle VOI drawn in the posterior part of the abdominal aorta.

Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

PubMed

Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

2012-01-01

Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

The arteries of brain base in species of Bovini tribe.

PubMed

Zdun, Maciej; Frąckowiak, Hieronim; Kiełtyka-Kurc, Agata; Kowalczyk, Karolina; Nabzdyk, Maria; Timm, Anita

2013-11-01

Studies were conducted on 78 preparations of head and brain arteries in four species of Bos genus, that is in domestic cattle (N = 59), including 22 foetuses (CRL 36.5-78.5 cm), in banteng (Bos javanicus, N = 3), yak (Bos mutus f. grunniens, N = 2), American bison (Bison bison, N = 4), and European bison (Bison bonasus, N = 10). The comparative analysis permitted to demonstrate a similar pattern of brain base arteries in the studied animals. In the studied species, blood vessels of the arterial circle of the brain were found to form by bifurcation of intracranial segments of inner carotid arteries, which protruded from the paired rostral epidural rete mirabile. In Bovidae arterial circle of the brain was supplied with blood mainly by maxillary artery through the blood vessels of the paired rostral epidural rete mirabile. The unpaired caudal epidural rete mirabile was participating in blood supply to the arterial circle of the brain from vertebral and occipital arteries. It manifested character of a taxonomic trait for species of Bos and Bison genera. Basilar artery in all the examined animals manifested a variable diameter, with preliminary portion markedly narrowed, which prevented its participation in blood supply to the arterial circle of the brain. The results and taxonomic position of the species made the authors to suggest a hypothesis that a similar arterial pattern on the brain base might be present also in other species, not included in this analysis. Copyright © 2013 Wiley Periodicals, Inc.

An open tool for input function estimation and quantification of dynamic PET FDG brain scans.

PubMed

Bertrán, Martín; Martínez, Natalia; Carbajal, Guillermo; Fernández, Alicia; Gómez, Álvaro

2016-08-01

Positron emission tomography (PET) analysis of clinical studies is mostly restricted to qualitative evaluation. Quantitative analysis of PET studies is highly desirable to be able to compute an objective measurement of the process of interest in order to evaluate treatment response and/or compare patient data. But implementation of quantitative analysis generally requires the determination of the input function: the arterial blood or plasma activity which indicates how much tracer is available for uptake in the brain. The purpose of our work was to share with the community an open software tool that can assist in the estimation of this input function, and the derivation of a quantitative map from the dynamic PET study. Arterial blood sampling during the PET study is the gold standard method to get the input function, but is uncomfortable and risky for the patient so it is rarely used in routine studies. To overcome the lack of a direct input function, different alternatives have been devised and are available in the literature. These alternatives derive the input function from the PET image itself (image-derived input function) or from data gathered from previous similar studies (population-based input function). In this article, we present ongoing work that includes the development of a software tool that integrates several methods with novel strategies for the segmentation of blood pools and parameter estimation. The tool is available as an extension to the 3D Slicer software. Tests on phantoms were conducted in order to validate the implemented methods. We evaluated the segmentation algorithms over a range of acquisition conditions and vasculature size. Input function estimation algorithms were evaluated against ground truth of the phantoms, as well as on their impact over the final quantification map. End-to-end use of the tool yields quantification maps with [Formula: see text] relative error in the estimated influx versus ground truth on phantoms. The main contribution of this article is the development of an open-source, free to use tool that encapsulates several well-known methods for the estimation of the input function and the quantification of dynamic PET FDG studies. Some alternative strategies are also proposed and implemented in the tool for the segmentation of blood pools and parameter estimation. The tool was tested on phantoms with encouraging results that suggest that even bloodless estimators could provide a viable alternative to blood sampling for quantification using graphical analysis. The open tool is a promising opportunity for collaboration among investigators and further validation on real studies.

Simplifications in analyzing positron emission tomography data: effects on outcome measures.

PubMed

Logan, Jean; Alexoff, David; Kriplani, Aarti

2007-10-01

Initial validation studies of new radiotracers generally involve kinetic models that require a measured arterial input function. This allows for the separation of tissue binding from delivery and blood flow effects. However, when using a tracer in a clinical setting, it is necessary to eliminate arterial blood sampling due to its invasiveness and the extra burden of counting and analyzing the blood samples for metabolites. In some cases, it may also be necessary to replace dynamic scanning with a shortened scanning period some time after tracer injection, as is done with FDG (F-18 fluorodeoxyglucose). These approximations represent loss of information. In this work, we considered several questions related to this: (1) Do differences in experimental conditions (drug treatments) or populations affect the input function, and what effect, if any, does this have on the final outcome measure? (2) How do errors in metabolite measurements enter into results? (3) What errors are incurred if the uptake ratio is used in place of the distribution volume ratio? (4) Is one- or two-point blood sampling any better for FDG data than the standardized uptake value? and (5) If blood sampling is necessary, what alternatives are there to arterial blood sampling? The first three questions were considered in terms of data from human dynamic positron emission tomography (PET) studies under conditions of baseline and drug pretreatment. Data from [11C]raclopride studies and those from the norepinephrine transporter tracer (S,S)-[11C]O-methyl reboxetine were used. Calculation of a metabolic rate for FDG using the operational equation requires a measured input function. We tested a procedure based on two blood samples to estimate the plasma integral and convolution that occur in the operational equation. There are some tracers for which blood sampling is necessary. Strategies for brain studies involve using the internal carotids in estimating the radioactivity after correcting for partial volume and spillover in order to eliminate arterial sampling. Some venous blood samples are still required for metabolite measurements. The ultimate solution to the problem of arterial sampling may be a wrist scanner, which acts as a small PET camera for imaging the arteries in the wrist. This is currently under development.

Automated detection of arterial input function in DSC perfusion MRI in a stroke rat model

NASA Astrophysics Data System (ADS)

Yeh, M.-Y.; Lee, T.-H.; Yang, S.-T.; Kuo, H.-H.; Chyi, T.-K.; Liu, H.-L.

2009-05-01

Quantitative cerebral blood flow (CBF) estimation requires deconvolution of the tissue concentration time curves with an arterial input function (AIF). However, image-based determination of AIF in rodent is challenged due to limited spatial resolution. We evaluated the feasibility of quantitative analysis using automated AIF detection and compared the results with commonly applied semi-quantitative analysis. Permanent occlusion of bilateral or unilateral common carotid artery was used to induce cerebral ischemia in rats. The image using dynamic susceptibility contrast method was performed on a 3-T magnetic resonance scanner with a spin-echo echo-planar-image sequence (TR/TE = 700/80 ms, FOV = 41 mm, matrix = 64, 3 slices, SW = 2 mm), starting from 7 s prior to contrast injection (1.2 ml/kg) at four different time points. For quantitative analysis, CBF was calculated by the AIF which was obtained from 10 voxels with greatest contrast enhancement after deconvolution. For semi-quantitative analysis, relative CBF was estimated by the integral divided by the first moment of the relaxivity time curves. We observed if the AIFs obtained in the three different ROIs (whole brain, hemisphere without lesion and hemisphere with lesion) were similar, the CBF ratios (lesion/normal) between quantitative and semi-quantitative analyses might have a similar trend at different operative time points. If the AIFs were different, the CBF ratios might be different. We concluded that using local maximum one can define proper AIF without knowing the anatomical location of arteries in a stroke rat model.

Brain arterial aging and its relationship to Alzheimer dementia

PubMed Central

Honig, Lawrence; Elkind, Mitchell S.V.; Mohr, Jay P.; Goldman, James; Dwork, Andrew J.; Morgello, Susan; Marshall, Randolph S.

2016-01-01

Objective: To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD). Methods: Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models. Results: We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002). Conclusions: Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD. PMID:26984942

Brain arterial aging and its relationship to Alzheimer dementia.

PubMed

Gutierrez, Jose; Honig, Lawrence; Elkind, Mitchell S V; Mohr, Jay P; Goldman, James; Dwork, Andrew J; Morgello, Susan; Marshall, Randolph S

2016-04-19

To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD). Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models. We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002). Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD. © 2016 American Academy of Neurology.

Stroke

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... body and lodges within an artery in the brain. When an internal arterial wall becomes damaged, various ... internal carotid artery, breaks loose, travels towards the brain and lodges in a cerebral artery. The blocked ...

Artery and vein segmentation of the cerebral vasculature in 4D CT using a 3D fully convolutional neural network

NASA Astrophysics Data System (ADS)

Meijs, Midas; Manniesing, Rashindra

2018-02-01

Segmentation of the arteries and veins of the cerebral vasculature is important for improved visualization and for the detection of vascular related pathologies including arteriovenous malformations. We propose a 3D fully convolutional neural network (CNN) using a time-to-signal image as input and the distance to the center of gravity of the brain as spatial feature integrated in the final layers of the CNN. The method was trained and validated on 6 and tested on 4 4D CT patient imaging data. The reference standard was acquired by manual annotations by an experienced observer. Quantitative evaluation showed a mean Dice similarity coefficient of 0.94 +/- 0.03 and 0.97 +/- 0.01, a mean absolute volume difference of 4.36 +/- 5.47 % and 1.79 +/- 2.26 % for artery and vein respectively and an overall accuracy of 0.96 +/- 0.02. The average calculation time per volume on the test set was approximately one minute. Our method shows promising results and enables fast and accurate segmentation of arteries and veins in full 4D CT imaging data.

Infra-red thermometry: the reliability of tympanic and temporal artery readings for predicting brain temperature after severe traumatic brain injury.

PubMed

Kirk, Danielle; Rainey, Timothy; Vail, Andy; Childs, Charmaine

2009-01-01

Temperature measurement is important during routine neurocritical care especially as differences between brain and systemic temperatures have been observed. The purpose of the study was to determine if infra-red temporal artery thermometry provides a better estimate of brain temperature than tympanic membrane temperature for patients with severe traumatic brain injury. Brain parenchyma, tympanic membrane and temporal artery temperatures were recorded every 15-30 min for five hours during the first seven days after admission. Twenty patients aged 17-76 years were recruited. Brain and tympanic membrane temperature differences ranged from -0.8 degrees C to 2.5 degrees C (mean 0.9 degrees C). Brain and temporal artery temperature differences ranged from -0.7 degrees C to 1.5 degrees C (mean 0.3 degrees C). Tympanic membrane temperature differed from brain temperature by an average of 0.58 degrees C more than temporal artery temperature measurements (95% CI 0.31 degrees C to 0.85 degrees C, P < 0.0001). At temperatures within the normal to febrile range, temporal artery temperature is closer to brain temperature than is tympanic membrane temperature.

A Functional Perspective on the Embryology and Anatomy of the Cerebral Blood Supply

PubMed Central

Menshawi, Khaled; Mohr, Jay P

2015-01-01

The anatomy of the arterial system supplying blood to the brain can influence the development of arterial disease such as aneurysms, dolichoectasia and atherosclerosis. As the arteries supplying blood to the brain develop during embryogenesis, variation in their anatomy may occur and this variation may influence the development of arterial disease. Angiogenesis, which occurs mainly by sprouting of parent arteries, is the first stage at which variations can occur. At day 24 of embryological life, the internal carotid artery is the first artery to form and it provides all the blood required by the primitive brain. As the occipital region, brain stem and cerebellum enlarge; the internal carotid supply becomes insufficient, triggering the development of the posterior circulation. At this stage, the posterior circulation consists of a primitive mesh of arterial networks that originate from projection of penetrators from the distal carotid artery and more proximally from carotid-vertebrobasilar anastomoses. These anastomoses regress when the basilar artery and the vertebral arteries become independent from the internal carotid artery, but their persistence is not uncommon in adults (e.g., persistent trigeminal artery). Other common remnants of embryological development include fenestration or duplication (most commonly of the basilar artery), hypoplasia (typically of the posterior communicating artery) or agenesis (typically of the anterior communicating artery). Learning more about the hemodynamic consequence that these variants may have on the brain territories they supply may help understand better the underlying physiopathology of cerebral arterial remodeling and stroke in patients with these variants. PMID:26060802

Comparing model-based and model-free analysis methods for QUASAR arterial spin labeling perfusion quantification.

PubMed

Chappell, Michael A; Woolrich, Mark W; Petersen, Esben T; Golay, Xavier; Payne, Stephen J

2013-05-01

Amongst the various implementations of arterial spin labeling MRI methods for quantifying cerebral perfusion, the QUASAR method is unique. By using a combination of labeling with and without flow suppression gradients, the QUASAR method offers the separation of macrovascular and tissue signals. This permits local arterial input functions to be defined and "model-free" analysis, using numerical deconvolution, to be used. However, it remains unclear whether arterial spin labeling data are best treated using model-free or model-based analysis. This work provides a critical comparison of these two approaches for QUASAR arterial spin labeling in the healthy brain. An existing two-component (arterial and tissue) model was extended to the mixed flow suppression scheme of QUASAR to provide an optimal model-based analysis. The model-based analysis was extended to incorporate dispersion of the labeled bolus, generally regarded as the major source of discrepancy between the two analysis approaches. Model-free and model-based analyses were compared for perfusion quantification including absolute measurements, uncertainty estimation, and spatial variation in cerebral blood flow estimates. Major sources of discrepancies between model-free and model-based analysis were attributed to the effects of dispersion and the degree to which the two methods can separate macrovascular and tissue signal. Copyright © 2012 Wiley Periodicals, Inc.

Kinetic Analysis and Quantification of [11C]Martinostat for in vivo HDAC Imaging of the Brain

PubMed Central

Wey, Hsiao-Ying; Wang, Changning; Schroeder, Frederick A.; Logan, Jean; Price, Julie C.; Hooker, Jacob M.

2015-01-01

Epigenetic mechanisms mediated by histone deacetylases (HDACs) have been implicated in a wide-range of CNS disorders and may offer new therapeutic opportunities. In vivo evaluation of HDAC density and drug occupancy has become possible with [11C]Martinostat, which exhibits selectivity for a subset of class I/IIb HDAC enzymes. In this study, we characterize the kinetic properties of [11C]Martinostat in the nonhuman primate (NHP) brain in preparation for human neuroimaging studies. The goal of this work was to determine whether classic compartmental analysis techniques were appropriate and to further determine if arterial plasma is required for future NHP studies. Using an arterial plasma input function, several analysis approaches were evaluated for robust outcome measurements. [11C]Martinostat showed high baseline distribution volume (VT) ranging from 29.9–54.4 mL/cm3 in the brain and large changes in occupancy (up to 99%) with a blocking dose approaches full enzyme saturation. An averaged nondisplaceable tissue uptake (VND) of 8.6 ± 3.7 mL/cm3 suggests high specific binding of [11C]Martinostat. From a two-tissue compartment model, [11C]Martinostat exhibits a high K1 (averaged K1 of 0.65 mL/cm3/min) and a small k4 (average of 0.0085 min−1). Our study supports that [11C]Martinostat can be used to detect changes in HDAC density and occupancy in vivo and that simplified analysis not using arterial blood could be appropriate. PMID:25768025

Kinetic Analysis and Quantification of [ 11C]Martinostat for in Vivo HDAC Imaging of the Brain

DOE PAGES

Wey, Hsiao-Ying; Wang, Changning; Schroeder, Frederick A.; ...

2015-03-13

We report that epigenetic mechanisms mediated by histone deacetylases (HDACs) have been implicated in a wide-range of CNS disorders and may offer new therapeutic opportunities. In vivo evaluation of HDAC density and drug occupancy has become possible with [ 11C]Martinostat, which exhibits selectivity for a subset of class I/IIb HDAC enzymes. In this study, we characterize the kinetic properties of [ 11C]Martinostat in the nonhuman primate (NHP) brain in preparation for human neuroimaging studies. The goal of this work was to determine whether classic compartmental analysis techniques were appropriate and to further determine if arterial plasma is required for futuremore » NHP studies. Using an arterial plasma input function, several analysis approaches were evaluated for robust outcome measurements. [ 11C]Martinostat showed high baseline distribution volume (V T) ranging from 29.9 to 54.4 mL/cm 3 in the brain and large changes in occupancy (up to 99%) with a blocking dose approaching full enzyme saturation. An averaged nondisplaceable tissue uptake (VND) of 8.6 ± 3.7 mL/cm 3 suggests high specific binding of [ 11C]Martinostat. From a two-tissue compartment model, [ 11C]Martinostat exhibits a high K 1 (averaged K 1 of 0.65 mL/cm 3/min) and a small k 4 (average of 0.0085 min –1). In conclusion, our study supports that [ 11C]Martinostat can be used to detect changes in HDAC density and occupancy in vivo and that simplified analysis not using arterial blood could be appropriate.« less

Reconstruction of an input function from a dynamic PET water image using multiple tissue curves

NASA Astrophysics Data System (ADS)

Kudomi, Nobuyuki; Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro

2016-08-01

Quantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. When CBF is assessed using PET with {{\\text{H}}2} 15O or C15O2, its calculation requires an arterial input function, which generally requires invasive arterial blood sampling. The aim of the present study was to develop a new technique to reconstruct an image derived input function (IDIF) from a dynamic {{\\text{H}}2} 15O PET image as a completely non-invasive approach. Our technique consisted of using a formula to express the input using tissue curve with rate constant parameter. For multiple tissue curves extracted from the dynamic image, the rate constants were estimated so as to minimize the sum of the differences of the reproduced inputs expressed by the extracted tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects (n  =  29) and was compared to the blood sampling method. Simulation studies were performed to examine the magnitude of potential biases in CBF and to optimize the number of multiple tissue curves used for the input reconstruction. In the PET study, the estimated IDIFs were well reproduced against the measured ones. The difference between the calculated CBF values obtained using the two methods was small as around  <8% and the calculated CBF values showed a tight correlation (r  =  0.97). The simulation showed that errors associated with the assumed parameters were  <10%, and that the optimal number of tissue curves to be used was around 500. Our results demonstrate that IDIF can be reconstructed directly from tissue curves obtained through {{\\text{H}}2} 15O PET imaging. This suggests the possibility of using a completely non-invasive technique to assess CBF in patho-physiological studies.

Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain.

PubMed

Iliff, Jeffrey J; Wang, Minghuan; Zeppenfeld, Douglas M; Venkataraman, Arun; Plog, Benjamin A; Liao, Yonghong; Deane, Rashid; Nedergaard, Maiken

2013-11-13

CSF from the subarachnoid space moves rapidly into the brain along paravascular routes surrounding penetrating cerebral arteries, exchanging with brain interstitial fluid (ISF) and facilitating the clearance of interstitial solutes, such as amyloid β, in a pathway that we have termed the "glymphatic" system. Prior reports have suggested that paravascular bulk flow of CSF or ISF may be driven by arterial pulsation. However, cerebral arterial pulsation could not be directly assessed. In the present study, we use in vivo two-photon microscopy in mice to visualize vascular wall pulsatility in penetrating intracortical arteries. We observed that unilateral ligation of the internal carotid artery significantly reduced arterial pulsatility by ~50%, while systemic administration of the adrenergic agonist dobutamine increased pulsatility of penetrating arteries by ~60%. When paravascular CSF-ISF exchange was evaluated in real time using in vivo two-photon and ex vivo fluorescence imaging, we observed that internal carotid artery ligation slowed the rate of paravascular CSF-ISF exchange, while dobutamine increased the rate of paravascular CSF-ISF exchange. These findings demonstrate that cerebral arterial pulsatility is a key driver of paravascular CSF influx into and through the brain parenchyma, and suggest that changes in arterial pulsatility may contribute to accumulation and deposition of toxic solutes, including amyloid β, in the aging brain.

The contribution of carotid rete variability to brain temperature variability in sheep in a thermoneutral environment.

PubMed

Maloney, Shane K; Mitchell, Duncan; Blache, Dominique

2007-03-01

The degree of variability in the temperature difference between the brain and carotid arterial blood is greater than expected from the presumed tight coupling between brain heat production and brain blood flow. In animals with a carotid rete, some of that variability arises in the rete. Using thermometric data loggers in five sheep, we have measured the temperature of arterial blood before it enters the carotid rete and after it has perfused the carotid rete, as well as hypothalamic temperature, every 2 min for between 6 and 12 days. The sheep were conscious, unrestrained, and maintained at an ambient temperature of 20-22 degrees C. On average, carotid arterial blood and brain temperatures were the same, with a decrease in blood temperature of 0.35 degrees C across the rete and then an increase in temperature of the same magnitude between blood leaving the rete and the brain. Rete cooling of arterial blood took place at temperatures below the threshold for selective brain cooling. All of the variability in the temperature difference between carotid artery and brain was attributable statistically to variability in the temperature difference across the rete. The temperature difference between arterial blood leaving the rete and the brain varied from -0.1 to 0.9 degrees C. Some of this variability was related to a thermal inertia of the brain, but the majority we attribute to instability in the relationship between brain blood flow and brain heat production.

Development of functional in vivo imaging of cerebral lenticulostriate artery using novel synchrotron radiation angiography

NASA Astrophysics Data System (ADS)

Lin, Xiaojie; Miao, Peng; Mu, Zhihao; Jiang, Zhen; Lu, Yifan; Guan, Yongjing; Chen, Xiaoyan; Xiao, Tiqiao; Wang, Yongting; Yang, Guo-Yuan

2015-02-01

The lenticulostriate artery plays a vital role in the onset and development of cerebral ischemia. However, current imaging techniques cannot assess the in vivo functioning of small arteries such as the lenticulostriate artery in the brain of rats. Here, we report a novel method to achieve a high resolution multi-functional imaging of the cerebrovascular system using synchrotron radiation angiography, which is based on spatio-temporal analysis of contrast density in the arterial cross section. This method provides a unique tool for studying the sub-cortical vascular elasticity after cerebral ischemia in rats. Using this technique, we demonstrated that the vascular elasticity of the lenticulostriate artery decreased from day 1 to day 7 after transient middle cerebral artery occlusion in rats and recovered from day 7 to day 28 compared to the controls (p < 0.001), which paralleled with brain edema formation and inversely correlated with blood flow velocity (p < 0.05). Our results demonstrated that the change of vascular elasticity was related to the levels of brain edema and the velocity of focal blood flow, suggesting that reducing brain edema is important for the improvement of the function of the lenticulostriate artery in the ischemic brain.

The arteries of the base of the brain in the N. American mink (Mustela vison (Brisson, 1756)).

PubMed

Gościcka, D; Stankiewicz, W; Szpinda, M

1995-01-01

110 brains of the N. American mink were studied for the arteries of the base of the brain, using the anatomical method and Digital Imaging Analysis. Two arterial circles were isolated: the larger cerebral circle (CC) and the smaller medullar circle (MC). These were connected by the basal artery of the brain. We found that in CC, its left part was larger, whereas in MC, it was the right part that was larger. Also, the capacity was larger in the caudal part of MC than in its rostral part.

Experimental study on the pressure wave propagation in the artificial arterial tree in brain

NASA Astrophysics Data System (ADS)

Shimada, Shinya; Tsurusaki, Ryo; Iwase, Fumiaki; Matsukawa, Mami; Lagrée, Pierre-Yves

2018-07-01

A pulse wave measurement is effective for the early detection of arteriosclerosis. The pulse wave consists of incident and reflected waves. The reflected wave of the pulse wave measured at the left common carotid artery seems to originate from the vascular beds in the brain. The aim of this study is to know if the reflected waves from the occlusions in cerebral arteries can affect the pulse waveform. The artificial arterial tree in the brain was therefore fabricated using polyurethane tubes. After investigating the effects of the bifurcation angle on the pulse waveform, we attempted to confirm whether the reflected waves from occlusions in the artificial arterial tree in the brain can be experimentally measured at the left common carotid artery. Results indicate that the bifurcation angle did not affect the pulse waveform, and that the reflected wave from an occlusion with a diameter of more than 1 mm in the brain could be observed.

Vessel segmentation in 4D arterial spin labeling magnetic resonance angiography images of the brain

NASA Astrophysics Data System (ADS)

Phellan, Renzo; Lindner, Thomas; Falcão, Alexandre X.; Forkert, Nils D.

2017-03-01

4D arterial spin labeling magnetic resonance angiography (4D ASL MRA) is a non-invasive and safe modality for cerebrovascular imaging procedures. It uses the patient's magnetically labeled blood as intrinsic contrast agent, so that no external contrast media is required. It provides important 3D structure and blood flow information but a sufficient cerebrovascular segmentation is important since it can help clinicians to analyze and diagnose vascular diseases faster, and with higher confidence as compared to simple visual rating of raw ASL MRA images. This work presents a new method for automatic cerebrovascular segmentation in 4D ASL MRA images of the brain. In this process images are denoised, corresponding image label/control image pairs of the 4D ASL MRA sequences are subtracted, and temporal intensity averaging is used to generate a static representation of the vascular system. After that, sets of vessel and background seeds are extracted and provided as input for the image foresting transform algorithm to segment the vascular system. Four 4D ASL MRA datasets of the brain arteries of healthy subjects and corresponding time-of-flight (TOF) MRA images were available for this preliminary study. For evaluation of the segmentation results of the proposed method, the cerebrovascular system was automatically segmented in the high-resolution TOF MRA images using a validated algorithm and the segmentation results were registered to the 4D ASL datasets. Corresponding segmentation pairs were compared using the Dice similarity coefficient (DSC). On average, a DSC of 0.9025 was achieved, indicating that vessels can be extracted successfully from 4D ASL MRA datasets by the proposed segmentation method.

Relations of arterial stiffness and endothelial function to brain aging in the community.

PubMed

Tsao, Connie W; Seshadri, Sudha; Beiser, Alexa S; Westwood, Andrew J; Decarli, Charles; Au, Rhoda; Himali, Jayandra J; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Larson, Martin G; Benjamin, Emelia J; Wolf, Philip A; Vasan, Ramachandran S; Mitchell, Gary F

2013-09-10

To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging. Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively). Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05). Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.

Image-derived input function in PET brain studies: blood-based methods are resistant to motion artifacts.

PubMed

Zanotti-Fregonara, Paolo; Liow, Jeih-San; Comtat, Claude; Zoghbi, Sami S; Zhang, Yi; Pike, Victor W; Fujita, Masahiro; Innis, Robert B

2012-09-01

Image-derived input function (IDIF) from carotid arteries is an elegant alternative to full arterial blood sampling for brain PET studies. However, a recent study using blood-free IDIFs found that this method is particularly vulnerable to patient motion. The present study used both simulated and clinical [11C](R)-rolipram data to assess the robustness of a blood-based IDIF method (a method that is ultimately normalized with blood samples) with regard to motion artifacts. The impact of motion on the accuracy of IDIF was first assessed with an analytical simulation of a high-resolution research tomograph using a numerical phantom of the human brain, equipped with internal carotids. Different degrees of translational (from 1 to 20 mm) and rotational (from 1 to 15°) motions were tested. The impact of motion was then tested on the high-resolution research tomograph dynamic scans of three healthy volunteers, reconstructed with and without an online motion correction system. IDIFs and Logan-distribution volume (VT) values derived from simulated and clinical scans with motion were compared with those obtained from the scans with motion correction. In the phantom scans, the difference in the area under the curve (AUC) for the carotid time-activity curves was up to 19% for rotations and up to 66% for translations compared with the motionless simulation. However, for the final IDIFs, which were fitted to blood samples, the AUC difference was 11% for rotations and 8% for translations. Logan-VT errors were always less than 10%, except for the maximum translation of 20 mm, in which the error was 18%. Errors in the clinical scans without motion correction appeared to be minor, with differences in AUC and Logan-VT always less than 10% compared with scans with motion correction. When a blood-based IDIF method is used for neurological PET studies, the motion of the patient affects IDIF estimation and kinetic modeling only minimally.

[Association of three anatomical variants of the anterior cerebral circulation].

PubMed

Reyes-Soto, Gervith; Pérez-Cruz, Julio; Delgado-Reyes, Luis; Ortega-Gutiérrez, César; Téllez-Palacios, Daniela

2012-01-01

As part of a study of the microsurgical anatomy of the pericallosal artery, we describe one brain with three unusual anatomical variants. From the autopsy of a 45 year-old female, we extracted the brain and all the arterial blood vessels were washed off with saline solution to be injected afterwards with red latex. The brain was then immersed in 10% formalin for two months. Finally, we dissected and measured the internal carotid artery segments, using a digital Vernier caliper under a Carl Zeiss OPMI surgical microscope with magnification of 6x up to 40x. The brain's weight was 1250 grams and three rare anatomical variants were found: 1) right accessory middle cerebral artery (ACMA-d), 2) right bihemispheric anterior cerebral artery (ACABihem-d), 3) median artery of the corpus callosum (AMCC). The association of the anatomical variations described previously is inconstant; furthermore, their appearance in a single case is rare.

N-terminal pro-brain natriuretic peptide in acute Kawasaki disease correlates with coronary artery involvement.

PubMed

Adjagba, Philippe M; Desjardins, Laurent; Fournier, Anne; Spigelblatt, Linda; Montigny, Martine; Dahdah, Nagib

2015-10-01

We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease. We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin. We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5-10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated. There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05-22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04-0.02), but not during convalescence at 2-3 months (odds ratio 1.28 [95% confidence interval 0.23-7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1). Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.

Photon dynamics in tissue imaging

NASA Astrophysics Data System (ADS)

Chance, Britton; Haselgrove, John C.; Wang, NaiGuang; Maris, Michael B.; Sevick-Muraca, Eva M.

1991-11-01

The emerging need for a fast, safe economical approach to global and localized measures of desaturation of hemoglobin with oxygen (HbO2) in the human brain motivates further research on time-resolved spectroscopy in four areas of study. (1) To afford quantization of hemoglobin saturation through time-resolved spectroscopy in the time domain (TD) and in the frequency domain (FD). Evaluation of dual-wavelength TD and FD spectrometers for determining quantitatively hemoglobin desaturation and blood-volume changes by calculations that are insensitive to mutual interference is proposed. The diffusion equation, as it applies especially to TD studies, and the absorption ((mu) a) and scattering ((mu) s) coefficients provide their independent determination from the late and early respective portions of the kinetics of the emergent photons in response to a short input pulse (50-100 psec). (2) The identification of the photon-pathlength change due to the arterial pulse in the brain tissue by FD methods with Fourier transformation affords an opportunity to employ principles of pulse oximetry to vessels localized deep within the brain tissue. (3) Localization of desaturation of hemoglobin in portions of the brain can be achieved through dual-wavelength scanning of the input/output optical fibers across the head for an X-Y coordinate and varying the distance between input and output ((rho) ) or the time delay in data acquisition to afford an in-depth Z scan. Localizations of shed blood, which have an effective concentration of over 10 times that of capillary-bed blood, are identified by X, Y, Z scans using only a single wavelength. (4) Independent measurements of absorption ((mu) a) and scattering ((mu) s) coefficients, particularly by TD techniques, affords structural mapping of the brain, which can be used to diagnose brain tumor and neuronal degeneration. Two experimental systems are used to critically evaluate these studies; the first, a hemoglobin/lipid/yeast model in which intermittent oxygenation gives saturation/desaturation effects and addition of hemoglobin simulates increased blood volume. These models can be global or may contain localized ''black'' absorbers simulating brain bleeds or model-stroke volumes in which oxygenation/deoxygenation simulates normoxia/hypoxia. Secondly, animal brains are used to model the following changes in vivo: global or localized hypoxia, brain bleeding, and hematomas by epidural blood injection, and physiological changes by epilepsy. Neuronal degeneration causing scattering effects is modeled by injection, epidurally or into the animal model brain, highly scattering material such as polystyrene spheres. The proposal envisages a basic science study of photon migration in the brain with important applications to stroke, epilepsy, brain trauma, and neuronal degenerative disease.

Brain Perfusion and Arterial Blood Flow Velocity During Prolonged Body Tilting.

PubMed

Montero, David; Rauber, Sven

2016-08-01

It remains unknown whether brain perfusion is preserved and mirrored by middle cerebral blood flow velocity (MCA BFV) during prolonged changes in body posture. Herein, we examined the impact of sustained (180 min) 30° head-up (HUT) and head-down (HDT) tilt on brain perfusion, as determined by MCA BFV and blood flow in the extracranial arteries. In 10 healthy male subjects, arterial diameters, BFVs, and blood flows were determined in the left internal carotid (ICA) and vertebral (VA) arteries using duplex Doppler ultrasound in supine rest, and 5, 20, 60, 120, and 180 min following 30° HUT and HDT. MCA BFV was recorded throughout with transcranial Doppler ultrasound. ICA as well as VA diameters and blood flows were unaltered during HUT. Likewise, brain blood flow and MCA BFV were preserved with HUT. In the HDT protocol, ICA and VA diameters were gradually increased, although ICA, VA, and brain blood flows were preserved. MCA BFV was progressively reduced during HDT. In addition, MCA BFV was positively associated with ICA BFV (β = 0.9) and negatively associated with ICA diameter (β = -125.5). MCA BFV was positively associated with brain blood flow during HUT (β = 0.2) but not HDT. Brain perfusion is preserved whereas MCA BFV is progressively decreased and associated with extracranial arterial BFV during sustained 30° HDT. Therefore, MCA BFV may not be a surrogate of brain perfusion in conditions including prolonged HDT. Montero D, Rauber S. Brain perfusion and arterial blood flow velocity during prolonged body tilting. Aerosp Med Hum Perform. 2016; 87(8):682-687.

Fluid Mechanics of the Vascular Basement Membrane in the Brain

NASA Astrophysics Data System (ADS)

Coloma, Mikhail; Hui, Jonathan; Chiarot, Paul; Huang, Peter; Carare, Roxana; McLeod, Kenneth; Schaffer, David

2013-11-01

Beta-amyloid is a normal product of brain metabolic function and is found within the interstitial fluid of the brain. Failure of the clearance of beta-amyloid from the aging brain leads to its accumulation within the walls of arteries and to Alzheimer's disease. The vascular basement membrane (VBM) within the walls of cerebral arteries surrounds the spirally arranged smooth muscle cells and represents an essential pathway for removal of beta-amyloid from the brain. This process fails with the stiffening of arterial walls associated with aging. In this study we hypothesize that the deformation of the VBM associated with arterial pulsations drives the interstitial fluid to drain in the direction opposite of the arterial blood flow. This hypothesis is theoretically investigated by modeling the VBM as a thin, coaxial, fluid-filled porous medium surrounding a periodically deforming cylindrical tube. Flow and boundary conditions required to achieve such a backward clearance are derived through a control volume analysis of mass, momentum, and energy.

Atypical moyamoya syndrome with brain calcification and stenosis of abdominal aorta and renal arteries.

PubMed

Uchikawa, Hideki; Fujii, Katsunori; Fujita, Mayuko; Okunushi, Tomoko; Shimojo, Naoki

2017-09-01

Moyamoya syndrome is a progressive cerebrovascular disease that is characterized by stenosis of the terminal portion of the internal carotid artery and its main branches, in combination with an accompanying disease. We herein describe an 8-year-old boy exhibiting transient loss of consciousness, who had recurrent seizures in infancy with progressive brain calcification. On admission, he was alert but magnetic resonance angiography showed bilateral stenosis of the whole internal carotid artery and proliferation of vascular collaterals, and brain CT revealed calcification on bilateral putamen. Given that this fulfilled diagnostic criteria, we finally diagnosed him as having moyamoya syndrome, though the etiology was unclear. Interestingly, a whole vessel survey revealed vascular stenosis of abdominal aorta and renal arteries, in which the former has not been reported in moyamoya syndrome. We considered that brain calcification was gradually formed by decreased cerebral vascular flow from infancy, and stenosis of abdominal aorta was possibly extended from renal arteries. This is, moyamoya syndrome with brain calcification and stenosis of abdominal aorta, suggesting that morphological screening of whole vessels containing cerebral and abdominal arteries should be considered in cases of slowly progressive brain calcification. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Carotid Artery Disease

MedlinePlus

... brain (cerebrovascular disease). Like the heart, the brain’s cells need a constant supply of oxygen-rich blood. This blood supply is delivered to the brain by the 2 large carotid arteries in the front of your neck and by 2 smaller vertebral arteries at the back of your ...

P-glycoprotein (ABCB1) inhibits the influx and increases the efflux of 11C-metoclopramide across the blood-brain barrier: a PET study on non-human primates.

PubMed

Auvity, Sylvain; Caillé, Fabien; Marie, Solène; Wimberley, Catriona; Bauer, Martin; Langer, Oliver; Buvat, Irène; Goutal, Sébastien; Tournier, Nicolas

2018-05-10

Rationale : PET imaging using radiolabeled high-affinity substrates of P-glycoprotein (ABCB1) has convincingly revealed the role of this major efflux transporter in limiting the influx of its substrates from blood into the brain across the blood-brain barrier (BBB). Many drugs, such as metoclopramide, are weak ABCB1 substrates and distribute into the brain even when ABCB1 is fully functional. In this study, we used kinetic modeling and validated simplified methods to highlight and quantify the impact of ABCB1 on the BBB influx and efflux of 11 C-metoclopramide, as a model weak ABCB1 substrate, in non-human primates. Methods : The regional brain kinetics of a tracer dose of 11 C-metoclopramide (298 ± 44 MBq) were assessed in baboons using PET without (n = 4) or with intravenous co-infusion of the ABCB1 inhibitor tariquidar (4 mg/kg/h, n = 4). Metabolite-corrected arterial input functions were generated to estimate the regional volume of distribution ( V T ) as well as the influx ( K 1 ) and efflux ( k 2 ) rate constants, using a one-tissue compartment model. Modeling outcome parameters were correlated with image-derived parameters, i.e. area under the curve AUC 0-30 min and AUC 30-60 min (SUV.min) as well as the elimination slope (k E ; min -1 ) from 30 to 60 min of the regional time-activity curves. Results : Tariquidar significantly increased the brain distribution of 11 C-metoclopramide ( V T = 4.3 ± 0.5 mL/cm 3 and 8.7 ± 0.5 mL/cm 3 for baseline and ABCB1 inhibition conditions, respectively, P<0.001), with a 1.28-fold increase in K 1 (P < 0.05) and a 1.64-fold decrease in k 2 (P < 0.001). The effect of tariquidar was homogeneous across different brain regions. The most sensitive parameters to ABCB1 inhibition were V T (2.02-fold increase) and AUC 30-60 min (2.02-fold increase). V T was significantly (P < 0.0001) correlated with AUC 30-60 min (r 2 = 0.95), AUC 0-30 min (r 2 = 0.87) and k E (r 2 = 0.62). Conclusion : 11 C-metoclopramide PET imaging revealed the relative importance of both the influx hindrance and efflux enhancement components of ABCB1 in a relevant model of the human BBB. The overall impact of ABCB1 on drug delivery to the brain can be non-invasively estimated from image-derived outcome parameters without the need for an arterial input function. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Bacterial lipopolysaccharide-induced systemic inflammation alters perfusion of white matter-rich regions without altering flow in brain-irrigating arteries: Relationship to blood-brain barrier breakdown?

PubMed

Dhaya, Ibtihel; Griton, Marion; Raffard, Gérard; Amri, Mohamed; Hiba, Bassem; Konsman, Jan Pieter

2018-01-15

To better understand brain dysfunction during sepsis, cerebral arterial blood flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance Imaging in rats after intraperitoneal administration of bacterial lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion of the corpus callosum region and diffusion parallel to its fibers were higher after lipopolysaccharide administration as compared to saline injection. In parallel, lipopolysaccharide induced perivascular immunoglobulin-immunoreactivity in white matter. These findings indicate that systemic inflammation can result in increased perfusion, blood-brain barrier breakdown and altered water diffusion in white matter. Copyright © 2017 Elsevier B.V. All rights reserved.

Systematization and description of the internal carotid arteries and their main ramifications at the brain base in turtles (Trachemys scripta elegans).

PubMed

Voll, Juliana; Campos, Rui

2016-08-01

Thirty turtle brains (Trachemys scripta elegans) were injected with latex to systematize and describe the internal carotid arteries and their main ramifications at the brain base. The internal carotid arteries had one intercarotid anastomosis. At the level of the tuber cinereum, the internal carotid artery bifurcated into its terminal branches, the rostral and the caudal branches. The rostral branch emitted the rostral choroid artery, the orbital artery, and a series of middle cerebral arteries. After giving off the last middle cerebral artery, the rostral branch continued as the rostral cerebral artery in the cerebral longitudinal fissure, and had one anastomosis with its contralateral homologous artery, the rostral communicating artery, making the first rostral closure of the cerebral arterial circle. Next, the rostral cerebral arteries anastomosed forming a rostral interhemispheric artery, making the second rostral closure of the cerebral arterial circle. The internal carotid artery, after emitting its rostral branch, continued caudally as the caudal branch. The caudal branch ran caudally along the ventral surface of the mesencephalic tegmentum, emitted the caudal cerebral artery and the mesencephalic artery, and continued caudomedially while progressively narrowing, and anastomosed with its contralateral homologous artery, forming the basilar artery. The narrower portion also emitted the trigeminal artery. The anastomosis of the caudal branches closed the cerebral arterial circle caudally. The internal carotid arteries exclusively supplied the cerebral arterial circle of the turtle. Anat Rec, 299:1090-1098, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The influence of the nasal mucosa and the carotid rete upon hypothalamic temperature in sheep

PubMed Central

Baker, Mary Ann; Hayward, James N.

1968-01-01

1. In chronically-prepared sheep, intracranial temperatures were measured in the cavernous sinus among the vessels of the carotid rete and at the circle of Willis extravascularly, and in the preoptic area and in other brain stem regions. Extracranial temperatures were measured intravascularly in the carotid or internal maxillary arteries and on the nasal mucosa and the skin of the ear. 2. At 20° C ambient temperature, shifts in temperature of the hypothalamus and of other brain sites paralleled temperature shifts in the cerebral arterial blood which was cooler than central arterial blood. During periods of arousal and of paradoxical sleep, vasoconstriction of the nasal mucosa and the ear skin occurred and temperatures at the cerebral arteries and in the brain rose without a comparable rise in central arterial blood temperature. 3. Anaesthetic doses of barbiturate abolished the temperature oscillations in the cerebral arterial blood and the brain. When air was blown rapidly over the nasal mucosa in anaesthetized animals, temperatures dropped precipitously in the cavernous sinus, at the cerebral arteries, and in the brain, while central arterial temperature fell only slightly. Injections of latex into the facial venous system demonstrated a venous pathway from the nasal mucosa to the cavernous sinus. 4. When sheep were exposed to 45-50° C ambient temperature, respiratory rate increased 5-10 times and the temperature gradient between central and cerebral arterial blood widened. 5. It is concluded that venous blood returning from the nasal mucosa and the skin of the head to the cavernous sinus cools the central arterial blood in the carotid rete. This is an important factor in the maintenance of hypothalamic temperature in the wool-covered, long-nosed, panting sheep and undoubtedly affects hypothalamic thermoreceptors and temperature regulation in artiodactyls. PMID:5685288

Influence of the carotid rete on brain temperature in cats exposed to hot environments.

PubMed

Baker, M A

1972-02-01

1. Thermocouples were chronically implanted in various intracranial and extracranial structures in adult cats. Temperature of arterial blood on the proximal and distal sides of the carotid rete was determined by measuring temperature in the aortic arch and at the anterior cerebral arteries. Temperatures of brain stem regions supplied by the carotid rete and by the vertebral-basilar system were determined by measuring temperature in the anterior hypothalamus and the caudal medulla. Nasal mucosal temperature was measured with a thermocouple implanted in the nasal cavity.2. In a cool environment (25 degrees C), the temperature of anterior cerebral arterial blood was lower than aortic arterial temperature. Anterior cerebral temperature showed shifts which were not present in central (aortic) arterial blood and which were clearly associated with changes in heat loss from the nasal mucosa and with the behaviour of the animal. When the cats were relaxed or in e.e.g. slow-wave sleep, the nasal mucosal temperature was high and the temperature at the anterior cerebral arteries was as much as 0.30 degrees C less than aortic temperature. During behavioural arousal and paradoxical sleep, the nasal mucosal temperature fell and the anterior cerebral arterial temperature rose toward central arterial temperature. Shifts in hypothalamic temperature followed the changes in anterior cerebral arterial temperature. Medullary temperature was higher than aortic temperature and showed shifts which suggested that blood from the rostral circle of Willis mixed with vertebral blood in the basilar artery.3. When the ambient temperature was raised to 40-45 degrees C the cooling of cerebral arterial blood and brain increased as the rate of thermal panting increased. Respiratory rate increased tenfold and aortic temperature rose by 2.0-2.5 degrees C. Anterior cerebral arterial temperature fell below aortic temperature by as much as 1 degrees C, hypothalamic temperature dropping in parallel with cerebral arterial temperature. Medullary temperature cooled below aortic temperature during heat exposure, but the temperature drop in the medulla was not as high as in the rostral brain stem.4. Blowing air into the nasal cavity of anaesthetized cats produced a large, rapid temperature drop at the anterior cerebral arteries and in the hypothalamus, with little effect on central arterial temperature. The same experiments in a dead animal cooled the brain after a longer period of time, suggesting that an active process is involved in the brain cooling observed in living animals.5. It is concluded that the cooling of the rostral cerebral arterial blood and brain which occurs in cats in a cool environment and is accelerated during thermal panting, is a result of countercurrent heat exchange between arterial blood in the carotid rete and venous blood draining the evaporative surfaces of the upper respiratory passages. Such direct brain cooling during thermal panting has now been demonstrated in the cat, the sheep and the gazelle, and probably explains the high heat tolerance of the carnivores and hoofed mammals in which a rete is present.

Population-based input function and image-derived input function for [¹¹C](R)-rolipram PET imaging: methodology, validation and application to the study of major depressive disorder.

PubMed

Zanotti-Fregonara, Paolo; Hines, Christina S; Zoghbi, Sami S; Liow, Jeih-San; Zhang, Yi; Pike, Victor W; Drevets, Wayne C; Mallinger, Alan G; Zarate, Carlos A; Fujita, Masahiro; Innis, Robert B

2012-11-15

Quantitative PET studies of neuroreceptor tracers typically require that arterial input function be measured. The aim of this study was to explore the use of a population-based input function (PBIF) and an image-derived input function (IDIF) for [(11)C](R)-rolipram kinetic analysis, with the goal of reducing - and possibly eliminating - the number of arterial blood samples needed to measure parent radioligand concentrations. A PBIF was first generated using [(11)C](R)-rolipram parent time-activity curves from 12 healthy volunteers (Group 1). Both invasive (blood samples) and non-invasive (body weight, body surface area, and lean body mass) scaling methods for PBIF were tested. The scaling method that gave the best estimate of the Logan-V(T) values was then used to determine the test-retest variability of PBIF in Group 1 and then prospectively applied to another population of 25 healthy subjects (Group 2), as well as to a population of 26 patients with major depressive disorder (Group 3). Results were also compared to those obtained with an image-derived input function (IDIF) from the internal carotid artery. In some subjects, we measured arteriovenous differences in [(11)C](R)-rolipram concentration to see whether venous samples could be used instead of arterial samples. Finally, we assessed the ability of IDIF and PBIF to discriminate depressed patients (MDD) and healthy subjects. Arterial blood-scaled PBIF gave better results than any non-invasive scaling technique. Excellent results were obtained when the blood-scaled PBIF was prospectively applied to the subjects in Group 2 (V(T) ratio 1.02±0.05; mean±SD) and Group 3 (V(T) ratio 1.03±0.04). Equally accurate results were obtained for two subpopulations of subjects drawn from Groups 2 and 3 who had very differently shaped (i.e. "flatter" or "steeper") input functions compared to PBIF (V(T) ratio 1.07±0.04 and 0.99±0.04, respectively). Results obtained via PBIF were equivalent to those obtained via IDIF (V(T) ratio 0.99±0.05 and 1.00±0.04 for healthy subjects and MDD patients, respectively). Retest variability of PBIF was equivalent to that obtained with full input function and IDIF (14.5%, 15.2%, and 14.1%, respectively). Due to [(11)C](R)-rolipram arteriovenous differences, venous samples could not be substituted for arterial samples. With both IDIF and PBIF, depressed patients had a 20% reduction in [(11)C](R)-rolipram binding as compared to control (two-way ANOVA: p=0.008 and 0.005, respectively). These results were almost equivalent to those obtained using 23 arterial samples. Although some arterial samples are still necessary, both PBIF and IDIF are accurate and precise alternatives to full arterial input function for [(11)C](R)-rolipram PET studies. Both techniques give accurate results with low variability, even for clinically different groups of subjects and those with very differently shaped input functions. Published by Elsevier Inc.

Real-time monitoring of human blood-brain barrier disruption

PubMed Central

Kiviniemi, Vesa; Korhonen, Vesa; Kortelainen, Jukka; Rytky, Seppo; Keinänen, Tuija; Tuovinen, Timo; Isokangas, Matti; Sonkajärvi, Eila; Siniluoto, Topi; Nikkinen, Juha; Alahuhta, Seppo; Tervonen, Osmo; Turpeenniemi-Hujanen, Taina; Myllylä, Teemu; Kuittinen, Outi; Voipio, Juha

2017-01-01

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery. PMID:28319185

[Case of brain infarction in the anterior choroidal artery territory with homonymous scotomas].

PubMed

Nakae, Yoshiharu; Higashiyama, Yuichi; Kuroiwa, Yoshiyuki

2009-08-01

We report a case of brain infarction in the anterior choroidal artery territory accompanied homonymous scotomas. A 59-year-old man with diabetes mellitus felt weakness in his left upper and lower extremities. He was admitted to our hospital with mild hemiparesis on his left side. He noticed a small black spot in the left inferior portion of his visual field; however, this disappeared within one minute. He had no visual defects as assessed by a confrontation test, but a Goldmann visual field test revealed that there were homonymous scotomas in the left inferior portion of the visual field. Brain MRI showed hyperintense signals on diffusion-weighted images in the territory of the right anterior choroidal artery. He was diagnosed as having a brain infarction. The anterior choroidal artery penetrates the lateral geniculate nucleus from the front, and branches of the artery usually supply the medial and lateral parts of the lateral geniculate nucleus. Occlusion of these branches causes the loss of the upper and lower homonymous sectors in the visual field. The present case exhibited homonymous scotomas. We assumed that our patient's homonymous scotomas were a variant form of wedge-shaped visual field deficits often seen in anterior choroidal artery syndrome. On the basis the experience gained in this case, we consider that patients with brain infarction in the anterior choroidal artery territory should undergo ophthalmological examination, even when no visual defects are detected by a confrontation test.

Transcranial doppler in sickle cell anaemia: evaluation of brain blood flow parameters in children of Aracaju, Northeast-Brazil.

PubMed

Melo, Hyder Aragão de; Barreto-Filho, José Augusto S; Prado, Roberto César P do; Cipolotti, Rosana

2008-06-01

Environmental factors interfere on sickle cell anaemia (SCA). Transcanial Doppler (TCD) is important to evaluate cerebrovascular disease. To evaluate brain haemodynamic profile of children with SCA in Sergipe. Cross sectional study (group1: SCA patients aged 3-18; group2: age and sex matched healthy individuals). Baseline brain flow was evaluated. Group1=34 patients; group 2=81 controls. SCA patients had mean velocity (MV)=125.69 cm/s+/-23.40; pulsatility index (PI)=0.66+/-0.10; middle cerebral artery ratio (MCAr)=14.53+/-15.23; right anterior cerebral artery/right middle cerebral artery=0.77+/-0.20; left anterior cerebral artery/left middle cerebral artery=0.78+/-0.20. Controls had MV=79.44+/-15.54; PI=0.82+/-0.11; MCAr=13.19+/-13.77; right anterior cerebral artery/right middle cerebral artery=0.80+/-0.16; left anterior cerebral artery/left middle cerebral artery=0.84+/-0.18. MV and PI differences were statistically significant between groups. MV was related to age but not to gender. MV evaluation using TCD was similar to international standards and possible to be used in our setting.

Nitrergic nerves derived from the pterygopalatine ganglion innervate arteries irrigating the cerebrum but not the cerebellum and brain stem in monkeys.

PubMed

Ayajiki, Kazuhide; Kobuchi, Shuhei; Tawa, Masashi; Okamura, Tomio

2012-01-01

The functional roles of the nitrergic nerves innervating the monkey cerebral artery were evaluated in a tension-response study examining isolated arteries in vitro and cerebral angiography in vivo. Nicotine produced relaxation of arteries by stimulation of nerve terminals innervating isolated monkey arteries irrigating the cerebrum, cerebellum and brain stem. Relaxation of arteries induced by nicotine was abolished by treatment with N(G)-nitro-L-arginine, a nitric oxide synthase inhibitor, and was restored by addition of L-arginine. Cerebral angiography showed that electrical stimulation of the unilateral greater petrosal nerve, which connects to the pterygopalatine ganglion via the parasympathetic ganglion synapse, produced vasodilatation of the anterior, middle and posterior cerebral arteries in the stimulated side. However, stimulation failed to produce vasodilatation of the superior and anterior-inferior cerebellar arteries and the basilar artery in anesthetized monkeys. Therefore, nitrergic nerves derived from the pterygopalatine ganglion appear to regulate cerebral vasomotor function. In contrast, circulation in the cerebellum and brain stem might be regulated by nitrergic nerves originating not from the pterygopalatine ganglion, but rather from an unknown ganglion (or ganglia).

A review of technical aspects of T1-weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in human brain tumors.

PubMed

Bergamino, M; Bonzano, L; Levrero, F; Mancardi, G L; Roccatagliata, L

2014-09-01

In the last few years, several imaging methods, such as magnetic resonance imaging (MRI) and computed tomography, have been used to investigate the degree of blood-brain barrier (BBB) permeability in patients with neurological diseases including multiple sclerosis, ischemic stroke, and brain tumors. One promising MRI method for assessing the BBB permeability of patients with neurological diseases in vivo is T1-weighted dynamic contrast-enhanced (DCE)-MRI. Here we review the technical issues involved in DCE-MRI in the study of human brain tumors. In the first part of this paper, theoretical models for the DCE-MRI analysis will be described, including the Toft-Kety models, the adiabatic approximation to the tissue homogeneity model and the two-compartment exchange model. These models can be used to estimate important kinetic parameters related to BBB permeability. In the second part of this paper, details of the data acquisition, issues related to the arterial input function, and procedures for DCE-MRI image analysis are illustrated. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Neural control of breathing and CO2 homeostasis

PubMed Central

Guyenet, P.G.; Bayliss, D.A

2015-01-01

Summary Recent advances have clarified how the brain detects CO2 to regulate breathing (central respiratory chemoreception). These mechanisms are reviewed and their significance is presented in the general context of CO2/pH homeostasis through breathing. At rest, respiratory chemoreflexes initiated at peripheral and central sites mediate rapid stabilization of arterial PCO2 and pH. Specific brainstem neurons (e.g., retrotrapezoid nucleus, RTN; serotonergic) are activated by PCO2 and stimulate breathing. RTN neurons detect CO2 via intrinsic proton receptors (TASK-2, GPR4), synaptic input from peripheral chemoreceptors and signals from astrocytes. Respiratory chemoreflexes are arousal state-dependent whereas chemoreceptor stimulation produces arousal. When abnormal, these interactions lead to sleep-disordered breathing. During exercise, “central command” and reflexes from exercising muscles produce the breathing stimulation required to maintain arterial PCO2 and pH despite elevated metabolic activity. The neural circuits underlying central command and muscle afferent control of breathing remain elusive and represent a fertile area for future investigation. PMID:26335642

Brain Arterial Diameters as a Risk Factor for Vascular Events.

PubMed

Gutierrez, Jose; Cheung, Ken; Bagci, Ahmet; Rundek, Tatjana; Alperin, Noam; Sacco, Ralph L; Wright, Clinton B; Elkind, Mitchell S V

2015-08-06

Arterial luminal diameters are routinely used to assess for vascular disease. Although small diameters are typically considered pathological, arterial dilatation has also been associated with disease. We hypothesize that extreme arterial diameters are biomarkers of the risk of vascular events. Participants in the Northern Manhattan Study who had a time-of-flight magnetic resonance angiography were included in this analysis (N=1034). A global arterial Z-score, called the brain arterial remodeling (BAR) score, was obtained by averaging the measured diameters within each individual. Individuals with a BAR score <-2 SDs were considered to have the smallest diameters, individuals with a BAR score >-2 and <2 SDs had average diameters, and individuals with a BAR score >2 SDs had the largest diameters. All vascular events were recorded prospectively after the brain magnetic resonance imaging. Spline curves and incidence rates were used to test our hypothesis. The association of the BAR score with death (P=0.001), vascular death (P=0.02), any vascular event (P=0.05), and myocardial infarction (P=0.10) was U-shaped except for ischemic stroke (P=0.74). Consequently, incidence rates for death, vascular death, myocardial infarction, and any vascular event were higher in individuals with the largest diameters, whereas individuals with the smallest diameters had a higher incidence of death, vascular death, any vascular event, and ischemic stroke compared with individuals with average diameters. The risk of death, vascular death, and any vascular event increased at both extremes of brain arterial diameters. The pathophysiology linking brain arterial remodeling to systemic vascular events needs further research. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Brain parenchyma PO2, PCO2, and pH during and after hypoxic, ischemic brain insult in dogs.

PubMed

McKinley, B A; Morris, W P; Parmley, C L; Butler, B D

1996-11-01

1) The investigation of fiberoptic PO2, PCO2, and pH sensor technology as a monitor of brain parenchyma during and after brain injury, and 2) the comparison of brain parenchyma PO2, PCO2, and pH with intracranial pressure during and after hypoxic, ischemic brain insult. Prospective, controlled, animal study in an acute experimental preparation. Physiology laboratory in a university medical school. Fourteen mongrel dogs (20 to 35 kg), anesthetized, room-air ventilated. Anesthesia was induced with thiopental and maintained after intubation using 1% to 1.5% halothane in room air (FiO2 0.21). Mechanical ventilation was established to maintain end-tidal PCO2 approximately 35 torr (-4.7 kPa). Intravenous, femoral artery, and pulmonary artery catheters were placed. The common carotid arteries were surgically exposed, and ultrasonic blood flow probes were applied. A calibrated intracranial pressure probe was placed through a right-side transcranial bolt, and a calibrated intracranial chemistry probe with optical sensors for PO2, PCO2, and pH was placed through a left-side bolt into brain parenchyma. Brain insult was induced in the experimental group (n = 6) by hypoxia (FiO2 0.1), ischemia (bilateral carotid artery occlusion), and hypotension (mean arterial pressure [MAP] approximately 40 mm Hg produced with isoflurane approximately 4%). After 45 mins, carotid artery occlusion was released, FiO2 was reset to 0.21, and anesthetic was returned to halothane (approximately 1.25%). The control group (n = 5) had the same surgical preparation and sequence of anesthetic agent exposure but no brain insult. Monitored variables included brain parenchyma PO2, PCO2, and pH, which were monitored at 1-min intervals, and intracranial pressure, MAP, arterial hemoglobin oxygen saturation (by pulse oximetry), end-tidal PCO2, and carotid artery blood flow rate, for which data were collected at 15-min intervals for 7 hrs. Arterial and mixed venous blood gas analyses were done at approximately 1-hr intervals. Baseline data agreed closely with other published results: brain parenchyma PO2 of 27 +/- 7 (SD) torr (3.6 +/- 0.9 kPa); brain parenchyma PCO2 of 69 +/- 12 torr (9.2 +/- 1.6 kPa); and brain parenchyma pH of 7.13 +/- 0.09. Postcalibration data were accurate, indicating stability and durability over several hours. In six experiments, during the brain insult, brain parenchyma PO2 decreased to 16 +/- 2 torr (2.1 +/- 0.3 kPa), brain parenchyma PCO2 increased to 105 +/- 44 torr (14 +/- 5.9 kPa) (p < .05), and brain parenchyma pH decreased to 6.75 +/- 0.08 (p < .05). Intracranial pressure (ICP) remained nearly constant (baseline 16 +/- 6 to 14 +/- 5 mm Hg at the end of the brain insult). Cerebral perfusion pressure (CPP = MAP - ICP) decreased (baseline 95 +/- 15 to 28 +/- 8 mm Hg; p < .05). On release of brain insult stresses, ICP increased to 30 +/- 9 mm Hg and CPP increased to 71 +/- 19 mm Hg (p < .05). A biphasic recovery was observed for brain parenchyma pH, which had the slowest recovery of the monitored variables. On average, brain parenchyma pH gradually returned toward baseline, and was no longer significantly different from baseline 3 hrs after release of insult stresses. Brain parenchyma PCO2 continued to decrease rapidly after brain insult and then remained approximately 52 +/- 10 torr (approximately 6.9 +/- 1.3 kPa) (p < .05). Brain parenchyma PO2 increased from a minimum at the end of brain insult to a maximum of 43 +/- 17 torr (5.7 +/- 2.3 kPa) within 1.25 hrs (p < .05), and then gradually decreased to approximately 35 +/- 10 torr (approximately 4.7 +/- 1.3 kPa). Cerebral perfusion pressure gradually decreased as ICP increased 3 to 5 hrs after insult. Intracranial chemistry probes with optical sensors demonstrated stable, reproducible monitoring of brain parenchyma PO2, PCO2, and pH in dogs for periods lasting > 8 hrs. Significant changes in brain p

The MRI-measured arterial input function resulting from a bolus injection of Gd-DTPA in a rat model of stroke slightly underestimates that of Gd-[14C]DTPA and marginally overestimates the blood-to-brain influx rate constant determined by Patlak plots

PubMed Central

Nagaraja, Tavarekere N.; Karki, Kishor; Ewing, James R.; Divine, George W.; Fenstermacher, Joseph D.; Patlak, Clifford S.; Knight, Robert A.

2009-01-01

The hypothesis that the arterial input function (AIF) of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) injected by intravenous (iv) bolus and measured by the change in the T1-relaxation rate (ΔR1; R1=1/T1) of superior sagittal sinus blood (AIF-I) approximates the AIF of 14C-labeled Gd-DTPA measured in arterial blood (AIF*) was tested in a rat stroke model (n=13). Contrary to the hypothesis, the initial part of the ΔR1-time curve was underestimated, and the area under the normalized curve for AIF-I was about 15% lower than that for AIF*, the reference AIF. Hypothetical AIF’s for Gd-DTPA (AIF-II) were derived from the AIF* values and averaged to obtain AIF-III. Influx rate constants (Ki) and proton distribution volumes at zero time (Vp+Vo) were estimated with Patlak plots of AIF-I, -II and -III and tissue ΔR1 data. For the regions of interest, the Ki’s estimated with AIF-I were slightly but not significantly higher than those obtained with AIF-II and AIF-III. In contrast, Vp+Vo was significantly higher when calculated with AIF-I. Similar estimates of Ki and Vp+Vo were obtained with AIF-II and AIF-III. In summary, AIF-I underestimated the reference AIF (AIF*); this shortcoming had little effect on the Ki calculated by Patlak plot but produced a significant overestimation of Vp+Vo. PMID:20512853

Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

PubMed Central

Tarumi, Takashi; de Jong, Daan L.K.; Zhu, David C.; Tseng, Benjamin Y.; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B.; Kerwin, Diana R.; Lu, Hanzhang; Cullum, C. Munro; Zhang, Rong

2015-01-01

Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults. PMID:25623500

[Brainstem auditory evoked potentials in neurophysiological assessment of brain stem dysfunction in patients with atherostenosis of vertebral arteries].

PubMed

Maksimova, M Yu; Sermagambetova, Zh N; Skrylev, S I; Fedin, P A; Koshcheev, A Yu; Shchipakin, V L; Sinicyn, I A

To assess brain stem dysfunction in patients with hemodynamically significant stenosis of vertebral arteries (VA) using short latency brainstem auditory evoked potentials (BAEP). The study group included 50 patients (mean age 64±6 years) with hemodynamically significant extracranial VA stenosis. Patients with hemodynamically significant extracranial VA stenosis had BAEP abnormalities including the elongation of interpeak intervals I-V and peak V latency as well as the reduction of peak I amplitude. After transluminal balloon angioplasty with stenting of VA stenoses, there was a shortening of peak V latency compared to the preoperative period that reflected the improvement of brain stem conductive functions. Atherostenosis of vertebral arteries is characterized by the signs of brain stem dysfunction, predominantly in the pontomesencephal brain stem. After transluminal balloon angioplasty with stenting of VA, the improvement of brain stem conductive functions was observed.

Contralateral Superior Cerebellar Artery Syndrome: A Consequence of Brain Herniation

PubMed Central

Mohseni, Meysam; Habibi, Zohreh; Nejat, Farideh

2017-01-01

Vascular compromise is a well-known consequence of brain herniation syndromes. Transtentorial brain herniation most often involves posterior cerebral arteries. However, isolated involvement of contralateral superior cerebellar artery (SCA) during unilateral impending brain herniation is reported only once and we present another case of this exceedingly rare entity. A 24-year-old man was referred to us with impending herniation due to a multiloculated hydrocephalus, and during the course of illness, he developed an isolated SCA ischemia in the opposite side of the most dilated entrapped horn. In the current article we discuss the probable pathophysiologic mechanisms of this phenomenon, as well as recommending more inclusive brain studies in cases suspected of Kernohan-Woltman notch phenomenon in unilateral brain herniation. The rationale for this commentary is that contralateral SCA transient ischemia or infarct might be the underdiagnosed underlying pathomechanism of ipsilateral hemiparesis occurring in many cases of this somehow vague phenomenon. PMID:28490164

Lacunar infarction and small vessel disease: pathology and pathophysiology.

PubMed

Caplan, Louis R

2015-01-01

Two major vascular pathologies underlie brain damage in patients with disease of small size penetrating brain arteries and arterioles; 1) thickening of the arterial media and 2) obstruction of the origins of penetrating arteries by parent artery intimal plaques. The media of these small vessels may be thickened by fibrinoid deposition and hypertrophy of smooth muscle and other connective tissue elements that accompanies degenerative changes in patients with hypertension and or diabetes or can contain foreign deposits as in amyloid angiopathy and genetically mediated conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These pathological changes lead to 2 different pathophysiologies: 1) brain ischemia in regions supplied by the affected arteries. The resultant lesions are deep small infarcts, most often involving the basal ganglia, pons, thalami and cerebral white matter. And 2) leakage of fluid causing edema and later gliosis in white matter tracts. The changes in the media and adventitia effect metalloproteinases and other substances within the matrix of the vessels and lead to abnormal blood/brain barriers in these small vessels. and chronic gliosis and atrophy of cerebral white matter.

Association between patency of the circle of Willis and diabetes mellitus in patients with cerebral ischaemic stroke

PubMed Central

Chi, Ying

2017-01-01

Objective To examine patency of the cerebral anterior and posterior communicating arteries in patients with ischaemic stroke with or without diabetes mellitus. Methods This retrospective study included patients with acute ischaemic stroke treated between July 2011 and May 2016. Cerebral infarction was evaluated by magnetic resonance imaging. Anterior and posterior communicating-artery patency was determined using magnetic resonance angiography. Vessels were defined as patent or occluded. Results Out of 1 406 patients, incidence of vertebral basilar artery brain infarction and posterior cerebral artery brain infarction were significantly higher in patients with diabetes versus those without diabetes (35.5% versus 22.3% and 11.7% versus 6.8%, respectively). Among patients with posterior cerebral artery brain infarction, anterior and posterior communicating-artery patency rates were higher in patients with diabetes versus those without diabetes (66.7 versus 23.5% and 33.3% versus 5.9% [bilateral], respectively). Among patients with vertebral basilar artery infarction and posterior cerebral artery P1 segment infarction, patency rate of the anterior communicating artery was higher in patients with diabetes versus those without diabetes (55.7% versus 45.9%). Conclusion Among patients with ischaemic stroke, patency rate of the circle of Willis may be higher in patients with diabetes than those without diabetes. PMID:28173711

[The effect of 18beta-glycyrrhetinic acid on gap junction among cerebral arteriolar smooth muscle cells in Wistar rat and spontaneously hypertensive rat].

PubMed

Chen, Xin-Yan; Si, Jun-Qiang; Li, Li; Zhao, Lei; Wei, Li-Li; Jiang, Xue-Wei; Ma, Ke-Tao

2013-05-01

This study compared Wistar rat with spontaneously hypertensive rat (SHR) on the electrophysiology and coupling force of the smooth muscle cells in the cerebral arteriolar segments and observe the influence of 18beta-glycyrrhetinic acid(18beta-GA) on the gap junctions between the arterial smooth muscle cells. The outer layer's connective tissue of the cerebral arteriolar segments was removed. Whole-cell patch clamp recordings were used to observe the 18beta-GA's impaction on the arteriolar segment membrane's input capacitance (C(input)), input conductance (G(input)) and input resistance (R(input)) of the smooth muscle cells. (1) The C(input) and G(input) of the SHR arteriolar segment smooth muscle cells was much higher than the Wistar rats, there was significant difference (P < 0.05). (2) 18beta-GA concentration-dependently reduced C(input) and G(input) (or increase R(input)) on smooth muscle cells in arteriolar segment. IC50 of 18beta-GA suppression's G(input) of the Wistar rat and SHR were 1.7 and 2.0 micromol/L respectively, there was not significant difference (P > 0.05). After application of 18beta-GA concentration > or = 100 micrmol/L, the C(input), G(input) and R(input) of the single smooth muscle cells was very close. Gap junctional coupling is enhanced in the SHR cerebral arterial smooth muscle cells. 18beta-GA concentration-dependent inhibits Wistar rat's and SHR cerebral arteriolar gap junctions between arterial smooth muscle cells. The inhibitory potency is similar between the two different rats. When 18beta-GA concentration is > or = 100 micromol/L, it can completely block gap junctions between arteriolar smooth muscle cells.

Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways.

PubMed

Albargothy, Nazira J; Johnston, David A; MacGregor-Sharp, Matthew; Weller, Roy O; Verma, Ajay; Hawkes, Cheryl A; Carare, Roxana O

2018-05-12

Tracers injected into CSF pass into the brain alongside arteries and out again. This has been recently termed the "glymphatic system" that proposes tracers enter the brain along periarterial "spaces" and leave the brain along the walls of veins. The object of the present study is to test the hypothesis that: (1) tracers from the CSF enter the cerebral cortex along pial-glial basement membranes as there are no perivascular "spaces" around cortical arteries, (2) tracers leave the brain along smooth muscle cell basement membranes that form the Intramural Peri-Arterial Drainage (IPAD) pathways for the elimination of interstitial fluid and solutes from the brain. 2 μL of 100 μM soluble, fluorescent fixable amyloid β (Aβ) were injected into the CSF of the cisterna magna of 6-10 and 24-30 month-old male mice and their brains were examined 5 and 30 min later. At 5 min, immunocytochemistry and confocal microscopy revealed Aβ on the outer aspects of cortical arteries colocalized with α-2 laminin in the pial-glial basement membranes. At 30 min, Aβ was colocalised with collagen IV in smooth muscle cell basement membranes in the walls of cortical arteries corresponding to the IPAD pathways. No evidence for drainage along the walls of veins was found. Measurements of the depth of penetration of tracer were taken from 11 regions of the brain. Maximum depths of penetration of tracer into the brain were achieved in the pons and caudoputamen. Conclusions drawn from the present study are that tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways. The exit route is along IPAD pathways in which Aβ accumulates in cerebral amyloid angiopathy (CAA) in Alzheimer's disease. Results from this study suggest that CSF may be a suitable route for delivery of therapies for neurological diseases, including CAA.

Spatiotemporal characterization of brain infarction by sequential multimodal MR imaging following transient focal ischemia in a Rat model of intra-arterial middle cerebral artery occlusion.

PubMed

Gory, Benjamin; Chauveau, Fabien; Bolbos, Radu; Langlois, Jean-Baptiste; Labeyrie, Paul-Emile; Signorelli, Francesco; Turjman, Alexis; Turjman, Francis

2016-12-01

To assess spatiotemporal brain infarction evolution by sequential multimodal magnetic resonance (MR) imaging in an endovascular model of acute stroke in rats. A microwire was selectively placed in the middle cerebral artery (MCA) in 16 consecutives rats during 90 minutes occlusion. Longitudinal 7-T MR imaging, including angiography, diffusion, and perfusion was performed during ischemia, immediately after reperfusion, 3 h and 24 h after subsequent reperfusion. MCA occlusion was complete in 75 % and partial in 18.7 %. Hypoperfusion (mean ± SD) was observed in all animals during ischemia (-59 ± 18 % of contralateral hemisphere, area 31 ± 5 mm 2 ). Infarction volume (mean ± SD) was 90 ± 64 mm 3 during ischemia and 57 ± 67 mm 3 at 24 h. Brain infarction was fronto-parietal cortical in five animals (31 %), striatal in four animals (25 %), and cortico-striatal in seven animals (44 %) at 24 h. All rats survived at 24 h. This model is suitable to neuroprotection studies because of possible acute and close characterization of spatiotemporal evolution of brain infarction by MR imaging techniques, and evidence of ischemic penumbra, the target of neuroprotection agents. However, optimization of the brain infarct reproducibility needs further technical and neurointerventional tools improvements. • Nitinol microwire is MRI compatible allowing spatiotemporal characterization of brain infarction in rats. • Microwire selective placement in middle cerebral artery allows complete artery occlusion in 75 %. • A diffusion/perfusion mismatch during arterial occlusion is observed in 77 % of rats.

Energy harvesting from arterial blood pressure for powering embedded micro sensors in human brain

NASA Astrophysics Data System (ADS)

Nanda, Aditya; Karami, M. Amin

2017-03-01

This manuscript investigates energy harvesting from arterial blood pressure via the piezoelectric effect for the purpose of powering embedded micro-sensors in the human brain. One of the major hurdles in recording and measuring electrical data in the human nervous system is the lack of implantable and long term interfaces that record neural activity for extended periods of time. Recently, some authors have proposed micro sensors implanted deep in the brain that measure local electrical and physiological data which are then communicated to an external interrogator. This paper proposes a way of powering such interfaces. The geometry of the proposed harvester consists of a piezoelectric, circular, curved bimorph that fits into the blood vessel (specifically, the Carotid artery) and undergoes bending motion because of blood pressure variation. In addition, the harvester thickness is constrained such that it does not modify arterial wall dynamics. This transforms the problem into a known strain problem and the integral form of Gauss's law is used to obtain an equation relating arterial wall motion to the induced voltage. The theoretical model is validated by means of a Multiphysics 3D-FEA simulation comparing the harvested power at different load resistances. The peak harvested power achieved for the Carotid artery (proximal to Brain), with PZT-5H, was 11.7 μW. The peak power for the Aorta was 203.4 μW. Further, the variation of harvested power with variation in the harvester width and thickness, arterial contractility, and pulse rate is investigated. Moreover, potential application of the harvester as a chronic, implantable and real-time Blood pressure sensor is considered. Energy harvested via this mechanism will also have applications in long-term, implantable Brain Micro-stimulation.

Spatial model of convective solute transport in brain extracellular space does not support a “glymphatic” mechanism

PubMed Central

Jin, Byung-Ju; Smith, Alex J.

2016-01-01

A “glymphatic system,” which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier–Stokes and convection–diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS. PMID:27836940

Spatial model of convective solute transport in brain extracellular space does not support a "glymphatic" mechanism.

PubMed

Jin, Byung-Ju; Smith, Alex J; Verkman, Alan S

2016-12-01

A "glymphatic system," which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier-Stokes and convection-diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS. © 2016 Jin et al.

Screening for Carotid Artery Stenosis

MedlinePlus

... build up and harden the arteries, limiting the flow of blood to the brain. Facts About Carotid Artery Stenosis Carotid artery stenosis is one of many risk factors for stroke, a leading cause of death and disability in the United States. However, carotid artery stenosis is uncommon—about ½ ...

Measurement of myocardial blood flow by cardiovascular magnetic resonance perfusion: comparison of distributed parameter and Fermi models with single and dual bolus.

PubMed

Papanastasiou, Giorgos; Williams, Michelle C; Kershaw, Lucy E; Dweck, Marc R; Alam, Shirjel; Mirsadraee, Saeed; Connell, Martin; Gray, Calum; MacGillivray, Tom; Newby, David E; Semple, Scott Ik

2015-02-17

Mathematical modeling of cardiovascular magnetic resonance perfusion data allows absolute quantification of myocardial blood flow. Saturation of left ventricle signal during standard contrast administration can compromise the input function used when applying these models. This saturation effect is evident during application of standard Fermi models in single bolus perfusion data. Dual bolus injection protocols have been suggested to eliminate saturation but are much less practical in the clinical setting. The distributed parameter model can also be used for absolute quantification but has not been applied in patients with coronary artery disease. We assessed whether distributed parameter modeling might be less dependent on arterial input function saturation than Fermi modeling in healthy volunteers. We validated the accuracy of each model in detecting reduced myocardial blood flow in stenotic vessels versus gold-standard invasive methods. Eight healthy subjects were scanned using a dual bolus cardiac perfusion protocol at 3T. We performed both single and dual bolus analysis of these data using the distributed parameter and Fermi models. For the dual bolus analysis, a scaled pre-bolus arterial input function was used. In single bolus analysis, the arterial input function was extracted from the main bolus. We also performed analysis using both models of single bolus data obtained from five patients with coronary artery disease and findings were compared against independent invasive coronary angiography and fractional flow reserve. Statistical significance was defined as two-sided P value < 0.05. Fermi models overestimated myocardial blood flow in healthy volunteers due to arterial input function saturation in single bolus analysis compared to dual bolus analysis (P < 0.05). No difference was observed in these volunteers when applying distributed parameter-myocardial blood flow between single and dual bolus analysis. In patients, distributed parameter modeling was able to detect reduced myocardial blood flow at stress (<2.5 mL/min/mL of tissue) in all 12 stenotic vessels compared to only 9 for Fermi modeling. Comparison of single bolus versus dual bolus values suggests that distributed parameter modeling is less dependent on arterial input function saturation than Fermi modeling. Distributed parameter modeling showed excellent accuracy in detecting reduced myocardial blood flow in all stenotic vessels.

Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

PubMed

Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić

2016-02-01

To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Influence of O-methylated metabolite penetrating the blood-brain barrier to estimation of dopamine synthesis capacity in human L-[β-(11)C]DOPA PET.

PubMed

Matsubara, Keisuke; Ikoma, Yoko; Okada, Maki; Ibaraki, Masanobu; Suhara, Tetsuya; Kinoshita, Toshibumi; Ito, Hiroshi

2014-02-01

O-methyl metabolite (L-[β-(11)C]OMD) of (11)C-labeled L-3,4-dihydroxyphenylalanine (L-[β-(11)C]DOPA) can penetrate into brain tissue through the blood-brain barrier, and can complicate the estimation of dopamine synthesis capacity by positron emission tomography (PET) study with L-[β-(11)C]DOPA. We evaluated the impact of L-[β-(11)C]OMD on the estimation of the dopamine synthesis capacity in a human L-[β-(11)C]DOPA PET study. The metabolite correction with mathematical modeling of L-[β-(11)C]OMD kinetics in a reference region without decarboxylation and further metabolism, proposed by a previous [(18)F]FDOPA PET study, were implemented to estimate radioactivity of tissue L-[β-(11)C]OMD in 10 normal volunteers. The component of L-[β-(11)C]OMD in tissue time-activity curves (TACs) in 10 regions were subtracted by the estimated radioactivity of L-[β-(11)C]OMD. To evaluate the influence of omitting blood sampling and metabolite correction, relative dopamine synthesis rate (kref) was estimated by Gjedde-Patlak analysis with reference tissue input function, as well as the net dopamine synthesis rate (Ki) by Gjedde-Patlak analysis with the arterial input function and TAC without and with metabolite correction. Overestimation of Ki was observed without metabolite correction. However, the kref and Ki with metabolite correction were significantly correlated. These data suggest that the influence of L-[β-(11)C]OMD is minimal for the estimation of kref as dopamine synthesis capacity.

Ventral medullary neurones excited from the hypothalamic and mid-brain defence areas.

PubMed

Hilton, S M; Smith, P R

1984-07-01

In cats anaesthetised with chloralose, the ventral medulla was explored in and around the strip previously identified as the location of the efferent pathway from the hypothalamic and mid-brain defence areas to the spinal cord, in a search for neurones excited by electrical stimulation of the defence areas. Such units were found mostly in the caudal part of this strip, at a depth of not more than 500 microns from the surface. Nearly all were located in the ventral part of nucleus paragigantocellularis lateralis (PGL) at the level of the rostral pole of the inferior olive. There was evidence of temporal and spatial facilitation, indicating a convergent excitatory input from the defence areas onto neurones in PGL. This is consistent with earlier evidence of a synaptic relay in the efferent pathway at this site. When the pathway is blocked at this site, arterial blood pressure falls profoundly, so activity in these neurones may be essential for the normal level of sympathetic nerve activity.

[Effects of introduction of short peptides before carotid artery occlusion on behaviour and caspase-3 activity in the brain of old rats].

PubMed

Mendzheritskiĭ, A M; Karantysh, G V; Ivonina, K O

2011-01-01

The comparative research of effect of Pinealon and Cortexin on behavior and activity of caspase-3 in a brain of old rats in a model of carotid arteries occlusion was conducted. It is shown that introduction of short peptides promotes a survival rate of the animals that have modeled occlusion of carotid arteries. Under Pinealon before occlusion of carotid arteries, behavioral dream has been increased and a position-finding behavior, a motivational behavior and a motor performance have been reduced. The rats that were introduced Cortexin before carotid arteries occlusion demonstrated the raise of behavioral dream time. At introduction of Pinealon activity of caspase-3 moderately raises in false-operated animals and in a model of occlusion of carotid arteries.

Diffusion-weighted imaging score of the brain stem: A predictor of outcome in acute basilar artery occlusion treated with the Solitaire FR device.

PubMed

Mourand, I; Machi, P; Nogué, E; Arquizan, C; Costalat, V; Picot, M-C; Bonafé, A; Milhaud, D

2014-06-01

The prognosis for ischemic stroke due to acute basilar artery occlusion is very poor: Early recanalization remains the main factor that can improve outcomes. The baseline extent of brain stem ischemic damage can also influence outcomes. We evaluated the validity of an easy-to-use DWI score to predict clinical outcome in patients with acute basilar artery occlusion treated by mechanical thrombectomy. We analyzed the baseline clinical and DWI parameters of 31 patients with acute basilar artery occlusion, treated within 24 hours of symptom onset by using a Solitaire FR device. The DWI score of the brain stem was assessed with a 12-point semiquantitative score that separately considered each side of the medulla, pons, and midbrain. Clinical outcome was assessed at 180 days by using the mRS. According to receiver operating characteristic analyses, the cutoff score determined the optimal positive predictive value for outcome. The Spearman rank correlation coefficient assessed the correlation between the DWI brain stem score and baseline characteristics. Successful recanalization (Thrombolysis in Cerebral Infarction 3-2b) was achieved in 23 patients (74%). A favorable outcome (mRS ≤ 2) was observed in 11 patients (35%). An optimal DWI brain stem score of <3 predicted a favorable outcome. The probability of a very poor outcome (mRS ≥ 5) if the DWI brain stem score was ≥5 reached 80% (positive predictive value) and 100% if this score was ≥6. Interobserver reliability of the DWI brain stem score was excellent, with an intraclass correlation coefficient of 0.97 (95% CI, 0.96-0.99). The DWI brain stem score was significantly associated with baseline tetraplegia (P = .001) and coma (P = .005). In patients with acute basilar artery occlusion treated by mechanical thrombectomy, the baseline DWI brain lesion score seems to predict clinical outcome. © 2014 by American Journal of Neuroradiology.

Brain Stem Infarction Due to Basilar Artery Dissection in a Patient with Moyamoya Disease Four Years after Successful Bilateral Revascularization Surgeries.

PubMed

Abe, Takatsugu; Fujimura, Miki; Mugikura, Shunji; Endo, Hidenori; Tominaga, Teiji

2016-06-01

Moyamoya disease (MMD) is a rare cerebrovascular disease with an unknown etiology and is characterized by intrinsic fragility in the intracranial vascular walls such as the affected internal elastic lamina and thinning medial layer. The association of MMD with intracranial arterial dissection is extremely rare, whereas that with basilar artery dissection (BAD) has not been reported previously. A 46-year-old woman developed brain stem infarction due to BAD 4 years after successful bilateral superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis for ischemic-onset MMD. She presented with sudden occipitalgia and subsequently developed transient dysarthria and mild hemiparesis. Although a transient ischemic attack was initially suspected, her condition deteriorated in a manner that was consistent with left hemiplegia with severe dysarthria. Magnetic resonance (MR) imaging revealed brain stem infarction, and MR angiography delineated a double-lumen sign in the basilar artery, indicating BAD. She was treated conservatively and brain stem infarction did not expand. One year after the onset of brain stem infarction, her activity of daily living is still dependent (modified Rankin Scale of 4), and there were no morphological changes associated with BAD or recurrent cerebrovascular events during the follow-up period. The association of MMD with BAD is extremely rare. While considering the common underlying pathology such as an affected internal elastic lamina and fragile medial layer, the occurrence of BAD in a patient with MMD in a stable hemodynamic state is apparently unique. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Thermal camera used for the assessment of metabolism and functions of the rat brain

NASA Astrophysics Data System (ADS)

Kastek, Mariusz; Piatkowski, Tadeusz; Polakowski, Henryk; Kaczmarska, Katarzyna; Czernicki, Zbigniew; Koźniewska, Ewa; Przykaza, Lukasz

2014-05-01

Motivation to undertake research on brain surface temperature in clinical practice is based on a strong conviction that the enormous progress in thermal imaging techniques and camera design has a great application potential. Intraoperative imaging of pathological changes and functionally important areas of the brain is not yet fully resolved in neurosurgery and remains a challenge. Extensive knowledge of the complex mechanisms controlling homeostasis (thermodynamic status of an organism being a part of it ) and laws of physics (which are the foundations of thermography), make this method very good and a simple imaging tool in comparison with other modern techniques, such as computed tomography, magnetic resonance imaging and angiography. Measurements of temperature distribution across the brain surface were performed on four rats (Wistar strain) weighing approximately 300 g each. Animals have remained under general anesthesia typically conducted using isoflurane. The brain was unveiled (the dura mater remained untouched) through the skin incision and removal of the bone cranial vault. Cerebrocortical microflow was measured using laser-Doppler flow meter. Arterial blood pressure was also measured in rat femoral artery. From the above data the cerebrovascular resistance index was calculated. Cerebral flow was modified by increasing the CO2 concentration in the inspired air to 5% for the duration of 6 minutes. Another change in cerebral flow was induced by periodic closing of right middle cerebral artery. Artery occlusion was performed by introducing a filament for a period of 15 minutes, then an artery was opened again. Measurements were carried out before, during and after the artery occlusion. Paper presents results and methodology of measurements.

Cerebral Arterial Occlusion Did Not Promote the Prevalence of Cerebral Amyloid Angiopathy.

PubMed

Honda, Kazuhiro

2016-08-01

An impairment of amyloid-β (Aβ) clearance has been suggested in Alzheimer's disease. Perivascular drainage along cerebrovascular vessels is considered an important amyloid clearance pathway. This study examined the effect of reduced arterial pulsation that could cause an impairment in cerebral amyloid drainage on the prevalence of cortical microbleeds (CMBs), a surrogate marker for cerebral amyloid angiopathy (CAA). Patients who lost depiction of either side of the carotid artery or the middle cerebral artery on magnetic resonance angiography were studied. Those who showed acute cerebral infarction or a previous cortical cerebral infarction were excluded. The number of CMBs was counted on the occluded and non-occluded sides of the brain in each subject. The number of subjects who showed more CMBs on the occluded side of the brain was compared with the number of subjects who showed more CMBs on the non-occluded side of the brain. Twenty-eight patients were studied. The extent of lacunar infarction and white matter lesions was not different, irrespective of the occluded vessels or the distribution of CMBs. The prevalence of CMBs was not different between the occluded and non-occluded sides of the brain. In this cross-sectional study, reduction of arterial pulsation was not associated with a higher prevalence of CAA. Therefore, reduced arterial pulsation alone may not be enough to promote CAA.

Temperature monitoring during cardiopulmonary bypass--do we undercool or overheat the brain?

PubMed

Kaukuntla, Hemanth; Harrington, Deborah; Bilkoo, Inderaj; Clutton-Brock, Tom; Jones, Timothy; Bonser, Robert S

2004-09-01

Brain cooling is an essential component of aortic surgery requiring circulatory arrest and inadequate cooling may lead to brain injury. Similarly, brain hyperthermia during the rewarming phase of cardiopulmonary bypass may also lead to neurological injury. Conventional temperature monitoring sites may not reflect the core brain temperature (Tdegrees). We compared jugular bulb venous temperatures (JB) during deep hypothermic circulatory arrest and normothermic bypass with Nasopharyngeal (NP), Arterial inflow (AI), Oesophageal (O), Venous return (VR), Bladder (B) and Orbital skin (OS) temperatures. 18 patients undergoing deep hypothermia (DH) and 8 patients undergoing normothermic bypass (mean bladder Tdegrees-36.29 degreesC) were studied. For DH, cooling was continued to 15 degreesC NP (mean cooling time-66 min). At pre-determined arterial inflow Tdegrees, NP, JB and O Tdegree's were measured. A 6-channel recorder continuously recorded all Tdegree's using calibrated thermocouples. During the cooling phase of DH, NP lagged behind AI and JB Tdegree's. All these equilibrated at 15 degreesC. During rewarming, JB and NP lagged behind AI and JB was higher than NP at any time point. During normothermic bypass, although NP was reflective of the AI and JB Tdegrees trends, it underestimated peak JB Tdegrees (P=0.001). Towards the end of bypass, peak JB was greater than the arterial inflow Tdegrees (P=0.023). If brain venous outflow Tdegrees (JB) accurately reflects brain Tdegrees, NP Tdegrees is a safe surrogate indicator of cooling. During rewarming, all peripheral sites underestimate brain temperature and caution is required to avoid hyperthermic arterial inflow, which may inadvertently, result in brain hyperthermia.

Evaluation of limited blood sampling population input approaches for kinetic quantification of [18F]fluorothymidine PET data.

PubMed

Contractor, Kaiyumars B; Kenny, Laura M; Coombes, Charles R; Turkheimer, Federico E; Aboagye, Eric O; Rosso, Lula

2012-03-24

Quantification of kinetic parameters of positron emission tomography (PET) imaging agents normally requires collecting arterial blood samples which is inconvenient for patients and difficult to implement in routine clinical practice. The aim of this study was to investigate whether a population-based input function (POP-IF) reliant on only a few individual discrete samples allows accurate estimates of tumour proliferation using [18F]fluorothymidine (FLT). Thirty-six historical FLT-PET data with concurrent arterial sampling were available for this study. A population average of baseline scans blood data was constructed using leave-one-out cross-validation for each scan and used in conjunction with individual blood samples. Three limited sampling protocols were investigated including, respectively, only seven (POP-IF7), five (POP-IF5) and three (POP-IF3) discrete samples of the historical dataset. Additionally, using the three-point protocol, we derived a POP-IF3M, the only input function which was not corrected for the fraction of radiolabelled metabolites present in blood. The kinetic parameter for net FLT retention at steady state, Ki, was derived using the modified Patlak plot and compared with the original full arterial set for validation. Small percentage differences in the area under the curve between all the POP-IFs and full arterial sampling IF was found over 60 min (4.2%-5.7%), while there were, as expected, larger differences in the peak position and peak height.A high correlation between Ki values calculated using the original arterial input function and all the population-derived IFs was observed (R2 = 0.85-0.98). The population-based input showed good intra-subject reproducibility of Ki values (R2 = 0.81-0.94) and good correlation (R2 = 0.60-0.85) with Ki-67. Input functions generated using these simplified protocols over scan duration of 60 min estimate net PET-FLT retention with reasonable accuracy.

Noninvasive quantification of cerebral metabolic rate for glucose in rats using 18F-FDG PET and standard input function

PubMed Central

Hori, Yuki; Ihara, Naoki; Teramoto, Noboru; Kunimi, Masako; Honda, Manabu; Kato, Koichi; Hanakawa, Takashi

2015-01-01

Measurement of arterial input function (AIF) for quantitative positron emission tomography (PET) studies is technically challenging. The present study aimed to develop a method based on a standard arterial input function (SIF) to estimate input function without blood sampling. We performed 18F-fluolodeoxyglucose studies accompanied by continuous blood sampling for measurement of AIF in 11 rats. Standard arterial input function was calculated by averaging AIFs from eight anesthetized rats, after normalization with body mass (BM) and injected dose (ID). Then, the individual input function was estimated using two types of SIF: (1) SIF calibrated by the individual's BM and ID (estimated individual input function, EIFNS) and (2) SIF calibrated by a single blood sampling as proposed previously (EIF1S). No significant differences in area under the curve (AUC) or cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIFNS-, and EIF1S-based methods using repeated measures analysis of variance. In the correlation analysis, AUC or CMRGlc derived from EIFNS was highly correlated with those derived from AIF and EIF1S. Preliminary comparison between AIF and EIFNS in three awake rats supported an idea that the method might be applicable to behaving animals. The present study suggests that EIFNS method might serve as a noninvasive substitute for individual AIF measurement. PMID:25966947

Noninvasive quantification of cerebral metabolic rate for glucose in rats using (18)F-FDG PET and standard input function.

PubMed

Hori, Yuki; Ihara, Naoki; Teramoto, Noboru; Kunimi, Masako; Honda, Manabu; Kato, Koichi; Hanakawa, Takashi

2015-10-01

Measurement of arterial input function (AIF) for quantitative positron emission tomography (PET) studies is technically challenging. The present study aimed to develop a method based on a standard arterial input function (SIF) to estimate input function without blood sampling. We performed (18)F-fluolodeoxyglucose studies accompanied by continuous blood sampling for measurement of AIF in 11 rats. Standard arterial input function was calculated by averaging AIFs from eight anesthetized rats, after normalization with body mass (BM) and injected dose (ID). Then, the individual input function was estimated using two types of SIF: (1) SIF calibrated by the individual's BM and ID (estimated individual input function, EIF(NS)) and (2) SIF calibrated by a single blood sampling as proposed previously (EIF(1S)). No significant differences in area under the curve (AUC) or cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIF(NS)-, and EIF(1S)-based methods using repeated measures analysis of variance. In the correlation analysis, AUC or CMRGlc derived from EIF(NS) was highly correlated with those derived from AIF and EIF(1S). Preliminary comparison between AIF and EIF(NS) in three awake rats supported an idea that the method might be applicable to behaving animals. The present study suggests that EIF(NS) method might serve as a noninvasive substitute for individual AIF measurement.

Venous or arterial blood components trigger more brain swelling, tissue death after acute subdural hematoma compared to elderly atrophic brain with subdural effusion (SDE) model rats.

PubMed

Wajima, Daisuke; Sato, Fumiya; Kawamura, Kenya; Sugiura, Keisuke; Nakagawa, Ichiro; Motoyama, Yasushi; Park, Young-Soo; Nakase, Hiroyuki

2017-09-01

Acute subdural hematoma (ASDH) is a frequent complication of severe head injury, whose secondary ischemic lesions are often responsible for the severity of the disease. We focused on the differences of secondary ischemic lesions caused by the components, 0.4ml venous- or arterial-blood, or saline, infused in the subdural space, evaluating the differences in vivo model, using rats. The saline infused rats are made for elderly atrophic brain with subdural effusion (SDE) model. Our data showed that subdural blood, both venous- and arterial-blood, aggravate brain edema and lesion development more than SDE. This study is the first study, in which different fluids in rats' subdural space, ASDH or SDE are compared with the extension of early and delayed brain damage by measuring brain edema and histological lesion volume. Blood constituents started to affect the degree of ischemia underneath the subdural hemorrhage, leading to more pronounced breakdown of the blood-brain barrier and brain damage. This indicates that further strategies to treat blood-dependent effects more efficiently are in view for patients with ASDH. Copyright © 2017 Elsevier B.V. All rights reserved.

Central Pulsatile Pressure and Flow Relationship in the Time and Frequency Domain to Characterise Hydraulic Input to the Brain and Cerebral Vascular Impedance.

PubMed

Kim, Mi Ok; O'Rourke, Michael F; Adji, Audrey; Avolio, Alberto P

2016-01-01

In the time domain, pulsatile flow and pressure can be characterised as the ratio of the late systolic boost of flow or pressure to the pulse amplitude so as to estimate the hydraulic input to the brain. While vascular impedance has been widely used to represent the load presented to the heart by the systemic circulation, it has not been applied to the cerebral circulation.We set out to study the relationship between the pressure and the flow augmentation index (AIx) in the time domain and to determine cerebral vascular impedance using aortic blood pressure and cerebral blood flow waveforms in the frequency domain. Twenty-four young subjects (aged 21-39 years) were recruited; aortic pressure was derived using SphygmoCor from radial pressure. Flow waveforms were recorded from the middle cerebral artery. In three subjects, we performed the Valsalva manoeuvre to investigate their response to physiological intervention. There was a linear relationship between flow and pressure AIx, and cerebral impedance values were similar to those estimated for low resistance vascular beds. Substantial change in pressure and flow wave contour was observed during the Valsalva manoeuvre; however, the relationship in both the time and the frequency domains were unchanged. This confirms that aortic pressure and cerebral flow waveform can be used to study cerebral impedance.

Human (13)N-ammonia PET studies: the importance of measuring (13)N-ammonia metabolites in blood.

PubMed

Keiding, Susanne; Sørensen, Michael; Munk, Ole Lajord; Bender, Dirk

2010-03-01

Dynamic (13)N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways, using arterial blood (13)N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of (13)N-content in blood into (13)N-ammonia, (13)N-urea, (13)N-glutamine and (13)N-glutamate. Due to a radioactive half-life for (13)N of 10 min, the procedure is not suitable for blood samples taken beyond 5-7 min after tracer injection. By modifying Rosenspire's method, we established a method enabling analysis of up to 10 blood samples in the course of 30 min. The modified procedure was validated by HPLC and by 30-min reproducibility studies in humans examined by duplicate (13)N-ammonia injections with a 60-min interval. Blood data from a (13)N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of (13)N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of (13)N-ammonia to (13)N-metabolites were in the order: healthy subjects > cirrhotic patients without HE > cirrhotic patients with HE; (3) kinetics of initial tracer distribution in tissue can be assessed by using total (13)N-concentration in blood as input function, whereas assessment of metabolic processes requires (13)N-ammonia measurements.

Quantitative myocardial perfusion from static cardiac and dynamic arterial CT

NASA Astrophysics Data System (ADS)

Bindschadler, Michael; Branch, Kelley R.; Alessio, Adam M.

2018-05-01

Quantitative myocardial blood flow (MBF) estimation by dynamic contrast enhanced cardiac computed tomography (CT) requires multi-frame acquisition of contrast transit through the blood pool and myocardium to inform the arterial input and tissue response functions. Both the input and the tissue response functions for the entire myocardium are sampled with each acquisition. However, the long breath holds and frequent sampling can result in significant motion artifacts and relatively high radiation dose. To address these limitations, we propose and evaluate a new static cardiac and dynamic arterial (SCDA) quantitative MBF approach where (1) the input function is well sampled using either prediction from pre-scan timing bolus data or measured from dynamic thin slice ‘bolus tracking’ acquisitions, and (2) the whole-heart tissue response data is limited to one contrast enhanced CT acquisition. A perfusion model uses the dynamic arterial input function to generate a family of possible myocardial contrast enhancement curves corresponding to a range of MBF values. Combined with the timing of the single whole-heart acquisition, these curves generate a lookup table relating myocardial contrast enhancement to quantitative MBF. We tested the SCDA approach in 28 patients that underwent a full dynamic CT protocol both at rest and vasodilator stress conditions. Using measured input function plus single (enhanced CT only) or plus double (enhanced and contrast free baseline CT’s) myocardial acquisitions yielded MBF estimates with root mean square (RMS) error of 1.2 ml/min/g and 0.35 ml/min/g, and radiation dose reductions of 90% and 83%, respectively. The prediction of the input function based on timing bolus data and the static acquisition had an RMS error compared to the measured input function of 26.0% which led to MBF estimation errors greater than threefold higher than using the measured input function. SCDA presents a new, simplified approach for quantitative perfusion imaging with an acquisition strategy offering substantial radiation dose and computational complexity savings over dynamic CT.

Comparison of quantitatively analyzed dynamic area-detector CT using various mathematic methods with FDG PET/CT in management of solitary pulmonary nodules.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Fujisawa, Yasuko; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Sugimura, Kazuro

2013-06-01

The objective of our study was to prospectively compare the capability of dynamic area-detector CT analyzed with different mathematic methods and PET/CT in the management of pulmonary nodules. Fifty-two consecutive patients with 96 pulmonary nodules underwent dynamic area-detector CT, PET/CT, and microbacterial or pathologic examinations. All nodules were classified into the following groups: malignant nodules (n = 57), benign nodules with low biologic activity (n = 15), and benign nodules with high biologic activity (n = 24). On dynamic area-detector CT, the total, pulmonary arterial, and systemic arterial perfusions were calculated using the dual-input maximum slope method; perfusion was calculated using the single-input maximum slope method; and extraction fraction and blood volume (BV) were calculated using the Patlak plot method. All indexes were statistically compared among the three nodule groups. Then, receiver operating characteristic analyses were used to compare the diagnostic capabilities of the maximum standardized uptake value (SUVmax) and each perfusion parameter having a significant difference between malignant and benign nodules. Finally, the diagnostic performances of the indexes were compared by means of the McNemar test. No adverse effects were observed in this study. All indexes except extraction fraction and BV, both of which were calculated using the Patlak plot method, showed significant differences among the three groups (p < 0.05). Areas under the curve of total perfusion calculated using the dual-input method, pulmonary arterial perfusion calculated using the dual-input method, and perfusion calculated using the single-input method were significantly larger than that of SUVmax (p < 0.05). The accuracy of total perfusion (83.3%) was significantly greater than the accuracy of the other indexes: pulmonary arterial perfusion (72.9%, p < 0.05), systemic arterial perfusion calculated using the dual-input method (69.8%, p < 0.05), perfusion (66.7%, p < 0.05), and SUVmax (60.4%, p < 0.05). Dynamic area-detector CT analyzed using the dual-input maximum slope method has better potential for the diagnosis of pulmonary nodules than dynamic area-detector CT analyzed using other methods and than PET/CT.

Traumatic dissection of extracranial vertebral artery with massive subtentorial cerebral infarction: report of an autopsy case.

PubMed

Saito, Kazuyuki; Takada, Aya; Kuroda, Naohito; Hara, Masaaki; Arai, Masaaki; Ro, Ayako

2009-04-01

We present an extremely rare autopsy case with traumatic dissection of the extracranial vertebral artery due to blunt injury caused by a traffic accident. The patient complained of nausea and numbness of the hands at the scene of the accident. His consciousness deteriorated and he fell into a coma within 12h, then died 4 days after the collision. Brain CT/MRI disclosed massive infratentorial cerebral infarction while MRA imaged neither of the vertebral arteries. Autopsy revealed a seatbelt mark on the right side of the lower neck, with fracture of the right transverse process of the sixth cervical vertebra. The right extracranial vertebral artery (V2) showed massive medial dissection from the portion adjacent to the fracture throughout the upper end of the extracranial part of the artery and was occluded by a thrombus. An intimal tear was confirmed near the starting point of the dissection. The brain disclosed massive infarction of posterior circulation territories with changes to the so-called respirator brain. The victim's left vertebral artery was considerably hypoplastic. We concluded that a massive infratentorial infarction was caused by dissection of the right extracranial vertebral artery and consecutive thrombus formation brought about by impact with the seatbelt at the time of the collision.

Microsurgical anatomy of the extracerebral segment of recurrent artery of Heubner in the Mexican population.

PubMed

Gasca-González, Oscar Octavio; Delgado-Reyes, Luis; Pérez-Cruz, Julio César

2011-01-01

The recurrent artery of Heubner (RAH) is originated commonly from the anterior cerebral artery. Its extracerebral segment is directed toward the anterior perforate substance where it penetrates the cortex. The RAH was dissected from 15 human brains from Mexican population, and the presence, length, branches, course and either RHAs or anterior communicating artery complex variants were reported. The RAH was found in 93% of the hemispheres and duplicated in 39% of the hemispheres. The RAH was duplicated in at least a hemisphere in 46.6% of the brains; 40% of the brains had a RAH in every hemisphere. It was duplicated in every hemisphere in 20%. A single artery at a hemisphere was found in 26.6% and double at the other hemisphere. With a length between 13.6 and 36.7 mm (mean: 24.2 mm) and giving rise to 1-9 branches (mean: 3.9 branches), the RAH originated from the juxtacommunicating segment in 44% of the cases, from A2 in 41%, from A1 in 5% and as a branch of the frontopolar artery in 10%. It had an oblique course in 38%, an L in 31%, sinuous in 18% and an inverted L in 13%. In 53.3% of the brains, some variant of the anterior communicating artery complex was found. Because of the common anatomy of the RAH and its variants, we must consider the probability of finding it duplicated; therefore, it is necessary to make minute dissections of the region to locate or to secure the absence of the RAH.

[Comparative anatomical study of the ventral brain arteries of the Pudu pudu (Molina, 1782) with those of the cow].

PubMed

Schweitzer-Delaunoy, W

1997-06-01

Comparative anatomical study of the ventral brain arteries of the Pudú pudu (Molina, 1782) with those of the cow. A comparison using the corrosion method was made between Pudú pudu (Molina, 1782) ventral brain arteries and those of the cow. The Pudú's Rete mirabile epidurale rostrale (Nomina Anatomica Veterinaria, 1994) is ventrally formed by branches of the A. maxillaris, and caudally formed by the A. vertebralis. The Hypophysis is surrounded by the Rete mirabile rostrale. The lateral parts are rostrally joined to that gland by a thin vascular bridge and caudally by thick arteries. The Pudú's Circulus arteriosus cerebri asymmetrical, that is, on the right side the A. cerebri rostralis ends in the A. cerebri media. The left-side A. cerebri rostralis irrigates every rostral portion of the encephalon. In the cow, practically the same arteries come out of the Circulus arteriosus cerebri, which is not asymmetrical. The A. cerebri caudalis comes first out of the A. communicans caudalis and then the branches for the Pons, and finally the A. cerebelli rostralis. In this species, there are arterial blocks that are not present in Pudú.

Developmental process emerges from extended brain-body-behavior networks

PubMed Central

Byrge, Lisa; Sporns, Olaf; Smith, Linda B.

2014-01-01

Studies of brain connectivity have focused on two modes of networks: structural networks describing neuroanatomy and the intrinsic and evoked dependencies of functional networks at rest and during tasks. Each mode constrains and shapes the other across multiple time scales, and each also shows age-related changes. Here we argue that understanding how brains change across development requires understanding the interplay between behavior and brain networks: changing bodies and activities modify the statistics of inputs to the brain; these changing inputs mold brain networks; these networks, in turn, promote further change in behavior and input. PMID:24862251

Brain blood flow and cardiovascular responses to hot flashes in postmenopausal women

PubMed Central

Lucas, Rebekah A. I.; Ganio, Matthew S.; Pearson, James; Crandall, Craig G.

2012-01-01

Objective This study tested two related hypotheses: 1) that brain blood flow is reduced during the postmenopausal hot flash; and, 2) the magnitude of this reduction in brain blood flow is greater during hot flashes where blood pressure is reduced. Methods Eleven healthy, normotensive, postmenopausal women rested in a temperature-controlled laboratory (~25°C) for approximately 120 minutes while waiting for a hot flash to occur. The onset of a hot flash was objectively identified by an abrupt increase in sternal sweat rate (capacitance hygrometry). Middle cerebral artery blood velocity (MCAv, transcranial Doppler) and mean arterial pressure (Finometer®) were measured continuously. Each hot flash was divided into 8 equal segments and the segment with the largest reduction in MCAv and mean arterial pressure identified for each hot flash. Results Twenty-five hot flashes occurred during the experimental sessions (lasting 6.2 ± 2.8 min, 3 ± 1 hot flashes per participant). Seventy-six percent of hot flashes were accompanied by a clear reduction (greater than 5%) in brain blood flow. For all hot flashes, the average maximum decrease in MCAv was 12 ± 9% (7 ± 6 cm.s−1). This value did not correlate with corresponding changes in mean arterial pressure (R=0.36). Conclusion These findings demonstrate that hot flashes are often accompanied by clear reductions in brain blood flow that do not correspond with acute reductions in mean arterial blood pressure. PMID:23435027

Penetration of intra-arterially administered vincristine in experimental brain tumor1,2

PubMed Central

Boyle, Frances M.; Eller, Susan L.; Grossman, Stuart A.

2004-01-01

Vincristine is an integral part of the “PCV” regimen that is commonly administered to treat primary brain tumors. The efficacy of vincristine as a single agent in these tumors has been poorly studied. This study was designed to determine whether vincristine enters normal rat brain or an intracranially or subcutaneously implanted glioma and to assess the presence of the efflux pump P-glycoprotein (P-gp) on tumor and vascular endothelial cells. The 9L rat gliosarcoma was implanted intracranially and subcutaneously in three Fischer 344 rats. On day 7, [3H]vincristine (50 μCi, 4.8 μg) was injected into the carotid artery, and the animals were euthanized 10 or 20 min later. Quantitative autoradiography revealed that vincristine levels in the liver were 6- to 11-fold greater than in the i.c. tumor, and 15- to 37-fold greater than in normal brain, the reverse of the expected pattern with intra-arterial delivery. Vincristine levels in the s.c. tumor were 2-fold higher than levels in the i.c. tumor. P-gp was detected with JSB1 antibody in vascular endothelium of both normal brain and the i.c. tumor, but not in the tumor cells in either location, or in endothelial cells in the s.c. tumor. These results demonstrate that vincristine has negligible penetration of normal rat brain or i.c. 9L glioma despite intra-arterial delivery and the presence of blood-brain barrier dysfunction as demonstrated by Evan’s blue. Furthermore, this study suggests that P-gp-mediated efflux from endothelium may explain these findings. The lack of penetration of vincristine into brain tumor and the paucity of single-agent activity studies suggest that vincristine should not be used in the treatment of primary brain tumors. PMID:15494097

Central angiotensin modulation of baroreflex control of renal sympathetic nerve activity in the rat: influence of dietary sodium.

PubMed

DiBona, G F

2003-03-01

Administration of angiotensin II (angII) into the cerebral ventricles or specific brain sites impairs arterial baroreflex regulation of renal sympathetic nerve activity (SNA). Further insight into this effect was derived from: (a) using specific non-peptide angII receptor antagonists to assess the role of endogenous angII acting on angII receptor subtypes, (b) microinjection of angII receptor antagonists into brain sites behind an intact blood-brain barrier to assess the role of endogenous angII of brain origin and (c) alterations in dietary sodium intake, a known physiological regulator of activity of the renin-angiotensin system (RAS), to assess the ability to physiologically regulate the activity of the brain RAS. In rats in balance on low, normal or dietary sodium intake, losartan or candesartan was injected into the lateral cerebral ventricle or the rostral ventrolateral medulla (RVLM) and the effects on basal renal SNA and the arterial baroreflex sigmoidal relationship between renal SNA and arterial pressure were determined. With both routes of administration, the effects were proportional to the activity of the RAS as indexed by plasma renin activity (PRA). The magnitude of both the decrease in basal renal SNA and the parallel resetting of arterial baroreflex regulation of renal SNA to a lower arterial pressure was greatest in low-sodium rats with highest PRA and least in high-sodium rats with lowest PRA. Disinhibition of the paraventricular nucleus (PVN) by injection of bicuculline causes pressor, tachycardic and renal sympathoexcitatory responses mediated via an angiotensinergic projection from PVN to RVLM. In comparison with responses in normal sodium rats, these responses were greatly diminished in high-sodium rats and greatly enhanced in low-sodium rats. Physiological changes in the activity of the RAS produced by alterations in dietary sodium intake regulate the contribution of endogenous angII of brain origin in the modulation of arterial baroreflex regulation of renal SNA.

Right-Brained Kids in Left-Brained Schools

ERIC Educational Resources Information Center

Hunter, Madeline

1976-01-01

Students who learn well through left hemisphere brain input (oral and written) have minimal practice in using the right hemisphere, while those who are more proficient in right hemisphere (visual) input processing are handicapped by having to use primarily their left brains. (MB)

Abnormal arterial flows by a distributed model of the fetal circulation.

PubMed

van den Wijngaard, Jeroen P H M; Westerhof, Berend E; Faber, Dirk J; Ramsay, Margaret M; Westerhof, Nico; van Gemert, Martin J C

2006-11-01

Modeling the propagation of blood pressure and flow along the fetoplacental arterial tree may improve interpretation of abnormal flow velocity waveforms in fetuses. The current models, however, either do not include a wide range of gestational ages or do not account for variation in anatomical, vascular, or rheological parameters. We developed a mathematical model of the pulsating fetoumbilical arterial circulation using Womersley's oscillatory flow theory and viscoelastic arterial wall properties. Arterial flow waves are calculated at different arterial locations from which the pulsatility index (PI) can be determined. We varied blood viscosity, placental and brain resistances, placental compliance, heart rate, stiffness of the arterial wall, and length of the umbilical arteries. The PI increases in the umbilical artery and decreases in the cerebral arteries, as a result of increasing placental resistance or decreasing brain resistance. Both changes in resistance decrease the flow through the placenta. An increased arterial stiffness increases the PIs in the entire fetoplacental circulation. Blood viscosity and peripheral bed compliance have limited influence on the flow profiles. Bradycardia and tachycardia increase and decrease the PI in all arteries, respectively. Umbilical arterial length has limited influence on the PI but affects the mean arterial pressure at the placental cord insertion. The model may improve the interpretation of arterial flow pulsations and thus may advance both the understanding of pathophysiological processes and clinical management.

PET/CT in giant cell arteritis: High 18F-FDG uptake in the temporal, occipital and vertebral arteries.

PubMed

Rehak, Z; Vasina, J; Ptacek, J; Kazda, T; Fojtik, Z; Nemec, P

18 F-FDG PET/CT imaging is useful in patients with fever of unknown origin and can detect giant cell arteritis in extracranial large arteries. However, it is usually assumed that temporal arteries cannot be visualized with a PET/CT scanner due to their small diameter. Three patients with clinical symptoms of temporal arteritis were examined using a standard whole body PET/CT protocol (skull base - mid thighs) followed by a head PET/CT scan using the brain protocol. High 18 F-FDG uptake in the aorta and some arterial branches were detected in all 3 patients with the whole body protocol. Using the brain protocol, head imaging led to detection of high 18 F-FDG uptake in temporal arteries as well as in their branches (3 patients), in occipital arteries (2 patients) and also in vertebral arteries (3 patients). Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Studying Arterial Stiffness Using High-Frequency Ultrasound in Mice with Alzheimer Disease.

PubMed

Huang, Chin-Chia; Cheng, Hsiang-Fan; Zhu, Ben-Peng; Chen, Pei-Yu; Beh, Suet Theng; Kuo, Yu-Min; Huang, Chih-Chung

2017-09-01

Alzheimer disease (AD) is an irreversible, progressive brain disorder that causes slow loss of memory and thinking skills, normally leading to death in 3-9 y. The etiology of AD is not fully understood but is widely believed to be induced by the production and deposition of amyloid-β peptide in the brain. Recently, a correlation was discovered between amyloid-β deposition and atherosclerosis in the cerebral arteries of postmortem brains, indicating that amyloid-β promotes atherogenesis and that in turn atherosclerosis promotes brain amyloid-β accumulation. However, a direct measurement of arterial stiffness for AD is lacking. In the present study, the pulse wave velocity (PWV) of the carotid artery was measured non-invasively in young (3-mo-old) and middle-aged (9-mo-old) wild-type (WT) and modeled AD mice to obtain quantitative data of arterial stiffness by using a 35-MHz high-frequency dual-element transducer. Experimental results show that the PWVs were 1.6 ± 0.5 m/s for young and 2.4 ± 0.4 m/s for middle-aged WT mice and 1.7 ± 0.4 m/s for young and 3.2 ± 0.6 m/s for middle-aged AD mice. Middle-aged groups had higher PWVs (p < 0.0001), which were more pronounced in the AD mice (p < 0.001). The differences in PWVs were not caused by arterial lumen diameter, wall thickness or contents of elastin or collagen. These results imply that AD increases the stiffness of the carotid artery and introduce ultrasound as a potential tool for AD research and diagnosis. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation.

PubMed

Achariyar, Thiyagaragan M; Li, Baoman; Peng, Weiguo; Verghese, Philip B; Shi, Yang; McConnell, Evan; Benraiss, Abdellatif; Kasper, Tristan; Song, Wei; Takano, Takahiro; Holtzman, David M; Nedergaard, Maiken; Deane, Rashid

2016-12-08

Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel. We reasoned that this system also serves to distribute essential molecules in CSF into brain. The aim was to establish whether apoE in CSF, secreted by the choroid plexus, is distributed into brain, and whether this distribution pattern was altered by sleep deprivation. We used fluorescently labeled lipidated apoE isoforms, lenti-apoE3 delivered to the choroid plexus, immunohistochemistry to map apoE brain distribution, immunolabeled cells and proteins in brain, Western blot analysis and ELISA to determine apoE levels and radiolabeled molecules to quantify CSF inflow into brain and brain clearance in mice. Data were statistically analyzed using ANOVA or Student's t- test. We show that the glymphatic fluid transporting system contributes to the delivery of choroid plexus/CSF-derived human apoE to neurons. CSF-delivered human apoE entered brain via the perivascular space of penetrating arteries and flows radially around arteries, but not veins, in an isoform specific manner (apoE2 > apoE3 > apoE4). Flow of apoE around arteries was facilitated by AQP4, a characteristic feature of the glymphatic system. ApoE3, delivered by lentivirus to the choroid plexus and ependymal layer but not to the parenchymal cells, was present in the CSF, penetrating arteries and neurons. The inflow of CSF, which contains apoE, into brain and its clearance from the interstitium were severely suppressed by sleep deprivation compared to the sleep state. Thus, choroid plexus/CSF provides an additional source of apoE and the glymphatic fluid transporting system delivers it to brain via the periarterial space. By implication, failure in this essential physiological role of the glymphatic fluid flow and ISF clearance may also contribute to apoE isoform-specific disorders in the long term.

Valsalva's maneuver revisited: a quantitative method yielding insights into human autonomic control

NASA Technical Reports Server (NTRS)

Smith, M. L.; Beightol, L. A.; Fritsch-Yelle, J. M.; Ellenbogen, K. A.; Porter, T. R.; Eckberg, D. L.

1996-01-01

Seventeen healthy supine subjects performed graded Valsalva maneuvers. In four subjects, transesophageal echographic aortic cross-sectional areas decreased during and increased after straining. During the first seconds of straining, when aortic cross-sectional area was declining and peripheral arterial pressure was rising, peroneal sympathetic muscle neurons were nearly silent. Then, as aortic cross-sectional area and peripheral pressure both declined, sympathetic muscle nerve activity increased, in proportion to the intensity of straining. Poststraining arterial pressure elevations were proportional to preceding increases of sympathetic activity. Sympathetic inhibition after straining persisted much longer than arterial and right atrial pressure elevations. Similarly, R-R intervals changed in parallel with peripheral arterial pressure, until approximately 45 s after the onset of straining, when R-R intervals were greater and arterial pressures were smaller than prestraining levels. Our conclusions are as follows: opposing changes of carotid and aortic baroreceptor inputs reduce sympathetic muscle and increase vagal cardiac motor neuronal firing; parallel changes of barorsensory inputs provoke reciprocal changes of sympathetic and direct changes of vagal firing; and pressure transients lasting only seconds reset arterial pressure-sympathetic and -vagal response relations.

Effects of noninvasive facial nerve stimulation in the dog middle cerebral artery occlusion model of ischemic stroke.

PubMed

Borsody, Mark K; Yamada, Chisa; Bielawski, Dawn; Heaton, Tamara; Castro Prado, Fernando; Garcia, Andrea; Azpiroz, Joaquín; Sacristan, Emilio

2014-04-01

Facial nerve stimulation has been proposed as a new treatment of ischemic stroke because autonomic components of the nerve dilate cerebral arteries and increase cerebral blood flow when activated. A noninvasive facial nerve stimulator device based on pulsed magnetic stimulation was tested in a dog middle cerebral artery occlusion model. We used an ischemic stroke dog model involving injection of autologous blood clot into the internal carotid artery that reliably embolizes to the middle cerebral artery. Thirty minutes after middle cerebral artery occlusion, the geniculate ganglion region of the facial nerve was stimulated for 5 minutes. Brain perfusion was measured using gadolinium-enhanced contrast MRI, and ATP and total phosphate levels were measured using 31P spectroscopy. Separately, a dog model of brain hemorrhage involving puncture of the intracranial internal carotid artery served as an initial examination of facial nerve stimulation safety. Facial nerve stimulation caused a significant improvement in perfusion in the hemisphere affected by ischemic stroke and a reduction in ischemic core volume in comparison to sham stimulation control. The ATP/total phosphate ratio showed a large decrease poststroke in the control group versus a normal level in the stimulation group. The same stimulation administered to dogs with brain hemorrhage did not cause hematoma enlargement. These results support the development and evaluation of a noninvasive facial nerve stimulator device as a treatment of ischemic stroke.

Systems proteomic analysis reveals that clusterin and tissue inhibitor of metalloproteinases 3 increase in leptomeningeal arteries affected by cerebral amyloid angiopathy.

PubMed

Manousopoulou, A; Gatherer, M; Smith, C; Nicoll, J A R; Woelk, C H; Johnson, M; Kalaria, R; Attems, J; Garbis, S D; Carare, R O

2017-10-01

Amyloid beta (Aβ) accumulation in the walls of leptomeningeal arteries as cerebral amyloid angiopathy (CAA) is a major feature of Alzheimer's disease. In this study, we used global quantitative proteomic analysis to examine the hypothesis that the leptomeningeal arteries derived from patients with CAA have a distinct endophenotypic profile compared to those from young and elderly controls. Freshly dissected leptomeningeal arteries from the Newcastle Brain Tissue Resource and Edinburgh Sudden Death Brain Bank from seven elderly (82.9 ± 7.5 years) females with severe capillary and arterial CAA, as well as seven elderly (88.3 ± 8.6 years) and five young (45.4 ± 3.9 years) females without CAA were used in this study. Arteries from four patients with CAA, two young and two elderly controls were individually analysed using quantitative proteomics. Key proteomic findings were then validated using immunohistochemistry. Bioinformatics interpretation of the results showed a significant enrichment of the immune response/classical complement and extracellular matrix remodelling pathways (P < 0.05) in arteries affected by CAA vs. those from young and elderly controls. Clusterin (apolipoprotein J) and tissue inhibitor of metalloproteinases-3 (TIMP3), validated using immunohistochemistry, were shown to co-localize with Aβ and to be up-regulated in leptomeningeal arteries from CAA patients compared to young and elderly controls. Global proteomic profiling of brain leptomeningeal arteries revealed that clusterin and TIMP3 increase in leptomeningeal arteries affected by CAA. We propose that clusterin and TIMP3 could facilitate perivascular clearance and may serve as novel candidate therapeutic targets for CAA. © 2016 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Model-free arterial spin labelling for cerebral blood flow quantification: introduction of regional arterial input functions identified by factor analysis.

PubMed

Knutsson, Linda; Bloch, Karin Markenroth; Holtås, Stig; Wirestam, Ronnie; Ståhlberg, Freddy

2008-05-01

To identify regional arterial input functions (AIFs) using factor analysis of dynamic studies (FADS) when quantification of perfusion is performed using model-free arterial spin labelling. Five healthy volunteers and one patient were examined on a 3-T Philips unit using quantitative STAR labelling of arterial regions (QUASAR). Two sets of images were retrieved, one where the arterial signal had been crushed and another where it was retained. FADS was applied to the arterial signal curves to acquire the AIFs. Perfusion maps were obtained using block-circulant SVD deconvolution and regional AIFs obtained by FADS. In the volunteers, the ASL experiment was repeated within 24 h. The patient was also examined using dynamic susceptibility contrast MRI. In the healthy volunteers, CBF was 64+/-10 ml/[min 100 g] (mean+/-S.D.) in GM and 24+/-4 ml/[min 100 g] in WM, while the mean aBV was 0.94% in GM and 0.25% in WM. Good CBF image quality and reasonable quantitative CBF values were obtained using the combined QUASAR/FADS technique. We conclude that FADS may be a useful supplement in the evaluation of ASL data using QUASAR.

Clinical importance of the anterior choroidal artery: a review of the literature.

PubMed

Yu, Jing; Xu, Ning; Zhao, Ying; Yu, Jinlu

2018-01-01

The anterior choroidal artery (AChA) is a critical artery in brain physiology and function. The AChA is involved in many diseases, including aneurysm, brain infarct, Moyamoya disease (MMD), brain tumor, arteriovenous malformation (AVM), etc. The AChA is vulnerable to damage during the treatment of these diseases and is thus a very important vessel. However, a comprehensive systematic review of the importance of the AChA is currently lacking. In this study, we used the PUBMED database to perform a literature review of the AChA to increase our understanding of its role in neurophysiology. Although the AChA is a small thin artery, it supplies an extremely important region of the brain. The AChA consists of cisternal and plexal segments, and the point of entry into the choroidal plexus is known as the plexal point. During treatment for aneurysms, tumors, AVM or AVF, the AChA cisternal segments should be preserved as a pathway to prevent the infarction of the AChA target region in the brain. In MMD, a dilated AChA provides collateral flow for posterior circulation. In brain infarcts, rapid treatment is necessary to prevent brain damage. In Parkinson disease (PD), the role of the AChA is unclear. In trauma, the AChA can tear and result in intracranial hematoma. In addition, both chronic and non-chronic branch vessel occlusions in the AChA are clinically silent and should not deter aneurysm treatment with flow diversion. Based on the data available, the AChA is a highly essential vessel.

Clinical interrogation and application of super-selective intracranial artery infusion chemotherapy for lung cancer patients with brain metastases.

PubMed

Rong, J; Chunhua, M; Yuan, L; Ning, M; Jinduo, L; Bin, W; Liwei, S

2015-11-01

The purpose of this study was to evaluate the clinical efficacy of super-selective intracranial artery infusion chemotherapy and to determine correlated prognostic parameters for advanced lung cancer patients with brain metastases. Fifty-four lung cancer patients with brain metastasis who had no previous treatment were enrolled for the study. These patients received super-selective intracranial artery infusion chemotherapy, as well as arterial infusion chemotherapy for primary and metastatic lesions. The procedure was performed once every 4 weeks. Patients were monitored to evaluate short-term clinical outcomes 4 weeks after the first 2 treatments, and follow-up visits performed every 4 weeks after the first 4 treatments until the appearance of disease progression or intolerable toxicity. All 54 cases were treated at least 4 times. The overall response rate was 55.56% (30/54), and the disease control rate was 85.19% (46/54). The median overall survival was 7 months, with a 95% confidence interval (CI) of 5.87-8.13 months, and the median progression-free survival was 4 months, with a 95% CI of 3.20-4.80 months. The 6-month survival rate and 1-year survival rate were 81.48% (44/54) and 18.52% (10/54), respectively. Super-selective intracranial artery infusion chemotherapy provides a clinically efficacious avenue of treatment for lung cancer patients with brain metastases. Pathological classification, Karnofsky performance status, and extracranial metastases may serve as reliable prognostic parameters in determining the clinical outcomes for lung cancer patients with brain metastases.

Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36

PubMed Central

Ettrup, Anders; da Cunha-Bang, Sophie; McMahon, Brenda; Lehel, Szabolcs; Dyssegaard, Agnete; Skibsted, Anine W; Jørgensen, Louise M; Hansen, Martin; Baandrup, Anders O; Bache, Søren; Svarer, Claus; Kristensen, Jesper L; Gillings, Nic; Madsen, Jacob; Knudsen, Gitte M

2014-01-01

[11C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT2A) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [11C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT2A receptors with [11C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [11C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [11C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT2A receptor antagonist ketanserin before a second PET scan significantly decreased [11C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [11C]Cimbi-36 binding is selective for 5-HT2A receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT2A receptors in the human brain. Thus, we here describe [11C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT2A receptors in the human brain. PMID:24780897

[Neuroprotective activity of the proline-containing dipeptide noopept on the model of brain ischemia induced by the middle cerebral artery occlusion].

PubMed

Gavrilova, S A; Us, K S; Ostrovskaia, R U; Koshelev, V B

2006-01-01

The influence of noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) on the extent of ischemic cortical stroke was investigated in experiments on white mongrel male rats with ischemia induced by a combination of the middle cerebral artery occlusion with ipsilateral common carotid artery ligation. Animals were treated with noopept (0.5 mg/kg, i.p.) according to the following schedule: 15 min and 2, 24, and 48 h after the occlusion. Test rats were decapitated 72 h after occlusion, brains were extracted and frozen, and thin brain slices were stained with 2,3,5-triphenyltetrazolium chloride. The slices were scanned and processed using Auc 1 computer program, which estimates the percentage of damaged area relative to that of the whole ipsilateral hemisphere. The conditions of coagulation the distal segment of middle cerebral artery were selected, which caused necrosis localized in the fronto-parietal and dorso-lateral regions of the brain cortex without any damage of subcortical structures. The extent of the brain damage in control group (treated by saline) was 18.6%, while that in the group treated with noopept was 12.2%, thus demonstrating a decrease in the infarction area by 34.5% (p < 05). The data on noopept efficacy on the model of the extensive ischemic injury of brain cortex show that this drug has good prospects for use in the neuroprotective treatment of stroke.

Noninvasive image derived heart input function for CMRglc measurements in small animal slow infusion FDG PET studies

NASA Astrophysics Data System (ADS)

Xiong, Guoming; Cumming, Paul; Todica, Andrei; Hacker, Marcus; Bartenstein, Peter; Böning, Guido

2012-12-01

Absolute quantitation of the cerebral metabolic rate for glucose (CMRglc) can be obtained in positron emission tomography (PET) studies when serial measurements of the arterial [18F]-fluoro-deoxyglucose (FDG) input are available. Since this is not always practical in PET studies of rodents, there has been considerable interest in defining an image-derived input function (IDIF) by placing a volume of interest (VOI) within the left ventricle of the heart. However, spill-in arising from trapping of FDG in the myocardium often leads to progressive contamination of the IDIF, which propagates to underestimation of the magnitude of CMRglc. We therefore developed a novel, non-invasive method for correcting the IDIF without scaling to a blood sample. To this end, we first obtained serial arterial samples and dynamic FDG-PET data of the head and heart in a group of eight anaesthetized rats. We fitted a bi-exponential function to the serial measurements of the IDIF, and then used the linear graphical Gjedde-Patlak method to describe the accumulation in myocardium. We next estimated the magnitude of myocardial spill-in reaching the left ventricle VOI by assuming a Gaussian point-spread function, and corrected the measured IDIF for this estimated spill-in. Finally, we calculated parametric maps of CMRglc using the corrected IDIF, and for the sake of comparison, relative to serial blood sampling from the femoral artery. The uncorrected IDIF resulted in 20% underestimation of the magnitude of CMRglc relative to the gold standard arterial input method. However, there was no bias with the corrected IDIF, which was robust to the variable extent of myocardial tracer uptake, such that there was a very high correlation between individual CMRglc measurements using the corrected IDIF with gold-standard arterial input results. Based on simulation, we furthermore find that electrocardiogram-gating, i.e. ECG-gating is not necessary for IDIF quantitation using our approach.

Brain Aneurysm

MedlinePlus

A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

Cerebral vessels segmentation for light-sheet microscopy image using convolutional neural networks

NASA Astrophysics Data System (ADS)

Hu, Chaoen; Hui, Hui; Wang, Shuo; Dong, Di; Liu, Xia; Yang, Xin; Tian, Jie

2017-03-01

Cerebral vessel segmentation is an important step in image analysis for brain function and brain disease studies. To extract all the cerebrovascular patterns, including arteries and capillaries, some filter-based methods are used to segment vessels. However, the design of accurate and robust vessel segmentation algorithms is still challenging, due to the variety and complexity of images, especially in cerebral blood vessel segmentation. In this work, we addressed a problem of automatic and robust segmentation of cerebral micro-vessels structures in cerebrovascular images acquired by light-sheet microscope for mouse. To segment micro-vessels in large-scale image data, we proposed a convolutional neural networks (CNNs) architecture trained by 1.58 million pixels with manual label. Three convolutional layers and one fully connected layer were used in the CNNs model. We extracted a patch of size 32x32 pixels in each acquired brain vessel image as training data set to feed into CNNs for classification. This network was trained to output the probability that the center pixel of input patch belongs to vessel structures. To build the CNNs architecture, a series of mouse brain vascular images acquired from a commercial light sheet fluorescence microscopy (LSFM) system were used for training the model. The experimental results demonstrated that our approach is a promising method for effectively segmenting micro-vessels structures in cerebrovascular images with vessel-dense, nonuniform gray-level and long-scale contrast regions.

Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

PubMed

Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

2018-04-01

Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for brain penetration. This indicates that variables influencing brain penetration may not be limiting factors for use of piracetam in ischemic stroke.

Function of circle of Willis

PubMed Central

Vrselja, Zvonimir; Brkic, Hrvoje; Mrdenovic, Stefan; Radic, Radivoje; Curic, Goran

2014-01-01

Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress. PMID:24473483

Early Detection of Increased Intracranial Pressure Episodes in Traumatic Brain Injury: External Validation in an Adult and in a Pediatric Cohort.

PubMed

Güiza, Fabian; Depreitere, Bart; Piper, Ian; Citerio, Giuseppe; Jorens, Philippe G; Maas, Andrew; Schuhmann, Martin U; Lo, Tsz-Yan Milly; Donald, Rob; Jones, Patricia; Maier, Gottlieb; Van den Berghe, Greet; Meyfroidt, Geert

2017-03-01

A model for early detection of episodes of increased intracranial pressure in traumatic brain injury patients has been previously developed and validated based on retrospective adult patient data from the multicenter Brain-IT database. The purpose of the present study is to validate this early detection model in different cohorts of recently treated adult and pediatric traumatic brain injury patients. Prognostic modeling. Noninterventional, observational, retrospective study. The adult validation cohort comprised recent traumatic brain injury patients from San Gerardo Hospital in Monza (n = 50), Leuven University Hospital (n = 26), Antwerp University Hospital (n = 19), Tübingen University Hospital (n = 18), and Southern General Hospital in Glasgow (n = 8). The pediatric validation cohort comprised patients from neurosurgical and intensive care centers in Edinburgh and Newcastle (n = 79). None. The model's performance was evaluated with respect to discrimination, calibration, overall performance, and clinical usefulness. In the recent adult validation cohort, the model retained excellent performance as in the original study. In the pediatric validation cohort, the model retained good discrimination and a positive net benefit, albeit with a performance drop in the remaining criteria. The obtained external validation results confirm the robustness of the model to predict future increased intracranial pressure events 30 minutes in advance, in adult and pediatric traumatic brain injury patients. These results are a large step toward an early warning system for increased intracranial pressure that can be generally applied. Furthermore, the sparseness of this model that uses only two routinely monitored signals as inputs (intracranial pressure and mean arterial blood pressure) is an additional asset.

Retinoblastoma and optic nerve enhancement in a brain magnetic resonance scan: is it always a metastasis?

PubMed

Correa-Acosta, A; González-Alviar, M E; Gaviria-Bravo, M L

2018-05-01

The case is presented on a girl with a unilateral retinoblastoma that required treatment with intra-arterial chemotherapy. In the nuclear magnetic resonance imaging of the brain performed 1 month after intra-arterial chemotherapy treatment, post-laminar optic nerve (ON) enhancement was observed, leading to the suspicion of an ON tumour infiltration. Additional examinations were requested by which a probable optic neuropathy was diagnosed. The ON enhancement in magnetic resonance imaging of the brain in retinoblastoma generally corresponds to tumour invasion of the ON. However, other diagnostic alternatives associated with the use of new treatments, such as intra-arterial chemotherapy, should be considered. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Junctional and nonjunctional effects of heptanol and glycyrrhetinic acid derivates in rat mesenteric small arteries

PubMed Central

Matchkov, Vladimir V; Rahman, Awahan; Peng, Hongli; Nilsson, Holger; Aalkjær, Christian

2004-01-01

Heptanol, 18α-glycyrrhetinic acid (18αGA) and 18β-glycyrrhetinic acid (18βGA) are known blockers of gap junctions, and are often used in vascular studies. However, actions unrelated to gap junction block have been repeatedly suggested in the literature for these compounds. We report here the findings from a comprehensive study of these compounds in the arterial wall. Rat isolated mesenteric small arteries were studied with respect to isometric tension (myography), [Ca2+]i (Ca2+-sensitive dyes), membrane potential and – as a measure of intercellular coupling – input resistance (sharp intracellular glass electrodes). Also, membrane currents (patch-clamp) were measured in isolated smooth muscle cells (SMCs). Confocal imaging was used for visualisation of [Ca2+]i events in single SMCs in the arterial wall. Heptanol (150 μM) activated potassium currents, hyperpolarised the membrane, inhibited the Ca2+ current, and reduced [Ca2+]i and tension, but had little effect on input resistance. Only at concentrations above 200 μM did heptanol elevate input resistance, desynchronise SMCs and abolish vasomotion. 18βGA (30 μM) not only increased input resistance and desynchronised SMCs but also had nonjunctional effects on membrane currents. 18αGA (100 μM) had no significant effects on tension, [Ca2+]i, total membrane current and synchronisation in vascular smooth muscle. We conclude that in mesenteric small arteries, heptanol and 18βGA have important nonjunctional effects at concentrations where they have little or no effect on intercellular communication. Thus, the effects of heptanol and 18βGA on vascular function cannot be interpreted as being caused only by effects on gap junctions. 18αGA apparently does not block communication between SMCs in these arteries, although an effect on myoendothelial gap junctions cannot be excluded. PMID:15210581

PET Quantification of the Norepinephrine Transporter in Human Brain with (S,S)-18F-FMeNER-D2.

PubMed

Moriguchi, Sho; Kimura, Yasuyuki; Ichise, Masanori; Arakawa, Ryosuke; Takano, Harumasa; Seki, Chie; Ikoma, Yoko; Takahata, Keisuke; Nagashima, Tomohisa; Yamada, Makiko; Mimura, Masaru; Suhara, Tetsuya

2017-07-01

Norepinephrine transporter (NET) in the brain plays important roles in human cognition and the pathophysiology of psychiatric disorders. Two radioligands, ( S , S )- 11 C-MRB and ( S , S )- 18 F-FMeNER-D 2 , have been used for imaging NETs in the thalamus and midbrain (including locus coeruleus) using PET in humans. However, NET density in the equally important cerebral cortex has not been well quantified because of unfavorable kinetics with ( S , S )- 11 C-MRB and defluorination with ( S , S )- 18 F-FMeNER-D 2 , which can complicate NET quantification in the cerebral cortex adjacent to the skull containing defluorinated 18 F radioactivity. In this study, we have established analysis methods of quantification of NET density in the brain including the cerebral cortex using ( S , S )- 18 F-FMeNER-D 2 PET. Methods: We analyzed our previous ( S , S )- 18 F-FMeNER-D 2 PET data of 10 healthy volunteers dynamically acquired for 240 min with arterial blood sampling. The effects of defluorination on the NET quantification in the superficial cerebral cortex was evaluated by establishing a time stability of NET density estimations with an arterial input 2-tissue-compartment model, which guided the less-invasive reference tissue model and area under the time-activity curve methods to accurately quantify NET density in all brain regions including the cerebral cortex. Results: Defluorination of ( S , S )- 18 F-FMeNER-D 2 became prominent toward the latter half of the 240-min scan. Total distribution volumes in the superficial cerebral cortex increased with the scan duration beyond 120 min. We verified that 90-min dynamic scans provided a sufficient amount of data for quantification of NET density unaffected by defluorination. Reference tissue model binding potential values from the 90-min scan data and area under the time-activity curve ratios of 70- to 90-min data allowed for the accurate quantification of NET density in the cerebral cortex. Conclusion: We have established methods of quantification of NET densities in the brain including the cerebral cortex unaffected by defluorination using ( S , S )- 18 F-FMeNER-D 2 These results suggest that we can accurately quantify NET density with a 90-min ( S , S )- 18 F-FMeNER-D 2 scan in broad brain areas. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Arterial relationships to the nerves and some rigid structures in the posterior cranial fossa.

PubMed

Surchev, N

2008-09-01

The close relationships between the cranial nerves and the arterial vessels in the posterior cranial fossa are one of the predisposing factors for artery-nerve compression. The aim of this study was to examine the relationships of the vertebral and basilar arteries to some skull and dural structures and the nerves in the posterior cranial fossa. For this purpose, the skull bases and brains of 70 cadavers were studied. The topographic relationships of the vertebral and basilar arteries to the cranial nerves in the posterior cranial fossa were studied and the distances between the arteries and some osseous formations were measured. The most significant variations in arterial position were registered in the lower half of the basilar artery. Direct contact with an artery was established for the hypoglossal canal, jugular tubercle, and jugular foramen. The results reveal additional information about the relationships of the nerves and arteries to the skull and dural formations in the posterior cranial fossa. New quantitative information is given to illustrate them. The conditions for possible artery-nerve compression due to arterial dislocation are discussed and two groups (lines) of compression points are suggested. The medial line comprises of the brain stem points, usually the nerve root entry/exit zone. The lateral line includes the skull eminences, on which the nerves lie, or skull and dural foramina through which they exit the cranial cavity. (c) 2008 Wiley-Liss, Inc.

Patient- and lesion-tailored algorithm of endovascular treatment for arterial occlusive disease of extracranial arteries supplying the brain: safety of the treatment at 30-day follow-up

PubMed Central

Simka, Marian; Brzegowy, Paweł; Janas, Piotr; Kazibudzki, Marek; Pieniążek, Piotr; Ochała, Andrzej; Popiela, Tadeusz; Mrowiecki, Tomasz

2017-01-01

Introduction Although surgical endarterectomy remains the treatment of choice for carotid artery stenosis, stenting plays an important role as an alternative treatment modality, especially in high-risk patients. The actual safety profile associated with stenting procedures is probably better than that reported by randomized controlled trials. Aim To assess the safety of stent implantations in extracranial arteries supplying the brain, and also to identify risk factors associated with this procedure. Material and methods This was a post hoc analysis, with 30-day follow-up. We analyzed the results of treatment of 372 patients who underwent 408 procedures, 197 such procedures in asymptomatic, and 211 in symptomatic individuals. Stenting procedures were performed using a technique and armamentarium which were tailored to the type and anatomy of lesions. Results There were 6 (1.5%) strokes, including 2 (0.5%) major strokes, 1 ipsi- and 1 contralateral, and 4 (1.0%) minor strokes. In asymptomatic patients there was 1 (0.3%) minor stroke. Transient ischemic attacks occurred in 5 (1.2%) patients. There were 2 (0.5%) non-STEMI myocardial infarctions and 2 (0.5%) non-stroke related fatalities. Risk factors of these adverse events were diabetes mellitus, lesions localized in a tortuous segment of the artery, embolic material in the filter and bilateral stenoses of carotid arteries. Additional risk factors in asymptomatic patients were renal impairment and advanced coronary artery disease; and in symptomatic patients, grade 3 arterial hypertension, dislipidemia, cigarette smoking and lesions requiring predilatation. Conclusions Stenting procedures of extracranial arteries supplying the brain, which are tailored to the type and anatomy of lesions, seem to be relatively safe. PMID:28344618

Patient- and lesion-tailored algorithm of endovascular treatment for arterial occlusive disease of extracranial arteries supplying the brain: safety of the treatment at 30-day follow-up.

PubMed

Latacz, Paweł; Simka, Marian; Brzegowy, Paweł; Janas, Piotr; Kazibudzki, Marek; Pieniążek, Piotr; Ochała, Andrzej; Popiela, Tadeusz; Mrowiecki, Tomasz

2017-01-01

Although surgical endarterectomy remains the treatment of choice for carotid artery stenosis, stenting plays an important role as an alternative treatment modality, especially in high-risk patients. The actual safety profile associated with stenting procedures is probably better than that reported by randomized controlled trials. To assess the safety of stent implantations in extracranial arteries supplying the brain, and also to identify risk factors associated with this procedure. This was a post hoc analysis, with 30-day follow-up. We analyzed the results of treatment of 372 patients who underwent 408 procedures, 197 such procedures in asymptomatic, and 211 in symptomatic individuals. Stenting procedures were performed using a technique and armamentarium which were tailored to the type and anatomy of lesions. There were 6 (1.5%) strokes, including 2 (0.5%) major strokes, 1 ipsi- and 1 contralateral, and 4 (1.0%) minor strokes. In asymptomatic patients there was 1 (0.3%) minor stroke. Transient ischemic attacks occurred in 5 (1.2%) patients. There were 2 (0.5%) non-STEMI myocardial infarctions and 2 (0.5%) non-stroke related fatalities. Risk factors of these adverse events were diabetes mellitus, lesions localized in a tortuous segment of the artery, embolic material in the filter and bilateral stenoses of carotid arteries. Additional risk factors in asymptomatic patients were renal impairment and advanced coronary artery disease; and in symptomatic patients, grade 3 arterial hypertension, dislipidemia, cigarette smoking and lesions requiring predilatation. Stenting procedures of extracranial arteries supplying the brain, which are tailored to the type and anatomy of lesions, seem to be relatively safe.

Detachable-Tip Microcatheters for Liquid Embolization of Brain Arteriovenous Malformations and Fistulas: A United States Single-Center Experience.

PubMed

Herial, Nabeel A; Khan, Asif A; Sherr, Gregory T; Qureshi, Mushtaq H; Suri, M Fareed K; Qureshi, Adnan I

2015-09-01

The US Food and Drug Administration recently approved a detachable-tip microcatheter, the Apollo microcatheter (eV3, Inc, Irvine, California), to prevent catheter entrapment during embolization of brain arteriovenous malformations (AVMs) using liquid embolic systems. To report technical aspects and clinical results of cerebral embolizations with the Apollo microcatheter in 7 embolizations in 3 adult patients. A 62-year-old man presented with an AVM in the parieto-occipital region measuring 3.6 × 1.6 cm with major cortical feeders from the right middle cerebral artery (MCA) and minor contribution from the distal right anterior cerebral artery. Two pedicles originating from the MCA were embolized. A 48-year-old woman presented with a left frontal AVM measuring 3.3 × 1.8 cm with arterial feeders from the left MCA, left middle meningeal artery, and contralateral anterior cerebral artery. Three pedicles originating from the left MCA were embolized. A 76-year-old man presented with an arteriovenous fistula with multiple fistulous connections and feeders from both vertebral and occipital arteries and the left posterior cerebral artery draining into the left transverse, torcula, and left sigmoid sinus. Two major occipital artery feeders were embolized. Seven Apollo microcatheters were used with the Onyx 18 liquid embolic system. The length of the detachable tip was 15 mm in 2 and 30 mm in 5 embolizations. The mean microcatheter in-position time within the pedicle was 20 minutes. Detachment of tip occurred in 3 instances. No limitations in accessing target arterial feeders and safe tip disengagement were noted despite prolonged injection times. Our initial experience supports the feasibility, safety, and effectiveness of detachable-tip microcatheters in treating brain AVMs and arteriovenous fistulas.

Optical-resolution photoacoustic microscopy of ischemic stroke

NASA Astrophysics Data System (ADS)

Hu, Song; Gonzales, Ernie; Soetikno, Brian; Gong, Enhao; Yan, Ping; Maslov, Konstantin; Lee, Jin-Moo; Wang, Lihong V.

2011-03-01

A major obstacle in understanding the mechanism of ischemic stroke is the lack of a tool to noninvasively or minimally invasively monitor cerebral hemodynamics longitudinally. Here, we applied optical-resolution photoacoustic microscopy (OR-PAM) to longitudinally study ischemic stroke induced brain injury in a mouse model with transient middle cerebral artery occlusion (MCAO). OR-PAM showed that, during MCAO, the average hemoglobin oxygen saturation (sO2) values of feeder arteries and draining veins within the stroke core region dropped ~10% and ~34%, respectively. After reperfusion, arterial sO2 recovered back to the baseline; however, the venous sO2 increased above the baseline value by ~7%. Thereafter, venous sO2 values were close to the arterial sO2 values, suggesting eventual brain tissue infarction.

Perfusion kinetics in human brain tumor with DCE-MRI derived model and CFD analysis.

PubMed

Bhandari, A; Bansal, A; Singh, A; Sinha, N

2017-07-05

Cancer is one of the leading causes of death all over the world. Among the strategies that are used for cancer treatment, the effectiveness of chemotherapy is often hindered by factors such as irregular and non-uniform uptake of drugs inside tumor. Thus, accurate prediction of drug transport and deposition inside tumor is crucial for increasing the effectiveness of chemotherapeutic treatment. In this study, a computational model of human brain tumor is developed that incorporates dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data into a voxelized porous media model. The model takes into account realistic transport and perfusion kinetics parameters together with realistic heterogeneous tumor vasculature and accurate arterial input function (AIF), which makes it patient specific. The computational results for interstitial fluid pressure (IFP), interstitial fluid velocity (IFV) and tracer concentration show good agreement with the experimental results. The computational model can be extended further for predicting the deposition of chemotherapeutic drugs in tumor environment as well as selection of the best chemotherapeutic drug for a specific patient. Copyright © 2017 Elsevier Ltd. All rights reserved.

21 CFR 882.5175 - Carotid artery clamp.

Code of Federal Regulations, 2014 CFR

2014-04-01

... carotid artery to treat intracranial aneurysms (balloonlike sacs formed on blood vessels) or other intracranial vascular malformations that are difficult to attach directly by reducing the blood pressure and... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting...

21 CFR 882.5175 - Carotid artery clamp.

Code of Federal Regulations, 2013 CFR

2013-04-01

... carotid artery to treat intracranial aneurysms (balloonlike sacs formed on blood vessels) or other intracranial vascular malformations that are difficult to attach directly by reducing the blood pressure and... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting...

21 CFR 882.5175 - Carotid artery clamp.

Code of Federal Regulations, 2010 CFR

2010-04-01

... carotid artery to treat intracranial aneurysms (balloonlike sacs formed on blood vessels) or other intracranial vascular malformations that are difficult to attach directly by reducing the blood pressure and... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting...

21 CFR 882.5175 - Carotid artery clamp.

Code of Federal Regulations, 2012 CFR

2012-04-01

... carotid artery to treat intracranial aneurysms (balloonlike sacs formed on blood vessels) or other intracranial vascular malformations that are difficult to attach directly by reducing the blood pressure and... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting...

21 CFR 882.5175 - Carotid artery clamp.

Code of Federal Regulations, 2011 CFR

2011-04-01

... carotid artery to treat intracranial aneurysms (balloonlike sacs formed on blood vessels) or other intracranial vascular malformations that are difficult to attach directly by reducing the blood pressure and... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting...

Viral-genetic tracing of the input-output organization of a central noradrenaline circuit.

PubMed

Schwarz, Lindsay A; Miyamichi, Kazunari; Gao, Xiaojing J; Beier, Kevin T; Weissbourd, Brandon; DeLoach, Katherine E; Ren, Jing; Ibanes, Sandy; Malenka, Robert C; Kremer, Eric J; Luo, Liqun

2015-08-06

Deciphering how neural circuits are anatomically organized with regard to input and output is instrumental in understanding how the brain processes information. For example, locus coeruleus noradrenaline (also known as norepinephrine) (LC-NE) neurons receive input from and send output to broad regions of the brain and spinal cord, and regulate diverse functions including arousal, attention, mood and sensory gating. However, it is unclear how LC-NE neurons divide up their brain-wide projection patterns and whether different LC-NE neurons receive differential input. Here we developed a set of viral-genetic tools to quantitatively analyse the input-output relationship of neural circuits, and applied these tools to dissect the LC-NE circuit in mice. Rabies-virus-based input mapping indicated that LC-NE neurons receive convergent synaptic input from many regions previously identified as sending axons to the locus coeruleus, as well as from newly identified presynaptic partners, including cerebellar Purkinje cells. The 'tracing the relationship between input and output' method (or TRIO method) enables trans-synaptic input tracing from specific subsets of neurons based on their projection and cell type. We found that LC-NE neurons projecting to diverse output regions receive mostly similar input. Projection-based viral labelling revealed that LC-NE neurons projecting to one output region also project to all brain regions we examined. Thus, the LC-NE circuit overall integrates information from, and broadcasts to, many brain regions, consistent with its primary role in regulating brain states. At the same time, we uncovered several levels of specificity in certain LC-NE sub-circuits. These tools for mapping output architecture and input-output relationship are applicable to other neuronal circuits and organisms. More broadly, our viral-genetic approaches provide an efficient intersectional means to target neuronal populations based on cell type and projection pattern.

Direct reperfusion of the right common carotid artery prior to cardiopulmonary bypass in patients with brain malperfusion complicated with acute aortic dissection.

PubMed

Okita, Yutaka; Matsumori, Masamichi; Kano, Hiroya

2016-04-01

The cases of 3 patients with brain malperfusion secondary to acute aortic dissection who underwent preoperative perfusion of the right common carotid artery are presented. The patients were 64, 65 and 72 years old and 2 were female. All were in a comatose or semi-comatose state with left hemiplegia. The right common carotid artery was exposed and directly cannulated, using a 12-Fr paediatric arterial cannula. The right common femoral artery was chosen for arterial drainage, using a 14-Fr double-lumen cannula. The circuit contained a small roller pump and heat exchanger coil. Target flow was set at 90 ml/min and blood temperature at 30 °C. Durations of right carotid perfusion were 120, 100 and 45 min, respectively. All underwent partial arch replacement and survived. Postoperative neurological sequelae were minimal in all cases. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Quantification of [(11)C]yohimbine binding to α2 adrenoceptors in rat brain in vivo.

PubMed

Phan, Jenny-Ann; Landau, Anne M; Wong, Dean F; Jakobsen, Steen; Nahimi, Adjmal; Doudet, Doris J; Gjedde, Albert

2015-03-01

We quantified the binding potentials (BPND) of [(11)C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [(11)C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [(11)C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution (VT) of [(11)C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [(11)C]yohimbine BPND of ~38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [(11)C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.

[Moyamoya disease as a rare cause of ischaemic stroke--case report].

PubMed

Kułakowska, Alina; Kapica-Topczewska, Katarzyna; Borowik, Helena; Drozdowski, Wiesław

2009-10-01

Moyamoya disease is a rare, progressive disease of the vessels diagnosed according to characteristic abnormalities of brain arteries in the angiography. The incidence of moyamoya disease in Europe is lower than in Asia and its clinical course in European population is probably different from Asiatic (older age of onset and rare incidence of hemorrhagic strokes). Two young patients were diagnosed as moyamoya disease on the basis of clinical symptoms (ischaemic stroke) and results of brain vessels' angiography, which documented an occlusion of both internal carotid arteries above branching-off the ocular arteries in the first patient and stenosis of distal internal carotid arteries and proximal medial and anterior cerebral arteries in the second one. Both patients are under control of the Neurological Outpatient Department and their neurological state is stable. Despite that moyamoya disease is a rare cause of ischaemic stroke, it should be always considered as one of etiologic factors, especially in young patients.

Bilateral cerebellar and brain stem infarction resulting from vertebral artery injury following cervical trauma without radiographic damage of the spinal column: a case report.

PubMed

Mimata, Yoshikuni; Murakami, Hideki; Sato, Kotaro; Suzuki, Yoshiaki

2014-01-01

Vertebral artery injury can be a complication of cervical spine injury. Although most cases are asymptomatic, the rare case progresses to severe neurological impairment and fatal outcomes. We experienced a case of bilateral cerebellar and brain stem infarction with fatal outcome resulting from vertebral artery injury associated with cervical spine trauma. A 69-year-old male was admitted to our hospital because of tetraplegia after falling down the stairs and hitting his head on the floor. Marked bony damage of the cervical spine was not apparent on radiographs and CT scans, so the injury was initially considered to be a cervical cord injury without bony damage. However, an intensity change in the intervertebral disc at C5/C6, and a ventral epidural hematoma were observed on MRI. A CT angiogram of the neck showed the right vertebral artery was completely occluded at the C4 level of the spine. Forty-eight hours after injury, the patient lapsed into drowsy consciousness. The cranial CT scan showed a massive low-density area in the bilateral cerebellar hemispheres and brain stem. Anticoagulation was initiated after a diagnosis of the right vertebral artery injury, but the patient developed bilateral cerebellar and brain stem infarction. The patient's brain herniation progressed and the patient died 52 h after injury. We considered that not only anticoagulation but also treatment for thrombosis would have been needed to prevent cranial embolism. We fully realize that early and appropriate treatment are essential to improve the treatment results, and constructing a medical system with a team of orthopedists, radiologists, and neurosurgeons is also very important.

Multiscale Modeling of Hematologic Disorders

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

Fedosov, Dmitry A.; Pivkin, Igor; Pan, Wenxiao

Parasitic infectious diseases and other hereditary hematologic disorders are often associated with major changes in the shape and viscoelastic properties of red blood cells (RBCs). Such changes can disrupt blood flow and even brain perfusion, as in the case of cerebral malaria. Modeling of these hematologic disorders requires a seamless multiscale approach, where blood cells and blood flow in the entire arterial tree are represented accurately using physiologically consistent parameters. In this chapter, we present a computational methodology based on dissipative particle dynamics (DPD) which models RBCs as well as whole blood in health and disease. DPD is a Lagrangianmore » method that can be derived from systematic coarse-graining of molecular dynamics but can scale efficiently up to small arteries and can also be used to model RBCs down to spectrin level. To this end, we present two complementary mathematical models for RBCs and describe a systematic procedure on extracting the relevant input parameters from optical tweezers and microfluidic experiments for single RBCs. We then use these validated RBC models to predict the behavior of whole healthy blood and compare with experimental results. The same procedure is applied to modeling malaria, and results for infected single RBCs and whole blood are presented.« less

Cocaine-Induced Structural Plasticity in Input Regions to Distinct Cell Types in Nucleus Accumbens.

PubMed

Barrientos, Cindy; Knowland, Daniel; Wu, Mingche M J; Lilascharoen, Varoth; Huang, Kee Wui; Malenka, Robert C; Lim, Byung Kook

2018-05-09

The nucleus accumbens (NAc) is a brain region implicated in pathological motivated behaviors such as drug addiction and is composed predominantly of two discrete populations of neurons, dopamine receptor-1- and dopamine receptor-2-expressing medium spiny neurons (D1-MSNs and D2-MSNs, respectively). It is unclear whether these populations receive inputs from different brain areas and whether input regions to these cell types undergo distinct structural adaptations in response to the administration of addictive drugs such as cocaine. Using a modified rabies virus-mediated tracing method, we created a comprehensive brain-wide monosynaptic input map to NAc D1- and D2-MSNs. Next, we analyzed nearly 2000 dendrites and 125,000 spines of neurons across four input regions (the prelimbic cortex, medial orbitofrontal cortex, basolateral amygdala, and ventral hippocampus) at four separate time points during cocaine administration and withdrawal to examine changes in spine density in response to repeated intraperitoneal cocaine injection in mice. D1- and D2-MSNs display overall similar input profiles, with the exception that D1-MSNs receive significantly more input from the medial orbitofrontal cortex. We found that neurons in distinct brain areas projecting to D1- and D2-MSNs display different adaptations in dendritic spine density at different stages of cocaine administration and withdrawal. While NAc D1- and D2-MSNs receive input from similar brain structures, cocaine-induced spine density changes in input regions are quite distinct and dynamic. While previous studies have focused on input-specific postsynaptic changes within NAc MSNs in response to cocaine, these findings emphasize the dramatic changes that occur in the afferent input regions as well. Published by Elsevier Inc.

Bilateral vertebral artery lesion after dislocating cervical spine trauma. A case report.

PubMed

Wirbel, R; Pistorius, G; Braun, C; Eichler, A; Mutschler, W

1996-06-01

This case report illustrates the problems associated with diagnosis and management of vertebral artery injuries resulting from dislocating cervical spine trauma. Treatment involved the principles of anterior stabilization of dislocating cervical spine fracture as well as the diagnostic procedures and therapeutic modalities appropriate for vertebral artery lesions. Because vertebral artery injuries with cervical spine trauma are rarely symptomatic, they can easily be overlooked. Bilateral or dominant vertebral artery occlusion, however, may cause fatal ischemic damage to the brain stem and cerebellum. Cervical spine dislocation was stabilized immediately after admission using internal fixation by ventral plate and corticocancellous bone graft. Immediate angiography was performed when brain stem neurologic dysfunction manifested 36 hours after surgery. The patient was treated with anticoagulation, osmotherapy, and controlled hypertension. A fatal outcome resulted in this case of dominant left vertebral artery occlusion. Necropsy even revealed bilateral vertebral artery damage at the level of the osseous lesion. The possibility of the complication of a vertebral artery lesion should be kept in mind when examining patients with cervical spine trauma, especially in patients with fracture-dislocation. Immediate identification by vertebral angiography, magnetic resonance imaging, or thin-slice computed tomography scan is necessary for optimal management of this injury.

Middle cerebral arterial flow changes on transcranial color and spectral Doppler sonography in patients with increased intracranial pressure.

PubMed

Wang, Yu; Duan, Yun-You; Zhou, Hai-Yan; Yuan, Li-Jun; Zhang, Li; Wang, Wei; Li, Li-Hong; Li, Liang

2014-12-01

Intracranial pressure usually increases after severe brain injury. However, a method for noninvasive evaluation of intracranial pressure is still lacking. The purpose of this study was to explore the potential role of transcranial color Doppler sonography in assessing intracranial pressure by observing the middle cerebral artery blood flow parameters in patients with increased intracranial pressure of varying etiology. The hemodynamic changes in the middle cerebral artery in patients with varying degrees of increased intracranial pressure were investigated by transcranial color Doppler sonography in 93 patients who had emergency surgery for brain injury. Middle cerebral artery Doppler flow spectra changed regularly as intracranial pressure increased. The pulsatility index (PI) and resistive index (RI) had a significantly positive correlation with intracranial pressure (r = 0.90 and 0.89, respectively; P< .001), whereas the middle cerebral artery diastolic velocity showed a significant negative correlation with intracranial pressure (r = -0.52; P< .01). A receiver operating characteristic curve showed that the RI and PI cutoff values were 0.705 and 1.335, respectively, for predicting increased intracranial pressure, with sensitivity of 0.885 and specificity of 0.970. In addition to the PI and RI, middle cerebral artery diastolic flow velocity measurement by transcranial color Doppler sonography may also be a useful variable for evaluating intracranial pressure in patients with acute brain injury. © 2013 by the American Institute of Ultrasound in Medicine.

Influence of Gender and Age on Average Dimensions of Arteries Forming the Circle of Willis Study by Magnetic Resonance Angiography on Kosovo's Population.

PubMed

Shatri, Jeton; Bexheti, Dorentina; Bexheti, Sadi; Kabashi, Serbeze; Krasniqi, Shaip; Ahmetgjekaj, Ilir; Zhjeqi, Valbona

2017-10-15

Circulus arteriosus cerebri is the main source of blood supply to the brain; it connects the left and right hemispheres with anterior and posterior parts. Located at the interpenducular fossa at the base of the brain the circle of Willis is the most important source of collateral circulation in the presence of the disease in the carotid or vertebral artery. The purpose of the research is to study the diameter and length of arteries and provide an important source of reference on Kosovo's population. This is an observative descriptive study performed at the University Clinical Center of Kosovo. A randomised sample of 133 angiographic examinations in adult patients of both sexes who were instructed to exploration is included. The diameters and lengths measured in our study were comparable with other brain-cadaver studies especially those performed by MRA. All dimensions of the arteries are larger in male than female, except the diameter of PCoA that is larger in female (p < 0.05) and length of the ACoA (p < 0.05). Significant differences were found in diameters of arteries between the younger and the older age groups. Knowing the dimensions of the arteries of the circle of Willis has a great importance in interventional radiology as well as during anatomy lessons.

Influence of Gender and Age on Average Dimensions of Arteries Forming the Circle of Willis Study by Magnetic Resonance Angiography on Kosovo’s Population

PubMed Central

Shatri, Jeton; Bexheti, Dorentina; Bexheti, Sadi; Kabashi, Serbeze; Krasniqi, Shaip; Ahmetgjekaj, Ilir; Zhjeqi, Valbona

2017-01-01

BACKGROUND: Circulus arteriosus cerebri is the main source of blood supply to the brain; it connects the left and right hemispheres with anterior and posterior parts. Located at the interpenducular fossa at the base of the brain the circle of Willis is the most important source of collateral circulation in the presence of the disease in the carotid or vertebral artery. AIM: The purpose of the research is to study the diameter and length of arteries and provide an important source of reference on Kosovo’s population. METHODS: This is an observative descriptive study performed at the University Clinical Center of Kosovo. A randomised sample of 133 angiographic examinations in adult patients of both sexes who were instructed to exploration is included. RESULTS: The diameters and lengths measured in our study were comparable with other brain-cadaver studies especially those performed by MRA. All dimensions of the arteries are larger in male than female, except the diameter of PCoA that is larger in female (p < 0.05) and length of the ACoA (p < 0.05). Significant differences were found in diameters of arteries between the younger and the older age groups. CONCLUSION: Knowing the dimensions of the arteries of the circle of Willis has a great importance in interventional radiology as well as during anatomy lessons. PMID:29104678

Reliability of temperatures measured at standard monitoring sites as an index of brain temperature during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction.

PubMed

Akata, Takashi; Setoguchi, Hidekazu; Shirozu, Kazuhiro; Yoshino, Jun

2007-06-01

It is essential to estimate the brain temperature of patients during deliberate deep hypothermia. Using jugular bulb temperature as a standard for brain temperature, we evaluated the accuracy and precision of 5 standard temperature monitoring sites (ie, pulmonary artery, nasopharynx, forehead deep-tissue, urinary bladder, and fingertip skin-surface tissue) during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction. In 20 adult patients with thoracic aortic aneurysms, the 5 temperature monitoring sites were recorded every 1 minute during deep hypothermic (<20 degrees C) cardiopulmonary bypass. The accuracy was evaluated by the difference from jugular bulb temperature, and the precision was evaluated by its standard deviation, as well as by the correlation with jugular bulb temperature. Pulmonary artery temperature and jugular bulb temperature began to change immediately after the start of cooling or rewarming, closely matching each other, and the other temperatures lagged behind these two temperatures. During either situation, the accuracy of pulmonary artery temperature measurement (0.3 degrees C-0.5 degrees C) was much superior to the other measurements, and its precision (standard deviation of the difference from jugular bulb temperature = 1.5 degrees C-1.8 degrees C; correlation coefficient = 0.94-0.95) was also best among the measurements, with its rank order being pulmonary artery > or = nasopharynx > forehead > bladder > fingertip. However, the accuracy and precision of pulmonary artery temperature measurement was significantly impaired during and for several minutes after infusion of cold cardioplegic solution. Pulmonary artery temperature measurement is recommended to estimate brain temperature during deep hypothermic cardiopulmonary bypass, even if it is conducted with the sternum opened; however, caution needs to be exercised in interpreting its measurements during periods of the cardioplegic solution infusion.

Effects of caffeine on the preterm brain: An observational study.

PubMed

Dix, Laura M L; van Bel, Frank; Baerts, Willem; Lemmers, Petra M A

2018-05-01

Caffeine improves neurodevelopmental outcome of preterm infants. This study analyses the effects of caffeine on the neonatal brain. We hypothesized that caffeine has a neuroprotective effect through an increase in oxygen metabolism; reflected by increased cerebral oxygen extraction, electrical function, and perfusion. Preterm infants <32 weeks gestation (GA) receiving their primary dose caffeine-base (10 mg/kg) were included. Ten minutes of stable monitoring were selected before, during, and every hour up to 6 h after caffeine. Near-infrared spectroscopy monitored regional cerebral oxygenation (rScO 2 ) and extraction (FTOE). Amplitude-integrated electroencephalogram (aEEG) monitored minimum, mean and maximum amplitudes. Spontaneous activity transients (SAT) rate and the interval between SATs (ISI) were calculated. Mean arterial blood pressure (MABP), heart rate (HR) and arterial oxygen saturation (SaO 2 ) were monitored. Arterial pCO 2 's were collected before and 4 h after caffeine. Brain perfusion was assessed 1 h before and 3 h after caffeine by Doppler-measured resistance-index (RI), peak systolic velocity (PSV) and end-diastolic velocity (EDV), in the anterior cerebral artery (ACA) and internal carotid artery (ICA). Results were presented in mean ± SD. 34 infants, mean GA 28.8 ± 2.1 wk, were included. rScO 2 significantly decreased from 69 ± 11 to 63 ± 12 1 h after caffeine, and recovered at 6 h (66 ± 10). FTOE increased correspondingly. MABP and HR increased significantly. PSV in the ACA decreased slightly. Other Doppler variables, aEEG parameters, and SaO 2 were unaffected. Caffeine increases oxygen extraction, suggesting a (transient) stimulating effect on brain metabolism. However, no substantial changes were found in brain perfusion and in electrical brain activity. Copyright © 2018 Elsevier B.V. All rights reserved.

A Simulation Model of Periarterial Clearance of Amyloid-β from the Brain

PubMed Central

Diem, Alexandra K.; Tan, Mingyi; Bressloff, Neil W.; Hawkes, Cheryl; Morris, Alan W. J.; Weller, Roy O.; Carare, Roxana O.

2016-01-01

The accumulation of soluble and insoluble amyloid-β (Aβ) in the brain indicates failure of elimination of Aβ from the brain with age and Alzheimer's disease (AD). There is a variety of mechanisms for elimination of Aβ from the brain. They include the action of microglia and enzymes together with receptor-mediated absorption of Aβ into the blood and periarterial lymphatic drainage of Aβ. Although the brain possesses no conventional lymphatics, experimental studies have shown that fluid and solutes, such as Aβ, are eliminated from the brain along 100 nm wide basement membranes in the walls of cerebral capillaries and arteries. This lymphatic drainage pathway is reflected in the deposition of Aβ in the walls of human arteries with age and AD as cerebral amyloid angiopathy (CAA). Initially, Aβ diffuses through the extracellular spaces of gray matter in the brain and then enters basement membranes in capillaries and arteries to flow out of the brain. Although diffusion through the extracellular spaces of the brain has been well characterized, the exact mechanism whereby perivascular elimination of Aβ occurs has not been resolved. Here we use a computational model to describe the process of periarterial drainage in the context of diffusion in the brain, demonstrating that periarterial drainage along basement membranes is very rapid compared with diffusion. Our results are a validation of experimental data and are significant in the context of failure of periarterial drainage as a mechanism underlying the pathogenesis of AD as well as complications associated with its immunotherapy. PMID:26903861

Contribution of the vertebral artery to cerebral circulation in the rat snake Elaphe obsoleta

NASA Technical Reports Server (NTRS)

Zippel, K. C.; Lillywhite, H. B.; Mladinich, C. R.; Hargens, A. (Principal Investigator)

1998-01-01

Blood supplying the brain in vertebrates is carried primarily by the carotid vasculature. In most mammals, cerebral blood flow is supplemented by the vertebral arteries, which anastomose with the carotids at the base of the brain. In other tetrapods, cerebral blood is generally believed to be supplied exclusively by the carotid vasculature, and the vertebral arteries are usually described as disappearing into the dorsal musculature between the heart and head. There have been several reports of a vertebral artery connection with the cephalic vasculature in snakes. We measured regional blood flows using fluorescently labeled microspheres and demonstrated that the vertebral artery contributes a small but significant fraction of cerebral blood flow (approximately 13% of total) in the rat snake Elaphe obsoleta. Vascular casts of the anterior vessels revealed that the vertebral artery connection is indirect, through multiple anastomoses with the inferior spinal artery, which connects with the carotid vasculature near the base of the skull. Using digital subtraction angiography, fluoroscopy, and direct observations of flow in isolated vessels, we confirmed that blood in the inferior spinal artery flows craniad from a point anterior to the vertebral artery connections. Such collateral blood supply could potentially contribute to the maintenance of cerebral circulation during circumstances when craniad blood flow is compromised, e.g., during the gravitational stress of climbing.

Evaluation of laser speckle contrast imaging as an intrinsic method to monitor blood brain barrier integrity

PubMed Central

Dufour, Suzie; Atchia, Yaaseen; Gad, Raanan; Ringuette, Dene; Sigal, Iliya; Levi, Ofer

2013-01-01

The integrity of the blood brain barrier (BBB) can contribute to the development of many brain disorders. We evaluate laser speckle contrast imaging (LSCI) as an intrinsic modality for monitoring BBB disruptions through simultaneous fluorescence and LSCI with vertical cavity surface emitting lasers (VCSELs). We demonstrated that drug-induced BBB opening was associated with a relative change of the arterial and venous blood velocities. Cross-sectional flow velocity ratio (veins/arteries) decreased significantly in rats treated with BBB-opening drugs, ≤0.81 of initial values. PMID:24156049

Simplifying [18F]GE-179 PET: are both arterial blood sampling and 90-min acquisitions essential?

PubMed

McGinnity, Colm J; Riaño Barros, Daniela A; Trigg, William; Brooks, David J; Hinz, Rainer; Duncan, John S; Koepp, Matthias J; Hammers, Alexander

2018-06-11

The NMDA receptor radiotracer [ 18 F]GE-179 has been used with 90-min scans and arterial plasma input functions. We explored whether (1) arterial blood sampling is avoidable and (2) shorter scans are feasible. For 20 existing [ 18 F]GE-179 datasets, we generated (1) standardised uptake values (SUVs) over eight intervals; (2) volume of distribution (V T ) images using population-based input functions (PBIFs), scaled using one parent plasma sample; and (3) V T images using three shortened datasets, using the original parent plasma input functions (ppIFs). Correlations with the original ppIF-derived 90-min V T s increased for later interval SUVs (maximal ρ = 0.78; 80-90 min). They were strong for PBIF-derived V T s (ρ = 0.90), but between-subject coefficient of variation increased. Correlations were very strong for the 60/70/80-min original ppIF-derived V T s (ρ = 0.97-1.00), which suffered regionally variant negative bias. Where arterial blood sampling is available, reduction of scan duration to 60 min is feasible, but with negative bias. The performance of SUVs was more consistent across participants than PBIF-derived V T s.

Image-derived arterial input function for quantitative fluorescence imaging of receptor-drug binding in vivo

PubMed Central

Elliott, Jonathan T.; Samkoe, Kimberley S.; Davis, Scott C.; Gunn, Jason R.; Paulsen, Keith D.; Roberts, David W.; Pogue, Brian W.

2017-01-01

Receptor concentration imaging (RCI) with targeted-untargeted optical dye pairs has enabled in vivo immunohistochemistry analysis in preclinical subcutaneous tumors. Successful application of RCI to fluorescence guided resection (FGR), so that quantitative molecular imaging of tumor-specific receptors could be performed in situ, would have a high impact. However, assumptions of pharmacokinetics, permeability and retention, as well as the lack of a suitable reference region limit the potential for RCI in human neurosurgery. In this study, an arterial input graphic analysis (AIGA) method is presented which is enabled by independent component analysis (ICA). The percent difference in arterial concentration between the image-derived arterial input function (AIFICA) and that obtained by an invasive method (ICACAR) was 2.0 ± 2.7% during the first hour of circulation of a targeted-untargeted dye pair in mice. Estimates of distribution volume and receptor concentration in tumor bearing mice (n = 5) recovered using the AIGA technique did not differ significantly from values obtained using invasive AIF measurements (p=0.12). The AIGA method, enabled by the subject-specific AIFICA, was also applied in a rat orthotopic model of U-251 glioblastoma to obtain the first reported receptor concentration and distribution volume maps during open craniotomy. PMID:26349671

Association between right-to-left shunts and brain lesions in sport divers.

PubMed

Gerriets, Tibo; Tetzlaff, Kay; Hutzelmann, Alfred; Liceni, Thomas; Kopiske, Gerrit; Struck, Niklas; Reuter, Michael; Kaps, Manfred

2003-10-01

Recent studies suggest that healthy sport divers may develop clinically silent brain damage, based on the association between a finding of multiple brain lesions on MRI and the presence of right-to-left shunt, a pathway for venous gas bubbles to enter the arterial system. We performed echocontrast transcranial Doppler sonography in 42 sport divers to determine the presence of a right-to-left shunt. Cranial MRI was carried out using a 1.5 T magnet. A lesion was counted if it was hyperintense on both T2-weighted and T2-weighted fluid attenuated inversion recovery sequences. To test the hypothesis that the occurrence of postdive arterial gas emboli is related to brain lesions on MRI, we measured postdive intravascular bubbles in a subset of 15 divers 30 min after open water scuba dives. Echocontrast transcranial Doppler sonography revealed a right-to-left shunt in 16 of the divers (38%). Only one hyperintensive lesion of the central white matter was found and that was in a diver with no evidence of a right-to-left shunt. Postdive arterial gas emboli were detected in 3 out of 15 divers; they had a right-to-left shunt, but no pathologic findings on cranial magnetic resonance imaging. Our data support the theory that right-to-left shunts can serve as a pathway for venous gas bubbles into the arterial circulation. However, we could not confirm an association between brain lesions and the presence of a right-to-left shunt in sport divers.

Split-brain phenomena in anterior communicating artery aneurysm rupture: A case report.

PubMed

Korsakova, Natalya; Liebson, Elizabeth; Moskovich, Lena

2017-06-01

In 1976, a patient with an anterior communicating artery aneurysm (ACoAA) rupture (diagnosed on angiography) and sub-arachnoid hemorrhage (SAH) underwent serial neuropsychological testing revealing a classical anterior cerebral artery (ACA) spasm picture with severe anterograde amnesia of Korsakoff's type and dysexecutive syndrome. In addition, the patient demonstrated impaired hemispheric interaction with alien hand syndrome, dyscopia-dysgraphia, complete left ear neglect, and other, more complex, split-brain phenomena. He was evaluated by A. R. Luria in 1976. Following surgery the patient demonstrated gradual improvement. © 2017 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Human PET studies of metabotropic glutamate receptor subtype 5 with 11C-ABP688.

PubMed

Ametamey, Simon M; Treyer, Valerie; Streffer, Johannes; Wyss, Matthias T; Schmidt, Mark; Blagoev, Milen; Hintermann, Samuel; Auberson, Yves; Gasparini, Fabrizio; Fischer, Uta C; Buck, Alfred

2007-02-01

3-(6-Methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-11C-methyl-oxime (11C-ABP688), a noncompetitive and highly selective antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5), was evaluated for its potential as a PET agent. Six healthy male volunteers (mean age, 25 y; range, 21-33 y) were studied. Brain perfusion (15O-H2O) was measured immediately before each 11C-ABP688 PET scan. For anatomic coregistration, T1-weighted MRI was performed on each subject. Arterial blood samples for the determination of the arterial input curve were obtained at predefined time points, and 11C-ABP688 uptake was assessed quantitatively using a 2-tissue-compartment model. An initial rapid uptake of radioactivity followed by a gradual clearance from all examined brain regions was observed. Relatively high radioactivity concentrations were observed in mGluR5-rich brain regions such as the anterior cingulate, medial temporal lobe, amygdala, caudate, and putamen, whereas radioactivity uptake in the cerebellum and white matter, regions known to contain low densities of mGluR5, was low. Specific distribution volume as an outcome measure of mGluR5 density in the various brain regions ranged from 5.45 +/- 1.47 (anterior cingulate) to 1.91 +/- 0.32 (cerebellum), and the rank order of the corresponding specific distribution volumes of 11C-ABP688 in cortical regions was temporal > frontal > occipital > parietal. The metabolism of 11C-ABP688 in plasma was rapid; at 60 min after injection, 25% +/- 0.03% of radioactivity measured in the plasma of healthy volunteers was intact parent compound. The results of these studies indicate that 11C-ABP688 has suitable characteristics and is a promising PET ligand for imaging mGluR5 distribution in humans. Furthermore, it could be of great value for the selection of appropriate doses of clinically relevant candidate drugs that bind to mGluR5 and for PET studies of patients with psychiatric and neurologic disorders.

Head-to-Head Visual Comparison between Brain Perfusion SPECT and Arterial Spin-Labeling MRI with Different Postlabeling Delays in Alzheimer Disease.

PubMed

Kaneta, T; Katsuse, O; Hirano, T; Ogawa, M; Yoshida, K; Odawara, T; Hirayasu, Y; Inoue, T

2017-08-01

Arterial spin-labeling MR imaging has been recently developed as a noninvasive technique with magnetically labeled arterial blood water as an endogenous contrast medium for the evaluation of CBF. Our aim was to compare arterial spin-labeling MR imaging and SPECT in the visual assessment of CBF in patients with Alzheimer disease. In 33 patients with Alzheimer disease or mild cognitive impairment due to Alzheimer disease, CBF images were obtained by using both arterial spin-labeling-MR imaging with a postlabeling delay of 1.5 seconds and 2.5 seconds (PLD 1.5 and PLD 2.5 , respectively) and brain perfusion SPECT. Twenty-two brain regions were visually assessed, and the diagnostic confidence of Alzheimer disease was recorded. Among all arterial spin-labeling images, 84.9% of PLD 1.5 and 9% of PLD 2.5 images showed the typical pattern of advanced Alzheimer disease (ie, decreased CBF in the bilateral parietal, temporal, and frontal lobes). PLD 1.5 , PLD 2.5 , and SPECT imaging resulted in obviously different visual assessments. PLD 1.5 showed a broad decrease in CBF, which could have been due to an early perfusion. In contrast, PLD 2.5 did not appear to be influenced by an early perfusion but showed fewer pathologic findings than SPECT. The distinctions observed by us should be carefully considered in the visual assessments of Alzheimer disease. Further studies are required to define the patterns of change in arterial spin-labeling-MR imaging associated with Alzheimer disease. © 2017 by American Journal of Neuroradiology.

Comparing performance of centerline algorithms for quantitative assessment of brain vascular anatomy.

PubMed

Diedrich, Karl T; Roberts, John A; Schmidt, Richard H; Parker, Dennis L

2012-12-01

Attributes like length, diameter, and tortuosity of tubular anatomical structures such as blood vessels in medical images can be measured from centerlines. This study develops methods for comparing the accuracy and stability of centerline algorithms. Sample data included numeric phantoms simulating arteries and clinical human brain artery images. Centerlines were calculated from segmented phantoms and arteries with shortest paths centerline algorithms developed with different cost functions. The cost functions were the inverse modified distance from edge (MDFE(i) ), the center of mass (COM), the binary-thinned (BT)-MDFE(i) , and the BT-COM. The accuracy of the centerline algorithms were measured by the root mean square error from known centerlines of phantoms. The stability of the centerlines was measured by starting the centerline tree from different points and measuring the differences between trees. The accuracy and stability of the centerlines were visualized by overlaying centerlines on vasculature images. The BT-COM cost function centerline was the most stable in numeric phantoms and human brain arteries. The MDFE(i) -based centerline was most accurate in the numeric phantoms. The COM-based centerline correctly handled the "kissing" artery in 16 of 16 arteries in eight subjects whereas the BT-COM was correct in 10 of 16 and MDFE(i) was correct in 6 of 16. The COM-based centerline algorithm was selected for future use based on the ability to handle arteries where the initial binary vessels segmentation exhibits closed loops. The selected COM centerline was found to measure numerical phantoms to within 2% of the known length. Copyright © 2012 Wiley Periodicals, Inc.

GORE Flow Reversal System and GORE Embolic Filter Extension Study

ClinicalTrials.gov

2016-01-22

Carotid Stenosis; Constriction, Pathologic; Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical

IMPROVED DERIVATION OF INPUT FUNCTION IN DYNAMIC MOUSE [18F]FDG PET USING BLADDER RADIOACTIVITY KINETICS

PubMed Central

Wong, Koon-Pong; Zhang, Xiaoli; Huang, Sung-Cheng

2013-01-01

Purpose Accurate determination of the plasma input function (IF) is essential for absolute quantification of physiological parameters in positron emission tomography (PET). However, it requires an invasive and tedious procedure of arterial blood sampling that is challenging in mice because of the limited blood volume. In this study, a hybrid modeling approach is proposed to estimate the plasma IF of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in mice using accumulated radioactivity in urinary bladder together with a single late-time blood sample measurement. Methods Dynamic PET scans were performed on nine isoflurane-anesthetized male C57BL/6 mice after a bolus injection of [18F]FDG at the lateral caudal vein. During a 60- or 90-min scan, serial blood samples were taken from the femoral artery. Image data were reconstructed using filtered backprojection with CT-based attenuation correction. Total accumulated radioactivity in the urinary bladder was fitted to a renal compartmental model with the last blood sample and a 1-exponential function that described the [18F]FDG clearance in blood. Multiple late-time blood sample estimates were calculated by the blood [18F]FDG clearance equation. A sum of 4-exponentials was assumed for the plasma IF that served as a forcing function to all tissues. The estimated plasma IF was obtained by simultaneously fitting the [18F]FDG model to the time-activity curves (TACs) of liver and muscle and the forcing function to early (0–1 min) left-ventricle data (corrected for delay, dispersion, partial-volume effects and erythrocytes uptake) and the late-time blood estimates. Using only the blood sample acquired at the end of the study to estimate the IF and the use of liver TAC as an alternative IF were also investigated. Results The area under the plasma TACs calculated for all studies using the hybrid approach was not significantly different from that using all blood samples. [18F]FDG uptake constants in brain, myocardium, skeletal muscle and liver computed by the Patlak analysis using estimated and measured plasma TACs were in excellent agreement (slope ~ 1; R2 > 0.938). The IF estimated using only the last blood sample acquired at the end of the study and the use of liver TAC as plasma IF provided less reliable results. Conclusions The estimated plasma IFs obtained with the hybrid model agreed well with those derived from arterial blood sampling. Importantly, the proposed method obviates the need of arterial catheterization, making it possible to perform repeated dynamic [18F]FDG PET studies on the same animal. Liver TAC is unsuitable as an input function for absolute quantification of [18F]FDG PET data. PMID:23322346

Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine

PubMed Central

Delp, Michael D; Armstrong, R B; Godfrey, Donald A; Laughlin, M Harold; Ross, C David; Wilkerson, M Keith

2001-01-01

The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (). Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 %, respectively. Mean brain blood flow increased 24 and 25 % at 70 and 100 %, respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis. PMID:11410640

On how whales avoid decompression sickness and why they sometimes strand.

PubMed

Blix, Arnoldus Schytte; Walløe, Lars; Messelt, Edward B

2013-09-15

Whales are unique in that the supply of blood to the brain is not by the internal carotid arteries, but by way of thoracic and intra-vertebral arterial retia. We found in the harbor porpoise (Phocoena phocoena) that these retia split up into smaller anastomosing vessels and thin-walled sinusoid structures that are embedded in fat. The solubility of nitrogen is at least six times larger in fat than in water, and we suggest that nitrogen in supersaturated blood will be absorbed in the fat, by diffusion, during the very slow passage of the blood through the arterial retia. Formation of nitrogen bubbles that may reach the brain is thereby avoided. We also suggest that mass stranding of whales may be due to disturbances to their normal dive profiles, resulting in extra release of nitrogen that may overburden the nitrogen 'trap' and allow bubbles to reach the brain and cause abnormal behavior.

Parameters of Blood Flow in Great Arteries in Hypertensive ISIAH Rats with Stress-Dependent Arterial Hypertension.

PubMed

Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel', A L

2016-08-01

Magnetic resonance angiography was used to examine blood flow in great arteries of hypertensive ISIAH and normotensive Wistar rats. In hypertensive ISIAH rats, increased vascular resistance in the basin of the abdominal aorta and renal arteries as well as reduced fraction of total renal blood flow were found. In contrast, blood flow through both carotid arteries in ISIAH rats was enhanced, which in suggests more intensive blood supply to brain regulatory centers providing enhanced stress reactivity of these rats characterized by stress-dependent arterial hypertension.

MRI measurements of Blood-Brain Barrier function in dementia: A review of recent studies.

PubMed

Raja, Rajikha; Rosenberg, Gary A; Caprihan, Arvind

2018-05-15

Blood-brain barrier (BBB) separates the systemic circulation and the brain, regulating transport of most molecules to protect the brain microenvironment. Multiple structural and functional components preserve the integrity of the BBB. Several imaging modalities are available to study disruption of the BBB. However, the subtle changes in BBB leakage that occurs in vascular cognitive impairment and Alzheimer's disease have been less well studied. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is the most widely adopted non-invasive imaging technique for evaluating BBB breakdown. It is used as a significant marker for a wide variety of diseases with large permeability leaks, such as brain tumors and multiple sclerosis, to more subtle disruption in chronic vascular disease and dementia. DCE-MRI analysis of BBB includes both model-free parameters and quantitative parameters using pharmacokinetic modelling. We review MRI studies of BBB breakdown in dementia. The challenges in measuring subtle BBB changes and the state of the art techniques are initially examined. Subsequently, a systematic review comparing methodologies from recent in-vivo MRI studies is presented. Various factors related to subtle BBB permeability measurement such as DCE-MRI acquisition parameters, arterial input assessment, T 1 mapping and data analysis methods are reviewed with the focus on finding the optimal technique. Finally, the reported BBB permeability values in dementia are compared across different studies and across various brain regions. We conclude that reliable measurement of low-level BBB permeability across sites remains a difficult problem and a standardization of the methodology for both data acquisition and quantitative analysis is required. This article is part of the Special Issue entitled 'Cerebral Ischemia'. Copyright © 2017 Elsevier Ltd. All rights reserved.

Feasibility and Safety of Intra-arterial Pericyte Progenitor Cell Delivery Following Mannitol-Induced Transient Blood-Brain Barrier Opening in a Canine Model.

PubMed

Youn, Sung Won; Jung, Keun-Hwa; Chu, Kon; Lee, Jong-Young; Lee, Soon-Tae; Bahn, Jae-jun; Park, Dong-Kyu; Yu, Jung-Suk; Kim, So-Yun; Kim, Manho; Lee, Sang Kun; Han, Moon-Hee; Roh, Jae-Kyu

2015-01-01

Stem cell therapy is currently being studied with a view to rescuing various neurological diseases. Such studies require not only the discovery of potent candidate cells but also the development of methods that allow optimal delivery of those candidates to the brain tissues. Given that the blood-brain barrier (BBB) precludes cells from entering the brain, the present study was designed to test whether hyperosmolar mannitol securely opens the BBB and enhances intra-arterial cell delivery. A noninjured normal canine model in which the BBB was presumed to be closed was used to evaluate the feasibility and safety of the tested protocol. Autologous adipose tissue-derived pericytes with platelet-derived growth factor receptor β positivity were utilized. Cells were administered 5 min after mannitol pretreatment using one of following techniques: (1) bolus injection of a concentrated suspension, (2) continuous infusion of a diluted suspension, or (3) bolus injection of a concentrated suspension that had been shaken by repeated syringe pumping. Animals administered a concentrated cell suspension without mannitol pretreatment served as a control group. Vital signs, blood parameters, neurologic status, and major artery patency were kept stable throughout the experiment and the 1-month posttreatment period. Although ischemic lesions were noted on magnetic resonance imaging in several mongrel dogs with concentrated cell suspension, the injection technique using repeated syringe shaking could avert this complication. The cells were detected in both ipsilateral and contralateral cortices and were more frequent at the ipsilateral and frontal locations, whereas very few cells were observed anywhere in the brain when mannitol was not preinjected. These data suggest that intra-arterial cell infusion with mannitol pretreatment is a feasible and safe therapeutic approach in stable brain diseases such as chronic stroke.

[The bioelectric activity of the brain in dyscirculatory encephalopathy and arterial hypertension developed in the Chernobyl nuclear disaster liquidators].

PubMed

Podsonnaia, I V; Efremushkin, G G; Zhelobetskaia, E D

2012-01-01

The long-term effects of the ionizing radiation on the bioelectric brain activity in the Chernobyl nuclear disaster liquidators with discirculatory encephalopathy and arterial hypertension were studied. We examined 195 male patients, aged from 30 to 65 years, with the clinical presentations of discirculatory encephalopathy, using electroencephalography: 105 patients were liquidators of the Chernobyl nuclear disaster (the main group) and 90 patients had no radiation anamnesis (the comparison group). It has been found that the development of discirculatory encephalopathy in liquidators of the Chernobyl nuclear disaster is mainly associated with the dysfunction of diencephalic and cortical structures. The specificity of the neurofunctional brain abnormalities in liquidators with discirculatory encephalopathy is characterized by the predominance of the low-amplitude and low-frequency alpha-activity or by the lack of alpha-rhythm and by its substitution for the high-frequency beta-rhythm with the presence of theta- and delta-activity and by the more significant flatness of the alpha-rhythm zonation. The presence of the radiation factor in the past history is correlated with the failure of the bioelectric brain activity in the alpha band (r=0.42) that increases risk of abnormal changes by a factor of 10 (p<0.001). The liquidators with arterial hypertension are characterized by the more frequent occurrence of the asymmetry of the recorded bioelectric potentials between the similar hemispheric areas, by the more significant difference in the external stimulus response of the brain (functional tests). The results indicate the more complicated and diffuse lesion of the brain in the liquidators of the Chernobyl nuclear disaster in the post-radiation period during the development of discirculatory encephalopathy and arterial hypertension.

Systematization and distribution of the middle cerebral artery on the brain surface in pampas fox (Pseudalopex gymnocercus).

PubMed

Depedrini, J S; Campos, R

2007-12-01

The present study has analysed 30 pampas fox brains (Pseudalopex gymnocercus), injected with latex, aiming to systematize and describe the distribution and vascularization territories of the middle cerebral artery. After being originated from the rostral branch of the internal carotid artery this vessel formed the following collateral branches: rostral choroidal artery, rostral and caudal central branches and cortical branches. Before crossing the lateral rhinal sulcus, the common trunk of the middle cerebral artery frequently bifurcated in a rostral and a caudal branch. In a smaller amount, the common trunk did not show any bifurcation, ramifying in arborescence. The vascular territory of the pampas fox middle cerebral artery included the lateral cerebral fossa, the lateral third of the olfactory trigone, the two rostral thirds of the piriform lobe, the lateral olfactory tract and most of the convex surface of the cerebral hemisphere, except for the more rostromedial areas of the frontal lobe bordering the endomarginal sulcus in the parietal and occipital lobes as well as the transverse fissure at the caudal pole of the cerebral hemisphere.

Advanced intimal hyperplasia without luminal narrowing of leptomeningeal arteries in CADASIL.

PubMed

Dong, Hairong; Ding, Haixia; Young, Kelly; Blaivas, Mila; Christensen, Paul J; Wang, Michael M

2013-05-01

Leptomeningeal artery abnormalities in Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) have not been extensively characterized. We quantified substructure and diameter of leptomeningeal arteries in CADASIL compared with age-matched controls and the very old; in addition, we characterized intimal thickening in CADASIL using immunohistochemistry. Frontal and temporal cortex of 6 genetically proven CADASIL brains (average age, 66 years), 6 controls without symptoms of cerebrovascular disease, and 6 very old brains (average age, 89 years) were examined for leptomeningeal artery intimal, medial, and adventitial thickness; inner diameter; and sclerotic index and for smooth muscle markers. The intima of CADASIL arteries was thickened 5-fold compared with controls and the very aged (P<0.0001). Medial thickness was lower in CADASIL compared with controls and the very old (P<0.01). The adventitia was not significantly increased in CADASIL compared with age-matched controls. Arterial diameters were not smaller in CADASIL compared with controls. Sclerotic index was significantly increased in CADASIL compared with other groups (P<0.00001). Intimal cells in CADASIL expressed smooth muscle actin, S100A4, and vimentin but not desmin. Principle changes of leptomeningeal arteries in CADASIL include intimal thickening and medial thinning, but not luminal narrowing. Smooth muscle-like cells participate in neointimal thickening of CADASIL arteries.

SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods.

PubMed

Schuitemaker, Alie; van Berckel, Bart N M; Kropholler, Marc A; Veltman, Dick J; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A; Boellaard, Ronald

2007-05-01

(R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to interobserver variation. In addition, results are only obtained for predefined areas and (unexpected) signals in undefined areas may be missed. On the other hand, standard pharmacokinetic models are too sensitive to noise to calculate (R)-[11C]PK11195 binding on a voxel-by-voxel basis. Linearised versions of both plasma input and reference tissue models have been described, and these are more suitable for parametric imaging. The purpose of this study was to compare the performance of these plasma input and reference tissue parametric methods on the outcome of statistical parametric mapping (SPM) analysis of (R)-[11C]PK11195 binding. Dynamic (R)-[11C]PK11195 PET scans with arterial blood sampling were performed in 7 younger and 11 elderly healthy subjects. Parametric images of volume of distribution (Vd) and binding potential (BP) were generated using linearised versions of plasma input (Logan) and reference tissue (Reference Parametric Mapping) models. Images were compared at the group level using SPM with a two-sample t-test per voxel, both with and without proportional scaling. Parametric BP images without scaling provided the most sensitive framework for determining differences in (R)-[11C]PK11195 binding between younger and elderly subjects. Vd images could only demonstrate differences in (R)-[11C]PK11195 binding when analysed with proportional scaling due to intersubject variation in K1/k2 (blood-brain barrier transport and non-specific binding).

Arterial input function of an optical tracer for dynamic contrast enhanced imaging can be determined from pulse oximetry oxygen saturation measurements

NASA Astrophysics Data System (ADS)

Elliott, Jonathan T.; Wright, Eric A.; Tichauer, Kenneth M.; Diop, Mamadou; Morrison, Laura B.; Pogue, Brian W.; Lee, Ting-Yim; St. Lawrence, Keith

2012-12-01

In many cases, kinetic modeling requires that the arterial input function (AIF)—the time-dependent arterial concentration of a tracer—be characterized. A straightforward method to measure the AIF of red and near-infrared optical dyes (e.g., indocyanine green) using a pulse oximeter is presented. The method is motivated by the ubiquity of pulse oximeters used in both preclinical and clinical applications, as well as the gap in currently available technologies to measure AIFs in small animals. The method is based on quantifying the interference that is observed in the derived arterial oxygen saturation (SaO2) following a bolus injection of a light-absorbing dye. In other words, the change in SaO2 can be converted into dye concentration knowing the chromophore-specific extinction coefficients, the true arterial oxygen saturation, and total hemoglobin concentration. A simple error analysis was performed to highlight potential limitations of the approach, and a validation of the method was conducted in rabbits by comparing the pulse oximetry method with the AIF acquired using a pulse dye densitometer. Considering that determining the AIF is required for performing quantitative tracer kinetics, this method provides a flexible tool for measuring the arterial dye concentration that could be used in a variety of applications.

Arterial input function of an optical tracer for dynamic contrast enhanced imaging can be determined from pulse oximetry oxygen saturation measurements.

PubMed

Elliott, Jonathan T; Wright, Eric A; Tichauer, Kenneth M; Diop, Mamadou; Morrison, Laura B; Pogue, Brian W; Lee, Ting-Yim; St Lawrence, Keith

2012-12-21

In many cases, kinetic modeling requires that the arterial input function (AIF)--the time-dependent arterial concentration of a tracer--be characterized. A straightforward method to measure the AIF of red and near-infrared optical dyes (e.g., indocyanine green) using a pulse oximeter is presented. The method is motivated by the ubiquity of pulse oximeters used in both preclinical and clinical applications, as well as the gap in currently available technologies to measure AIFs in small animals. The method is based on quantifying the interference that is observed in the derived arterial oxygen saturation (SaO₂) following a bolus injection of a light-absorbing dye. In other words, the change in SaO₂ can be converted into dye concentration knowing the chromophore-specific extinction coefficients, the true arterial oxygen saturation, and total hemoglobin concentration. A simple error analysis was performed to highlight potential limitations of the approach, and a validation of the method was conducted in rabbits by comparing the pulse oximetry method with the AIF acquired using a pulse dye densitometer. Considering that determining the AIF is required for performing quantitative tracer kinetics, this method provides a flexible tool for measuring the arterial dye concentration that could be used in a variety of applications.

Verapamil-induced breakdown of the blood-brain barrier presenting as a transient right middle cerebral artery syndrome.

PubMed

Pace, Jonathan; Nelson, Jeffrey; Ray, Abhishek; Hu, Yin

2017-12-01

A middle-aged patient presented for elective embolization of an incidentally found right internal carotid aneurysm. An angiogram was performed, during which the left internal carotid artery was visualized to evaluate a second, small aneurysm. During the embolization of the right internal carotid artery aneurysm, a catheter-induced vasospasm was identified that prompted treatment with intra-arterial verapamil. The procedure was uncomplicated; a postoperative rotational flat-panel computed tomography scan was performed on the angiography table that demonstrated right hemisphere contrast staining. The patient developed a right middle cerebral artery (MCA) syndrome after extubation with repeat cerebral angiography negative for occlusion and magnetic resonance imaging negative for stroke. The patient was observed for 48 hours, during which time the patient had slowly improved. At a six-week follow up visit, the patient had fully recovered. We present an interesting case of a verapamil-induced breakdown of the blood-brain barrier and self-limited right MCA syndrome.

A curve-fitting approach to estimate the arterial plasma input function for the assessment of glucose metabolic rate and response to treatment.

PubMed

Vriens, Dennis; de Geus-Oei, Lioe-Fee; Oyen, Wim J G; Visser, Eric P

2009-12-01

For the quantification of dynamic (18)F-FDG PET studies, the arterial plasma time-activity concentration curve (APTAC) needs to be available. This can be obtained using serial sampling of arterial blood or an image-derived input function (IDIF). Arterial sampling is invasive and often not feasible in practice; IDIFs are biased because of partial-volume effects and cannot be used when no large arterial blood pool is in the field of view. We propose a mathematic function, consisting of an initial linear rising activity concentration followed by a triexponential decay, to describe the APTAC. This function was fitted to 80 oncologic patients and verified for 40 different oncologic patients by area-under-the-curve (AUC) comparison, Patlak glucose metabolic rate (MR(glc)) estimation, and therapy response monitoring (Delta MR(glc)). The proposed function was compared with the gold standard (serial arterial sampling) and the IDIF. To determine the free parameters of the function, plasma time-activity curves based on arterial samples in 80 patients were fitted after normalization for administered activity (AA) and initial distribution volume (iDV) of (18)F-FDG. The medians of these free parameters were used for the model. In 40 other patients (20 baseline and 20 follow-up dynamic (18)F-FDG PET scans), this model was validated. The population-based curve, individually calibrated by AA and iDV (APTAC(AA/iDV)), by 1 late arterial sample (APTAC(1 sample)), and by the individual IDIF (APTAC(IDIF)), was compared with the gold standard of serial arterial sampling (APTAC(sampled)) using the AUC. Additionally, these 3 methods of APTAC determination were evaluated with Patlak MR(glc) estimation and with Delta MR(glc) for therapy effects using serial sampling as the gold standard. Excellent individual fits to the function were derived with significantly different decay constants (P < 0.001). Correlations between AUC from APTAC(AA/iDV), APTAC(1 sample), and APTAC(IDIF) with the gold standard (APTAC(sampled)) were 0.880, 0.994, and 0.856, respectively. For MR(glc), these correlations were 0.963, 0.994, and 0.966, respectively. In response monitoring, these correlations were 0.947, 0.982, and 0.949, respectively. Additional scaling by 1 late arterial sample showed a significant improvement (P < 0.001). The fitted input function calibrated for AA and iDV performed similarly to IDIF. Performance improved significantly using 1 late arterial sample. The proposed model can be used when an IDIF is not available or when serial arterial sampling is not feasible.

A comparison of postnatal arterial patterns in a growth series of giraffe (Artiodactyla: Giraffa camelopardalis)

PubMed Central

Gignac, Paul M.; Hieronymus, Tobin L.; Witmer, Lawrence M.

2016-01-01

Nearly all living artiodactyls (even-toed ungulates) possess a derived cranial arterial pattern that is highly distinctive from most other mammals. Foremost among a suite of atypical arterial configurations is the functional and anatomical replacement of the internal carotid artery with an extensive, subdural arterial meshwork called the carotid rete. This interdigitating network branches from the maxillary artery and is housed within the cavernous venous sinus. As the cavernous sinus receives cooled blood draining from the nasal mucosa, heat rapidly dissipates across the high surface area of the rete to be carried away from the brain by the venous system. This combination yields one of the most effective mechanisms of selective brain cooling. Although arterial development begins from the same embryonic scaffolding typical of mammals, possession of a rete is typically accompanied by obliteration of the internal carotid artery. Among taxa with available ontogenetic data, the point at which the internal carotid obliterates is variable throughout development. In small-bodied artiodactyls, the internal carotid typically obliterates prior to parturition, but in larger species, the vessel may remain patent for several years. In this study, we use digital anatomical data collection methods to describe the cranial arterial patterns for a growth series of giraffe (Giraffa camelopardalis), from parturition to senescence. Giraffes, in particular, have unique cardiovascular demands and adaptations owing to their exceptional body form and may not adhere to previously documented stages of cranial arterial development. We find the carotid arterial system to be conserved between developmental stages and that obliteration of the giraffe internal carotid artery occurs prior to parturition. PMID:26925324

A comparison of postnatal arterial patterns in a growth series of giraffe (Artiodactyla: Giraffa camelopardalis).

PubMed

O'Brien, Haley D; Gignac, Paul M; Hieronymus, Tobin L; Witmer, Lawrence M

2016-01-01

Nearly all living artiodactyls (even-toed ungulates) possess a derived cranial arterial pattern that is highly distinctive from most other mammals. Foremost among a suite of atypical arterial configurations is the functional and anatomical replacement of the internal carotid artery with an extensive, subdural arterial meshwork called the carotid rete. This interdigitating network branches from the maxillary artery and is housed within the cavernous venous sinus. As the cavernous sinus receives cooled blood draining from the nasal mucosa, heat rapidly dissipates across the high surface area of the rete to be carried away from the brain by the venous system. This combination yields one of the most effective mechanisms of selective brain cooling. Although arterial development begins from the same embryonic scaffolding typical of mammals, possession of a rete is typically accompanied by obliteration of the internal carotid artery. Among taxa with available ontogenetic data, the point at which the internal carotid obliterates is variable throughout development. In small-bodied artiodactyls, the internal carotid typically obliterates prior to parturition, but in larger species, the vessel may remain patent for several years. In this study, we use digital anatomical data collection methods to describe the cranial arterial patterns for a growth series of giraffe (Giraffa camelopardalis), from parturition to senescence. Giraffes, in particular, have unique cardiovascular demands and adaptations owing to their exceptional body form and may not adhere to previously documented stages of cranial arterial development. We find the carotid arterial system to be conserved between developmental stages and that obliteration of the giraffe internal carotid artery occurs prior to parturition.

A simple brain atrophy measure improves the prediction of malignant middle cerebral artery infarction by acute DWI lesion volume.

PubMed

Beck, Christoph; Kruetzelmann, Anna; Forkert, Nils D; Juettler, Eric; Singer, Oliver C; Köhrmann, Martin; Kersten, Jan F; Sobesky, Jan; Gerloff, Christian; Fiehler, Jens; Schellinger, Peter D; Röther, Joachim; Thomalla, Götz

2014-06-01

In patients with malignant middle cerebral artery infarction (MMI) decompressive surgery within 48 h improves functional outcome. In this respect, early identification of patients at risk of developing MMI is crucial. While the acute diffusion weighted imaging (DWI) lesion volume was found to predict MMI with high predictive values, the potential impact of preexisting brain atrophy on the course of space-occupying middle cerebral artery (MCA) infarction and the development of MMI remains unclear. We tested the hypothesis that the combination of the acute DWI lesion volume with simple measures of brain atrophy improves the early prediction of MMI. Data from a prospective, multicenter, observational study, which included patients with acute middle cerebral artery main stem occlusion studied by MRI within 6 h of symptom onset, was analyzed retrospectively. The development of MMI was defined according to the European randomized controlled trials of decompressive surgery. Acute DWI lesion volume, as well as brain and cerebrospinal fluid volume (CSF) were delineated. The intercaudate distance (ICD) was assessed as a linear brain atrophy marker by measuring the hemi-ICD of the intact hemisphere to account for local brain swelling. Binary logistic regression analysis was used to identify significant predictors of MMI. Cut-off values were determined by Classification and Regression Trees analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the resulting models were calculated. Twenty-one (18 %) of 116 patients developed a MMI. Malignant middle cerebral artery infarctions patients had higher National Institutes of Health Stroke Scale scores on admission and presented more often with combined occlusion of the internal carotid artery and MCA. There were no differences in brain and CSF volume between the two groups. Diffusion weighted imaging lesion volume was larger (p < 0.001), while hemi-ICD was smaller (p = 0.029) in MMI patients. Inclusion of hemi-ICD improved the prediction of MMI. Best cut-off values to predict the development of MMI were DWI lesion volume > 87 ml and hemi-ICD ≤ 9.4 mm. The addition of hemi-ICD to the decision tree strongly increased PPV (0.93 vs. 0.70) resulting in a reduction of false positive findings from 7/23 (30 %) to 1/15 (7 %), while there were only slight changes in specificity, sensitivity and NPV. The absolute number of correct classifications increased by 4 (3.4 %). The integration of hemi-ICD as a linear marker of brain atrophy, that can easily be assessed in an emergency setting, may improve the prediction of MMI by lesion volume based predictive models.

[Microsurgical anatomy importance of A1-anterior communicating artery complex].

PubMed

Monroy-Sosa, Alejandro; Pérez-Cruz, Julio César; Reyes-Soto, Gervith; Delgado-Hernández, Carlos; Macías-Duvignau, Mario Alberto; Delgado-Reyes, Luis

2013-01-01

The anterior cerebral artery originates from the bifurcation of the internal carotid artery lateral to the optic chiasm, then joins with its contralateral counterpart via the anterior communicating artery. A1-anterior communicating artery complex is the most frequent anatomical variants and is the major site of aneurysms between 30 to 37%. Know the anatomy microsurgical, variants anatomical and importance of complex precommunicating segment-artery anterior communicating in surgery neurological of the pathology vascular, mainly aneurysms, in Mexican population. The study was performed in 30 brains injected. Microanatomy was studied (length and diameter) of A1-anterior communicating artery complex and its variants. 60 segments A1, the average length of left side was 11.35 mm and 11.84 mm was right. The average diameter of left was 1.67 mm and the right was 1.64 mm. The average number of perforators on the left side was 7.9 and the right side was 7.5. Anterior communicating artery was found in 29 brains of the optic chiasm, its course depended on the length of the A1 segment. The average length of the segment was 2.84 mm, the average diameter was 1.41 mm and the average number of perforators was 3.27. A1-anterior communicating artery complex variants were found in 18 (60%) and the presence of two blister-like aneurysms. It is necessary to understand the A1-anterior communicating artery complex microanatomy of its variants to have a three-dimensional vision during aneurysm surgery.

Combining image-derived and venous input functions enables quantification of serotonin-1A receptors with [carbonyl-11C]WAY-100635 independent of arterial sampling.

PubMed

Hahn, Andreas; Nics, Lukas; Baldinger, Pia; Ungersböck, Johanna; Dolliner, Peter; Frey, Richard; Birkfellner, Wolfgang; Mitterhauser, Markus; Wadsak, Wolfgang; Karanikas, Georgios; Kasper, Siegfried; Lanzenberger, Rupert

2012-08-01

image- derived input functions (IDIFs) represent a promising technique for a simpler and less invasive quantification of PET studies as compared to arterial cannulation. However, a number of limitations complicate the routine use of IDIFs in clinical research protocols and the full substitution of manual arterial samples by venous ones has hardly been evaluated. This study aims for a direct validation of IDIFs and venous data for the quantification of serotonin-1A receptor binding (5-HT(1A)) with [carbonyl-(11)C]WAY-100635 before and after hormone treatment. Fifteen PET measurements with arterial and venous blood sampling were obtained from 10 healthy women, 8 scans before and 7 after eight weeks of hormone replacement therapy. Image-derived input functions were derived automatically from cerebral blood vessels, corrected for partial volume effects and combined with venous manual samples from 10 min onward (IDIF+VIF). Corrections for plasma/whole-blood ratio and metabolites were done separately with arterial and venous samples. 5-HT(1A) receptor quantification was achieved with arterial input functions (AIF) and IDIF+VIF using a two-tissue compartment model. Comparison between arterial and venous manual blood samples yielded excellent reproducibility. Variability (VAR) was less than 10% for whole-blood activity (p>0.4) and below 2% for plasma to whole-blood ratios (p>0.4). Variability was slightly higher for parent fractions (VARmax=24% at 5 min, p<0.05 and VAR<13% after 20 min, p>0.1) but still within previously reported values. IDIFs after partial volume correction had peak values comparable to AIFs (mean difference Δ=-7.6 ± 16.9 kBq/ml, p>0.1), whereas AIFs exhibited a delay (Δ=4 ± 6.4s, p<0.05) and higher peak width (Δ=15.9 ± 5.2s, p<0.001). Linear regression analysis showed strong agreement for 5-HT(1A) binding as obtained with AIF and IDIF+VIF at baseline (R(2)=0.95), after treatment (R(2)=0.93) and when pooling all scans (R(2)=0.93), with slopes and intercepts in the range of 0.97 to 1.07 and -0.05 to 0.16, respectively. In addition to the region of interest analysis, the approach yielded virtually identical results for voxel-wise quantification as compared to the AIF. Despite the fast metabolism of the radioligand, manual arterial blood samples can be substituted by venous ones for parent fractions and plasma to whole-blood ratios. Moreover, the combination of image-derived and venous input functions provides a reliable quantification of 5-HT(1A) receptors. This holds true for 5-HT(1A) binding estimates before and after treatment for both regions of interest-based and voxel-wise modeling. Taken together, the approach provides less invasive receptor quantification by full independence of arterial cannulation. This offers great potential for the routine use in clinical research protocols and encourages further investigation for other radioligands with different kinetic characteristics. Copyright © 2012 Elsevier Inc. All rights reserved.

Cerebral blood flow and metabolism during exercise: implications for fatigue.

PubMed

Secher, Neils H; Seifert, Thomas; Van Lieshout, Johannes J

2008-01-01

During exercise: the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position. In contrast, when CBF is evaluated by (133)Xe clearance, by flow in the internal carotid artery, or by flow velocity in basal cerebral arteries, a approximately 25% increase is detected with a parallel increase in metabolism. During activation, an increase in cerebral O(2) supply is required because there is no capillary recruitment within the brain and increased metabolism becomes dependent on an enhanced gradient for oxygen diffusion. During maximal whole body exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF. Reduced cerebral oxygenation affects recruitment of motor units, and supplemental O(2) enhances cerebral oxygenation and work capacity without effects on muscle oxygenation. Also, the work of breathing and the increasing temperature of the brain during exercise are of importance for the development of so-called central fatigue. During prolonged exercise, the perceived exertion is related to accumulation of ammonia in the brain, and data support the theory that glycogen depletion in astrocytes limits the ability of the brain to accelerate its metabolism during activation. The release of interleukin-6 from the brain when exercise is prolonged may represent a signaling pathway in matching the metabolic response of the brain. Preliminary data suggest a coupling between the circulatory and metabolic perturbations in the brain during strenuous exercise and the ability of the brain to access slow-twitch muscle fiber populations.

Hawthorn extract reduces infarct volume and improves neurological score by reducing oxidative stress in rat brain following middle cerebral artery occlusion.

PubMed

Elango, Chinnasamy; Jayachandaran, Kasevan Sawaminathan; Niranjali Devaraj, S

2009-12-01

In our present investigation the neuroprotective effect of alcoholic extract of Hawthorn (Crataegus oxycantha) was evaluated against middle cerebral artery occlusion induced ischemia/reperfusion injury in rats. Male Sprague-Dawley rats were pretreated with 100 mg/kg body weight of the extract by oral gavage for 15 days. The middle cerebral artery was then occluded for 75 min followed by 24 h of reperfusion. The pretreated rats showed significantly improved neurological behavior with reduced brain infarct when compared to vehicle control rats. The glutathione level in brain was found to be significantly (p<0.05) low in vehicle control rats after 24 h of reperfusion when compared to sham operated animals. However, in Hawthorn extract pretreated rats the levels were found to be close to that of sham. Malondialdehyde levels in brain of sham and pretreated group were found to be significantly lower than the non-treated vehicle group (p<0.05). The nitric oxide levels in brain were measured and found to be significantly (p<0.05) higher in vehicle than in sham or extract treated rats. Our results suggest that Hawthorn extract which is a well known prophylactic for cardiac conditions may very well protect the brain against ischemia-reperfusion. The reduced brain damage and improved neurological behavior after 24 h of reperfusion in Hawthorn extract pretreated group may be attributed to its antioxidant property which restores glutathione levels, circumvents the increase in lipid peroxidation and nitric oxide levels thereby reducing peroxynitrite formation and free radical induced brain damage.

Polymorphisms in the microglial marker molecule CX3CR1 affect the blood volume of the human brain.

PubMed

Sakai, Mai; Takeuchi, Hikaru; Yu, Zhiqian; Kikuchi, Yoshie; Ono, Chiaki; Takahashi, Yuta; Ito, Fumiaki; Matsuoka, Hiroo; Tanabe, Osamu; Yasuda, Jun; Taki, Yasuyuki; Kawashima, Ryuta; Tomita, Hiroaki

2018-06-01

CX3CR1, a G-protein-coupled receptor, is involved in various inflammatory processes. Two non-synonymous single nucleotide polymorphisms, V249I (rs3732379) and T280M (rs3732378), are located in the sixth and seventh transmembrane domains of the CX3CR1 protein, respectively. Previous studies have indicated significant associations between T280M and leukocyte functional characteristics, including adhesion, signaling, and chemotaxis, while the function of V249I is unclear. In the brain, microglia are the only proven and widely accepted CX3CR1-expressing cells. This study aimed to specify whether there were specific brain regions on which these two single nucleotide polymorphisms exert their biological impacts through their functional effects on microglia. Associations between the single nucleotide polymorphisms and brain characteristics, including gray and white matter volumes, white matter integrity, resting arterial blood volume, and cerebral blood flow, were evaluated among 1300 healthy Japanese individuals. The major allele carriers (V249 and T280) were significantly associated with an increased total arterial blood volume of the whole brain, especially around the bilateral precuneus, left posterior cingulate cortex, and left posterior parietal cortex. There were no significant associations between the genotypes and other brain structural indicators. This finding suggests that the CX3CR1 variants may affect arterial structures in the brain, possibly via interactions between microglia and brain microvascular endothelial cells. © 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

Fluid Intake Related to Brain Edema in Acute Middle Cerebral Artery Infarction.

PubMed

Dharmasaroja, Pornpatr A

2016-02-01

Evidence of the appropriate amount of fluid intake during the first few days after acute stroke was scarce. Concerns were raised in patients with acute malignant middle cerebral infarction, who tended to have malignant brain edema later. The purpose of the study was to evaluate the effect of fluid intake on the occurrence of malignant brain edema in patients with acute middle cerebral artery infarction. Patients with acute middle cerebral artery infarction who had National Institute of Health Stroke Scale (NIHSS) score of at least 15 were included. Baseline characteristics and amount of fluid intake during the first few days were compared in patients with and without malignant brain edema. One hundred ninety-three patients were studied. Mean NIHSS score was 20. Malignant brain edema occurred in 69 patients (36%). Higher amount of fluid intake (>1650 ml or >28 ml/kg/day or >93% of daily maintenance fluid) showed a significant association with malignant brain edema (OR = 13.86, 95% CI 5.11-37.60, p value <0.001). Decompressive surgery was performed in 35 patients (18%). With mean follow-up of 12 months, 49 patients (49/184, 27%) had favorable outcomes (modified Rankin scale (mRS) 0-2) at final follow-up. Seventy-nine patients (79/184, 43%) died. In the subgroup of patients with malignant brain edema, 39 patients (39/65, 60%) died and only 11% (7/65 patients) had favorable outcome. High amount of fluid intake in the first few days of acute middle cerebral infarction was related to the occurrence of malignant brain edema.

Inner-ear decompression sickness: 'hubble-bubble' without brain trouble?

PubMed

Tremolizzo, Lucio; Malpieri, Massimo; Ferrarese, Carlo; Appollonio, Ildebrando

2015-06-01

Inner-ear decompression sickness (DCS) is an incompletely understood and increasingly recognized condition in compressed-air divers. Previous reports show a high association of inner-ear DCS with persistent foramen ovale (PFO), suggesting that a moderate-to-severe right-to-left shunt might represent a major predisposing factor, and more properly defining it as an event from arterial gas embolism (AGE). However, other conditions characterized by bubbles entering the arterial circulation, such as open-chamber cardiac surgery, do not produce inner-ear involvement, while sometimes damaging the brain extensively. Moreover, in other sites, such as the spinal cord, the prevailing mechanism for DCS is not AGE, but more likely local bubble formation with subsequent compression of venules and capillaries. Thus, AGE might be, more properly, a predisposing condition, neither sufficient, nor possibly even strictly necessary for inner-ear DCS. A 'two-hit hypothesis' has been proposed, implying a locally selective vulnerability of the inner ear to AGE. Modelled kinetics for gas removal are slower in the inner ear compared to the brain, leading to a supersaturated environment which allows bubbles to grow until they eventually obstruct the labyrinthine artery. Since this artery is relatively small, there is a low probability for a bubble to enter it; this might explain the disproportion between the high prevalence of PFO in the general population (25-30%) and the very low incidence of inner-ear DCS in compressed-air diving (approximately 0.005%). Furthermore, given that the labyrinthine artery usually originates either from the anterior inferior cerebellar artery, or directly from the basilar artery, shunting bubbles will more frequently swarm through the entire brain. In this case, however, the brain's much faster gas removal kinetics might allow for them to be reabsorbed without damaging brain tissue. In line with this scenario is the low probability (approx. 15%) of inner-ear DCS presenting with concomitant symptoms suggestive of brain involvement. Interestingly, PFO is a putative risk factor not only for DCS but also for ischaemic stroke, and it has been hypothesized that a predominantly silent ischaemic cerebral burden might represent a meaningful surrogate of end-organ damage in divers with PFO, with implications for stroke or cognitive decline. Here we report the case of a 44-year-old diving instructor (> 350 dives) who suffered from inner-ear DCS about 10 min after a routine dive (5 min/40 metres' fresh water (mfw), ascent 7.5 mfw·min⁻¹, stop 10 min/5 mfw), resulting in severe left cochlear/vestibular impairment (complete deafness and marked vertigo, only the latter slowly receding after a few hours). The patient was not recompressed. A few months later, transcranial Doppler ultrasonography demonstrated a moderate-to-severe shunt (> 30 bubbles), presumably due to a PFO (he refused confirmatory echocardiography), while a brain MRI (1.5 T) was reported as negative for both recent and remote lacunar infarcts (Figure 1). We believe this may be evidence that inner-ear DCS could occur while the brain is completely spared, not only clinically, but also at neuroimaging. This would support either of two hypotheses: (a) that the brain is indeed relatively protected from arterial bubbles that preferentially harm the inner ear where, however, they only rarely infiltrate, or (b) that direct bubble formation within the inner ear cannot be completely discarded, and that the elevated PFO-inner-ear DCS association might be, in this latter case, merely circumstantial. We favour the hypothesis that inner-ear DCS might be related to AGE in an anatomically vulnerable region. More precise data regarding the exact incidence of inner-ear involvement, isolating those subjects with moderate-to-severe shunt, should be obtained before exploring the risk-to-benefit ratio given by transcatheter occlusion of a PFO for prevention of inner-ear DCS; odds that could end up to be sensibly different with respect to other types of DCS presentation.

Image quality improvement in three-dimensional time-of-flight magnetic resonance angiography using the subtraction method for brain and temporal bone diseases.

PubMed

Peng, Shu-Hui; Shen, Chao-Yu; Wu, Ming-Chi; Lin, Yue-Der; Huang, Chun-Huang; Kang, Ruei-Jin; Tyan, Yeu-Sheng; Tsao, Teng-Fu

2013-08-01

Time-of-flight (TOF) magnetic resonance (MR) angiography is based on flow-related enhancement using the T1-weighted spoiled gradient echo, or the fast low-angle shot gradient echo sequence. However, materials with short T1 relaxation times may show hyperintensity signals and contaminate the TOF images. The objective of our study was to determine whether subtraction three-dimensional (3D) TOF MR angiography improves image quality in brain and temporal bone diseases with unwanted contaminations with short T1 relaxation times. During the 12-month study period, patients who had masses with short T1 relaxation times noted on precontrast T1-weighted brain MR images and 24 healthy volunteers were scanned using conventional and subtraction 3D TOF MR angiography. The qualitative evaluation of each MR angiogram was based on signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and scores in three categories, namely, (1) presence of misregistration artifacts, (2) ability to display arterial anatomy selectively (without contamination by materials with short T1 relaxation times), and (3) arterial flow-related enhancement. We included 12 patients with intracranial hematomas, brain tumors, or middle-ear cholesterol granulomas. Subtraction 3D TOF MR angiography yielded higher CNRs between the area of the basilar artery (BA) and normal-appearing parenchyma of the brain and lower SNRs in the area of the BA compared with the conventional technique (147.7 ± 77.6 vs. 130.6 ± 54.2, p < 0.003 and 162.5 ± 79.9 vs. 194.3 ± 62.3, p < 0.001, respectively) in all 36 cases. The 3D subtraction angiography did not deteriorate image quality with misregistration artifacts and showed a better selective display of arteries (p < 0.0001) and arterial flow-related enhancement (p < 0.044) than the conventional method. Subtraction 3D TOF MR angiography is more appropriate than the conventional method in improving the image quality in brain and temporal bone diseases with unwanted contaminations with short T1 relaxation times. Copyright © 2013. Published by Elsevier B.V.

Can vascular risk factors influence number and size of cerebral metastases? A 3D-MRI study in patients with different tumor entities.

PubMed

Nagel, Sandra; Berk, Benjamin-Andreas; Kortmann, Rolf-Dieter; Hoffmann, Karl-Titus; Seidel, Clemens

2018-02-01

There is increasing evidence that cerebral microangiopathy reduces number of brain metastases. Aim of this study was to analyse if vascular risk factors (arterial hypertension, diabetes mellitus, smoking, and hypercholesterolemia) or the presence of peripheral arterial occlusive disease (PAOD) can have an impact on number or size of brain metastases. 200 patients with pre-therapeutic 3D-brain MRI and available clinical data were analyzed retrospectively. Mean number of metastases (NoM) and mean diameter of metastases (mDM) were compared between patients with/without vascular risk factors (vasRF). No general correlation of vascular risk factors with brain metastases was found in this monocentric analysis of a patient cohort with several tumor types. Arterial hypertension, diabetes mellitus, hypercholesterolemia and smoking did not show an effect in uni- and multivariate analysis. In patients with PAOD the number of BM was lower than without PAOD. This was the case independent from cerebral microangiopathy but did not persist in multivariate analysis. From this first screening approach vascular risk factors do not appear to strongly influence brain metastasation. However, larger prospective multi-centric studies with better characterized severity of vascular risk are needed to more accurately detect effects of individual factors. Copyright © 2018 Elsevier B.V. All rights reserved.

Stroke - discharge

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Brain oxygen utilization is unchanged by hypoglycemia in normal humans: lactate, alanine, and leucine uptake are not sufficient to offset energy deficit.

PubMed

Lubow, Jeffrey M; Piñón, Ivan G; Avogaro, Angelo; Cobelli, Claudio; Treeson, David M; Mandeville, Katherine A; Toffolo, Gianna; Boyle, Patrick J

2006-01-01

During hypoglycemia, substrates other than glucose have been suggested to serve as alternate neural fuels. We evaluated brain uptake of endogenously produced lactate, alanine, and leucine at euglycemia and during insulin-induced hypoglycemia in 17 normal subjects. Cross-brain arteriovenous differences for plasma glucose, lactate, alanine, leucine, and oxygen content were quantitated. Cerebral blood flow (CBF) was measured by Fick methodology using N(2)O as the dilution indicator gas. Substrate uptake was measured as the product of CBF and the arteriovenous concentration difference. As arterial glucose concentration fell, cerebral oxygen utilization and CBF remained unchanged. Brain glucose uptake (BGU) decreased from 36.3+/-2.6 to 26.6+/-2.1 micromol.100 g of brain(-1).min(-1) (P<0.001), equivalent to a drop in ATP of 291 micromol.100 g(-1).min(-1). Arterial lactate rose (P<0.001), whereas arterial alanine and leucine fell (P<0.009 and P<0.001, respectively). Brain lactate uptake (BLU) increased from a net release of -1.8+/- 0.6 to a net uptake of 2.5+/-1.2 micromol.100 g(-1).min(-1) (P<0.001), equivalent to an increase in ATP of 74 micromol.100 g(-1).min(-1). Brain leucine uptake decreased from 7.1+/-1.2 to 2.5 +/- 0.5 micromol.100 g(-1).min(-1) (P<0.001), and brain alanine uptake trended downward (P<0.08). We conclude that the ATP generated from the physiological increase in BLU during hypoglycemia accounts for no more than 25% of the brain glucose energy deficit.

Responses of aortic depressor nerve-evoked neurones in rat nucleus of the solitary tract to changes in blood pressure

PubMed Central

Zhang, Jing; Mifflin, Steven W

2000-01-01

Using electrophysiological techniques, the discharge of neurones in the nucleus of the solitary tract (NTS) receiving aortic depressor nerve (ADN) inputs was examined during blood pressure changes induced by I.V. phenylephrine or nitroprusside in anaesthetized, paralysed and artificially ventilated rats. Various changes in discharge rate were observed during phenylephrine-induced blood pressure elevations: an increase (n = 38), a decrease (n = 5), an increase followed by a decrease (n = 4) and no response (n = 11). In cells receiving a monosynaptic ADN input (MSNs), the peak discharge frequency response was correlated to the rate of increase in mean arterial pressure (P < 0.01) but was not correlated to the absolute increase in blood pressure. The peak discharge frequency response of cells receiving a polysynaptic ADN input (PSNs) was correlated to neither the absolute increase in blood pressure nor the rate of increase in mean arterial pressure. Diverse changes in discharge rate were observed during nitroprusside-induced reductions in blood pressure: an increase (n = 3), a decrease (n = 10), an increase followed by a decrease (n = 3) and no response (n = 6). Reductions in pressure of 64 ± 2 mmHg produced weak reductions in spontaneous discharge of 1.3 ± 0.9 Hz and only totally abolished spontaneous discharge in one neurone. These response patterns of NTS neurones during changes in arterial pressure suggest that baroreceptor inputs are integrated differently in MSNs compared to PSNs. The sensitivity of MSNs to the rate of change of pressure provides a mechanism for the rapid regulation of cardiovascular function. The lack of sensitivity to the mean level of a pressure increase in both MSNs and PSNs suggests that steady-state changes in pressure are encoded by the number of active neurones and not graded changes in the discharge of individual neurones. Both MSNs and PSNs receive tonic excitatory inputs from the arterial baroreceptors; however, these tonic inputs appear to be insufficient to totally account for their spontaneous discharge. PMID:11101652

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Ophthalmic artery obstruction and cerebral infarction following periocular injection of autologous fat.

PubMed

Lee, Chang Mok; Hong, In Hwan; Park, Sung Pyo

2011-10-01

We report a case of ophthalmic artery obstruction combined with brain infarction following periocular autologous fat injection. The patient, a 44-year-old woman, visited our hospital for decreased visual acuity in her left eye and dysarthria one hour after receiving an autologous fat injection in the periocular area. Her best corrected visual acuity for the concerned eye was no light perception. Also, a relative afferent pupillary defect was detected in this eye. The left fundus exhibited widespread retinal whitening with visible emboli in several retinal arterioles. Diffusion-weighted magnetic resonance imaging of the brain showed a hyperintense lesion at the left insular cortex. Therefore, we diagnosed ophthalmic artery obstruction and left middle cerebral artery infarction due to fat emboli. The patient was managed with immediate ocular massage, carbon dioxide, and oxygen therapy. Following treatment, dysarthria improved considerably but there was no improvement in visual acuity.

Development of a realistic, dynamic digital brain phantom for CT perfusion validation

NASA Astrophysics Data System (ADS)

Divel, Sarah E.; Segars, W. Paul; Christensen, Soren; Wintermark, Max; Lansberg, Maarten G.; Pelc, Norbert J.

2016-03-01

Physicians rely on CT Perfusion (CTP) images and quantitative image data, including cerebral blood flow, cerebral blood volume, and bolus arrival delay, to diagnose and treat stroke patients. However, the quantification of these metrics may vary depending on the computational method used. Therefore, we have developed a dynamic and realistic digital brain phantom upon which CTP scans can be simulated based on a set of ground truth scenarios. Building upon the previously developed 4D extended cardiac-torso (XCAT) phantom containing a highly detailed brain model, this work consisted of expanding the intricate vasculature by semi-automatically segmenting existing MRA data and fitting nonuniform rational B-spline surfaces to the new vessels. Using time attenuation curves input by the user as reference, the contrast enhancement in the vessels changes dynamically. At each time point, the iodine concentration in the arteries and veins is calculated from the curves and the material composition of the blood changes to reflect the expected values. CatSim, a CT system simulator, generates simulated data sets of this dynamic digital phantom which can be further analyzed to validate CTP studies and post-processing methods. The development of this dynamic and realistic digital phantom provides a valuable resource with which current uncertainties and controversies surrounding the quantitative computations generated from CTP data can be examined and resolved.

Brain glucose transport and phosphorylation under acute insulin-induced hypoglycemia in mice: an 18F-FDG PET study.

PubMed

Alf, Malte F; Duarte, João M N; Schibli, Roger; Gruetter, Rolf; Krämer, Stefanie D

2013-12-01

We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are. Quantitative (18)F-FDG PET combined with the acquisition of real-time arterial input function was performed on mice. Hypoglycemia was induced and maintained by insulin infusion. PET data were analyzed with the 2-tissue-compartment model for (18)F-FDG, and the results were evaluated with Michaelis-Menten saturation kinetics. Glucose clearance from plasma to brain (K1,glc) and the phosphorylation rate constant increased with decreasing plasma glucose (Gp), in particular at a Gp of less than 2.5 mmol/L. Estimated cerebral glucose extraction ratios taking into account an increased cerebral blood flow (CBF) at a Gp of less than 2 mmol/L were between 0.14 and 0.79. CBF-normalized K1,glc values were in agreement with saturation kinetics. Phosphorylation rate constants indicated intracellular glucose depletion at a Gp of less than 2-3 mmol/L. When brain regions were compared, glucose transport under hypoglycemia was lowest in the hypothalamus. Alterations in glucose transport and phosphorylation, as well as intracellular glucose depletion, under acute hypoglycemia can be modeled by saturation kinetics taking into account an increase in CBF. Distinct transport kinetics in the hypothalamus may be involved in its glucose-sensing function.

Quantification of [11C]yohimbine binding to α2 adrenoceptors in rat brain in vivo

PubMed Central

Phan, Jenny-Ann; Landau, Anne M; Wong, Dean F; Jakobsen, Steen; Nahimi, Adjmal; Doudet, Doris J; Gjedde, Albert

2015-01-01

We quantified the binding potentials (BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution (VT) of [11C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ~38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission. PMID:25564241

Effects of respiratory acidosis and alkalosis on the distribution of cyanide into the rat brain.

PubMed

Djerad, A; Monier, C; Houzé, P; Borron, S W; Lefauconnier, J M; Baud, F J

2001-06-01

The aim of this study was to determine whether respiratory acidosis favors the cerebral distribution of cyanide, and conversely, if respiratory alkalosis limits its distribution. The pharmacokinetics of a nontoxic dose of cyanide were first studied in a group of 7 rats in order to determine the distribution phase. The pharmacokinetics were found to best fit a 3-compartment model with very rapid distribution (whole blood T(1/2)alpha = 21.6 +/- 3.3 s). Then the effects of the modulation of arterial pH on the distribution of a nontoxic dose of intravenously administered cyanide into the brains of rats were studied by means of the determination of the permeability-area product (PA). The modulation of arterial blood pH was performed by variation of arterial carbon dioxide tension (PaCO2) in 3 groups of 8 anesthetized mechanically ventilated rats. The mean arterial pH measured 20 min after the start of mechanical ventilation in the acidotic, physiologic, and alkalotic groups were 7.07 +/- 0.03, 7.41 +/- 0.01, and 7.58 +/- 0.01, respectively. The mean PAs in the acidotic, physiologic, and alkalotic groups, determined 30 s after the intravenous administration of cyanide, were 0.015 +/- 0.002, 0.011 +/- 0.001, and 0.008 +/- 0.001 s(-1), respectively (one-way ANOVA; p < 0.0087). At alkalotic pH the mean permeability-area product was 43% of that measured at acidotic pH. This effect of pH on the rapidity of cyanide distribution does not appear to be limited to specific areas of the brain. We conclude that modulation of arterial pH by altering PaCO2 may induce significant effects on the brain uptake of cyanide.

Hypothalamic modulation of the arterial chemoreceptor reflex in the anaesthetized cat: role of the nucleus tractus solitarii.

PubMed Central

Silva-Carvalho, L; Dawid-Milner, M S; Goldsmith, G E; Spyer, K M

1995-01-01

1. There is evidence in the literature of a mutual facilitatory interaction between the arterial chemoreceptor reflex and the alerting stage of the defence reaction, particularly in relation to the patterning of cardiorespiratory activity. The present study has been designed to test the hypothesis that a portion of this interaction involves synaptic interactions within the nucleus tractus solitarii (NTS). 2. The study has involved an analysis of the effective interactions between the stimulation of the arterial chemoreceptors and the hypothalamic defence area (HDA) on the activity of NTS neurones recorded in anaesthetized, paralysed and artificially ventilated cats. 3. A group of eighteen NTS neurones was classified as chemosensitive, on the basis of displaying EPSPs on sinus nerve stimulation (SN) and their failure to show an excitatory response to baroreceptor stimulation. Thirteen of these neurones displayed pronounced excitatory responses to chemoreceptor stimulation. In sixteen of these neurones HDA stimulation elicited an EPSP; in four of these sixteen neurones this early EPSP was followed by an IPSP. In the remaining two (of 18) neurones HDA stimulation provoked no obvious synaptic response but facilitated the efficacy of both chemoreceptor inputs and SN stimulation. 4. Neurones shown to receive convergent inputs from the arterial chemoreceptors (and SN stimulation) and HDA, often displayed excitatory responses to stimulation of other peripheral inputs. Vagally evoked EPSPs were observed in nine neurones, SLN-evoked responses in seven neurones and aortic nerve-evoked EPSPs in three neurones. 5. The organization of these synaptic interactions is discussed and these data are used to explain the pattern of interaction between chemoreceptor, baroreceptor and HDA inputs within the NTS. Conclusions are drawn regarding the functional role of different classes of NTS neurone, based on the findings in this and the accompanying two papers. PMID:8544136

ANTONIA perfusion and stroke. A software tool for the multi-purpose analysis of MR perfusion-weighted datasets and quantitative ischemic stroke assessment.

PubMed

Forkert, N D; Cheng, B; Kemmling, A; Thomalla, G; Fiehler, J

2014-01-01

The objective of this work is to present the software tool ANTONIA, which has been developed to facilitate a quantitative analysis of perfusion-weighted MRI (PWI) datasets in general as well as the subsequent multi-parametric analysis of additional datasets for the specific purpose of acute ischemic stroke patient dataset evaluation. Three different methods for the analysis of DSC or DCE PWI datasets are currently implemented in ANTONIA, which can be case-specifically selected based on the study protocol. These methods comprise a curve fitting method as well as a deconvolution-based and deconvolution-free method integrating a previously defined arterial input function. The perfusion analysis is extended for the purpose of acute ischemic stroke analysis by additional methods that enable an automatic atlas-based selection of the arterial input function, an analysis of the perfusion-diffusion and DWI-FLAIR mismatch as well as segmentation-based volumetric analyses. For reliability evaluation, the described software tool was used by two observers for quantitative analysis of 15 datasets from acute ischemic stroke patients to extract the acute lesion core volume, FLAIR ratio, perfusion-diffusion mismatch volume with manually as well as automatically selected arterial input functions, and follow-up lesion volume. The results of this evaluation revealed that the described software tool leads to highly reproducible results for all parameters if the automatic arterial input function selection method is used. Due to the broad selection of processing methods that are available in the software tool, ANTONIA is especially helpful to support image-based perfusion and acute ischemic stroke research projects.

Dynamic causal modelling of brain-behaviour relationships.

PubMed

Rigoux, L; Daunizeau, J

2015-08-15

In this work, we expose a mathematical treatment of brain-behaviour relationships, which we coin behavioural Dynamic Causal Modelling or bDCM. This approach aims at decomposing the brain's transformation of stimuli into behavioural outcomes, in terms of the relative contribution of brain regions and their connections. In brief, bDCM places the brain at the interplay between stimulus and behaviour: behavioural outcomes arise from coordinated activity in (hidden) neural networks, whose dynamics are driven by experimental inputs. Estimating neural parameters that control network connectivity and plasticity effectively performs a neurobiologically-constrained approximation to the brain's input-outcome transform. In other words, neuroimaging data essentially serves to enforce the realism of bDCM's decomposition of input-output relationships. In addition, post-hoc artificial lesions analyses allow us to predict induced behavioural deficits and quantify the importance of network features for funnelling input-output relationships. This is important, because this enables one to bridge the gap with neuropsychological studies of brain-damaged patients. We demonstrate the face validity of the approach using Monte-Carlo simulations, and its predictive validity using empirical fMRI/behavioural data from an inhibitory control task. Lastly, we discuss promising applications of this work, including the assessment of functional degeneracy (in the healthy brain) and the prediction of functional recovery after lesions (in neurological patients). Copyright © 2015 Elsevier Inc. All rights reserved.

Nonstationary multivariate modeling of cerebral autoregulation during hypercapnia.

PubMed

Kostoglou, Kyriaki; Debert, Chantel T; Poulin, Marc J; Mitsis, Georgios D

2014-05-01

We examined the time-varying characteristics of cerebral autoregulation and hemodynamics during a step hypercapnic stimulus by using recursively estimated multivariate (two-input) models which quantify the dynamic effects of mean arterial blood pressure (ABP) and end-tidal CO2 tension (PETCO2) on middle cerebral artery blood flow velocity (CBFV). Beat-to-beat values of ABP and CBFV, as well as breath-to-breath values of PETCO2 during baseline and sustained euoxic hypercapnia were obtained in 8 female subjects. The multiple-input, single-output models used were based on the Laguerre expansion technique, and their parameters were updated using recursive least squares with multiple forgetting factors. The results reveal the presence of nonstationarities that confirm previously reported effects of hypercapnia on autoregulation, i.e. a decrease in the MABP phase lead, and suggest that the incorporation of PETCO2 as an additional model input yields less time-varying estimates of dynamic pressure autoregulation obtained from single-input (ABP-CBFV) models. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

The effects of hypertension on the cerebral circulation

PubMed Central

Pires, Paulo W.; Dams Ramos, Carla M.; Matin, Nusrat

2013-01-01

Maintenance of brain function depends on a constant blood supply. Deficits in cerebral blood flow are linked to cognitive decline, and they have detrimental effects on the outcome of ischemia. Hypertension causes alterations in cerebral artery structure and function that can impair blood flow, particularly during an ischemic insult or during periods of low arterial pressure. This review will focus on the historical discoveries, novel developments, and knowledge gaps in 1) hypertensive cerebral artery remodeling, 2) vascular function with emphasis on myogenic reactivity and endothelium-dependent dilation, and 3) blood-brain barrier function. Hypertensive artery remodeling results in reduction in the lumen diameter and an increase in the wall-to-lumen ratio in most cerebral arteries; this is linked to reduced blood flow postischemia and increased ischemic damage. Many factors that are increased in hypertension stimulate remodeling; these include the renin-angiotensin-aldosterone system and reactive oxygen species levels. Endothelial function, vital for endothelium-mediated dilation and regulation of myogenic reactivity, is impaired in hypertension. This is a consequence of alterations in vasodilator mechanisms involving nitric oxide, epoxyeicosatrienoic acids, and ion channels, including calcium-activated potassium channels and transient receptor potential vanilloid channel 4. Hypertension causes blood-brain barrier breakdown by mechanisms involving inflammation, oxidative stress, and vasoactive circulating molecules. This exposes neurons to cytotoxic molecules, leading to neuronal loss, cognitive decline, and impaired recovery from ischemia. As the population ages and the incidence of hypertension, stroke, and dementia increases, it is imperative that we gain a better understanding of the control of cerebral artery function in health and disease. PMID:23585139

Complete filter-based cerebral embolic protection with transcatheter aortic valve replacement.

PubMed

Van Gils, Lennart; Kroon, Herbert; Daemen, Joost; Ren, Claire; Maugenest, Anne-Marie; Schipper, Marguerite; De Jaegere, Peter P; Van Mieghem, Nicolas M

2018-03-01

To evaluate the value of left vertebral artery filter protection in addition to the current filter-based embolic protection technology to achieve complete cerebral protection during TAVR. The occurrence of cerebrovascular events after transcatheter aortic valve replacement (TAVR) has fueled concern for its potential application in younger patients with longer life expectancy. Transcatheter cerebral embolic protection (TCEP) devices may limit periprocedural cerebrovascular events by preventing macro and micro-embolization to the brain. Conventional filter-based TCEP devices cover three extracranial contributories to the brain, yet leave the left vertebral artery unprotected. Patients underwent TAVR with complete TCEP. A dual-filter system was deployed in the brachiocephalic trunk and left common carotid artery with an additional single filter in the left vertebral artery. After TAVR all filters were retrieved and sent for histopathological evaluation by an experienced pathologist. Eleven patients received a dual-filter system and nine of them received an additional left vertebral filter. In the remaining two patients, the left vertebral filter could not be deployed. No periprocedural strokes occurred. We found debris in all filters, consisting of thrombus, tissue derived debris, and foreign body material. The left vertebral filter contained debris in an equal amount of patients as the Sentinel filters. The size of the captured particles was similar between all filters. The left vertebral artery is an important entry route for embolic material to the brain during TAVR. Selective filter protection of the left vertebral artery revealed embolic debris in all patients. The clinical value of complete filter-based TCEP during TAVR warrants further research. © 2017 Wiley Periodicals, Inc.

Corrections of arterial input function for dynamic H215O PET to assess perfusion of pelvic tumours: arterial blood sampling versus image extraction

NASA Astrophysics Data System (ADS)

Lüdemann, L.; Sreenivasa, G.; Michel, R.; Rosner, C.; Plotkin, M.; Felix, R.; Wust, P.; Amthauer, H.

2006-06-01

Assessment of perfusion with 15O-labelled water (H215O) requires measurement of the arterial input function (AIF). The arterial time activity curve (TAC) measured using the peripheral sampling scheme requires corrections for delay and dispersion. In this study, parametrizations with and without arterial spillover correction for fitting of the tissue curve are evaluated. Additionally, a completely noninvasive method for generation of the AIF from a dynamic positron emission tomography (PET) acquisition is applied to assess perfusion of pelvic tumours. This method uses a volume of interest (VOI) to extract the TAC from the femoral artery. The VOI TAC is corrected for spillover using a separate tissue TAC and for recovery by determining the recovery coefficient on a coregistered CT data set. The techniques were applied in five patients with pelvic tumours who underwent a total of 11 examinations. Delay and dispersion correction of the blood TAC without arterial spillover correction yielded in seven examinations solutions inconsistent with physiology. Correction of arterial spillover increased the fitting accuracy and yielded consistent results in all patients. Generation of an AIF from PET image data was investigated as an alternative to arterial blood sampling and was shown to have an intrinsic potential to determine the AIF noninvasively and reproducibly. The AIF extracted from a VOI in a dynamic PET scan was similar in shape to the blood AIF but yielded significantly higher tissue perfusion values (mean of 104.0 ± 52.0%) and lower partition coefficients (-31.6 ± 24.2%). The perfusion values and partition coefficients determined with the VOI technique have to be corrected in order to compare the results with those of studies using a blood AIF.

P/Q-type and T-type voltage-gated calcium channels are involved in the contraction of mammary and brain blood vessels from hypertensive patients.

PubMed

Thuesen, A D; Lyngsø, K S; Rasmussen, L; Stubbe, J; Skøtt, O; Poulsen, F R; Pedersen, C B; Rasmussen, L M; Hansen, P B L

2017-03-01

Calcium channel blockers are widely used in cardiovascular diseases. Besides L-type channels, T- and P/Q-type calcium channels are involved in the contraction of human renal blood vessels. It was hypothesized that T- and P/Q-type channels are involved in the contraction of human brain and mammary blood vessels. Internal mammary arteries from bypass surgery patients and cerebral arterioles from patients with brain tumours with and without hypertension were tested in a myograph and perfusion set-up. PCR and immunohistochemistry were performed on isolated blood vessels. The P/Q-type antagonist ω-agatoxin IVA (10 -8  mol L -1 ) and the T-type calcium blocker mibefradil (10 -7  mol L -1 ) inhibited KCl depolarization-induced contraction in mammary arteries from hypertensive patients with no effect on blood vessels from normotensive patients. ω-Agatoxin IVA decreased contraction in cerebral arterioles from hypertensive patients. L-type blocker nifedipine abolished the contraction in mammary arteries. PCR analysis showed expression of P/Q-type (Ca v 2.1), T-type (Ca v 3.1 and Ca v 3.2) and L-type (Ca v 1.2) calcium channels in mammary and cerebral arteries. Immunohistochemical labelling of mammary and cerebral arteries revealed the presence of Ca v 2.1 in endothelial and smooth muscle cells. Ca v 3.1 was also detected in mammary arteries. P/Q- and T-type Ca v are present in human internal mammary arteries and in cerebral penetrating arterioles. P/Q- and T-type calcium channels are involved in the contraction of mammary arteries from hypertensive patients but not from normotensive patients. Furthermore, in cerebral arterioles P/Q-type channels importance was restricted to hypertensive patients might lead to that T- and P/Q-type channels could be a new target in hypertensive patients. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Reversed Robin Hood Syndrome in the Light of Nonlinear Model of Cerebral Circulation

NASA Astrophysics Data System (ADS)

Piechna, A.; Cieslicki, K.

2017-05-01

The brain is supplied by the internal carotid and vertebro-basilar systems of vessels interconnected by arterial anastomoses and forming at the base of the brain a structure called the Circle of Willis (CoW). An active intrinsic ability of cerebral vascular bed maintains constant Cerebral Blood Flow (CBF) in a certain range of systemic pressure changes. This ability is called autoregulation and together with the redundant structure of the CoW guarantee maintaining CBF even in partial occlusion of supplying arteries. However, there are some situations when the combination of those two mechanisms causes an opposite effect called the Reversed Robin Hood Syndrome (RRHS). In this work we proposed a model of the CoW with autoregulation mechanism and investigated a RRHS which may occur in the case of Internal Carotid Artery (ICA) stenosis combined with hypercapnia. We showed and analyzed the mechanism of stealing the blood by the contralateral side of the brain. Our results were qualitatively compared with the clinical reports available in the literature.

Neuroprotective effect of combined ultrasound and microbubbles in a rat model of middle cerebral artery infarction

NASA Astrophysics Data System (ADS)

Fatar, M.; Griebe, M.; Stroick, M.; Kern, R.; Hennerici, M.; Meairs, S.

2005-03-01

Ultrasound-mediated microbubble thrombolysis (UMT) was performed in a middle cerebral artery occlusion model in rats to evaluate possible effects upon brain infarct volume, apoptosis, IL-6 and TNF-alpha levels, and disruption of the blood-brain barrier (BBB). The results show that infarct volume was significantly reduced (p<0.04) in the microbubble + ultrasound (MB + US) group as compared to control animals. The levels of IL-6 and TNF-alpha concentrations, as markers of tissue damage, were not significantly different. In trypan blue treated animals, no additional BBB disruption was observed for the UMT group. Likewise, there was no increase in apoptotic cell death outside the infarction area in animals treated with MB + US. The results demonstrate that UMT does not have a harmful effect upon ischemic stroke in a middle cerebral artery occlusion model of the rat. The significant reduction in brain infarction following insonation with ultrasound and microbubbles suggests a novel neuroprotective effect in ischemic stroke.

Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

PubMed

Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

2017-03-01

Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Arterial Spin Labeling: a one-stop-shop for measurement of brain perfusion in the clinical settings.

PubMed

Golay, Xavier; Petersen, Esben T; Zimine, Ivan; Lim, Tchoyoson C C

2007-01-01

Arterial Spin Labeling (ASL) has opened a unique window into the human brain function and perfusion physiology. Altogether fast and of intrinsic high spatial resolution, ASL is a technique very appealing not only for the diagnosis of vascular diseases, but also in basic neuroscience for the follow-up of small perfusion changes occurring during brain activation. However, due to limited signal-to-noise ratio and complex flow kinetics, ASL is one of the more challenging disciplines within magnetic resonance imaging. In this paper, the theoretical background and main implementations of ASL are revisited. In particular, the different uses of ASL, the pitfalls and possibilities are described and illustrated using clinical cases.

Fetal brain hypometabolism during prolonged hypoxaemia in the llama

PubMed Central

Ebensperger, Germán; Ebensperger, Renato; Herrera, Emilio A; Riquelme, Raquel A; Sanhueza, Emilia M; Lesage, Florian; Marengo, Juan J; Tejo, Rodrigo I; Llanos, Aníbal J; Reyes, Roberto V

2005-01-01

In this study we looked for additional evidence to support the hypothesis that fetal llama reacts to hypoxaemia with adaptive brain hypometabolism. We determined fetal llama brain temperature, Na+ and K+ channel density and Na+–K+-ATPase activity. Additionally, we looked to see whether there were signs of cell death in the brain cortex of llama fetuses submitted to prolonged hypoxaemia. Ten fetal llamas were instrumented under general anaesthesia to measure pH, arterial blood gases, mean arterial pressure, heart rate, and brain and core temperatures. Measurements were made 1 h before and every hour during 24 h of hypoxaemia (n = 5), which was imposed by reducing maternal inspired oxygen fraction to reach a fetal arterial partial pressure of oxygen (Pa,O2) of about 12 mmHg. A normoxaemic group was the control (n = 5). After 24 h of hypoxaemia, we determined brain cortex Na+–K+-ATPase activity, ouabain binding, and the expression of NaV1.1, NaV1.2, NaV1.3, NaV1.6, TREK1, TRAAK and KATP channels. The lack of brain cortex damage was assessed as poly ADP-ribose polymerase (PARP) proteolysis. We found a mean decrease of 0.56°C in brain cortex temperature during prolonged hypoxaemia, which was accompanied by a 51% decrease in brain cortex Na+–K+-ATPase activity, and by a 44% decrease in protein content of NaV1.1, a voltage-gated Na+ channel. These changes occurred in absence of changes in PARP protein degradation, suggesting that the cell death of the brain was not enhanced in the fetal llama during hypoxaemia. Taken together, these results provide further evidence to support the hypothesis that the fetal llama responds to prolonged hypoxaemia with adaptive brain hypometabolism, partly mediated by decreases in Na+–K+-ATPase activity and expression of NaV channels. PMID:16037083

Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine

NASA Technical Reports Server (NTRS)

Delp, M. D.; Armstrong, R. B.; Godfrey, D. A.; Laughlin, M. H.; Ross, C. D.; Wilkerson, M. K.

2001-01-01

1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

Vascular basement membranes as pathways for the passage of fluid into and out of the brain.

PubMed

Morris, Alan W J; Sharp, Matthew MacGregor; Albargothy, Nazira J; Fernandes, Rute; Hawkes, Cheryl A; Verma, Ajay; Weller, Roy O; Carare, Roxana O

2016-05-01

In the absence of conventional lymphatics, drainage of interstitial fluid and solutes from the brain parenchyma to cervical lymph nodes is along basement membranes in the walls of cerebral capillaries and tunica media of arteries. Perivascular pathways are also involved in the entry of CSF into the brain by the convective influx/glymphatic system. The objective of this study is to differentiate the cerebral vascular basement membrane pathways by which fluid passes out of the brain from the pathway by which CSF enters the brain. Experiment 1: 0.5 µl of soluble biotinylated or fluorescent Aβ, or 1 µl 15 nm gold nanoparticles was injected into the mouse hippocampus and their distributions determined at 5 min by transmission electron microscopy. Aβ was distributed within the extracellular spaces of the hippocampus and within basement membranes of capillaries and tunica media of arteries. Nanoparticles did not enter capillary basement membranes from the extracellular spaces. Experiment 2: 2 µl of 15 nm nanoparticles were injected into mouse CSF. Within 5 min, groups of nanoparticles were present in the pial-glial basement membrane on the outer aspect of cortical arteries between the investing layer of pia mater and the glia limitans. The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved. The significance of these findings for neuroimmunology, Alzheimer's disease, drug delivery to the brain and the concept of the Virchow-Robin space are discussed.

Autologous Fat Used for Facial Filling Can Lead to Massive Cerebral Infarction Through Middle Cerebral Artery or Facial Intracranial Branches.

PubMed

Wang, Xian; Wu, Min; Zhou, Xing; Liu, Hengdeng; Zhang, Yongchao; Wang, Haiping

2018-05-31

Autologous fat injection is a procedure aimed at eliminating grave defects in the skin surface by subcutaneous injection of the patient's fatty tissue. Fat embolism is a rare but severe complication of this procedure, especially cerebral infarction. It is first reported by Thaunat in 2004. were presented to the hospital with sudden unconsciousness and left limb weakness in 24 hours after facial fat injection. Brain computed tomography and magnetic resonance imaging were performed immediately after admission. Frontal temporoparietal decompressive craniectomy plus multiple treatments scheduled for patients. Pictures and videos were taken during follow-up. Figures are edited with Adobe Photograph CS6. Patients were diagnosed with extensive cerebral infarction of the right hemisphere through the middle cerebral artery or facial-intracranial branches. Routine cosmetic procedures of facial fat injections could cause devastating and even fatal complications to patients. The small volume of fat grafts can be inserted through the internal carotid artery or go through the communicating branches between the facial artery and the intracranial artery into the brain.

Infarcts presenting with a combination of medial medullary and posterior inferior cerebellar artery syndromes.

PubMed

Lee, Hyung; Baik, Seung Kug

2004-09-15

Cerebellar and medial medullary infarctions are well-known vertebrobasilar stroke syndromes. However, their development in a patient with distal vertebral artery occlusion has not been previously reported. A 49-year-old man with longstanding hypertension suddenly developed vertigo, right-sided Horner syndrome, and left-sided weakness. An MRI of the brain showed acute infarcts in the right inferior cerebellum (posterior inferior cerebellar artery territory) and the right upper medial medulla (direct penetrating branches of vertebral artery). Magnetic resonance angiogram showed occlusion of the distal vertebral artery on the right side. Atherothrombotic occlusion of the distal vertebral artery may cause this unusual combination of vertebrobasilar stroke.

Modelling Effects on Grid Cells of Sensory Input During Self-motion

DTIC Science & Technology

2016-04-20

input during self-motion Florian Raudies, James R. Hinman and Michael E. Hasselmo Center for Systems Neuroscience , Centre for Memory and Brain...Department of Psychological and Brain Sciences and Graduate Program for Neuroscience , Boston University, 2 Cummington Mall, Boston, MA 02215, USA Visual...Psychological and Brain Sciences and the Centre for Computational Neuroscience and Neural Technology before taking his current position as a Research

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

PubMed Central

Sawant, Onkar B.; Ramadoss, Jayanth; Hankins, Gary D.; Wu, Guoyao

2014-01-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid–base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid–base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy. PMID:24810329

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol.

PubMed

Sawant, Onkar B; Ramadoss, Jayanth; Hankins, Gary D; Wu, Guoyao; Washburn, Shannon E

2014-08-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75-2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid-base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid-base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.

The Kringle-2 domain of tissue plasminogen activator significantly reduces mortality and brain infarction in middle cerebral artery occlusion rats.

PubMed

Zhang, Haitao; Bi, Feng; Xiao, Chunlan; Liu, Jianxia; Wang, Zhixia; Liu, Jian-Ning; Zhang, Jing

2010-08-01

Tissue plasminogen activator (TPA) showed brain-protective activity within the first 15 min after cerebral ischemia in rats. To understand its molecular mechanism, TPA derivates were intracerebroventricularly administered at 15 min before, and 15, 90, 120 min after middle cerebral artery occlusion (MCAO) in rats. The reduction in mortality and cerebral infarction at 24 h was seen only with TPA administered at 15 min after MCAO. The down-regulation of endogenous TPA by the intracerebroventricular injection of TPA was found to be responsible for the protective effect on the integrity of blood-brain barrier after MCAO, as well as for the reduction in mortality and cerebral infarction. Moreover, for the first time we have found that the Kringle-2 domain is essential for the brain-protective activity of TPA.

Double Stent Assist Coiling of Ruptured Large Saccular Aneurysm in Proximal Basilar Artery Fenestration.

PubMed

Park, Woong Bae; Sung, Jae Hoon; Huh, Joon; Cho, Chul Bum; Yang, Seung Ho; Kim, Il Sup; Hong, Jae Taek; Lee, Sang Won

2015-09-01

Basilar artery fenestration is infrequent and even rarer in association with a large aneurysm. With proximity to brain stem and vital perforators, endovascular coiling can be considered first. If the large ruptured aneurysm with a wide neck originated from fenestra of the proximal basilar artery and the fenestration loop has branches of posterior circulation, therapeutic consideration should be thorough and fractionized. We report endovascular therapeutic details for a case of a ruptured large saccular aneurysm in proximal basilar artery fenestration.

Development of the Aortic Baroreflex in Microgravity

NASA Technical Reports Server (NTRS)

Shimizu, Tsuyoshi; Yamasaki, Masao; Waki, Hidefumi; Katsuda, Shin-ichiro; Oishi, Hirotaka; Katahira, Kiyoaki; Nagayama, Tadanori; Miyake, Masao; Miyamoto, Yukako

2003-01-01

Baroreceptors sense pressure in blood vessels and send this information to the brain. The primary baroreceptors are located in the main blood vessel leaving the heart (the aorta) and in the arteries in the neck (the carotid arteries). The brain uses information from the baroreceptors to determine whether blood pressure should be raised or lowered. These reflex responses are called baroreflexes. Changing position within a gravity field (i.e., moving from lying to sitting or standing) powerfully stimulates the baroreflexes. In weightlessness, the amount of stimuli that the baroreflexes receive is dramatically reduced. If this reduction occurs when the pathways that control the baroreflexes are being formed, it is possible that either the structure or function of the baroreceptors may be permanently changed. To study the effect of microgravity on structural and functional development of the aortic baroreflex system, we studied young rats (eight days old at launch) that flew on the Space Shuttle Columbia for 16 days. Six rats were studied on landing day; another six were studied after re-adapting to Earth's gravity for 30 days. On both landing day and 30 days after landing, we tested the sensitivity of the rats' baroreflex response. While the rats were anaesthetized, we recorded their arterial pressure, heart rate, and aortic nerve activity. After the tissues were preserved with perfusion fixation, we also examined the baroreflex structures. On landing day, we found that, compared to the controls, the flight rats had: fewer unmyelinated nerve fibers in their aortic nerves lower baroreflex sensitivity significantly lower contraction ability and wall tension of the aorta a reduced number of smooth muscle cells in the aorta. In the 30-day recovery group, the sensitivity of the baroreflex showed no difference between the flight rats and the control groups, although the unmyelinated fibers of the aortic nerve remained reduced in the flight rats. The results show that spaceflight does affect the development of the aortic baroreflex. The sensitivity of the reflex may be suppressed; however, the function of the blood pressure control system can re-adapt to Earth's gravity if the rats return before maturation. The structural differences in the input pathway of the reflex (Le., the reduction in nerve fibers) may remain permanently.

Clinical application of 3D arterial spin-labeled brain perfusion imaging for Alzheimer disease: comparison with brain perfusion SPECT.

PubMed

Takahashi, H; Ishii, K; Hosokawa, C; Hyodo, T; Kashiwagi, N; Matsuki, M; Ashikaga, R; Murakami, T

2014-05-01

Alzheimer disease is the most common neurodegenerative disorder with dementia, and a practical and economic biomarker for diagnosis of Alzheimer disease is needed. Three-dimensional arterial spin-labeling, with its high signal-to-noise ratio, enables measurement of cerebral blood flow precisely without any extrinsic tracers. We evaluated the performance of 3D arterial spin-labeling compared with SPECT, and demonstrated the 3D arterial spin-labeled imaging characteristics in the diagnosis of Alzheimer disease. This study included 68 patients with clinically suspected Alzheimer disease who underwent both 3D arterial spin-labeling and SPECT imaging. Two readers independently assessed both images. Kendall W coefficients of concordance (K) were computed, and receiver operating characteristic analyses were performed for each reader. The differences between the images in regional perfusion distribution were evaluated by means of statistical parametric mapping, and the incidence of hypoperfusion of the cerebral watershed area, referred to as "borderzone sign" in the 3D arterial spin-labeled images, was determined. Readers showed K = 0.82/0.73 for SPECT/3D arterial spin-labeled imaging, and the respective areas under the receiver operating characteristic curve were 0.82/0.69 for reader 1 and 0.80/0.69 for reader 2. Statistical parametric mapping showed that the perisylvian and medial parieto-occipital perfusion in the arterial spin-labeled images was significantly higher than that in the SPECT images. Borderzone sign was observed on 3D arterial spin-labeling in 70% of patients misdiagnosed with Alzheimer disease. The diagnostic performance of 3D arterial spin-labeling and SPECT for Alzheimer disease was almost equivalent. Three-dimensional arterial spin-labeled imaging was more influenced by hemodynamic factors than was SPECT imaging. © 2014 by American Journal of Neuroradiology.

Brain sparing effect in growth-restricted fetuses is associated with decreased cardiac acceleration and deceleration capacities: a case-control study.

PubMed

Stampalija, T; Casati, D; Monasta, L; Sassi, R; Rivolta, M W; Muggiasca, M L; Bauer, A; Ferrazzi, E

2016-11-01

Phase rectified signal averaging (PRSA) is a new method of fetal heart rate variability (fHRV) analysis that quantifies the average acceleration (AC) and deceleration capacity (DC) of the heart. The aim of this study was to evaluate AC and DC of fHR [recorded by trans-abdominal fetal electrocardiogram (ta-fECG)] in relation to Doppler velocimetry characteristics of intrauterine growth restriction (IUGR). Prospective case-control study. Single third referral centre. IUGR (n = 66) between 25 and 40 gestational weeks and uncomplicated pregnancies (n = 79). In IUGR the nearest ta-fECG monitoring to delivery was used for PRSA analysis and Doppler velocimetry parameters obtained within 48 hours. AC and DC were computed at s = T = 9. The relation was evaluated between either AC or DC and Doppler velocimetry parameters adjusting for gestational age at monitoring, as well as the association between either AC or DC and IUGR with or without brain sparing. In IUGRs there was a significant association between either AC and DC and middle cerebral artery pulsatility index (PI; P = 0.01; P = 0.005), but the same was not true for uterine or umbilical artery PI (P > 0.05). Both IUGR fetuses with and without brain sparing had lower AC and DC than controls, but this association was stronger for IUGRs with brain sparing. Our study observed for the first time that AC and DC at PRSA analysis are associated with middle cerebral artery PI, but not with uterine or umbilical artery PI, and that there is a significant decrease of AC and DC in association with brain sparing in IUGR fetuses from 25 weeks of gestation to term. Brain sparing in IUGR fetuses is associated with decreased acceleration and deceleration capacities of the heart. © 2015 Royal College of Obstetricians and Gynaecologists.

Combination of blood flow asymmetry in the cerebral and cerebellar hemispheres on brain perfusion SPECT predicts 5-year outcome in patients with symptomatic unilateral major cerebral artery occlusion.

PubMed

Nomura, Jun-ichi; Ogasawara, Kuniaki; Saito, Hideo; Terasaki, Kazunori; Matsumoto, Yoshiyasu; Takahashi, Yoshihiro; Ogasawara, Yasushi; Saura, Hiroaki; Yoshida, Koji; Sato, Yuiko; Kubo, Yoshitaka; Ogawa, Akira

2014-03-01

Misery perfusion increases the risk of stroke recurrence in patients with symptomatic major cerebral artery occlusion. The ratio of brain perfusion contralateral-to-affected asymmetry in the cerebellar hemisphere to brain perfusion affected-to-contralateral asymmetry in the cerebral hemisphere (CblPR/CbrPR) indicates affected-to-contralateral asymmetry of oxygen extraction fraction (OEF) in the cerebral hemisphere. The purpose of the present study was to determine whether the CblPR/CbrPR on brain perfusion single-photon emission computed tomography (SPECT) predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the middle cerebral artery (MCA) or internal carotid artery (ICA). Brain perfusion was assessed using N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) SPECT in 70 patients. A region of interest (ROI) was manually placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres, and the CblPR/CbrPR was calculated. All patients were prospectively followed for 5 years. The primary end points were stroke recurrence or death. A total of 17 patients exhibited the primary end points, 11 of whom experienced subsequent ipsilateral strokes. Multivariate analysis revealed that only high CblPR/CbrPR was significantly associated with the development of the primary end point or subsequent ipsilateral strokes (95% confidential limits [CIs], 1.130-3.145; P  =  0.0114 or 95% CIs, 2.558-5.140; P  =  0.0045, respectively). The CblPR/CbrPR provided 65% (11/17) or 91% (10/11) sensitivity and 88% (47/53) or 88% (52/59) specificity in predicting the primary end point or subsequent ipsilateral strokes, respectively. The CblPR/CbrPR on brain perfusion SPECT predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the MCA or ICA.

Kinetic Modeling of PET Data Without Blood Sampling

NASA Astrophysics Data System (ADS)

Bentourkia, M.

2005-06-01

In positron emission tomography (PET) imaging, application of kinetic modeling always requires an input curve (IC) together with the PET data. The IC can be obtained by means of external blood sampling or, in the case of cardiac studies, by means of a region-of-interest (ROI) drawn on the blood pool. It is, however, very unsuitable to withdraw and to analyze blood samples, and in small animals, these operations become difficult, while ICs determined from ROIs are generally contaminated by emissions from neighboring sites, or they are underestimated because of partial volume effect. In this paper, we report a new method to extract kinetic parameters from dynamic PET studies without a priori knowledge of the IC. The method is applied in human brain data measured with fluorodeoxyglucose (FDG) human-brain and in cardiac-rat perfusion studies with /sup 13/N-ammonia and /sup 11/C-acetate. The tissue blood volume (TBV), usually fitted together with the rate constants, is extracted simultaneously with the tissue time activity curves for cardiac studies, while for brain gray matter, TBV is known to be about 4% to 7%. The shape of IC is obtained by means of factor analysis from an ROI drawn around a cardiac tissue or a brain artery. The results show a good correlation (p<0.05) between the cerebral metabolic rate of glucose, myocardial blood flow, and oxygen consumption obtained with the new method in comparison to the usual method. In conclusion, it is possible to apply kinetic modeling without any blood sampling, which significantly simplifies PET acquisition and data analysis.

Advanced Pediatric Brain Imaging Research and Training Program

DTIC Science & Technology

2013-10-01

diffusion tensor imaging and perfusion ( arterial spin labeling) MRI data and to relate measures of global and regional brain microstructural organization...AD_________________ Award Number: W81XWH-11-2-0198 TITLE: Advanced Pediatric Brain Imaging...September 2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Advanced Pediatric Brain Imaging Research and Training Program 5b. GRANT NUMBER W81XWH

Dendritic integration: 60 years of progress.

PubMed

Stuart, Greg J; Spruston, Nelson

2015-12-01

Understanding how individual neurons integrate the thousands of synaptic inputs they receive is critical to understanding how the brain works. Modeling studies in silico and experimental work in vitro, dating back more than half a century, have revealed that neurons can perform a variety of different passive and active forms of synaptic integration on their inputs. But how are synaptic inputs integrated in the intact brain? With the development of new techniques, this question has recently received substantial attention, with new findings suggesting that many of the forms of synaptic integration observed in vitro also occur in vivo, including in awake animals. Here we review six decades of progress, which collectively highlights the complex ways that single neurons integrate their inputs, emphasizing the critical role of dendrites in information processing in the brain.

Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein.

PubMed

Fan, Zhen; Calsolaro, Valeria; Atkinson, Rebecca A; Femminella, Grazia D; Waldman, Adam; Buckley, Christopher; Trigg, William; Brooks, David J; Hinz, Rainer; Edison, Paul

2016-11-01

Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide ( 18 F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18 F-GE180 PET in (older) healthy controls. Ten healthy controls, 6 TSPO high-affinity binders, and 4 mixed-affinity binders were recruited. All subjects underwent detailed neuropsychologic tests, MRI, and a 210-min 18 F-GE180 dynamic PET/CT scan using metabolite-corrected arterial plasma input function. We evaluated 5 different kinetic models: irreversible and reversible 2-tissue-compartment models, a reversible 1-tissue model, and 2 models with an extra irreversible vascular compartment. The minimal scan duration was established using 210-min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. 18 F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. The volume of distribution (V T ) was 0.17 in high-affinity binders and 0.12 in mixed-affinity binders using the kinetic model. The model that best represented brain 18 F-GE180 kinetics across regions was the reversible 2-tissue-compartment model (2TCM4k), and 90 min resulted as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a V T highly consistent with V T in the kinetic model, which could be used for voxelwise analysis. We report for the first time, to our knowledge, the kinetic properties of the novel third-generation TSPO PET ligand 18 F-GE180 in humans: 2TCM4k is the optimal method to quantify the brain uptake, 90 min is the optimal scan length, and the Logan approach could be used to generate parametric maps. Although these control subjects have shown relatively low V T , the methodology presented here forms the basis for quantification for future PET studies using 18 F-GE180 in different pathologies. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

The effects of Mucuna pruriens extract on histopathological and biochemical features in the rat model of ischemia.

PubMed

Nayak, Vanishri S; Kumar, Nitesh; D'Souza, Antony S; Nayak, Sunil S; Cheruku, Sri P; Pai, K Sreedhara Ranganath

2017-12-13

Stroke is considered to be one of the most important causes of death worldwide. Global ischemia causes widespread brain injury and infarctions in various regions of the brain. Oxidative stress can be considered an important factor in the development of tissue damage, which is caused because of arterial occlusion with subsequent reperfusion. Kapikacchu or Mucuna pruriens, commonly known as velvet bean, is well known for its aphrodisiac activities. It is also used in the treatment of snakebites, depressive neurosis, and Parkinson's disease. Although this plant has different pharmacological actions, its neuroprotective activity has received minimal attention. Thus, this study was carried out with the aim of evaluating the neuroprotective action of M. pruriens in bilateral carotid artery occlusion-induced global cerebral ischemia in Wistar rats. The carotid arteries of both sides were occluded for 30 min and reperfused to induce global cerebral ischemia. The methanolic plant extract was administered to the study animals for 10 days. The brains of the Wistar rats were isolated by decapitation and observed for histopathological and biochemical changes. Cerebral ischemia resulted in significant neurological damage in the brains of the rats that were not treated by M. pruriens. The group subjected to treatment by the M. pruriens extract showed significant protection against brain damage compared with the negative control group, which indicates the therapeutic potential of this plant in ischemia.

Acute lipophilicity-dependent effect of intravascular simvastatin in the early phase of focal cerebral ischemia.

PubMed

Beretta, S; Pastori, C; Sala, G; Piazza, F; Ferrarese, C; Cattalini, A; de Curtis, M; Librizzi, L

2011-05-01

The acute effects of simvastatin lactone (lipophilic) and simvastatin acid (hydrophilic) on transient focal ischemia were assessed using the isolated guinea pig brain maintained in vitro by arterial perfusion. This new model of cerebral ischemia allows the assessment of the very early phase of the ischemic process, with the functional preservation of the vascular and neuronal compartments and the blood-brain barrier (bbb). The middle cerebral artery was transiently tied for 30 min followed by reperfusion for 60 min. Statins (nanomolar doses) were administered by intravascular continuous infusion starting 60 min before ischemia induction. Brain cortical activity and arterial vascular tone were continuously recorded. At the end of the experiment immunoreactivity for microtubule-associated protein 2 (MAP-2), expression of survival kinases (ERK and Akt) and total anti-oxidant capacity were assayed. Brains treated with simvastatin lactone showed i) reduced amplitude and delayed onset of ischemic depressions, ii) preservation of MAP-2 immunoreactivity, iii) activation of ERK signaling in the ischemic hemisphere and iv) increase in whole-brain anti-oxidant capacity. Treatment with the bbb-impermeable simvastatin acid was ineffective on the above-mentioned parameters. Vascular resistance recordings and Akt signaling were unchanged by any statin treatment. Our findings suggest that intravascular-delivered simvastatin exerts an acute lipophilicity-dependent protective effect in the early phase of cerebral ischemia. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cell type-specific long-range connections of basal forebrain circuit.

PubMed

Do, Johnny Phong; Xu, Min; Lee, Seung-Hee; Chang, Wei-Cheng; Zhang, Siyu; Chung, Shinjae; Yung, Tyler J; Fan, Jiang Lan; Miyamichi, Kazunari; Luo, Liqun; Dan, Yang

2016-09-19

The basal forebrain (BF) plays key roles in multiple brain functions, including sleep-wake regulation, attention, and learning/memory, but the long-range connections mediating these functions remain poorly characterized. Here we performed whole-brain mapping of both inputs and outputs of four BF cell types - cholinergic, glutamatergic, and parvalbumin-positive (PV+) and somatostatin-positive (SOM+) GABAergic neurons - in the mouse brain. Using rabies virus -mediated monosynaptic retrograde tracing to label the inputs and adeno-associated virus to trace axonal projections, we identified numerous brain areas connected to the BF. The inputs to different cell types were qualitatively similar, but the output projections showed marked differences. The connections to glutamatergic and SOM+ neurons were strongly reciprocal, while those to cholinergic and PV+ neurons were more unidirectional. These results reveal the long-range wiring diagram of the BF circuit with highly convergent inputs and divergent outputs and point to both functional commonality and specialization of different BF cell types.

The inverse problem of brain energetics: ketone bodies as alternative substrates

NASA Astrophysics Data System (ADS)

Calvetti, D.; Occhipinti, R.; Somersalo, E.

2008-07-01

Little is known about brain energy metabolism under ketosis, although there is evidence that ketone bodies have a neuroprotective role in several neurological disorders. We investigate the inverse problem of estimating reaction fluxes and transport rates in the different cellular compartments of the brain, when the data amounts to a few measured arterial venous concentration differences. By using a recently developed methodology to perform Bayesian Flux Balance Analysis and a new five compartment model of the astrocyte-glutamatergic neuron cellular complex, we are able to identify the preferred biochemical pathways during shortage of glucose and in the presence of ketone bodies in the arterial blood. The analysis is performed in a minimally biased way, therefore revealing the potential of this methodology for hypothesis testing.

Pure Motor Stroke Secondary to Cerebral Infarction of Recurrent Artery of Heubner after Mild Head Trauma: A Case Report.

PubMed

Yilmaz, Ali; Kizilay, Zahir; Ozkul, Ayca; Çirak, Bayram

2016-03-15

The recurrent Heubner's artery is the distal part of the medial striate artery. Occlusion of the recurrent artery of Heubner, classically contralateral hemiparesis with fasciobrachiocrural predominance, is attributed to the occlusion of the recurrent artery of Heubner and is widely known as a stroke syndrome in adults. However, isolated occlusion of the deep perforating arteries following mild head trauma also occurs extremely rarely in childhood. Here we report the case of an 11-year-old boy with pure motor stroke. The brain MRI showed an acute ischemia in the recurrent artery of Heubner supply area following mild head trauma. His fasciobrachial hemiparesis and dysarthria were thought to be secondary to the stretching of deep perforating arteries leading to occlusion of the recurrent artery of Heubner. Post-traumatic pure motor ischemic stroke can be secondary to stretching of the deep perforating arteries especially in childhood.

Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies

NASA Astrophysics Data System (ADS)

Asselin, Marie-Claude; Cunningham, Vincent J.; Amano, Shigeko; Gunn, Roger N.; Nahmias, Claude

2004-03-01

A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[18F]fluoro-L-DOPA and one subject injected with [11C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 ± 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest.

The effects of Y-27632 on pial microvessels during global brain ischemia and reperfusion in rabbits.

PubMed

Shintani, Noriyuki; Ishiyama, Tadahiko; Kotoda, Masakazu; Asano, Nobumasa; Sessler, Daniel I; Matsukawa, Takashi

2017-03-07

Global brain ischemia-reperfusion during propofol anesthesia provokes persistent cerebral pial constriction. Constriction is likely mediated by Rho-kinase. Cerebral vasoconstriction possibly exacerbates ischemic brain injury. Because Y-27632 is a potent Rho-kinase inhibitor, it should be necessary to evaluate its effects on cerebral pial vessels during ischemia-reperfusion period. We therefore tested the hypotheses that Y-27632 dilates cerebral pial arterioles after the ischemia-reperfusion injury, and evaluated the time-course of cerebral pial arteriolar status after the ischemia-reperfusion. Japanese white rabbits were anesthetized with propofol, and a closed cranial window inserted over the left hemisphere. Global brain ischemia was produced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Rabbits were assigned to cranial window perfusion with: (1) artificial cerebrospinal fluid (Control group, n = 7); (2) topical infusion of Y-27632 10 -6 mol · L -1 for 30 min before the initiation of global brain ischemia (Pre group, n = 7); (3) topical infusion of Y-27632 10 -6 mol · L -1 starting 30 min before ischemia and continuing throughout the study period (Continuous group, n = 7); and, (4) topical infusion of Y-27632 10 -6 mol · L -1 starting 10 min after the ischemia and continuing until the end of the study (Post group, n = 7). Cerebral pial arterial and venule diameters were recorded 30 min before ischemia, just before arterial clamping, 10 min after clamping, and 5, 10, 20, 40, 60, 80, 100, and 120 min after unclamping. Mean arterial blood pressure and blood glucose concentration increased significantly after global brain ischemia except in the Continuous group. In the Pre and Continuous groups, topical application of Y-27632 produced dilation of large (mean 18-19%) and small (mean; 25-29%) pial arteries, without apparent effect on venules. Compared with the Control and Pre groups, arterioles were significantly dilated during the reperfusion period in the Continuous and Post groups (mean at 120 min: 5-8% in large arterioles and 11-12% in small arterioles). Y-27632 dilated cerebral pial arterioles during reperfusion. Y-27632 may enhance recovery from ischemia by preventing arteriolar vasoconstriction during reperfusion.

P14.21 Can vascular risk factors influence number of brain metastases?

PubMed Central

Berk, B.; Nagel, S.; Kortmann, R.; Hoffmann, K.; Gaudino, C.; Seidel, C.

2017-01-01

Abstract BACKGROUND: Up to 30-40% of patients with solid tumors develop cerebral metastases. Number of cerebral metastases is relevant for treatment and prognosis. However, factors that determine number of metastases are not well defined. Distribution of metastases is influenced by blood vessels and cerebral small vessel disease can reduce number of metastases. Aim of this pilot study was to analyze the influence of vascular risk factors (arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia) and of peripheral arterial occlusive disease (PAOD) on number of brain metastases. METHODS: 200 patients with pre-therapeutic 3D-brain MRI and available clinical data were analyzed retrospectively. Number of metastases (NoM) was compared between patients with/without vascular risk factors (vasRF). Results: Patients with PAOD had significant less brain metastases than patients without PAOD (NoM=4.43 vs. 6.02, p=0.043), no other single vasRF conferred a significant effect on NoM. NoM differed significantly between different tumor entities. CONCLUSION: Presence of PAOD showed some effect on number of brain metastases implying that tumor-independent vascular factors can influence brain metastasation.

Acute basilar artery occlusion treated by thromboaspiration in a cocaine and ecstasy abuser.

PubMed

Vallée, J-N; Crozier, S; Guillevin, R; Obadia, M; Lo, D; Barragan-Campos, H M; Samson, Y; Chiras, J

2003-09-23

Thromboaspiration was performed in a young adult in a coma because of acute basilar artery occlusion associated with cocaine and ecstasy abuse 30 hours after symptom onset. There was complete recanalization of the basilar artery and favorable recovery. Because cocaine and ecstasy abuse has been reported to be a risk factor for ischemic stroke and fatal brain hemorrhage, thromboaspiration may be an alternative therapy to thrombolysis.

Patient-specific system for prognosis of surgical treatment outcomes of human cardiovascular system

NASA Astrophysics Data System (ADS)

Golyadkina, Anastasiya A.; Kalinin, Aleksey A.; Kirillova, Irina V.; Kossovich, Elena L.; Kossovich, Leonid Y.; Menishova, Liyana R.; Polienko, Asel V.

2015-03-01

Object of study: Improvement of life quality of patients with high stroke risk ia the main goal for development of system for patient-specific modeling of cardiovascular system. This work is dedicated at increase of safety outcomes for surgical treatment of brain blood supply alterations. The objects of study are common carotid artery, internal and external carotid arteries and bulb. Methods: We estimated mechanical properties of carotid arteries tissues and patching materials utilized at angioplasty. We studied angioarchitecture features of arteries. We developed and clinically adapted computer biomechanical models, which are characterized by geometrical, physical and mechanical similarity with carotid artery in norm and with pathology (atherosclerosis, pathological tortuosity, and their combination). Results: Collaboration of practicing cardiovascular surgeons and specialists in the area of Mathematics and Mechanics allowed to successfully conduct finite-element modeling of surgical treatment taking into account various features of operation techniques and patching materials for a specific patient. Numerical experiment allowed to reveal factors leading to brain blood supply decrease and atherosclerosis development. Modeling of carotid artery reconstruction surgery for a specific patient on the basis of the constructed biomechanical model demonstrated the possibility of its application in clinical practice at approximation of numerical experiment to the real conditions.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI.

PubMed

Iliff, Jeffrey J; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-03-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

PubMed Central

Iliff, Jeffrey J.; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-01-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer’s disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer’s disease susceptibility and progression in the live human brain. PMID:23434588

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation.

PubMed

Jin, Rong; Xiao, Adam Y; Chen, Rui; Granger, D Neil; Li, Guohong

2017-12-01

Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147 (cluster of differentiation 147), also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown. In this study, we show that CD147 acts as a key player in ischemic stroke by driving thrombotic and inflammatory responses. Focal cerebral ischemia was induced in C57BL/6 mice by a 60-minute transient middle cerebral artery occlusion. Animals were treated with anti-CD147 function-blocking antibody (αCD147) or isotype control antibody. Blood-brain barrier permeability, thrombus formation, and microvascular patency were assessed 24 hours after ischemia. Infarct size, neurological deficits, and inflammatory cells invaded in the brain were assessed 72 hours after ischemia. CD147 expression was rapidly increased in ischemic brain endothelium after transient middle cerebral artery occlusion. Inhibition of CD147 reduced infarct size and improved functional outcome on day 3 after transient middle cerebral artery occlusion. The neuroprotective effects were associated with (1) prevented blood-brain barrier damage, (2) decreased intravascular fibrin and platelet deposition, which in turn reduced thrombosis and increased cerebral perfusion, and (3) reduced brain inflammatory cell infiltration. The underlying mechanism may include reduced NF-κB (nuclear factor κB) activation, MMP-9 (matrix metalloproteinase-9) activity, and PAI-1 (plasminogen activator inhibitor-1) expression in brain microvascular endothelial cells. Inhibition of CD147 ameliorates acute ischemic stroke by reducing thromboinflammation. CD147 might represent a novel and promising therapeutic target for ischemic stroke and possibly other thromboinflammatory disorders. © 2017 American Heart Association, Inc.

Vasoparalysis associated with brain damage in asphyxiated term infants

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

Pryds, O.; Greisen, G.; Lou, H.

1990-07-01

The relationship of cerebral blood flow to acute changes in arterial carbon dioxide and mean arterial blood pressure (MABP) was determined during the first day of life in 19 severely asphyxiated term infants supported by mechanical ventilation. For comparison, 12 infants without perinatal asphyxia were also investigated. Global cerebral blood flow (CBF infinity) was determined by xenon 133 clearance two or three times within approximately 2 hours. During the cerebral blood flow measurement, the amplitude-integrated electroencephalogram and visual-evoked potential were recorded. Changes in arterial carbon dioxide pressure followed adjustments of the ventilator settings, whereas MABP fluctuated spontaneously. Arterial oxygen pressuremore » and blood glucose concentration were in the normal range. Five of the asphyxiated infants had isoelectric electroencephalograms and died subsequently with severe brain damage. They had a high CBF infinity (mean 30.6 ml/100 gm/min) and abolished carbon dioxide and MABP reactivity. Lower CBF infinity (mean 14.7 ml/100 gm/min) and abolished MABP reactivity were found in another five asphyxiated infants with burst-suppression electroencephalograms in whom computed tomographic or clinical signs of brain lesions developed. The carbon dioxide reactivity was preserved in these infants. In the remaining nine asphyxiated infants without signs of central nervous system abnormality, carbon dioxide and MABP reactivity were preserved, as was also the case in the control group. We conclude that abolished autoregulation is associated with cerebral damage in asphyxiated infants and that the combination of isoelectric electroencephalograms and cerebral hyperperfusion is an early indicator of very severe brain damage.« less

Selective Heart, Brain and Body Perfusion in Open Aortic Arch Replacement.

PubMed

Maier, Sven; Kari, Fabian; Rylski, Bartosz; Siepe, Matthias; Benk, Christoph; Beyersdorf, Friedhelm

2016-09-01

Open aortic arch replacement is a complex and challenging procedure, especially in post dissection aneurysms and in redo procedures after previous surgery of the ascending aorta or aortic root. We report our experience with the simultaneous selective perfusion of heart, brain, and remaining body to ensure optimal perfusion and to minimize perfusion-related risks during these procedures. We used a specially configured heart-lung machine with a centrifugal pump as arterial pump and an additional roller pump for the selective cerebral perfusion. Initial arterial cannulation is achieved via femoral artery or right axillary artery. After lower body circulatory arrest and selective antegrade cerebral perfusion for the distal arch anastomosis, we started selective lower body perfusion simultaneously to the selective antegrade cerebral perfusion and heart perfusion. Eighteen patients were successfully treated with this perfusion strategy from October 2012 to November 2015. No complications related to the heart-lung machine and the cannulation occurred during the procedures. Mean cardiopulmonary bypass time was 239 ± 33 minutes, the simultaneous selective perfusion of brain, heart, and remaining body lasted 55 ± 23 minutes. One patient suffered temporary neurological deficit that resolved completely during intensive care unit stay. No patient experienced a permanent neurological deficit or end-organ dysfunction. These high-risk procedures require a concept with a special setup of the heart-lung machine. Our perfusion strategy for aortic arch replacement ensures a selective perfusion of heart, brain, and lower body during this complex procedure and we observed excellent outcomes in this small series. This perfusion strategy is also applicable for redo procedures.

[Effect on tranquilizing and allaying excitement needling method on brain blood flow in the patients of insomnia of heart and spleen deficiency].

PubMed

Yan, Xing-ke; Zhang, Yan; Yu, Lu; Yue, Gong-lei; Li, Tie; Chen, Cheng; Cui, Hai-fu; Wang, Fu-chun

2010-02-01

To observe the therapeutic effect of tranquilizing and allaying excitement needling method on insomnia of heart and spleen deficiency and the effect of brain blood flow. Sixty cases were randomly divided into a tranquilizing and allaying excitement needling method group (observation group) and an eight confluence points selected group (control group), 30 cases in each group. The observation group was treated by acupuncture at Sishencong (EX-HN 1), Shenmen (HT 7), and Sanyinjiao (SP 6) with tranquilizing and allaying excitement needling method. The control group was treated by acupuncture at Shenmai (BL 62) and Zhaohai (KI 6). Their therapeutic effects and changes of brain blood flow were observed. The total effective rate was 93.3% (28/30) in the observation group which was better than 83.3% (25/30) in the control group (P < 0.05). After treatment, the peak velocity of systolic (Vp) and diastolic blood flow velocity (Vd) of middle cerebral artery, basilar artery and vertebral artery were increased in the both groups (P < 0.01, P < 0.05), with more obvious increase in the observation group (P < 0.01, P < 0.05), except the Vd of left vertebral artery. Both the tranquilizing and allaying excitement needling method and the eight confluence points selected needling method can improve the clinical signs and symptoms. Meanwhile, the therapeutic effect of acupuncture is related with improvement of brain blood flow. However, the tranquilizing and allaying excitement needling method has better therapeutic effect on insomnia of heart and spleen deficiency.

Three-dimensional whole-brain perfusion quantification using pseudo-continuous arterial spin labeling MRI at multiple post-labeling delays: accounting for both arterial transit time and impulse response function.

PubMed

Qin, Qin; Huang, Alan J; Hua, Jun; Desmond, John E; Stevens, Robert D; van Zijl, Peter C M

2014-02-01

Measurement of the cerebral blood flow (CBF) with whole-brain coverage is challenging in terms of both acquisition and quantitative analysis. In order to fit arterial spin labeling-based perfusion kinetic curves, an empirical three-parameter model which characterizes the effective impulse response function (IRF) is introduced, which allows the determination of CBF, the arterial transit time (ATT) and T(1,eff). The accuracy and precision of the proposed model were compared with those of more complicated models with four or five parameters through Monte Carlo simulations. Pseudo-continuous arterial spin labeling images were acquired on a clinical 3-T scanner in 10 normal volunteers using a three-dimensional multi-shot gradient and spin echo scheme at multiple post-labeling delays to sample the kinetic curves. Voxel-wise fitting was performed using the three-parameter model and other models that contain two, four or five unknown parameters. For the two-parameter model, T(1,eff) values close to tissue and blood were assumed separately. Standard statistical analysis was conducted to compare these fitting models in various brain regions. The fitted results indicated that: (i) the estimated CBF values using the two-parameter model show appreciable dependence on the assumed T(1,eff) values; (ii) the proposed three-parameter model achieves the optimal balance between the goodness of fit and model complexity when compared among the models with explicit IRF fitting; (iii) both the two-parameter model using fixed blood T1 values for T(1,eff) and the three-parameter model provide reasonable fitting results. Using the proposed three-parameter model, the estimated CBF (46 ± 14 mL/100 g/min) and ATT (1.4 ± 0.3 s) values averaged from different brain regions are close to the literature reports; the estimated T(1,eff) values (1.9 ± 0.4 s) are higher than the tissue T1 values, possibly reflecting a contribution from the microvascular arterial blood compartment. Copyright © 2013 John Wiley & Sons, Ltd.

Effect of pyrrolidone-pyroglutamic acid composition on blood flow in rat middle cerebral artery.

PubMed

Semkina, G A; Matsievskii, D D; Mirzoyan, N R

2006-01-01

We compared the effects of a pyrrolidone-pyroglutamic acid composition and nimodipine on blood circulation in the middle cerebral artery in rats. The composition produced a strong effect on blood supply to the brain, stimulated blood flow in the middle cerebral artery (by 60 +/- 9%) and decreased blood pressure (by 25.0 +/- 2.7%). The cerebrovascular effects of this composition differed from those of nimodipine. Nimodipine not only increased middle cerebral artery blood flow, but also decreased cerebral blood flow in the early period after treatment.

Latin American Consensus on the use of transcranial Doppler in the diagnosis of brain death

PubMed Central

2014-01-01

Transcranial Doppler evaluates cerebral hemodynamics in patients with brain injury and is a useful technical tool in diagnosing cerebral circulatory arrest, usually present in the brain-dead patient. This Latin American Consensus was formed by a group of 26 physicians experienced in the use of transcranial Doppler in the context of brain death. The purpose of this agreement was to make recommendations regarding the indications, technique, and interpretation of the study of transcranial ultrasonography in patients with a clinical diagnosis of brain death or in the patient whose clinical diagnosis presents difficulties; a working group was formed to enable further knowledge and to strengthen ties between Latin American physicians working on the same topic. A review of the literature, concepts, and experiences were exchanged in two meetings and via the Internet. Questions about pathophysiology, equipment, techniques, findings, common problems, and the interpretation of transcranial Doppler in the context of brain death were answered. The basic consensus statements are the following: cerebral circulatory arrest is the final stage in the evolution of progressive intracranial hypertension, which is visualized with transcranial Doppler as a "pattern of cerebral circulatory arrest". The following are accepted as the standard of cerebral circulatory arrest: reverberant pattern, systolic spikes, and absence of previously demonstrated flow. Ultrasonography should be used - in acceptable hemodynamic conditions - in the anterior circulation bilaterally (middle cerebral artery) and in the posterior (basilar artery) territory. If no ultrasonographic images are found in any or all of these vessels, their proximal arteries are acceptable to be studied to look for a a pattern of cerebral circulatory arrest. PMID:25295818

Acute Hyperglycemia Does Not Affect Brain Swelling or Infarction Volume After Middle Cerebral Artery Occlusion in Rats.

PubMed

McBride, Devin W; Matei, Nathanael; Câmara, Justin R; Louis, Jean-Sébastien; Oudin, Guillaume; Walker, Corentin; Adam, Loic; Liang, Xiping; Hu, Qin; Tang, Jiping; Zhang, John H

2016-01-01

Stroke disproportionally affects diabetic and hyperglycemic patients with increased incidence and is associated with higher morbidity and mortality due to brain swelling. In this study, the intraluminal suture middle cerebral artery occlusion (MCAO) model was used to examine the effects of blood glucose on brain swelling and infarct volume in acutely hyperglycemic rats and normo-glycemic controls. Fifty-four rats were distributed into normo-glycemic sham surgery, hyperglycemic sham surgery, normo-glycemic MCAO, and hyperglycemic MCAO. To induce hyperglycemia, 15 min before MCAO surgery, animals were injected with 50 % dextrose. Animals were subjected to 90 min of MCAO and sacrificed 24 h after reperfusion for hemispheric brain swelling and infarct volume calculations using standard equations. While normo-glycemic and hyperglycemic animals after MCAO presented with significantly higher brain swelling and larger infarcts than their respective controls, no statistical difference was observed for either brain swelling or infarct volume between normo-glycemic shams and hyperglycemic shams or normo-glycemic MCAO animals and hyperglycemic MCAO animals. The findings of this study suggest that blood glucose does not have any significant effect on hemispheric brain swelling or infarct volume after MCAO in rats.

Paravascular channels, cisterns, and the subarachnoid space in the rat brain: A single compartment with preferential pathways

PubMed Central

Bedussi, Beatrice; van der Wel, Nicole N; de Vos, Judith; van Veen, Henk; Siebes, Maria; VanBavel, Ed

2016-01-01

Recent evidence suggests an extensive exchange of fluid and solutes between the subarachnoid space and the brain interstitium, involving preferential pathways along blood vessels. We studied the anatomical relations between brain vasculature, cerebrospinal fluid compartments, and paravascular spaces in male Wistar rats. A fluorescent tracer was infused into the cisterna magna, without affecting intracranial pressure. Tracer distribution was analyzed using a 3D imaging cryomicrotome, confocal microscopy, and correlative light and electron microscopy. We found a strong 3D colocalization of tracer with major arteries and veins in the subarachnoid space and large cisterns, attributed to relatively large subarachnoid space volumes around the vessels. Confocal imaging confirmed this colocalization and also revealed novel cisternal connections between the subarachnoid space and ventricles. Unlike the vessels in the subarachnoid space, penetrating arteries but not veins were surrounded by tracer. Correlative light and electron microscopy images indicated that this paravascular space was located outside of the endothelial layer in capillaries and just outside of the smooth muscle cells in arteries. In conclusion, the cerebrospinal fluid compartment, consisting of the subarachnoid space, cisterns, ventricles, and para-arteriolar spaces, forms a continuous and extensive network that surrounds and penetrates the rat brain, in which mixing may facilitate exchange between interstitial fluid and cerebrospinal fluid. PMID:27306753

Paravascular channels, cisterns, and the subarachnoid space in the rat brain: A single compartment with preferential pathways.

PubMed

Bedussi, Beatrice; van der Wel, Nicole N; de Vos, Judith; van Veen, Henk; Siebes, Maria; VanBavel, Ed; Bakker, Erik Ntp

2017-04-01

Recent evidence suggests an extensive exchange of fluid and solutes between the subarachnoid space and the brain interstitium, involving preferential pathways along blood vessels. We studied the anatomical relations between brain vasculature, cerebrospinal fluid compartments, and paravascular spaces in male Wistar rats. A fluorescent tracer was infused into the cisterna magna, without affecting intracranial pressure. Tracer distribution was analyzed using a 3D imaging cryomicrotome, confocal microscopy, and correlative light and electron microscopy. We found a strong 3D colocalization of tracer with major arteries and veins in the subarachnoid space and large cisterns, attributed to relatively large subarachnoid space volumes around the vessels. Confocal imaging confirmed this colocalization and also revealed novel cisternal connections between the subarachnoid space and ventricles. Unlike the vessels in the subarachnoid space, penetrating arteries but not veins were surrounded by tracer. Correlative light and electron microscopy images indicated that this paravascular space was located outside of the endothelial layer in capillaries and just outside of the smooth muscle cells in arteries. In conclusion, the cerebrospinal fluid compartment, consisting of the subarachnoid space, cisterns, ventricles, and para-arteriolar spaces, forms a continuous and extensive network that surrounds and penetrates the rat brain, in which mixing may facilitate exchange between interstitial fluid and cerebrospinal fluid.

Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion.

PubMed

Liu, Yanqun; Tang, Guanghui; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

2014-09-05

Current studies demonstrated that metformin is not only a hypoglycemic drug, but also a neuro-protective agent. However, the effect of metformin during ischemic brain injury is unclear. The aim of the present study is to explore the effect of metformin during ischemic brain injury. Adult male CD1 mice underwent 90min transient middle cerebral artery occlusion. Metformin (200mg/kg) was given at the time of reperfusion daily until sacrifice. Results showed that metformin treatment significantly reduced ischemia-induced brain atrophy volume compared to the control (p<0.05). Immunostaining results showed that the microvessel density in the peri-focal region of metformin treated mice was greatly increased compared to the control (p<0.05). Similarly, the numbers of BrdU+/DCX+ and nestin+ cells in the subventricular zone were increased in metformin treated mice compared to the control (p<0.05). Furthermore, we demonstrated that metformin treatment activated AMPK signaling pathway and promoted eNOS phosphorylation. Thus, we concluded that metformin promoted focal angiogenesis and neurogenesis and attenuated ischemia-induced brain injury in mice after middle cerebral artery occlusion, suggesting that metformin is a potential new drug for ischemic stroke therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Separation of input function for rapid measurement of quantitative CMRO2 and CBF in a single PET scan with a dual tracer administration method

NASA Astrophysics Data System (ADS)

Kudomi, Nobuyuki; Watabe, Hiroshi; Hayashi, Takuya; Iida, Hidehiro

2007-04-01

Cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF) and cerebral blood flow (CBF) images can be quantified using positron emission tomography (PET) by administrating 15O-labelled water (H152O) and oxygen (15O2). Conventionally, those images are measured with separate scans for three tracers C15O for CBV, H152O for CBF and 15O2 for CMRO2, and there are additional waiting times between the scans in order to minimize the influence of the radioactivity from the previous tracers, which results in a relatively long study period. We have proposed a dual tracer autoradiographic (DARG) approach (Kudomi et al 2005), which enabled us to measure CBF, OEF and CMRO2 rapidly by sequentially administrating H152O and 15O2 within a short time. Because quantitative CBF and CMRO2 values are sensitive to arterial input function, it is necessary to obtain accurate input function and a drawback of this approach is to require separation of the measured arterial blood time-activity curve (TAC) into pure water and oxygen input functions under the existence of residual radioactivity from the first injected tracer. For this separation, frequent manual sampling was required. The present paper describes two calculation methods: namely a linear and a model-based method, to separate the measured arterial TAC into its water and oxygen components. In order to validate these methods, we first generated a blood TAC for the DARG approach by combining the water and oxygen input functions obtained in a series of PET studies on normal human subjects. The combined data were then separated into water and oxygen components by the present methods. CBF and CMRO2 were calculated using those separated input functions and tissue TAC. The quantitative accuracy in the CBF and CMRO2 values by the DARG approach did not exceed the acceptable range, i.e., errors in those values were within 5%, when the area under the curve in the input function of the second tracer was larger than half of the first one. Bias and deviation in those values were also compatible to that of the conventional method, when noise was imposed on the arterial TAC. We concluded that the present calculation based methods could be of use for quantitatively calculating CBF and CMRO2 with the DARG approach.

Whole-Brain Mapping of Direct Inputs to and Axonal Projections from GABAergic Neurons in the Parafacial Zone.

PubMed

Su, Yun-Ting; Gu, Meng-Yang; Chu, Xi; Feng, Xiang; Yu, Yan-Qin

2018-06-01

The GABAergic neurons in the parafacial zone (PZ) play an important role in sleep-wake regulation and have been identified as part of a sleep-promoting center in the brainstem, but the long-range connections mediating this function remain poorly characterized. Here, we performed whole-brain mapping of both the inputs and outputs of the GABAergic neurons in the PZ of the mouse brain. We used the modified rabies virus EnvA-ΔG-DsRed combined with a Cre/loxP gene-expression strategy to map the direct monosynaptic inputs to the GABAergic neurons in the PZ, and found that they receive inputs mainly from the hypothalamic area, zona incerta, and parasubthalamic nucleus in the hypothalamus; the substantia nigra, pars reticulata and deep mesencephalic nucleus in the midbrain; and the intermediate reticular nucleus and medial vestibular nucleus (parvocellular part) in the pons and medulla. We also mapped the axonal projections of the PZ GABAergic neurons with adeno-associated virus, and defined the reciprocal connections of the PZ GABAergic neurons with their input and output nuclei. The newly-found inputs and outputs of the PZ were also listed compared with the literature. This cell-type-specific neuronal whole-brain mapping of the PZ GABAergic neurons may reveal the circuits underlying various functions such as sleep-wake regulation.

MRI evaluation of frequent complications after intra-arterial transplantation of mesenchymal stem cells in rats

NASA Astrophysics Data System (ADS)

Namestnikova, D.; Gubskiy, I.; Gabashvili, A.; Sukhinich, K.; Melnikov, P.; Vishnevskiy, D.; Soloveva, A.; Vitushev, E.; Chekhonin, V.; Gubsky, L.; Yarygin, K.

2017-08-01

Intra-arterial transplantation of mesenchymal stem cells (MSCs) is an effective delivery route for treatment of ischemic brain injury. Despite significant therapeutic effects and targeted cells delivery to the brain infraction, serious adverse events such as cerebral embolism have been reported and may restrict potential clinical applications of this method. In current study, we evaluate potential complications of intra-arterial MSCs administration and determine the optimum parameters for cell transplantation. We injected SPIO-labeled human MSCs via internal carotid artery with different infusion parameters and cell dose in intact rats and in rats with the middle cerebral occlusion stroke model. Cerebrovascular complications and labeled cells were visualized in vivo using MRI. We have shown that the incidence of cerebral embolic events depends on such parameters as cell dose, infusion rate and maintenance of blood flow in the internal carotid artery (ICA). Optimal parameters were considered to be 5×105 hMSC in 1 ml of PBS by syringe pump with velocity 100 μ/min and maintenance of blood flow in the ICA. Obtained data should be considered before planning experiments in rats and, potentially, can help in planning clinical trials in stroke patients.

Systematization, distribution and territory of the middle cerebral artery on the brain surface in chinchilla (Chinchilla lanigera).

PubMed

De Araujo, A C P; Campos, R

2009-02-01

The aim of the present study was to analyse thirty chinchilla (Chinchilla lanigera) brains, injected with latex, and to systematize and describe the distribution and the vascularization territories of the middle cerebral artery. This long vessel, after it has originated from the terminal branch of the basilar artery, formed the following collateral branches: rostral, caudal and striated (perforating) central branches. After crossing the lateral rhinal sulcus, the middle cerebral artery emitted a sequence of rostral and caudal convex hemispheric cortical collateral branches on the convex surface of the cerebral hemisphere to the frontal, parietal, temporal and occipital lobes. Among the rostral convex hemispheric branches, a trunk was observed, which reached the frontal and parietal lobes and, in a few cases, the occipital lobe. The vascular territory of the chinchilla's middle cerebral artery included, in the cerebral hemisphere basis, the lateral cerebral fossa, the caudal third of the olfactory trigone, the rostral two-thirds of the piriform lobe, the lateral olfactory tract, and most of the convex surface of the cerebral hemisphere, except for a strip between the cerebral longitudinal fissure and the vallecula, which extended from the rostral to the caudal poles bordering the cerebral transverse fissure.

Bringing physiology into PET of the liver.

PubMed

Keiding, Susanne

2012-03-01

Several physiologic features make interpretation of PET studies of liver physiology an exciting challenge. As with other organs, hepatic tracer kinetics using PET is quantified by dynamic recording of the liver after the administration of a radioactive tracer, with measurements of time-activity curves in the blood supply. However, the liver receives blood from both the portal vein and the hepatic artery, with the peak of the portal vein time-activity curve being delayed and dispersed compared with that of the hepatic artery. The use of a flow-weighted dual-input time-activity curve is of importance for the estimation of hepatic blood perfusion through initial dynamic PET recording. The portal vein is inaccessible in humans, and methods of estimating the dual-input time-activity curve without portal vein measurements are being developed. Such methods are used to estimate regional hepatic blood perfusion, for example, by means of the initial part of a dynamic (18)F-FDG PET/CT recording. Later, steady-state hepatic metabolism can be assessed using only the arterial input, provided that neither the tracer nor its metabolites are irreversibly trapped in the prehepatic splanchnic area within the acquisition period. This is used in studies of regulation of hepatic metabolism of, for example, (18)F-FDG and (11)C-palmitate.

Possible role of brain stem respiratory neurons in mediating vomiting during space motion sickness

NASA Technical Reports Server (NTRS)

Miller, A. D.; Tan, L. K.

1987-01-01

The object of this study was to determine if brain stem expiratory neurons control abdominal muscle activity during vomiting. The activity of 27 ventral respiratory group expiratory neurons, which are known to be of primary importance for control of abdominal muscle activity during respiration, was recorded. It is concluded that abdominal muscle activity during vomiting must be controlled not only by some brain stem expiratory neurons but also by other input(s).

Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice

PubMed Central

Trueba-Sáiz, A; Cavada, C; Fernandez, A M; Leon, T; González, D A; Fortea Ormaechea, J; Lleó, A; Del Ser, T; Nuñez, A; Torres-Aleman, I

2013-01-01

Circulating insulin-like growth factor I (IGF-I) enters the brain and promotes clearance of amyloid peptides known to accumulate in Alzheimer's disease (AD) brains. Both patients and mouse models of AD show decreased level of circulating IGF-I enter the brain as evidenced by a lower ratio of cerebrospinal fluid/plasma IGF-I. Importantly, in presymptomatic AD mice this reduction is already manifested as a decreased brain input of serum IGF-I in response to environmental enrichment. To explore a potential diagnostic use of this early loss of IGF-I input, we monitored electrocorticogram (ECG) responses to systemic IGF-I in mice. Whereas control mice showed enhanced ECG activity after IGF-I, presymptomatic AD mice showed blunted ECG responses. Because nonhuman primates showed identically enhanced electroencephalogram (EEG) activity in response to systemic IGF-I, loss of the EEG signature of serum IGF-I may be exploited as a disease biomarker in AD patients. PMID:24301648

ConnectViz: Accelerated Approach for Brain Structural Connectivity Using Delaunay Triangulation.

PubMed

Adeshina, A M; Hashim, R

2016-03-01

Stroke is a cardiovascular disease with high mortality and long-term disability in the world. Normal functioning of the brain is dependent on the adequate supply of oxygen and nutrients to the brain complex network through the blood vessels. Stroke, occasionally a hemorrhagic stroke, ischemia or other blood vessel dysfunctions can affect patients during a cerebrovascular incident. Structurally, the left and the right carotid arteries, and the right and the left vertebral arteries are responsible for supplying blood to the brain, scalp and the face. However, a number of impairment in the function of the frontal lobes may occur as a result of any decrease in the flow of the blood through one of the internal carotid arteries. Such impairment commonly results in numbness, weakness or paralysis. Recently, the concepts of brain's wiring representation, the connectome, was introduced. However, construction and visualization of such brain network requires tremendous computation. Consequently, previously proposed approaches have been identified with common problems of high memory consumption and slow execution. Furthermore, interactivity in the previously proposed frameworks for brain network is also an outstanding issue. This study proposes an accelerated approach for brain connectomic visualization based on graph theory paradigm using compute unified device architecture, extending the previously proposed SurLens Visualization and computer aided hepatocellular carcinoma frameworks. The accelerated brain structural connectivity framework was evaluated with stripped brain datasets from the Department of Surgery, University of North Carolina, Chapel Hill, USA. Significantly, our proposed framework is able to generate and extract points and edges of datasets, displays nodes and edges in the datasets in form of a network and clearly maps data volume to the corresponding brain surface. Moreover, with the framework, surfaces of the dataset were simultaneously displayed with the nodes and the edges. The framework is very efficient in providing greater interactivity as a way of representing the nodes and the edges intuitively, all achieved at a considerably interactive speed for instantaneous mapping of the datasets' features. Uniquely, the connectomic algorithm performed remarkably fast with normal hardware requirement specifications.

ConnectViz: Accelerated approach for brain structural connectivity using Delaunay triangulation.

PubMed

Adeshina, A M; Hashim, R

2015-02-06

Stroke is a cardiovascular disease with high mortality and long-term disability in the world. Normal functioning of the brain is dependent on the adequate supply of oxygen and nutrients to the brain complex network through the blood vessels. Stroke, occasionally a hemorrhagic stroke, ischemia or other blood vessel dysfunctions can affect patients during a cerebrovascular incident. Structurally, the left and the right carotid arteries, and the right and the left vertebral arteries are responsible for supplying blood to the brain, scalp and the face. However, a number of impairment in the function of the frontal lobes may occur as a result of any decrease in the flow of the blood through one of the internal carotid arteries. Such impairment commonly results in numbness, weakness or paralysis. Recently, the concepts of brain's wiring representation, the connectome, was introduced. However, construction and visualization of such brain network requires tremendous computation. Consequently, previously proposed approaches have been identified with common problems of high memory consumption and slow execution. Furthermore, interactivity in the previously proposed frameworks for brain network is also an outstanding issue. This study proposes an accelerated approach for brain connectomic visualization based on graph theory paradigm using Compute Unified Device Architecture (CUDA), extending the previously proposed SurLens Visualization and Computer Aided Hepatocellular Carcinoma (CAHECA) frameworks. The accelerated brain structural connectivity framework was evaluated with stripped brain datasets from the Department of Surgery, University of North Carolina, Chapel Hill, United States. Significantly, our proposed framework is able to generates and extracts points and edges of datasets, displays nodes and edges in the datasets in form of a network and clearly maps data volume to the corresponding brain surface. Moreover, with the framework, surfaces of the dataset were simultaneously displayed with the nodes and the edges. The framework is very efficient in providing greater interactivity as a way of representing the nodes and the edges intuitively, all achieved at a considerably interactive speed for instantaneous mapping of the datasets' features. Uniquely, the connectomic algorithm performed remarkably fast with normal hardware requirement specifications.

Cognitive Outcome following Unilateral Arterial Ischaemic Stroke in Childhood: Effects of Age at Stroke and Lesion Location

ERIC Educational Resources Information Center

Westmacott, Robyn; Askalan, Rand; MacGregor, Daune; Anderson, Peter; deVeber, Gabrielle

2010-01-01

Aim: Plasticity in the developing brain is a controversial issue. Although language and motor function often recover remarkably well following early brain injury, recent evidence suggests that damage to the developing brain results in significant long-term neuropsychological impairment. Our aim was to investigate the relationship among age at…

Material properties of rat middle cerebral arteries at high strain rates.

PubMed

Bell, E David; Converse, Matthew; Mao, Haojie; Unnikrishnan, Ginu; Reifman, Jaques; Monson, Kenneth L

2018-03-19

Traumatic brain injury (TBI), resulting from either impact- or non-impact blast-related mechanisms, is a devastating cause of death and disability. The cerebral blood vessels, which provide critical support for brain tissue in both health and disease, are commonly injured in TBI. However, little is known about how vessels respond to traumatic loading, particularly at rates relevant to blast. To better understand vessel responses to trauma, the objective of this project was to characterize the high-rate response of passive cerebral arteries. Rat middle cerebral arteries were isolated and subjected to high-rate deformation in the axial direction. Vessels were perfused at physiological pressures and stretched to failure at strain rates ranging from approximately 100 to 1300 s-1. Although both in vivo stiffness and failure stress increased significantly with strain rate, failure stretch did not depend on rate.

Bessel beam OCM for analysis of global ischemia in mouse brain

NASA Astrophysics Data System (ADS)

Rapolu, Mounika; Dolezyczek, Hubert; Tamborski, Szymon; Malinowska, Monika; Wilczynski, Grzegorz; Szkulmowski, Maciej; Wojtkowski, Maciej

2017-07-01

We present the in-vivo imaging of the global mouse brain ischemia using Bessel beam optical coherence microscopy. This method allows to monitor changes in brain structure with extra control of blood flow during the process of artery occlusion. The results show the capability and sensitivity of OCM system with Bessel beam to analyze brain plasticity after severe injury within a period of 8 days.

Beta-thalassemia intermedia associated with moyamoya syndrome.

PubMed

Göksel, Basak Karakurum; Ozdogu, Hakan; Yildirim, Tulin; Oğuzkurt, Levent; Asma, Suheyl

2010-07-01

Moyamoya syndrome (MMS) is a progressive disorder. We report a 19-year-old boy with beta-thalassemia who presented with a left hemiparesis. Brain MRI showed old middle cerebral artery and left frontal subcortical white matter infarcts. Brain magnetic resonance angiography and digital subtraction angiography revealed occlusion of the bilateral internal carotid arteries with a rich network of basal collateral vessels. To our knowledge this is the third report of beta-thalassemia intermedia and MMS, and the first report of a patient in Turkey. It emphasizes the potential for cerebral infarct due to anemia, protein S and thrombocytosis.

Automated construction of arterial and venous trees in retinal images.

PubMed

Hu, Qiao; Abràmoff, Michael D; Garvin, Mona K

2015-10-01

While many approaches exist to segment retinal vessels in fundus photographs, only a limited number focus on the construction and disambiguation of arterial and venous trees. Previous approaches are local and/or greedy in nature, making them susceptible to errors or limiting their applicability to large vessels. We propose a more global framework to generate arteriovenous trees in retinal images, given a vessel segmentation. In particular, our approach consists of three stages. The first stage is to generate an overconnected vessel network, named the vessel potential connectivity map (VPCM), consisting of vessel segments and the potential connectivity between them. The second stage is to disambiguate the VPCM into multiple anatomical trees, using a graph-based metaheuristic algorithm. The third stage is to classify these trees into arterial or venous (A/V) trees. We evaluated our approach with a ground truth built based on a public database, showing a pixel-wise classification accuracy of 88.15% using a manual vessel segmentation as input, and 86.11% using an automatic vessel segmentation as input.

Effect of Progressive Heart Failure on Cerebral Hemodynamics and Monoamine Metabolism in CNS.

PubMed

Mamalyga, M L; Mamalyga, L M

2017-07-01

Compensated and decompensated heart failure are characterized by different associations of disorders in the brain and heart. In compensated heart failure, the blood flow in the common carotid and basilar arteries does not change. Exacerbation of heart failure leads to severe decompensation and is accompanied by a decrease in blood flow in the carotid and basilar arteries. Changes in monoamine content occurring in the brain at different stages of heart failure are determined by various factors. The functional exercise test showed unequal monoamine-synthesizing capacities of the brain in compensated and decompensated heart failure. Reduced capacity of the monoaminergic systems in decompensated heart failure probably leads to overstrain of the central regulatory mechanisms, their gradual exhaustion, and failure of the compensatory mechanisms, which contributes to progression of heart failure.

The cerebral arterial circle (circulus arteriosus cerebri): an anatomical study in fetus and infant samples.

PubMed

Ardakani, Shahab Kamali; Dadmehr, Majid; Nejat, Farideh; Ansari, Saeed; Eftekhar, Behzad; Tajik, Parvin; El Khashab, Mostafa; Yazdani, Shahrooz; Ghodsi, Mohammad; Mahjoub, Fatemeh; Monajemzadeh, Maryam; Nazparvar, Bashir; Abdi-Rad, Afshin

2008-01-01

Many studies have investigated the variations in the anatomy of each segment of the cerebral arterial circle while a few have addressed the variations of the cerebral arterial circle as a whole. Thirty brains of recently deceased Iranian infants and fetuses were dissected. The dissection process was filmed and digitized so as to be readily available for further studies. The variations of the circle as a whole and segmental variations were evaluated. Variants with uni- and bilateral hypoplasia of posterior communicating arteries (PcoAs) were the most common in our study, similar to previous works. No aplasia of the precommunicating part of the anterior cerebral artery (A1), the precommunicating part of the posterior cerebral artery (P1) and anterior communicating artery was seen. Hypoplasia of the right and left PcoA was observed in 8 and 5 cases, respectively. Aplasia of the right PcoA was found in 16.6% and of the left PcoA in 3.3%. In this study, we confirmed the previously described finding that the symmetrical, circular configuration of the circulus arteriosus cerebri is present in only about 42.1%. The main differences between the fetal and adult disposition are the diameter of the PcoA and the circular part of the posterior cerebral artery. According to previous studies, the fetal brain older than 4 months has anatomical characteristics very similar to the adult's circle; our finding was mostly similar to adult samples as most samples were from infants, not fetuses. (c) 2008 S. Karger AG, Basel.

Endothelial Mineralocorticoid Receptor Mediates Parenchymal Arteriole and Posterior Cerebral Artery Remodeling During Angiotensin II-Induced Hypertension.

PubMed

Diaz-Otero, Janice M; Fisher, Courtney; Downs, Kelsey; Moss, M Elizabeth; Jaffe, Iris Z; Jackson, William F; Dorrance, Anne M

2017-12-01

The brain is highly susceptible to injury caused by hypertension because the increased blood pressure causes artery remodeling that can limit cerebral perfusion. Mineralocorticoid receptor (MR) antagonism prevents hypertensive cerebral artery remodeling, but the vascular cell types involved have not been defined. In the periphery, the endothelial MR mediates hypertension-induced vascular injury, but cerebral and peripheral arteries are anatomically distinct; thus, these findings cannot be extrapolated to the brain. The parenchymal arterioles determine cerebrovascular resistance. Determining the effects of hypertension and MR signaling on these arterioles could lead to a better understanding of cerebral small vessel disease. We hypothesized that endothelial MR signaling mediates inward cerebral artery remodeling and reduced cerebral perfusion during angiotensin II (AngII) hypertension. The biomechanics of the parenchymal arterioles and posterior cerebral arteries were studied in male C57Bl/6 and endothelial cell-specific MR knockout mice and their appropriate controls using pressure myography. AngII increased plasma aldosterone and decreased cerebral perfusion in C57Bl/6 and MR-intact littermates. Endothelial cell MR deletion improved cerebral perfusion in AngII-treated mice. AngII hypertension resulted in inward hypotrophic remodeling; this was prevented by MR antagonism and endothelial MR deletion. Our studies suggest that endothelial cell MR mediates hypertensive remodeling in the cerebral microcirculation and large pial arteries. AngII-induced inward remodeling of cerebral arteries and arterioles was associated with a reduction in cerebral perfusion that could worsen the outcome of stroke or contribute to vascular dementia. © 2017 American Heart Association, Inc.

Endogenous angiotensin affects responses to stimulation of baroreceptor afferent nerves.

PubMed

DiBona, Gerald F; Jones, Susan Y

2003-08-01

To study effects of endogenous angiotensin II on responses to standardized stimulation of afferent neural input into the central portion of the arterial and cardiac baroreflexes. Different dietary sodium intakes were used to physiologically alter endogenous angiotensin II activity. Candesartan, an angiotensin II type 1 receptor antagonist, was used to assess dependency of observed effects on angiotensin II stimulation of angiotensin II type 1 receptors. Electrical stimulation of arterial and cardiac baroreflex afferent nerves was used to provide a standardized input to the central portion of the arterial and cardiac baroreflexes. In anesthetized rats in balance on low, normal and high dietary sodium intake, arterial pressure, heart rate and renal sympathetic nerve activity responses to electrical stimulation of vagus and aortic depressor nerves were determined. Compared with plasma renin activity values in normal dietary sodium intake rats, those from low dietary sodium intake rats were higher and those from high dietary sodium intake rats were lower. During vagus nerve stimulation, the heart rate, arterial pressure and renal sympathetic nerve activity responses were similar in all three dietary sodium intake groups. During aortic depressor nerve stimulation, the heart rate and arterial pressure responses were similar in all three dietary sodium intake groups. However, the renal sympathetic nerve activity response was significantly greater in the low sodium group than in the normal and high sodium group at 4, 8 and 16 Hz. Candesartan administered to low dietary sodium intake rats had no effect on the heart rate and arterial pressure responses to either vagus or aortic depressor nerve stimulation but increased the magnitude of the renal sympathoinhibitory responses. Increased endogenous angiotensin II in rats on a low dietary sodium intake attenuates the renal sympathoinhibitory response to activation of the cardiac and sinoaortic baroreflexes by standardized vagus and aortic depressor nerve stimulation, respectively.

Systematization, description, and territory of the caudal cerebral artery in surface of the brain of the ostrich (Struthio camelus).

PubMed

Nazer, Manoel; Campos, Rui

2014-08-01

Brain specimens from 30 ostriches were injected with red-dyed latex via the internal carotid arteries, and the caudal cerebral arteries and their branches were systematically described. On the right side, the caudal cerebral artery was double-, triple-, quadruple-, and single-branched in 73.5%, 23.3%, 3.3%, and 3.3% of cases, respectively; on the left side, it was double-, triple-, quadruple-, and single-branched in 76.7%, 20%, 3.3%, and 3.3% of cases, respectively. The dorsal tectal mesencephalic artery appeared as a single vessel in 96.7% of cases, emerging as a collateral branch of the caudal cerebral artery. The dorsal mesencephalic tectal artery originated from the right dorsal cerebellar artery in 40% of cases and from the left side in 63.3% of cases. On the right side, there were four and three medial occipital hemispheric branches in 46.7% and 20% of cases, respectively; on the left side, there were four and three branches in 30% and 26.7% of cases. On the right side, the pineal artery was double-, single-, triple-, and quadruple-branched in 50%, 23.3%, 20%, and 6.7% of cases, respectively; on the left side, this artery was double-, single-, triple-, and quadruple-branched in 50%, 23.3%, 16.7%, and 10% of cases, respectively. The diencephalic artery was on the right side in 43.3% of cases and on the left side in 56.7% of cases. The interhemispheric artery was on the right side in 56.7% of cases and on the left side in 43.3% of cases; four, three, two, five, and one dorsal hemispheric trunks branched off of the interhemispheric artery in 40%, 40%, 10%, 6.7%, and 26.7% of cases, respectively. The caudal cerebral artery was classified as Type I in 56.7% of cases (subtype IA in 33.3% of cases and IB in 23.3% of cases), Type II in 40% of cases (subtype IIA in 20% of cases and IIB in 20% of cases), and Type III in 3.3% of cases. Copyright © 2014 Wiley Periodicals, Inc.

Intra-Arterial Delivery of AAV Vectors to the Mouse Brain After Mannitol Mediated Blood Brain Barrier Disruption

PubMed Central

Santillan, Alejandro; Sondhi, Dolan; Dyke, Jonathan P.; Crystal, Ronald G.; Gobin, Y. Pierre; Ballon, Douglas J.

2014-01-01

The delivery of therapeutics to neural tissue is greatly hindered by the blood brain barrier (BBB). Direct local delivery via diffusive release from degradable implants or direct intra-cerebral injection can bypass the BBB and obtain high concentrations of the therapeutic in the targeted tissue, however the total volume of tissue that can be treated using these techniques is limited. One treatment modality that can potentially access large volumes of neural tissue in a single treatment is intra-arterial (IA) injection after osmotic blood brain barrier disruption. In this technique, the therapeutic of interest is injected directly into the arteries that feed the target tissue after the blood brain barrier has been disrupted by exposure to a hyperosmolar mannitol solution, permitting the transluminal transport of the therapy. In this work we used contrast enhanced magnetic resonance imaging (MRI) studies of IA injections in mice to establish parameters that allow for extensive and reproducible BBB disruption. We found that the volume but not the flow rate of the mannitol injection has a significant effect on the degree of disruption. To determine whether the degree of disruption we observed with this method was sufficient for delivery of nanoscale therapeutics, we performed IA injections of an adeno-associated viral vector containing the CLN2 gene (AAVrh.10CLN2), which is mutated in the lysosomal storage disorder Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL). We demonstrated that IA injection of AAVrh.10CLN2 after BBB disruption can achieve widespread transgene production in the mouse brain after a single administration. Further, we showed that there exists a minimum threshold of BBB disruption necessary to permit the AAV.rh10 vector to pass into the brain parenchyma from the vascular system. These results suggest that IA administration may be used to obtain widespread delivery of nanoscale therapeutics throughout the murine brain after a single administration. PMID:25270115

[Assessment of blood flow in the middle cerebral artery and the umbilical artery in fetuses with umbilical venous pulsations].

PubMed

Borowski, Dariusz; Czuba, Bartosz; Kaczmarek, Piotr; Włoch, Agata; Pawłowicz, Paweł; Wyrwas, Dorota; Wielgos, Mirosław; Sodowski, Krzysztof; Szaflik, Krzysztof

2006-03-01

Umbilical venous pulsation is an important sign of hemodynamic compromise, especially during fetal heart failure and asphyxia. The aim of this study was to determine of the blow flow in the middle cerebral artery and the umbilical artery in fetuses with umbilical venous pulsations. The investigation included 18 fetuses with signs of the intrauterine growth restriction and umbilical venous pulsations after 28th weeks of gestation. We evaluated cerebral-placental ratio (CPR) and pulsation index (PI) in the middle cerebral artery (MCA) and the umbilical artery (UA). We observed brain sparring effect in all cases of analyzing fetuses. There were 77,8% of abnormal flow pattern in umbilical artery. 13 fetuses had a single pulsation pattern in umbilical vein and another 5 had double pulsation pattern. The coexistence of umbilical vein pulsation and abnormal flow pattern in umbilical artery is closely related to increased perinatal mortality.

Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle

PubMed Central

Hartman, William; Helan, Martin; Smelter, Dan; Sathish, Venkatachalem; Thompson, Michael; Pabelick, Christina M.; Johnson, Bruce; Prakash, Y. S.

2015-01-01

Background Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs). Methods and Results 48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1α inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia. Conclusions Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia-induced pulmonary vascular diseases, and thus a potential target for therapy. PMID:26192455

Incidental occlusion of anterior spinal artery due to Onyx reflux in embolization of spinal type II arteriovenous malformation.

PubMed

Kim, Joohyun; Lee, Jang-Bo; Cho, Tai-Hyoung; Hur, Junseok W

2017-05-01

Onyx embolization is one of the standard treatments for brain arteriovenous malformations (AVMs) and is a promising method for spinal AVMs as well. Its advantages have been emphasized, and few complications have been reported with Onyx embolization in spinal AVMs. Here, we report an incidental anterior spinal artery (ASA) occlusion due to Onyx reflux during embolization of a spinal type II AVM. A 15-year-old boy presented with weakness in both upper and lower extremities. Magnetic resonance imaging and spinal angiogram revealed a spinal type II AVM with two feeders including the right vertebral artery (VA) and the right deep cervical artery. Onyx embolization was performed gradually from the VA to the deep cervical artery and an unexpected Onyx reflux to the ASA was observed during the latter stage deep cervical artery embolization. Post-operative quadriplegia and low cranial nerves (CN) dysfunction were observed. Rehabilitation treatment was performed and the patient showed marked improvement of neurologic deterioration at 1-year follow-up. Onyx is an effective treatment choice for spinal AVMs. However, due to the small vasculature of the spine compared to the brain, the nidus is rapidly packed with a small amount of Onyx, which allows Onyx reflux to unexpected vessels. Extreme caution is required and dual-lumen balloon catheter could be considered for Onyx embolization in spinal AVMs treatment.

[Frequency and characteristics of strokes involving the perforating arteries in the Department of Neurology at the Befelatanana General Hospital, Antananarivo].

PubMed

Rasaholiarison, Nomena Finiavana; Randrianasolo, Rahamefy Odilon; Rajaonarison, Lala Andriamasinavalona; Rakotomanana, Jenny Larissa; Razafimahefa, Julien; Tehindrazanarivelo, Alain Djacoba

2017-01-01

Strokes of the perforating arteries are mainly arteriolopathies. They result in dementia and stroke recurrence. This study aimed to evaluate the frequency and characteristics of these strokes to better prevent these complications. We conducted a descriptive, retrospective study in the department of neurology at the Befelatanana general hospital, Antananarivo over the period 01 March-25 September 2015. All patients with abrupt neurological deficit and deep brain involvement on brain scanner were included in the study. The features of strokes involving the perforating arteries were collected. Data were processed with SPSS 20 software. Out of 172 patients with a stroke, 83(48.25%) had stroke involving the perforating arteries. Stroke involving the perforating arteries affected young people (65.06%) aged less than 65 years and preferentially the male population (61.44%). Haemorrhagic forms accounted for 67.46%. Thirty-one patients (37.34%) had stroke recurrences and, among them, almost a quarter had 2 recurrences (38.70%) in less than a year. All patients with recurrence had dysexecutive disorder (p < 0.0001) and poor antihypertensive medication adherence. Mortality accounted for only 6.02% in patients with onset of these strokes during hospitalization. Specific neurologic follow-up is necessary after a first stroke involving perforating arteries in order to make an early diagnosis of dementia and to prevent recurrences.

No effect of ablation of surfactant protein-D on acute cerebral infarction in mice.

PubMed

Lambertsen, Kate L; Østergaard, Kamilla; Clausen, Bettina H; Hansen, Søren; Stenvang, Jan; Thorsen, Stine B; Meldgaard, Michael; Kristensen, Bjarne W; Hansen, Pernille B; Sorensen, Grith L; Finsen, Bente

2014-07-19

Crosstalk between the immune system in the brain and the periphery may contribute to the long-term outcome both in experimental and clinical stroke. Although, the immune defense collectin surfactant protein-D (SP-D) is best known for its role in pulmonary innate immunity, SP-D is also known to be involved in extrapulmonary modulation of inflammation in mice. We investigated whether SP-D affected cerebral ischemic infarction and ischemia-induced inflammatory responses in mice. The effect of SP-D was studied by comparing the size of ischemic infarction and the inflammatory and astroglial responses in SP-D knock out (KO) and wild type (WT) mice subjected to permanent middle cerebral artery occlusion. SP-D mRNA production was assessed in isolated cerebral arteries and in the whole brain by PCR, and SP-D protein in normal appearing and ischemic human brain by immunohistochemistry. Changes in plasma SP-D and TNF were assessed by ELISA and proximity ligation assay, respectively. Infarct volumetric analysis showed that ablation of SP-D had no effect on ischemic infarction one and five days after induction of ischemia. Further, ablation of SP-D had no effect on the ischemia-induced increase in TNF mRNA production one day after induction of ischemia; however the TNF response to the ischemic insult was affected at five days. SP-D mRNA was not detected in parenchymal brain cells in either naïve mice or in mice subjected to focal cerebral ischemia. However, SP-D mRNA was detected in middle cerebral artery cells in WT mice and SP-D protein in vascular cells both in normal appearing and ischemic human brain tissue. Measurements of the levels of SP-D and TNF in plasma in mice suggested that levels were unaffected by the ischemic insult. Microglial-leukocyte and astroglial responses were comparable in SP-D KO and WT mice. SP-D synthesis in middle cerebral artery cells is consistent with SP-D conceivably leaking into the infarcted area and affecting local cytokine production. However, there was no SP-D synthesis in parenchymal brain cells and ablation of SP-D had no effect on ischemic cerebral infarction.

CO2 microbubble contrast enhancement in x-ray angiography.

PubMed

Kariya, S; Komemushi, A; Nakatani, M; Yoshida, R; Sawada, S; Tanigawa, N

2013-04-01

To demonstrate that carbon dioxide (CO2) microbubble contrast enhancement depicts blood vessels when used for x-ray examinations. Microbubbles were generated by cavitation of physiological saline to which CO2 gas had been added using an ejector-type microbubble generator. The input pressure values for CO2 gas and physiological saline that produced a large quantity of CO2 microbubbles were obtained in a phantom. In an animal study, angiography was performed in three swine using three types of contrast: CO2 microbubbles, conventional CO2 gas, and iodinated contrast medium. For CO2 microbubble contrast enhancement, physiological saline, and CO2 gas were supplied at the input pressures calculated in the phantom experiment. Regions of interest were set in the abdominal aorta, external iliac arteries, and background. The difference in digital values between each artery and the background was calculated. The input pressures obtained in the phantom experiment were 0.16 MPa for physiological saline and 0.5 MPa for CO2 gas, with physiological saline input volume being 8.1 ml/s. Three interventional radiologists all evaluated the depictions of all arteries as "present" in the CO2 microbubble contrast enhancement, conventional CO2 contrast enhancement, and iodinated contrast enhancement performed in three swine. Digital values for all vessels with microbubble CO2 contrast enhancement were higher than background values. In x-ray angiography, blood vessels can be depicted by CO2 microbubble contrast enhancement, in which a large quantity of CO2 microbubbles is generated within blood vessels. Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Principles of cerebral hemodynamics when intracranial pressure is raised: lessons from the peripheral circulation

PubMed Central

Kim, Mi Ok; Adji, Audrey; O’Rourke, Michael F.; Avolio, Alberto P.; Smielewski, Peter; Pickard, John D.; Czosnyka, Marek

2015-01-01

Background: The brain is highly vascular and richly perfused, and dependent on continuous flow for normal function. Although confined within the skull, pressure within the brain is usually less than 15 mmHg, and shows small pulsations related to arterial pulse under normal circumstances. Pulsatile arterial hemodynamics in the brain have been studied before, but are still inadequately understood, especially during changes of intracranial pressure (ICP) after head injury. Method: In seeking cohesive explanations, we measured ICP and radial artery pressure (RAP) invasively with high-fidelity manometer systems, together with middle cerebral artery flow velocity (MCAFV) (transcranial Doppler) and central aortic pressure (CAP) generated from RAP, using a generalized transfer function technique, in eight young unconscious, ventilated adults following closed head trauma. We focused on vascular effects of spontaneous rises of ICP (‘plateau waves’). Results: A rise in mean ICP from 29 to 53 mmHg caused no consistent change in pressure outside the cranium, or in heart rate, but ICP pulsations increased in amplitude from 8 to 20 mmHg, and ICP waveform came to resemble that in the aorta. Cerebral perfusion pressure (=central aortic pressure – ICP), which equates with transmural pressure, fell from 61 to 36 mmHg. Mean MCAFV fell from 53 to 40 cm/s, whereas pulsatile MCAFV increased from 77 to 98 cm/s. These significant changes (all P < 0.01) may be explained using the Monro–Kellie doctrine, because of compression of the brain, as occurs in a limb when external pressure is applied. Conclusion: The findings emphasize importance of reducing ICP, when raised, and on the additional benefits of reducing wave reflection from the lower body. PMID:25764046

Application of a time-resolved optical brain imager for monitoring cerebral oxygenation during carotid surgery.

PubMed

Kacprzak, Michal; Liebert, Adam; Staszkiewicz, Walerian; Gabrusiewicz, Andrzej; Sawosz, Piotr; Madycki, Grzegorz; Maniewski, Roman

2012-01-01

Recent studies have shown that time-resolved optical measurements of the head can estimate changes in the absorption coefficient with depth discrimination. Thus, changes in tissue oxygenation, which are specific to intracranial tissues, can be assessed using this advanced technique, and this method allows us to avoid the influence of changes to extracerebral tissue oxygenation on the measured signals. We report the results of time-resolved optical imaging that was carried out during carotid endarterectomy. This surgery remains the "gold standard" treatment for carotid stenosis, and intraoperative brain oxygenation monitoring may improve the safety of this procedure. A time-resolved optical imager was utilized within the operating theater. This instrument allows for the simultaneous acquisition of 32 distributions of the time-of-flight of photons at two wavelengths on both hemispheres. Analysis of the statistical moments of the measured distributions of the time-of-flight of photons was applied for estimating changes in the absorption coefficient as a function of depth. Time courses of changes in oxy- and deoxyhemoglobin of the extra- and intracerebral compartments during cross-clamping of the carotid arteries were obtained. A decrease in the oxyhemoglobin concentration and an increase in the deoxyhemoglobin concentrations were observed in a large area of the head. Large changes were observed in the hemisphere ipsilateral to the site of clamped carotid arteries. Smaller amplitude changes were noted at the contralateral site. We also found that changes in the hemoglobin signals, as estimated from intracerebral tissue, are very sensitive to clamping of the internal carotid artery, whereas its sensitivity to clamping of the external carotid artery is limited. We concluded that intraoperative multichannel measurements allow for imaging of brain tissue hemodynamics. However, when monitoring the brain during carotid surgery, a single-channel measurement may be sufficient.

[Spinal manipulative therapy and cervical artery dissections].

PubMed

Saxler, G; Schopphoff, E; Quitmann, H; Quint, U

2005-06-01

Severe complications after cervical spine manipulation are rare. As experts for medical treatment errors, we received between July 2002 and February 2004 cases with serious complications in the central nervous system after manipulation. 5 vertebral artery dissections with subsequent brain infarction were registered. In all cases, the patients showed complete persisting remission of symptoms. In addition, a kinematic estimation model was developed to study the possible causes of vertebral artery damage. We were able to demonstrate that material extension is dependent on cervical rotation and the "free length" of the vertebral artery in the upper cervical spine.

Bilateral Medial Medullary Infarction with Nondominant Vertebral Artery Occlusion.

PubMed

Zhang, Lei; Zhang, Gui-lian; Du, Ju-mei; Ma, Zhu-lin

2015-09-01

Bilateral medial medullary infarction (MMI) is a rare stroke subtype. Here, we report a case with bilateral MMI caused by nondominant vertebral artery occlusion confirmed by brain digital subtraction angiography and magnetic resonance imaging basi-parallel-anatomical-scanning. We highlight that anterior spinal arteries could originate from a unilateral vertebral artery (VA). Radiologists and neurologists should pay attention to the nondominant VA as bilateral MMI may be induced by occlusion of nondominant VA that supplies the bilateral anteromedial territories of the medulla. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. 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.

A novel non-contrast-enhanced MRA using silent scan for evaluation of brain arteriovenous malformation: A case report and review of literature.

PubMed

Moon, Jin Il; Baek, Hye Jin; Ryu, Kyeong Hwa; Park, Hyun

2017-11-01

Brain arteriovenous malformations (AVMs) are congenital vascular abnormalities involving abnormal connections between arteries and veins. In clinical practice, imaging studies help evaluate feeding arteries, niduses, draining venous systems, and coexisting complications in patients with brain AVM. They also have an impact on decision-making regarding clinical management. We applied a novel non-contrast-enhanced MR angiography (MRA) technique, termed "silent MRA," for evaluating an incidental brain AVM. Here, we describe the clinical case with radiological review and highlight the technical background and clinical usefulness of silent MRA. A 60-year-old woman underwent neuroimaging study including MRA to evaluate intracranial cause of headache. The brain AVM, including its nidus and draining veins, was conspicuously delineated on silent MRA images; these findings correlated well with conventional angiographic findings. The patient did not receive interventional or surgical treatment. The patient is being followed up regularly at the outpatient department. The silent MRA can be a suitable imaging modality for repeated follow-up evaluation for not only brain AVMs but also various intracranial vascular diseases without the use of contrast materials.

Vasopressin responses to unloading arterial baroreceptors during cardiac nerve blockade in conscious dogs

NASA Technical Reports Server (NTRS)

O'Donnell, C. P.; Keil, L. C.; Thrasher, T. N.

1992-01-01

We examined the relative contributions of afferent input from the heart and from arterial baroreceptors in the stimulation of arginine vasopressin (AVP) secretion in response to hypotension caused by thoracic inferior vena caval constriction (TIVCC). Afferent input from cardiac receptors was reversibly blocked by infusing 2% procaine into the pericardial space to anesthetize the cardiac nerves. Acute cardiac nerve blockade (CNB) alone caused a rise in mean arterial pressure (MAP) of 24 +/- 3 mmHg but no change in plasma AVP. If the rise in MAP was prevented by TIVCC, plasma AVP increased by 39 +/- 15 pg/ml, and if MAP was allowed to increase and then was forced back to control by TIVCC, plasma AVP increased by 34 +/- 15 pg/ml. Thus the rise in MAP during CNB stimulated arterial baroreceptors, which in turn compensated for the loss of inhibitory input from cardiac receptors on AVP secretion. These results indicate that the maximum secretory response resulting from complete unloading of cardiac receptors at a normal MAP results in a mean increase in plasma AVP of 39 pg/ml in this group of dogs. When MAP was reduced 25% below control levels (from 95 +/- 5 to 69 +/- 3 mmHg) by TIVCC during pericardial saline infusion, plasma AVP increased by 79 +/- 42 pg/ml. However, the same degree of hypotension during CNB (MAP was reduced from 120 +/- 5 to 71 +/- 3 mmHg) led to a greater (P less than 0.05) increase in plasma AVP of 130 +/- 33 pg/ml. Because completely unloading cardiac receptors can account for an increase of only 39 pg/ml on average in this group of dogs, the remainder of the increase in plasma AVP must be due to other sources of stimulation. We suggest that the principal stimulus to AVP secretion after acute CNB in these studies arises from unloading the arterial baroreceptors.

MRI-based noninvasive measurement of intracranial compliance derived from the relationship between transcranial blood and cerebrospinal fluid flows: modeling vs. direct approach

NASA Astrophysics Data System (ADS)

Tain, Rong-Wen; Alperin, Noam

2008-03-01

Intracranial compliance (ICC) determines the ability of the intracranial space to accommodate increase in volume (e.g., brain swelling) without a large increase in intracranial pressure (ICP). Therefore, measurement of ICC is potentially important for diagnosis and guiding treatment of related neurological problems. Modeling based approach uses an assumed lumped-parameter model of the craniospinal system (CSS) (e.g., RCL circuit), with either the arterial or the net transcranial blood flow (arterial inflow minus venous outflow) as input and the cranio-spinal cerebrospinal fluid (CSF) flow as output. The phase difference between the output and input is then often used as a measure of ICC However, it is not clear whether there is a predetermined relationship between ICC and the phase difference between these waveforms. A different approach for estimation of ICC has been recently proposed. This approach estimates ICC from the ratio of the intracranial volume and pressure changes that occur naturally with each heartbeat. The current study evaluates the sensitivity of the phase-based and the direct approach to changes in ICC. An RLC circuit model of the cranio-spinal system is used to simulate the cranio-spinal CSF flow for 3 different ICC states using the transcranial blood flows measured by MRI phase contrast from healthy human subjects. The effect of the increase in the ICC on the magnitude and phase response is calculated from the system's transfer function. We observed that within the heart rate frequency range, changes in ICC predominantly affected the amplitude of CSF pulsation and less so the phases. The compliance is then obtained for the different ICC states using the direct approach. The measures of compliance calculated using the direct approach demonstrated the highest sensitivity for changes in ICC. This work explains why phase shift based measure of ICC is less sensitive than amplitude based measures such as the direct approach method.

Arterial Spin Labeling (ASL) fMRI: advantages, theoretical constrains, and experimental challenges in neurosciences.

PubMed

Borogovac, Ajna; Asllani, Iris

2012-01-01

Cerebral blood flow (CBF) is a well-established correlate of brain function and therefore an essential parameter for studying the brain at both normal and diseased states. Arterial spin labeling (ASL) is a noninvasive fMRI technique that uses arterial water as an endogenous tracer to measure CBF. ASL provides reliable absolute quantification of CBF with higher spatial and temporal resolution than other techniques. And yet, the routine application of ASL has been somewhat limited. In this review, we start by highlighting theoretical complexities and technical challenges of ASL fMRI for basic and clinical research. While underscoring the main advantages of ASL versus other techniques such as BOLD, we also expound on inherent challenges and confounds in ASL perfusion imaging. In closing, we expound on several exciting developments in the field that we believe will make ASL reach its full potential in neuroscience research.

Cerebrovascular aspects of converting-enzyme inhibition II: Blood-brain barrier permeability and effect of intracerebroventricular administration of captopril.

PubMed

Jarden, J O; Barry, D I; Juhler, M; Graham, D I; Strandgaard, S; Paulson, O B

1984-12-01

The blood-brain barrier permeability to captopril, and the cerebrovascular effects of intracerebroventricular administration of captopril, were studied in normotensive Wistar rats. The blood-brain barrier permeability-surface area product (PS), determined by an integral-uptake method, was about 1 X 10(-5) cm3/g/s in all brain regions studied. This was three to four times lower than the simultaneously determined PS of Na+ and Cl-, both of which are known to have very low blood-brain barrier permeability. Cerebral blood flow, determined by the intra-arterial 133xenon injection method, was unaffected by intracerebroventricular administration of 100 micrograms captopril. Furthermore the lower limit of cerebral blood flow autoregulation during haemorrhagic hypotension was also unaffected, being in the mean arterial pressure range (50-69 mmHg) in both controls and captopril-treated rats. It was concluded that the blood-brain barrier permeability of captopril was negligible and that inhibition of the brain renin-angiotensin system has no effect on global cerebral blood flow. The cerebrovascular effects of intravenously administered captopril (a resetting to lower pressure of the limits and range of cerebral blood flow autoregulation) are probably exerted via converting enzyme on the luminal surface of cerebral vessels.

PAMAM Dendrimers Cross the Blood-Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice.

PubMed

Srinageshwar, Bhairavi; Peruzzaro, Sarah; Andrews, Melissa; Johnson, Kayla; Hietpas, Allison; Clark, Brittany; McGuire, Crystal; Petersen, Eric; Kippe, Jordyn; Stewart, Andrew; Lossia, Olivia; Al-Gharaibeh, Abeer; Antcliff, Aaron; Culver, Rebecca; Swanson, Douglas; Dunbar, Gary; Sharma, Ajit; Rossignol, Julien

2017-03-14

Drug delivery into the central nervous system (CNS) is challenging due to the blood-brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH₂ and G4-NH₂) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders.

Effect of contrast leakage on the detection of abnormal brain tumor vasculature in high-grade glioma.

PubMed

LaViolette, Peter S; Daun, Mitchell K; Paulson, Eric S; Schmainda, Kathleen M

2014-02-01

Abnormal brain tumor vasculature has recently been highlighted by a dynamic susceptibility contrast (DSC) MRI processing technique. The technique uses independent component analysis (ICA) to separate arterial and venous perfusion. The overlap of the two, i.e. arterio-venous overlap or AVOL, preferentially occurs in brain tumors and predicts response to anti-angiogenic therapy. The effects of contrast agent leakage on the AVOL biomarker have yet to be established. DSC was acquired during two separate contrast boluses in ten patients undergoing clinical imaging for brain tumor diagnosis. Three components were modeled with ICA, which included the arterial and venous components. The percentage of each component as well as a third component were determined within contrast enhancing tumor and compared. AVOL within enhancing tumor was also compared between doses. The percentage of enhancing tumor classified as not arterial or venous and instead into a third component with contrast agent leakage apparent in the time-series was significantly greater for the first contrast dose compared to the second. The amount of AVOL detected within enhancing tumor was also significantly greater with the second dose compared to the first. Contrast leakage results in large signal variance classified as a separate component by the ICA algorithm. The use of a second dose mitigates the effect and allows measurement of AVOL within enhancement.

BOLD delay times using group delay in sickle cell disease

NASA Astrophysics Data System (ADS)

Coloigner, Julie; Vu, Chau; Bush, Adam; Borzage, Matt; Rajagopalan, Vidya; Lepore, Natasha; Wood, John

2016-03-01

Sickle cell disease (SCD) is an inherited blood disorder that effects red blood cells, which can lead to vasoocclusion, ischemia and infarct. This disease often results in neurological damage and strokes, leading to morbidity and mortality. Functional Magnetic Resonance Imaging (fMRI) is a non-invasive technique for measuring and mapping the brain activity. Blood Oxygenation Level-Dependent (BOLD) signals contain also information about the neurovascular coupling, vascular reactivity, oxygenation and blood propagation. Temporal relationship between BOLD fluctuations in different parts of the brain provides also a mean to investigate the blood delay information. We used the induced desaturation as a label to profile transit times through different brain areas, reflecting oxygen utilization of tissue. In this study, we aimed to compare blood flow propagation delay times between these patients and healthy subjects in areas vascularized by anterior, middle and posterior cerebral arteries. In a group comparison analysis with control subjects, BOLD changes in these areas were found to be almost simultaneous and shorter in the SCD patients, because of their increased brain blood flow. Secondly, the analysis of a patient with a stenosis on the anterior cerebral artery indicated that signal of the area vascularized by this artery lagged the MCA signal. These findings suggest that sickle cell disease causes blood propagation modifications, and that these changes could be used as a biomarker of vascular damage.

Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease.

PubMed

Peng, Weiguo; Achariyar, Thiyagarajan M; Li, Baoman; Liao, Yonghong; Mestre, Humberto; Hitomi, Emi; Regan, Sean; Kasper, Tristan; Peng, Sisi; Ding, Fengfei; Benveniste, Helene; Nedergaard, Maiken; Deane, Rashid

2016-09-01

Glymphatic transport, defined as cerebrospinal fluid (CSF) peri-arterial inflow into brain, and interstitial fluid (ISF) clearance, is reduced in the aging brain. However, it is unclear whether glymphatic transport affects the distribution of soluble Aβ in Alzheimer's disease (AD). In wild type mice, we show that Aβ40 (fluorescently labeled Aβ40 or unlabeled Aβ40), was distributed from CSF to brain, via the peri-arterial space, and associated with neurons. In contrast, Aβ42 was mostly restricted to the peri-arterial space due mainly to its greater propensity to oligomerize when compared to Aβ40. Interestingly, pretreatment with Aβ40 in the CSF, but not Aβ42, reduced CSF transport into brain. In APP/PS1 mice, a model of AD, with and without extensive amyloid-β deposits, glymphatic transport was reduced, due to the accumulation of toxic Aβ species, such as soluble oligomers. CSF-derived Aβ40 co-localizes with existing endogenous vascular and parenchymal amyloid-β plaques, and thus, may contribute to the progression of both cerebral amyloid angiopathy and parenchymal Aβ accumulation. Importantly, glymphatic failure preceded significant amyloid-β deposits, and thus, may be an early biomarker of AD. By extension, restoring glymphatic inflow and ISF clearance are potential therapeutic targets to slow the onset and progression of AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Arterial injuries after penetrating brain injury in civilians: risk factors on admission head computed tomography.

PubMed

Bodanapally, Uttam K; Saksobhavivat, Nitima; Shanmuganathan, Kathirkamanathan; Aarabi, Bizhan; Roy, Ashis K

2015-01-01

The object of this study was to determine the specific CT findings of the injury profile in penetrating brain injury (PBI) that are risk factors related to intracranial arterial injuries. The authors retrospectively evaluated admission head CTs and accompanying digital subtraction angiography (DSA) studies from patients with penetrating trauma to the head in the period between January 2005 and December 2012. Two authors reviewed the CT images to determine the presence or absence of 30 injury profile variables and quantified selected variables. The CT characteristics in patients with and without arterial injuries were compared using univariate analysis, multivariate analysis, and receiver operating characteristic (ROC) curve analysis to determine the respective risk factors, independent predictors, and optimal threshold values for the continuous variables. Fifty-five patients were eligible for study inclusion. The risk factors for an intracranial arterial injury on univariate analysis were an entry wound over the frontobasal-temporal regions, a bihemispheric wound trajectory, a wound trajectory in proximity to the circle of Willis (COW), a subarachnoid hemorrhage (SAH), a higher SAH score, an intraventricular hemorrhage (IVH), and a higher IVH score. A trajectory in proximity to the COW was the best predictor of injury (OR 6.8 and p = 0.005 for all penetrating brain injuries [PBIs]; OR 13.3 and p = 0.001 for gunshot wounds [GSWs]). Significant quantitative variables were higher SAH and IVH scores. An SAH score of 3 (area under the ROC curve [AUC] for all PBIs 0.72; AUC for GSWs 0.71) and an IVH score of 3 (AUC for all PBIs 0.65; AUC for GSWs 0.65) could be used as threshold values to suggest an arterial injury. The risk factors identified may help radiologists suggest the possibility of arterial injury and prioritize neurointerventional consultation and potential DSA studies.

[Correlations of pharmacokinetics and pharmacodynamics of a combined preparation containing pyrrolidone and pyroglutamic acid].

PubMed

Sariev, A K; Lun'shina, E V; Zherdev, V P; Mirzoian, N R

2006-01-01

Experiments showed that a new drug composition containing pyrrolidone and pyroglutamic acid exhibits a significant cerebrovascular effect upon peroral administration in rats. The pharmacokinetics of pyrrolidone monitored upon its combined administration with pyroglutamic acid shows that this drug, as a component of the composition, is characterized by a high absolute bioavailability and permeability trough the blood-brain barrier. The presence of pyroglutamic acid slows down the absorption and elimination of pyrrolidone and enhances its distribution in the organs and tissues. There is a correlation between the concentration of pyrrolidone in the brain, on the one hand, and the levels of cerebral microcirculation and arterial pressure on the other hand. An increase in the concentration of pyrrolidone in the brain is accompanied by more intensive cerebral blood flow and by a decrease in the arterial pressure.

Occlusion of carotid artery and hypergravity loading of animals caused similar effects on L-[14C]glutamate uptake in rat brain nerve terminals

NASA Astrophysics Data System (ADS)

Borisova, Tatiana; Sivko, Roman; Krisanova, Natalia

Changes in sodium-dependent L-[14C]glutamate uptake in rat brain nerve terminals was com-paratively analysed after hypergravity loading of animals (centrifugation of rats in special con-tainers at 10 G for 1 hour) and unilateral occlusion of carotid artery (20 min). The initial velocity of L-[14C]glutamate uptake was decreased from 2.5 ± 0.2 nmol x min-1 x mg-1 of proteins to 2.05 ± 0.1 nmol x min-1 x mg-1 of proteins after hypergravity and after occlusion -up to 2.25 ± 0.1 nmol x min-1 x mg-1 of proteins. Recently, we have shown that a decrease in L-[14C]glutamate uptake was at least partially caused by the redaction in the membrane potential of nerve terminals and the proton gradient of synaptic vesicles. These parameters were analysed after unilateral occlusion of carotid artery, where one brain hemisphere was used as a control, whereas the second one as subjected to ischemic/hypoxic conditions. Similarly with hypergravity, we revealed a decrease in the membrane potential of nerve terminals by ˜ 10 % and a reduction of the proton gradient of synaptic vesicles by ˜ 5 % after occlusion of carotid artery. Thus, a decrease in the activity of glutamate transporters after hypergrav-ity and unilateral occlusion of carotid artery was at least partially caused by changes in the membrane potential of nerve terminals and the proton gradient of synaptic vesicles. This fact may be considered in support of the suggestion that ischemia/hypoxia was a main unspecific stressor, which caused the alterations in glutamatergic neurotransmission under conditions of hypergravity.

Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: a potential mechanism for fetal neuroprotection.

PubMed

Zlotnik, Alexander; Tsesis, Svetlana; Gruenbaum, Benjamin Fredrick; Ohayon, Sharon; Gruenbaum, Shaun Evan; Boyko, Matthew; Sheiner, Eyal; Brotfain, Evgeny; Shapira, Yoram; Teichberg, Vivian Itzhak

2012-09-01

Excess glutamate in the brain is thought to be implicated in the pathophysiology of fetal anoxic brain injury, yet little is known about the mechanisms by which glutamate is regulated in the fetal brain. This study examines whether there are differences between maternal and fetal glutamate concentrations, and whether a correlation between them exists. 10 ml of venous blood was extracted from 87 full-term (>37 weeks gestation) pregnant women in active labor. Immediately after delivery of the neonate, 10 ml of blood from the umbilical artery and vein was extracted. Samples were analyzed for levels of glutamate, glutamate-oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT). Fetal blood glutamate concentrations in both the umbilical artery and vein were found to be significantly higher than maternal blood (p<0.001). Similarly, fetal serum GOT levels in the umbilical artery and vein were found to be significantly higher than maternal GOT levels (p<0.001). The difference in GPT levels between maternal and fetal serum was not statistically significant. There was no difference in fetal glutamate, GOT or GPT between the umbilical artery and vein. There was an association observed between glutamate levels in maternal blood and glutamate levels in both venous (R=0.32, p<0.01) and arterial (R=0.33, p<0.05) fetal blood. This study demonstrated that higher baseline concentrations of blood glutamate are present in fetal blood compared with maternal blood, and this was associated with elevated GOT, but not GPT levels. An association was observed between maternal and fetal blood glutamate levels. Copyright © 2012 Elsevier Ltd. All rights reserved.

Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

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

Feng, Tao; Tsui, Benjamin M. W.; Li, Xin

Purpose: The radioligand {sup 11}C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of {sup 11}C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method inmore » pigs with the goal of translation into human studies. Methods: The experimental animals were injected with [{sup 11}C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function. Results: In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent phase of the ID-IF. The combined use of FBP and OS-EM resulted in reduced bias and noise. After performing all the necessary corrections, the areas under the curves (AUCs) of the AD-IF were close to that of the AD-IF (average AUC ratio =1 ± 0.08) during the early phase. When applied in a two-tissue-compartmental kinetic model, the average difference between the estimated model parameters from ID-IF and AD-IF was 10% which was within the error of the estimation method. Conclusions: The bias of radioligand concentration in the aorta from the OS-EM image reconstruction is significantly affected by radioligand uptake in the adjacent kidney and cannot be neglected for quantitative evaluation. With careful calibrations and corrections, the ID-IF derived from quantitative dynamic PET images can be used as the input function of the compartmental model to quantify the renal kinetics of {sup 11}C-KR31173 in experimental animals and the authors intend to evaluate this method in future human studies.« less

Marfan syndrome presenting with headache and coincidental ophthalmic artery aneurysm.

PubMed

Vandersteen, Anthony Martin; Kenny, Joanna; Khan, Naheed L; Male, Alison

2013-03-15

A 24-year-old Ugandan woman was referred for a neurology opinion after complaining of a year long history of right-sided retro-orbital stabbing pain. Brain imaging revealed a coincidental 3 mm left ophthalmic artery aneurysm. Marfanoid habitus was noted; after further investigations she was diagnosed with mild aortic root dilatation, subtle lens dislocation and Marfan syndrome. Her symptoms were secondary to temporomandibular joint dysfunction, an under-recognised complication of Marfan syndrome. Her ophthalmic artery aneurysm is likely to be a coincidental finding.

Release of serum S-100β protein and neuron-specific enolase after off-pump coronary artery bypass grafting with and without intracranial and cervical artery stenosis.

PubMed

Tamura, Atsushi; Imamaki, Mizuho; Shimura, Hitoshi; Niitsuma, Yuriko; Miyazaki, Masaru

2011-01-01

The aim of this study was to quantify the amount of brain damage suffered by patients who underwent off-pump coronary artery bypass grafting (OPCAB) in which S-100β protein and neuron-specific enolase were used. Thirty-four patients undergoing scheduled OPCAB were enrolled in the study. The patients were divided into two groups according to the results of their magnetic resonance angiography (MRA) and cervical ultrasonography: 13 patients had cervical or intracranial arterial stenosis (Group A), and 21 patients did not (Group B). Blood samples were collected from the arterial catheters immediately before surgery, upon arrival to the intensive care unit, and 6 and 24 hours after surgery. In blood samples collected from patients upon arrival to the intensive care unit, the maximum concentration of serum s-100β protein in Group A was significantly higher than that of Group B (p = 0.029). Though patients in Group A tended to have higher maximum neuron-specific enolase (NSE) concentrations, there were no significant differences in NSE concentrations at any point between the two groups. Our findings show a correlation between the stenosis detected by MRA or cervical ultrasonography and brain damage after OPCAB.

Validation of an arterial tortuosity measure with application to hypertension collection of clinical hypertensive patients

PubMed Central

2011-01-01

Background Hypertension may increase tortuosity or twistedness of arteries. We applied a centerline extraction algorithm and tortuosity metric to magnetic resonance angiography (MRA) brain images to quantitatively measure the tortuosity of arterial vessel centerlines. The most commonly used arterial tortuosity measure is the distance factor metric (DFM). This study tested a DFM based measurement’s ability to detect increases in arterial tortuosity of hypertensives using existing images. Existing images presented challenges such as different resolutions which may affect the tortuosity measurement, different depths of the area imaged, and different artifacts of imaging that require filtering. Methods The stability and accuracy of alternative centerline algorithms was validated in numerically generated models and test brain MRA data. Existing images were gathered from previous studies and clinical medical systems by manually reading electronic medical records to identify hypertensives and negatives. Images of different resolutions were interpolated to similar resolutions. Arterial tortuosity in MRA images was measured from a DFM curve and tested on numerically generated models as well as MRA images from two hypertensive and three negative control populations. Comparisons were made between different resolutions, different filters, hypertensives versus negatives, and different negative controls. Results In tests using numerical models of a simple helix, the measured tortuosity increased as expected with more tightly coiled helices. Interpolation reduced resolution-dependent differences in measured tortuosity. The Korean hypertensive population had significantly higher arterial tortuosity than its corresponding negative control population across multiple arteries. In addition one negative control population of different ethnicity had significantly less arterial tortuosity than the other two. Conclusions Tortuosity can be compared between images of different resolutions by interpolating from lower to higher resolutions. Use of a universal negative control was not possible in this study. The method described here detected elevated arterial tortuosity in a hypertensive population compared to the negative control population and can be used to study this relation in other populations. PMID:22166145

Validation of an arterial tortuosity measure with application to hypertension collection of clinical hypertensive patients.

PubMed

Diedrich, Karl T; Roberts, John A; Schmidt, Richard H; Kang, Chang-Ki; Cho, Zang-Hee; Parker, Dennis L

2011-10-18

Hypertension may increase tortuosity or twistedness of arteries. We applied a centerline extraction algorithm and tortuosity metric to magnetic resonance angiography (MRA) brain images to quantitatively measure the tortuosity of arterial vessel centerlines. The most commonly used arterial tortuosity measure is the distance factor metric (DFM). This study tested a DFM based measurement's ability to detect increases in arterial tortuosity of hypertensives using existing images. Existing images presented challenges such as different resolutions which may affect the tortuosity measurement, different depths of the area imaged, and different artifacts of imaging that require filtering. The stability and accuracy of alternative centerline algorithms was validated in numerically generated models and test brain MRA data. Existing images were gathered from previous studies and clinical medical systems by manually reading electronic medical records to identify hypertensives and negatives. Images of different resolutions were interpolated to similar resolutions. Arterial tortuosity in MRA images was measured from a DFM curve and tested on numerically generated models as well as MRA images from two hypertensive and three negative control populations. Comparisons were made between different resolutions, different filters, hypertensives versus negatives, and different negative controls. In tests using numerical models of a simple helix, the measured tortuosity increased as expected with more tightly coiled helices. Interpolation reduced resolution-dependent differences in measured tortuosity. The Korean hypertensive population had significantly higher arterial tortuosity than its corresponding negative control population across multiple arteries. In addition one negative control population of different ethnicity had significantly less arterial tortuosity than the other two. Tortuosity can be compared between images of different resolutions by interpolating from lower to higher resolutions. Use of a universal negative control was not possible in this study. The method described here detected elevated arterial tortuosity in a hypertensive population compared to the negative control population and can be used to study this relation in other populations.

Individual variability of cerebral autoregulation, posterior cerebral circulation and white matter hyperintensity.

PubMed

Liu, Jie; Tseng, Benjamin Y; Khan, Muhammad Ayaz; Tarumi, Takashi; Hill, Candace; Mirshams, Niki; Hodics, Timea M; Hynan, Linda S; Zhang, Rong

2016-06-01

Cerebral autoregulation (CA) is a key mechanism to protect brain perfusion in the face of changes in arterial blood pressure, but little is known about individual variability of CA and its relationship to the presence of brain white matter hyperintensity (WMH) in older adults, a type of white matter lesion related to cerebral small vessel disease (SVD). This study demonstrated the presence of large individual variability of CA in healthy older adults during vasoactive drug-induced changes in arterial pressure assessed at the internal carotid and vertebral arteries. We also observed, unexpectedly, that it was the 'over-' rather than the 'less-reactive' CA measured at the vertebral artery that was associated with WMH severity. These findings challenge the traditional concept of CA and suggest that the presence of cerebral SVD, manifested as WMH, is associated with posterior brain hypoperfusion during acute increase in arterial pressure. This study measured the individual variability of static cerebral autoregulation (CA) and determined its associations with brain white matter hyperintensity (WMH) in older adults. Twenty-seven healthy older adults (13 females, 66 ± 6 years) underwent assessment of CA during steady-state changes in mean arterial pressure (MAP) induced by intravenous infusion of sodium nitroprusside (SNP) and phenylephrine. Cerebral blood flow (CBF) was measured using colour-coded duplex ultrasonography at the internal carotid (ICA) and vertebral arteries (VA). CA was quantified by a linear regression slope (CA slope) between percentage changes in cerebrovascular resistance (CVR = MAP/CBF) and MAP relative to baseline values. Periventricular and deep WMH volumes were measured with T2-weighted magnetic resonance imaging. MAP was reduced by -11 ± 7% during SNP, and increased by 21 ± 8% during phenylephrine infusion. CA demonstrated large individual variability with the CA slopes ranging from 0.37 to 2.20 at the ICA and from 0.17 to 3.18 at the VA; no differences in CA were found between the ICA and VA. CA slopes measured at the VA had positive correlations with the total and periventricular WMH volume (r = 0.55 and 0.59, P < 0.01). Collectively, these findings demonstrated the presence of large individual variability of CA in older adults, and that, when measured in the posterior cerebral circulation, it is the higher rather than lower CA reactivity that is associated with WMH severity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Modeling the circle of Willis to assess the effect of anatomical variations on the development of unilateral internal carotid artery stenosis.

PubMed

Zhang, Chi; Wang, Ling; Li, Xiaoyun; Li, Shuyu; Pu, Fang; Fan, Yubo; Li, Deyu

2014-01-01

Circle of Willis (CoW) plays a significant role in maintaining the blood supply for the brain. Specifically, when the stenosis occurs in the internal carotid artery (ICA), abnormal structures of CoW would decrease the compensatory capacity, leading to the local insufficiency of cerebral blood supply. The present paper built a series of lumped parameter models for CoW, and simulated the blood redistribution caused by the unilateral ICA stenosis with different severities in cerebral arteries in the normal and abnormal CoW respectively. The results showed that when unilateral ICA stenosis occurred, the collateral circulation was built through the anterior communicating artery and the ipsilateral posterior communicating artery, maintaining the flow in cerebral arteries. The absence of the two communicating arteries would cause an obvious decrease of flow in local cerebral arteries in the anterior circulation. In conclusion, the two arteries play a significant role in maintaining the balance of cerebral blood supply in the development of ICA stenosis.

Age differences in arterial and venous extra-cerebral blood flow in healthy adults: contributions of vascular risk factors and genetic variants.

PubMed

Raz, Naftali; Daugherty, Ana M; Sethi, Sean K; Arshad, Muzamil; Haacke, E Mark

2017-08-01

Sufficient cerebral blood flow (CBF) and venous drainage are critical for normal brain function, and their alterations can affect brain aging. However, to date, most studies focused on arterial CBF (inflow) with little attention paid to the age differences in venous outflow. We measured extra-cerebral arterial and venous blood flow rates with phase-contrast MRI and assessed the influence of vascular risk factors and genetic polymorphisms (ACE insertion/deletion, COMT val158met, and APOEε4) in 73 adults (age 18-74 years). Advanced age, elevated vascular risk, ACE Deletion, and COMT met alleles were linked to lower in- and outflow, with no effects of APOE ε4 noted. Lower age-related CBF rate was unrelated to brain volume and was observed only in val homozygotes of COMTval158met. Thus, in a disease-free population, age differences in CBF may be notable only in persons with high vascular risk and carriers of genetic variants associated with vasoconstriction and lower dopamine availability. It remains to be established if treatments targeting alleviation of the mutable factors can improve the course of cerebrovascular aging in spite of the immutable genetic influence.

Measurement of brain perfusion in newborns: Pulsed arterial spin labeling (PASL) versus pseudo-continuous arterial spin labeling (pCASL)

PubMed Central

Boudes, Elodie; Gilbert, Guillaume; Leppert, Ilana Ruth; Tan, Xianming; Pike, G. Bruce; Saint-Martin, Christine; Wintermark, Pia

2014-01-01

Background Arterial spin labeling (ASL) perfusion-weighted imaging (PWI) by magnetic resonance imaging (MRI) has been shown to be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not therapeutic hypothermia was administered. However, this technique has been only rarely used in newborns until now, because of the challenges to obtain sufficient signal-to-noise ratio (SNR) and spatial resolution in newborns. Objective To compare two methods of ASL-PWI (i.e., single inversion-time pulsed arterial spin labeling [single TI PASL], and pseudo-continuous arterial spin labeling [pCASL]) to assess brain perfusion in asphyxiated newborns treated with therapeutic hypothermia and in healthy newborns. Design/methods We conducted a prospective cohort study of term asphyxiated newborns meeting the criteria for therapeutic hypothermia; four additional healthy term newborns were also included as controls. Each of the enrolled newborns was scanned at least once during the first month of life. Each MRI scan included conventional anatomical imaging, as well as PASL and pCASL PWI-MRI. Control and labeled images were registered separately to reduce the effect of motion artifacts. For each scan, the axial slice at the level of the basal ganglia was used for comparisons. Each scan was scored for its image quality. Quantification of whole-slice cerebral blood flow (CBF) was done afterwards using previously described formulas. Results A total number of 61 concomitant PASL and pCASL scans were obtained in nineteen asphyxiated newborns treated with therapeutic hypothermia and four healthy newborns. After discarding the scans with very poor image quality, 75% (46/61) remained for comparison between the two ASL methods. pCASL images presented a significantly superior image quality score compared to PASL images (p < 0.0001). Strong correlation was found between the CBF measured by PASL and pCASL (r = 0.61, p < 0.0001). Conclusion This study demonstrates that both ASL methods are feasible to assess brain perfusion in healthy and sick newborns. However, pCASL might be a better choice over PASL in newborns, as pCASL perfusion maps had a superior image quality that allowed a more detailed identification of the different brain structures. PMID:25379424

Notch3 is necessary for blood vessel integrity in the central nervous system.

PubMed

Henshall, Tanya L; Keller, Annika; He, Liqun; Johansson, Bengt R; Wallgard, Elisabet; Raschperger, Elisabeth; Mäe, Maarja Andaloussi; Jin, Shaobo; Betsholtz, Christer; Lendahl, Urban

2015-02-01

Vascular smooth muscle cells (VSMC) are important for contraction, blood flow distribution, and regulation of blood vessel diameter, but to what extent they contribute to the integrity of blood vessels and blood-brain barrier function is less well understood. In this report, we explored the impact of the loss of VSMC in the Notch3(-/-) mouse on blood vessel integrity in the central nervous system. Notch3(-/-) mice showed focal disruptions of the blood-brain barrier demonstrated by extravasation of tracers accompanied by fibrin deposition in the retinal vasculature. This blood-brain barrier leakage was accompanied by a regionalized and patchy loss of VSMC, with VSMC gaps predominantly in arterial resistance vessels of larger caliber. The loss of VSMC appeared to be caused by progressive degeneration of VSMC resulting in a gradual loss of VSMC marker expression and a progressive acquisition of an aberrant VSMC phenotype closer to the gaps, followed by enhanced apoptosis and cellular disintegration in the gaps. Arterial VSMC were the only mural cell type that was morphologically affected, despite Notch3 also being expressed in pericytes. Transcriptome analysis of isolated brain microvessels revealed gene expression changes in Notch3(-/-) mice consistent with loss of arterial VSMC and presumably secondary transcriptional changes were observed in endothelial genes, which may explain the compromised vascular integrity. We demonstrate that Notch3 is important for survival of VSMC, and reveal a critical role for Notch3 and VSMC in blood vessel integrity and blood-brain barrier function in the mammalian vasculature. © 2014 American Heart Association, Inc.

Dynamical systems characterization of inertial effects of fluid flow in a curved artery model under pulsatile flow forcing

NASA Astrophysics Data System (ADS)

Leggiero, Michael; Bulusu, Kartik V.; Plesniak, Michael W.

2013-11-01

The main objective of this study was to examine inertial effects in a 180-degree model of curved arteries under pulsatile inflow conditions. Two-component, two-dimensional particle image velocimetery (2C-2D PIV) data were acquired upstream of and at several cross-sectional locations in the curved artery model. A blood-analog fluid comprised of 71% saturated sodium iodide solution, 28% glycerol and 1% distilled water (by volume) was subjected to multi-harmonic pulsatile inflow functions. First, signal time-lag was quantified by cross-correlating the input (voltage-time) supplied to a programmable pump and the output PIV (flow rate-time) measurements. The experiment was then treated as a linear, time-invariant system, and frequency response was estimated for phase shifts across a certain spectrum. Input-output signal dissimilarities were attributable to intrinsic inertial effects of flow. By coupling pressure-time and upstream flow rate-time measurements, the experiment was modeled using system identification methods. Results elucidate the role of inertial effects in fluid flow velocity measurements and the effect of these delays on secondary flow structure detection in a curved artery model. Supported by the NSF Grant No. CBET- 0828903 and GW Center for Biomimetics and Bioinspired Engineering.

Contributions of tidal lung inflation to human R-R interval and arterial pressure fluctuations

NASA Technical Reports Server (NTRS)

Koh, J.; Brown, T. E.; Beightol, L. A.; Eckberg, D. L.

1998-01-01

We studied the effects of mechanical lung inflation on respiratory frequency R-R interval and arterial pressure fluctuations in nine healthy young adults undergoing elective orthopedic surgery. We conducted this research to define the contribution of pulmonary and thoracic stretch receptor input to respiratory sinus arrhythmia. We compared fast Fourier transform spectral power during three modes of ventilation: (1) spontaneous, frequency-controlled (0.25 Hz) breathing, (2) intermittent positive pressure ventilation (0.25 Hz, with a tidal volume of 8 ml/kg) and (3) high frequency jet ventilation (5.0 Hz, 2.5 kg/cm2), after sedation and vecuronium paralysis. Mean R-R intervals, arterial pressures and arterial blood gas levels were comparable during all three breathing conditions. Respiratory frequency systolic pressure spectral power was comparable during spontaneous breathing and conventional mechanical ventilation, but was significantly reduced during high frequency jet ventilation (P < 0.05). Respiratory frequency R-R interval spectral power (used as an index of respiratory sinus arrhythmia) declined dramatically with sedation and muscle paralysis (P < 0.05), but was greater during conventional mechanical, than high frequency jet ventilation (P < 0.05). These results suggest that although phasic inputs from pulmonary and thoracic stretch receptors make a statistically significant contribution to respiratory sinus arrhythmia, that contribution is small.

Connectivity in the human brain dissociates entropy and complexity of auditory inputs.

PubMed

Nastase, Samuel A; Iacovella, Vittorio; Davis, Ben; Hasson, Uri

2015-03-01

Complex systems are described according to two central dimensions: (a) the randomness of their output, quantified via entropy; and (b) their complexity, which reflects the organization of a system's generators. Whereas some approaches hold that complexity can be reduced to uncertainty or entropy, an axiom of complexity science is that signals with very high or very low entropy are generated by relatively non-complex systems, while complex systems typically generate outputs with entropy peaking between these two extremes. In understanding their environment, individuals would benefit from coding for both input entropy and complexity; entropy indexes uncertainty and can inform probabilistic coding strategies, whereas complexity reflects a concise and abstract representation of the underlying environmental configuration, which can serve independent purposes, e.g., as a template for generalization and rapid comparisons between environments. Using functional neuroimaging, we demonstrate that, in response to passively processed auditory inputs, functional integration patterns in the human brain track both the entropy and complexity of the auditory signal. Connectivity between several brain regions scaled monotonically with input entropy, suggesting sensitivity to uncertainty, whereas connectivity between other regions tracked entropy in a convex manner consistent with sensitivity to input complexity. These findings suggest that the human brain simultaneously tracks the uncertainty of sensory data and effectively models their environmental generators. Copyright © 2014. Published by Elsevier Inc.

Trigeminal, Visceral and Vestibular Inputs May Improve Cognitive Functions by Acting through the Locus Coeruleus and the Ascending Reticular Activating System: A New Hypothesis

PubMed Central

De Cicco, Vincenzo; Tramonti Fantozzi, Maria P.; Cataldo, Enrico; Barresi, Massimo; Bruschini, Luca; Faraguna, Ugo; Manzoni, Diego

2018-01-01

It is known that sensory signals sustain the background discharge of the ascending reticular activating system (ARAS) which includes the noradrenergic locus coeruleus (LC) neurons and controls the level of attention and alertness. Moreover, LC neurons influence brain metabolic activity, gene expression and brain inflammatory processes. As a consequence of the sensory control of ARAS/LC, stimulation of a sensory channel may potential influence neuronal activity and trophic state all over the brain, supporting cognitive functions and exerting a neuroprotective action. On the other hand, an imbalance of the same input on the two sides may lead to an asymmetric hemispheric excitability, leading to an impairment in cognitive functions. Among the inputs that may drive LC neurons and ARAS, those arising from the trigeminal region, from visceral organs and, possibly, from the vestibular system seem to be particularly relevant in regulating their activity. The trigeminal, visceral and vestibular control of ARAS/LC activity may explain why these input signals: (1) affect sensorimotor and cognitive functions which are not directly related to their specific informational content; and (2) are effective in relieving the symptoms of some brain pathologies, thus prompting peripheral activation of these input systems as a complementary approach for the treatment of cognitive impairments and neurodegenerative disorders. PMID:29358907

Magnetic Resonance Imaging Measurement of Transmission of Arterial Pulsation to the Brain on Propranolol Versus Amlodipine.

PubMed

Webb, Alastair J S; Rothwell, Peter M

2016-06-01

Cerebral arterial pulsatility is associated with leukoaraiosis and depends on central arterial pulsatility and arterial stiffness. The effect of antihypertensive drugs on transmission of central arterial pulsatility to the cerebral circulation is unknown, partly because of limited methods of assessment. In a technique-development pilot study, 10 healthy volunteers were randomized to crossover treatment with amlodipine and propranolol. At baseline and on each drug, we assessed aortic (Sphygmocor) and middle cerebral artery pulsatility (TCDtranscranial ultrasound). We also performed whole-brain, 3-tesla multiband blood-oxygen level dependent magnetic resonance imaging (multiband factor 6, repetition time=0.43s), concurrent with a novel method of continuous noninvasive blood pressure monitoring. Drug effects on relationships between cardiac cycle variation in blood pressure and blood-oxygen level dependent imaging were determined (fMRI Expert Analysis Tool, fMRIB Software Library [FEAT-FSL]). Aortic pulsatility was similar on amlodipine (27.3 mm Hg) and propranolol (27.9 mm Hg, P diff=0.33), while MCA pulsatility increased nonsignificantly more from baseline on propranolol (+6%; P=0.09) than amlodipine (+1.5%; P=0.58). On magnetic resonance imaging, cardiac frequency blood pressure variations were found to be significantly more strongly associated with blood-oxygen level dependent imaging on propranolol than amlodipine. We piloted a novel method of assessment of arterial pulsatility with concurrent high-frequency blood-oxygen level dependent magnetic resonance imaging and noninvasive blood pressure monitoring. This method was able to identify greater transmission of aortic pulsation on propranolol than amlodipine, which warrants further investigation. © 2016 American Heart Association, Inc.

Assessing mental stress from the photoplethysmogram: a numerical study

PubMed Central

Charlton, Peter H; Celka, Patrick; Farukh, Bushra; Chowienczyk, Phil; Alastruey, Jordi

2018-01-01

Abstract Objective: Mental stress is detrimental to cardiovascular health, being a risk factor for coronary heart disease and a trigger for cardiac events. However, it is not currently routinely assessed. The aim of this study was to identify features of the photoplethysmogram (PPG) pulse wave which are indicative of mental stress. Approach: A numerical model of pulse wave propagation was used to simulate blood pressure signals, from which simulated PPG pulse waves were estimated using a transfer function. Pulse waves were simulated at six levels of stress by changing the model input parameters both simultaneously and individually, in accordance with haemodynamic changes associated with stress. Thirty-two feature measurements were extracted from pulse waves at three measurement sites: the brachial, radial and temporal arteries. Features which changed significantly with stress were identified using the Mann–Kendall monotonic trend test. Main results: Seventeen features exhibited significant trends with stress in measurements from at least one site. Three features showed significant trends at all three sites: the time from pulse onset to peak, the time from the dicrotic notch to pulse end, and the pulse rate. More features showed significant trends at the radial artery (15) than the brachial (8) or temporal (7) arteries. Most features were influenced by multiple input parameters. Significance: The features identified in this study could be used to monitor stress in healthcare and consumer devices. Measurements at the radial artery may provide superior performance than the brachial or temporal arteries. In vivo studies are required to confirm these observations. PMID:29658894

Carbon Dioxide Fluctuations Are Associated with Changes in Cerebral Oxygenation and Electrical Activity in Infants Born Preterm.

PubMed

Dix, Laura Marie Louise; Weeke, Lauren Carleen; de Vries, Linda Simone; Groenendaal, Floris; Baerts, Willem; van Bel, Frank; Lemmers, Petra Maria Anna

2017-08-01

To evaluate the effects of acute arterial carbon dioxide partial pressure changes on cerebral oxygenation and electrical activity in infants born preterm. This retrospective observational study included ventilated infants born preterm with acute fluctuations of continuous end-tidal CO 2 (etCO 2 ) as a surrogate marker for arterial carbon dioxide partial pressure, during the first 72 hours of life. Regional cerebral oxygen saturation and fractional tissue oxygen extraction were monitored with near-infrared spectroscopy. Brain activity was monitored with 2-channel electroencephalography. Spontaneous activity transients (SATs) rate (SATs/minute) and interval between SATs (in seconds) were calculated. Ten-minute periods were selected for analysis: before, during, and after etCO 2 fluctuations of ≥5  mm Hg. Thirty-eight patients (mean ± SD gestational age of 29 ± 1.8 weeks) were included, with 60 episodes of etCO 2 increase and 70 episodes of etCO 2 decrease. During etCO 2 increases, brain oxygenation increased (regional cerebral oxygen saturation increased, fractional tissue oxygen extraction decreased; P < .01) and electrical activity decreased (SATs/minute decreased, interval between SATs increased; P < .01). All measures recovered when etCO 2 returned to baseline. During etCO 2 decreases, brain oxygenation decreased (regional cerebral oxygen saturation decreased, fractional tissue oxygen extraction decreased; P < .01) and brain activity increased (SATs/minute increased, P < .05), also with recovery after return of etCO 2 to baseline. An acute increase in etCO 2 is associated with increased cerebral oxygenation and decreased brain activity, whereas an acute decrease is associated with decreased cerebral oxygenation and slightly increased brain activity. Combining continuous CO 2 monitoring with near-infrared spectroscopy may enable the detection of otherwise undetected fluctuations in arterial carbon dioxide partial pressure that may be harmful to the neonatal brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Validation and quantification of [18F]altanserin binding in the rat brain using blood input and reference tissue modeling

PubMed Central

Riss, Patrick J; Hong, Young T; Williamson, David; Caprioli, Daniele; Sitnikov, Sergey; Ferrari, Valentina; Sawiak, Steve J; Baron, Jean-Claude; Dalley, Jeffrey W; Fryer, Tim D; Aigbirhio, Franklin I

2011-01-01

The 5-hydroxytryptamine type 2a (5-HT2A) selective radiotracer [18F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats. Metabolite-corrected plasma input modeling was compared with reference tissue modeling using the cerebellum as reference tissue. [18F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT2A receptors. Full binding saturation and displacement was documented, and no significant uptake of radioactive metabolites was detected in the brain. Blood input as well as reference tissue models were equally appropriate to describe the radiotracer kinetics. [18F]altanserin is suitable for quantification of 5-HT2A receptor availability in rats. PMID:21750562

Epilepsy in Hemiplegic Cerebral Palsy Due to Perinatal Arterial Ischaemic Stroke

ERIC Educational Resources Information Center

Wanigasinghe, Jithangi; Reid, Susan M.; Mackay, Mark T.; Reddihough, Dinah S.; Harvey, A. Simon; Freeman, Jeremy L.

2010-01-01

Aim: The aim of this study was to describe the frequency, risk factors, manifestations, and outcome of epilepsy in children with hemiplegic cerebral palsy (CP) due to perinatal arterial ischaemic stroke (AIS). Method: The study group comprised 63 participants (41 males, 22 females) from a population-based CP register whose brain imaging showed…

Bilateral Internal Carotid Artery Occlusion, External Carotid Artery Stenosis, and Vertebral Artery Kinking: May It Be Asymptomatic?

PubMed

Fatic, Nikola; Jaffer, Usman; Ivana, Saicic; Gordana, Globarevic-Vukcevic; Markovic, Dragan; Kostic, Dusan; Davidovic, Lazar

2017-10-01

The clinical spectrum of internal carotid artery occlusion ranges from being a completely asymptomatic occlusion to a devastating stroke or death. The prevalence of asymptomatic internal carotid artery occlusion is unknown, particularly for bilateral occlusion. The distal branches of the external carotid artery anastomose with distal branches of the internal carotid artery provide important sources of collateral circulation to the brain. Stenosis of the external carotid artery with ipsilateral/bilateral internal occlusion may result in ischemic sequelae. Coiling or kinking of the vertebral artery is a rare morphological entity that is infrequently reported because it remains asymptomatic and has no clinical relevance. Currently, there is little evidence to support management strategies for this disease entity and no official recommendations for asymptomatic bilateral carotid artery occlusion. We present a case of a 62-year-old female with asymptomatic bilateral internal carotid artery occlusion, bilateral external carotid artery stenoses, and bilateral kinking of the vertebral artery at the V2 segment, who has been successfully managed conservatively for over 5 years. An individualized approach to management of patients with bilateral internal carotid artery occlusion, especially in combination with external carotid artery stenosis and elongation malformations of the vertebral artery is key to a successful strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

Simulation and assessment of cerebrovascular damage in deep brain stimulation using a stereotactic atlas of vasculature and structure derived from multiple 3- and 7-tesla scans.

PubMed

Nowinski, Wieslaw L; Chua, Beng Choon; Volkau, Ihar; Puspitasari, Fiftarina; Marchenko, Yevgen; Runge, Val M; Knopp, Michael V

2010-12-01

The most severe complication of deep brain stimulation (DBS) is intracranial hemorrhage. Detailed knowledge of the cerebrovasculature could reduce the rate of this disorder. Morphological scans typically acquired in stereotactic and functional neurosurgery (SFN) by using 1.5-T (or sometimes even 3-T) imaging units poorly depict the vasculature. Advanced angiographic imaging, including 3- and 7-T 3D time-of-flight and susceptibility weighted imaging as well as 320-slice CT angiography, depict the vessels in great detail. However, these acquisitions are not used in SFN clinical practice, and robust methods for their processing are not available yet. Therefore, the authors proposed the use of a detailed 3D stereotactic cerebrovascular atlas to assist in SFN planning and to potentially reduce DBS-induced hemorrhage. A very detailed 3D cerebrovascular atlas of arteries, veins, and dural sinuses was constructed from multiple 3- and 7-T scans. The atlas contained>900 vessels, each labeled with a name and diameter with the smallest having a 90-μm diameter. The cortical areas, ventricular system, and subcortical structures were fully segmented and labeled, including the main stereotactic target structures: subthalamic nucleus, ventral intermediate nucleus of the thalamus, and internal globus pallidus. The authors also developed a computer simulator with the embedded atlas that was able to compute the effective electrode trajectory by minimizing penetration of the cerebrovascular system and vital brain structures by a DBS electrode. The simulator provides the neurosurgeon with functions for atlas manipulation, target selection, trajectory planning and editing, 3D display and manipulation, and electrode-brain penetration calculation. This simulation demonstrated that a DBS electrode inserted in the middle frontal gyrus may intersect several arteries and veins including 1) the anteromedial frontal artery of the anterior cerebral artery as well as the prefrontal artery and the precentral sulcus artery of the middle cerebral artery (range of diameters 0.4-0.6 mm); and 2) the prefrontal, anterior caudate, and medullary veins (range of diameters 0.1-2.3 mm). This work also shows that field strength and pulse sequence have a substantial impact on vessel depiction. The numbers of 3D vascular segments are 215, 363, and 907 for 1.5-, 3-, and 7-T scans, respectively. Inserting devices into the brain during microrecording and stimulation may cause microbleeds not discernible on standard scans. A small change in the location of the DBS electrode can result in a major change for the patient. The described simulation increases the neurosurgeon's awareness of this phenomenon. The simulator enables the neurosurgeon to analyze the spatial relationships between the track and the cerebrovasculature, ventricles, subcortical structures, and cortical areas, which allows the DBS electrode to be placed more effectively, and thus potentially reducing the invasiveness of the stimulation procedure for the patient.

Osmotic blood-brain barrier disruption. Computerized tomographic monitoring of chemotherapeutic agent delivery.

PubMed Central

Neuwelt, E A; Maravilla, K R; Frenkel, E P; Rapaport, S I; Hill, S A; Barnett, P A

1979-01-01

The present study describes a canine model of transient reversible blood-brain barrier disruption with hyperosmolar mannitol infusion into the internal carotid artery. Studies in this model show that osmotic blood-brain barrier disruption before intracarotid infusion of methotrexate results in markedly elevated (therapeutic) levels of drug in the ipsilateral cerebral hemisphere. Levels in the cerebrospinal fluid correlate poorly and inconsistently with brain levels. Computerized tomograms in this canine model provide a noninvasive monitor of the degree, time-course, and localization of osmotic blood-brain barrier disruption. Images PMID:457877

Occlusion of the artery of Percheron: an unusual cause of bilateral stroke.

PubMed

Anderson, Clare; O'Brien, Richard

2012-11-19

The artery of Percheron is a rare anatomical variant whereby a single vessel arising from the proximal segment of one posterior cerebral artery supplies both medial thalami. This is a rare example of a single arterial supply to brain structures on both sides of the midline. Occlusion of the artery of Percheron results in bilateral medial thalamic infarction, which is manifest clinically as gaze paresis, cognitive disturbance and altered consciousness. The presentation can mimic subarachnoid haemorrhage, drug intoxication, encephalitis and other inflammatory or infective conditions. The presentation is similar to the 'top of the basilar syndrome' and early recognition should prompt further investigation for underlying stroke aetiologies and consideration can be given to thrombolysis if vascular occlusion can be confirmed.

Toward fully automated processing of dynamic susceptibility contrast perfusion MRI for acute ischemic cerebral stroke.

PubMed

Kim, Jinsuh; Leira, Enrique C; Callison, Richard C; Ludwig, Bryan; Moritani, Toshio; Magnotta, Vincent A; Madsen, Mark T

2010-05-01

We developed fully automated software for dynamic susceptibility contrast (DSC) MR perfusion-weighted imaging (PWI) to efficiently and reliably derive critical hemodynamic information for acute stroke treatment decisions. Brain MR PWI was performed in 80 consecutive patients with acute nonlacunar ischemic stroke within 24h after onset of symptom from January 2008 to August 2009. These studies were automatically processed to generate hemodynamic parameters that included cerebral blood flow and cerebral blood volume, and the mean transit time (MTT). To develop reliable software for PWI analysis, we used computationally robust algorithms including the piecewise continuous regression method to determine bolus arrival time (BAT), log-linear curve fitting, arrival time independent deconvolution method and sophisticated motion correction methods. An optimal arterial input function (AIF) search algorithm using a new artery-likelihood metric was also developed. Anatomical locations of the automatically determined AIF were reviewed and validated. The automatically computed BAT values were statistically compared with estimated BAT by a single observer. In addition, gamma-variate curve-fitting errors of AIF and inter-subject variability of AIFs were analyzed. Lastly, two observes independently assessed the quality and area of hypoperfusion mismatched with restricted diffusion area from motion corrected MTT maps and compared that with time-to-peak (TTP) maps using the standard approach. The AIF was identified within an arterial branch and enhanced areas of perfusion deficit were visualized in all evaluated cases. Total processing time was 10.9+/-2.5s (mean+/-s.d.) without motion correction and 267+/-80s (mean+/-s.d.) with motion correction on a standard personal computer. The MTT map produced with our software adequately estimated brain areas with perfusion deficit and was significantly less affected by random noise of the PWI when compared with the TTP map. Results of image quality assessment by two observers revealed that the MTT maps exhibited superior quality over the TTP maps (88% good rating of MTT as compared to 68% of TTP). Our software allowed fully automated deconvolution analysis of DSC PWI using proven efficient algorithms that can be applied to acute stroke treatment decisions. Our streamlined method also offers promise for further development of automated quantitative analysis of the ischemic penumbra. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Differential inputs to striatal cholinergic and parvalbumin interneurons imply functional distinctions

PubMed Central

Klug, Jason R; Engelhardt, Max D; Cadman, Cara N; Li, Hao; Smith, Jared B; Ayala, Sarah; Williams, Elora W; Hoffman, Hilary

2018-01-01

Striatal cholinergic (ChAT) and parvalbumin (PV) interneurons exert powerful influences on striatal function in health and disease, yet little is known about the organization of their inputs. Here using rabies tracing, electrophysiology and genetic tools, we compare the whole-brain inputs to these two types of striatal interneurons and dissect their functional connectivity in mice. ChAT interneurons receive a substantial cortical input from associative regions of cortex, such as the orbitofrontal cortex. Amongst subcortical inputs, a previously unknown inhibitory thalamic reticular nucleus input to striatal PV interneurons is identified. Additionally, the external segment of the globus pallidus targets striatal ChAT interneurons, which is sufficient to inhibit tonic ChAT interneuron firing. Finally, we describe a novel excitatory pathway from the pedunculopontine nucleus that innervates ChAT interneurons. These results establish the brain-wide direct inputs of two major types of striatal interneurons and allude to distinct roles in regulating striatal activity and controlling behavior. PMID:29714166

Temporary cerebral revascularization using a radial artery in the hand-eyeshade posture: technical note.

PubMed

Hiramoto, Jun; Tanaka, Yuichiro

2014-06-17

Kamiyama introduced a unique method of temporary cerebral revascularization using a radial artery graft (RAG) in his technical review. We tried original method with Sugita frame, and pointed out some disadvantages that include to avoid taking instruments or hands in and out, stability of hands, and unrestricted usage of brain retractors during temporary bypass between radial artery and M2 potion of middle cerebral artery (RA-M2 bypass). To solve those disadvantages, especially for Sugita head frame users, we here present a modified Kamiyama's method of temporary cerebral revascularization with the forearm elevated over the face like as hand-eyeshade posture.

Neuroprotection of dietary virgin olive oil on brain lipidomics during stroke.

PubMed

Rabiei, Zahra; Bigdeli, Mohammad Reza; Rasoulian, Bahram

2013-08-01

Recent studies suggest that dietary virgin olive oil reduces hypoxia-reoxygenation injury in rat brain. This study investigated the effect of pretreatment with different doses of dietary virgin olive oil on brain lipidomics during stroke. In this experimental trial, 60 male Wistar rats were studied in 5 groups of 12 each. The control group received distilled water while three treatment groups received oral virgin olive oil for 30 days (0.25, 0.5 and 0.75 ml/kg/day respectively). Also the sham group received distilled water. Two hours after the last dose, the animals divided two groups. The middle cerebral artery occlusion (MCAO) group subjected to 60 min of middle cerebral artery occlusion (MCAO) and intact groups for brain lipids analysis. The brain phosphatidylcholine, cholesterol ester and cholesterol levels increased significantly in doses of 0.5 and 0.75 ml/kg/day compare with control group. VOO in all three doses increased the brain triglyceride levels. VOO with dose 0.75 ml/kg increased the brain cerebroside levels when compared with control group. VOO pretreatment for 30 days decreased the brain ceramide levels in doses of 0.5 and 0.75 ml/kg/day (p<0.05). Although further studies are needed, the results indicate that the VOO pretreatment improved the injury of ischemia and reperfusion and might be beneficial in patients with these disorders and seems to partly exert their effects via change in brain lipid levels in rat.

Communication among neurons.

PubMed

Marner, Lisbeth

2012-04-01

The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are considered and the relation to the prevailing beta-amyloid hypothesis is discussed.

Evaluation in Monkey of Two Candidate PET Radioligands, [11C]RX-1 and [18F]RX-2, for Imaging Brain 5-HT4 Receptors

PubMed Central

LOHITH, TALAKAD G.; XU, RONG; TSUJIKAWA, TETSUYA; MORSE, CHERYL L.; ANDERSON, KACEY B.; GLADDING, ROBERT L.; ZOGHBI, SAMI S.; FUJITA, MASAHIRO; INNIS, ROBERT B.; PIKE, VICTOR W.

2014-01-01

The serotonin subtype-4 (5-HT4) receptor, which is known to be involved physiologically in learning and memory, and pathologically in Alzheimer’s disease, anxiety and other neuropsychiatric disorders – has few radioligands readily available for imaging in vivo. We have previously reported two novel 5-HT4 receptor radioligands, namely [methoxy-11C](1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate; [11C]RX-1) and the [18F]3-fluoromethoxy analog ([18F]RX-2), and in this study we evaluated them by PET in rhesus monkey. Brain scans were performed at baseline, receptor preblock or displacement conditions using SB 207710, a 5-HT4 receptor antagonist, on the same day for [11C]RX-1 and on different days for [18F]RX-2. Specific-to-nondisplaceable ratio (BPND) was measured with the simplified reference tissue model from all baseline scans. To determine specific binding, total distribution volume (VT) was also measured in some monkeys by radiometabolite-corrected arterial input function after ex vivo inhibition of esterases from baseline and blocked scans. Both radioligands showed moderate to high peak brain uptake of radioactivity (2–6 SUV). Regional BPND values were in the rank order of known 5-HT4 receptor distribution with a trend for higher BPND values from [18F]RX-2. One-tissue compartmental model provided good fits with well identified VT values for both radioligands. In the highest 5-HT4 receptor density region, striatum, 50–60% of total binding was specific. The VT in receptor-poor cerebellum reached stable values by about 60 min for both radioligands indicating little influence of radiometabolites on brain signal. In conclusion, both [11C]RX-1 and [18F]RX-2 showed positive attributes for PET imaging of brain 5-HT4 receptors, validating the radioligand design strategy. PMID:25088028

Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension.

PubMed

Hunter, Kendall S; Lee, Po-Feng; Lanning, Craig J; Ivy, D Dunbar; Kirby, K Scott; Claussen, Lori R; Chan, K Chen; Shandas, Robin

2008-01-01

Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated a method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero harmonic impedance value and PVR and suggested a correlation between higher-harmonic impedance values and pulmonary vascular stiffness. Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and pulmonary vascular stiffness from a single measurement, and that impedance is a better predictor of disease outcomes compared with PVR. Pressure and velocity waveforms within the main pulmonary artery were measured during right heart catheterization of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH undergoing reactivity evaluation (49 subjects, 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n = 25), cumulative logistic regression between outcomes to total indexed impedance was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 = 0.3131). Input impedance can be consistently and easily obtained from pulse-wave Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient outcomes compared with PVR alone.

Coronary Artery Diagnosis Aided by Neural Network

NASA Astrophysics Data System (ADS)

Stefko, Kamil

2007-01-01

Coronary artery disease is due to atheromatous narrowing and subsequent occlusion of the coronary vessel. Application of optimised feed forward multi-layer back propagation neural network (MLBP) for detection of narrowing in coronary artery vessels is presented in this paper. The research was performed using 580 data records from traditional ECG exercise test confirmed by coronary arteriography results. Each record of training database included description of the state of a patient providing input data for the neural network. Level and slope of ST segment of a 12 lead ECG signal recorded at rest and after effort (48 floating point values) was the main component of input data for neural network was. Coronary arteriography results (verified the existence or absence of more than 50% stenosis of the particular coronary vessels) were used as a correct neural network training output pattern. More than 96% of cases were correctly recognised by especially optimised and a thoroughly verified neural network. Leave one out method was used for neural network verification so 580 data records could be used for training as well as for verification of neural network.

[System analytical approach of lung function and hemodynamics].

PubMed

Naszlady, Attila; Kiss, Lajos

2009-02-15

The authors critically analyse the traditional views in physiology and complete them with new statements based on computer model simulations of lung function and of hemodynamics. Conclusions are derived for the clinical practice as follows: the four-dimensional function curves are similar in both systems; there is a "waterfall" zone in the pulmonary blood perfusion; the various time constants of pulmonary regions can modify the blood gas values; pulmonary capillary pressure is equal to pulmonary arterial diastole pressure; heart is not a pressure pump, but a flow source; ventricles are loaded by the input impedance of the arterial systems and not by the total vascular (ohmlike) resistance; optimum heart rate in rest depends on the length of the aorta; this law of heart rate, based on the principle of resonance is valid along the mammalian allometric line; tachycardia decreases the input impedance; using positive end expiratory pressure respirators the blood gas of pulmonary artery should be followed; coronary circulation should be assessed in beat per milliliter, the milliliter per minute may be false. These statements are compared to related references.

Automated construction of arterial and venous trees in retinal images

PubMed Central

Hu, Qiao; Abràmoff, Michael D.; Garvin, Mona K.

2015-01-01

Abstract. While many approaches exist to segment retinal vessels in fundus photographs, only a limited number focus on the construction and disambiguation of arterial and venous trees. Previous approaches are local and/or greedy in nature, making them susceptible to errors or limiting their applicability to large vessels. We propose a more global framework to generate arteriovenous trees in retinal images, given a vessel segmentation. In particular, our approach consists of three stages. The first stage is to generate an overconnected vessel network, named the vessel potential connectivity map (VPCM), consisting of vessel segments and the potential connectivity between them. The second stage is to disambiguate the VPCM into multiple anatomical trees, using a graph-based metaheuristic algorithm. The third stage is to classify these trees into arterial or venous (A/V) trees. We evaluated our approach with a ground truth built based on a public database, showing a pixel-wise classification accuracy of 88.15% using a manual vessel segmentation as input, and 86.11% using an automatic vessel segmentation as input. PMID:26636114

The pathogenesis of small arterial lesions in nephrectomized rats by the administration of renin.

PubMed Central

Kai, M.; Kanaide, H.; Yamamoto, H.; Kurozumi, T.; Tanaka, K.; Nakamura, M.

1981-01-01

Intraperitoneal injection of purified hog renal renin produced a marked and sustained elevation of arterial pressure and lesions of the "fibrinoid necrosis" type in the small arteries and arterioles of the pancreas, heart and mesentery, but not of the brain, in bilaterally nephrectomized rats. Both the elevation of arterial pressure and the production of arterial lesions were completely prevented by pretreatment with oral SQ14225. Plasma renin clearance in bilaterally nephrectomized rats was markedly slower than that in sham-nephrectomized rats. Pre-treatment with oral SQ14225 did not affect renin clearance. It is suggested that sustained high blood pressure due to the sustained high plasma renin concentration in bilaterally nephrectomized rat was responsible for the production by renin of lesions of the fibrinoid necrosis type in the arteries. Images Fig. 1 Fig. 4 PMID:7016159

A dual-input nonlinear system analysis of autonomic modulation of heart rate

NASA Technical Reports Server (NTRS)

Chon, K. H.; Mullen, T. J.; Cohen, R. J.

1996-01-01

Linear analyses of fluctuations in heart rate and other hemodynamic variables have been used to elucidate cardiovascular regulatory mechanisms. The role of nonlinear contributions to fluctuations in hemodynamic variables has not been fully explored. This paper presents a nonlinear system analysis of the effect of fluctuations in instantaneous lung volume (ILV) and arterial blood pressure (ABP) on heart rate (HR) fluctuations. To successfully employ a nonlinear analysis based on the Laguerre expansion technique (LET), we introduce an efficient procedure for broadening the spectral content of the ILV and ABP inputs to the model by adding white noise. Results from computer simulations demonstrate the effectiveness of broadening the spectral band of input signals to obtain consistent and stable kernel estimates with the use of the LET. Without broadening the band of the ILV and ABP inputs, the LET did not provide stable kernel estimates. Moreover, we extend the LET to the case of multiple inputs in order to accommodate the analysis of the combined effect of ILV and ABP effect on heart rate. Analyzes of data based on the second-order Volterra-Wiener model reveal an important contribution of the second-order kernels to the description of the effect of lung volume and arterial blood pressure on heart rate. Furthermore, physiological effects of the autonomic blocking agents propranolol and atropine on changes in the first- and second-order kernels are also discussed.

Polycythemia and high levels of erythropoietin in blood and brain blunt the hypercapnic ventilatory response in adult mice.

PubMed

Menuet, Clément; Khemiri, Hanan; de la Poëze d'Harambure, Théodora; Gestreau, Christian

2016-05-15

Changes in arterial Po2, Pco2, and pH are the strongest stimuli sensed by peripheral and central chemoreceptors to adjust ventilation to the metabolic demand. Erythropoietin (Epo), the main regulator of red blood cell production, increases the hypoxic ventilatory response, an effect attributed to the presence of Epo receptors in both carotid bodies and key brainstem structures involved in integration of peripheral inputs and control of breathing. However, it is not known whether Epo also has an effect on the hypercapnic chemoreflex. In a first attempt to answer this question, we tested the hypothesis that Epo alters the ventilatory response to increased CO2 levels. Basal ventilation and hypercapnic ventilatory response (HCVR) were recorded from control mice and from two transgenic mouse lines constitutively expressing high levels of human Epo in brain only (Tg21) or in brain and plasma (Tg6), the latter leading to polycythemia. To tease apart the potential effects of polycythemia and levels of plasma Epo in the HCVR, control animals were injected with an Epo analog (Aranesp), and Tg6 mice were treated with the hemolytic agent phenylhydrazine after splenectomy. Ventilatory parameters measured by plethysmography in conscious mice were consistent with data from electrophysiological recordings in anesthetized animals and revealed a blunted HCVR in Tg6 mice. Polycythemia alone and increased levels of plasma Epo blunt the HCVR. In addition, Tg21 mice with an augmented level of cerebral Epo also had a decreased HCVR. We discuss the potential implications of these findings in several physiopathological conditions. Copyright © 2016 the American Physiological Society.

Rat model of blood-brain barrier disruption to allow targeted neurovascular therapeutics.

PubMed

Martin, Jacob A; Maris, Alexander S; Ehtesham, Moneeb; Singer, Robert J

2012-11-30

Endothelial cells with tight junctions along with the basement membrane and astrocyte end feet surround cerebral blood vessels to form the blood-brain barrier(1). The barrier selectively excludes molecules from crossing between the blood and the brain based upon their size and charge. This function can impede the delivery of therapeutics for neurological disorders. A number of chemotherapeutic drugs, for example, will not effectively cross the blood-brain barrier to reach tumor cells(2). Thus, improving the delivery of drugs across the blood-brain barrier is an area of interest. The most prevalent methods for enhancing the delivery of drugs to the brain are direct cerebral infusion and blood-brain barrier disruption(3). Direct intracerebral infusion guarantees that therapies reach the brain; however, this method has a limited ability to disperse the drug(4). Blood-brain barrier disruption (BBBD) allows drugs to flow directly from the circulatory system into the brain and thus more effectively reach dispersed tumor cells. Three methods of barrier disruption include osmotic barrier disruption, pharmacological barrier disruption, and focused ultrasound with microbubbles. Osmotic disruption, pioneered by Neuwelt, uses a hypertonic solution of 25% mannitol that dehydrates the cells of the blood-brain barrier causing them to shrink and disrupt their tight junctions. Barrier disruption can also be accomplished pharmacologically with vasoactive compounds such as histamine(5) and bradykinin(6). This method, however, is selective primarily for the brain-tumor barrier(7). Additionally, RMP-7, an analog of the peptide bradykinin, was found to be inferior when compared head-to-head with osmotic BBBD with 25% mannitol(8). Another method, focused ultrasound (FUS) in conjunction with microbubble ultrasound contrast agents, has also been shown to reversibly open the blood-brain barrier(9). In comparison to FUS, though, 25% mannitol has a longer history of safety in human patients that makes it a proven tool for translational research(10-12). In order to accomplish BBBD, mannitol must be delivered at a high rate directly into the brain's arterial circulation. In humans, an endovascular catheter is guided to the brain where rapid, direct flow can be accomplished. This protocol models human BBBD as closely as possible. Following a cut-down to the bifurcation of the common carotid artery, a catheter is inserted retrograde into the ECA and used to deliver mannitol directly into the internal carotid artery (ICA) circulation. Propofol and N2O anesthesia are used for their ability to maximize the effectiveness of barrier disruption(13). If executed properly, this procedure has the ability to safely, effectively, and reversibly open the blood-brain barrier and improve the delivery of drugs that do not ordinarily reach the brain (8,13,14).

Cranial arterial patterns of the alpaca (Camelidae: Vicugna pacos).

PubMed

O'Brien, Haley D

2017-03-01

Artiodactyl cranial arterial patterns deviate significantly from the standard mammalian pattern, most notably in the possession of a structure called the carotid rete (CR)-a subdural arterial meshwork that is housed within the cavernous venous sinus, replacing the internal carotid artery (ICA). This relationship between the CR and the cavernous sinus facilitates a suite of unique physiologies, including selective brain cooling. The CR has been studied in a number of artiodactyls; however, to my knowledge, only a single study to date documents a subset of the cranial arteries of New World camelids (llamas, alpacas, vicugñas and guanacoes). This study is the first complete description of the cranial arteries of a New World camelid species, the alpaca ( Vicugna pacos ), and the first description of near-parturition cranial arterial morphology within New World camelids. This study finds that the carotid arterial system is conserved between developmental stages in the alpaca, and differs significantly from the pattern emphasized in other long-necked ruminant artiodactyls in that a patent, homologous ICA persists through the animal's life.

[Microsurgical anatomy of the perforating arteries in the superior space of the internal carotid artery through a pterional approach].

PubMed

Qi, Song-tao; Huang, Chuan-ping; Lu, Yun-tao; Pan, Jun; Fan, Jun

2007-05-01

To study the microanatomy of the perforating arteries in the superior space of the internal carotid artery visualized through a pterional approach. Twelve (24 sides) perfused cadaver heads were dissected via the pterional approach, and the perforating arteries in the superior space of the internal carotid artery were studied under microscope. The diameter, course and distribution in the anterior perforated substance of the perforating arteries were recorded. All the perforating arteries exposed lied on the side of the brain tissue. The carotid bifurcation on 8 sides had perforating arteries, and 11 sides showed medial lenticulostriate artery of the middle cerebral arteries, with short course and overlapped with another perforating arteries upon entry into the anterior perforated substance. On 4 sides, the medial lenticulostriate artery coincided with the perforating arteries in A1. All 24 sides showed middle lenticulostriate artery and lateral lenticulostriate artery of the middle cerebral arteries. Most of the lenticulostriate arteries originated from the anterior segment of the bifurcation of the middle cerebral arteries. The earlier bifurcation occurred in M1 of the middle cerebral arteries, the more perforating arteries originated. On 22 sides, the anterior cerebral arteries had perforating arteries with many branches, and fewer perforating arteries in a main artery were associated with greater diameter of them. The superior space of the internal carotid artery allows a space for operation, and in some cases, part of the medial leticulostriate arteries and A1 perforating arteries can be severed to obtain larger space for the operation.

Alterations of pulsation absorber characteristics in experimental hydrocephalus.

PubMed

Park, Eun-Hyoung; Dombrowski, Stephen; Luciano, Mark; Zurakowski, David; Madsen, Joseph R

2010-08-01

Analysis of waveform data in previous studies suggests that the pulsatile movement of CSF may play a role in attenuating strong arterial pulsations entering the cranium, and its effectiveness in attenuating these pulsations may be altered by changes in intracranial pressure (ICP). These findings were obtained in studies performed in canines with normal anatomy of the CSF spaces. How then would pulsation absorbance respond to changes in CSF movement under obstructive conditions such as the development of hydrocephalus? In the present study, chronic obstructive hydrocephalus was induced by the injection of cyanoacrylate gel into the fourth ventricle of canines, and pulsation absorbance was compared before and after hydrocephalus induction. Five animals were evaluated with simultaneous recordings of ICP and arterial blood pressure (ABP) before and at 4 and 12 weeks after fourth ventricle obstruction by cyanoacrylate. To assess how the intracranial system responds to the arterial pulsatile component, ABP and ICP waveforms recorded in a time domain had to be analyzed in a frequency domain. In an earlier study the authors introduced a particular technique that allows characterization of the intracranial system in the frequency domain with sufficient accuracy and efficiency. This same method was used to analyze the relationship between ABP and ICP waveforms recorded during several acute states including hyperventilation as well as CSF withdrawal and infusion under conditions before and after inducing chronic obstructive hydrocephalus. Such a relationship is reflected in terms of a gain, which is a function of frequency. The cardiac pulsation absorbance (CPA) index, which is simply derived from a gain evaluated at the cardiac frequency, was used to quantitatively evaluate the changes in pulsation absorber function associated with the development of hydrocephalus within each of the animals, which did become hydrocephalic. To account for normal and hydrocephalic conditions within the same animal and at multiple time points, statistical analysis was performed by repeated-measures ANOVA. The performance of the pulsation absorber as assessed by CPA significantly deteriorated after the development of chronic hydrocephalus. In these animals the decrement in CPA was far more significant than other anticipated changes including those in ICP, compliance, or ICP pulse amplitude. To the extent that the free CSF movement acts as a buffer of arterial pulsation input to flow in microvessels, alterations in the pulsation absorber may play a pathophysiological role. One measure of alterations in the way the brain deals with pulsatile input-the CPA measurement-changes dramatically with the imposition of hydrocephalus. Results in the present study suggest that CPA may serve as a complementary metric to the conventional static measure of intracranial compliance in other experimental and clinical studies.

Intrinsic Cholinergic Mechanisms Regulating Cerebral Blood Flow as a Target for Organophosphate Action

DTIC Science & Technology

1988-10-01

autoregulation, render the cerebral circulation dependent upon systemic circulation exposing brain to ischernic damage or edema in shock or stress...Thus, sharp reductions of arterial pressure, as might occur in hemorrhagic or traumatic shock, will render the cerebral circulation vulnerable to...autoregulated range, rendering local areas of the brain vulnerable to cerebral edema and breakdown of the blood brain barrier. -2- 8. Cerebral blood

Diagnosis of brain death by transcranial Doppler sonography.

PubMed

Bode, H; Sauer, M; Pringsheim, W

1988-12-01

The blood flow velocities in the basal cerebral arteries can be recorded at any age by transcranial Doppler sonography. We examined nine children with either initial or developing clinical signs of brain death. Soon after successful resuscitation increased diastolic flow velocities indicated a probable decrease in cerebrovascular resistance; this was of no particular prognostic importance. As soon as there was a clinical deterioration, there was a reduction in flow velocities with retrograde flow during early diastole, probably due to an increase in cerebrovascular resistance; this indicated a doubtful prognosis. In eight of the nine children with clinical signs of brain death a typical reverberating flow pattern was found, which was characterised by a counterbalancing short forward flow in systole and a short retrograde flow in early diastole. This indicated arrest of cerebral blood flow. One newborn showed normal systolic and end diastolic flow velocities in the basal cerebral arteries for two days despite clinical and electroencephalographic signs of brain death. Shunting of blood through the circle of Willis without effective cerebral perfusion may explain this phenomenon. No patient had the typical reverberating flow pattern without being clinically brain dead. Transcranial Doppler sonography is a reliable technique, which can be used at the bedside for the confirmation or the exclusion of brain death in children in addition to the clinical examination.

Diagnosis of brain death by transcranial Doppler sonography.

PubMed Central

Bode, H; Sauer, M; Pringsheim, W

1988-01-01

The blood flow velocities in the basal cerebral arteries can be recorded at any age by transcranial Doppler sonography. We examined nine children with either initial or developing clinical signs of brain death. Soon after successful resuscitation increased diastolic flow velocities indicated a probable decrease in cerebrovascular resistance; this was of no particular prognostic importance. As soon as there was a clinical deterioration, there was a reduction in flow velocities with retrograde flow during early diastole, probably due to an increase in cerebrovascular resistance; this indicated a doubtful prognosis. In eight of the nine children with clinical signs of brain death a typical reverberating flow pattern was found, which was characterised by a counterbalancing short forward flow in systole and a short retrograde flow in early diastole. This indicated arrest of cerebral blood flow. One newborn showed normal systolic and end diastolic flow velocities in the basal cerebral arteries for two days despite clinical and electroencephalographic signs of brain death. Shunting of blood through the circle of Willis without effective cerebral perfusion may explain this phenomenon. No patient had the typical reverberating flow pattern without being clinically brain dead. Transcranial Doppler sonography is a reliable technique, which can be used at the bedside for the confirmation or the exclusion of brain death in children in addition to the clinical examination. PMID:3069052

Brain Ischemia Induces Diversified Neuroantigen-Specific T-Cell Responses That Exacerbate Brain Injury.

PubMed

Jin, Wei-Na; Gonzales, Rayna; Feng, Yan; Wood, Kristofer; Chai, Zhi; Dong, Jing-Fei; La Cava, Antonio; Shi, Fu-Dong; Liu, Qiang

2018-06-01

Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury. Using a mouse strain that harbors a transgenic T-cell receptor to a central nervous system antigen, MOG 35-55 (myelin oligodendrocyte glycoprotein) epitope (2D2), we determined the anatomic location and involvement of antigen-presenting cells in the development of T-cell reactivity after brain ischemia and how T-cell reactivity impacts stroke outcome. Transient middle cerebral artery occlusion and photothrombotic stroke models were used in this study. We also quantified the presence and status of T cells from brain slices of ischemic patients. By coupling transfer of labeled MOG 35-55 -specific (2D2) T cells with tetramer tracking, we show an expansion in reactivity of 2D2 T cells to MOG 91-108 and MOG 103-125 in transient middle cerebral artery occlusion and photothrombotic stroke models. This reactivity and T-cell activation first occur locally in the brain after ischemia. Also, microglia act as antigen-presenting cells that effectively present MOG antigens, and depletion of microglia ablates expansion of 2D2 reactive T cells. Notably, the adoptive transfer of neuroantigen-experienced 2D2 T cells exacerbates Th1/Th17 responses and brain injury. Finally, T-cell activation and MOG-specific T cells are present in the brain of patients with ischemic stroke. Our findings suggest that brain ischemia activates and diversifies T-cell responses locally, which exacerbates ischemic brain injury. © 2018 The Authors.

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

PubMed

Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

2005-01-01

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

A cross-circulated bicephalic model of head transplantation.

PubMed

Li, Peng-Wei; Zhao, Xin; Zhao, Yun-Long; Wang, Bing-Jian; Song, Yang; Shen, Zi-Long; Jiang, Hong-Jun; Jin, Hai; Canavero, Sergio; Ren, Xiao-Ping

2017-06-01

A successful cephalosomatic anastomosis ("head transplant") requires, among others, the ability to control long-term immune rejection and avoidance of ischemic events during the head transference phase. We developed a bicephalic model of head transplantation to study these aspects. The thoracic aorta and superior vena cava of a donor rat were anastomosed with the carotid artery and extracorporeal veins of a recipient rat by vascular grafts. Before thoracotomy in the donor rat, the axillary artery and vein of the donor were connected to the carotid and the extracranial vein of the third rat through a silicone tube. The silicone tube was passed through a peristaltic pump to ensure donor brain tissue blood supply. There is no ischemia reperfusion injury in donor brain tissue analyzed by electroencephalogram. Postoperative donor has pain reflex and corneal reflex. Peristaltic pump application can guarantee the blood supply of donor brain tissue per unit time, while the application of temperature change device to the silicone tube can protect the brain tissue hypothermia, postoperative experimental data show that there is no brain tissue ischemia during the whole operation. The application of vascular grafting can also provide the possibility of long-term survival of the model. © 2017 John Wiley & Sons Ltd.

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.

Skull metastases detecting on arterial spin labeling perfusion: Three case reports and review of literature.

PubMed

Ryu, Kyeong H; Baek, Hye J; Cho, Soo B; Moon, Jin I; Choi, Bo H; Park, Sung E; An, Hyo J

2017-11-01

Detection of skull metastases is as important as detection of brain metastases because early diagnosis of skull metastases is a crucial determinant of treatment. However, the skull can be a blind spot for assessing metastases on routine brain magnetic resonance imaging (MRI). To the best of our knowledge, the finding of skull metastases on arterial spin labeling (ASL) has not been reported. ASL is a specific MRI sequence for evaluating cerebral blood flow using magnetized endogenous inflow blood. This study uses ASL as a routine sequence of brain MRI protocol and describes 3 clinical cases of skull metastases identified by ASL. The study also highlights the clinical usefulness of ASL in detecting skull metastases. Three patients with known malignancy underwent brain MRI to evaluate for brain metastases. All of the skull metastases were conspicuously depicted on routine ASL images, and the lesions correlated well with other MRI sequences. Three patients received palliative chemotherapy. Three patients are being followed up regularly at the outpatient department. The routine use of ASL may help to detect lesions in blind spots, such as skull metastases, and to facilitate the evaluation of intracranial pathologies without the use of contrast materials in exceptional situations.

Ultrasonographic character of carotid plaque and postprocedural brain embolisms in carotid artery stenting and carotid endarterectomy.

PubMed

Mitsuoka, Hiroshi; Shintani, Tsunehiro; Furuya, Hidekazu; Nakao, Yoshinaga; Higashi, Shigeki

2011-01-01

To investigate ultrasonographic character of carotid plaques, and incidences of brain embolism in carotid angioplasty and stenting (CAS) and carotid endarterectomy (CEA). CEA (22/25 symptomatic lesions) and CAS (17/20 symptomatic lesions) between 2007 and 2010. Embolic protection devices (15 occlusion and 5 filtering devices) were used during CAS. Carotid plaques were classified into three categories (I: calcificated, II: intermediately echogenic, III: echolucent). Magnetic resonance imaging (MRI) was used to investigate brain emboli. Ultrasonographic character of the plaques in CEA cases (I: 4%, II: 88%, III: 8%) was different from the one in CAS cases (I: 10%, II: 90%, III: 0%). The incidence of brain embolism in the CAS cases was 52.6% while 0% in the CEA cases (p = 0.00037). CAS had high incidences of brain embolism in any plaques (I: 100%, II: 43.8%). In the most recent 9 procedures of CAS using occlusion devices, averaged number of embolic lesion was 1.0 (0 post operative day; 0 POD). The number increased as 1.4 (1 POD) and 2.0 (7 POD). CEA should be currently the first choice for most patients with a high-grade and symptomatic carotid artery stenosis.

Brain architecture of the Pacific White Shrimp Penaeus vannamei Boone, 1931 (Malacostraca, Dendrobranchiata): correspondence of brain structure and sensory input?

PubMed

Meth, Rebecca; Wittfoth, Christin; Harzsch, Steffen

2017-08-01

Penaeus vannamei (Dendrobranchiata, Decapoda) is best known as the "Pacific White Shrimp" and is currently the most important crustacean in commercial aquaculture worldwide. Although the neuroanatomy of crustaceans has been well examined in representatives of reptant decapods ("ground-dwelling decapods"), there are only a few studies focusing on shrimps and prawns. In order to obtain insights into the architecture of the brain of P. vannamei, we use neuroanatomical methods including X-ray micro-computed tomography, 3D reconstruction and immunohistochemical staining combined with confocal laser-scanning microscopy and serial sectioning. The brain of P. vannamei exhibits all the prominent neuropils and tracts that characterize the ground pattern of decapod crustaceans. However, the size proportion of some neuropils is salient. The large lateral protocerebrum that comprises the visual neuropils as well as the hemiellipsoid body and medulla terminalis is remarkable. This observation corresponds with the large size of the compound eyes of these animals. In contrast, the remaining median part of the brain is relatively small. It is dominated by the paired antenna 2 neuropils, while the deutocerebral chemosensory lobes play a minor role. Our findings suggest that visual input from the compound eyes and mechanosensory input from the second pair of antennae are major sensory modalities, which this brain processes.

Revisiting intra-arterial drug delivery for treating brain diseases or is it "déjà-vu, all over again"?

PubMed

Joshi, Shailendra; Ellis, Jason A; Emala, Charles W

2014-05-01

For over six decades intra-arterial (IA) drugs have been sporadically used for the treatment of lethal brain diseases. In recent years considerable advance has been made in the IA treatment of retinoblastomas, liver and locally invasive breast cancers, but relatively little progress has been made in the treatment of brain cancers. High resting blood flow and the presence of the blood-brain barrier (BBB), makes IA delivery to the brain tissue far more challenging, compared to other organs. The lack of advance in the field is also partly due to the inability to understand the complex pharmacokinetics of IA drugs as it is difficult to track drug concentrations in sub-second time frame by conventional chemical methods. The advances in optical imaging now provide unprecedented insights into the pharmacokinetics of IA drug and optical tracer delivery. Novel delivery methods, improved IA drug formulations, and optical pharmacokinetics, present us with untested paradigms in pharmacology that could lead to new therapeutic interventions for brain cancers and stroke. The object of this review is to bring into focus the current practice, problems, and the potential of IA drug delivery for treating brain diseases. A concerted effort is needed at basic sciences (pharmacology and drug imaging), and translational (drug delivery techniques and protocol development) levels by the interventional neuroradiology community to advance the field.

Relationship between the posterior cerebral artery and the cisternal segment of the oculomotor nerve.

PubMed

Uz, Aysun; Tekdemir, Ibrahim

2006-12-01

The aim of this study was to evaluate the relationship between the cisternal segment of the oculomotor nerve and the posterior cerebral artery and its branches. The oculomotor nerve and the posterior cerebral artery of 15 cadaver brains (30 hemispheres) were examined using a surgical microscope. The dorsal portion of the cisternal segment of the oculomotor nerve had a close relationship with the P(1) and P(2) segments of the posterior cerebral artery in 100% of cases, the thalamoperforating arteries in 97%, the collicular arteries in 97%, the short circumferential arteries in 33% and the posterior medial choroidal arteries in 20%. The proximal portion of the nerve had a close relationship with the P(1) segment of the posterior cerebral artery, the thalamoperforating arteries, the collicular arteries and the short circumferential arteries, whereas the distal portion had a close relationship with the P(2) segment of the posterior cerebral artery and the posterior medial choroidal arteries. The oculomotor nerve was perforated by various arteries in different portions. These arteries were the thalamoperforating arteries in 10% of the hemispheres, the collicular arteries in 16% and the short circumferential arteries in 11%. It can be concluded that the dorsal portion of the cisternal segment of the oculomotor nerve has a close relationship with the branches arising from the P(1) and P(2) segments of the posterior cerebral artery. These arteries supply the cisternal segment of the oculomotor nerve.

Acute and chronic head-down tail suspension diminishes cerebral perfusion in rats

NASA Technical Reports Server (NTRS)

Wilkerson, M. Keith; Colleran, Patrick N.; Delp, Michael D.

2002-01-01

The purpose of this study was to test the hypothesis that regional brain blood flow and vascular resistance are altered by acute and chronic head-down tail suspension (HDT). Regional cerebral blood flow, arterial pressure, heart rate, and vascular resistance were measured in a group of control rats during normal standing and following 10 min of HDT and in two other groups of rats after 7 and 28 days of HDT. Heart rate was not different among conditions, whereas mean arterial pressure was elevated at 10 min of HDT relative to the other conditions. Total brain blood flow was reduced from that during standing by 48, 24, and 27% following 10 min and 7 and 28 days of HDT, respectively. Regional blood flows to all cerebral tissues and the eyes were reduced with 10 min of HDT and remained lower in the eye, olfactory bulbs, left and right cerebrum, thalamic region, and the midbrain with 7 and 28 days of HDT. Total brain vascular resistance was 116, 44, and 38% greater following 10 min and 7 and 28 days of HDT, respectively, relative to that during control standing. Vascular resistance was elevated in all cerebral regions with 10 min of HDT and remained higher than control levels in most brain regions. These results demonstrate that HDT results in chronic elevations in total and regional cerebral vascular resistance, and this may be the underlying stimulus for the HDT-induced smooth muscle hypertrophy of cerebral resistance arteries.

PAMAM Dendrimers Cross the Blood–Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice

PubMed Central

Srinageshwar, Bhairavi; Peruzzaro, Sarah; Andrews, Melissa; Johnson, Kayla; Hietpas, Allison; Clark, Brittany; McGuire, Crystal; Petersen, Eric; Kippe, Jordyn; Stewart, Andrew; Lossia, Olivia; Al-Gharaibeh, Abeer; Antcliff, Aaron; Culver, Rebecca; Swanson, Douglas; Dunbar, Gary; Sharma, Ajit; Rossignol, Julien

2017-01-01

Drug delivery into the central nervous system (CNS) is challenging due to the blood–brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH2 and G4-NH2) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders PMID:28335421

[The role of arteriovenous interrelations in the formation of clinical-pathogenetic variants of hypertonic encephalopathy].

PubMed

Belova, L A

2012-01-01

We studied 209 patients with chronic brain ischemia due to arterial hypertension (hypertonic encephalopathy). 93 patients (44.5%) had clinical-anamnestic features of constitutional phlebopathy and 116 (55.5%) had not. Based on the conception of 5 functional-morphological levels of the vascular brain system, a complex ultrasound study was conducted. The control group included 30 people without cerebrovascular pathology. In hypertonic encephalopathy, pathological processes developing in the 1st and 2nd structural-functional levels (extra- and intracerebral arteries) correspond to remodeling, that is characteristic of arterial hypertension, and do not depend on the presence of the constitutional venous insufficiency. Changes in parameters of the blood flow in the 3rd, 4th and 5th structural-functional levels of the brain's blood supply (microcirculatory bed, head venous system, jugular and spine veins) form a dopplerographic pattern of the cerebral venous dyscirculation which is mostly pronounced in constitutional phlebopathy in patients with hypertonic encephalopathy. This pattern includes the reduction of linear blood flow velocity in nitroglycerine test, lower values of the resistance index and the increase in the linear blood flow velocity in the sinus transversus and Rosenthal vein, lack of ostial valves of the inner jugular veinas well as the decrease of linear and increase in the volume blood flow velocity along it. The methodology of the system approach based on using clinical and instrumental method in the study of cerebral hemodynamics is important for treatment optimization in patients with chronic brain ischemia.

Beta-Blockers: An Abstracted Bibliography.

DTIC Science & Technology

1989-04-04

on subjects in the supine position. Blood flow was measured by venous occlusion plethys- mography. Prugs were administered via indwelling catheter (one...PROCEDURES: Noninvasive measuremert of maximum oxygen intake, invasive measurement of systemic and pulmonary arterial pressures, arterial and mixed venous ...ratio was approximately 0.1:1. Central nervous system-related effects associated with propranolol and metoprolol appear to be the result of high brain

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.

In vivo MRI assessment of permanent middle cerebral artery occlusion by electrocoagulation: pitfalls of procedure

PubMed Central

2010-01-01

Permanent middle cerebral artery (MCA) occlusion (pMCAO) by electrocoagulation is a commonly used model but with potential traumatic lesions. Early MRI monitoring may assess pMCAO for non-specific brain damage. The surgical steps of pMCAO were evaluated for traumatic cerebral injury in 22 Swiss mice using diffusion and T2-weighted MRI (7T) performed within 1 h and 24 h after surgery. Temporal muscle cauterization without MCA occlusion produced an early T2 hyperintensity mimicking an infarct. No lesion was visible after temporal muscle incision or craniotomy. Early MRI monitoring is useful to identify non-specific brain injury that could hamper neuroprotective drugs assessment. PMID:20298536

Anatomical Variability in the Termination of the Basilar Artery in the Human Cadaveric Brain.

PubMed

Gunnal, Sandhya; Farooqui, Mujeebuddin; Wabale, Rajendra

2015-01-01

The basilar artery (BA) is the prominent median vessel of the vertebrobasilar circulation and usually terminates into two posterior cerebral arteries forming the posterior angle of the Circle of Willis (CW). To tackle different variations of CW, basilar artery acts as a guideline for neuroradiologists and neurosurgeons. Basilar termination is the most frequent site of aneurysm. Abnormalities at the site of termination may compress the oculomotor nerve. Variations at the termination may complicate surgeries at the base of brain. The present study aims to add to the knowledge regarding the termination pattern of the BA. 170 BA terminations were studied. Morphological variations in the termination pattern were noted. Frequency of variations in termination patterns was recorded. Dimensions of BA were measured. Data were analyzed. Morphological variations in termination were seen in 17.64%. Bifurcation, Trifurcation, Quadrifurcation, Pentafurcation and Nonfurcation of BA was seen in 82.35%, 5.29%, 5.88%, 3.52% and 2.94% respectively. BA associated with aneurysm and Fenestration was seen in 3.52% and 1.17% respectively. Mean length and diameter of BA was 30.27 mm and 4.8 mm respectively. Awareness of these anatomical variations in termination patterns of BA is important in neurovascular procedures.

2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-Glucoside Attenuates Ischemia/Reperfusion-Induced Brain Injury in Rats by Promoting Angiogenesis.

PubMed

Mu, Ying; Xu, Zhaohui; Zhou, Xuanxuan; Zhang, Huinan; Yang, Qian; Zhang, Yunlong; Xie, Yanhua; Kang, Juan; Li, Feng; Wang, Siwang

2017-05-01

Cerebral ischemia can cause brain infarcts, which are difficult to recover due to poor angiogenesis. 2,3,5,4'-Tetrahydroxystilbene-2-O- β -D-glucoside is a natural polyphenol, has antioxidant and anti-inflammatory activity, and can protect from ischemic neuronal injury. However, little is known about the effect of 2,3,5,4'-tetrahydroxystilbene-2-O- β -D-glucoside on brain microcirculation after stroke. This study aimed at investigating the influence of 2,3,5,4'-tetrahydroxystilbene-2-O- β -D-glucoside on brain lesions and angiogenesis after stroke. Sprague-Dawley rats were subjected to right middle cerebral artery occlusion and treated with vehicle, nimodipine, or different doses of 2,3,5,4'-tetrahydroxystilbene-2-O- β -D-glucoside daily beginning at 6 h post-middle cerebral artery occlusion for 14 days. The volume of cerebral infarcts, degree of neurological dysfunction, and level of microvessel density were determined longitudinally. The levels of vascular endothelial growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the brain lesions were characterized by immunohistochemistry and Western blot assays at 14 days post-middle cerebral artery occlusion. We found that 2,3,5,4'-tetrahydroxystilbene-2-O- β -D-glucoside significantly promoted postoperative recovery in rats by minimizing the volume of cerebral infarcts and improving neurological dysfunction in a dose- and time-dependent manner. Additionally, 2,3,5,4'-tetrahydroxystilbene-2-O- β -D-glucoside significantly increased the microvessel density in the brain and upregulated CD31 expression in ischemic penumbra, relative to that in the control. Finally, treatment with 2,3,5,4'-tetrahydroxystilbene-2-O- β -D-glucoside significantly upregulated the relative levels of vascular endothelial growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the brain lesions of rats. Therefore, these data indicated that 2,3,5,4'-tetrahydroxystilbene-2-O- β -D-glucoside treatment promoted angiogenesis and recovery from ischemia/reperfusion-induced brain injury in rats. Georg Thieme Verlag KG Stuttgart · New York.

Congenital atresia of the external ear and tinnitus: a new syndrome.

PubMed

Shulman, Abraham; Strashun, Arnold M; Goldstein, Barbara; Lenhardt, Martin L

2006-01-01

Congenital atresia of the external ears and severe tinnitus has been reported by two patients to be contralateral to the atretic ear. The use of the nuclear medicine imaging technique of single-photon emission computed tomography (SPECT) of brain has demonstrated hypoperfusion in brain areas supplied by the middle cerebral artery on the side of the atretic ear. Ultrahigh-frequency audiometry (UHFA) has revealed a bilateral loss of hearing greater than expected for the age of affected patients. Quantitative electroencephalography (QEEG) has shown a significant central nervous system electrical dysfunction correlated with the SPECT of brain findings. One case is reported in detail at this time. Completion of the medical audiological tinnitus patient protocol, including SPECT of brain, UHFA, and QEEG, accurately established the clinical tinnitus diagnosis of predominantly a central-type tinnitus, a clinical hypothesis that the medical significance of the tinnitus is a "soft" sign of cerebrovascular disease, and provided a rationale for treatment directed to a presumed ischemia of brain based on a receptor-targeted therapy targeted to the GABA-A receptor, resulting in significant tinnitus relief. Questions that have arisen include (1) the incidence of occurrence of hypoperfusion of the middle cerebral artery in congenital atresia patients; (2) implications and long-term consequences of this finding in this patient population for development of cerebrovascular disease; (3) brain plasticity for tinnitus relief (i.e., neuronal reprogramming, particularly in response to treatment recommendations for complaints of the cochleovestibular system in general and specifically for tinnitus); (4) the clinical significance of the UHFA thresholds of bilateral hearing loss greater than expected for the age of the patient; and (5) whether congenital atresia of the external ear may be part of a syndrome that includes hypoperfusion in brain areas supplied by the middle cerebral artery on the side of the atretic ear, ultra-high-frequency bilateral loss of hearing greater than expected for the age of the patient, and significant central nervous system electrical dysfunction. As far as we can determine, these findings, highlighted by the brain SPECT, have not previously been reported in patients with congenital atresia of the external ear.

Recruitment of Additional Corticospinal Pathways in the Human Brain with State-Dependent Paired Associative Stimulation.

PubMed

Kraus, Dominic; Naros, Georgios; Guggenberger, Robert; Leão, Maria Teresa; Ziemann, Ulf; Gharabaghi, Alireza

2018-02-07

Standard brain stimulation protocols modify human motor cortex excitability by modulating the gain of the activated corticospinal pathways. However, the restoration of motor function following lesions of the corticospinal tract requires also the recruitment of additional neurons to increase the net corticospinal output. For this purpose, we investigated a novel protocol based on brain state-dependent paired associative stimulation.Motor imagery (MI)-related electroencephalography was recorded in healthy males and females for brain state-dependent control of both cortical and peripheral stimulation in a brain-machine interface environment. State-dependency was investigated with concurrent, delayed, and independent stimulation relative to the MI task. Specifically, sensorimotor event-related desynchronization (ERD) in the β-band (16-22 Hz) triggered peripheral stimulation through passive hand opening by a robotic orthosis and transcranial magnetic stimulation to the respective cortical motor representation, either synchronously or subsequently. These MI-related paradigms were compared with paired cortical and peripheral input applied independent of the brain state. Cortical stimulation resulted in a significant increase in corticospinal excitability only when applied brain state-dependently and synchronously to peripheral input. These gains were resistant to a depotentiation task, revealed a nonlinear evolution of plasticity, and were mediated via the recruitment of additional corticospinal neurons rather than via synchronization of neuronal firing. Recruitment of additional corticospinal pathways may be achieved when cortical and peripheral inputs are applied concurrently, and during β-ERD. These findings resemble a gating mechanism and are potentially important for developing closed-loop brain stimulation for the treatment of hand paralysis following lesions of the corticospinal tract. SIGNIFICANCE STATEMENT The activity state of the motor system influences the excitability of corticospinal pathways to external input. State-dependent interventions harness this property to increase the connectivity between motor cortex and muscles. These stimulation protocols modulate the gain of the activated pathways, but not the overall corticospinal recruitment. In this study, a brain-machine interface paired peripheral stimulation through passive hand opening with transcranial magnetic stimulation to the respective cortical motor representation during volitional β-band desynchronization. Cortical stimulation resulted in the recruitment of additional corticospinal pathways, but only when applied brain state-dependently and synchronously to peripheral input. These effects resemble a gating mechanism and may be important for the restoration of motor function following lesions of the corticospinal tract. Copyright © 2018 the authors 0270-6474/18/381397-12$15.00/0.

The Effects of Audiovisual Inputs on Solving the Cocktail Party Problem in the Human Brain: An fMRI Study.

PubMed

Li, Yuanqing; Wang, Fangyi; Chen, Yongbin; Cichocki, Andrzej; Sejnowski, Terrence

2017-09-25

At cocktail parties, our brains often simultaneously receive visual and auditory information. Although the cocktail party problem has been widely investigated under auditory-only settings, the effects of audiovisual inputs have not. This study explored the effects of audiovisual inputs in a simulated cocktail party. In our fMRI experiment, each congruent audiovisual stimulus was a synthesis of 2 facial movie clips, each of which could be classified into 1 of 2 emotion categories (crying and laughing). Visual-only (faces) and auditory-only stimuli (voices) were created by extracting the visual and auditory contents from the synthesized audiovisual stimuli. Subjects were instructed to selectively attend to 1 of the 2 objects contained in each stimulus and to judge its emotion category in the visual-only, auditory-only, and audiovisual conditions. The neural representations of the emotion features were assessed by calculating decoding accuracy and brain pattern-related reproducibility index based on the fMRI data. We compared the audiovisual condition with the visual-only and auditory-only conditions and found that audiovisual inputs enhanced the neural representations of emotion features of the attended objects instead of the unattended objects. This enhancement might partially explain the benefits of audiovisual inputs for the brain to solve the cocktail party problem. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis

PubMed Central

Martin, Neil A.; McArthur, David L.; Hovda, David A.; Vespa, Paul; Johnson, Matthew L.; Horning, Michael A.; Brooks, George A.

2015-01-01

Abstract We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-2H2]glucose, i.e., D2-glucose, and [3-13C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2–10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain. PMID:25279664

Graph theory analysis of cortical thickness networks in adolescents with d-transposition of the great arteries.

PubMed

Watson, Christopher G; Stopp, Christian; Newburger, Jane W; Rivkin, Michael J

2018-02-01

Adolescents with d-transposition of the great arteries (d-TGA) who had the arterial switch operation in infancy have been found to have structural brain differences compared to healthy controls. We used cortical thickness measurements obtained from structural brain MRI to determine group differences in global brain organization using a graph theoretical approach. Ninety-two d-TGA subjects and 49 controls were scanned using one of two identical 1.5-Tesla MRI systems. Mean cortical thickness was obtained from 34 regions per hemisphere using Freesurfer. A linear model was used for each brain region to adjust for subject age, sex, and scanning location. Structural connectivity for each group was inferred based on the presence of high inter-regional correlations of the linear model residuals, and binary connectivity matrices were created by thresholding over a range of correlation values for each group. Graph theory analysis was performed using packages in R. Permutation tests were performed to determine significance of between-group differences in global network measures. Within-group connectivity patterns were qualitatively different between groups. At lower network densities, controls had significantly more long-range connections. The location and number of hub regions differed between groups: controls had a greater number of hubs at most network densities. The control network had a significant rightward asymmetry compared to the d-TGA group at all network densities. Using graph theory analysis of cortical thickness correlations, we found differences in brain structural network organization among d-TGA adolescents compared to controls. These may be related to the white matter and gray matter differences previously found in this cohort, and in turn may be related to the cognitive deficits this cohort presents.

Use of Transcranial Doppler in Patients with Severe Traumatic Brain Injuries.

PubMed

Ziegler, Daniel; Cravens, George; Poche, Gerard; Gandhi, Raj; Tellez, Mark

2017-01-01

Severe traumatic brain injuries (TBI) are associated with a high rate of mortality and disability. Transcranial Doppler (TCD) sonography permits a noninvasive measurement of cerebral blood flow. The purpose of this study is to determine the usefulness of TCD in patients with severe TBI. TCD was performed, from April 2008 to April 2013, on 255 patients with severe TBI, defined as a Glasgow Coma Scale score of ≤8 on admission. TCD was performed on hospital days 1, 2, 3, and 7. Hypoperfusion was defined by having two out of three of the following: 1) mean velocity (Vm) of the middle cerebral artery <35 cm/sec, 2) diastolic velocity (Vd) of the middle cerebral artery <20 cm/sec, or 3) pulsatility index (PI) of >1.4. Vasospasm was defined by the following: Vm of the middle cerebral artery >120 cm/sec and/or a Lindegaard index (LI) >3. One hundred fourteen (45%) had normal measurements. Of these, 92 (80.7%) had a good outcome, 6 (5.3%) had moderate disability, and 16 (14%) died, 4 from brain death. Seventy-two patients (28%) had hypoperfusion and 71 (98.6%) died, 65 from brain death, and 1 patient survived with moderate disability. Sixty-nine patients (27%) had vasospasm, 31 (44.9%) had a good outcome, 16 (23.2%) had severe disability, and 22 (31.9%) died, 13 from brain death. The vasospasm was detected on hospital day 1 in 8 patients, on day 2 in 23 patients, on day 3 in 22 patients, and on day 7 in 16 patients. Patients with normal measurements can be expected to survive. Patients with hypoperfusion have a poor prognosis. Patients with vasospasm have a high incidence of mortality and severe disability. TCD is useful in determining early prognosis.

Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

PubMed

Glenn, Thomas C; Martin, Neil A; McArthur, David L; Hovda, David A; Vespa, Paul; Johnson, Matthew L; Horning, Michael A; Brooks, George A

2015-06-01

We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e., D2-glucose, and [3-(13)C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2-10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain.

Clinical utility of third-trimester uterine artery Doppler in the prediction of brain hemodynamic deterioration and adverse perinatal outcome in small-for-gestational-age fetuses.

PubMed

Cruz-Martinez, R; Savchev, S; Cruz-Lemini, M; Mendez, A; Gratacos, E; Figueras, F

2015-03-01

To assess the clinical value of third-trimester uterine artery (UtA) Doppler ultrasound in the prediction of hemodynamic deterioration and adverse perinatal outcome in term small-for-gestational-age (SGA) fetuses. UtA Doppler parameters, cerebroplacental ratio (CPR) and fetal middle cerebral artery (MCA) pulsatility index (PI) were evaluated weekly, starting from the time of SGA diagnosis until 24 h before induction of labor, in a cohort of 327 SGA fetuses with normal umbilical artery PI (< 95th centile), delivered at > 37 weeks' gestation. Differences in the sequence of CPR and MCA-PI changes < 5th centile, between the group with normal UtA Doppler indices at diagnosis and those with abnormal UtA indices, were analyzed by survival analysis. In addition, the use of UtA Doppler value, alone or in combination with a brain Doppler scan before delivery, to predict the risk of Cesarean section, Cesarean section for non-reassuring fetal status (NRFS), neonatal acidosis and neonatal hospitalization was evaluated by logistic regression analysis, adjusted for gestational age at birth and birth-weight percentile. Abnormal UtA Doppler at diagnosis of SGA was associated with a higher risk of developing abnormal brain Doppler indices before induction of labor than in those with a normal UtA at diagnosis (62.7% vs 34.6%, respectively; P < 0.01). Compared to those with normal UtA Doppler indices, those with abnormal UtA Doppler findings were associated with a higher risk of intrapartum Cesarean section (52.2% vs 37.3%, respectively; P = 0.03), Cesarean section for NRFS (35.8% vs 23.1%, respectively; P = 0.03), neonatal acidosis (10.4% vs 7.7%, respectively; P = 0.47) and neonatal hospitalization (23.9% vs 16.5%, respectively; P = 0.16). Logistic regression analysis indicated that UtA Doppler findings were not significantly associated with adverse perinatal outcome independent of brain Doppler findings. UtA Doppler indices predict adverse perinatal outcome, but do not help to improve the predictive value of brain Doppler indices. However, at the time of SGA diagnosis they identify the subgroup of fetuses at highest risk of progression to abnormal brain Doppler findings. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Multiclassifier fusion in human brain MR segmentation: modelling convergence.

PubMed

Heckemann, Rolf A; Hajnal, Joseph V; Aljabar, Paul; Rueckert, Daniel; Hammers, Alexander

2006-01-01

Segmentations of MR images of the human brain can be generated by propagating an existing atlas label volume to the target image. By fusing multiple propagated label volumes, the segmentation can be improved. We developed a model that predicts the improvement of labelling accuracy and precision based on the number of segmentations used as input. Using a cross-validation study on brain image data as well as numerical simulations, we verified the model. Fit parameters of this model are potential indicators of the quality of a given label propagation method or the consistency of the input segmentations used.

Diameter of fluorescent microspheres determines their distribution throughout the cortical watershed area in mice.

PubMed

Tsukada, Naoki; Katsumata, Masahiro; Oki, Koichi; Minami, Kazushi; Abe, Takato; Takahashi, Shinichi; Itoh, Yoshiaki; Suzuki, Norihiro

2018-01-15

A hemodynamic mechanism has long been assumed to play an important role in watershed infarction. In recent years, however, clinical evidence has indicated that an embolic mechanism is involved. The mechanism by which emboli are trapped preferentially in watershed areas remains unclear. In the present study, we developed a mouse embolus model using fluorescent microspheres with different diameters and evaluated the role of the microspheres' diameters in the generation of a watershed-patterned distribution. We injected fluorescent microspheres of four different diameters (i.e., 13, 24, 40, and 69 μm) into the internal carotid artery of C57BL/6 mice either (1) without ligation of the common carotid artery (normal perfusion pressure model: NPPM) or (2) with ligation of the common carotid artery (low perfusion pressure model: LPPM). Left common carotid artery ligation induced reductions in local cerebral blood flow in both the periphery and the core area of the left middle cerebral artery. A greater reduction in the border-zone area between the left anterior cerebral artery and the middle cerebral artery was also noted. After 24 h, the brains were removed and the distribution of the microspheres in the brain was evaluated using a fluorescence microscope. The 24-μm microspheres were distributed in the watershed area more frequently than the other microsphere sizes (P < .05, ANOVA followed by Tukey's test). Meanwhile, the distribution rates were similar between the NPPM and LPPM models for all microsphere sizes. This study suggested that the distribution pattern of the microspheres was only affected by the microspheres' diameters. Copyright © 2017 Elsevier B.V. All rights reserved.

Subcortical hematoma caused by cerebral amyloid angiopathy: does the first evidence of hemorrhage occur in the subarachnoid space?

PubMed

Takeda, Shigeki; Yamazaki, Kazunori; Miyakawa, Teruo; Onda, Kiyoshi; Hinokuma, Kaoru; Ikuta, Fusahiro; Arai, Hiroyuki

2003-12-01

Six autopsy cases of subcortical hematoma caused by CAA were examined to elucidate the primary site of hemorrhage. Immunohistochemistry for amyloid beta-protein (A beta) revealed extensive CAA in the intrasulcal meningeal vessels rather than in the cerebral cortical vessels. All of the examined cases had multiple hematomas in the subarachnoid space, mainly in the cerebral sulci, as well as intracerebral hematomas. Each intracerebral hematoma was connected to the subarachnoid hematomas at the depth of cerebral sulci or through the lateral side of the cortex. There was no debris of the cerebral cortical tissue in the subarachnoid hematomas. In case 2, another solitary subarachnoid hematoma, which was not connected to any intracerebral hematoma, was seen. In all of these subarachnoid hematomas, many ruptured A beta-immunopositive arteries were observed. These ruptured arteries did not accompany any debris of the brain tissue, some of them were large in diameter (250-300 microm), and several of them were far from the cerebral cortex. Therefore, it was considered that they were not cortical arteries but meningeal arteries. Within the cerebral cortex, there were only a few ruptured arteries associated with small hemorrhages. There were no ruptured vessels within the intracerebral hematomas. There was a strong suggestion that all of the subarachnoid hematomas, including the solitary one in case 2, originated from the rupture of the meningeal arteries. The present study indicates that in some cases of subcortical hematoma caused by CAA, the primary hemorrhage occurs in the subarachnoid space, in particular the cerebral sulci, because of rupture of multiple meningeal arteries. Infarction occurs subsequently in the cortex around the hematoma, the hematoma penetrates into the brain parenchyma, and finally, a subcortical hematoma is formed.

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy.

PubMed

Shin, Jong Wook; Jeong, Hye Seon; Kwon, Hyon-Jo; Song, Kyu Sang; Kim, Jei

2018-01-01

We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2-3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images.

Intracerebral Hemorrhage Caused by Cerebral Hyperperfusion after Superficial Temporal Artery to Middle Cerebral Artery Bypass for Atherosclerotic Occlusive Cerebrovascular Disease

PubMed Central

Matano, Fumihiro; Murai, Yasuo; Mizunari, Takayuki; Adachi, Koji; Kobayashi, Shiro; Morita, Akio

Few papers have reported detailed accounts of intracerebral hemorrhage caused by cerebral hyperperfusion after superficial temporal artery to middle cerebral artery bypass (STA-MCA) bypass for atherosclerotic occlusive cerebrovascular disease. We report a case of vasogenic edema and subsequent intracerebral hemorrhage caused by the cerebral hyperperfusion syndrome (CHS) after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease disease without intense postoperative blood pressure control. A 63-year-old man with repeating left hemiparesis underwent magnetic resonance angiography (MRA), which revealed right internal carotid artery (ICA) occlusion. We performed a double bypass superficial temporal artery (STA)–middle cerebral artery (MCA) bypass surgery for the M2 and M3 branches. While the patient’s postoperative course was relatively uneventful, he suffered generalized convulsions, and computed tomography revealed a low area in the right frontal lobe on Day 4 after surgery. We considered this lesion to be pure vasogenic edema caused by cerebral hyperperfusion after revascularization. Intravenous drip infusion of a free radical scavenger (edaravone) and efforts to reduce systolic blood pressure to <120 mmHg were continued. The patient experienced severe left hemiparesis and disturbance of consciousness on Day 8 after surgery, due to intracerebral hemorrhage in the right frontal lobe at the site of the earlier vasogenic edema. Brain edema associated with cerebral hyperperfusion after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease should be recognized as a risk factor for intracerebral hemorrhage. The development of brain edema associated with CHS after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease requires not only intensive control of blood pressure, but also consideration of sedation therapy with propofol. PMID:28664022

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy

PubMed Central

Shin, Jong Wook; Jeong, Hye Seon; Kwon, Hyon-Jo; Song, Kyu Sang

2018-01-01

We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2–3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images. PMID:29782513

Pelvic artery calcification detection on CT scans using convolutional neural networks

NASA Astrophysics Data System (ADS)

Liu, Jiamin; Lu, Le; Yao, Jianhua; Bagheri, Mohammadhadi; Summers, Ronald M.

2017-03-01

Artery calcification is observed commonly in elderly patients, especially in patients with chronic kidney disease, and may affect coronary, carotid and peripheral arteries. Vascular calcification has been associated with many clinical outcomes. Manual identification of calcification in CT scans requires substantial expert interaction, which makes it time-consuming and infeasible for large-scale studies. Many works have been proposed for coronary artery calcification detection in cardiac CT scans. In these works, coronary artery extraction is commonly required for calcification detection. However, there are few works about abdominal or pelvic artery calcification detection. In this work, we present a method for automatic pelvic artery calcification detection on CT scan. This method uses the recent advanced faster region-based convolutional neural network (R-CNN) to directly identify artery calcification without a need for artery extraction since pelvic artery extraction itself is challenging. Our method first generates category-independent region proposals for each slice of the input CT scan using region proposal networks (RPN). Then, each region proposal is jointly classified and refined by softmax classifier and bounding box regressor. We applied the detection method to 500 images from 20 CT scans of patients for evaluation. The detection system achieved a 77.4% average precision and a 85% sensitivity at 1 false positive per image.

Body water conservation through selective brain cooling by the carotid rete: a physiological feature for surviving climate change?

PubMed Central

Hetem, Robyn S.; Mitchell, Duncan; Maloney, Shane K.; O'Brien, Haley D.; Meyer, Leith C. R.; Fuller, Andrea

2017-01-01

Abstract Some mammals have the ability to lower their hypothalamic temperature below that of carotid arterial blood temperature, a process termed selective brain cooling. Although the requisite anatomical structure that facilitates this physiological process, the carotid rete, is present in members of the Cetartiodactyla, Felidae and Canidae, the carotid rete is particularly well developed in the artiodactyls, e.g. antelopes, cattle, sheep and goats. First described in the domestic cat, the seemingly obvious function initially attributed to selective brain cooling was that of protecting the brain from thermal damage. However, hyperthermia is not a prerequisite for selective brain cooling, and selective brain cooling can be exhibited at all times of the day, even when carotid arterial blood temperature is relatively low. More recently, it has been shown that selective brain cooling functions primarily as a water-conservation mechanism, allowing artiodactyls to save more than half of their daily water requirements. Here, we argue that the evolutionary success of the artiodactyls may, in part, be attributed to the evolution of the carotid rete and the resulting ability to conserve body water during past environmental conditions, and we suggest that this group of mammals may therefore have a selective advantage in the hotter and drier conditions associated with current anthropogenic climate change. A better understanding of how selective brain cooling provides physiological plasticity to mammals in changing environments will improve our ability to predict their responses and to implement appropriate conservation measures. PMID:29383253

Energy harvesting from arterial blood pressure for powering embedded brain sensors

NASA Astrophysics Data System (ADS)

Nanda, Aditya; Karami, M. Amin

2016-04-01

This paper investigates energy harvesting from arterial blood pressure via the piezoelectric effect by using a novel streaked cylinder geometry for the purpose of powering embedded micro-sensors in the brain. Initially, we look at the energy harvested by a piezoelectric cylinder placed inside an artery acted upon by blood pressure. Such an arrangement would be tantamount to constructing a stent out of piezoelectric materials. A stent is a cylinder placed in veins and arteries to prevent obstruction in blood flow. The governing equations of a conductor coated piezoelectric cylinder are obtained using Hamilton's principle. Pressure acting in arteries is radially directed and this is used to simplify the modal analysis and obtain the transfer function relating pressure to the induced voltage across the surface of the harvester. The power harvested by the cylindrical harvester is obtained for different shunt resistances. Radially directed pressure occurs elsewhere and we also look at harvesting energy from oil flow in pipelines. Although the energy harvested by the cylindrical energy harvester is significant at resonance, the natural frequency of the system is found to be very high. To decrease the natural frequency, we propose a novel streaked stent design by cutting it along the length, transforming it to a curved plate and decreasing the natural frequency. The governing equations corresponding to the new geometry are derived using Hamilton's principle and modal analysis is used to obtain the transfer function.

Hypertrophy of the vasa vasorum: vascular response to the hungry brain.

PubMed

Cho, Hyun-Ji; Roh, Hong Gee; Chun, Young Il; Moon, Chang Taek; Chung, Hyun Woo; Kim, Hahn Young

2012-05-01

The vasa vasorum is a network of microvessels that supplies nutrients to the vessel wall itself. In pathologic conditions, the vasa vasorum can develop as potential collateral channels. Previous research documents revascularization through hypertrophy of the vasa vasorum after occlusion of the carotid artery. However, the relationship between the cerebral vascular demands and the hypertrophy of the vasa vasorum has not been well delineated by functional studies. A 66-year-old man presented with left hemiparesis, dysarthria, and hemineglect. Magnetic resonance imaging revealed an acute infarction in the vascular territory of the right middle cerebral artery. Transfemoral cerebral angiography revealed occlusion of the right proximal internal carotid artery (ICA). Single-photon emission computed tomography study showed decreased vascular reserve in the right cerebral hemisphere. Right superficial temporal artery-middle cerebral artery bypass surgery was performed in an attempt to improve hemispheric perfusion. Follow-up angiography 1 year later showed revascularization of the distal ICA by the hypertrophied vasa vasorum. Follow-up single-photon emission computed tomography study showed persistent decreased vascular reserve. In cases of ICA occlusion, a 1-year or less hungry period for the cerebral vascular demand may activate potential collateral channels of the vasa vasorum. In addition to the metabolic demand of the occluded vessel wall itself, the vascular demands of the hypoperfused brain may be a trigger factor that leads to hypertrophy of the vasa vasorum as collateral channels.

Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: Occurrence and perfusion characteristics

PubMed Central

Sommer, Wieland H; Bollwein, Christine; Thierfelder, Kolja M; Baumann, Alena; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F; Plate, Annika; Straube, Andreas

2015-01-01

We aimed to investigate the overall prevalence and possible factors influencing the occurrence of crossed cerebellar diaschisis after acute middle cerebral artery infarction using whole-brain CT perfusion. A total of 156 patients with unilateral hypoperfusion of the middle cerebral artery territory formed the study cohort; 352 patients without hypoperfusion served as controls. We performed blinded reading of different perfusion maps for the presence of crossed cerebellar diaschisis and determined the relative supratentorial and cerebellar perfusion reduction. Moreover, imaging patterns (location and volume of hypoperfusion) and clinical factors (age, sex, time from symptom onset) resulting in crossed cerebellar diaschisis were analysed. Crossed cerebellar diaschisis was detected in 35.3% of the patients with middle cerebral artery infarction. Crossed cerebellar diaschisis was significantly associated with hypoperfusion involving the left hemisphere, the frontal lobe and the thalamus. The degree of the relative supratentorial perfusion reduction was significantly more pronounced in crossed cerebellar diaschisis-positive patients but did not correlate with the relative cerebellar perfusion reduction. Our data suggest that (i) crossed cerebellar diaschisis is a common feature after middle cerebral artery infarction which can robustly be detected using whole-brain CT perfusion, (ii) its occurrence is influenced by location and degree of the supratentorial perfusion reduction rather than infarct volume (iii) other clinical factors (age, sex and time from symptom onset) did not affect the occurrence of crossed cerebellar diaschisis. PMID:26661242

Variability of perceptual multistability: from brain state to individual trait

PubMed Central

Kleinschmidt, Andreas; Sterzer, Philipp; Rees, Geraint

2012-01-01

Few phenomena are as suitable as perceptual multistability to demonstrate that the brain constructively interprets sensory input. Several studies have outlined the neural circuitry involved in generating perceptual inference but only more recently has the individual variability of this inferential process been appreciated. Studies of the interaction of evoked and ongoing neural activity show that inference itself is not merely a stimulus-triggered process but is related to the context of the current brain state into which the processing of external stimulation is embedded. As brain states fluctuate, so does perception of a given sensory input. In multistability, perceptual fluctuation rates are consistent for a given individual but vary considerably between individuals. There has been some evidence for a genetic basis for these individual differences and recent morphometric studies of parietal lobe regions have identified neuroanatomical substrates for individual variability in spontaneous switching behaviour. Moreover, disrupting the function of these latter regions by transcranial magnetic stimulation yields systematic interference effects on switching behaviour, further arguing for a causal role of these regions in perceptual inference. Together, these studies have advanced our understanding of the biological mechanisms by which the brain constructs the contents of consciousness from sensory input. PMID:22371620

Respiratory modulation of human autonomic function on Earth.

PubMed

Eckberg, Dwain L; Cooke, William H; Diedrich, André; Biaggioni, Italo; Buckey, Jay C; Pawelczyk, James A; Ertl, Andrew C; Cox, James F; Kuusela, Tom A; Tahvanainen, Kari U O; Mano, Tadaaki; Iwase, Satoshi; Baisch, Friedhelm J; Levine, Benjamin D; Adams-Huet, Beverley; Robertson, David; Blomqvist, C Gunnar

2016-10-01

We studied healthy supine astronauts on Earth with electrocardiogram, non-invasive arterial pressure, respiratory carbon dioxide concentrations, breathing depth and sympathetic nerve recordings. The null hypotheses were that heart beat interval fluctuations at usual breathing frequencies are baroreflex mediated, that they persist during apnoea, and that autonomic responses to apnoea result from changes of chemoreceptor, baroreceptor or lung stretch receptor inputs. R-R interval fluctuations at usual breathing frequencies are unlikely to be baroreflex mediated, and disappear during apnoea. The subjects' responses to apnoea could not be attributed to changes of central chemoreceptor activity (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex gain declined and muscle sympathetic nerve burst areas, frequencies and probabilities increased, even as arterial pressure climbed to new levels); or altered pulmonary stretch receptor activity (major breathing frequency and tidal volume changes did not alter vagal tone or sympathetic activity). Apnoea responses of healthy subjects may result from changes of central respiratory motoneurone activity. We studied eight healthy, supine astronauts on Earth, who followed a simple protocol: they breathed at fixed or random frequencies, hyperventilated and then stopped breathing, as a means to modulate and expose to view important, but obscure central neurophysiological mechanisms. Our recordings included the electrocardiogram, finger photoplethysmographic arterial pressure, tidal volume, respiratory carbon dioxide concentrations and peroneal nerve muscle sympathetic activity. Arterial pressure, vagal tone and muscle sympathetic outflow were comparable during spontaneous and controlled-frequency breathing. Compared with spontaneous, 0.1 and 0.05 Hz breathing, however, breathing at usual frequencies (∼0.25 Hz) lowered arterial baroreflex gain, and provoked smaller arterial pressure and R-R interval fluctuations, which were separated by intervals that were likely to be too short and variable to be attributed to baroreflex physiology. R-R interval fluctuations at usual breathing frequencies disappear during apnoea, and thus cannot provide evidence for the existence of a central respiratory oscillation. Apnoea sets in motion a continuous and ever changing reorganization of the relations among stimulatory and inhibitory inputs and autonomic outputs, which, in our study, could not be attributed to altered chemoreceptor, baroreceptor, or pulmonary stretch receptor activity. We suggest that responses of healthy subjects to apnoea are driven importantly, and possibly prepotently, by changes of central respiratory motoneurone activity. The companion article extends these observations and asks the question, Might terrestrial responses to our 20 min breathing protocol find expression as long-term neuroplasticity in serial measurements made over 20 days during and following space travel? Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Respiratory modulation of human autonomic function on Earth

PubMed Central

Cooke, William H.; Diedrich, André; Biaggioni, Italo; Buckey, Jay C.; Pawelczyk, James A.; Ertl, Andrew C.; Cox, James F.; Kuusela, Tom A.; Tahvanainen, Kari U. O.; Mano, Tadaaki; Iwase, Satoshi; Baisch, Friedhelm J.; Levine, Benjamin D.; Adams‐Huet, Beverley; Robertson, David; Blomqvist, C. Gunnar

2016-01-01

Key points We studied healthy supine astronauts on Earth with electrocardiogram, non‐invasive arterial pressure, respiratory carbon dioxide concentrations, breathing depth and sympathetic nerve recordings.The null hypotheses were that heart beat interval fluctuations at usual breathing frequencies are baroreflex mediated, that they persist during apnoea, and that autonomic responses to apnoea result from changes of chemoreceptor, baroreceptor or lung stretch receptor inputs.R‐R interval fluctuations at usual breathing frequencies are unlikely to be baroreflex mediated, and disappear during apnoea.The subjects’ responses to apnoea could not be attributed to changes of central chemoreceptor activity (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex gain declined and muscle sympathetic nerve burst areas, frequencies and probabilities increased, even as arterial pressure climbed to new levels); or altered pulmonary stretch receptor activity (major breathing frequency and tidal volume changes did not alter vagal tone or sympathetic activity). Apnoea responses of healthy subjects may result from changes of central respiratory motoneurone activity. Abstract We studied eight healthy, supine astronauts on Earth, who followed a simple protocol: they breathed at fixed or random frequencies, hyperventilated and then stopped breathing, as a means to modulate and expose to view important, but obscure central neurophysiological mechanisms. Our recordings included the electrocardiogram, finger photoplethysmographic arterial pressure, tidal volume, respiratory carbon dioxide concentrations and peroneal nerve muscle sympathetic activity. Arterial pressure, vagal tone and muscle sympathetic outflow were comparable during spontaneous and controlled‐frequency breathing. Compared with spontaneous, 0.1 and 0.05 Hz breathing, however, breathing at usual frequencies (∼0.25 Hz) lowered arterial baroreflex gain, and provoked smaller arterial pressure and R‐R interval fluctuations, which were separated by intervals that were likely to be too short and variable to be attributed to baroreflex physiology. R‐R interval fluctuations at usual breathing frequencies disappear during apnoea, and thus cannot provide evidence for the existence of a central respiratory oscillation. Apnoea sets in motion a continuous and ever changing reorganization of the relations among stimulatory and inhibitory inputs and autonomic outputs, which, in our study, could not be attributed to altered chemoreceptor, baroreceptor, or pulmonary stretch receptor activity. We suggest that responses of healthy subjects to apnoea are driven importantly, and possibly prepotently, by changes of central respiratory motoneurone activity. The companion article extends these observations and asks the question, Might terrestrial responses to our 20 min breathing protocol find expression as long‐term neuroplasticity in serial measurements made over 20 days during and following space travel? PMID:27028958

Connectivity in the human brain dissociates entropy and complexity of auditory inputs☆

PubMed Central

Nastase, Samuel A.; Iacovella, Vittorio; Davis, Ben; Hasson, Uri

2015-01-01

Complex systems are described according to two central dimensions: (a) the randomness of their output, quantified via entropy; and (b) their complexity, which reflects the organization of a system's generators. Whereas some approaches hold that complexity can be reduced to uncertainty or entropy, an axiom of complexity science is that signals with very high or very low entropy are generated by relatively non-complex systems, while complex systems typically generate outputs with entropy peaking between these two extremes. In understanding their environment, individuals would benefit from coding for both input entropy and complexity; entropy indexes uncertainty and can inform probabilistic coding strategies, whereas complexity reflects a concise and abstract representation of the underlying environmental configuration, which can serve independent purposes, e.g., as a template for generalization and rapid comparisons between environments. Using functional neuroimaging, we demonstrate that, in response to passively processed auditory inputs, functional integration patterns in the human brain track both the entropy and complexity of the auditory signal. Connectivity between several brain regions scaled monotonically with input entropy, suggesting sensitivity to uncertainty, whereas connectivity between other regions tracked entropy in a convex manner consistent with sensitivity to input complexity. These findings suggest that the human brain simultaneously tracks the uncertainty of sensory data and effectively models their environmental generators. PMID:25536493

Combined contributions of feedforward and feedback inputs to bottom-up attention

PubMed Central

Khorsand, Peyman; Moore, Tirin; Soltani, Alireza

2015-01-01

In order to deal with a large amount of information carried by visual inputs entering the brain at any given point in time, the brain swiftly uses the same inputs to enhance processing in one part of visual field at the expense of the others. These processes, collectively called bottom-up attentional selection, are assumed to solely rely on feedforward processing of the external inputs, as it is implied by the nomenclature. Nevertheless, evidence from recent experimental and modeling studies points to the role of feedback in bottom-up attention. Here, we review behavioral and neural evidence that feedback inputs are important for the formation of signals that could guide attentional selection based on exogenous inputs. Moreover, we review results from a modeling study elucidating mechanisms underlying the emergence of these signals in successive layers of neural populations and how they depend on feedback from higher visual areas. We use these results to interpret and discuss more recent findings that can further unravel feedforward and feedback neural mechanisms underlying bottom-up attention. We argue that while it is descriptively useful to separate feedforward and feedback processes underlying bottom-up attention, these processes cannot be mechanistically separated into two successive stages as they occur at almost the same time and affect neural activity within the same brain areas using similar neural mechanisms. Therefore, understanding the interaction and integration of feedforward and feedback inputs is crucial for better understanding of bottom-up attention. PMID:25784883

An optimal frequency range for assessing the pressure reactivity index in patients with traumatic brain injury.

PubMed

Howells, Tim; Johnson, Ulf; McKelvey, Tomas; Enblad, Per

2015-02-01

The objective of this study was to identify the optimal frequency range for computing the pressure reactivity index (PRx). PRx is a clinical method for assessing cerebral pressure autoregulation based on the correlation of spontaneous variations of arterial blood pressure (ABP) and intracranial pressure (ICP). Our hypothesis was that optimizing the methodology for computing PRx in this way could produce a more stable, reliable and clinically useful index of autoregulation status. The patients studied were a series of 131 traumatic brain injury patients. Pressure reactivity indices were computed in various frequency bands during the first 4 days following injury using bandpass filtering of the input ABP and ICP signals. Patient outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The optimization criterion was the strength of the correlation with GOSe of the mean index value over the first 4 days following injury. Stability of the indices was measured as the mean absolute deviation of the minute by minute index value from 30-min moving averages. The optimal index frequency range for prediction of outcome was identified as 0.018-0.067 Hz (oscillations with periods from 55 to 15 s). The index based on this frequency range correlated with GOSe with ρ=-0.46 compared to -0.41 for standard PRx, and reduced the 30-min variation by 23%.

Licorice Pretreatment Protects Against Brain Damage Induced by Middle Cerebral Artery Occlusion in Mice.

PubMed

Lim, Chiyeon; Lim, Sehyun; Lee, Byoungho; Kim, Buyeo; Cho, Suin

2018-05-01

Licorice is extracted from the roots of plants in the Glycyrrhiza genus, especially Glycyrrhiza uralensis in China and Korea. It has several pharmacological activities, including neuro-protective, anti-fungal, and anti-cariogenic effects. Ischemia/reperfusion-induced brain injury is a leading cause of adult disability and death; thus, the identification of anti-apoptotic, neuro-protective therapeutic agents is viewed as an attractive drug development strategy. Infarct volumes and the expression of several apoptosis-related proteins, including Bcl-xL, Bcl-2, caspase-8, and caspase-9, were evaluated by western blotting in the brains of mice subjected to middle cerebral artery occlusion (MCAO). Three consecutive days of oral pretreatment with the methanol extract of licorice (GRex) significantly reduced infarct volumes 24 h after MCAO. In addition, GRex effectively inhibited the activation of caspase-9 by upregulating protein expression of Bcl-xL and Bcl-2. The neuro-protective effect of licorice was due to its regulation of apoptosis-related proteins. These data suggest that licorice could be a potential candidate for the treatment of ischemia-induced brain damage.

Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availability After Acute Brain Injury.

PubMed

Carteron, Laurent; Solari, Daria; Patet, Camille; Quintard, Hervé; Miroz, John-Paul; Bloch, Jocelyne; Daniel, Roy T; Hirt, Lorenz; Eckert, Philippe; Magistretti, Pierre J; Oddo, Mauro

2018-06-19

Lactate promotes cerebral blood flow and is an efficient substrate for the brain, particularly at times of glucose shortage. Hypertonic lactate is neuroprotective after experimental brain injury; however, human data are limited. Prospective study (clinicaltrials.gov NCT01573507). Academic ICU. Twenty-three brain-injured subjects (13 traumatic brain injury/10 subarachnoid hemorrhage; median age, 59 yr [41-65 yr]; median Glasgow Coma Scale, 6 [3-7]). Three-hour IV infusion of hypertonic lactate (sodium lactate, 1,000 mmol/L; concentration, 30 µmol/kg/min) administered 39 hours (26-49 hr) from injury. We examined the effect of hypertonic lactate on cerebral perfusion (using transcranial Doppler) and brain energy metabolism (using cerebral microdialysis). The majority of subjects (13/23 = 57%) had reduced brain glucose availability (baseline pretreatment cerebral microdialysis glucose, < 1 mmol/L) despite normal baseline intracranial pressure (10 [7-15] mm Hg). Hypertonic lactate was associated with increased cerebral microdialysis lactate (+55% [31-80%]) that was paralleled by an increase in middle cerebral artery mean cerebral blood flow velocities (+36% [21-66%]) and a decrease in pulsatility index (-21% [13-26%]; all p < 0.001). Cerebral microdialysis glucose increased above normal range during hypertonic lactate (+42% [30-78%]; p < 0.05); reduced brain glucose availability correlated with a greater improvement of cerebral microdialysis glucose (Spearman r = -0.53; p = 0.009). No significant changes in cerebral perfusion pressure, mean arterial pressure, systemic carbon dioxide, and blood glucose were observed during hypertonic lactate (all p > 0.1). This is the first clinical demonstration that hypertonic lactate resuscitation improves both cerebral perfusion and brain glucose availability after brain injury. These cerebral vascular and metabolic effects appeared related to brain lactate supplementation rather than to systemic effects.

Regulation of brain temperature in winter-acclimatized reindeer under heat stress.

PubMed

Blix, Arnoldus Schytte; Walløe, Lars; Folkow, Lars P

2011-11-15

Reindeer (Rangifer tarandus) are protected against the Arctic winter cold by thick fur of prime insulating capacity and hence have few avenues of heat loss during work. We have investigated how these animals regulate brain temperature under heavy heat loads. Animals were instrumented for measurements of blood flow, tissue temperatures and respiratory frequency (f) under full anaesthesia, whereas measurements were also made in fully conscious animals while in a climatic chamber or running on a treadmill. At rest, brain temperature (T(brain)) rose from 38.5±0.1°C at 10°C to 39.5±0.2°C at 50°C, while f increased from ×7 to ×250 breaths min(-1), with a change to open-mouth panting (OMP) at T(brain) 39.0±0.1°C, and carotid and sublingual arterial flows increased by 160% and 500%, respectively. OMP caused jugular venous and carotid arterial temperatures to drop, presumably owing to a much increased respiratory evaporative heat loss. Angular oculi vein (AOV) flow was negligible until T(brain) reached 38.9±0.1°C, but it increased to 0.81 ml min(-1) kg(-1) at T(brain) 39.2±0.2°C. Bilateral occlusion of both AOVs induced OMP and a rise in T(brain) and f at T(brain) >38.8°C. We propose that reindeer regulate body and, particularly, brain temperature under heavy heat loads by a combination of panting, at first through the nose, but later, when the heat load and the minute volume requirements increase due to exercise, primarily through the mouth and that they eventually resort to selective brain cooling.

Cerebral arterial oxygen saturation measurements using a fiber-optic pulse oximeter.

PubMed

Phillips, J P; Langford, R M; Chang, S H; Maney, K; Kyriacou, P A; Jones, D P

2010-10-01

A pilot investigation was undertaken to assess the performance of a novel fiber-optic cerebral pulse oximetry system. A fiber-optic probe designed to pass through the lumen of a cranial bolt of the type used to make intracranial pressure measurements was used to obtain optical reflectance signals directly from brain tissue. Short-duration measurements were made in six patients undergoing neurosurgery. These were followed by a longer duration measurement in a patient recovering from an intracerebral hematoma. Estimations of cerebral arterial oxygen saturation derived from a frequency domain-based algorithm are compared with simultaneous pulse oximetry (SpO2) and hemoximeter (SaO2) blood samples. The short-duration measurements showed that reliable photoplethysmographic signals could be obtained from the brain tissue. In the long-duration study, the mean (±SD) difference between cerebral oxygen saturation (ScaO2) and finger SpO2 (in saturation units) was -7.47(±3.4)%. The mean (±SD) difference between ScaO2 and blood SaO2 was -7.37(±2.8)%. This pilot study demonstrated that arterial oxygen saturation may be estimated from brain tissue via a fiber-optic pulse oximeter used in conjunction with a cranial bolt. Further studies are needed to confirm the clinical utility of the technique.

Neural correlates of brain state in chronic ischemia and stroke: combined resting state electroencephalogram and transcranial Doppler ultrasonographic study.

PubMed

Martynova, Olga V; Portnova, Galina V; Gladun, Ksenya V

2017-02-08

Clinical neurology is constantly searching for reliable indices of ischemic brain damage to prevent a possible development of stroke. We suggest that resting state electroencephalogram (rsEEG) with respect to other clinical data may provide important information about the severity of ischemia. We carried out correlation analysis of rsEEG, data of transcranial Doppler ultrasonography of head vessels, and clinical assessment scores collected from healthy volunteers and four groups of patients with mild chronic microvascular ischemia (CMI-1), moderate CMI (CMI-2), severe atrophy of the cerebral hemisphere, ischemic stroke in the left middle cerebral artery stroke, and ischemic stroke in the right middle cerebral artery stroke. Using independent component analysis and k-mean clustering of EEG data, we observed prominent changes in rsEEG reflected in specific distributions of spectral peaks in all groups of patients. We found a significant correlation of EEG spectral distribution and the blood flow velocity in coronal arteries, which was also affected by the severity of ischemia and the localization of stroke. Moreover, EEG spectral distribution was more indicative of early stages of ischemia than the blood flow velocity. Our data support the hypothesis that rsEEG may reflect altered neural activity caused by ischemic brain damage.

Modeling and Simulation of Cardiogenic Embolic Particle Transport to the Brain

NASA Astrophysics Data System (ADS)

Mukherjee, Debanjan; Jani, Neel; Shadden, Shawn C.

2015-11-01

Emboli are aggregates of cells, proteins, or fatty material, which travel along arteries distal to the point of their origin, and can potentially block blood flow to the brain, causing stroke. This is a prominent mechanism of stroke, accounting for about a third of all cases, with the heart being a prominent source of these emboli. This work presents our investigations towards developing numerical simulation frameworks for modeling the transport of embolic particles originating from the heart along the major arteries supplying the brain. The simulations are based on combining discrete particle method with image based computational fluid dynamics. Simulations of unsteady, pulsatile hemodynamics, and embolic particle transport within patient-specific geometries, with physiological boundary conditions, are presented. The analysis is focused on elucidating the distribution of particles, transport of particles in the head across the major cerebral arteries connected at the Circle of Willis, the role of hemodynamic variables on the particle trajectories, and the effect of considering one-way vs. two-way coupling methods for the particle-fluid momentum exchange. These investigations are aimed at advancing our understanding of embolic stroke using computational fluid dynamics techniques. This research was supported by the American Heart Association grant titled ``Embolic Stroke: Anatomic and Physiologic Insights from Image-Based CFD.''

Estimation of Hidden State Variables of the Intracranial System Using Constrained Nonlinear Kalman Filters

PubMed Central

Nenov, Valeriy; Bergsneider, Marvin; Glenn, Thomas C.; Vespa, Paul; Martin, Neil

2007-01-01

Impeded by the rigid skull, assessment of physiological variables of the intracranial system is difficult. A hidden state estimation approach is used in the present work to facilitate the estimation of unobserved variables from available clinical measurements including intracranial pressure (ICP) and cerebral blood flow velocity (CBFV). The estimation algorithm is based on a modified nonlinear intracranial mathematical model, whose parameters are first identified in an offline stage using a nonlinear optimization paradigm. Following the offline stage, an online filtering process is performed using a nonlinear Kalman filter (KF)-like state estimator that is equipped with a new way of deriving the Kalman gain satisfying the physiological constraints on the state variables. The proposed method is then validated by comparing different state estimation methods and input/output (I/O) configurations using simulated data. It is also applied to a set of CBFV, ICP and arterial blood pressure (ABP) signal segments from brain injury patients. The results indicated that the proposed constrained nonlinear KF achieved the best performance among the evaluated state estimators and that the state estimator combined with the I/O configuration that has ICP as the measured output can potentially be used to estimate CBFV continuously. Finally, the state estimator combined with the I/O configuration that has both ICP and CBFV as outputs can potentially estimate the lumped cerebral arterial radii, which are not measurable in a typical clinical environment. PMID:17281533

Delayed Development of Brain Abscesses Following Stent-Graft Placement in a Head and Neck Cancer Patient Presenting with Carotid Blowout Syndrome

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

Oweis, Yaseen; Gemmete, Joseph J., E-mail: gemmete@umich.edu; Chaudhary, Neeraj

2011-02-15

We describe the delayed development of intracranial abscesses following emergent treatment with a covered stent-graft for carotid blowout syndrome (CBS) in a patient with head and neck cancer. The patient presented with hemoptysis and frank arterial bleeding through the tracheostomy site. A self-expandable stent-graft was deployed across a small pseudoaneurysm arising from the right common carotid artery (RCCA) and resulted in immediate hemostasis. Three months later, the patient suffered a recurrent hemorrhage. CT of the neck demonstrated periluminal fluid around the caudal aspect of the stent-graft with intraluminal thrombus and a small pseudoaneurysm. Subsequently, the patient underwent a balloon testmore » occlusion study and endovascular sacrifice of the RCCA and right internal carotid artery. MRI of the brain demonstrated at least four ring-enhancing lesions within the right cerebral hemisphere consistent with intracranial abscesses that resolved with broad-spectrum antibiotic coverage.« less

[The blood-brain barrier in ageing persons].

PubMed

Haaning, Nina; Damsgaard, Else Marie; Moos, Torben

2018-03-26

Brain capillary endothelial cells (BECs) form the ultra-tight blood-brain barrier (BBB). The permeability of the BBB increases with increasing age and neurovascular and neurodegenerative diseases. Major defects of the BBB can be initiated by increased permeability to plasma proteins in small arteriosclerotic arteries and release of proteins from degenerating neurons into the brain extracellular space. These proteins deposit in perivascular spaces, and subsequently negatively influence the BECs leading to decreased expression of barrier proteins. Detection of BBB defects by the use of non-invasive techniques is relevant for clinical use in settings with advanced age and severe brain disorders.

Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice

PubMed Central

Nielsen, Corinne M.; Cuervo, Henar; Ding, Vivianne W.; Kong, Yupeng; Huang, Eric J.; Wang, Rong A.

2014-01-01

Arteriovenous malformations (AVMs) are tortuous vessels characterized by arteriovenous (AV) shunts, which displace capillaries and shunt blood directly from artery to vein. Notch signaling regulates embryonic AV specification by promoting arterial, as opposed to venous, endothelial cell (EC) fate. To understand the essential role of endothelial Notch signaling in postnatal AV organization, we used inducible Cre-loxP recombination to delete Rbpj, a mediator of canonical Notch signaling, from postnatal ECs in mice. Deletion of endothelial Rbpj from birth resulted in features of AVMs by P14, including abnormal AV shunting and tortuous vessels in the brain, intestine and heart. We further analyzed brain AVMs, as they pose particular health risks. Consistent with AVM pathology, we found cerebral hemorrhage, hypoxia and necrosis, and neurological deficits. AV shunts originated from capillaries (and possibly venules), with the earliest detectable morphological abnormalities in AV connections by P8. Prior to AV shunt formation, alterations in EC gene expression were detected, including decreased Efnb2 and increased Pai1, which encodes a downstream effector of TGFβ signaling. After AV shunts had formed, whole-mount immunostaining showed decreased Efnb2 and increased Ephb4 expression within AV shunts, suggesting that ECs were reprogrammed from arterial to venous identity. Deletion of Rbpj from adult ECs led to tortuosities in gastrointestinal, uterine and skin vascular beds, but had mild effects in the brain. Our results demonstrate a temporal requirement for Rbpj in postnatal ECs to maintain proper artery, capillary and vein organization and to prevent abnormal AV shunting and AVM pathogenesis. PMID:25209249

Measuring the labeling efficiency of pseudocontinuous arterial spin labeling.

PubMed

Chen, Zhensen; Zhang, Xingxing; Yuan, Chun; Zhao, Xihai; van Osch, Matthias J P

2017-05-01

Optimization and validation of a sequence for measuring the labeling efficiency of pseudocontinuous arterial spin labeling (pCASL) perfusion MRI. The proposed sequence consists of a labeling module and a single slice Look-Locker echo planar imaging readout. A model-based algorithm was used to calculate labeling efficiency from the signal acquired from the main brain-feeding arteries. Stability of the labeling efficiency measurement was evaluated with regard to the use of cardiac triggering, flow compensation and vein signal suppression. Accuracy of the measurement was assessed by comparing the measured labeling efficiency to mean brain pCASL signal intensity over a wide range of flip angles as applied in the pCASL labeling. Simulations show that the proposed algorithm can effectively calculate labeling efficiency when correcting for T1 relaxation of the blood spins. Use of cardiac triggering and vein signal suppression improved stability of the labeling efficiency measurement, while flow compensation resulted in little improvement. The measured labeling efficiency was found to be linearly (R = 0.973; P < 0.001) related to brain pCASL signal intensity over a wide range of pCASL flip angles. The optimized labeling efficiency sequence provides robust artery-specific labeling efficiency measurement within a short acquisition time (∼30 s), thereby enabling improved accuracy of pCASL CBF quantification. Magn Reson Med 77:1841-1852, 2017. © 2016 International Society for Magnetic Resonance in Medicine Magn Reson Med 77:1841-1852, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

A novel atherothrombotic model of ischemic stroke induced by injection of collagen into the cerebral vasculature

PubMed Central

Schunke, Kathryn J.; Toung, Thomas K.; Zhang, Jian; Pathak, Arvind P.; Xu, Jiadi; Zhang, Jiangyang; Koehler, Raymond C.; Faraday, Nauder

2017-01-01

Background Most ischemic strokes in humans are caused by ruptured arterial atheroma, which activate platelets and produce thrombi that occlude cerebral vessels. Methods To simulate these events, we threaded a catheter through the internal carotid artery toward the middle cerebral artery (MCA) orifice and injected collagen directly into the cerebral circulation of male C57Bl/6 mice and Wistar rats. Results Laser-Doppler flowmetry demonstrated reductions in cerebral blood flow (CBF) of ~80% in mice and ~60% in rats. CBF spontaneously increased but remained depressed after catheter withdrawal. Magnetic resonance imaging showed that ipsilateral CBF was reduced at 3 h after collagen injection and markedly improved at 48 h. Micro-computed tomography revealed reduced blood vessel density in the ipsilateral MCA territory at 3 h. Gross examination of excised brains revealed thrombi within ipsilateral cerebral arteries at 3 h, but not 24 h, after collagen injection. Immunofluorescence microscopy confirmed that platelets and fibrinogen/fibrin were major components of these thrombi at both macrovascular and microvascular levels. Cerebral infarcts comprising ~30% of hemispheric volume and neurobehavioral deficits were observed 48 h after ischemic injury in both mice and rats. Comparison with existing methods Collagen injection caused brain injury that was similar in magnitude and variability to mechanical MCA occlusion or injection of a pre-formed clot; however, alterations in CBF and the mechanism of vascular occlusion were more consistent with clinical ischemic stroke. Conclusion This novel rodent model of ischemic stroke has pathophysiologic characteristics consistent with clinical atherothrombotic stroke, is technically feasible, and creates reproducible brain injury. PMID:25314906

Modeling the Afferent Dynamics of the Baroreflex Control System

PubMed Central

Mahdi, Adam; Sturdy, Jacob; Ottesen, Johnny T.; Olufsen, Mette S.

2013-01-01

In this study we develop a modeling framework for predicting baroreceptor firing rate as a function of blood pressure. We test models within this framework both quantitatively and qualitatively using data from rats. The models describe three components: arterial wall deformation, stimulation of mechanoreceptors located in the BR nerve-endings, and modulation of the action potential frequency. The three sub-systems are modeled individually following well-established biological principles. The first submodel, predicting arterial wall deformation, uses blood pressure as an input and outputs circumferential strain. The mechanoreceptor stimulation model, uses circumferential strain as an input, predicting receptor deformation as an output. Finally, the neural model takes receptor deformation as an input predicting the BR firing rate as an output. Our results show that nonlinear dependence of firing rate on pressure can be accounted for by taking into account the nonlinear elastic properties of the artery wall. This was observed when testing the models using multiple experiments with a single set of parameters. We find that to model the response to a square pressure stimulus, giving rise to post-excitatory depression, it is necessary to include an integrate-and-fire model, which allows the firing rate to cease when the stimulus falls below a given threshold. We show that our modeling framework in combination with sensitivity analysis and parameter estimation can be used to test and compare models. Finally, we demonstrate that our preferred model can exhibit all known dynamics and that it is advantageous to combine qualitative and quantitative analysis methods. PMID:24348231

Wavelet-based system identification of short-term dynamic characteristics of arterial baroreflex.

PubMed

Kashihara, Koji; Kawada, Toru; Sugimachi, Masaru; Sunagawa, Kenji

2009-01-01

The assessment of arterial baroreflex function in cardiovascular diseases requires quantitative evaluation of dynamic and static baroreflex properties because of the frequent modulation of baroreflex properties with unstable hemodynamics. The purpose of this study was to identify the dynamic baroreflex properties from transient changes of step pressure inputs with background noise during a short-duration baroreflex test in anesthetized rabbits with isolated carotid sinuses, using a modified wavelet-based time-frequency analysis. The proposed analysis was able to identify the transfer function of baroreflex as well as static properties from the transient input-output responses under normal [gain at 0.04 Hz from carotid sinus pressure (CSP) to arterial pressure (n = 8); 0.29 +/- 0.05 at low (40-60 mmHg), 1.28 +/- 0.12 at middle (80-100 mmHg), and 0.38 +/- 0.07 at high (120-140 mmHg) CSP changes] and pathophysiological [gain in control vs. phenylbiguanide (n = 8); 0.32 +/- 0.07 vs. 0.39 +/- 0.09 at low, 1.39 +/- 0.15 vs. 0.59 +/- 0.09 (p < 0.01) at middle, and 0.35 +/- 0.04 vs. 0.15 +/- 0.02 (p < 0.01) at high CSP changes] conditions. Subsequently, we tested the proposed wavelet-based method under closed-loop baroreflex responses; the simulation study indicates that it may be applicable to clinical situations for accurate assessment of dynamic baroreflex function. In conclusion, the dynamic baroreflex property to various pressure inputs could be simultaneously extracted from the step responses with background noise.

Cerebral oxygen delivery is reduced in newborns with congenital heart disease.

PubMed

Lim, Jessie Mei; Kingdom, Theodore; Saini, Brahmdeep; Chau, Vann; Post, Martin; Blaser, Susan; Macgowan, Christopher; Miller, Steven P; Seed, Mike

2016-10-01

To investigate preoperative cerebral hemodynamics in newborns with congenital heart disease. We hypothesized that cerebral blood flow and oxygen delivery would be decreased in newborns with congenital heart disease compared with controls. Using a "feed-and-sleep" approach to performing neonatal magnetic resonance imaging, we measured cerebral blood flow by using a slice prescription perpendicular to the right and left internal carotid arteries and basilar artery at the level of the clivus. We calculated brain volume by segmenting a 3-dimensional steady-state free procession acquisition of the whole brain, allowing quantification of cerebral blood flow indexed to brain volume. Cerebral oxygen delivery was calculated as the product of cerebral blood flow and preductal systemic arterial oxygen content obtained via a combination of conventional pulse oximetry and laboratory analysis of venous blood samples for hemoglobin concentration. A complete set of measurements were obtained in 32 newborns with heart disease and 31 controls. There was no difference in gestational age between the heart disease and control groups. There was no difference in cerebral blood flow compared with controls (103.5 ± 34.0 vs 119.7 ± 40.4 mL/min), whereas cerebral oxygen delivery was significantly lower in the congenital heart disease subjects (1881 ± 625.7 vs 2712 ± 915.7 mLO2/min). Ten newborns with congenital heart disease had diffuse excessive high signal intensity in their white matter and 2 had white matter injury whereas another 5 had both. Newborns with unrepaired cyanotic congenital heart disease have decreased cerebral oxygen delivery due to arterial desaturation. If brain growth and development are adversely affected through oxygen conformance, our findings could have clinical implications in terms of timing of surgical repair. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice.

PubMed

Ramanathan, Muthiah; Abdul, Khadar K; Justin, Antony

2016-10-01

Glutamate, an excitatory neurotransmitter in the brain, produces excitotoxicity through its agonistic action on postsynaptic N-methyl-D-aspartate receptor, resulting in neurodegeneration. We hypothesized that the administration of low doses of glutamate in cerebral ischemia could attenuate the excitotoxicity in neurons through its autoreceptor regulatory mechanism, and thereby control neurodegeneration. To test the hypothesis, the effect of L-glutamic acid (L-GA) 400 μmol/l/kg was evaluated in a bilateral common carotid artery occlusion-induced global ischemic mouse model. Memantine was used as a positive control. Global ischemia in mice was induced by occlusion of both the common carotid artery (bilateral common carotid artery occlusion) for 20 min, followed by reperfusion injury. L-GA was infused slowly through the tail vein 30 min before the surgery and every 24 h thereafter until the end of the experiment. The time-dependent change in cerebral blood flow was monitored using a laser Doppler image analyzer. The neurotransmitters glutamate and γ-aminobutyric acid (GABA) and the neurobiochemicals ATP, glutathione, and nitric oxide were measured in the different regions of brain at 0, 24, 48, and 72 h after reperfusion injury. L-GA increased locomotor activity, muscle coordination, and cerebral blood flow in ischemic mice at 72 h after ischemic insult. L-GA reduced glutamate levels in the cortex, striatum, and hippocampus at 72 h, whereas GABA levels were elevated in all three brain regions studied. Further, L-GA elevated glutathione levels and attenuated nitric oxide levels, but failed to restore ATP levels 72 h after ischemia-reperfusion. We conclude that the gradual reduction of glutamate along with elevation of GABA in different brain regions could have contributed toward the neuroprotective effect of L-GA. Hence, a slow infusion of a low dose of L-GA could be beneficial in controlling excitotoxicity-induced neurodegeneration following ischemia.

Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats.

PubMed

Kim, Eun Soo; Lee, Seung-Koo; Kwon, Mi Jung; Lee, Phil Hye; Ju, Young-Su; Yoon, Dae Young; Kim, Hye Jeong; Lee, Kwan Seop

2016-01-01

The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min(-1) vs. 0.07 ± 0.02 min(-1), p = 0.661 for K(trans); 0.30 ± 0.05 min(-1) vs. 0.37 ± 0.11 min(-1), p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group.

Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats

PubMed Central

Kim, Eun Soo; Kwon, Mi Jung; Lee, Phil Hye; Ju, Young-Su; Yoon, Dae Young; Kim, Hye Jeong; Lee, Kwan Seop

2016-01-01

Objective The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Materials and Methods Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Results Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min-1 vs. 0.07 ± 0.02 min-1, p = 0.661 for Ktrans; 0.30 ± 0.05 min-1 vs. 0.37 ± 0.11 min-1, p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Conclusion Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group. PMID:27587960

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.

Effects of diabetes and gender on mechanical properties of the arterial system in rats: aortic impedance analysis.

PubMed

Chang, Kuo-Chu; Hsu, Kwan-Lih; Tseng, Yung-Zu

2003-01-01

We determined the effects of diabetes and gender on the physical properties of the vasculature in streptozotocin (STZ)-treated rats based on the aortic input impedance analysis. Rats given STZ 65 mg/kg i.v. were compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured and were then subjected to Fourier transformation for the analysis of aortic input impedance. Wave transit time was determined using the impulse response function of the filtered aortic input impedance spectra. Male but not female diabetic rats exhibited an increase in cardiac output in the absence of any significant changes in arterial blood pressure, resulting in a decline in total peripheral resistance. However, in each gender group, diabetes contributed to an increase in wave reflection factor, from 0.47 +/- 0.04 to 0.84 +/- 0.03 in males and from 0.46 +/- 0.03 to 0.81 +/- 0.03 in females. Diabetic rats had reduced wave transit time, at 18.82 +/- 0.60 vs 21.34 +/- 0.51 msec in males and at 19.63 +/- 0.37 vs 22.74 +/- 0.57 msec in females. Changes in wave transit time and reflection factor indicate that diabetes can modify the timing and magnitude of the wave reflection in the rat arterial system. Meanwhile, diabetes produced a fall in aortic characteristic impedance from 0.023 +/- 0.002 to 0.009 +/- 0.001 mmHg/min/kg/ml in males and from 0.028 +/- 0.002 to 0.014 +/- 0.001 mmHg/min/kg/ml in females. With unaltered aortic pressure, both the diminished aortic characteristic impedance and wave transit time suggest that the muscle inactivation in diabetes may occur in aortas and large arteries and may cause a detriment to the aortic distensibility in rats with either sex. We conclude that only rats with male gender diabetes produce a detriment to the physical properties of the resistance arterioles. In spite of male or female gender, diabetes decreases the aortic distensibility and impairs the wave reflection phenomenon in the rat arterial system.

Dynamic cerebral autoregulation during brain activation paradigms.

PubMed

Panerai, Ronney B; Moody, Michelle; Eames, Penelope J; Potter, John F

2005-09-01

Dynamic cerebral autoregulation (CA) describes the transient response of cerebral blood flow (CBF) to rapid changes in arterial blood pressure (ABP). We tested the hypothesis that the efficiency of dynamic CA is increased by brain activation paradigms designed to induce hemispheric lateralization. CBF velocity [CBFV; bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal Pco(2) were continuously recorded in 14 right-handed healthy subjects (21-43 yr of age), in the seated position, at rest and during 10 repeated presentations (30 s on-off) of a word generation test and a constructional puzzle. Nonstationarities were not found during rest or activation. Transfer function analysis of the ABP-CBFV (i.e., input-output) relation was performed for the 10 separate 51.2-s segments of data during activation and compared with baseline data. During activation, the coherence function below 0.05 Hz was significantly increased for the right MCA recordings for the puzzle tasks compared with baseline values (0.36 +/- 0.16 vs. 0.26 +/- 0.13, P < 0.05) and for the left MCA recordings for the word paradigm (0.48 +/- 0.23 vs. 0.29 +/- 0.16, P < 0.05). In the same frequency range, significant increases in gain were observed during the puzzle paradigm for the right (0.69 +/- 0.37 vs. 0.46 +/- 0.32 cm.s(-1).mmHg(-1), P < 0.05) and left (0.61 +/- 0.29 vs. 0.45 +/- 0.24 cm.s(-1).mmHg(-1), P < 0.05) hemispheres and during the word tasks for the left hemisphere (0.66 +/- 0.31 vs. 0.39 +/- 0.15 cm.s(-1).mmHg(-1), P < 0.01). Significant reductions in phase were observed during activation with the puzzle task for the right (-0.04 +/- 1.01 vs. 0.80 +/- 0.86 rad, P < 0.01) and left (0.11 +/- 0.81 vs. 0.57 +/- 0.51 rad, P < 0.05) hemispheres and with the word paradigm for the right hemisphere (0.05 +/- 0.87 vs. 0.64 +/- 0.59 rad, P < 0.05). Brain activation also led to changes in the temporal pattern of the CBFV step response. We conclude that transfer function analysis suggests important changes in dynamic CA during mental activation tasks.

Test-retest reproducibility of quantitative binding measures of [11C]Ro15-4513, a PET ligand for GABAA receptors containing alpha5 subunits.

PubMed

McGinnity, Colm J; Riaño Barros, Daniela A; Rosso, Lula; Veronese, Mattia; Rizzo, Gaia; Bertoldo, Alessandra; Hinz, Rainer; Turkheimer, Federico E; Koepp, Matthias J; Hammers, Alexander

2017-05-15

Alteration of γ-aminobutyric acid "A" (GABA A ) receptor-mediated neurotransmission has been associated with various neurological and psychiatric disorders. [ 11 C]Ro15-4513 is a PET ligand with high affinity for α5-subunit-containing GABA A receptors, which are highly expressed in limbic regions of the human brain (Sur et al., 1998). We quantified the test-retest reproducibility of measures of [ 11 C]Ro15-4513 binding derived from six different quantification methods (12 variants). Five healthy males (median age 40 years, range 38-49 years) had a 90-min PET scan on two occasions (median interval 12 days, range 11-30 days), after injection of a median dose of 441 MegaBequerels of [ 11 C]Ro15-4513. Metabolite-corrected arterial plasma input functions (parent plasma input functions, ppIFs) were generated for all scans. We quantified regional binding using six methods (12 variants), some of which were region-based (applied to the average time-activity curve within a region) and others were voxel-based: 1) Models requiring arterial ppIFs - regional reversible compartmental models with one and two tissue compartments (2kbv and 4kbv); 2) Regional and voxelwise Logan's graphical analyses (Logan et al., 1990), which required arterial ppIFs; 3) Model-free regional and voxelwise (exponential) spectral analyses (SA; (Cunningham and Jones, 1993)), which also required arterial ppIFs; 4) methods not requiring arterial ppIFs - voxelwise standardised uptake values (Kenney et al., 1941), and regional and voxelwise simplified reference tissue models (SRTM/SRTM2) using brainstem or alternatively cerebellum as pseudo-reference regions (Lammertsma and Hume, 1996; Gunn et al., 1997). To compare the variants, we sampled the mean values of the outcome parameters within six bilateral, non-reference grey matter regions-of-interest. Reliability was quantified in terms of median absolute percentage test-retest differences (MA-TDs; preferentially low) and between-subject coefficient of variation (BS-CV, preferentially high), both compounded by the intraclass correlation coefficient (ICC). These measures were compared between variants, with particular interest in the hippocampus. Two of the six methods (5/12 variants) yielded reproducible data (i.e. MA-TD <10%): regional SRTMs and voxelwise SRTM2s, both using either the brainstem or the cerebellum; and voxelwise SA. However, the SRTMs using the brainstem yielded a lower median BS-CV (7% for regional, 7% voxelwise) than the other variants (8-11%), resulting in lower ICCs. The median ICCs across six regions were 0.89 (interquartile range 0.75-0.90) for voxelwise SA, 0.71 (0.64-0.84) for regional SRTM-cerebellum and 0.83 (0.70-0.86) for voxelwise SRTM-cerebellum. The ICCs for the hippocampus were 0.89 for voxelwise SA, 0.95 for regional SRTM-cerebellum and 0.93 for voxelwise SRTM-cerebellum. Quantification of [ 11 C]Ro15-4513 binding shows very good to excellent reproducibility with SRTM and with voxelwise SA which, however, requires an arterial ppIF. Quantification in the α5 subunit-rich hippocampus is particularly reliable. The very low expression of the α5 in the cerebellum (Fritschy and Mohler, 1995; Veronese et al., 2016) and the substantial α1 subunit density in this region may hamper the application of reference tissue methods. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Electrophysiological monitoring during basilar aneurysm operation.

PubMed

Little, J R; Lesser, R P; Luders, H

1987-03-01

Intraoperative brain stem auditory evoked potential (BAEP) and somatosensory evoked potential (SEP) monitoring was evaluated in 16 patients each undergoing intracranial operation for basilar artery aneurysm. The 16 patients had 18 posterior circulation aneurysms, including 2 patients with 2 aneurysms. Fourteen aneurysms arose from the rostral basilar artery, 2 arose from the midbasilar artery, 1 arose from the vertebrobasilar junction, and 1 arose from the proximal segment of the posterior cerebral artery. Five aneurysms were classified as giant (i.e., greater than 25 mm), and 5 aneurysms were large (i.e., 15 to 25 mm). Ten patients had BAEP and SEP monitoring, 4 had BAEP monitoring only, and 2 had SEP monitoring only. Two patients showed significant abnormalities during operation, including 1 patient with transient changes in the BAEP when the lower pons and the 8th cranial nerve were retracted. Another patient had progressive increases in latency and decreases in amplitude and subsequent loss of the SEP cortical components during a period of intermittent temporary rostral basilar artery occlusion. Wave P13 was also lost during that period. The cortical components as well as Wave P13 returned after circulation was restored. The BAEPs were unchanged in the same patient during the period of temporary basilar artery occlusion. Fourteen patients had no significant abnormalities. There were no consistent changes during the various stages of operation. BAEP and SEP monitoring failed to identify ischemic events in 4 patients with neurological findings of brain stem ischemia immediately after operation (i.e., 25% false-negative studies).(ABSTRACT TRUNCATED AT 250 WORDS)

Bioreactivity: Studies on a Simple Brain Stem Reflex in Behaving Animals

DTIC Science & Technology

1990-08-10

problem in attempting to understand complex physiological processes, such as brain neuromodulation , or complex behavioral processes, such as arousal...containing only one synapse in brain, and receives dense inputs from two neurochemical systems important in neuromodulation and arousal. Initial

Bioreactivity: Studies on a Simple Brain Stem Reflex in Behaving Animals

DTIC Science & Technology

1990-01-04

attempting to understand complex physiological processes, such as brain neuromodulation , or complex behavioral processes, such as arousal, is finding a...one synapse in brain, and receives dense inputs from two neurochemical systems important in neuromodulation and arousal. Initial pharmacologic studies

Brain Friendly School Libraries

ERIC Educational Resources Information Center

Sykes, Judith Anne

2006-01-01

This title gives concrete practical examples of how to align school library programs and instructional practice with the six key concepts of brain-compatible learning: increasing input to the brain; increasing experiential data; multiple source feedback; reducing threat; involving students in learning decision making; and interdisciplinary unit…

Physiological properties of brain-machine interface input signals.

PubMed

Slutzky, Marc W; Flint, Robert D

2017-08-01

Brain-machine interfaces (BMIs), also called brain-computer interfaces (BCIs), decode neural signals and use them to control some type of external device. Despite many experimental successes and terrific demonstrations in animals and humans, a high-performance, clinically viable device has not yet been developed for widespread usage. There are many factors that impact clinical viability and BMI performance. Arguably, the first of these is the selection of brain signals used to control BMIs. In this review, we summarize the physiological characteristics and performance-including movement-related information, longevity, and stability-of multiple types of input signals that have been used in invasive BMIs to date. These include intracortical spikes as well as field potentials obtained inside the cortex, at the surface of the cortex (electrocorticography), and at the surface of the dura mater (epidural signals). We also discuss the potential for future enhancements in input signal performance, both by improving hardware and by leveraging the knowledge of the physiological characteristics of these signals to improve decoding and stability. Copyright © 2017 the American Physiological Society.

Stress-sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation.

PubMed

Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel, A L; Akulov, A E

2017-05-01

What is the central question of this study? Stress-sensitive arterial hypertension is considered to be controlled by changes in central and peripheral sympathetic regulating mechanisms, which eventually result in haemodynamic alterations and blood pressure elevation. Therefore, study of the early stages of development of hypertension is of particular interest, because it helps in understanding the aetiology of the disease. What is the main finding and its importance? Non-invasive in vivo investigation in ISIAH rats demonstrated that establishment of sustainable stress-sensitive hypertension is accompanied by a decrease in prefrontal cortex activity and mobilization of hypothalamic processes, with considerable correlations between haemodynamic parameters and individual metabolite ratios. The study of early development of arterial hypertension in association with emotional stress is of great importance for better understanding of the aetiology and pathogenesis of the hypertensive disease. Magnetic resonance imaging (MRI) was applied to evaluate the changes in haemodynamics and brain metabolites in 1- and 3-month-old inherited stress-induced arterial hypertension (ISIAH) rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive Wistar Albino Glaxo (WAG) rats (eight male rats). In the 3-month-old ISIAH rats, the age-dependent increase in blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of the abdominal aorta. The renal vascular resistance in the ISIAH rats decreased during ageing, although at both ages it remained higher than the renal vascular resistance in WAG rats. An integral metabolome portrait demonstrated that development of hypertension in the ISIAH rats was associated with an attenuation of the excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats the opposite age-dependent changes were observed. In contrast, in the hypothalamus of 3-month-old ISIAH rats, an increase in energetic activity and prevalence of excitatory over inhibitory neurotransmitters was noticed. The blood flow through the main arteries showed a positive correlation with glutamate and glutamine levels in the hypothalamus and a negative correlation with the hypothalamic GABA level. The blood pressure values were positively correlated with hypothalamic choline levels. Thus, the early development of stress-sensitive hypertension in the ISIAH rats is accompanied by considerable changes both in brain metabolite ratios and in the parameters of blood flow through the main arteries. © 2017 Institute of Cytology and Genetics (SB RAS). Experimental Physiology © 2017 The Physiological Society.

Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion: Progesterone receptor levels may play an important role

PubMed Central

Allen, Rachael S.; Sayeed, Iqbal; Oumarbaeva, Yuliya; Morrison, Katherine C.; Choi, Paul H.; Pardue, Machelle T.; Stein, Donald G.

2018-01-01

Background/Objective To determine whether inflammation increases in retina as it does in brain following middle cerebral artery occlusion (MCAO), and whether the neurosteroid progesterone, shown to have protective effects in both retina and brain after MCAO, reduces inflammation in retina as well as brain. Methods MCAO rats treated systemically with progesterone or vehicle were compared with shams. Protein levels of cytosolic NF-κB, nuclear NF-κB, phosphorylated NF-κB, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane × receptor were assessed in retinas and brains at 24 and 48 h using western blots. Results Following MCAO, significant increases were observed in the following inflammatory markers: pNF-κB and CD11b at 24 h in both brain and retina, nuclear NF-κB at 24 h in brain and 48 h in retina, and TNF-α at 24 h in brain. Progesterone treatment in MCAO animals significantly attenuated levels of the following markers in brain: pNF-κB, nuclear NF-κB, IL-6, TNF-α, and CD11b, with significantly increased levels of cytosolic NF-κB. Retinas from progesterone-treated animals showed significantly reduced levels of nuclear NF-κB and IL-6 and increased levels of cytosolic NF-κB, with a trend for reduction in other markers. Post-MCAO, progesterone receptors A and B were upregulated in brain and downregulated in retina. Conclusion Inflammatory markers increased in both brain and retina after MCAO, with greater increases observed in brain. Progesterone treatment reduced inflammation, with more dramatic reductions observed in brain than retina. This differential effect may be due to differences in the response of progesterone receptors in brain and retina after injury. PMID:27802245

Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion: Progesterone receptor levels may play an important role.

PubMed

Allen, Rachael S; Sayeed, Iqbal; Oumarbaeva, Yuliya; Morrison, Katherine C; Choi, Paul H; Pardue, Machelle T; Stein, Donald G

2016-11-22

To determine whether inflammation increases in retina as it does in brain following middle cerebral artery occlusion (MCAO), and whether the neurosteroid progesterone, shown to have protective effects in both retina and brain after MCAO, reduces inflammation in retina as well as brain. MCAO rats treated systemically with progesterone or vehicle were compared with shams. Protein levels of cytosolic NF-κB, nuclear NF-κB, phosphorylated NF-κB, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane X receptor were assessed in retinas and brains at 24 and 48 h using western blots. Following MCAO, significant increases were observed in the following inflammatory markers: pNF-κB and CD11b at 24 h in both brain and retina, nuclear NF-κB at 24 h in brain and 48 h in retina, and TNF-α at 24 h in brain.Progesterone treatment in MCAO animals significantly attenuated levels of the following markers in brain: pNF-κB, nuclear NF-κB, IL-6, TNF-α, and CD11b, with significantly increased levels of cytosolic NF-κB. Retinas from progesterone-treated animals showed significantly reduced levels of nuclear NF-κB and IL-6 and increased levels of cytosolic NF-κB, with a trend for reduction in other markers. Post-MCAO, progesterone receptors A and B were upregulated in brain and downregulated in retina. Inflammatory markers increased in both brain and retina after MCAO, with greater increases observed in brain. Progesterone treatment reduced inflammation, with more dramatic reductions observed in brain than retina. This differential effect may be due to differences in the response of progesterone receptors in brain and retina after injury.

[Case of acute ischemic stroke due to cardiac myxoma treated by intravenous thrombolysis and endovascular therapy].

PubMed

Kamiya, Yuki; Ichikawa, Hiroo; Mizuma, Keita; Itaya, Kazuhiro; Shimizu, Yuki; Kawamura, Mitsuru

2014-01-01

A 48-year-old woman with no previous neurological diseases was transferred to our hospital because of sudden-onset unconsciousness. On arrival, she showed consciousness disturbance (E1V1M3 on the Glasgow Coma Scale), tetraplegia, right conjugate deviation and bilateral pathological reflexes. These symptoms resulted in a NIH stroke scale score of 32. Brain diffusion-weighted MR imaging (DWI) showed multiple hyper-intense lesions, and MR angiography revealed occlusions of the basilar artery (BA) and superior branch of the right middle cerebral artery (MCA). Transthoracic echocardiography disclosed a 51 × 24 mm myxoma in the left atrium. These findings led to diagnosis of acute ischemic stroke due to embolization from cardiac myxoma. Thrombolytic therapy with intravenous tissue plasminogen activator (IV tPA) was started 120 min after onset because there were no contraindications for this treatment. However, the symptoms did not resolve, and thus endovascular therapy was performed immediately after IV tPA. Angiography of the left vertebral artery initially showed BA occlusion, but a repeated angiogram resulted in spontaneous recanalization of the BA. However, the left posterior cerebral artery remained occluded by a residual embolus. Subsequently, occlusion found in the superior branch of the right MCA was treated by intra-arterial local thrombolysis using urokinase and thrombectomy with a foreign body retrieval device, but the MCA remained occluded. DWI after endovascular therapy showed new hyper-intense lesions in the bilateral medial thalamus and left occipital cortex. Clinically, neurological status did not improve, with a score of 5 on the modified Rankin Scale. IV tPA can be used for stroke due to cardiac myxoma, but development of brain aneurysms and metastases caused by myxoma is a concern. Given the difficulty of predicting an embolus composite from a thrombus or tumor particle, aspiration thrombectomy may be safer and more effective for stroke due to cardiac myxoma to avoid delayed formation of brain aneurysms and metastases.

Cranial arterial patterns of the alpaca (Camelidae: Vicugna pacos)

PubMed Central

2017-01-01

Artiodactyl cranial arterial patterns deviate significantly from the standard mammalian pattern, most notably in the possession of a structure called the carotid rete (CR)—a subdural arterial meshwork that is housed within the cavernous venous sinus, replacing the internal carotid artery (ICA). This relationship between the CR and the cavernous sinus facilitates a suite of unique physiologies, including selective brain cooling. The CR has been studied in a number of artiodactyls; however, to my knowledge, only a single study to date documents a subset of the cranial arteries of New World camelids (llamas, alpacas, vicugñas and guanacoes). This study is the first complete description of the cranial arteries of a New World camelid species, the alpaca (Vicugna pacos), and the first description of near-parturition cranial arterial morphology within New World camelids. This study finds that the carotid arterial system is conserved between developmental stages in the alpaca, and differs significantly from the pattern emphasized in other long-necked ruminant artiodactyls in that a patent, homologous ICA persists through the animal's life. PMID:28405385

A Novel Combined Hybrid Approach to Enable Revascularisation of a Trauma-Induced Subclavian Artery Injury.

PubMed

Sabbagh, C N; Chowdhury, M M; Durrani, A; Van Rensburg, L; Koo, B; Coughlin, P A

2016-01-01

This case highlights the complexity of upper limb revascularization after a subclavian artery traumatic injury and strengthens the role of a hybrid/multi-disciplinary approach to such injuries. A 45-year-old male patient presented with an acute right upper limb following a traumatic injury to the right subclavian artery due to a motor vehicle accident (MVA). Associated injuries included an unstable cervical spine injury, a large open right clavicular injury, and a brain injury, which limited the potential revascularisation options available. The arm was revascularised using a hybrid endovascular/open surgical approach, namely embolization of the proximal subclavian artery (just distal to vertebral artery) and a right common femoral artery to distal axillary artery bypass using prosthetic material. Blunt injuries to the subclavian artery are often high impact, complex and associated with multiple injuries to surrounding structures, which limit the role of standard procedures used in the elective setting. This case highlights the role of multidisciplinary team involvement, using a hybrid approach and a novel distal inflow site to restore upper limb perfusion.

Complex neurological symptoms in bilateral thalamic stroke due to Percheron artery occlusion.

PubMed

Caruso, Paola; Manganotti, Paolo; Moretti, Rita

2017-01-01

The artery of Percheron is a rare anatomical variant where a single thalamic perforating artery arises from the proximal posterior cerebral artery (P1 segment) between the basilar artery and the posterior communicating artery and supplies the rostral mesencephalon and both paramedian territories of the thalami. Almost one-third of human brains present this variant. Occlusion of the artery of Percheron mostly results in a bilateral medial thalamic infarction, which usually manifests with altered consciousness (including coma), vertical gaze paresis, and cognitive disturbance. The presentation is similar to the "top of the basilar syndrome", and early recognition should be prompted. We describe the case of a young female with this vessel variant who experienced a bilateral thalamic stroke. Magnetic resonance angiography demonstrated bilateral thalamic infarcts and a truncated artery of Percheron. Occlusion of the vessel was presumably due to embolism from a patent foramen ovale. Thrombolysis was performed, with incomplete symptom remission, cognitive impairment, and persistence of speech disorders. Early recognition and treatment of posterior circulation strokes is mandatory, and further investigation for underlying stroke etiologies is needed.

Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.

PubMed

Zarubina, I V; Shabanov, P D

2009-03-01

Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia.

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

[Vertebral artery dissection due to the C6 transverse process and laryngeal cartilage associated with vertebral artery anomaly].

PubMed

Kusunoki Nakamoto, Fumiko; Hashimoto Maeda, Meiko; Mori, Kentaro; Hara, Takayuki; Uesaka, Yoshikazu

2014-01-01

A 52-year-old woman complained of the sudden onset of a left temporal headache, left neck stiffness and dizziness. Brain magnetic resonance imaging showed a high-intensity lesion in the right medial medulla. Dynamic cerebral angiography revealed vertebral artery dissection and compression at the C6 level due to a transverse process at the C6 level associated with rightward head rotation. Removal of bone and decompression of the vertebral artery were performed from the C5 to C6 levels. Intraoperasively, obstruction of blood flow due to a laryngeal cartilage that rotated with the passive rotation of the patient's head to the right was found. To the best of our knowledge this is the first reported case of vertebral artery occlusion due to a laryngeal cartilage associated with head rotation.

Middle Cerebral Artery, Ophthalmic Artery, and Multibranch Retinal Vessel Occlusion After Cosmetic Autologous Fat Transfer to Forehead.

PubMed

Roshandel, Danial; Soheilian, Masoud; Pakravan, Mohammad; Aghayan, Sara; Peyman, Gholam A

2015-05-01

A 65-year-old woman with left hemiparesis and sudden loss of visual acuity in her right eye presented a few hours after cosmetic injection of autologous fat to her forehead. Right eye visual acuity was no light perception. Funduscopy revealed widespread retinal whitening and multibranch retinal vessel occlusion. Fluorescein angiography showed markedly delayed choroidal and retinal filling together with occlusion of multiple branches of retinal arteries and veins. On magnetic resonance imaging of the brain, multiple lesions compatible with recent infarction were detected. The authors diagnosed multibranch retinal artery and vein occlusion in the right ophthalmic and middle cerebral arteries due to fat emboli. This case emphasizes the need to reevaluate the safety of such aesthetic procedures, particularly in the facial zone to prevent devastating complications. Copyright 2015, SLACK Incorporated.

Neural systemic impairment from whole-body vibration.

PubMed

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; LoGiudice, John; Sanger, James R; Matloub, Hani S; Havlik, Robert

2015-05-01

Insidious brain microinjury from motor vehicle-induced whole-body vibration (WBV) has not yet been investigated. For a long time we have believed that WBV would cause cumulative brain microinjury and impair cerebral function, which suggests an important risk factor for motor vehicle accidents and secondary cerebral vascular diseases. Fifty-six Sprague-Dawley rats were divided into seven groups (n = 8): 1) 2-week normal control group, 2) 2-week sham control group (restrained in the tube without vibration), 3) 2-week vibration group (exposed to whole-body vibration at 30 Hz and 0.5g acceleration for 4 hr/day, 5 days/week, for 2 weeks), 4) 4-week sham control group, 5) 4-week vibration group, 6) 8-week sham control group, and 7) 8-week vibration group. At the end point, all rats were evaluated in behavior, physiological, and brain histopathological studies. The cerebral injury from WBV is a cumulative process starting with vasospasm squeezing of the endothelial cells, followed by constriction of the cerebral arteries. After the 4-week vibration, brain neuron apoptosis started. After the 8-week vibration, vacuoles increased further in the brain arteries. Brain capillary walls thickened, mean neuron size was obviously reduced, neuron necrosis became prominent, and wide-ranging chronic cerebral edema was seen. These pathological findings are strongly correlated with neural functional impairments. © 2014 Wiley Periodicals, Inc.

Focal epidural cooling reduces the infarction volume of permanent middle cerebral artery occlusion in swine.

PubMed

Zhang, Lihua; Cheng, Huilin; Shi, Jixin; Chen, Jun

2007-02-01

The protective effect against ischemic stroke by systemic hypothermia is limited by the cooling rate and it has severe complications. This study was designed to evaluate the effect of SBH induced by epidural cooling on infarction volume in a swine model of PMCAO. Permanent middle cerebral artery occlusion was performed in 12 domestic swine assigned to groups A and B. In group A, the cranial and rectal temperatures were maintained at normal range (37 degrees C-39 degrees C) for 6 hours after PMCAO. In group B, cranial temperature was reduced to moderate (deep brain, <30 degrees C) and deep (brain surface, <20 degrees C) temperature and maintained at that level for 5 hours after 1 hour after PMCAO, by the epidural cooling method. All animals were euthanized 6 hours after MCAO; their brains were sectioned and stained with 2,3,5-triphenyltetrazolium chloride and their infarct volumes were calculated. The moderate and deep brain temperature (at deep brain and brain surface) can be induced by rapid epidural cooling, whereas the rectal temperature was maintained within normal range. The infarction volume after PMCAO was significantly reduced by epidural cooling compared with controls (13.73% +/- 1.82% vs 5.62% +/- 2.57%, P < .05). The present study has demonstrated, with histologic confirmation, that epidural cooling may be a useful strategy for reducing infarct volume after the onset of ischemia.

EFFECT OF WEARING AN N95 FILTERING FACEPIECE RESPIRATOR ON SUPEROMEDIAL ORBITAL INFRARED INDIRECT BRAIN TEMPERATURE MEASUREMENTS

PubMed Central

DiLeo, Travis; Roberge, Raymond J.; Kim, Jung-Hyun

2016-01-01

Purpose To determine any effect of wearing a filtering facepiece respirator on brain temperature. Methods Subjects (n=18) wore a filtering facepiece respirator (FFR) for 1h at rest while undergoing infrared thermography measurements of the superomedial periobital region of the eye, a non-invasive indirect method of brain temperature measurements we termed the superomedial orbital infrared indirect brain temperature (SOIIBT) measurement. Temperature of the facial skin covered by the FFR, infrared temperature measurements of the tympanic membrane and superficial temporal artery region were concurrently measured, and subjective impressions of thermal comfort obtained simultaneously. Results The temperature of the skin under the FFR and subjective impressions of thermal discomfort both increased significantly. The mean tympanic membrane temperature did not increase, and the superficial temporal artery region temperature decreased significantly. The SOIIBT values did not change significantly, but subjects who switched from nasal to oronasal breathing during the study (n=5) experienced a slight increase in the SOIIBT measurements. Conclusions Wearing a FFR for 1h at rest does not have a significant effect on brain temperatures, as evaluated by the SOIIBT measurements, but a change in the route of breathing may impact these measurements. These findings suggest that subjective impressions of thermal discomfort from wearing a FFR under the study conditions are more likely the result of local dermal sensations rather than brain warming. PMID:26759336

Resting state cerebral blood flow with arterial spin labeling MRI in developing human brains.

PubMed

Liu, Feng; Duan, Yunsuo; Peterson, Bradley S; Asllani, Iris; Zelaya, Fernando; Lythgoe, David; Kangarlu, Alayar

2018-07-01

The development of brain circuits is coupled with changes in neurovascular coupling, which refers to the close relationship between neural activity and cerebral blood flow (CBF). Studying the characteristics of CBF during resting state in developing brain can be a complementary way to understand the functional connectivity of the developing brain. Arterial spin labeling (ASL), as a noninvasive MR technique, is particularly attractive for studying cerebral perfusion in children and even newborns. We have collected pulsed ASL data in resting state for 47 healthy subjects from young children to adolescence (aged from 6 to 20 years old). In addition to studying the developmental change of static CBF maps during resting state, we also analyzed the CBF time series to reveal the dynamic characteristics of CBF in differing age groups. We used the seed-based correlation analysis to examine the temporal relationship of CBF time series between the selected ROIs and other brain regions. We have shown the developmental patterns in both static CBF maps and dynamic characteristics of CBF. While higher CBF of default mode network (DMN) in all age groups supports that DMN is the prominent active network during the resting state, the CBF connectivity patterns of some typical resting state networks show distinct patterns of metabolic activity during the resting state in the developing brains. Copyright © 2018 European Paediatric Neurology Society. All rights reserved.

Development and performance test of an online blood sampling system for determination of the arterial input function in rats.

PubMed

Roehrbacher, Friedrich; Bankstahl, Jens P; Bankstahl, Marion; Wanek, Thomas; Stanek, Johann; Sauberer, Michael; Muellauer, Julia; Schroettner, Thales; Langer, Oliver; Kuntner, Claudia

2015-12-01

For positron emission tomography (PET) kinetic modelling, an accurate determination of the arterial input function is required. In this study, a blood sampling system was developed and tested using different radiotracers in rats. The detector consists of pairs of lutetium yttrium oxyorthosilicate (LYSO) detectors, photomultiplier tubes and lead shield assembled within a steel casing working in coincidence mode. Rats were cannulated with microtubes in the femoral artery and vein for arterial blood sampling as well as administration of the PET tracers. Connected PTFE microtubes were centred between the LYSO crystals using a special holder. To enhance sensitivity, three layers with two coils were used. A flexible tube pump was used to ensure a constant blood flow. Performance of the detector was assessed with [(18)F]fludeoxyglucose (FDG), [(18)F]ciprofloxacin, (R)-[(11)C]verapamil, [(11)C]tariquidar, [(11)C]mephobarbital and [(11)C]MC113. Obtained input function curves were compared with manual samples drawn every 5 s during the first 3 min and further on at 5, 10, 20, 30, 40, 50 and 60 min after radiotracer injection. After manual sampling, an arterio/venous shunt was established. Shape and area-under-the-curve (AUC; Bq/μl*h) of the input functions were evaluated. The developed detector system provided an absolute sensitivity of 6.5%. Maximum peak values agreed well between manual samples and the detector with a mean difference of -0.4% ± 7.0% (max 12.0%, min -9.9%). AUC values also exhibited an excellent correlation (R = 0.996) between manual sampling and detector measurements with a mean difference of 9.3% ± 9.7% (max 24.1%, min -3.2%). The system was able to measure peak blood activity concentration levels of 110 to 2,000 Bq/μl which corresponds to injected activities from 5.5 to 100 MBq depending on the used radiotracer, applied volume and weight of the animal. This study demonstrates that the developed blood sampling system can be used for in vivo small animal PET studies in rats in a reliable way. The usage of the systems enhances the accuracy of the input curve as handling of small blood samples especially with low activity (as for C-11) is prone to measurement errors. Additionally, the radiation dose of the experimenters can be reduced, as it is not required anymore to continuously draw samples where the personal is in close contact to the radioactive animals and blood.

Comparison of histamine and hyperosmotic arabinose infusion on brain capillary permeability to hydrophilic solutes

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

Lucchesi, K.J.

1986-03-01

The effect of bilateral intracarotid infusion of histamine (HA) on capillary permeability-surface area products (PS) of two metabolically inert tracers was determined and compared to that of L(+)arabinose (ARAB) in rat brain. Ringer's solution alone, or with 1 mg/kg HA diphosphate or 1.6M ARAB added, was infused (0.9 ml over 0.5 min) into each external carotid artery (CA). Five minutes later, a bolus of /sup 14/C-sucrose and /sup 3/H-L-glucose was injected i.v. Estimates of PS for both tracers were computed by the method of Ohno et al after brain concentration was corrected for tracer within cerebral blood vessels. Brain bloodmore » volume, based on the /sup 14/C-dextran space, was the same (.016 ml/g) in discrete cortical and midbrain regions of all rats except those treated with ARAB. The latter yielded .033 ml/g, presumably due to dextran extravasation. Infusion of ARAB, HA and Ringer's increased the PS's of sucrose and L-glucose by 10x, 8x, and 3x in brain regions perfused by the internal CA's. The ratio, PS-sucrose/PS-L-glucose was unchanged by any treatment. Both ARAB and HA caused transient falls in arterial pressure, but only ARAB caused deaths (3 of 9 rats). While as effective as ARAB in opening the blood-brain barrier, HA may be safer than hyperosmotic shock to enhance delivery of chemotherapeutic agents to brain tumors.« less

The horizontal brain slice preparation: a novel approach for visualizing and recording from all layers of the tadpole tectum.

PubMed

Hamodi, Ali S; Pratt, Kara G

2015-01-01

The Xenopus tadpole optic tectum is a multisensory processing center that receives direct visual input as well as nonvisual mechanosensory input. The tectal neurons that comprise the optic tectum are organized into layers. These neurons project their dendrites laterally into the neuropil where visual inputs target the distal region of the dendrite and nonvisual inputs target the proximal region of the same dendrite. The Xenopus tadpole tectum is a popular model to study the development of sensory circuits. However, whole cell patch-clamp electrophysiological studies of the tadpole tectum (using the whole brain or in vivo preparations) have focused solely on the deep-layer tectal neurons because only neurons of the deep layer are visible and accessible for whole cell electrophysiological recordings. As a result, whereas the development and plasticity of these deep-layer neurons has been well-studied, essentially nothing has been reported about the electrophysiology of neurons residing beyond this layer. Hence, there exists a large gap in our understanding about the functional development of the amphibian tectum as a whole. To remedy this, we developed a novel isolated brain preparation that allows visualizing and recording from all layers of the tectum. We refer to this preparation as the "horizontal brain slice preparation." Here, we describe the preparation method and illustrate how it can be used to characterize the electrophysiology of neurons across all of the layers of the tectum as well as the spatial pattern of synaptic input from the different sensory modalities. Copyright © 2015 the American Physiological Society.

Latent NOTCH3 epitopes unmasked in CADASIL and regulated by protein redox state.

PubMed

Zhang, Xiaojie; Lee, Soo Jung; Young, Kelly Z; Josephson, David A; Geschwind, Michael D; Wang, Michael M

2014-10-02

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy CADASIL is caused by more than a hundred NOTCH3 mutations. Virtually all encoded mutant proteins contain an odd number of cysteines. As such, structural changes in NOTCH3 may be the primary molecular abnormality in CADASIL. Thus, we sought evidence for structurally altered NOTCH3 protein in CADASIL tissue. Four antibodies were raised in rabbits against two non-overlapping N-terminal NOTCH3 sequences. These reagents were used in immunohistochemical experiments to detect epitopes in post-mortem CADASIL brains (n=8), control brains, and cells overexpressing NOTCH3. To determine the biochemical nature of NOTCH3 epitopes, we used these antibodies to probe pure NOTCH3-Fc fusion proteins treated with acid, urea, guanidinium, ionic detergents, acrylamide, and thiol- and phosphorus-based reductants. All antibodies avidly stained arteries in 8 of 8 CADASIL brain samples. The most prominent staining was in degenerating media of leptomeningeal arteries and sclerotic penetrating vessels. Normal appearing vessels from control brains were not reactive. Antibodies did not react with cultured cells overexpressing NOTCH3 or with purified NOTCH3-Fc protein. Furthermore, treatment of pure protein with acid, chaotropic denaturants, alkylators, and detergents failed to unmask N-terminal NOTCH3 epitopes. Antibodies, however, recognized novel N-terminal epitopes in purified NOTCH3-Fc protein treated with three different reductants (DTT, beta-mercaptoethanol, and TCEP). We conclude that CADASIL arteries feature latent N-terminal NOTCH3 epitopes, suggesting the first evidence in vivo of NOTCH3 structural alterations. Published by Elsevier B.V.

Lesional perfusion abnormalities in Leigh disease demonstrated by arterial spin labeling correlate with disease activity.

PubMed

Whitehead, Matthew T; Lee, Bonmyong; Gropman, Andrea

2016-08-01

Leigh disease is a metabolic disorder of the mitochondrial respiratory chain culminating in symmetrical necrotizing lesions in the deep gray nuclei or brainstem. Apart from classic gliotic/necrotic lesions, small-vessel proliferation is also characteristic on histopathology. We have observed lesional hyperperfusion on arterial spin-labeling (ASL) sequence in children with Leigh disease. In this cross-sectional analysis, we evaluated lesional ASL perfusion characteristics in children with Leigh syndrome. We searched the imaging database from an academic children's hospital for "arterial spin labeling, perfusion, necrosis, lactate, and Leigh" to build a cohort of children for retrospective analysis. We reviewed each child's medical record to confirm a diagnosis of Leigh disease, excluding exams with artifact, technical limitations, and without ASL images. We evaluated the degree and extent of cerebral blood flow and relationship to brain lesions. Images were compared to normal exams from an aged-matche cohort. The database search yielded 45 exams; 30 were excluded. We evaluated 15 exams from 8 children with Leigh disease and 15 age-matched normal exams. In general, Leigh brain perfusion ranged from hyperintense (n=10) to hypointense (n=5). Necrotic lesions appeared hypointense/hypoperfused. Active lesions with associated restricted diffusion demonstrated hyperperfusion. ASL perfusion patterns differed significantly from those on age-matched normal studies (P=<.0001). Disease activity positively correlated with cerebral deep gray nuclei hyperperfusion (P=0.0037) and lesion grade (P=0.0256). Children with Leigh disease have abnormal perfusion of brain lesions. Hyperperfusion can be found in active brain lesions, possibly associated with small-vessel proliferation characteristic of the disease.

Acute onset quadriplegia.

PubMed

Rajasekharan, Chandrasekharan; Deepak, Menon

2012-07-10

A 50-year-old man, with history of chronic alcohol intake was brought in a stuporous state to the emergency services having been found in that condition in his home the same day. Examination revealed the patient in an akinteic mute state with apparently normal cranial nerves, hypotonia and quadriplegia with bilateral extensor plantar reflex. CT scan and MRI of the brain revealed bilateral infarct parasagittally with normal Magnetic resonance venogram suggestive of bilateral anterior cerebral artery infarct. Follow-up magnetic resonance angiogram revealed an azygous anterior cerebral artery thus proving an infarct of unpaired anterior cerebral artery infarct as the cause for quadriplegia in this patient.

Imaging Human Brain Perfusion with Inhaled Hyperpolarized 129Xe MR Imaging.

PubMed

Rao, Madhwesha R; Stewart, Neil J; Griffiths, Paul D; Norquay, Graham; Wild, Jim M

2018-02-01

Purpose To evaluate the feasibility of directly imaging perfusion of human brain tissue by using magnetic resonance (MR) imaging with inhaled hyperpolarized xenon 129 ( 129 Xe). Materials and Methods In vivo imaging with 129 Xe was performed in three healthy participants. The combination of a high-yield spin-exchange optical pumping 129 Xe polarizer, custom-built radiofrequency coils, and an optimized gradient-echo MR imaging protocol was used to achieve signal sensitivity sufficient to directly image hyperpolarized 129 Xe dissolved in the human brain. Conventional T1-weighted proton (hydrogen 1 [ 1 H]) images and perfusion images by using arterial spin labeling were obtained for comparison. Results Images of 129 Xe uptake were obtained with a signal-to-noise ratio of 31 ± 9 and demonstrated structural similarities to the gray matter distribution on conventional T1-weighted 1 H images and to perfusion images from arterial spin labeling. Conclusion Hyperpolarized 129 Xe MR imaging is an injection-free means of imaging the perfusion of cerebral tissue. The proposed method images the uptake of inhaled xenon gas to the extravascular brain tissue compartment across the intact blood-brain barrier. This level of sensitivity is not readily available with contemporary MR imaging methods. © RSNA, 2017.

Coarctation of the aorta

MedlinePlus

... brain Early development of coronary artery disease (CAD) Endocarditis (infection in the heart) Heart failure Hoarseness Kidney ... include: Continued or repeated narrowing of the aorta Endocarditis High blood pressure

Increased permeability-glycoprotein inhibition at the human blood-brain barrier can be safely achieved by performing PET during peak plasma concentrations of tariquidar.

PubMed

Kreisl, William C; Bhatia, Ritwik; Morse, Cheryl L; Woock, Alicia E; Zoghbi, Sami S; Shetty, H Umesha; Pike, Victor W; Innis, Robert B

2015-01-01

The permeability-glycoprotein (P-gp) efflux transporter is densely expressed at the blood-brain barrier, and its resultant spare capacity requires substantial blockade to increase the uptake of avid substrates, blunting the ability of investigators to measure clinically meaningful alterations in P-gp function. This study, conducted in humans, examined 2 P-gp inhibitors (tariquidar, a known inhibitor, and disulfiram, a putative inhibitor) and 2 routes of administration (intravenous and oral) to maximally increase brain uptake of the avid and selective P-gp substrate (11)C-N-desmethyl-loperamide (dLop) while avoiding side effects associated with high doses of tariquidar. Forty-two (11)C-dLop PET scans were obtained from 37 healthy volunteers. PET was performed with (11)C-dLop under the following 5 conditions: injected under baseline conditions without P-gp inhibition, injected 1 h after intravenous tariquidar infusion, injected during intravenous tariquidar infusion, injected after oral tariquidar, and injected after disulfiram. (11)C-dLop uptake was quantified with kinetic modeling using metabolite-corrected arterial input function or by measuring the area under the time-activity curve in the brain from 10 to 30 min. Neither oral tariquidar nor oral disulfiram increased brain uptake of (11)C-dLop. Injecting (11)C-dLop during tariquidar infusion, when plasma tariquidar concentrations reach their peak, resulted in a brain uptake of the radioligand approximately 5-fold greater than baseline. Brain uptake was similar with 2 and 4 mg of intravenous tariquidar per kilogram; however, the lower dose was better tolerated. Injecting (11)C-dLop after tariquidar infusion also increased brain uptake, though higher doses (up to 6 mg/kg) were required. Brain uptake of (11)C-dLop increased fairly linearly with increasing plasma tariquidar concentrations, but we are uncertain whether maximal uptake was achieved. We sought to increase the dynamic range of P-gp function measured after blockade. Performing (11)C-dLop PET during peak plasma concentrations of tariquidar, achieved with concurrent administration of intravenous tariquidar, resulted in greater P-gp inhibition at the human blood-brain barrier than delayed administration and allowed the use of a lower, more tolerable dose of tariquidar. On the basis of prior monkey studies, we suspect that plasma concentrations of tariquidar did not fully block P-gp; however, higher doses of tariquidar would likely be associated with unacceptable side effects. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A patient-specific CFD-based study of embolic particle transport for stroke

NASA Astrophysics Data System (ADS)

Mukherjee, Debanjan; Shadden, Shawn C.

2014-11-01

Roughly 1/3 of all strokes are caused by an embolus traveling to a cerebral artery and blocking blood flow in the brain. A detailed understanding of the dynamics of embolic particles within arteries is the basis for this study. Blood flow velocities and emboli trajectories are resolved using a coupled Euler-Lagrange approach. Computer model of the major arteries is extracted from patient image data. Blood is modeled as a Newtonian fluid, discretized using the Finite Volume method, with physiologically appropriate inflow and outflow boundary conditions. The embolus trajectory is modeled using Lagrangian particle equations accounting for embolus interaction with blood as well as vessel wall. Both one and two way fluid-particle coupling are considered, the latter being implemented using momentum sources augmented to the discretized flow equations. The study determines individual embolus path up to arteries supplying the brain, and compares the size-dependent distribution of emboli amongst vessels superior to the aortic-arch, and the role of fully coupled blood-embolus interactions in modifying both trajectory and distribution when compared with one-way coupling. Specifically for intermediate particle sizes the model developed will better characterize the risks for embolic stroke. American Heart Association (AHA) Grant: Embolic Stroke: Anatomic and Physiologic Insights from Image-Based CFD.

Regional reliability of quantitative signal targeting with alternating radiofrequency (STAR) labeling of arterial regions (QUASAR).

PubMed

Tatewaki, Yasuko; Higano, Shuichi; Taki, Yasuyuki; Thyreau, Benjamin; Murata, Takaki; Mugikura, Shunji; Ito, Daisuke; Takase, Kei; Takahashi, Shoki

2014-01-01

Quantitative signal targeting with alternating radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling technique that could improve the reliability of brain perfusion measurements. Although it is considered reliable for measuring gray matter as a whole, it has never been evaluated regionally. Here we assessed this regional reliability. Using a 3-Tesla Philips Achieva whole-body system, we scanned four times 10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We computed perfusion images and ran a voxel-based analysis within all brain structures. We also calculated mean regional cerebral blood flow (rCBF) within regions of interest configured for each arterial territory distribution. The mean CBF over whole gray matter was 37.74 with intraclass correlation coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel-wise ICC and coefficient-of-variation maps showed relatively lower reliability in watershed areas and white matter especially in deeper white matter. The absolute mean rCBF values were consistent with the ones reported from PET, as was the relatively low variability in different feeding arteries. Thus, QUASAR reliability for regional perfusion is high within gray matter, but uncertain within white matter. © 2014 The Authors. Journal of Neuroimaging published by the American Society of Neuroimaging.

Regional Reliability of Quantitative Signal Targeting with Alternating Radiofrequency (STAR) Labeling of Arterial Regions (QUASAR)

PubMed Central

Tatewaki, Yasuko; Higano, Shuichi; Taki, Yasuyuki; Thyreau, Benjamin; Murata, Takaki; Mugikura, Shunji; Ito, Daisuke; Takase, Kei; Takahashi, Shoki

2014-01-01

BACKGROUND AND PURPOSE Quantitative signal targeting with alternating radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling technique that could improve the reliability of brain perfusion measurements. Although it is considered reliable for measuring gray matter as a whole, it has never been evaluated regionally. Here we assessed this regional reliability. METHODS Using a 3-Tesla Philips Achieva whole-body system, we scanned four times 10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We computed perfusion images and ran a voxel-based analysis within all brain structures. We also calculated mean regional cerebral blood flow (rCBF) within regions of interest configured for each arterial territory distribution. RESULTS The mean CBF over whole gray matter was 37.74 with intraclass correlation coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel-wise ICC and coefficient-of-variation maps showed relatively lower reliability in watershed areas and white matter especially in deeper white matter. The absolute mean rCBF values were consistent with the ones reported from PET, as was the relatively low variability in different feeding arteries. CONCLUSIONS Thus, QUASAR reliability for regional perfusion is high within gray matter, but uncertain within white matter. PMID:25370338

Model of the transient neurovascular response based on prompt arterial dilation

PubMed Central

Kim, Jung Hwan; Khan, Reswanul; Thompson, Jeffrey K; Ress, David

2013-01-01

Brief neural stimulation results in a stereotypical pattern of vascular and metabolic response that is the basis for popular brain-imaging methods such as functional magnetic resonance imagine. However, the mechanisms of transient oxygen transport and its coupling to cerebral blood flow (CBF) and oxygen metabolism (CMRO2) are poorly understood. Recent experiments show that brief stimulation produces prompt arterial vasodilation rather than venous vasodilation. This work provides a neurovascular response model for brief stimulation based on transient arterial effects using one-dimensional convection–diffusion transport. Hemoglobin oxygen dissociation is included to enable predictions of absolute oxygen concentrations. Arterial CBF response is modeled using a lumped linear flow model, and CMRO2 response is modeled using a gamma function. Using six parameters, the model successfully fit 161/166 measured extravascular oxygen time courses obtained for brief visual stimulation in cat cerebral cortex. Results show how CBF and CMRO2 responses compete to produce the observed features of the hemodynamic response: initial dip, hyperoxic peak, undershoot, and ringing. Predicted CBF and CMRO2 response amplitudes are consistent with experimental measurements. This model provides a powerful framework to quantitatively interpret oxygen transport in the brain; in particular, its intravascular oxygen concentration predictions provide a new model for fMRI responses. PMID:23756690

Factors associated with the misdiagnosis of cerebellar infarction.

PubMed

Masuda, Yoko; Tei, Hideaki; Shimizu, Satoru; Uchiyama, Shinichiro

2013-10-01

Cerebellar infarction is easily misdiagnosed or underdiagnosed. In this study, we investigated factors leading to misdiagnosis of cerebellar infarction in patients with acute ischemic stroke. Data on neurological and radiological findings from 114 consecutive patients with acute cerebellar infarction were analyzed. We investigated factors associated with misdiagnosis from the data on clinical findings. Thirty-two (28%) patients were misdiagnosed on admission. Misdiagnosis was significantly more frequent in patients below 60 years of age and in patients with vertebral artery dissection, and significantly less frequent in patients with dysarthria. It tended to be more frequent in patients with the medial branch of posterior inferior cerebellar artery territory infarction, and infrequent in patients with the medial branch of the superior cerebellar artery territory infarction. Thirty out of 32 (94%) misdiagnosed patients were seen by physicians that were not neurologists at the first visit. Twenty-four of 32 (75%) misdiagnosed patients were screened only by brain CT. However, patients were not checked by brain MRI or follow-up CT until their conditions worsened. Patients below 60 years of age and patients with vertebral artery dissection are more likely to have a cerebellar infarction misdiagnosed by physicians other than neurologists. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Relationship between haemodynamic impairment and collateral blood flow in carotid artery disease.

PubMed

Hartkamp, Nolan S; Petersen, Esben T; Chappell, Michael A; Okell, Thomas W; Uyttenboogaart, Maarten; Zeebregts, Clark J; Bokkers, Reinoud Ph

2017-01-01

Collateral blood flow plays a pivotal role in steno-occlusive internal carotid artery (ICA) disease to prevent irreversible ischaemic damage. Our aim was to investigate the effect of carotid artery disease upon cerebral perfusion and cerebrovascular reactivity and whether haemodynamic impairment is influenced at brain tissue level by the existence of primary and/or secondary collateral. Eighty-eight patients with steno-occlusive ICA disease and 29 healthy controls underwent MR examination. The presence of collaterals was determined with time-of-flight, two-dimensional phase contrast MRA and territorial arterial spin labeling (ASL) imaging. Cerebral blood flow and cerebrovascular reactivity were assessed with ASL before and after acetazolamide. Cerebral haemodynamics were normal in asymptomatic ICA stenosis patients, as opposed to patients with ICA occlusion, in whom the haemodynamics in both hemispheres were compromised. Haemodynamic impairment in the affected brain region was always present in symptomatic patients. The degree of collateral blood flow was inversely correlated with haemodynamic impairment. Recruitment of secondary collaterals only occurred in symptomatic ICA occlusion patients. In conclusion, both CBF and cerebrovascular reactivity were found to be reduced in symptomatic patients with steno-occlusive ICA disease. The presence of collateral flow is associated with further haemodynamic impairment. Recruitment of secondary collaterals is associated with severe haemodynamic impairment.

Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries

PubMed Central

Wu, Celeste Yin-Chieh; Chen, Po-Yi; Chen, Mei-Fang; Kuo, Jon-Son; Lee, Tony Jer-Fu

2012-01-01

Memantine, an NMDA receptor antagonist used for treatment of Alzheimer’s disease (AD), is known to block the nicotinic acetylcholine receptors (nAChRs) in the central nervous system (CNS). In the present study, we examined by wire myography if memantine inhibited α3β2-nAChRs located on cerebral perivascular sympathetic nerve terminals originating in the superior cervical ganglion (SCG), thus, leading to inhibition of nicotine-induced nitrergic neurogenic dilation of isolated porcine basilar arteries. Memantine concentration-dependently blocked nicotine-induced neurogenic dilation of endothelium-denuded basilar arteries without affecting that induced by transmural nerve stimulation, sodium nitroprusside, or isoproterenol. Furthermore, memantine significantly inhibited nicotine-elicited inward currents in Xenopous oocytes expressing α3β2-, α7- or α4β2-nAChR, and nicotine-induced calcium influx in cultured rat SCG neurons. These results suggest that memantine is a non-specific antagonist for nAChR. By directly inhibiting α3β2-nAChRs located on the sympathetic nerve terminals, memantine blocks nicotine-induced neurogenic vasodilation of the porcine basilar arteries. This effect of memantine is expected to reduce the blood supply to the brain stem and possibly other brain regions, thus, decreasing its clinical efficacy in the treatment of Alzheimer’s disease. PMID:22792283

Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: Occurrence and perfusion characteristics.

PubMed

Sommer, Wieland H; Bollwein, Christine; Thierfelder, Kolja M; Baumann, Alena; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F; Plate, Annika; Straube, Andreas; von Baumgarten, Louisa

2016-04-01

We aimed to investigate the overall prevalence and possible factors influencing the occurrence of crossed cerebellar diaschisis after acute middle cerebral artery infarction using whole-brain CT perfusion. A total of 156 patients with unilateral hypoperfusion of the middle cerebral artery territory formed the study cohort; 352 patients without hypoperfusion served as controls. We performed blinded reading of different perfusion maps for the presence of crossed cerebellar diaschisis and determined the relative supratentorial and cerebellar perfusion reduction. Moreover, imaging patterns (location and volume of hypoperfusion) and clinical factors (age, sex, time from symptom onset) resulting in crossed cerebellar diaschisis were analysed. Crossed cerebellar diaschisis was detected in 35.3% of the patients with middle cerebral artery infarction. Crossed cerebellar diaschisis was significantly associated with hypoperfusion involving the left hemisphere, the frontal lobe and the thalamus. The degree of the relative supratentorial perfusion reduction was significantly more pronounced in crossed cerebellar diaschisis-positive patients but did not correlate with the relative cerebellar perfusion reduction. Our data suggest that (i) crossed cerebellar diaschisis is a common feature after middle cerebral artery infarction which can robustly be detected using whole-brain CT perfusion, (ii) its occurrence is influenced by location and degree of the supratentorial perfusion reduction rather than infarct volume (iii) other clinical factors (age, sex and time from symptom onset) did not affect the occurrence of crossed cerebellar diaschisis. © The Author(s) 2015.

Cerebrospinal fluid bulk flow is driven by the cardiac cycle

NASA Astrophysics Data System (ADS)

Tithof, Jeffrey; Mestre, Humberto; Thomas, John; Nedergaard, Maiken; Kelley, Douglas

2017-11-01

Recent discoveries have uncovered a cerebrospinal fluid (CSF) transport system in the perivascular spaces (PVS) of the mammalian brain which clears excess extracellular fluid and protein waste products. The oscillatory pattern of CSF flow has long been attributed to arterial pulsations due to cardiac contractility but limitations in imaging techniques have impeded quantitative measurement of flow rates within the PVS. In this talk, we describe quantitative measurements from the first ever direct imaging of CSF flow in the PVS of a mouse brain. We perform particle tracking velocimetry to obtain time-resolved velocity measurements. To identify the cardiac and/or respiratory dependence of the flow, while imaging, we simultaneously record the mouse's electrocardiogram and respiration. Our measurements conclusively indicate that CSF pulsatility in the arterial PVS is directly driven by the cardiac cycle and not by the respiratory cycle or cerebral vasomotion. These results offer a substantial step forward in understanding bulk flow of CSF in the mammalian brain and may have important implications related to neurodegenerative diseases.

Carbon-11-cocaine binding compared at subpharmacological and pharmacological doses: A PET study

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

Volkow, N.D.; Fowler, J.S.; Logan, J.

The authors have characterized cocaine binding in the brain to a high-affinity site on the dopamine transporter using PET and tracer doses of [{sup 11}C]cocaine in the baboon in vivo. The binding pattern, however, of cocaine at tracer (subpharmacological) doses may differ from that observed when the drug is taken in behaviorally active doses, particularly since in vitro studies have shown that cocaine also binds to low affinity binding sites. PET was used to compare and characterize [{sup 11}C]cocaine binding in the baboon brain at low subpharmacological (18 {mu}g average dose) and at pharmacological (8000 {mu}g) doses. Serial studies onmore » the same day in the same baboon were used to assess the reproducibility of repeated measures and to assess the effects of drugs which inhibit the dopamine, norepinephrine and serotonin transporters. Time-activity curves from brain and the arterial plasma input function were used to calculate the steady-state distribution volume (DV). At subpharmacological doses, [{sup 11}C]cocaine had a more homogeneous distribution. Bmax/Kd for sub-pharmacological [{sup 11}C]cocaine corresponded to 0.5-0.6 and for pharmacological [{sup 11}C]cocaine it corresponded to 0.1-0.2. Two-point Scatchard analysis gave Bmax = 2300 pmole/g and Kd = 3600 nM. Bmax/Kd for sub-pharmacological doses of [{sup 11}C]cocaine was decreased by cocaine and drugs that inhibit the dopamine transporter, to 0.1-0.2, but not by drugs that inhibit the serotonin or the norepinephrine transporter. None of these drugs changed Bmax/Kd for a pharmacological dose of [{sup 11}C]cocaine. At subpharmacological doses, [{sup 11}C]cocaine binds predominantly to a high-affinity site on the dopamine transporter. 36 refs., 4 figs., 5 tabs.« less

Evaluation of the brain anaesthesia response monitor during anaesthesia for cardiac surgery: a double-blind, randomised controlled trial using two doses of fentanyl.

PubMed

Shoushtarian, Mehrnaz; McGlade, Desmond P; Delacretaz, Louis J; Liley, David T J

2016-12-01

The brain anaesthesia response (BAR) monitor uses a method of EEG analysis, based on a model of brain electrical activity, to monitor the cerebral response to anaesthetic and sedative agents via two indices, composite cortical state (CCS) and cortical input (CI). It was hypothesised that CCS would respond to the hypnotic component of anaesthesia and CI would differentiate between two groups of patients receiving different doses of fentanyl. Twenty-five patients scheduled to undergo elective first-time coronary artery bypass graft surgery were randomised to receive a total fentanyl dose of either 12 μg/kg (fentanyl low dose, FLD) or 24 μg/kg (fentanyl moderate dose, FMD), both administered in two divided doses. Propofol was used for anaesthesia induction and pancuronium for intraoperative paralysis. Hemodynamic management was protocolised using vasoactive drugs. BIS, CCS and CI were simultaneously recorded. Response of the indices (CI, CCS and BIS) to propofol and their differences between the two groups at specific points from anaesthesia induction through to aortic cannulation were investigated. Following propofol induction, CCS and BIS but not CI showed a significant reduction. Following the first dose of fentanyl, CI, CCS and BIS decreased in both groups. Following the second dose of fentanyl, there was a significant reduction in CI in the FLD group but not the FMD group, with no significant change found for BIS or CCS in either group. The BAR monitor demonstrates the potential to monitor the level of hypnosis following anaesthesia induction with propofol via the CCS index and to facilitate the titration of fentanyl as a component of balanced anaesthesia via the CI index.

Spatial resonance in a small artery excited by vibration input as a possible mechanism to cause hand-arm vascular disorders

NASA Astrophysics Data System (ADS)

Pattnaik, Shrikant; Banerjee, Rupak; Kim, Jay

2012-04-01

Hand-arm vibration syndrome (HAVS) is collectively a vasospastic and neurodegenerative occupational disease. One of the major symptoms of HAVS is vibration white finger (VWF) caused by exaggerated vasoconstriction of the arteries and skin arterioles. While VWF is a very painful and costly occupational illness, its pathology has not been well understood. In this study a small artery is modeled as a fluid filled elastic tube whose diameter changes along the axial direction. Equations of motion are developed by considering interactions between the fluid, artery wall and soft-tissue bed. It is shown that the resulting wave equation is the same as that of the basilar membrane in the cochlea of mammals. Therefore, the artery system shows a spatial resonance as in the basilar membrane, which responds with the highest amplitude at the location determined by the vibration frequency. This implies that a long-term use of one type of tool will induce high-level stresses at a few identical locations of the artery that correspond to the major frequency components of the tool. Hardening and deterioration of the artery at these locations may be a possible cause of VWF.

Can target-to-pons ratio be used as a reliable method for the analysis of [11C]PIB brain scans?

PubMed

Edison, P; Hinz, R; Ramlackhansingh, A; Thomas, J; Gelosa, G; Archer, H A; Turkheimer, F E; Brooks, D J

2012-04-15

(11)C]PIB is the most widely used PET imaging marker for amyloid in dementia studies. In the majority of studies the cerebellum has been used as a reference region. However, cerebellar amyloid may be present in genetic Alzheimer's (AD), cerebral amyloid angiopathy and prion diseases. Therefore, we investigated whether the pons could be used as an alternative reference region for the analysis of [(11)C]PIB binding in AD. The aims of the study were to: 1) Evaluate the pons as a reference region using arterial plasma input function and Logan graphical analysis of binding. 2) Assess the power of target-to-pons ratios to discriminate controls from AD subjects. 3) Determine the test-retest reliability in AD subjects. 4) Demonstrate the application of target-to-pons ratio in subjects with elevated cerebellar [(11)C]PIB binding. 12 sporadic AD subjects aged 65 ± 4.5 yrs with a mean MMSE 21.4 ± 4 and 10 age-matched control subjects had [(11)C]PIB PET with arterial blood sampling. Three additional subjects (two subjects with pre-symptomatic presenilin-1 mutation carriers and one probable familial AD) were also studied. Object maps were created by segmenting individual MRIs and spatially transforming the gray matter images into standard stereotaxic MNI space and then superimposing a probabilistic atlas. Cortical [(11)C]PIB binding was assessed with an ROI (region of interest) analysis. Parametric maps of the volume of distribution (V(T)) were generated with Logan analysis. Additionally, parametric maps of the 60-90 min target-to-cerebellar ratio (RATIO(CER)) and the 60-90 min target-to-pons ratio (RATIO(PONS)) were computed. All three approaches were able to differentiate AD from controls (p<0.0001, nonparametric Wilcoxon rank sum test) in the target regions with RATIO(CER) and RATIO(PONS) differences higher than V(T) with use of an arterial input function. All methods had a good reproducibility (intraclass correlation coefficient>0.83); RATIO(CER) performed best closely followed by RATIO(PONS). The two subjects with presenilin-1 mutations and the probable familial AD case showed no significant differences in cortical binding using RATIO(CER), but the RATIO(PONS) approach revealed higher [(11)C]PIB binding in cortex and cerebellum. This study established 60-90 min target-to-pons RATIOs as a reliable method of analysis in [(11)C]PIB PET studies where cerebellum is not an appropriate reference region. Copyright © 2012 Elsevier Inc. All rights reserved.

ROLE OF ENDOTHELIAL NITRIC OXIDE SYNTHETASE IN ARTERIOGENESIS AFTER STROKE IN MICE

PubMed Central

CUI, X.; CHOPP, M.; ZACHAREK, A.; ZHANG, C.; ROBERTS, C.; CHEN, J.

2009-01-01

Arteriogenesis supports restored perfusion in the ischemic brain and improves long-term functional outcome after stroke. We investigate the role of endothelial nitric oxide synthetase (eNOS) and an NO donor, [(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) aminio] diazen-1-ium-1, 2-diolate (DETA-NONOate), in promoting arteriogenesis after stroke. Adult wild-type (WT, n=18) and eNOS-knockout (eNOS-/-, n=36) mice were subjected to transient (2.5 hours) right middle cerebral artery occlusion (MCAo) and were treated with or without DETA-NONOate (0.4 mg/kg) 24 hours after MCAo. Functional evaluation was performed. Animals were sacrificed 3 days after MCAo for arterial cell culture studies, or 14 days for immunohistochemical analysis. Consistent with previous studies, eNOS-/- mice exhibited a higher mortality rate (p<0.05, n=18/group) and more severe neurological functional deficit after MCAo than WT mice (p<0.05, n=12/group). Decreased arteriogenesis, was evident in eNOS-/- mice compared with WT mice, as demonstrated by reduced vascular smooth muscle cell (VSMC) proliferation, arterial density and diameter in the ischemic brain. eNOS-/- mice treated with DETA-NONOate had a significantly decreased mortality rate and improved functional recovery, and exhibited enhanced arteriogenesis identified by increased VSMC proliferation, and upregulated arterial density and diameter compared to eNOS-/- mice after stroke (p<0.05, n=12/group). To elucidate the mechanisms underlying eNOS/NO mediated arteriogenesis, VSMC migration was measured in vitro. Arterial cell migration significantly decreased in the cultured common carotid artery (CCA) derived from eNOS-/- mice 3 days after MCAo compared to WT arterial cells. DETA-NONOate-treatment significantly attenuated eNOS-/--induced decrease of arterial cell migration compared to eNOS-/- control artery (p<0.05. n=6/group). Using VSMC culture, DETA-NONOate significantly increased VSMC migration, while inhibition of NOS significantly decreased VSMC migration (p<0.05. n=6/group). Our data indicated that eNOS not only promotes vascular dilation but also increases VSMC proliferation and migration, and thereby enhances arteriogenesis after stroke. Therefore, increase eNOS may play an important role in regulating of arteriogenesis after stroke. PMID:19154781

Role of endothelial nitric oxide synthetase in arteriogenesis after stroke in mice.

PubMed

Cui, X; Chopp, M; Zacharek, A; Zhang, C; Roberts, C; Chen, J

2009-03-17

Arteriogenesis supports restored perfusion in the ischemic brain and improves long-term functional outcome after stroke. We investigate the role of endothelial nitric oxide synthetase (eNOS) and a nitric oxide (NO) donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA-NONOate), in promoting arteriogenesis after stroke. Adult wild-type (WT, n=18) and eNOS-knockout (eNOS(-/-), n=36) mice were subjected to transient (2.5 h) right middle cerebral artery occlusion (MCAo) and were treated with or without DETA-NONOate (0.4 mg/kg) 24 h after MCAo. Functional evaluation was performed. Animals were sacrificed 3 days after MCAo for arterial cell culture studies, or 14 days for immunohistochemical analysis. Consistent with previous studies, eNOS(-/-) mice exhibited a higher mortality rate (P<0.05, n=18/group) and more severe neurological functional deficit after MCAo than WT mice (P<0.05, n=12/group). Decreased arteriogenesis, was evident in eNOS(-/-) mice compared with WT mice, as demonstrated by reduced vascular smooth muscle cell (VSMC) proliferation, arterial density and diameter in the ischemic brain. eNOS(-/-) mice treated with DETA-NONOate had a significantly decreased mortality rate and improved functional recovery, and exhibited enhanced arteriogenesis identified by increased VSMC proliferation, and upregulated arterial density and diameter compared to eNOS(-/-) mice after stroke (P<0.05, n=12/group). To elucidate the mechanisms underlying eNOS/NO mediated arteriogenesis, VSMC migration was measured in vitro. Arterial cell migration significantly decreased in the cultured common carotid artery (CCA) derived from eNOS(-/-) mice 3 days after MCAo compared to WT arterial cells. DETA-NONOate-treatment significantly attenuated eNOS(-/-)-induced decrease of arterial cell migration compared to eNOS(-/-) control artery (P<0.05; n=6/group). Using VSMC culture, DETA-NONOate significantly increased VSMC migration, while inhibition of NOS significantly decreased VSMC migration (P<0.05; n=6/group). Our data indicated that eNOS not only promotes vascular dilation but also increases VSMC proliferation and migration, and thereby enhances arteriogenesis after stroke. Therefore, increase eNOS may play an important role in regulating of arteriogenesis after stroke.

Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly: A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness.

PubMed

Gustavsson, Anna-Märta; Stomrud, Erik; Abul-Kasim, Kasim; Minthon, Lennart; Nilsson, Peter M; Hansson, Oskar; Nägga, Katarina

2015-01-01

Arterial stiffness reflects the ageing processes in the vascular system, and studies have shown an association between reduced cognitive function and cerebral small vessel disease. Small vessel disease can be visualized as white matter hyperintensities (WMH) and lacunar infarcts but also as cerebral microbleeds on brain magnetic resonance imaging (MRI). We aimed to investigate if arterial stiffness influences the presence of microbleeds, WMH and cognitive function in a population of cognitively healthy elderly. The study population is part of the Swedish BioFinder study and consisted of 208 individuals without any symptoms of cognitive impairment, who scored >27 points on the Mini-Mental State Examination. The participants (mean age, 72 years; 59% women) underwent MRI of the brain with visual rating of microbleeds and WMH. Arterial stiffness was measured with carotid-femoral pulse wave velocity (cfPWV). Eight cognitive tests covering different cognitive domains were performed. Microbleeds were detected in 12% and WMH in 31% of the participants. Mean (±standard deviation, SD) cfPWV was 10.0 (±2.0) m/s. There was no association between the presence of microbleeds and arterial stiffness. There was a positive association between arterial stiffness and WMH independent of age or sex (odds ratio, 1.58; 95% confidence interval, 1.04-2.40, p < 0.05), but the effect was attenuated when further adjustments for several cardiovascular risk factors were performed (p > 0.05). Cognitive performance was not associated with microbleeds, but individuals with WMH performed slightly worse than those without WMH on the Symbol Digit Modalities Test (mean ± SD, 35 ± 7.8 vs. 39 ± 8.1, p < 0.05). Linear regression revealed no direct associations between arterial stiffness and the results of the cognitive tests. Arterial stiffness was not associated with the presence of cerebral microbleeds or cognitive function in cognitively healthy elderly. However, arterial stiffness was related to the presence of WMH, but the association was attenuated when multiple adjustments were made. There was a weak negative association between WMH and performance in one specific test of attention. Longitudinal follow-up studies are needed to further assess the associations.

Daily ethanol exposure during late ovine pregnancy: physiological effects in the mother and fetus in the apparent absence of overt fetal cerebral dysmorphology.

PubMed

Kenna, Kelly; De Matteo, Robert; Hanita, Takushi; Rees, Sandra; Sozo, Foula; Stokes, Victoria; Walker, David; Bocking, Alan; Brien, James; Harding, Richard

2011-10-01

High levels of ethanol (EtOH) consumption during pregnancy adversely affect fetal development; however, the effects of lower levels of exposure are less clear. Our objectives were to assess the effects of daily EtOH exposure (3.8 USA standard drinks) on fetal-maternal physiological variables and the fetal brain, particularly white matter. Pregnant ewes received daily intravenous infusions of EtOH (0.75 g/kg maternal body wt over 1 h, 8 fetuses) or saline (8 fetuses) from 95 to 133 days of gestational age (DGA; term ∼145 DGA). Maternal and fetal arterial blood was sampled at 131-133 DGA. At necropsy (134 DGA) fetal brains were collected for analysis. Maternal and fetal plasma EtOH concentrations reached similar maximal concentration (∼0.11 g/dl) and declined at the same rate. EtOH infusions produced mild reductions in fetal arterial oxygenation but there were no changes in maternal oxygenation, maternal and fetal Pa(CO(2)), or in fetal mean arterial pressure or heart rate. Following EtOH infusions, plasma lactate levels were elevated in ewes and fetuses, but arterial pH fell only in ewes. Fetal body and brain weights were similar between groups. In three of eight EtOH-exposed fetuses there were small subarachnoid hemorrhages in the cerebrum and cerebellum associated with focal cortical neuronal death and gliosis. Overall, there was no evidence of cystic lesions, inflammation, increased apoptosis, or white matter injury. We conclude that daily EtOH exposure during the third trimester-equivalent of ovine pregnancy has modest physiological effects on the fetus and no gross effects on fetal white matter development.

Assessment of intracranial vessels in association with carotid atherosclerosis and brain vascular lesions in rheumatoid arthritis.

PubMed

Oláh, Csaba; Kardos, Zsófia; Sepsi, Mariann; Sas, Attila; Kostyál, László; Bhattoa, Harjit Pal; Hodosi, Katalin; Kerekes, György; Tamási, László; Valikovics, Attila; Bereczki, Dániel; Szekanecz, Zoltán

2017-09-26

Stroke has been associated with rheumatoid arthritis (RA). We assessed patients with RA and healthy control subjects by transcranial Doppler (TCD), carotid ultrasonography and brain magnetic resonance imaging (MRI). Altogether, 41 female patients with RA undergoing methotrexate (MTX) or biologic treatment and 60 age-matched control subjects underwent TCD assessment of the middle cerebral artery (MCA) and basilar artery. Pulsatility index (PI), resistivity (resistance) index (RI) and circulatory reserve capacity (CRC) were determined at rest (r) and after apnoea (a) and hyperventilation (h). The presence of carotid plaques and carotid intima-media thickness (cIMT) were also determined. Intracerebral vascular lesions were investigated by brain MRI. MCA PI and RI values at rest and after apnoea were significantly increased in the total and MTX-treated RA populations vs control subjects. MCA CRC was also impaired, and basilar artery PI was higher in RA. More patients with RA had carotid plaques and increased cIMT. Linear regression analysis revealed that left PI(r) and RI(r) correlated with disease duration and that left PI(r), RI(r), PI(a), PI(h) and basilar PI correlated with disease activity. Right CRC inversely correlated with 28-joint Disease Activity Score. Disease activity was an independent determinant of left PI(a) and right CRC. Compared with long-term MTX treatment alone, the use of biologics in combination with MTX was associated with less impaired cerebral circulation. Impaired cerebral circulation was also associated with measures of carotid atherosclerosis. To our knowledge, this is the first study to show increased distal MCA and basilar artery occlusion in RA as determined by TCD. Patients with RA also had CRC defects. We also confirmed increased carotid plaque formation and increased cIMT. Biologics may beneficially influence some parameters in the intracranial vessels.

From Input to Intake: Towards a Brain-Based Perspective of Selective Attention.

ERIC Educational Resources Information Center

Sato, Edynn; Jacobs, Bob

1992-01-01

Addresses, from a neurobiological perspective, the input-intake distinction commonly made in applied linguistics and the role of selective attention in transforming input to intake. The study places primary emphasis upon a neural structure (the nucleus reticularis thalami) that appears to be essential for selective attention. (79 references)…

Importance of the perforating arteries in the proximal part of the PICA for surgical approaches to the brain stem and fourth ventricle--an anatomical study.

PubMed

Kayaci, Selim; Caglar, Yusuf Sukru; Bas, Orhan; Ozveren, Mehmet Faik

2013-10-01

The purpose of this study is to examine the perforating arteries (PAs) in the proximal part of the posterior inferior cerebellar artery (PICA) for surgical approaches to the brain stem and fourth ventricle, and to stress their importance in microsurgical procedures. Twenty-six adult cadaver obtained from routine autopsies were used. During the examination, the PAs and the segmental structure of the proximal part of the PICAs and their relation to the neighbouring anatomical structures were demonstrated. We classified the PICAs into 4 types on the basis of the distance of the middle point of the width of the caudal loop to the midline, and their presence or absence as Group A (symmetrical, anterior medullary type: 26.9%), Group B (lateral medullary type: 15.4%), Group C (asymmetrical type: 38.5%), and Group D (unilateral type: 19.2%). The number of the PAs in the tonsillomedullary segment and the caudal loop was higher than those originating from the other segments. Approaches to the medial or lateral of the PICA should be made in a way that protects the PAs (avoiding retraction of the PICA). Otherwise the PAs will be damaged and as a result brain stem ischaemia may occur, which can have serious clinical outcomes. Copyright © 2013 Elsevier B.V. All rights reserved.

The usefulness of the ivy sign on fluid-attenuated intensity recovery images in improved brain hemodynamic changes after superficial temporal artery-middle cerebral artery anastomosis in adult patients with moyamoya disease.

PubMed

Lee, Jung Keun; Yoon, Byul Hee; Chung, Seung Young; Park, Moon Sun; Kim, Seong Min; Lee, Do Sung

2013-10-01

MR perfusion and single photon emission computerized tomography (SPECT) are well known imaging studies to evaluate hemodynamic change between prior to and following superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis in moyamoya disease. But their side effects and invasiveness make discomfort to patients. We evaluated the ivy sign on MR fluid attenuated inversion recovery (FLAIR) images in adult patients with moyamoya disease and compared it with result of SPECT and MR perfusion images. We enrolled twelve patients (thirteen cases) who were diagnosed with moyamoya disease and underwent STA-MCA anastomosis at our medical institution during a period ranging from September of 2010 to December of 2012. The presence of the ivy sign on MR FLAIR images was classified as Negative (0), Minimal (1), and Positive (2). Regions were classified into four territories: the anterior cerebral artery (ACA), the anterior MCA, the posterior MCA and the posterior cerebral artery. Ivy signs on preoperative and postoperative MR FLAIR were improved (8 and 4 in the ACA regions, 13 and 4 in the anterior MCA regions and 19 and 9 in the posterior MCA regions). Like this result, the cerebrovascular reserve (CVR) on SPECT was significantly increased in the sum of CVR in same regions after STA-MCA anastomosis. After STA-MCA anastomosis, ivy signs were decreased in the cerebral hemisphere. As compared with conventional diagnostic modalities such as SPECT and MR perfusion images, the ivy sign on MR FLAIR is considered as a useful indicator in detecting brain hemodynamic changes between preoperatively and postoperatively in adult moyamoya patients.

The Usefulness of the Ivy Sign on Fluid-Attenuated Intensity Recovery Images in Improved Brain Hemodynamic Changes after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis in Adult Patients with Moyamoya Disease

PubMed Central

Lee, Jung Keun; Yoon, Byul Hee; Park, Moon Sun; Kim, Seong Min; Lee, Do Sung

2013-01-01

Objective MR perfusion and single photon emission computerized tomography (SPECT) are well known imaging studies to evaluate hemodynamic change between prior to and following superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis in moyamoya disease. But their side effects and invasiveness make discomfort to patients. We evaluated the ivy sign on MR fluid attenuated inversion recovery (FLAIR) images in adult patients with moyamoya disease and compared it with result of SPECT and MR perfusion images. Methods We enrolled twelve patients (thirteen cases) who were diagnosed with moyamoya disease and underwent STA-MCA anastomosis at our medical institution during a period ranging from September of 2010 to December of 2012. The presence of the ivy sign on MR FLAIR images was classified as Negative (0), Minimal (1), and Positive (2). Regions were classified into four territories: the anterior cerebral artery (ACA), the anterior MCA, the posterior MCA and the posterior cerebral artery. Results Ivy signs on preoperative and postoperative MR FLAIR were improved (8 and 4 in the ACA regions, 13 and 4 in the anterior MCA regions and 19 and 9 in the posterior MCA regions). Like this result, the cerebrovascular reserve (CVR) on SPECT was significantly increased in the sum of CVR in same regions after STA-MCA anastomosis. Conclusion After STA-MCA anastomosis, ivy signs were decreased in the cerebral hemisphere. As compared with conventional diagnostic modalities such as SPECT and MR perfusion images, the ivy sign on MR FLAIR is considered as a useful indicator in detecting brain hemodynamic changes between preoperatively and postoperatively in adult moyamoya patients. PMID:24294453

Attenuation and recovery of brain stem autoregulation in spontaneously hypertensive rats.

PubMed

Toyoda, K; Fujii, K; Ibayashi, S; Kitazono, T; Nagao, T; Takaba, H; Fujishima, M

1998-03-01

Cerebral large arteries dilate actively around the lower limits of CBF autoregulation, mediated at least partly by nitric oxide, and maintain CBF during severe hypotension. We tested the hypothesis that this autoregulatory response of large arteries, as well as the response of arterioles, is altered in spontaneously hypertensive rats (SHR) and that the altered response reverts to normal during long-term antihypertensive treatment with cilazapril, an angiotensin-converting enzyme inhibitor. In anesthetized 6- to 7-month-old normotensive Wistar-Kyoto rats (WKY), 4- and 6- to 7-month-old SHR without antihypertensive treatment, and 6- to 7-month-old SHR treated with cilazapril for 10 weeks, local CBF to the brain stem was determined with laser-Doppler flowmetry and diameters of the basilar artery and its branches were measured through a cranial window during stepwise hemorrhagic hypotension. The lower limit of CBF autoregulation shifted upward in untreated SHR to 90 to 105 mm Hg from 30 to 45 mm Hg in WKY, and it reverted to 30 to 45 mm Hg in treated SHR. In response to severe hypotension, the basilar artery dilated by 21 +/- 6% (mean +/- SD) of the baseline internal diameter in WKY. The vasodilation was impaired in untreated SHR (10 +/- 8% in 4-mo-old SHR and 4 +/- 5% in 6- to 7-month-old SHR), and was restored to 22 +/- 10% by treatment with cilazapril (P < 0.005). Dilator responses of branch arterioles to hypotension showed similar attenuation and recovery as that of the basilar artery. The data indicate that chronic hypertension impairs the autoregulatory dilation of the basilar artery as well as branch arterioles and that antihypertensive treatment with cilazapril restores the diminished dilation toward normal.

Carotid Artery Stenting and Blood-Brain Barrier Permeability in Subjects with Chronic Carotid Artery Stenosis.

PubMed

Szarmach, Arkadiusz; Halena, Grzegorz; Kaszubowski, Mariusz; Piskunowicz, Maciej; Studniarek, Michal; Lass, Piotr; Szurowska, Edyta; Winklewski, Pawel J

2017-05-08

Failure of the blood-brain barrier (BBB) is a critical event in the development and progression of diseases such as acute ischemic stroke, chronic ischemia or small vessels disease that affect the central nervous system. It is not known whether BBB breakdown in subjects with chronic carotid artery stenosis can be restrained with postoperative recovery of cerebral perfusion. The aim of the study was to assess the short-term effect of internal carotid artery stenting on basic perfusion parameters and permeability surface area-product (PS) in such a population. Forty subjects (23 males) with stenosis of >70% within a single internal carotid artery and neurological symptoms who underwent a carotid artery stenting procedure were investigated. Differences in the following computed tomography perfusion (CTP) parameters were compared before and after surgery: global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and PS. PS acquired by CTP is used to measure the permeability of the BBB to contrast material. In all baseline cases, the CBF and CBV values were low, while MTT and TTP were high on both the ipsi- and contralateral sides compared to reference values. PS was approximately twice the normal value. CBF was higher (+6.14%), while MTT was lower (-9.34%) on the contralateral than on the ipsilateral side. All perfusion parameters improved after stenting on both the ipsilateral (CBF +22.66%; CBV +18.98%; MTT -16.09%, TTP -7.62%) and contralateral (CBF +22.27%, CBV +19.72%, MTT -14.65%, TTP -7.46%) sides. PS decreased by almost half: ipsilateral -48.11%, contralateral -45.19%. The decline in BBB permeability was symmetrical on the ipsi- and contralateral sides to the stenosis. Augmented BBB permeability can be controlled by surgical intervention in humans.

Ultrasonic assessment of cerebral blood flow changes during ischemia-reperfusion in 7-day-old rats.

PubMed

Bonnin, Philippe; Debbabi, Haythem; Mariani, Jean; Charriaut-Marlangue, Christiane; Renolleau, Sylvain

2008-06-01

A model of ischemic brain injury in 7-day-old rat pups has been developed to study perinatal ischemia. It combines permanent occlusion of the distal left middle cerebral artery (LMCA) and transient occlusion of homolateral common carotid artery (LCCA). At removal of the clip on LCCA, reflow allowed brain reperfusion through cortical anastomoses. In 10 rat pups, we measured blood flow velocities (BFV) in main cerebral arteries with 12-MHz ultrasound imaging. At basal states, peak systolic BFV in proximal LMCA was 16.0 +/- 3.0 cm.s(-1). Occlusion of LMCA did not yield significant modifications. Occlusion of LCCA involved only a decrease in BFV to 9.5 +/- 2.6 cm.s(-1) (p < 0.001). Indeed, LMCA was then supply by the right internal carotid and the vertebral arteries through the circle of Willis. In three rat pups, release of occlusion of LCCA was followed by restoration of BFV in the left internal carotid artery and in LMCA, in seven pups, by a reversed flow in the LICA and lower BFV in LMCA (11.9 +/- 2.3, p < 0.05). BFV returned to basal values from h5 to h48 in all animals. In addition, ultrasound imaging is a useful, reproducible, non invasive, easy-to-repeat, method to assess and monitor arterial cerebral blood flow supply in small animals. It helps to characterize changes occurring during cerebral ischemia and reperfusion, particularly the depth of the hypoperfusion, as well as the variability of reflow. In preclinical studies, this method could help to identify what can be assigned to a neuroprotective treatment and what depends on changes in cerebral blood flow supply.

Association of the Fractal Dimension of Retinal Arteries and Veins with Quantitative Brain MRI Measures in HIV-Infected and Uninfected Women

PubMed Central

Crystal, Howard A.; Holman, Susan; Lui, Yvonne W.; Baird, Alison E.; Yu, Hua; Klein, Ronald; Rojas-Soto, Diana Marcella; Gustafson, Deborah R.; Stebbins, Glenn T.

2016-01-01

Objective The fractal dimension of retinal arteries and veins is a measure of the complexity of the vascular tree. We hypothesized that retinal fractal dimension would be associated with brain volume and white matter integrity in HIV-infected women. Design Nested case-control within longitudinal cohort study. Methods Women were recruited from the Brooklyn site of the Women’s Interagency HIV study (WIHS); 34 HIV-infected and 21 HIV-uninfected women with analyzable MRIs and retinal photographs were included. Fractal dimension was determined using the SIVA software program on skeletonized retinal images. The relationship between predictors (retinal vascular measures) and outcomes (quantitative MRI measures) were analyzed with linear regression models. All models included age, intracranial volume, and both arterial and venous fractal dimension. Some models were adjusted for blood pressure, race/ethnicity, and HIV-infection. Results The women were 45.6 ± 7.3 years of age. Higher arterial dimension was associated with larger cortical volumes, but higher venous dimension was associated with smaller cortical volumes. In fully adjusted models, venous dimension was significantly associated with fractional anisotropy (standardized β = -0.41, p = 0.009) and total gray matter volume (β = -0.24, p = 0.03), and arterial dimension with mean diffusivity (β = -0.33,.p = 0.04) and fractional anisotropy (β = 0.34, p = 0.03). HIV-infection was not associated with any retinal or MRI measure. Conclusions Higher venous fractal dimension was associated with smaller cortical volumes and lower fractional anisotropy, whereas higher arterial fractal dimension was associated with the opposite patterns. Longitudinal studies are needed to validate this finding. PMID:27158911

[Prevalence of carotid artery stenosis in nonagenarians: Survey in a primary care hospital].

PubMed

Bohlender, J; Nussberger, J; Ménard, J; Bohlender, B

2017-06-01

Carotid artery stenosis increases with age and may cause brain ischemia if arterial hypotension occurs. We performed a monocentric pilot study to investigate its prevalence in the very elderly and to assess its potential influence on blood pressure (BP) goals during antihypertensive treatment. All patients≥90 years of a primary care medical ward were prospectively included over 15 months. Ultrasound exams of the precerebral arteries were offered to all elderly patients for routine evaluation of their cardiovascular risk. Frequencies of stenosed common, internal and external carotid arteries (CCA, ICA, ECA) were analyzed together with clinical BP and antihypertensive therapy. Patients with circulatory shock and readmissions were excluded. Sixty-three patients aged 92±3 years (78% female) hospitalized for a median of 11 days were included. On admission, 76% were on antihypertensive drugs vs. 86% at discharge. Mean admission BP was 149/77 vs. 129/72mmHg at discharge; systolic BP<140mmHg 36% vs 64% (P<0.05). Mean intima-media thickness (ACC, right/left) was 8.7/9.4mm. Prevalence of plaque or stenosis<60% was: CCA 19.0%, ICA 19.0%, ECA 31.7%, bulb 74.6%; of stenosis≥60%: CCA 0%, ICA 7.9%, ECA 19.0%, ICA bilateral 1.6% (unilateral occlusion 3.1%, no bilateral). Coincidence of systolic BP<120mmHg and ACI stenosis≥60% had a probability of 1-2%. Concerning the risk of brain ischemia due to carotid artery stenosis, a BP goal<140mmHg should be safe for most nonagenarians. If individual BP goals are lower, searching for significant stenosis by ultrasound may be useful. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Perforating arteries originating from the posterior communicating artery: a 7.0-Tesla MRI study.

PubMed

Conijn, Mandy M A; Hendrikse, Jeroen; Zwanenburg, Jaco J M; Takahara, Taro; Geerlings, Mirjam I; Mali, Willem P Th M; Luijten, Peter R

2009-12-01

The aim of this study was to investigate the ability of time-of-flight (TOF) magnetic resonance (MR) angiography at 7.0 Tesla to show the perforating branches of the posterior communicating artery (PCoA), and to investigate the presence of such visible perforating branches in relation to the size of the feeding PCoA. The secondary aim was to visualise and describe the anterior choroidal artery and the perforating branches of the P1-segment of posterior cerebral artery (P1). Forty-six healthy volunteers underwent TOF MR angiography at 7.0 Tesla. With 7.0-Tesla imaging, we visualised for the first time perforating arteries originating from the PCoA in vivo without the use of contrast agents. A perforating artery from the PCoA was found in a large proportion of the PCoAs (64%). The presence was associated with a larger diameter of the underlying PCoA (1.23 versus 1.06 mm, P = 0.03). The anterior choroidal artery was visible bilaterally in all participants. In 83% of all P1s, one or two perforating branches were visible. Non-invasive assessment of the perforating arteries of the PCoA together with the anterior choroidal artery and the perforating arteries of the P1 may increase our understanding of infarcts in the deep brain structures supplied by these arteries.

Cerebral Perfusion Is Perturbed by Preterm Birth and Brain Injury.

PubMed

Mahdi, E S; Bouyssi-Kobar, M; Jacobs, M B; Murnick, J; Chang, T; Limperopoulos, C

2018-05-10

Early disturbances in systemic and cerebral hemodynamics are thought to mediate prematurity-related brain injury. However, the extent to which CBF is perturbed by preterm birth is unknown. Our aim was to compare global and regional CBF in preterm infants with and without brain injury on conventional MR imaging using arterial spin-labeling during the third trimester of ex utero life and to examine the relationship between clinical risk factors and CBF. We prospectively enrolled preterm infants younger than 32 weeks' gestational age and <1500 g and performed arterial spin-labeling MR imaging studies. Global and regional CBF in the cerebral cortex, thalami, pons, and cerebellum was quantified. Preterm infants were stratified into those with and without structural brain injury. We further categorized preterm infants by brain injury severity: moderate-severe and mild. We studied 78 preterm infants: 31 without brain injury and 47 with brain injury (29 with mild and 18 with moderate-severe injury). Global CBF showed a borderline significant increase with increasing gestational age at birth ( P = .05) and trended lower in preterm infants with brain injury ( P = .07). Similarly, regional CBF was significantly lower in the right thalamus and midpons ( P < .05) and trended lower in the midtemporal, left thalamus, and anterior vermis regions ( P < .1) in preterm infants with brain injury. Regional CBF in preterm infants with moderate-severe brain injury trended lower in the midpons, right cerebellar hemisphere, and dentate nuclei compared with mild brain injury ( P < .1). In addition, a significant, lower regional CBF was associated with ventilation, sepsis, and cesarean delivery ( P < .05). We report early disturbances in global and regional CBF in preterm infants following brain injury. Regional cerebral perfusion alterations were evident in the thalamus and pons, suggesting regional vulnerability of the developing cerebro-cerebellar circuitry. © 2018 by American Journal of Neuroradiology.

Cerebral arteriovenous malformation

MedlinePlus

AVM - cerebral; Arteriovenous hemangioma; Stroke - AVM; Hemorrhagic stroke - AVM ... The cause of cerebral AVM is unknown. An AVM occurs when arteries in the brain connect directly to nearby veins without having the ...

A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics.

PubMed

Coccarelli, Alberto; Edwards, David Hughes; Aggarwal, Ankush; Nithiarasu, Perumal; Parthimos, Dimitris

2018-02-01

Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways. Experimental probes used on ring segments from the rabbit central ear artery are: phenylephrine, a selective α 1-adrenergic receptor agonist that induces vasoconstriction; cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase; and ryanodine, a diterpenoid that modulates Ca 2+ release from the sarcoplasmic reticulum. These interventions were able to delineate the role of membrane versus intracellular signalling, previously identified as main factors in smooth muscle contraction and the generation of vessel tone. Each SMC was modelled by a system of nonlinear differential equations that account for intracellular ionic signalling, and in particular Ca 2+ dynamics. Cytosolic Ca 2+ concentrations formed the catalytic input to a cross-bridge kinetics model. Contractile output from these cellular components forms the input to the finite-element model of the arterial rings under isometric conditions that reproduces the experimental conditions. The model does not account for the role of the endothelium, as the nitric oxide production was suppressed by the action of L-NAME, and also due to the absence of shear stress on the arterial ring, as the experimental set-up did not involve flow. Simulations generated by the integrated model closely matched experimental observations qualitatively, as well as quantitatively within a range of physiological parametric values. The model also illustrated how increased intercellular coupling led to smooth muscle coordination and the genesis of vascular tone. © 2018 The Authors.

Does linguistic input play the same role in language learning for children with and without early brain injury?

PubMed

Rowe, Meredith L; Levine, Susan C; Fisher, Joan A; Goldin-Meadow, Susan

2009-01-01

Children with unilateral pre- or perinatal brain injury (BI) show remarkable plasticity for language learning. Previous work highlights the important role that lesion characteristics play in explaining individual variation in plasticity in the language development of children with BI. The current study examines whether the linguistic input that children with BI receive from their caregivers also contributes to this early plasticity, and whether linguistic input plays a similar role in children with BI as it does in typically developing (TD) children. Growth in vocabulary and syntactic production is modeled for 80 children (53 TD, 27 BI) between 14 and 46 months. Findings indicate that caregiver input is an equally potent predictor of vocabulary growth in children with BI and in TD children. In contrast, input is a more potent predictor of syntactic growth for children with BI than for TD children. Controlling for input, lesion characteristics (lesion size, type, seizure history) also affect the language trajectories of children with BI. Thus, findings illustrate how both variability in the environment (linguistic input) and variability in the organism (lesion characteristics) work together to contribute to plasticity in language learning.

Effects of the methylene chloride fraction from modified Boyang-Hwan-o-Tang, a polyherbal medicine on transient middle cerebral artery occlusion-induced ischemia in rats.

PubMed

Oh, Tae Woo; Jung, Hyo Won; Shin, Gil Jo; Park, Yong-Ki

2014-01-28

To study the neuroprotective effect of the methylene chloride fraction from modified Boyang-Hwan-o-Tang (mBHT-MC), especially against neuronal apoptosis. mBHT-MC (10, 25 or 50 mg/kg) was orally administered once per day for 7 days in transient middle cerebral artery occlusion (MCAO)-induced ischemic rats. Infarction volumes was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological deficit score and the expression of apoptotic proteins such as Bcl-2, Bax and caspase-3 by Western blot in MCAO-induced ischemic brain. Neuronal apoptosis in ischemic phenumbra was also investigated by staining with hematoxylin and eosin, Nissl and Hoechst 33342. mBHT-MC administration in MCAO rats significantly decreased infarction volume and neurological deficit scores. mBHT-MC significantly enhanced Bcl-2 expression, and inhibited Bax and caspase-3 expression in ischemic brain. In addition, mBHT-MC significantly decreased the number of apoptotic neuronal cells in ischemic brains. mBHT-MC administration inhibits neuronal death induced by cerebral ischemia in rats, suggesting that mBHT-MC has a neuroprotective property in brain ischemia.

Arterial Stiffening Precedes Systolic Hypertension in Diet-induced Obesity

PubMed Central

Weisbrod, Robert M.; Shiang, Tina; Sayah, Leona Al; Fry, Jessica L.; Bajpai, Saumendra; Reinhart-King, Cynthia A.; Lob, Heinrich E.; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A.; Seta, Francesca

2014-01-01

Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs such as the heart, brain and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension, although the mechanisms contributing to hypertension are unknown. Here we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within one month of the initiation of the diet and precedes the development of hypertension by five months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss returned arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause, rather than a consequence of hypertension. PMID:24060894

Arterial stiffening precedes systolic hypertension in diet-induced obesity.

PubMed

Weisbrod, Robert M; Shiang, Tina; Al Sayah, Leona; Fry, Jessica L; Bajpai, Saumendra; Reinhart-King, Cynthia A; Lob, Heinrich E; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A; Seta, Francesca

2013-12-01

Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension.

Inflammatory pathways are central to posterior cerebrovascular artery remodelling prior to the onset of congenital hypertension.

PubMed

Walas, Dawid; Nowicki-Osuch, Karol; Alibhai, Dominic; von Linstow Roloff, Eva; Coghill, Jane; Waterfall, Christy; Paton, Julian Fr

2018-01-01

Cerebral artery hypoperfusion may provide the basis for linking ischemic stroke with hypertension. Brain hypoperfusion may induce hypertension that may serve as an auto-protective mechanism to prevent ischemic stroke. We hypothesised that hypertension is caused by remodelling of the cerebral arteries, which is triggered by inflammation. We used a congenital rat model of hypertension and examined age-related changes in gene expression of the cerebral arteries using RNA sequencing. Prior to hypertension, we found changes in signalling pathways associated with the immune system and fibrosis. Validation studies using second harmonics generation microscopy revealed upregulation of collagen type I and IV in both tunica externa and media. These changes in the extracellular matrix of cerebral arteries pre-empted hypertension accounting for their increased stiffness and resistance, both potentially conducive to stroke. These data indicate that inflammatory driven cerebral artery remodelling occurs prior to the onset of hypertension and may be a trigger elevating systemic blood pressure in genetically programmed hypertension.

Control channels in the brain and their influence on brain executive functions

NASA Astrophysics Data System (ADS)

Meng, Qinglei; Choa, Fow-Sen; Hong, Elliot; Wang, Zhiguang; Islam, Mohammad

2014-05-01

In a computer network there are distinct data channels and control channels where massive amount of visual information are transported through data channels but the information streams are routed and controlled by intelligent algorithm through "control channels". Recent studies on cognition and consciousness have shown that the brain control channels are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person's brain using binaural beats technique and identify the individual's preferred control channels. The identified control channels can then be used to influence the subject's brain executive functions. In the experiment, an EEG measurement system was used to record and identify a subject's control channels. After these channels were identified, the subject was asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject's brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the subject's executive function performance and reduced the time to complete incongruent tests, while the alpha signal didn't seem to be able to slow down the executive function performance.

Glymphatic solute transport does not require bulk flow

PubMed Central

Asgari, Mahdi; de Zélicourt, Diane; Kurtcuoglu, Vartan

2016-01-01

Observations of fast transport of fluorescent tracers in mouse brains have led to the hypothesis of bulk water flow directed from arterial to venous paravascular spaces (PVS) through the cortical interstitium. At the same time, there is evidence for interstitial solute transport by diffusion rather than by directed bulk fluid motion. It has been shown that the two views may be consolidated by intracellular water flow through astrocyte networks combined with mainly diffusive extracellular transport of solutes. This requires the presence of a driving force that has not been determined to date, but for which arterial pulsation has been suggested as the origin. Here we show that arterial pulsation caused by pulse wave propagation is an unlikely origin of this hypothetical driving force. However, we further show that such pulsation may still lead to fast para-arterial solute transport through dispersion, that is, through the combined effect of local mixing and diffusion in the para-arterial space. PMID:27929105

Bilateral ophthalmic artery occlusion in rhino-orbito-cerebral mucormycosis.

PubMed

Song, Yoo Mi; Shin, Sun Young

2008-03-01

To report a case of bilateral ophthalmic artery occlusion in rhino-orbito-cerebral mucormycosis. Reviewed clinical charts, photographs, and fluorescein angiography An 89-year-old man with poorly controlled diabetes developed sudden bilateral ptosis, complete ophthalmoplegia of the right eye, and superior rectus palsy of the left eye. Brain and orbit magnetic resonance imaging showed midbrain infarction and mild diffuse sinusitis. On the 2nd day of hospitalization, sudden visual loss and light reflex loss developed. There were retinal whitening, absence of retinal arterial filling, and a total lack of choroidal perfusion on fluorescein angiography of the right eye. The left eye showed a cherry red spot in the retina and the absence of retinal arterial filling and partial choroidal perfusion on fluorescein angiography. On rhinologic examination, mucormyosis was noticed. Despite treatment, visual acuity and light reflex did not recover and he died 4 days after admission. Bilateral ophthalmic artery occlusion can occur in rhino-orbital-cerebral mucormycosis.

Validation and augmentation of Inrix arterial travel time data using independent sources.

DOT National Transportation Integrated Search

2015-02-01

Travel time data is a key input to Intelligent Transportation Systems (ITS) applications. Advancement in vehicle : tracking and identification technologies and proliferation of location-aware and connected devices has made network-wide travel time da...

Effects of postural changes and removal of vestibular inputs on blood flow to and from the hindlimb of conscious felines

PubMed Central

Yavorcik, K. J.; Reighard, D. A.; Misra, S. P.; Cotter, L. A.; Cass, S. P.; Wilson, T. D.

2009-01-01

Considerable data show that the vestibular system contributes to blood pressure regulation. Prior studies reported that lesions that eliminate inputs from the inner ears attenuate the vasoconstriction that ordinarily occurs in the hindlimbs of conscious cats during head-up rotations. These data led to the hypothesis that labyrinthine-deficient animals would experience considerable lower body blood pooling during head-up postural alterations. The present study tested this hypothesis by comparing blood flow though the femoral artery and vein of conscious cats during 20–60° head-up tilts from the prone position before and after removal of vestibular inputs. In vestibular-intact animals, venous return from the hindlimb dropped considerably at the onset of head-up tilts and, at 5 s after the initiation of 60° rotations, was 66% lower than when the animals were prone. However, after the animals were maintained in the head-up position for another 15 s, venous return was just 33% lower than before the tilt commenced. At the same time point, arterial inflow to the limb had decreased 32% from baseline, such that the decrease in blood flow out of the limb due to the force of gravity was precisely matched by a reduction in blood reaching the limb. After vestibular lesions, the decline in femoral artery blood flow that ordinarily occurs during head-up tilts was attenuated, such that more blood flowed into the leg. Contrary to expectations, in most animals, venous return was facilitated, such that no more blood accumulated in the hindlimb than when labyrinthine signals were present. These data show that peripheral blood pooling is unlikely to account for the fluctuations in blood pressure that can occur during postural changes of animals lacking inputs from the inner ear. Instead, alterations in total peripheral resistance following vestibular dysfunction could affect the regulation of blood pressure. PMID:19793952

[The importance of Willis ring as valvular mechanism in cerebral circulation in patients with different degree of internal carotid artery occlusion].

PubMed

Volievica, Alma; Kulenovic, Amela; Lujinovic, Almira; Talovic, Elvira

2006-01-01

Cerebrovascular deseases , cerebral vessels deseases, represents one of the greatest problems of humankind. The reasons are not just the high incidence and relatively high prevalence of letal outcomes in the acute faze of the desease, but also high level of disfunctionality caused by this disease in numerous patients who survived cerebrovascular insult and haemorraghe The onset, course and outcome of cerebrovascular diseases depends among other things on the possibility o f colateral brain circulation establishment. Willis ring onthe base of the brain is the most important anastomosis between circulation in both carotid arteries and basilar artery. First precondition for Willis ring t o function as valvular mechanisam is its intact configuration. But, it is found in almost half of th e subjectsincluded in the study that certain anatomical abnormalities in the Willis ring structure exist. Presence of these abnormalities favors onset of vascular diseases since they unables colateral circulation establishment. Studies till now have shown that all components of Willis ring do not contribute equally in colateral function among obstructive diseases.

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

Boehling, Nicholas S.; Grosshans, David R., E-mail: dgrossha@mdanderson.org; Bluett, Jaques B.

Purpose: Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas. Methods and Materials: IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV)more » coverage of 95% or better. Integral dose data were calculated from differential dose-volume histograms. Results: The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3%{sup Asterisk-Operator }), dentate gyrus (27.3, 75.0%{sup Asterisk-Operator }), and subventricular zone (4.5, 57.8%{sup Asterisk-Operator }). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3{sup Asterisk-Operator }, 100.0%{sup Asterisk-Operator }; middle cerebral arteries, 25.9%{sup Asterisk-Operator }, 100%{sup Asterisk-Operator }; anterior communicating arteries, 30.8{sup Asterisk-Operator }, 41.7%{sup Asterisk-Operator }; and carotid arteries, 51.5{sup Asterisk-Operator }, 77.6{sup Asterisk-Operator }). Relative reduction of integral dose to the infratentorial brain (190.7{sup Asterisk-Operator }, 109.7%{sup Asterisk-Operator }), supratentorial brain without PTV (9.6, 26.8%{sup Asterisk-Operator }), brainstem (45.6, 22.4%{sup Asterisk-Operator }), and whole brain without PTV (19.4{sup Asterisk-Operator }, 34.4%{sup Asterisk-Operator }) were recorded with the use of proton therapy. ({sup Asterisk-Operator }Differences were significant based on Friedman's test with Bonferroni-Dunn correction, {alpha} = 0.05) Conclusions: The current study found that proton therapy was able to avoid excess integral radiation dose to a variety of normal structures at all dose levels while maintaining equal target coverage. Future studies will examine the clinical benefits of these dosimetric advantages.« less

Coherence and decoherence in the brain

NASA Astrophysics Data System (ADS)

Hepp, K.

2012-09-01

This review provides many entry points to controversies in neuroscience, where input from mathematical physics could be fruitful, especially about coherence and decoherence in the brain, both on the level of classical and quantum mechanics.

Analysis of fMRI data using noise-diffusion network models: a new covariance-coding perspective.

PubMed

Gilson, Matthieu

2018-04-01

Since the middle of the 1990s, studies of resting-state fMRI/BOLD data have explored the correlation patterns of activity across the whole brain, which is referred to as functional connectivity (FC). Among the many methods that have been developed to interpret FC, a recently proposed model-based approach describes the propagation of fluctuating BOLD activity within the recurrently connected brain network by inferring the effective connectivity (EC). In this model, EC quantifies the strengths of directional interactions between brain regions, viewed from the proxy of BOLD activity. In addition, the tuning procedure for the model provides estimates for the local variability (input variances) to explain how the observed FC is generated. Generalizing, the network dynamics can be studied in the context of an input-output mapping-determined by EC-for the second-order statistics of fluctuating nodal activities. The present paper focuses on the following detection paradigm: observing output covariances, how discriminative is the (estimated) network model with respect to various input covariance patterns? An application with the model fitted to experimental fMRI data-movie viewing versus resting state-illustrates that changes in local variability and changes in brain coordination go hand in hand.

The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow mesenchymal stem cells in rats is related to cell dose and infusion velocity.

PubMed

Cui, Li-li; Kerkelä, Erja; Bakreen, Abdulhameed; Nitzsche, Franziska; Andrzejewska, Anna; Nowakowski, Adam; Janowski, Miroslaw; Walczak, Piotr; Boltze, Johannes; Lukomska, Barbara; Jolkkonen, Jukka

2015-01-27

Intra-arterial cell infusion is an efficient delivery route with which to target organs such as the ischemic brain. However, adverse events including microembolisms and decreased cerebral blood flow were recently reported after intra-arterial cell delivery in rodent models, raising safety concerns. We tested the hypothesis that cell dose, infusion volume, and velocity would be related to the severity of complications after intra-arterial cell delivery. In this study, 38 rats were subjected to a sham middle cerebral artery occlusion (sham-MCAO) procedure before being infused with allogeneic bone-marrow mesenchymal stem cells at different cell doses (0 to 1.0 × 10(6)), infusion volumes (0.5 to 1.0 ml), and infusion times (3 to 6 minutes). An additional group (n = 4) was infused with 1.0 × 10(6) cells labeled with iron oxide for in vivo tracking of cells. Cells were infused through the external carotid artery under laser Doppler flowmetry monitoring 48 hours after sham-MCAO. Magnetic resonance imaging (MRI) was performed 24 hours after cell infusion to reveal cerebral embolisms or hemorrhage. Limb placing, cylinder, and open field tests were conducted to assess sensorimotor functions before the rats were perfused for histology. A cell dose-related reduction in cerebral blood flow was noted, as well as an increase in embolic events and concomitant lesion size, and sensorimotor impairment. In addition, a low infusion velocity (0.5 ml/6 minutes) was associated with high rate of complications. Lesions on MRI were confirmed with histology and corresponded to necrotic cell loss and blood-brain barrier leakage. Particularly cell dose but also infusion velocity contribute to complications encountered after intra-arterial cell transplantation. This should be considered before planning efficacy studies in rats and, potentially, in patients with stroke.

First-in-human PET quantification study of cerebral α4β2* nicotinic acetylcholine receptors using the novel specific radioligand (-)-[(18)F]Flubatine.

PubMed

Sabri, Osama; Becker, Georg-Alexander; Meyer, Philipp M; Hesse, Swen; Wilke, Stephan; Graef, Susanne; Patt, Marianne; Luthardt, Julia; Wagenknecht, Gudrun; Hoepping, Alexander; Smits, René; Franke, Annegret; Sattler, Bernhard; Habermann, Bernd; Neuhaus, Petra; Fischer, Steffen; Tiepolt, Solveig; Deuther-Conrad, Winnie; Barthel, Henryk; Schönknecht, Peter; Brust, Peter

2015-09-01

α4β2* nicotinic receptors (α4β2* nAChRs) could provide a biomarker in neuropsychiatric disorders (e.g., Alzheimer's and Parkinson's diseases, depressive disorders, and nicotine addiction). However, there is a lack of α4β2* nAChR specific PET radioligands with kinetics fast enough to enable quantification of nAChR within a reasonable time frame. Following on from promising preclinical results, the aim of the present study was to evaluate for the first time in humans the novel PET radioligand (-)-[(18)F]Flubatine, formerly known as (-)-[(18)F]NCFHEB, as a tool for α4β2* nAChR imaging and in vivo quantification. Dynamic PET emission recordings lasting 270min were acquired on an ECAT EXACT HR+ scanner in 12 healthy male non-smoking subjects (71.0±5.0years) following the intravenous injection of 353.7±9.4MBq of (-)-[(18)F]Flubatine. Individual magnetic resonance imaging (MRI) was performed for co-registration. PET frames were motion-corrected, before the kinetics in 29 brain regions were characterized using 1- and 2-tissue compartment models (1TCM, 2TCM). Given the low amounts of metabolite present in plasma, we tested arterial input functions with and without metabolite corrections. In addition, pixel-based graphical analysis (Logan plot) was used. The model's goodness of fit, with and without metabolite correction was assessed by Akaike's information criterion. Model parameters of interest were the total distribution volume VT (mL/cm(3)), and the binding potential BPND relative to the corpus callosum, which served as a reference region. The tracer proved to have high stability in vivo, with 90% of the plasma radioactivity remaining as untransformed parent compound at 90min, fast brain kinetics with rapid uptake and equilibration between free and receptor-bound tracer. Adequate fits of brain TACs were obtained with the 1TCM. VT could be reliably estimated within 90min for all regions investigated, and within 30min for low-binding regions such as the cerebral cortex. The rank order of VT by region corresponded well with the known distribution of α4β2* receptors (VT [thalamus] 27.4±3.8, VT [putamen] 12.7±0.9, VT [frontal cortex] 10.0±0.8, and VT [corpus callosum] 6.3±0.8). The BPND, which is a parameter of α4β2* nAChR availability, was 3.41±0.79 for the thalamus, 1.04±0.25 for the putamen and 0.61±0.23 for the frontal cortex, indicating high specific tracer binding. Use of the arterial input function without metabolite correction resulted in a 10% underestimation in VT, and was without important biasing effects on BPND. Altogether, kinetics and imaging properties of (-)-[(18)F]Flubatine appear favorable and suggest that (-)-[(18)F]Flubatine is a very suitable and clinically applicable PET tracer for in vivo imaging of α4β2* nAChRs in neuropsychiatric disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

[Character of brain interhemispheric relation in children at forming labile arterial hypertension].

PubMed

Koroleva, N V; Kolesnikov, S I; Bugun, O V; Dolgikh, V V

2010-01-01

Electroencephalography investigations were carried out twice in 26 schoolchildren in the age of 7-8 years and in the age of 9-10 years. The control group included healthy children: the research group included children in whom in the age of 7-8 years the normal level of arterial pressure was registered, and in whom in the age of 9-10 years labile arterial hypertension was revealed. It is revealed, that in children of younger school age forming of the labile form of arterial hypertension is connected whit infringement of processes of age changes of intercortical and cortical-subcortical interrelations and forming of rigidly integrated system of interhemispheric relations. Its mechanism of realization is carried out due to hyperactivation of the right hemisphere and it is incorporated on preclinical stage.

Acute onset quadriplegia

PubMed Central

Rajasekharan, Chandrasekharan; Deepak, Menon

2012-01-01

A 50-year-old man, with history of chronic alcohol intake was brought in a stuporous state to the emergency services having been found in that condition in his home the same day. Examination revealed the patient in an akinteic mute state with apparently normal cranial nerves, hypotonia and quadriplegia with bilateral extensor plantar reflex. CT scan and MRI of the brain revealed bilateral infarct parasagittally with normal Magnetic resonance venogram suggestive of bilateral anterior cerebral artery infarct. Follow-up magnetic resonance angiogram revealed an azygous anterior cerebral artery thus proving an infarct of unpaired anterior cerebral artery infarct as the cause for quadriplegia in this patient. PMID:22783005

[Medial longitudinal fasciculus (MLF) syndrome in a patient with giant cell arteritis].

PubMed

Uenaka, Takeshi; Hamaguchi, Hirotoshi; Sekiguchi, Kenji; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

2015-01-01

A 76-year-old female was referred to our department because of diplopia for two months and intermittent claudication for five months. She showed medial longitudinal fasciculus (MLF) syndrome. Brain MRI (T2WI) showed multiple infarctions in the right pontine tegmentum and left paramedian midbrain. A biopsy of superficial temporal artery showed the characteristic findings of glanulomatous inflammation indicative of giant cell arteritis. We thought the mechanism of this cerebral infarction as artery to artery embolization or intracranial arteritis. Treatment with oral prednisolone (1 mg/kg/day) improved her limb claudication and normalized serum C-reactive protein level.

Quantification of Load Dependent Brain Activity in Parametric N-Back Working Memory Tasks using Pseudo-continuous Arterial Spin Labeling (pCASL) Perfusion Imaging.

PubMed

Zou, Qihong; Gu, Hong; Wang, Danny J J; Gao, Jia-Hong; Yang, Yihong

2011-04-01

Brain activation and deactivation induced by N-back working memory tasks and their load effects have been extensively investigated using positron emission tomography (PET) and blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). However, the underlying mechanisms of BOLD fMRI are still not completely understood and PET imaging requires injection of radioactive tracers. In this study, a pseudo-continuous arterial spin labeling (pCASL) perfusion imaging technique was used to quantify cerebral blood flow (CBF), a well understood physiological index reflective of cerebral metabolism, in N-back working memory tasks. Using pCASL, we systematically investigated brain activation and deactivation induced by the N-back working memory tasks and further studied the load effects on brain activity based on quantitative CBF. Our data show increased CBF in the fronto-parietal cortices, thalamus, caudate, and cerebellar regions, and decreased CBF in the posterior cingulate cortex and medial prefrontal cortex, during the working memory tasks. Most of the activated/deactivated brain regions show an approximately linear relationship between CBF and task loads (0, 1, 2 and 3 back), although several regions show non-linear relationships (quadratic and cubic). The CBF-based spatial patterns of brain activation/deactivation and load effects from this study agree well with those obtained from BOLD fMRI and PET techniques. These results demonstrate the feasibility of ASL techniques to quantify human brain activity during high cognitive tasks, suggesting its potential application to assessing the mechanisms of cognitive deficits in neuropsychiatric and neurological disorders.

Mild Thyrotoxicosis Leads to Brain Perfusion Changes: An Arterial Spin Labelling Study.

PubMed

Göbel, A; Heldmann, M; Sartorius, A; Göttlich, M; Dirk, A-L; Brabant, G; Münte, T F

2017-01-01

Hypo- and hyperthyroidism have effects on brain structure and function, as well as cognitive processes, including memory. However, little is known about the influence of thyroid hormones on brain perfusion and the relationship of such perfusion changes with cognition. The present study aimed to demonstrate the effect of short-term experimental hyperthyroidism on brain perfusion in healthy volunteers and to assess whether perfusion changes, if present, are related to cognitive performance. It is known that an interaction exists between brain perfusion and cerebral oxygen consumption rate and it is considered that neural activation increases cerebral regional perfusion rate in brain areas associated with memory. Measuring cerebral blood flow may therefore represent a proxy for neural activity. Therefore, arterial spin labelling (ASL) measurements were conducted and later analysed to evaluate brain perfusion in 29 healthy men before and after ingesting thyroid hormones for 8 weeks. Psychological tests concerning memory were performed at the same time-points and the results were correlated with the imaging results. In the hyperthyroid condition, perfusion was increased in the posterior cerebellum in regions connected with cerebral networks associated with cognitive control and the visual cortex compared to the euthyroid condition. In addition, these perfusion changes were positively correlated with changes of performance in the German version of the Auditory Verbal Learning Task [AVLT, Verbaler Lern-und-Merkfähigkeits-Test (VLMT)]. Cerebellar perfusion and function therefore appears to be modulated by thyroid hormones, likely because the cerebellum hosts a high number of thyroid hormone receptors. © 2016 British Society for Neuroendocrinology.

Functional brain development in growth-restricted and constitutionally small fetuses: a fetal magnetoencephalography case-control study.

PubMed

Morin, E C; Schleger, F; Preissl, H; Braendle, J; Eswaran, H; Abele, H; Brucker, S; Kiefer-Schmidt, I

2015-08-01

Fetal magnetoencephalography records fetal brain activity non-invasively. Delayed brain responses were reported for fetuses weighing below the tenth percentile. To investigate whether this delay indicates delayed brain maturation resulting from placental insufficiency, this study distinguished two groups of fetuses below the tenth percentile: growth-restricted fetuses with abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for-gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were compared with fetuses of adequate weight for gestational age (AGA), matched for age and behavioural state. A case-control study of matched pairs. Fetal magnetoencephalography-Center at the University Hospital of Tuebingen. Fourteen IUGR fetuses and 23 SGA fetuses were matched for gestational age and fetal behavioural state with 37 healthy, normal-sized fetuses. A 156-channel fetal magentoencephalography system was used to record fetal brain activity. Light flashes as visual stimulation were applied to the fetus. The Student's t-test for paired groups was performed. Latency of fetal visual evoked magnetic responses (VER). The IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms; controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828). Behavioural states were similarly distributed. Visual evoked responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as an influencing factor of brain response latency was accounted for in the comparison. This reinforces that delayed brain maturation is the result of placental insufficiency. © 2015 Royal College of Obstetricians and Gynaecologists.

Dynamic change in cerebral microcirculation and focal cerebral metabolism in experimental subarachnoid hemorrhage in rabbits.

PubMed

Song, Jin-Ning; Chen, Hu; Zhang, Ming; Zhao, Yong-Lin; Ma, Xu-Dong

2013-03-01

Regional cerebral blood flow (rCBF) in the cerebral metabolism and energy metabolism measurements can be used to assess blood flow of brain cells and to detect cell activity. Changes of rCBF in the cerebral microcirculation and energy metabolism were determined in an experimental model of subarachnoid hemorrhage (SAH) model in 56 large-eared Japanese rabbits about 12 to 16-month old. Laser Doppler flowmetry was used to detect the blood supply to brain cells. Internal carotid artery and vein blood samples were used for duplicate blood gas analysis to assess the energy metabolism of brain cells. Cerebral blood flow (CBF) was detected by single photon emission computed tomography (SPECT) perfusion imaging using Tc-99m ethyl cysteinate dimer (Tc-99m ECD) as an imaging reagent. The percentage of injected dose per gram of brain tissue was calculated and analyzed. There were positive correlations between the percentage of radionuclide injected per gram of brain tissue and rCBF supply and cerebral metabolic rate for oxygen (P < 0.05). However, there was a negative correlation between radioactivity counts per unit volume detected on the SPECT rheoencephalogram and lactic acid concentration in the homolateral internal carotid artery and vein. In summary, this study found abnormal CBF in metabolism and utilization of brain cells after SAH, and also found that deterioration of energy metabolism of brain cells played a significant role in the development of SAH. There are matched reductions in CBF and metabolism. Thus, SPECT imaging could be used as a noninvasive method to detect CBF.

Scaling of cerebral blood perfusion in primates and marsupials.

PubMed

Seymour, Roger S; Angove, Sophie E; Snelling, Edward P; Cassey, Phillip

2015-08-01

The evolution of primates involved increasing body size, brain size and presumably cognitive ability. Cognition is related to neural activity, metabolic rate and rate of blood flow to the cerebral cortex. These parameters are difficult to quantify in living animals. This study shows that it is possible to determine the rate of cortical brain perfusion from the size of the internal carotid artery foramina in skulls of certain mammals, including haplorrhine primates and diprotodont marsupials. We quantify combined blood flow rate in both internal carotid arteries as a proxy of brain metabolism in 34 species of haplorrhine primates (0.116-145 kg body mass) and compare it to the same analysis for 19 species of diprotodont marsupials (0.014-46 kg). Brain volume is related to body mass by essentially the same exponent of 0.70 in both groups. Flow rate increases with haplorrhine brain volume to the 0.95 power, which is significantly higher than the exponent (0.75) expected for most organs according to 'Kleiber's Law'. By comparison, the exponent is 0.73 in marsupials. Thus, the brain perfusion rate increases with body size and brain size much faster in primates than in marsupials. The trajectory of cerebral perfusion in primates is set by the phylogenetically older groups (New and Old World monkeys, lesser apes) and the phylogenetically younger groups (great apes, including humans) fall near the line, with the highest perfusion. This may be associated with disproportionate increases in cortical surface area and mental capacity in the highly social, larger primates. © 2015. Published by The Company of Biologists Ltd.

Sensory experience modifies feature map relationships in visual cortex

PubMed Central

Cloherty, Shaun L; Hughes, Nicholas J; Hietanen, Markus A; Bhagavatula, Partha S

2016-01-01

The extent to which brain structure is influenced by sensory input during development is a critical but controversial question. A paradigmatic system for studying this is the mammalian visual cortex. Maps of orientation preference (OP) and ocular dominance (OD) in the primary visual cortex of ferrets, cats and monkeys can be individually changed by altered visual input. However, the spatial relationship between OP and OD maps has appeared immutable. Using a computational model we predicted that biasing the visual input to orthogonal orientation in the two eyes should cause a shift of OP pinwheels towards the border of OD columns. We then confirmed this prediction by rearing cats wearing orthogonally oriented cylindrical lenses over each eye. Thus, the spatial relationship between OP and OD maps can be modified by visual experience, revealing a previously unknown degree of brain plasticity in response to sensory input. DOI: http://dx.doi.org/10.7554/eLife.13911.001 PMID:27310531

Arterial blood gas management in retrograde cerebral perfusion: the importance of carbon dioxide.

PubMed

Ueno, K; Takamoto, S; Miyairi, T; Morota, T; Shibata, K; Murakami, A; Kotsuka, Y

2001-11-01

Many interventional physiological assessments for retrograde cerebral perfusion (RCP) have been explored. However, the appropriate arterial gas management of carbon dioxide (CO2) remains controversial. The aim of this study is to determine whether alpha-stat or pH-stat could be used for effective brain protection under RCP in terms of cortical cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and distribution of regional cerebral blood flow. Fifteen anesthetized dogs (25.1+/-1.1 kg) on cardiopulmonary bypass (CPB) were cooled to 18 degrees C under alpha-stat management and had RCP for 90 min under: (1), alpha-stat; (2), pH-stat; or (3), deep hypothermic (18 degrees C) antegrade CPB (antegrade). RCP flow was regulated for a sagittal sinus pressure of around 25 mmHg. CBF was monitored by a laser tissue flowmeter. Serial analyses of blood gas were made. The regional cerebral blood flow was measured with colored microspheres before discontinuation of RCP. CBF and CMRO2 were evaluated as the percentage of the baseline level (%CBF, %CMRO2). The oxygen content of arterial inflow and oxygen extraction was not significantly different between the RCP groups. The %CBF and %CMRO2 were significantly higher for pH-stat RCP than for alpha-stat RCP. The regional cerebral blood flow, measured with colored microspheres, tended to be higher for pH-stat RCP than for alpha-stat RCP, at every site in the brain. Irrespective of CO2 management, regional differences were not significant among any site in the brain. CO2 management is crucial for brain protection under deep hypothermic RCP. This study revealed that pH-stat was considered to be better than alpha-stat in terms of CBF and oxygen metabolism in the brain. The regional blood flow distribution was considered to be unchanged irrespective of CO2 management.

Interrupted intracarotid artery cold saline infusion as an alternative method for neuroprotection after ischemic stroke.

PubMed

Ji, Ya-Bin; Wu, Yong-Ming; Ji, Zhong; Song, Wei; Xu, Sui-Yi; Wang, Yao; Pan, Su-Yue

2012-07-01

Intracarotid artery cold saline infusion (ICSI) is an effective method for protecting brain tissue, but its use is limited because of undesirable secondary effects, such as severe decreases in hematocrit levels, as well as its relatively brief duration. In this study, the authors describe and investigate the effects of a novel ICSI pattern (interrupted ICSI) relative to the traditional method (uninterrupted ICSI). Ischemic strokes were induced in 85 male Sprague-Dawley rats by occluding the middle cerebral artery for 3 hours using an intraluminal filament. Uninterrupted infusion groups received an infusion at 15 ml/hour for 30 minutes continuously. The same infusion speed was used in the interrupted infusion groups, but the whole duration was divided into trisections, and there was a 20-minute interval without infusion between sections. Forty-eight hours after reperfusion, H & E and silver nitrate staining were utilized for morphological assessment. Infarct sizes and brain water contents were determined using H & E staining and the dry-wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100β protein, and matrix metalloproteinase 9 (MMP-9) in the serum were determined using enzyme-linked immunosorbent assay. Neurological deficits were also evaluated. Histology showed that interrupted ICSI did not affect neurons or fibers in rat brains, which suggests that this method is safe for brain tissues with ischemia. The duration of hypothermia induced by interrupted ICSI was longer than that induced via the traditional method, and the decrease in hematocrit levels was less pronounced. There were no differences in infarct size or brain water content between uninterrupted and interrupted ICSI groups, but neuron-specific enolase and matrix metalloproteinase 9 serum levels were more reduced after interrupted ICSI than after the traditional method. Interrupted ICSI is a safe method. Compared with traditional ICSI, the interrupted method has a longer duration of hypothermia and less effect on hematocrit and offers more potentially improved neuroprotection, thereby making it more attractive as an infusion technique in the clinic.

Neuropilin 2 deficiency does not affect cortical neuronal viability in response to oxygen-glucose-deprivation and transient middle cerebral artery occlusion.

PubMed

Hou, Sheng T; Jiang, Susan X; Slinn, Jacqueline; O'Hare, Michael; Karchewski, Laurie

2010-04-01

Neuropilin 2 (NRP2) is a type I transmembrane protein that binds to distinct members of the class III secreted Semaphorin subfamily. NRP2 plays important roles in repulsive axon guidance, angiogenesis and vasculogenesis through partnering with co-receptors such as vascular endothelial growth factor receptors (VEGFRs) during development. Emerging evidence also suggests that NRP2 contributes to injury response and environment changes in adult brains. In this study, we examined the contribution of NRP2 gene to cerebral ischemia-induced brain injury using NRP2 deficient mouse. To our surprise, the lack of NRP2 expression does not affect the outcome of brain injury induced by transient occlusion of the middle cerebral artery (MCAO) in mouse. The cerebral vasculature in terms of the middle cerebral artery anatomy and microvessel density in the cerebral cortex of NRP2 deficient homozygous (NRP2(-/-)) mice are normal and almost identical to those of the heterozygous (NRP2(+/-)) and wild type (NRP2(+/+)) littermates. MCAO (1h) and 24h reperfusion caused a brain infarction of 23% (compared to the contralateral side) in NRP2(-/-) mice, which is not different from those in NRP2(+/- and +/+) mice at 22 and 21%, respectively (n=19, p>0.05). Correspondingly, NRP2(-/-) mouse also showed a similar level of deterioration of neurological functions after stroke compared with their NRP2(+/- and +/+) littermates. Oxygen-glucose-deprivation (OGD) caused a significant neuronal death in NRP2(-/-) cortical neurons, at the level similar to that in NRP(+/+) cortical neurons (72% death in NRP(-/-) neurons vs. 75% death in NRP2(+/+) neurons; n=4; p>0.05). Together, these loss-of-function studies demonstrated that despite of its critical role in neuronal guidance and vascular formation during development, NRP2 expression dose not affect adult brain response to cerebral ischemia. Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.

Monitoring fetal electrocortical activity during labour for predicting worsening acidemia: a prospective study in the ovine fetus near term.

PubMed

Frasch, Martin G; Keen, Ashley E; Gagnon, Robert; Ross, Michael G; Richardson, Bryan S

2011-01-01

Severe fetal acidemia during labour with arterial pH below 7.00 is associated with increased risk of hypoxic-ischemic brain injury. Electronic fetal heart rate (FHR) monitoring, the mainstay of intrapartum surveillance, has poor specificity for detecting fetal acidemia. We studied brain electrical activity measured with electrocorticogram (ECOG) in the near term ovine fetus subjected to repetitive umbilical cord occlusions (UCO) inducing FHR decelerations, as might be seen in human labour, to delineate the time-course for ECOG changes with worsening acidemia and thereby assess the potential clinical utility of fetal ECOG. Ten chronically catheterized fetal sheep were studied through a series of mild, moderate and severe UCO until the arterial pH was below 7.00. At a pH of 7.24 ± 0.04, 52 ± 13 min prior to the pH dropping <7.00, spectral edge frequency (SEF) increased to 23 ± 2 Hz from 3 ± 1 Hz during each FHR deceleration (p<0.001) and was correlated to decreases in FHR and in fetal arterial blood pressure during each FHR deceleration (p<0.001). The UCO-related changes in ECOG occurred in advance of the pH decreasing below 7.00. These ECOG changes may be a protective mechanism suppressing non-essential energy needs when oxygen supply to the fetal brain is decreased acutely. By detecting such "adaptive brain shutdown," the need for delivery in high risk pregnant patients may be more accurately predicted than with FHR monitoring alone. Therefore, monitoring fetal electroencephalogram (EEG, the human equivalent of ECOG) during human labour may be a useful adjunct to FHR monitoring.

Monitoring Fetal Electrocortical Activity during Labour for Predicting Worsening Acidemia: A Prospective Study in the Ovine Fetus Near Term

PubMed Central

Frasch, Martin G.; Keen, Ashley E.; Gagnon, Robert; Ross, Michael G.; Richardson, Bryan S.

2011-01-01

Background Severe fetal acidemia during labour with arterial pH below 7.00 is associated with increased risk of hypoxic-ischemic brain injury. Electronic fetal heart rate (FHR) monitoring, the mainstay of intrapartum surveillance, has poor specificity for detecting fetal acidemia. We studied brain electrical activity measured with electrocorticogram (ECOG) in the near term ovine fetus subjected to repetitive umbilical cord occlusions (UCO) inducing FHR decelerations, as might be seen in human labour, to delineate the time-course for ECOG changes with worsening acidemia and thereby assess the potential clinical utility of fetal ECOG. Methodology/Principal Findings Ten chronically catheterized fetal sheep were studied through a series of mild, moderate and severe UCO until the arterial pH was below 7.00. At a pH of 7.24±0.04, 52±13 min prior to the pH dropping <7.00, spectral edge frequency (SEF) increased to 23±2 Hz from 3±1 Hz during each FHR deceleration (p<0.001) and was correlated to decreases in FHR and in fetal arterial blood pressure during each FHR deceleration (p<0.001). Conclusions/Significance The UCO-related changes in ECOG occurred in advance of the pH decreasing below 7.00. These ECOG changes may be a protective mechanism suppressing non-essential energy needs when oxygen supply to the fetal brain is decreased acutely. By detecting such “adaptive brain shutdown,” the need for delivery in high risk pregnant patients may be more accurately predicted than with FHR monitoring alone. Therefore, monitoring fetal electroencephalogram (EEG, the human equivalent of ECOG) during human labour may be a useful adjunct to FHR monitoring. PMID:21789218

Tissue oxidative metabolism can increase the difference between local temperature and arterial blood temperature by up to 1.3oC: Implications for brain, brown adipose tissue, and muscle physiology.

PubMed

Zaretsky, Dmitry V; Romanovsky, Andrej A; Zaretskaia, Maria V; Molkov, Yaroslav I

2018-01-01

Tissue temperature increases, when oxidative metabolism is boosted. The source of nutrients and oxygen for this metabolism is the blood. The blood also cools down the tissue, and this is the only cooling mechanism, when direct dissipation of heat from the tissue to the environment is insignificant, e.g. , in the brain. While this concept is relatively simple, it has not been described quantitatively. The purpose of the present work was to answer two questions: 1) to what extent can oxidative metabolism make the organ tissue warmer than the body core, and, 2) how quickly are changes in the local metabolism reflected in the temperature of the tissue? Our theoretical analysis demonstrates that, at equilibrium, given that heat exchange with the organ is provided by the blood, the temperature difference between the organ tissue and the arterial blood is proportional to the arteriovenous difference in oxygen content, does not depend on the blood flow, and cannot exceed 1.3 o C. Unlike the equilibrium temperature difference, the rate of change of the local temperature, with respect to time, does depend on the blood flow. In organs with high perfusion rates, such as the brain and muscles, temperature changes occur on a time scale of a few minutes. In organs with low perfusion rates, such changes may have characteristic time constants of tens or hundreds of minutes. Our analysis explains, why arterial blood temperature is the main determinant of the temperature of tissues with limited heat exchange, such as the brain.

Stroke Location and Brain Function in an Embolic Rabbit Stroke Model

PubMed Central

Brown, Aliza T.; Skinner, Robert D.; Flores, Rene; Hennings, Leah; Borrelli, Michael J.; Lowery, John; Culp, William C.

2010-01-01

Purpose Current rabbit stroke models often depend on symptoms as endpoints for embolization and produce wide variation in location, size, and severity of strokes. To further refine our angiographic embolic stroke model we correlated localized infarctions to neurological deficits. Our goal is a rabbit model for long term studies of therapies after stroke. Materials and Methods New Zealand White rabbits (4–5 kg) (n=71) had selective internal carotid artery (ICA) angiography and a single clot was injected. At 24 hours neurological assessment scores (NAS) were measured on a 0=normal to 10=dead scale. Brains were removed and stained to identify stroke areas. All animals with single strokes, N=31, were analyzed by specific brain structure involvement and NAS values were correlated. Results Stroke incidence differed by location with cortex, subcortical, and basal ganglia regions highest. Distributions of middle cerebral artery (MCA) at 52% and anterior cerebral artery (ACA) at 29% were most commonly involved with largest stroke volumes in the ACA distribution. Brain stem and cerebellum strokes had disproportionately severe neurological deficits, scoring 2.25±1.0 vs. cortex (0.5±0.2), subcortical (1.3±0.4) and basal ganglia (0.5±0.3) all in the frontal or parietal regions on NAS (P≤0.02). Conclusions MCA and ACA distributions included 81% of strokes. These sites were relatively silent (potentially allowing longer term survival studies) while others in the posterior circulation produced disproportionately severe symptoms. Symptoms were not reliable indicators of stroke occurrence and other endpoints such as imaging may be required. These are important steps towards refinement of the rabbit stroke model. PMID:20417119

Brain volume and cognitive function in patients with revascularized coronary artery disease.

PubMed

Ottens, Thomas H; Hendrikse, Jeroen; Nathoe, Hendrik M; Biessels, Geert Jan; van Dijk, Diederik

2017-03-01

The pathogenesis of cognitive dysfunction in patients with CAD remains unclear. CAD is associated with brain atrophy and specific lesions. Detailed knowledge about the association of brain volume measured with MRI, and cognitive function in patients with CAD is lacking. We therefore investigated brain volume and cognitive function in patients with revascularized coronary artery disease (CAD), and controls without CAD. Brain MRI scans and cognitive tests from patients with CAD were compared with data from control subjects without CAD. Cognitive performance was assessed with the Rey Auditory Verbal Learning (short term memory) and Trailmaking (divided attention) tests. Multivariable regression analysis was used to study associations between CAD, brain volume and cognitive function. A total of 102 patients with CAD and 48 control subjects were included. Level of education and age were comparable between the groups. Compared with controls, patients with CAD had smaller total brain volume (expressed as fraction of intracranial volume) [%ICV, mean (SD), 0.78 (0.03) vs 0.80 (0.02), P=0.001] and larger volume of non-ventricular cerebrospinal fluid [%ICV, median (IQR) 0.19 (0.18 to 0.21) vs 0.18 (0.17 to 0.20), P=0.001]. Patients in the CAD group had poorer cognitive function [mean (SD) Z-score -0.16 (0.72) vs 0.41 (0.69), P<0.01]. Multivariable regression showed that CAD, higher age, lower level of education and greater cerebrospinal fluid volume were independent predictors of poorer cognitive function. CAD patients had a smaller total brain volume and poorer cognitive function than controls. Greater volume of cerebrospinal fluid was an independent predictor of poorer cognitive function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Non-invasive optical monitoring of the newborn piglet brain using continuous-wave and frequency-domain spectroscopy

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Hueber, Dennis; Franceschini, Maria Angela; Gratton, Enrico; Rosenfeld, Warren; Stubblefield, Phillip G.; Maulik, Dev; Stankovic, Miljan R.

1999-06-01

We have used continuous-wave (CW) and frequency-domain spectroscopy to investigate the optical properties of the newborn piglet brain in vivo and non-invasively. Three anaesthetized, intubated, ventilated and instrumented newborn piglets were placed into a stereotaxic instrument for optimal experimental stability, reproducible probe-to-scalp optical contact and 3D adjustment of the optical probe. By measuring the absolute values of the brain absorption and reduced scattering coefficients at two wavelengths (758 and 830 nm), frequency-domain spectroscopy provided absolute readings (in contrast to the relative readings of CW spectroscopy) of cerebral haemoglobin concentration and saturation during experimentally induced perturbations in cerebral haemodynamics and oxygenation. Such perturbations included a modulation of the inspired oxygen concentration, transient brain asphyxia, carotid artery occlusion and terminal brain asphyxia. The baseline cerebral haemoglobin saturation and concentration, measured with frequency-domain spectroscopy, were about 60% and 42 µM respectively. The cerebral saturation values ranged from a minimum of 17% (during transient brain asphyxia) to a maximum of 80% (during recovery from transient brain asphyxia). To analyse the CW optical data, we have (a) derived a mathematical relationship between the cerebral optical properties and the differential pathlength factor and (b) introduced a method based on the spatial dependence of the detected intensity (dc slope method). The analysis of the cerebral optical signals associated with the arterial pulse and with respiration demonstrates that motion artefacts can significantly affect the intensity recorded from a single optode pair. Motion artefacts can be strongly reduced by combining data from multiple optodes to provide relative readings in the dc slope method. We also report significant biphasic changes (initial decrease and successive increase) in the reduced scattering coefficient measured in the brain after the piglet had been sacrificed.

[Clinical and pathological significance of carotid siphon calcification observed on bone condition of brain CT].

PubMed

Matsumoto, Hideyuki; Hamaguchi, Hirotoshi; Nakayama, Takahiro; Oda, Tetsuya; Ikagawa, Takashi; Imafuku, Ichiro

2008-02-01

On plain brain computed tomography (CT), it is difficult to evaluate stenosis of internal carotid artery (ICA) because ICA is surrounded by structures, even though we can observe calcification of carotid siphon in some patients by using bone condition. However the pathologic significance has not been well known. We studied the pathologic significance of carotid siphon calcification observed on bone condition of brain CT. A total of 112 patients who were diagnosed or suspected as cerebrovascular diseases were registered. We classified the calcification into four levels (none, mild, moderate, severe) based on the degree of calcification. Then we compared it with the degree of stenosis of carotid siphon seen on brain magnetic resonance angiography (MRA) and with max intima-medial thickness (IMT) from common carotid artery (CCA) to ICA on carotid ultrasonography. The mean +/- standard deviation of max IMT to none, mild, moderate and severe in the degree of calcification were 1.03 +/- 0.64 (0.4-2.8), 1.65 +/- 0.83 (0.5-4.1), 2.03 +/- 0.83 (0.8-4.1) and 2.81 +/- 1.15 (0.7-6.5) mm, respectively. The calcification on brain CT significantly correlated with the degree of stenosis on brain MRA and with max IMT on carotid ultrasonography. The calcification of carotid siphon on bone condition of brain CT correlated with stenosis of the same portion and atherosclerosis of CCA bifurcation. Recently, on DICOM viewer, clinicians can convert plain condition into bone condition on brain CT due to popularization of PACS. We should pay attention to calcification of carotid siphon in patients with ischemic cerebrovascular diseases because we can estimate the atherosclerosis of both carotid siphon and CCA bifurcation easily and immediately.

Effect of baculovirus P35 protein on apoptosis in brain tissue of rats with acute cerebral infarction.

PubMed

Ji, J F; Ma, X H

2015-08-10

We explored the effect of baculovirus P35 protein on apoptosis in the brain tissue of rats with acute cerebral infarction (ACI). A rat model of middle cerebral artery infarction was created. The rats were randomly divided into sham, model, and treatment groups. Baculovirus P35 protein was injected into the intracranial arteries of the treatment group rats. The rats in the model group were given an equal volume of phosphate-buffered saline. The rats were sacrificed after 72 h and the brain tissue was separated. The levels of caspase-3, Bcl-2, and Bax mRNA, the brain cell apoptosis index, and the infarct size were determined. After 72 h, the levels of caspase-3 and Bax mRNA in the model and treatment groups were significantly greater than in the sham group, and the levels of Bcl-2 mRNA were significantly smaller (P < 0.05). The levels of caspase-3 and Bax mRNA were significantly lower in the treatment group than in the model group, and the level of Bcl-2 mRNA was significantly greater (P < 0.05). Compared with the sham group, the brain tissue apoptosis index and the cerebral infarction area increased significantly in the model and treatment groups (P < 0.05). The brain tissue apoptosis index and cerebral infarction area in the treatment group were significantly lower than in the model group (P < 0.05). Baculovirus P35 protein can effectively inhibit brain cell apoptosis in rats with ACI. It delayed apoptosis and necrosis in subjects with ACI tissue and had a protective effect on brain tissue.

The Evolution and Development of Neural Superposition

PubMed Central

Agi, Egemen; Langen, Marion; Altschuler, Steven J.; Wu, Lani F.; Zimmermann, Timo

2014-01-01

Visual systems have a rich history as model systems for the discovery and understanding of basic principles underlying neuronal connectivity. The compound eyes of insects consist of up to thousands of small unit eyes that are connected by photoreceptor axons to set up a visual map in the brain. The photoreceptor axon terminals thereby represent neighboring points seen in the environment in neighboring synaptic units in the brain. Neural superposition is a special case of such a wiring principle, where photoreceptors from different unit eyes that receive the same input converge upon the same synaptic units in the brain. This wiring principle is remarkable, because each photoreceptor in a single unit eye receives different input and each individual axon, among thousands others in the brain, must be sorted together with those few axons that have the same input. Key aspects of neural superposition have been described as early as 1907. Since then neuroscientists, evolutionary and developmental biologists have been fascinated by how such a complicated wiring principle could evolve, how it is genetically encoded, and how it is developmentally realized. In this review article, we will discuss current ideas about the evolutionary origin and developmental program of neural superposition. Our goal is to identify in what way the special case of neural superposition can help us answer more general questions about the evolution and development of genetically “hard-wired” synaptic connectivity in the brain. PMID:24912630

The evolution and development of neural superposition.

PubMed

Agi, Egemen; Langen, Marion; Altschuler, Steven J; Wu, Lani F; Zimmermann, Timo; Hiesinger, Peter Robin

2014-01-01

Visual systems have a rich history as model systems for the discovery and understanding of basic principles underlying neuronal connectivity. The compound eyes of insects consist of up to thousands of small unit eyes that are connected by photoreceptor axons to set up a visual map in the brain. The photoreceptor axon terminals thereby represent neighboring points seen in the environment in neighboring synaptic units in the brain. Neural superposition is a special case of such a wiring principle, where photoreceptors from different unit eyes that receive the same input converge upon the same synaptic units in the brain. This wiring principle is remarkable, because each photoreceptor in a single unit eye receives different input and each individual axon, among thousands others in the brain, must be sorted together with those few axons that have the same input. Key aspects of neural superposition have been described as early as 1907. Since then neuroscientists, evolutionary and developmental biologists have been fascinated by how such a complicated wiring principle could evolve, how it is genetically encoded, and how it is developmentally realized. In this review article, we will discuss current ideas about the evolutionary origin and developmental program of neural superposition. Our goal is to identify in what way the special case of neural superposition can help us answer more general questions about the evolution and development of genetically "hard-wired" synaptic connectivity in the brain.

Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools.

PubMed

Kelsen, Jesper; Larsen, Marianne H; Sørensen, Jens Christian; Møller, Arne; Frøkiaer, Jørgen; Nielsen, Søren; Nyengaard, Jens R; Mikkelsen, Jens D; Rønn, Lars Christian B

2010-04-06

We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats (SHRs) and Sprague-Dawley rats (SDs) one week after tMCAo; (2) to present the practical use of the optical fractionator and 2D nucleator in stereological brain tissue analyses; and (3) to report our experiences with an intraluminal tMCAo model where the occluding filament is advanced 22 mm beyond the carotid bifurcation and the common carotid artery is clamped during tMCAo. Twenty-three SDs and twenty SHRs were randomized into four groups subjected to 90 minutes tMCAo or sham. BrdU (50 mg/kg) was administered intraperitoneally twice daily on Day 4 to 7 after surgery. On Day 8 all animals were euthanized. NeuN-stained tissue sections were used for brain and infarct volume estimation with the 2D nucleator and Cavalieri principle. Brains were studied for the presence of activated microglia (ED-1) and hippocampal BrdU incorporation using the optical fractionator. We found no significant difference or increase in post-ischemic NPC proliferation between the two strains. However, the response to remote ischemia may differ between SDs and SHRs. In three animals increased post-stroke NPC proliferation was associated with hippocampal ischemic injury. The mean infarct volume was 89.2 +/- 76.1 mm3 in SHRs and 16.9 +/- 22.7 mm3 in SDs (p < 0.005). Eight out of eleven SHRs had ischemic neocortical damage in contrast to only one out of 12 SDs. We observed involvement of the anterior choroidal and hypothalamic arteries in several animals from both strains and the anterior cerebral artery in two SHRs. We found no evidence of an early hippocampal NPC proliferation one week after tMCAo in both strains. Infarction within the anterior choroidal artery could induce hippocampal ischemia and increase NPC proliferation profoundly. NPC proliferation was not aggravated by the presence of activated microglia. Intraluminal tMCAo in SHRs gave a more reliable infarct with neocortical involvement, but affected territories supplied by the anterior cerebral, anterior choroidal and hypothalamic arteries.

Lactate: Brain Fuel in Human Traumatic Brain Injury: A Comparison with Normal Healthy Control Subjects

PubMed Central

Martin, Neil A.; Horning, Michael A.; McArthur, David L.; Hovda, David A.; Vespa, Paul; Brooks, George A.

2015-01-01

Abstract We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-2H2]glucose, that is, D2-glucose, and [3-13C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives. Written and informed consent was obtained from control volunteers (n=6). Patients were studied 5.7±2.2 (mean±SD) days post-injury; during periods when arterial glucose concentration tended to be higher in TBI patients. As in previous investigations, the cerebral metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly suppressed following TBI (p<0.001). However, lactate fractional extraction, an index of cerebral lactate uptake related to systemic lactate supply, approximated 11% in both healthy control subjects and TBI patients. Further, neither the CMR for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral lactate uptake differed between healthy controls and TBI patients. The percentages of lactate tracer taken up and released as 13CO2 into the JB accounted for 92% and 91% for control and TBI conditions, respectively, suggesting that most cerebral lactate uptake was oxidized following TBI. Comparisons of isotopic enrichments of lactate oxidation from infused [3-13C]lactate tracer and 13C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75–80% of 13CO2 released into the JB was from lactate and that the remainder was from the oxidation of glucose secondarily labeled from lactate. Hence, either directly as lactate uptake, or indirectly via GNG, peripheral lactate production accounted for ∼70% of carbohydrate (direct lactate uptake+uptake of glucose from lactate) consumed by the injured brain. Undiminished cerebral lactate fractional extraction and uptake suggest that arterial lactate supplementation may be used to compensate for decreased CMRgluc following TBI. PMID:25594628