These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Neurobiology of Aging 26 (2005) 491510 Measures of brain morphology and infarction in the framingham  

E-print Network

Neurobiology of Aging 26 (2005) 491­510 Measures of brain morphology and infarction to the possible impact of brain infarction on age-related differences in regional brain volumes. Given the current, particularly with regard to the impact of brain infarctions, we chose to quantify brain MRIs from more than

California at Davis, University of

2

Paradoxical brain embolism associated with kimura disease mimics watershed infarction.  

PubMed

Kimura disease (KD) is an uncommon chronic inflammatory disease presenting as subcutaneous lymphadenopathy with eosinophilia. To date, only a single case of brain embolism caused by fibroblastic endocarditis associated with KD has been reported. Watershed infarction was seen in patients with episodes of severe hypotension or cardiac surgery. We here report a young case of KD who developed ischemic stroke and showed multiple small infarcts in the border zones between the territories of major cerebral arteries, mimicking watershed infarction. Transesophageal echocardiography revealed patent foramen ovale and atrial septal aneurysm. Concurrently, deep venous thrombus in the femoral vein was found on duplex ultrasonography. Our case supports the notion that paradoxical brain embolism associated with KD can cause multiple small embolisms and mimic watershed infarction. PMID:25447210

Tanaka, Yasutaka; Ueno, Yuji; Shimada, Yoshiaki; Yamashiro, Kazuo; Tanaka, Ryota; Urabe, Takao; Hattori, Nobutaka

2015-02-01

3

Silent brain infarction in the presence of systemic vascular disease  

PubMed Central

Objective To determine the prevalence of asymptomatic brain ischaemic in the presence of vascular disease in other arterial territories. Design Studies up to January 2011 were identified through comprehensive search strategies. Arcsine transformation for meta-analysis was used to calculate the standardized mean difference (SMD) and 95% confidence intervals (CI). Setting A systematic review and meta-analysis were performed. Participants For each study, the proportion of patients positive for SBI in the presence of other systemic vascular disease was extracted and analyzed. Main outcome measures Using a random-effects model, a pooled effect estimate interpreted as a percentage prevalence of disease was calculated. Results SBI in the presence of acute ischaemic stroke was found in 23% (SMD 0.99; P < 0.001; 95% CI 0.88–1.10); a 35% prevalence was found in patients with coronary artery disease (SMD 1.26; P < 0.001; 95% CI 0.95–1.58); and a 14% prevalence in patients with peripheral artery disease (SMD 0.48; P < 0.002; 95% CI 0.42–0.54), although the data-set in the latter is smaller. Conclusions Patients with systemic vascular disease are at an increased risk of silent brain infarction. PMID:24175060

Slark, Julia; Bentley, Paul; Sharma, Pankaj

2012-01-01

4

Brain natriuretic peptide release in acute myocardial infarction  

PubMed Central

Brain natriuretic peptide (BNP) is released from ventricular myocites due to their stretching and volume overload. In heart failure there is BNP release. Aim of this study was to observe BNP release in acute myocardial infarction (AMI). We measured BNP in 75 patients with AMI. Control group (n=61) was similar by age and gender to AMI group. We found statistically significant elevation of BNP compared to controls (462.875 pg/ml vs 35.356 pg/ml,p< 0.001). Patients with severe systolic dysfunction had the highest BNP levels, while patients with the preserved systolic function had the lowest BNP levels (Group with EF<30% BNP= 1129.036 pg/ml vs Group with EF31-40 % BNP= 690.177 pg/ml vs Group with EF 41-50% BNP= 274.396 pg/ml vs Group with EF>51% BNP= 189.566 pg/ml, p< 0.001). We found statistically significant light positive correlation between BNP and left ventricle end-diastolic diameter (LVDd) (r= 0.246,p<0.05). and real positive correlation between BNP and peak troponin levels (r= 0.441,p < 0.05). BNP levels were higher in anteroseptal allocation of AMI compared to inferior allocation (835.80 pg/ml vs 243.03 pg/ml, p< 0.001) and in patients who were treated with heparin compared to fibrinolitic therapy (507.885 pg/ml vs 354.73 pg/ml, p< 0.05). BNP is elevated in AMI and is a quantitative biochemical marker related to the extent of infarction and the left ventricle systolic dysfunction. Besides echocardiographic calculation, elevation of BNP could be used for quick and easy determination of the left ventricle systolic dysfunction. PMID:22938543

Durak-Nalbanti?, Azra; Džubur, Alen; Dili?, Mirza; Pozderac, Žana; Mujanovi?-Naran?i?, Alma; Kuli?, Mehmed; Hodži?, Enisa; Resi?, Nerma; Brdjanovi?, Snežana; Zvizdi?, Faris

2012-01-01

5

Silent brain infarcts and the risk of dementia and cognitive decline  

Microsoft Academic Search

BACKGROUND: Silent brain infarcts are frequently seen on magnetic\\u000a resonance imaging (MRI) in healthy elderly people and may be associated\\u000a with dementia and cognitive decline. METHODS: We studied the association\\u000a between silent brain infarcts and the risk of dementia and cognitive\\u000a decline in 1015 participants of the prospective, population-based\\u000a Rotterdam Scan Study, who were 60 to 90 years of age

Sarah E. Vermeer; Niels D. Prins; Tom den Heijer; P. J. Koudstaal; M. M. B. Breteler; A. Hofman

2003-01-01

6

The allometric model in chronic myocardial infarction  

PubMed Central

Background An allometric relationship between different electrocardiogram (ECG) parameters and infarcted ventricular mass was assessed in a myocardial infarction (MI) model in New Zealand rabbits. Methods A total of fifteen animals were used, out of which ten underwent left anterior descending coronary artery ligation to induce infarction (7–35% area). Myocardial infarction (MI) evolved and stabilized during a three month-period, after which, rabbits were sacrificed and the injured area was histologically confirmed. Right before sacrifice, ECGs were obtained to correlate several of its parameters to the infarcted mass. The latter was normalized after combining data from planimetry measurements and heart weight. The following ECG parameters were studied: RR and PR intervals, P-wave duration (PD), QRS duration (QRSD) and amplitude (QRSA), Q-wave (QA), R-wave (RA) and S-wave (SA) amplitudes, T-wave peak amplitude (TA), the interval from the peak to the end of the T-wave (TPE), ST-segment deviation (STA), QT interval (QT), corrected QT and JT intervals. Corrected QT was analyzed with different correction formulae, i.e., Bazett (QTB), Framingham (QTFRA), Fridericia (QTFRI), Hodge (QTHO) and Matsunaga (QTMA) and compared thereafter. The former variables and infarcted ventricular mass were then fitted to the allometric equation in terms of deviation from normality, in turn derived after ECGs in 5 healthy rabbits. Results Six variables (JT, QTB, QA, SA, TA and STA) presented statistical differences among leads. QT showed the best allometric fit (r?=?0.78), followed by TA (r?=?0.77), STA (r?=?0.75), QTFRA (r?=?0.72), TPE (r?=?0.69), QTFRI (r?=?0.68) and QTMA (r?=?0.68). Corrected QT’s (QTFRA, QTFRI and QTMA) performed worse than the uncorrected counterpart (QT), the former scaling allometrically with similar goodness of fits. Conclusions QT, TA, STA and TPE could possibly be used to assess infarction extent in an old MI event through the allometric model as a first approach. Moreover, the TPE also produced a good allometric scaling, leading to the potential existence of promising allometric indexes to diagnose malignant arrhythmias. PMID:22578057

2012-01-01

7

Effect of delayed albumin hemodilution on infarction volume and brain edema after transient middle cerebral artery occlusion in rats.  

PubMed

The authors examined the effect of delayed high-concentration albumin therapy on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Male Sprague-Dawley rats weighing 270 to 320 g were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion induced by means of a poly-L-lysine-coated intraluminal nylon suture inserted retrograde via the external carotid artery into the internal carotid artery and MCA. The agent (20% human serum albumin [HSA]) or control solution (sodium chloride 0.9%) was administered intravenously at a dosage of 1% of body weight immediately after suture removal following a 2-hour period of MCA occlusion. The animals' neurological status was evaluated during MCA occlusion (at 60 minutes) and daily for 3 days thereafter. The brains were perfusion-fixed, and infarct volumes and brain edema were determined. The HSA significantly improved the neurological score compared with saline at 24 hours after MCA occlusion. The rats treated with HSA also had significantly reduced total infarct volume (by 34%) and brain edema (by 81%) compared with saline-treated rats. There was a strong correlation between hematocrit level and brain edema (p < 0.01), and between total infarct volume or brain edema and neurological score at 24, 48, and 72 hours postinjury (p < 0.0002). These results strongly support the beneficial effect of delayed albumin therapy in transient focal ischemia and indicate its possible usefulness in treating patients with acute ischemic stroke. PMID:9322848

Belayev, L; Busto, R; Zhao, W; Clemens, J A; Ginsberg, M D

1997-10-01

8

Physiological Correlates of Intellectual Function in Children with Sickle Cell Disease: Hypoxaemia, Hyperaemia and Brain Infarction  

ERIC Educational Resources Information Center

Lowered intelligence relative to controls is evident by mid-childhood in children with sickle cell disease. There is consensus that brain infarct contributes to this deficit, but the subtle lowering of IQ in children with normal MRI scans might be accounted for by chronic systemic complications leading to insufficient oxygen delivery to the brain.…

Hogan, Alexandra M.; Pit-ten Cate, Ineke M.; Vargha-Khadem, Faraneh; Prengler, Mara; Kirkham, Fenella J.

2006-01-01

9

Surgery-Related Thrombosis Critically Affects the Brain Infarct Volume in Mice Following Transient Middle Cerebral Artery Occlusion  

PubMed Central

Transient middle cerebral artery occlusion (tMCAO) model is widely used to mimic human focal ischemic stroke in order to study ischemia/reperfusion brain injury in rodents. In tMCAO model, intraluminal suture technique is widely used to achieve ischemia and reperfusion. However, variation of infarct volume in this model often requires large sample size, which hinders the progress of preclinical research. Our previous study demonstrated that infarct volume was related to the success of reperfusion although the reason remained unclear. The aim of present study is to explore the relationship between focal thrombus formation and model reproducibility with respect to infarct volume. We hypothesize that suture-induced thrombosis causes infarct volume variability due to insufficient reperfusion after suture withdrawal. Seventy-two adult male CD-1 mice underwent 90 minutes of tMCAO with or without intraperitoneal administration of heparin. Dynamic synchrotron radiation microangiography (SRA) and laser speckle contrast imaging (LSCI) were performed before and after tMCAO to observe the cerebral vascular morphology and to measure the cerebral blood flow in vivo. Infarct volume and neurological score were examined to evaluate severity of ischemic brain injury. We found that the rate of successful reperfusion was much higher in heparin-treated mice compared to that in heparin-free mice according to the result of SRA and LSCI at 1 and 3 hours after suture withdrawal (p<0.05). Pathological features and SRA revealed that thrombus formed in the internal carotid artery, middle cerebral artery or anterior cerebral artery, which blocked reperfusion following tMCAO. LSCI showed that cortical collateral circulation could be disturbed by thrombi. Our results demonstrated that suture-induced thrombosis was a critical element, which affects the success of reperfusion. Appropriate heparin management provides a useful approach for improving reproducibility of reperfusion model in mice. PMID:24086572

Lin, Xiaojie; Miao, Peng; Wang, Jixian; Yuan, Falei; Guan, Yongjing; Tang, Yaohui; He, Xiaosong; Wang, Yongting; Yang, Guo-Yuan

2013-01-01

10

The influence of meteorological and geomagnetic factors on acute myocardial infarction and brain stroke in Moscow, Russia  

NASA Astrophysics Data System (ADS)

Evidence of the impact of air temperature and pressure on cardiovascular morbidity is still quite limited and controversial, and even less is known about the potential influence of geomagnetic activity. The objective of this study was to assess impacts of air temperature, barometric pressure and geomagnetic activity on hospitalizations with myocardial infarctions and brain strokes. We studied 2,833 myocardial infarctions and 1,096 brain strokes registered in two Moscow hospitals between 1992 and 2005. Daily event rates were linked with meteorological and geomagnetic conditions, using generalized linear model with controls for day of the week, seasonal and long-term trends. The number of myocardial infarctions decreased with temperature, displayed a U-shaped relationship with pressure and variations in pressure, and increased with geomagnetic activity. The number of strokes increased with temperature, daily temperature range and geomagnetic activity. Detrimental effects on strokes of low pressure and falling pressure were observed. Relative risks of infarctions and strokes during geomagnetic storms were 1.29 (95 % CI 1.19-1.40) and 1.25 (1.10-1.42), respectively. The number of strokes doubled during cold spells. The influence of barometric pressure on hospitalizations was relatively greater than the influence of geomagnetic activity, and the influence of temperature was greater than the influence of pressure. Brain strokes were more sensitive to inclement weather than myocardial infarctions. This paper provides quantitative estimates of the expected increases in hospital admissions on the worst days and can help to develop preventive health plans for cardiovascular diseases.

Shaposhnikov, Dmitry; Revich, Boris; Gurfinkel, Yuri; Naumova, Elena

2014-07-01

11

Sex differences in the risk profile and male predominance in silent brain infarction in community-dwelling elderly subjects: the Sefuri brain MRI study  

Microsoft Academic Search

Although brain infarction is more common in men, the male predominance of silent brain infarction (SBI) was inconsistent in the earlier studies. This study was to examine the relationship between sex differences in the risk profile and SBI. We conducted a population-based, cross-sectional analysis of cardiovascular risk factors and SBI on MRI. We asked all the female participants about the

Yuki Takashima; Yoshikazu Miwa; Takahiro Mori; Manabu Hashimoto; Akira Uchino; Takefumi Yuzuriha; Toshiyuki Sasaguri; Hiroshi Yao

2010-01-01

12

Near-infrared diffuse reflectance imaging of infarct core and peri-infarct depolarization in a rat middle cerebral artery occlusion model  

NASA Astrophysics Data System (ADS)

To understand the pathophysiology of ischemic stroke, in vivo imaging of the brain tissue viability and related spreading depolarization is crucial. In the infarct core, impairment of energy metabolism causes anoxic depolarization (AD), which considerably increases energy consumption, accelerating irreversible neuronal damage. In the peri-infarct penumbra region, where tissue is still reversible despite limited blood flow, peri-infarct depolarization (PID) occurs, exacerbating energy deficit and hence expanding the infarct area. We previously showed that light-scattering signal, which is sensitive to cellular/subcellular structural integrity, was correlated with AD and brain tissue viability in a rat hypoxia-reoxygenation model. In the present study, we performed transcranial NIR diffuse reflectance imaging of the rat brain during middle cerebral artery (MCA) occlusion and examined whether the infarct core and PIDs can be detected. Immediately after occluding the left MCA, light scattering started to increase focally in the occlusion site and a bright region was generated near the occlusion site and spread over the left entire cortex, which was followed by a dark region, showing the occurrence of PID. The PID was generated repetitively and the number of times of occurrence in a rat ranged from four to ten within 1 hour after occlusion (n=4). The scattering increase in the occlusion site was irreversible and the area with increased scattering expanded with increasing the number of PIDs, indicating an expansion of the infarct core. These results suggest the usefulness of NIR diffuse reflectance signal to visualize spatiotemporal changes in the infarct area and PIDs.

Kawauchi, Satoko; Nishidate, Izumi; Nawashiro, Hiroshi; Sato, Shunichi

2014-03-01

13

Cardiomyocyte Transplantation in a Porcine Myocardial Infarction Model  

Microsoft Academic Search

Transplantation of cardiomyocytes into the heart is a potential treatment for replacing damaged cardiac muscle. To investigate the feasibility and efficiency of this technique, either a cardiac-derived cell line (HL-1 cells), or normal fetal or neonatal pig cardiomyocytes were grafted into a porcine model of myocardial infarction. The myocardial infarction was created by the placement of an embolization coil in

Eiichi Watanabe; Duane M Smith; Joseph B Delcarpio; Jian Sun; Frank W Smart; Clifford H Van Meter; William C Claycomb

1998-01-01

14

High-b-value Diffusion-weighted MR Imaging of Suspected Brain Infarction  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Recent technological advances in MR instrumentation al- low acquisition of whole-brain diffusion-weighted MR scans to be obtained with b values great- er than 1000. Our purpose was to determine whether high-b-value diffusion-weighted MR imaging improved contrast and detection of signal changes in acute and chronic brain infarction. METHODS: We prospectively evaluated the MR scans of 30 subjects

Joel R. Meyer; Arturo Gutierrez; Bryan Mock; Delon Hebron; Jordan M. Prager; Michael T. Gorey; Daniel Homer

2000-01-01

15

Intracranial MR angiography: Its role in the integrated approach to brain infarction  

SciTech Connect

To determine the contribution of cranial MR angiography (MRA) for the evaluation of patients with acute and subacute brain infarction. MR and MRA studies performed on 78 adult patients with acute and subacute stroke were retrospectively reviewed and correlated with the clinical records. There were 50 acute and 28 subacute infarctions in our series. Five of 78 MRA exams (6%) were nondiagnostic. Sixty examinations (80%) were positive for stenosis or occlusion. The distribution of stenotic or occlusive vascular lesions correlated with the location of infarction in 56 of the 60 positive cases (93%). MRA provided information not obtained from the MR images in 40 cases (55%). One hundred four individual vessels in 8 patients who underwent conventional cerebral angiography were compared with the MRA appearance. The MRA interpretations correlated with the conventional angiographic evaluations for 90 vessels (87%). Vascular lesions demonstrated on intracranial MRA show a high correlation with infarct distribution. MRA provides information adjunctive to conventional MR in a majority of cases. We conclude that MRA is an important component of the complete evaluation of brain infarction. 39 refs., 3 figs., 2 tabs.

Johnson, B.A.; Heiserman, J.E.; Drayer, B.P.; Keller, P.J. [Barrow Neurological Institute, Phoenix, AZ (United States)

1994-05-01

16

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

NASA Astrophysics Data System (ADS)

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.

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

2005-03-01

17

Functional electrical stimulation-facilitated proliferation and regeneration of neural precursor cells in the brains of rats with cerebral infarction  

PubMed Central

Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plasticity, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin (a neural precursor cell marker)-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic fibroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was significantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats. PMID:25206808

Xiang, Yun; Liu, Huihua; Yan, Tiebin; Zhuang, Zhiqiang; Jin, Dongmei; Peng, Yuan

2014-01-01

18

Photothrombotic infarction triggers multiple episodes of cortical spreading depression in distant brain regions.  

PubMed

The purposes of this study were to determine whether cortical spreading depression occurs outside of the infarct produced by photothrombotic vascular occlusion, and also the direction of spreading. Focal cerebral thrombotic infarction was produced by irradiating the exposed skull of anesthetized rats with green light (560 nm) following systemic injection of rose bengal dye. At proximal sites (approximately 2 mm anterior to the infarct border), transient, severe hyperemic episodes (THEs) lasting 1-2 min were intermittently recorded. THE frequency was greatest in the first hour and declined over a 3-h period. THEs were accompanied (and usually preceded) by a precipitous rise in [K+]0 (from approximately 3 to > 40 mM) and were associated with increases in local tissue oxygen tension (tPO2). Following the rise in [K+]0, clearance of [K+]0 to its pre-THE baseline preceded baseline recovery of CBF. These data indicate that THEs were reactive to physiologic events resembling cortical spreading depression (CSD), which provoked increased demand for oxygen and blood flow, and which spread from proximal sites to areas more distal (approximately 4 mm) from the rim of the evolving infarct. MK-801 (1 mg/kg, i.v.) inhibited subsequent CSD-like episodes. We conclude that photothrombosis-induced ischemia provoked CSD which was triggered either within the infarct core or in the infarct rim and spread to more distal sites. Whether multiple episodes of CSD during infarct generation are responsible for the remote consequences of focal brain injury remains to be determined. PMID:8263054

Dietrich, W D; Feng, Z C; Leistra, H; Watson, B D; Rosenthal, M

1994-01-01

19

A novel mouse model of subcortical infarcts with dementia.  

PubMed

Subcortical white matter (WM) is a frequent target of ischemic injury and extensive WM lesions are important substrates of vascular cognitive impairment (VCI) in humans. However, ischemic stroke rodent models have been shown to mainly induce cerebral infarcts in the gray matter, while cerebral hypoperfusion models show only WM rarefaction without infarcts. The lack of animal models consistently replicating WM infarct damage may partially explain why many neuroprotective drugs for ischemic stroke or VCI have failed clinically, despite earlier success in preclinical experiments. Here, we report a novel animal model of WM infarct damage with cognitive impairment can be generated by surgical implantation of different devices to the right and left common carotid artery (CCA) in C57BL/6J mice. Implantation of an ameroid constrictor to the right CCA resulted in gradual occlusion of the vessel over 28 d, whereas placement of a microcoil to the left CCA induced ?50% arterial stenosis. Arterial spin labeling showed a gradual reduction of cerebral blood flow over 28 d post operation. Such reductions were more marked in the right, compared with the left, hemisphere and in subcortical, rather than the cortical, areas. Histopathological analysis showed multiple infarct damage in right subcortical regions, including the corpus callosum, internal capsule, hippocampal fimbria, and caudoputamen, in 81% of mice. Mice displaying such damage performed significantly poorer in locomotor and cognitive tests. The current mouse model replicates the phenotypes of human subcortical VCI, including multiple WM infarcts with motor and cognitive impairment. PMID:25740520

Hattori, Yorito; Enmi, Jun-Ichiro; Kitamura, Akihiro; Yamamoto, Yumi; Saito, Satoshi; Takahashi, Yukako; Iguchi, Satoshi; Tsuji, Masahiro; Yamahara, Kenichi; Nagatsuka, Kazuyuki; Iida, Hidehiro; Ihara, Masafumi

2015-03-01

20

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

PubMed

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. PMID:24687898

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

21

Domains and determinants of quality of life after stroke caused by brain infarction  

Microsoft Academic Search

Kauhanen M-L, Korpelainen JT, Hiltunen P, Nieminen P, Sotaniemi KA, Myllylä VV. Domains and determinants of quality of life after stroke caused by brain infarction. Arch Phys Med Rehabil 2000;81:1541-46. Objective: To evaluate the domain-specific quality of life (QOL), including physical, social and role functioning, mental health, vitality, bodily pain, and general health domains, and to assess QOL's clinical and

Marja-Liisa Kauhanen; Juha T. Korpelainen; Pirkko Hiltunen; Pentti Nieminen; Kyösti A. Sotaniemi; Vilho V. Myllylä

2000-01-01

22

Increases in brain and cardiac AT1 receptor and ACE densities after myocardial infarct in rats.  

PubMed

In the brain, ouabain-like compounds (OLC) and the reninangiotensin system (RAS) contribute to sympathetic hyperactivity in rats after myocardial infarction (MI). This study aimed to evaluate changes in components of the central vs. the peripheral RAS. Angiotensin-converting enzyme (ACE) and angiotensin type 1 (AT1) receptor binding densities were determined by measuring 125I-labeled 351A and 125I-labeled ANG II binding 4 and 8 wk after MI. In the brain, ACE and AT1 receptor binding increased 8-15% in the subfornical organ, 14-22% in the organum vasculosum laminae terminalis, 20-34% in the paraventricular nucleus, and 13-15% in the median preoptic nucleus. In the heart, the greatest increase in ACE and AT1 receptor binding occurred at the infarct scar (approximately 10-fold) and the least in the right ventricle (2-fold). In kidneys, ACE and AT1 receptor binding decreased 10-15%. After intracerebroventricular infusion of Fab fragments to block brain OLC from 0.5 to 4 wk after MI, increases in ACE and AT1 receptors in the subfornical organ, organum vasculosum laminae terminalis, paraventricular nucleus, and medial preoptic nucleus were markedly inhibited, and ACE and AT1 receptor densities in the heart increased less (6-fold in the infarct scar). In kidneys, decreases in ACE and AT1 receptor binding were absent after treatment with Fab fragments. These results demonstrate that ACE and AT1 receptor binding densities increase not only in the heart but also in relevant areas of the brain of rats after MI. Brain OLC appears to play a major role in activation of brain RAS in rats after MI and, to a modest degree, in activation of the cardiac RAS. PMID:14693687

Tan, Junhui; Wang, Hao; Leenen, Frans H H

2004-05-01

23

Surgical Porcine Myocardial Infarction Model through Permanent Coronary Occlusion  

PubMed Central

Using domestic pigs as an animal model, we here validated a reproducible and standardized myocardial infarction (MI) surgical model, to achieve the largest possible infarct extent with the lowest morbidity and mortality. To this end, we included several anesthetic and perisurgical precautions to minimize surgical complications. Mortality and morbidity rates were compared among groups of pigs that underwent permanent occlusion at different locations of either the left circumflex or left anterior descending artery. In addition, to compare the resulting MI between groups, data were collected by using cardiac biomarkers (including troponin I), electrocardiography, and echocardiography. These data were correlated to the final mean infarct size calculated by microscopic studies. Proximal occlusions lead to high mortality rates, whereas distal occlusions induced rather small MI areas. The optimal occlusion site in terms of morbidity, mortality, and lesion extent was the midpoint of the left anterior descending artery. In this group, only one pig died, and group cardiac data showed a rise in biomarker levels, marked left ventricular dysfunction on electrocardiography and echocardiography, and well-defined transmural MI in both ventricles. Infarct size quantitated through histologic studies revealed an average 15% ventricular lesion. Because interanimal variability in results from this group was negligible, we consider that the induced myocardial injury of this model is reliable. PMID:22330353

Munz, Maria R; Faria, Miguel A; Monteiro, Joana R; Águas, Artur P; Amorim, Mário J

2011-01-01

24

Brain choline concentration: early quantitative marker of ischemia and infarct expansion?   

E-print Network

, after ischemic stroke. We compared choline, lactate, NAA, creatine concentrations in normal-appearing voxels that became infarcted("infarct expansion”), with normal-appearing voxels around the infarct that remained “healthy”(“non-expansion”) on follow...

Karaszewski, B.; Thomas, R.G.R.; Chappell, F.M.; Armitage, P.A.; Carpenter, T.K.; Lymer, G.K.S.; Dennis, M.S.; Marshall, I.; Wardlaw, J.M.

25

Gastroschisis, Destructive Brain Lesions, and Placental Infarction in the Second Trimester Suggest a Vascular Pathogenesis  

PubMed Central

The cause and pathogenesis of gastroschisis are uncertain. We report the autopsy and placental pathology of a stillbirth at 20 gestational weeks, in which gastroschisis was accompanied by destructive lesions in the cerebral cortex and brainstem, as well as cardiac calcification, consistent with ischemic injury during the 2nd trimester. An important potential underlying mechanism explaining the fetal abnormalities is the presence of infarcts in the placenta, indicative at this gestational age of maternal vascular underperfusion. The association of gastroschisis with ischemic lesions in the brain, heart, and placenta in this case supports the concept that gastroschisis, at least in some instances, may result from vascular event(s) causing disruption of the fetal abdominal wall and resulting in the extrusion of the abdominal organs, as well as hypoxic–ischemic brain and cardiac injury. PMID:23895144

Folkerth, Rebecca D.; Habbe, Donald M.; Boyd, Theonia K.; McMillan, Kristin; Gromer, Jessica; Sens, Mary Ann; Elliott, Amy J.

2014-01-01

26

MRI and PET in mouse models of myocardial infarction.  

PubMed

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ideal model for testing novel therapeutic strategies. In vivo magnetic resonance imaging (MRI) gives excellent views of the heart noninvasively with clear anatomical detail, which can be used for accurate functional assessment. Contrast agents can provide basic measures of tissue viability but these are nonspecific. Positron emission tomography (PET) is a complementary technique that is highly specific for molecular imaging, but lacks the anatomical detail of MRI. Used together, these techniques offer a sensitive, specific and quantitative tool for the assessment of the heart in disease and recovery following treatment. In this paper we explain how these methods are carried out in mouse models of acute myocardial infarction. The procedures described here were designed for the assessment of putative protective drug treatments. We used MRI to measure systolic function and infarct size with late gadolinium enhancement, and PET with fluorodeoxyglucose (FDG) to assess metabolic function in the infarcted region. The paper focuses on practical aspects such as slice planning, accurate gating, drug delivery, segmentation of images, and multimodal coregistration. The methods presented here achieve good repeatability and accuracy maintaining a high throughput. PMID:24378323

Buonincontri, Guido; Methner, Carmen; Carpenter, T Adrian; Hawkes, Robert C; Sawiak, Stephen J; Krieg, Thomas

2013-01-01

27

Brain-Derived Neurotrophic Factor Regulates TRPC3/6 Channels and Protects Against Myocardial Infarction in Rodents  

PubMed Central

Background: Brain-derived neurotrophic factor (BDNF) is associated with coronary artery diseases. However, its role and mechanism in myocardial infarction (MI) is not fully understood. Methods: Wistar rat and Kunming mouse model of MI were induced by the ligation of left coronary artery. Blood samples were collected from MI rats and patients. Plasma BDNF level, protein expression of BDNF, tropomyosin-related kinase B (TrkB) and its downstream transient receptor potential canonical (TRPC)3/6 channels were examined by enzyme-linked immunosorbent assay and Western blot. Infarct size, cardiac function and cardiomyocyte apoptosis were measured after intra-myocardium injection with recombinant human BDNF. Protective role of BDNF against cardiomyocyte apoptosis was confirmed by BDNF scavenger TrkB-Fc. The regulation of TRPC3/6 channels by BDNF was validated by pretreating with TRPC blocker (2-Aminoethyl diphenylborinate, 2-APB) and TRPC3/6 siRNAs. Results: Circulating BDNF was significantly enhanced in MI rats and patients. Protein expression of BDNF, TrkB and TRPC3/6 channels were upregulated in MI. 3 days post-MI, BDNF treatment markedly reduced the infarct size and serum lactate dehydrogenase activity. Meanwhile, echocardiography indicated that BDNF significantly improved cardiac function of MI mice. Furthermore, BDNF markedly inhibited cardiomyocyte apoptosis by upregulating Bcl-2 expression and downregulating caspase-3 expression and activity in ischemic myocardium. In neonatal rat ventricular myocytes, cell viability was dramatically increased by BDNF in hypoxia, which was restored by TrkB-Fc. Furthermore, protective role of BDNF against hypoxia-induced apoptosis was reversed by 2-APB and TRPC3/6 siRNAs. Conclusion: BDNF/TrkB alleviated cardiac ischemic injury and inhibited cardiomyocytes apoptosis by regulating TRPC3/6 channels, which provides a novel potential therapeutic candidate for MI.

Hang, Pengzhou; Zhao, Jing; Cai, Benzhi; Tian, Shanshan; Huang, Wei; Guo, Jing; Sun, Chuan; Li, Yue; Du, Zhimin

2015-01-01

28

Risk reduction of brain infarction during carotid endarterectomy or stenting using sonolysis - Prospective randomized study pilot data  

NASA Astrophysics Data System (ADS)

Sonolysis is a new therapeutic option for the acceleration of arterial recanalization. The aim of this study was to confirm risk reduction of brain infarction during endarterectomy (CEA) and stenting (CAS) of the internal carotid artery (ICA) using sonolysis with continuous transcranial Doppler (TCD) monitoring by diagnostic 2 MHz probe, additional interest was to assess impact of new brain ischemic lesions on cognitive functions. Methods: All consecutive patients 1/ with ICA stenosis >70%, 2/ indicated to CEA or CAS, 3/ with signed informed consent, were enrolled to the prospective study during 17 months. Patients were randomized into 2 groups: Group 1 with sonolysis during intervention and Group 2 without sonolysis. Neurological examination, assessment of cognitive functions and brain magnetic resonance imaging (MRI) were performed before and 24 hours after intervention in all patients. Occurrence of new brain infarctions (including infarctions >0.5 cm3), and the results of Mini-Mental State Examination, Clock Drawing and Verbal Fluency tests were statistically evaluated using T-test. Results: 97 patients were included into the study. Out of the 47 patients randomized to sonolysis group (Group 1) 25 underwent CEA (Group 1a) and 22 CAS (Group 1b). Out of the 50 patients randomized to control group (Group 2), 22 underwent CEA (Group 2a) and 28 CAS (Group 2b). New ischemic brain infarctions on follow up MRI were found in 14 (29.8%) patients in Group 1-4 (16.0%) in Group 1a and 10 (45.5%) in Group 1b. In Group 2, new ischemic brain infarctions were found in 18 (36.0%) patients-6 (27.3%) in Group 2a and 12 (42.9%) in Group 2b (p>0.05 in all cases). New ischemic brain infarctions >0.5 cm3 were found in 4 (8.5 %) patients in Group 1 and in 11 (22.0 %) patients in Group 2 (p= 0.017). No significant differences were found in cognitive tests results between subgroups (p>0.05 in all tests). Conclusion: Sonolysis seems to be effective in the prevention of large ischemic brain infarctions during CEA and CAS.

Kuliha, Martin; Školoudík, David; Martin Roubec, Martin; Herzig, Roman; Procházka, Václav; Jonszta, Tomáš; Kraj?a, Jan; Czerný, Dan; Hrbá?, Tomáš; Otáhal, David; Langová, Kate?ina

2012-11-01

29

Plasma brain natriuretic peptide is a biochemical marker for the prediction of progressive ventricular remodeling after acute myocardial infarction  

Microsoft Academic Search

To investigate the relation between plasma brain natriuretic peptide (BNP) and progressive ventricular remodeling, we measured plasma BNP and atrial natriuretic peptide (ANP) in 30 patients with acute myocardial infarction on days 2, 7, 14, and 30 after the onset. Left ventricular end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and ejection fraction (EF) on admission and 1 month after

Noritoshi Nagaya; Toshio Nishikimi; Yoichi Goto; Yuji Miyao; Yoshio Kobayashi; Isao Morii; Satoshi Daikoku; Takahiro Matsumoto; Shunichi Miyazaki; Hiroaki Matsuoka; Shuichi Takishita; Kenji Kangawa; Hisayuki Matsuo; Hiroshi Nonogi

1998-01-01

30

Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients  

Microsoft Academic Search

The role of preceding infection as a risk factor for ischaemic stroke was investigated in a case-control study of 54 consecutive patients under 50 years of age with brain infarction and 54 randomly selected controls from the community matched for sex and age. Information about previous illnesses, smoking, consumption of alcohol, and use of drugs was taken. A blood sample

Jaana Syrjänen; Ville V Valtonen; Matti Iivanainen; Markku Kaste; Jussi K Huttunen

1988-01-01

31

Association of Reduced Folate Carrier-1 (RFC-1) Polymorphisms with Ischemic Stroke and Silent Brain Infarction  

PubMed Central

Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke. PMID:25659099

Cho, Yunkyung; Kim, Jung O; Lee, Jeong Han; Park, Hye Mi; Jeon, Young Joo; Oh, Seung Hun; Bae, Jinkun; Park, Young Seok; Kim, Ok Joon; Kim, Nam Keun

2015-01-01

32

Spatiotemporal brain imaging and modeling  

E-print Network

This thesis integrates hardware development, data analysis, and mathematical modeling to facilitate our understanding of brain cognition. Exploration of these brain mechanisms requires both structural and functional knowledge ...

Lin, Fa-Hsuan, 1972-

2004-01-01

33

Neuronal Ca2+-Activated K+ Channels Limit Brain Infarction and Promote Survival  

PubMed Central

Neuronal calcium-activated potassium channels of the BK type are activated by membrane depolarization and intracellular Ca2+ ions. It has been suggested that these channels may play a key neuroprotective role during and after brain ischemia, but this hypothesis has so far not been tested by selective BK-channel manipulations in vivo. To elucidate the in vivo contribution of neuronal BK channels in acute focal cerebral ischemia, we performed middle cerebral artery occlusion (MCAO) in mice lacking BK channels (homozygous mice lacking the BK channel alpha subunit, BK?/?). MCAO was performed in BK?/? and WT mice for 90 minutes followed by a 7-hour-reperfusion period. Coronal 1 mm thick sections were stained with 2,3,5-triphenyltetrazolium chloride to reveal the infarction area. We found that transient focal cerebral ischemia by MCAO produced larger infarct volume, more severe neurological deficits, and higher post-ischemic mortality in BK?/? mice compared to WT littermates. However, the regional cerebral blood flow was not significantly different between genotypes as measured by Laser Doppler (LD) flowmetry pre-ischemically, intra-ischemically, and post-ischemically, suggesting that the different impact of MCAO in BK?/? vs. WT was not due to vascular BK channels. Furthermore, when NMDA was injected intracerebrally in non-ischemic mice, NMDA-induced neurotoxicity was found to be larger in BK?/? mice compared to WT. Whole-cell patch clamp recordings from CA1 pyramidal cells in organotypic hippocampal slice cultures revealed that BK channels contribute to rapid action potential repolarization, as previously found in acute slices. When these cultures were exposed to ischemia-like conditions this induced significantly more neuronal death in BK?/? than in WT cultures. These results indicate that neuronal BK channels are important for protection against ischemic brain damage. PMID:21209897

Liao, Yiliu; Gu, Ning; Rundén-Pran, Elise; Ruth, Peter; Sausbier, Matthias; Storm, Johan F.

2010-01-01

34

The Seattle Post Myocardial Infarction Model (SPIM): prediction of mortality after acute myocardial infarction with left ventricular dysfunction  

PubMed Central

Aims: Ischemic heart disease is a leading worldwide cause of death. The Seattle Post Myocardial Infarction Model (SPIM) was developed to predict survival 6 months to 2 years after an acute myocardial infarction with evidence of left ventricular dysfunction. Methods and Results: A total of 6632 subjects from the EPHESUS trial were used to derive the predictive model, while 5477 subjects from the OPTIMAAL trial were used to validate the model. Cox proportional hazards modeling was used to develop a multivariate risk score predictive of all-cause mortality. The SPIM risk score integrated lab and vital parameters, Killip class, reperfusion or revascularization, the number of cardiac evidence-based medicines (aspirin, statin, ? blocker, ACEI/ARB, aldosterone blocker), and the number of cardiac risk factors. The model was predictive of all-cause mortality after myocardial infarction, with an AUC of 0.75 at 6 months and 0.75 at 2 years in the derivation cohort and 0.77 and 0.78 for the same time points in the validation cohort. Model predicted versus Kaplan-Meier observed survival was excellent in the derivation cohort. It remained so in the validation cohort—84.9% versus 85.0% at 2 years. The 10% of subjects with the highest predicted risk had approximately 25 times higher mortality at 2 years than the 10% of subjects with the lowest predicted risk. Conclusion: The SPIM score was a powerful predictor of outcomes after myocardial infarction with left ventricular dysfunction. Its highly accurate predictions should improve patient and physician understanding of survival and may prove a useful tool in post-infarct risk stratification. PMID:24562803

Dickstein, Kenneth; Kjekshus, John; Pitt, Bertram; Wong, Meagan F; Linker, David T; Levy, Wayne C

2014-01-01

35

Systematic characterization of myocardial inflammation, repair, and remodeling in a mouse model of reperfused myocardial infarction.  

PubMed

Mouse models of myocardial infarction are essential tools for the study of cardiac injury, repair, and remodeling. Our current investigation establishes a systematic approach for quantitative evaluation of the inflammatory and reparative response, cardiac function, and geometry in a mouse model of reperfused myocardial infarction. Reperfused mouse infarcts exhibited marked induction of inflammatory cytokines that peaked after 6 hr of reperfusion. In the infarcted heart, scar contraction and chamber dilation continued for at least 28 days after reperfusion; infarct maturation was associated with marked thinning of the scar, accompanied by volume loss and rapid clearance of cellular elements. Echocardiographic measurements of end-diastolic dimensions correlated well with morphometric assessment of dilative remodeling in perfusion-fixed hearts. Hemodynamic monitoring was used to quantitatively assess systolic and diastolic function; the severity of diastolic dysfunction following myocardial infarction correlated with cardiomyocyte hypertrophy and infarct collagen content. Expression of molecular mediators of inflammation and cellular infiltration needs to be investigated during the first 72 hr, whereas assessment of dilative remodeling requires measurement of geometric parameters for at least four weeks after the acute event. Rapid initiation and resolution of the inflammatory response, accelerated scar maturation, and extensive infarct volume loss are important characteristics of infarct healing in mice. PMID:23714783

Christia, Panagiota; Bujak, Marcin; Gonzalez-Quesada, Carlos; Chen, Wei; Dobaczewski, Marcin; Reddy, Anilkumar; Frangogiannis, Nikolaos G

2013-08-01

36

Clinical Characteristics and Brain Activation Patterns of Mirror Movements in Patients with Corona Radiata Infarct  

Microsoft Academic Search

Objective: Mirror movements (MMs) are a phenomenon of involuntary movements that accompany physically intended movements of the opposite side of the body. In the current study, we investigated the clinical characteristics and cortical activation patterns of MMs in patients with corona radiata (CR) infarct, using functional MRI. Subjects and Methods: We recruited 31 consecutive hemiparetic stroke patients with CR infarct.

Mi Young Lee; Jin Ho Choi; Rae Joon Park; Yong Hyun Kwon; Jong Sung Chang; Jun Lee; Sang Ho Ahn; Sung Ho Jang

2010-01-01

37

[A trial of surgical management of brain edema in cerebral infarction--a review with our own experiences in 31 cases (author's transl)].  

PubMed

We have analyzed the clinical course of 31 cases with cerebral infarction for 4 years. Of the 31 patients, 6 cases (19%) showed the brain edema on the cerebral angiograms as manifested by the shift of the midline arteries. The patients were divided into two groups, normotensive (15 cases) and hypertensive cerebral infarction (16 cases). The clinical and angiographic findings in the normotensive groups have been differed significantly from those of the hypertensive groups. The findings of brain edema on the angiograms were prominent in the hypertensive groups, and the clinical course was generally good and fair in the normotensive groups. We have reviewed the literatures about brain edema associated with cerebral infarction and have discussed on the mechanisms. From the study of our cases, it was concluded that systemic hypertension could be a facilitatory factor in the occurrence of brain edema in cerebral infarction. Furthermore, the management of massive cerebral infarction should be reduction of increased intracranial pressure and prevention of cerebral herniation. So, it will be necessary to perform a surgical treatment such as internal decompression; removal of the infarcted, necrotized area and excision of herniated tissue, and external decompression; removal of boneflap. PMID:944869

Kakita, K; Miyazaki, T; Kadowaki, H; Izawa, M; Kubota, S

1976-03-01

38

Therapeutic Potential of Human Umbilical Cord Derived Stem Cells in a Rat Myocardial Infarction Model  

Microsoft Academic Search

Background. Cell transplantation offers the promise in the restoration of cardiac function after myocardial in- farction. We investigate the therapeutic potential of hu- man umbilical cord derived stem (UCDS) cells in a rat myocardial infarction model. Methods. Two weeks after induction of myocardial infarction, the surviving rats with left ventricular ejec- tion fraction less than 60% were randomly divided into

Kai Hong Wu; Bin Zhou; Cun Tao Yu; Bin Cui; Shi Hong Lu; Zhong Chao Han; Ying Long Liu

2010-01-01

39

Specific Removal of C-Reactive Protein by Apheresis in a Porcine Cardiac Infarction Model  

Microsoft Academic Search

Background: C-reactive protein (CRP) is a possible causative factor of the destructive processes observed during the weeks after myocardial infarction. Methods: We developed a clinically relevant animal model including the removal of CRP from blood plasma utilizing a specific CRP adsorber and the visualization of the infarct scar in the living animal by cardiovascular magnetic resonance imaging as a tool

Anna Christine Slagman; Christopher Bock; Hassan Abdel-Aty; Birgit Vogt; Frank Gebauer; Gunnar Janelt; Franziska Wohlgemuth; Rene Morgenstern; Gülcan Yapici; Astrid Puppe; Diethelm Modersohn; Dörte Mans; Timo Jerichow; Sascha Ott; Rudolf Kunze; Wieland Schrödl; Christina Janko; Martin Hermann; Joachim R. Kalden; Peter Kern; Hans Parsch; Michael Kirschfink; Jeanette Schulz-Menger; Rainer Röttgen; Juliane K. Unger; Ulrich Frei; Ralf Schindler; Martin Möckel; Ahmed Sheriff

2011-01-01

40

Relationship of Ocular Microcirculation, Measured by Laser Speckle Flowgraphy, and Silent Brain Infarction in Primary Aldosteronism  

PubMed Central

Purpose Recent studies have shown that the risk of cerebro- and cardiovascular events (CVEs) is higher in patients with primary aldosteronism (PA) than in those with essential hypertension (EH), and that silent brain infarction (SBI) is a risk factor and predictor of CVEs. Here, we evaluated the relationship between findings from laser speckle flowgraphy (LSFG), a recently introduced non-invasive means of measuring mean blur rate (MBR), an important biomarker of ocular blood flow, and the occurrence of SBI in patients with PA. Methods 87 PA patients without symptomatic cerebral events (mean 55.1 ± 11.2 years old, 48 male and 39 female) were enrolled in this study. We measured MBR in the optic nerve head (ONH) with LSFG and checked the occurrence of SBI with magnetic resonance imaging. We examined three MBR waveform variables: skew, blowout score (BOS) and blowout time (BOT). We also recorded clinical findings, including age, blood pressure, and plasma aldosterone concentration. Results PA patients with SBI (15 of 87 patients; 17%) were significantly older and had significantly lower BOT in the capillary area of the ONH than the patients without SBI (P = 0.02 and P = 0.03, respectively). Multiple logistic regression analysis revealed that age and BOT were independent factors for the presence of SBI in PA patients (OR, 1.15, 95% CI 1.01–1.38; P = .03 and OR, 0.73, 95% CI 0.45–0.99; P = .04, respectively). Conclusion PA patients with SBI were older and had lower MBR BOT than those without SBI. Our analysis showed that age was a risk factor for SBI, and that BOT was a protective factor, in patients with PA. This suggests that BOT, a non-invasive and objective biomarker, may be a useful predictor of SBI and form part of future PA evaluations and clinical decision-making. PMID:25675373

Kunikata, Hiroshi; Aizawa, Naoko; Kudo, Masataka; Mugikura, Shunji; Nitta, Fumihiko; Morimoto, Ryo; Iwakura, Yoshitsugu; Ono, Yoshikiyo; Satoh, Fumitoshi; Takahashi, Hidetoshi; Ito, Sadayoshi; Takahashi, Shoki; Nakazawa, Toru

2015-01-01

41

'Iatrogenic' brain stem infarction. A complication of x-ray examination of the cervical spine and following posterior tamponation of the nose.  

PubMed

Two patients sustained an ischemic brain stem infarction during medical examination and treatment. The first patient lost consciousness and the spontaneous respiration ceased during X-ray examination of the cervical spine when the neck was hyperextended. After some minutes he regained conciousness but was found to be tetraplegic, and the patient deceased 4 months later. The angiogram revealed thrombosis of the basilar artery. The other patient had profuse nosebleed and was treated with posterior tamponation during which she sat for about 10 min with the neck hyperextended. Some hours after this procedure symptoms and signs of lateral caudal brain stem infarction emerged. PMID:1126348

Fogelholm, R; Karli, P

1975-01-01

42

Neuroprotective mechanisms of SMTP-7 in cerebral infarction model in mice.  

PubMed

Reactive oxygen species (ROS) formation has been found to induce the brain damage following stroke-like events. The aim of the present study was to investigate the effect of Stachybotrys microspora triprenyl phenol-7 (SMTP-7) on the generation of ROS in ischemia-induced cerebral infarction model and in vitro lipid peroxidation. We used immunohistochemistry and real-time reverse-transcription PCR for ex vivo evaluation and thiobarbituric acid-reactive substance reagent assay for in vitro evaluation. We demonstrated that SMTP-7 did not induce enhancement of 4-hydroxynonenal or neutrophil cytosolic factor 2 like t-PA administration at 3 h after ischemia ex vivo and reduce lipid peroxidation in vitro. This compound is the first low molecular weight compound with triplet activities of thrombolytic, anti-inflammatory, and antioxidant activities. We theorized that SMTP-7 is among the pharmacological agents that reduce ROS formation and have been found to limit the extent of brain damage following stroke-like events. PMID:21533990

Shibata, Keita; Hashimoto, Terumasa; Nobe, Koji; Hasumi, Keiji; Honda, Kazuo

2011-07-01

43

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model  

E-print Network

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may

44

Bone marrow-derived cells are the major source of MMP-9 contributing to blood-brain barrier dysfunction and infarct formation after ischemic stroke in mice  

PubMed Central

Matrix metalloproteinase (MMP)-9 has been shown to contribute to blood-brain barrier (BBB) disruption, infarct formation, and hemorrhagic transformation after ischemic stroke. The cellular source of MMP-9 detectable in the ischemic brain remains controversial since extracellular molecules in the brain may be derived from blood. We here demonstrate that bone marrow-derived cells are the major source of MMP-9 in the ischemic brain. We made bone marrow chimeric mice with MMP-9 null and wild-type as donor and recipient. After 90 min of transient focal cerebral ischemia, MMP-9 null mice receiving wild-type bone marrow showed comparable outcomes to wild-type in brain MMP-9 levels and BBB disruption (endogenous albumin extravasation) at 1 h post-reperfusion and infarct size at 24 h post-reperfusion. In contrast, wild-type animals replaced with MMP-9 null bone marrow showed barely detectable levels of MMP-9 in the ischemic brain, with attenuations in BBB disruption and infarct size. MMP-9 null mice receiving wild-type bone marrow showed enhanced Evans blue extravasation as early as 1 h post-reperfusion compared to wild-type mice replaced with MMP-9 null bone marrow. These findings suggest that MMP-9 released from bone marrow-derived cells influences the progression of BBB disruption in the ischemic brain. PMID:19646426

Wang, Guangming; Guo, Qingmin; Hossain, Mohammed; Fazio, Vince; Zeynalov, Emil; Janigro, Damir; Mayberg, Marc R.; Namura, Shobu

2009-01-01

45

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  

Microsoft Academic Search

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

T. Nomura; O. Honmou; K. Harada; K. Houkin; H. Hamada; J. D. Kocsis

2005-01-01

46

Therapeutic Effects of Human Multilineage-Differentiating Stress Enduring (MUSE) Cell Transplantation into Infarct Brain of Mice  

PubMed Central

Objective Bone marrow stromal cells (BMSCs) are heterogeneous and their therapeutic effect is pleiotropic. Multilineage-differentiating stress enduring (Muse) cells are recently identified to comprise several percentages of BMSCs, being able to differentiate into triploblastic lineages including neuronal cells and act as tissue repair cells. This study was aimed to clarify how Muse and non-Muse cells in BMSCs contribute to functional recovery after ischemic stroke. Methods Human BMSCs were separated into stage specific embryonic antigen-3-positive Muse cells and -negative non-Muse cells. Immunodeficient mice were subjected to permanent middle cerebral artery occlusion and received transplantation of vehicle, Muse, non-Muse or BMSCs (2.5×104 cells) into the ipsilateral striatum 7 days later. Results Motor function recovery in BMSC and non-Muse groups became apparent at 21 days after transplantation, but reached the plateau thereafter. In Muse group, functional recovery was not observed for up to 28 days post-transplantation, but became apparent at 35 days post-transplantation. On immunohistochemistry, only Muse cells were integrated into peri-infarct cortex and differentiate into Tuj-1- and NeuN-expressing cells, while negligible number of BMSCs and non-Muse cells remained in the peri-infarct area at 42 days post-transplantation. Conclusions These findings strongly suggest that Muse cells and non-Muse cells may contribute differently to tissue regeneration and functional recovery. Muse cells may be more responsible for replacement of the lost neurons through their integration into the peri-infarct cortex and spontaneous differentiation into neuronal marker-positive cells. Non-Muse cells do not remain in the host brain and may exhibit trophic effects rather than cell replacement. PMID:25747577

Yamauchi, Tomohiro; Kuroda, Yasumasa; Morita, Takahiro; Shichinohe, Hideo; Houkin, Kiyohiro; Dezawa, Mari; Kuroda, Satoshi

2015-01-01

47

Tachycardia in post-infarction hearts: insights from 3D image-based ventricular models.  

PubMed

Ventricular tachycardia, a life-threatening regular and repetitive fast heart rhythm, frequently occurs in the setting of myocardial infarction. Recently, the peri-infarct zones surrounding the necrotic scar (termed gray zones) have been shown to correlate with ventricular tachycardia inducibility. However, it remains unknown how the latter is determined by gray zone distribution and size. The goal of this study is to examine how tachycardia circuits are maintained in the infarcted heart and to explore the relationship between the tachycardia organizing centers and the infarct gray zone size and degree of heterogeneity. To achieve the goals of the study, we employ a sophisticated high-resolution electrophysiological model of the infarcted canine ventricles reconstructed from imaging data, representing both scar and gray zone. The baseline canine ventricular model was also used to generate additional ventricular models with different gray zone sizes, as well as models in which the gray zone was represented as different heterogeneous combinations of viable tissue and necrotic scar. The results of the tachycardia induction simulations with a number of high-resolution canine ventricular models (22 altogether) demonstrated that the gray zone was the critical factor resulting in arrhythmia induction and maintenance. In all models with inducible arrhythmia, the scroll-wave filaments were contained entirely within the gray zone, regardless of its size or the level of heterogeneity of its composition. The gray zone was thus found to be the arrhythmogenic substrate that promoted wavebreak and reentry formation. We found that the scroll-wave filament locations were insensitive to the structural composition of the gray zone and were determined predominantly by the gray zone morphology and size. The findings of this study have important implications for the advancement of improved criteria for stratifying arrhythmia risk in post-infarction patients and for the development of new approaches for determining the ablation targets of infarct-related tachycardia. PMID:23844245

Arevalo, Hermenegild; Plank, Gernot; Helm, Patrick; Halperin, Henry; Trayanova, Natalia

2013-01-01

48

P2X7 receptor modulation on microglial cells and reduction of brain infarct caused by middle cerebral artery occlusion in rat.  

PubMed

Adenosine 5'-triphosphate outflow increases after an ischemic insult in the brain and may induce the expression of P2X7 receptors in resting microglia, determining its modification into an activated state. To assess the effects of P2X7 receptor blockade in preventing microglia activation and ameliorating brain damage and neurological impairment, we delivered the P2 unselective antagonist Reactive Blue 2 to rats after middle cerebral artery occlusion. In sham-operated animals, devoid of brain damage, double immunofluorescence verified the absence of P2X7 immunoreactivity on resting microglia, astrocytes, and neurons, identified, respectively, by OX-42, glial fibrillary acid protein, and neuronal nuclei (NeuN) immunoreactivity. After ischemia, vehicle-treated rats showed monolateral sensorimotor deficit and tissue damage in striatum and frontoparietal cortex. Moreover, P2X7 immunoreactivity was de novo expressed on activated microglia in infarcted and surrounding areas, as well as on a reactive form of microglia, resting in shape but P2X7 immunoreactive, present in ipsi- and contralateral cingulate and medial frontal cortex. Reactive Blue 2 improved sensorimotor deficit and restricted the volume of infarction, without preventing the expression of P2X7, but inducing it in the microglia of contralateral frontal and parietal cortex and striatum, which had lost reciprocal connections with the remote infarct area. De novo expression of P2X7 occurred in both activated and reactive microglia, suggesting their differentiated roles in the area of infarct and in remote regions. Reactive Blue 2 reduced ischemic brain damage, likely blocking the function of activated microglia in the infarct area, but in the remote brain regions promoted the expression of P2X7 on reactive microglia, developing defense and reparative processes. PMID:16395292

Melani, Alessia; Amadio, Susanna; Gianfriddo, Marco; Vannucchi, Maria G; Volontè, Cinzia; Bernardi, Giorgio; Pedata, Felicita; Sancesario, Giuseppe

2006-07-01

49

Delayed Brain Infarction due to Bilateral Vertebral Artery Occlusion Which Occurred 5 Days after Cervical Trauma  

PubMed Central

Vertebral artery (VA) injuries usually accompany cervical trauma. Although these injuries are commonly asymptomatic, some result in vertebrobasilar infarction. The symptoms of VA occlusion have been reported to usually manifest within 24 hours after trauma. The symptoms of bilateral VA occlusions seem to be more severe and seem to occur with shorter latencies than those of unilateral occlusions. A 48-year-old man had a C3-4 fracture-dislocation with spinal cord compression that resulted from a traffic accident. After surgery, his initial quadriparesis gradually improved. However, he complained of sudden headache and dizziness on the 5th postoperative day. His motor weakness was abruptly aggravated. Radiologic evaluation revealed an infarction in the occipital lobe and cerebellum. Cerebral angiography revealed complete bilateral VA occlusion. We administered anticoagulation therapy. After 6 months, his weakness had only partially improved. This case demonstrates that delayed infarction due to bilateral VA occlusion can occur at latencies as long as 5 days. Thus, we recommend that patients with cervical traumas that may be accompanied by bilateral VA occlusion should be closely observed for longer than 5 days. PMID:25328652

Jang, Donghwan; Kim, Choonghyo; Lee, Seung Jin

2014-01-01

50

The KCa3.1 blocker TRAM-34 reduces infarction and neurological deficit in a rat model of ischemia/reperfusion stroke  

PubMed Central

Microglia and brain infiltrating macrophages significantly contribute to the secondary inflammatory damage in the wake of ischemic stroke. Here, we investigated whether inhibition of KCa3.1 (IKCa1/KCNN4), a calcium-activated K+ channel that is involved in microglia and macrophage activation and expression of which increases on microglia in the infarcted area, has beneficial effects in a rat model of ischemic stroke. Using an HPLC/MS assay, we first confirmed that our small molecule KCa3.1 blocker TRAM-34 effectively penetrates into the brain and achieves micromolar plasma and brain concentrations after intraperitoneal injection. Then, we subjected male Wistar rats to 90?minutes of middle cerebral artery occlusion (MCAO) and administered either vehicle or TRAM-34 (10 or 40?mg/kg intraperitoneally twice daily) for 7 days starting 12?hours after reperfusion. Both compound doses reduced infarct area by ?50% as determined by hematoxylin & eosin staining on day 7 and the higher dose also significantly improved neurological deficit. We further observed a significant reduction in ED1+-activated microglia and TUNEL-positive neurons as well as increases in NeuN+ neurons in the infarcted hemisphere. Our findings suggest that KCa3.1 blockade constitutes an attractive approach for the treatment of ischemic stroke because it is still effective when initiated 12?hours after the insult. PMID:21750563

Chen, Yi-Je; Raman, Girija; Bodendiek, Silke; O'Donnell, Martha E; Wulff, Heike

2011-01-01

51

Surfactant reduction of cerebral infarct size and behavioral deficit in a rat model of cerebrovascular arterial gas embolism  

PubMed Central

Gas embolism occurs commonly in cardiac and vascular surgery and decompression sickness. The goals of this study were to develop a new in vivo rat model of cerebrovascular arterial gas embolism and to determine the effects of exogenous surfactants on resultant brain infarct volume and accompanying long-term neurological dysfunction using the model. Unilateral cerebral arterial gas embolism was induced in Sprague Dawley rats, including groups receiving intravenous Pluronic F-127 (PF-127) and Oxycyte perflourocarbon surfactant pretreatment. Magnetic resonance imaging (MRI) was performed at 24 and 72 h postembolism to determine infarct volume. The elevated body swing test (EBST), limb-placement test, proprioception forelimb and hindlimb tests, whisker tactile test, and Morris Water Maze test were performed to assess motor behavior, somatosensory deficit, and spatial cognitive function out to 29 days after embolization. A stable stroke model was developed with MRI examination revealing infarction in the ipsilateral cerebral hemisphere. Gas embolized rats had significant cognitive and sensorimotor dysfunction, including approximately threefold increase in Morris Water Maze latency time, ?20% left-sided biasing in EBST performance, 0.5 to 1.5 (mean) point score elevations in the proprioception and whisker tactile tests, and 3.0 point (mean) elevation in the limb-placement test, all of which were persistent throughout the postembolic period. Surfactant prophylaxis with either PF-127 or Oxycyte rendered stroke undetectable by MRI scanning and markedly reduced the postembolic deficits in both cognitive and sensorimotor performance in treated rats, with normalization of EBST and whisker tactile tests within 7 days. PMID:23845977

Armstead, Stephen C.

2013-01-01

52

Comparison of two preclinical myocardial infarct models: coronary coil deployment versus surgical ligation  

PubMed Central

Background Despite recent advances, myocardial infarction (MI) remains the leading cause of death worldwide. Pre-clinical animal models that closely mimic human MI are pivotal for a quick translation of research and swine have similarities in anatomy and physiology. Here, we compared coronary surgical ligation versus coil embolization MI models in swine. Methods Fifteen animals were randomly distributed to undergo surgical ligation (n?=?7) or coil embolization (n?=?8). We evaluated infarct size, scar fibrosis, inflammation, myocardial vascularization, and cardiac function by magnetic resonance imaging (MRI). Results Thirty-five days after MI, there were no differences between the models in infarct size (P?=?0.53), left ventricular (LV) ejection fraction (P?=?0.19), LV end systolic volume (P?=?0.22), LV end diastolic volume (P?=?0.84), and cardiac output (P?=?0.89). Histologically, cardiac scars did not differ and the collagen content, collagen type I (I), collagen type III (III), and the I/III ratio were similar in both groups. Inflammation was assessed using specific anti-CD3 and anti-CD25 antibodies. There was similar activation of inflammation throughout the heart after coil embolization (P?=?0.78); while, there were more activated lymphocytes in the infarcted myocardium in the surgical occlusion model (P?=?0.02). Less myocardial vascularization in the infarction areas compared with the border and remote zones only in coil embolization animals was observed (P?=?0.004 and P?=?0.014, respectively). Conclusions Our results support that surgical occlusion and coil embolization MI models generate similar infarct size, cardiac function impairment, and myocardial fibrosis; although, inflammation and myocardial vascularization levels were closer to those found in humans when coil embolization was performed. PMID:24885652

2014-01-01

53

Validation of a biomechanical heart model using animal data with acute myocardial infarction  

E-print Network

Experimental data The experimental data consisted of animal data obtained with a farm pig of 25kg. The inValidation of a biomechanical heart model using animal data with acute myocardial infarction R Hospital, Cr´eteil, France Abstract. In this paper, we validate a biomechanical heart model with animal

Paris-Sud XI, Université de

54

A Nonthoracotomy Myocardial Infarction Model in an Ovine Using Autologous Platelets  

PubMed Central

Objective. There is a paucity of a biological large animal model of myocardial infarction (MI). We hypothesized that, using autologous-aggregated platelets, we could create an ovine model that was reproducible and more closely mimicked the pathophysiology of MI. Methods. Mepacrine stained autologous platelets from male sheep (n = 7) were used to create a myocardial infarction via catheter injection into the mid-left anterior descending (LAD) coronary artery. Serial daily serum troponin measurements were taken and tissue harvested on post-embolization day three. Immunofluorescence microscopy was used to detect the mepacrine-stained platelet-induced thrombus, and histology performed to identify three distinct myocardial (infarct, peri-ischemic “border zone,” and remote) zones. Results. Serial serum troponin levels (?g/mL) measured 0.0 ± 0.0 at baseline and peaked at 297.4 ± 58.0 on post-embolization day 1, followed by 153.0 ± 38.8 on day 2 and 76.7 ± 19.8 on day 3. Staining confirmed distinct myocardial regions of inflammation and fibrosis as well as mepacrine-stained platelets as the cause of intravascular thrombosis. Conclusion. We report a reproducible, unique model of a biological myocardial infarction in a large animal model. This technique can be used to study acute, regional myocardial changes following a thrombotic injury. PMID:24367790

Spata, Tyler; Bobek, Daniel; Whitson, Bryan A.; Parthasarathy, Sampath; Mohler, Peter J.; Higgins, Robert S. D.; Kilic, Ahmet

2013-01-01

55

Plasma N-Terminal Pro-Brain Natriuretic Peptide and Adrenomedullin New Neurohormonal Predictors of Left Ventricular Function and Prognosis After Myocardial Infarction  

Microsoft Academic Search

Background—Newly discovered circulating peptides, N-terminal pro- brain natriuretic peptide (N-BNP) and ad- renomedullin (ADM), were examined for prediction of cardiac function and prognosis and compared with previously reported markers in 121 patients with myocardial infarction. Methods and Results—The association between radionuclide left ventricular ejection fraction (LVEF) and N-BNP at 2 to 4 days (r52.63, P,.0001) and 3 to 5 months

A. Mark Richards; M. Gary Nicholls; Tim G. Yandle; Chris Frampton; Eric A. Espiner; John G. Turner; Rona C. Buttimore; John G. Lainchbury; John M. Elliott; Hamid Ikram; Ian G. Crozier; David W. Smyth

56

Sulfonylurea receptor 1 expression in human cerebral infarcts.  

PubMed

In animal models of stroke, sulfonylurea receptor 1 (Sur1), a member of the adenosine triphosphate binding cassette transporter gene family, is transcriptionally upregulated in neural and vascular cells in which it plays a leading role in edema formation and necrotic cell death. To date, expression of Sur1 in the brains of humans with cerebral infarcts has not been systematically evaluated. We examined Sur1 expression in postmortem specimens obtained from 13 patients within the first 31 days after focal infarcts, 5 patients with lacunar infarcts, and 6 normal control brains using immunohistochemistry. Elevated immunoreactivity for Sur1 was detected in all cases of focal infarcts, with 3 distinct temporal patterns of expression: 1) neurons and endothelium showed the greatest elevation during the first week, after which levels declined; 2) astrocytes and microglia/macrophages showed progressive increases during the first 31 days; and 3) neutrophils near the infarct showed prominent immunoreactivity that did not change over time. Upregulation of Sur1 was corroborated using in situ hybridization for Abcc8 mRNA. Sulfonylurea receptor 1 immunoreactivity in lacunar infarcts was less prominent and more sporadic than in nonlacunar infarcts. In conjunction with previous studies, these data suggest that Sur1 may be a promising treatment target in patients with acute cerebral infarction. PMID:23965746

Mehta, Rupal I; Ivanova, Svetlana; Tosun, Cigdem; Castellani, Rudy J; Gerzanich, Volodymyr; Simard, J Marc

2013-09-01

57

Neuronal Ca2+Activated K+ Channels Limit Brain Infarction and Promote Survival  

Microsoft Academic Search

Neuronal calcium-activated potassium channels of the BK type are activated by membrane depolarization and intracellular Ca2+ ions. It has been suggested that these channels may play a key neuroprotective role during and after brain ischemia, but this hypothesis has so far not been tested by selective BK-channel manipulations in vivo. To elucidate the in vivo contribution of neuronal BK channels

Yiliu Liao; Ase-Marit Kristiansen; Cecilie P. Oksvold; Frode A. Tuvnes; Ning Gu; Elise Rundén-Pran; Peter Ruth; Matthias Sausbier; Johan F. Storm; Mark P. Mattson

2010-01-01

58

Delayed progesterone treatment reduces brain infarction and improves functional outcomes after ischemic stroke: a time-window study in middle-aged rats.  

PubMed

We evaluated the neuroprotective effects of delayed progesterone (PROG) treatment against ischemic stroke-induced neuronal death, inflammation, and functional deficits. We induced transient focal cerebral ischemia in male rats and administered PROG (8?mg/kg) or vehicle intraperitoneally at 3, 6, or 24?hours post occlusion, subcutaneously 5?hours later and then every 24?hours for 7 days. Behavioral outcomes were evaluated over 22 days. Infarct size and other biomarkers of injury were evaluated by cresyl violet staining, and matrix metalloproteinase-9 (MMP-9), glial fibrillary acidic protein (GFAP), and vascular endothelial growth factor (VEGF) by immunofluorescence. Progesterone treatment started at 3 and 6?hours post occlusion significantly (P<0.05) improved behavioral performance at all time points (74.01%) and reduced infarction volume (61.68%) compared with vehicle. No significant difference was observed between the 3 and 6?hour PROG treatment groups. Matrix metalloproteinase-9 and VEGF were upregulated in the PROG groups compared with vehicle. Glial fibrillary acidic protein expression was increased in the vehicle group but markedly lower in the PROG groups. Treatment delayed for 24?hours did not significantly improve functional outcomes or reduce infarction volume. We conclude that, under the right treatment conditions, PROG treatment delayed up to 6?hours can improve functional deficits and reduce brain infarction, possibly by modulating GFAP, VEGF, and MMP-9 expression. PMID:24301297

Yousuf, Seema; Sayeed, Iqbal; Atif, Fahim; Tang, Huiling; Wang, Jun; Stein, Donald G

2014-02-01

59

Brain Graphs: Graphical Models of the Human Brain Connectome  

Microsoft Academic Search

Brain graphs provide a relatively simple and increasingly popular way of modeling the human brain connectome, using graph theory to abstractly define a nervous system as a set of nodes (denoting anatomical regions or recording electrodes) and interconnecting edges (denoting structural or functional connections). Topological and geometrical properties of these graphs can be measured and compared to random graphs and

Edward T. Bullmore; Danielle S. Bassett

2011-01-01

60

Brain Graphs: Graphical Models of the Human Brain Connectome  

Microsoft Academic Search

Brain graphs provide a relatively simple and increasingly popular way of modeling the human brain connectome, using graph theory to abstractly define a nervous system as a set of nodes (denoting anatomical regions or recording electrodes) and interconnecting edges (denoting structural or functional connections). Topological and geometrical properties of these graphs can be measured and compared to random graphs and

Edward T. Bullmore; Danielle S. Bassett

61

Plasticity of Adult Sensorimotor System in Severe Brain Infarcts: Challenges and Opportunities  

PubMed Central

Functional reorganization forms the critical mechanism for the recovery of function after brain damage. These processes are driven by inherent changes within the central nervous system (CNS) triggered by the insult and further depend on the neural input the recovering system is processing. Therefore these processes interact with not only the interventions a patient receives, but also the activities and behaviors a patient engages in. In recent years, a wide range of research programs has addressed the association between functional reorganization and the spontaneous and treatment-induced recovery. The bulk of this work has focused on upper-limb and hand function, and today there are new treatments available that capitalize on the neuroplasticity of the brain. However, this is only true for patients with mild to moderated impairments; for those with very limited hand function, the basic understanding is much poorer and directly translates into limited treatment opportunities for these patients. The present paper aims to highlight the knowledge gap on severe stroke with a brief summary of the literature followed by a discussion of the challenges involved in the study and treatment of severe stroke and poor long-term outcome. PMID:22548196

Sterr, Annette; Conforto, Adriana Bastos

2012-01-01

62

Apolipoprotein A1 regulates coenzyme Q10 absorption, mitochondrial function, and infarct size in a mouse model of myocardial infarction.  

PubMed

HDL and apolipoprotein A1 (apoA1) concentrations inversely correlate with risk of death from ischemic heart disease; however, the role of apoA1 in the myocardial response to ischemia has not been well defined. To test whether apoA1, the primary HDL apolipoprotein, has an acute anti-inflammatory role in ischemic heart disease, we induced myocardial infarction via direct left anterior descending coronary artery ligation in apoA1 null (apoA1(-/-)) and apoA1 heterozygous (apoA1(+/-)) mice. We observed that apoA1(+/-) and apoA1(-/-) mice had a 52% and 125% increase in infarct size as a percentage of area at risk, respectively, compared with wild-type (WT) C57BL/6 mice. Mitochondrial oxidation contributes to tissue damage in ischemia-reperfusion injury. A substantial defect was present at baseline in the electron transport chain of cardiac myocytes from apoA1(-/-) mice localized to the coenzyme Q (CoQ) pool with impaired electron transfer (67% decrease) from complex II to complex III. Administration of coenzyme Q10 (CoQ10) to apoA1 null mice normalized the cardiac mitochondrial CoQ pool and reduced infarct size to that observed in WT mice. CoQ10 administration did not significantly alter infarct size in WT mice. These data identify CoQ pool content leading to impaired mitochondrial function as major contributors to infarct size in the setting of low HDL/apoA1. These data suggest a previously unappreciated mechanism for myocardial stunning, cardiac dysfunction, and muscle pain associated with low HDL and low apoA1 concentrations that can be corrected by CoQ10 supplementation and suggest populations of patients that may benefit particularly from CoQ10 supplementation. PMID:24759932

Dadabayev, Alisher R; Yin, Guotian; Latchoumycandane, Calivarathan; McIntyre, Thomas M; Lesnefsky, Edward J; Penn, Marc S

2014-07-01

63

Hierarchical models in the brain.  

PubMed

This paper describes a general model that subsumes many parametric models for continuous data. The model comprises hidden layers of state-space or dynamic causal models, arranged so that the output of one provides input to another. The ensuing hierarchy furnishes a model for many types of data, of arbitrary complexity. Special cases range from the general linear model for static data to generalised convolution models, with system noise, for nonlinear time-series analysis. Crucially, all of these models can be inverted using exactly the same scheme, namely, dynamic expectation maximization. This means that a single model and optimisation scheme can be used to invert a wide range of models. We present the model and a brief review of its inversion to disclose the relationships among, apparently, diverse generative models of empirical data. We then show that this inversion can be formulated as a simple neural network and may provide a useful metaphor for inference and learning in the brain. PMID:18989391

Friston, Karl

2008-11-01

64

Cardiac Motion Analysis Using High-Speed Video Images in a Rat Model for Myocardial Infarction  

NASA Astrophysics Data System (ADS)

In this study, we performed a cardiac motion analysis by using 1000-frames per second (fps) stereo images to capture the three-dimensional motion of small color markers in a rat heart. This method of recording cardiac motion could quantify the rate of change in the myocardial area, which indicated localized myocardial activity of rhythmic expansion and contraction. We analyzed the three-dimensional motion distributions in a rat model for myocardial infarction, in which the heart rate was 4 times/s or more. In the analysis, we spatiotemporally quantified the characteristic cardiac motion in ischemic heart diseases and found that infarction due to ischemia in the rat heart was spread around the left ventricle.

Ishii, Idaku; Okuda, Toshikazu; Nie, Yuman; Takaki, Takeshi; Orito, Kensuke; Tanaka, Akane; Matsuda, Hiroshi

65

Rosuvastatin prevents myocardial necrosis in an experimental model of acute myocardial infarction.  

PubMed

Dyslipidemia is related to the progression of atherosclerosis and is an important risk factor for acute coronary syndromes. Our objective was to determine the effect of rosuvastatin on myocardial necrosis in an experimental model of acute myocardial infarction (AMI). Male Wistar rats (8-10 weeks old, 250-350 g) were subjected to definitive occlusion of the left anterior descending coronary artery to cause AMI. Animals were divided into 6 groups of 8 to 11 rats per group: G1, normocholesterolemic diet; G2, normocholesterolemic diet and rosuvastatin (1 mg·kg(-1)·day-1) 30 days after AMI; G3, normocholesterolemic diet and rosuvastatin (1 mg·kg(-1)·day-1) 30 days before and after AMI; G4, hypercholesterolemic diet; G5, hypercholesterolemic diet and rosuvastatin (1 mg·kg(-1)·day-1) 30 days after AMI; G6, hypercholesterolemic diet and rosuvastatin (1 mg·kg(-1)·day-1) 30 days before and after AMI. Left ventricular function was determined by echocardiography and percent infarct area by histology. Fractional shortening of the left ventricle was normal at baseline and decreased significantly after AMI (P < 0.05 in all groups), being lower in G4 and G5 than in the other groups. No significant difference in fractional shortening was observed between G6 and the groups on the normocholesterolemic diet. Percent infarct area was significantly higher in G4 than in G3. No significant differences were observed in infarct area among the other groups. We conclude that a hypercholesterolemic diet resulted in reduced cardiac function after AMI, which was reversed with rosuvastatin when started 30 days before AMI. A normocholesterolemic diet associated with rosuvastatin before and after AMI prevented myocardial necrosis when compared with the hypercholesterolemic condition. PMID:21445530

Dourado, P M M; Tsutsui, J M; Landim, M B P; Casella Filho, A; Galvao, T F G; Aiello, V D; Mathias, W; da Luz, P L; Chagas, A C P

2011-05-01

66

Intraperitoneal bilirubin administration decreases infarct area in a rat coronary ischemia/reperfusion model  

PubMed Central

Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a mounting body of evidence suggests that at physiological doses, bilirubin is a powerful antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings with genetically-induced hyperbilirubinemia (Gilbert Syndrome) are protected against coronary heart disease. The purpose of this study was to investigate whether administration of exogenous bilirubin to normal rats would convey similar protective effects in an experimental model of coronary ischemia. We hypothesized that intraperitoneal bilirubin administration 1 h before injury would decrease infarct area and preserve left ventricular (LV) systolic function when compared to non-treated rats. Coronary ischemia was induced by temporary (30 min) ligation of the left anterior descending coronary artery in control or bilirubin treated rats, followed by a 1-h period of reperfusion. LV function was estimated by measurements of fractional shortening (FS) and fractional area shortening using echocardiography. LV function decreased in both experimental groups after ischemia and reperfusion, although in bilirubin-treated rats FS was less depressed during the period of ischemia (18.8 vs. 25.8%, p = 0.034). Infarct size was significantly reduced in the bilirubin treated group compared to the non-treated group (13.34 vs. 25.5%, p = 0.0067). Based on the results of this study, bilirubin supplementation appears to provide significant decrease in infarct size although protective effects on LV function were noted only during the period of ischemia. This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia. PMID:24600401

Ben-Amotz, Ron; Bonagura, John; Velayutham, Murugesan; Hamlin, Robert; Burns, Patrick; Adin, Christopher

2014-01-01

67

Transient Body Fluid Accumulation and Enhanced NKCC2 Expression in Gerbils with Brain Infarction  

Microsoft Academic Search

Background: Enhanced expression of a kidney-specific sodium co-transporter (NKCC2: Na-K-2Cl co-transporter) in the thick ascending limb of Henle has been identified in rat models of congestive heart failure and liver cirrhosis, suggesting that high NKCC2 expression underlies edema formation. An increased abundance of NKCC2, however, has also been noted in rats with the syndrome of inappropriate secretion of antidiuretic hormone;

Yutaka Ejima; Yohsuke Nakamura; Mari Michimata; Ryo Hatano; Itsuro Kazama; Satoru Sanada; Tomohiro Arata; Michiko Suzuki; Noriyuki Miyama; Akira Sato; Susumu Satomi; Shinji Fushiya; Sei Sasaki; Mitsunobu Matsubara

2006-01-01

68

Nitrates in myocardial infarction  

Microsoft Academic Search

Until two decades ago nitroglycerin was contraindicated in acute myocardial infarction (MI). Studies in the canine model demonstrated that low-dose intravenous (IV) infusion, carefully titrated to decrease mean blood pressure by 10% but not below 80 mmHg, during early stages of acute MI produced marked reduction of left ventricular (LV) preload, improvement in regional perfusion, and limitation of infarct size

Bodh I. Jugdutt

1994-01-01

69

Splenic infarction  

MedlinePLUS

Splenic infarction is the death of tissue ( necrosis ) in the spleen due to a blockage in blood flow. ... Common causes of splenic infarction include: Blood clots Blood diseases such as sickle cell anemia Infections such as endocarditis

70

Mean hemoglobin concentration after acute subarachnoid hemorrhage and the relation to outcome, mortality, vasospasm, and brain infarction.  

PubMed

Lower mean hemoglobin (HGB) levels are associated with unfavorable outcome after spontaneous subarachnoid hemorrhage (SAH). Currently, there is no cutoff level for mean HGB levels associated with unfavorable outcome. This study was conducted to evaluate a threshold for mean HGB concentrations after SAH, and to observe the relation to outcome. The medical records of 702 patients with spontaneous SAH were reviewed. Predictors of outcome were proved by univariate analysis. Predictors with p<0.1 were included in a multivariate binary logistic regression model. Cutoff points for mean HGB levels were calculated by receiver operating characteristic curve analysis. Mean HGB was 11.9g/dl (±standard deviation [SD] 1.7g/dl) in patients with favorable outcome compared to 10.8g/dl (±SD 1.1g/dl) in patients with unfavorable outcome (p<0.001). The highest Youden's index value was found for a HGB cutoff at 11.1g/dl. In a binary logistic regression model, predictors of unfavorable outcome were identified as an initially high Hunt-Hess grade (odds ratio [OR]: 7.7; 95% confidence interval [CI]: 4.4-13.4; p<0.001), cerebral infarction on a CT scan during hospital stay (OR: 3.8; 95% CI: 2.0-7.3; p<0.001), rebleeding during the hospital stay (OR: 3.5; 95% CI: 1.6-8.0; p=0.002), mean HGB concentration <11.1g/dl (OR: 3.3; 95% CI: 2.0-5.3; p<0.001), and hydrocephalus (OR: 2.3; 95% CI: 1.4-3.7; p=0.001). In conclusion, a mean HGB concentration <11.1g/dl during the hospital stay was associated with unfavorable outcome after acute SAH. PMID:25533213

Stein, Marco; Brokmeier, Lisa; Herrmann, Johannes; Scharbrodt, Wolfram; Schreiber, Vanessa; Bender, Michael; Oertel, Matthias F

2015-03-01

71

Experimental model of transthoracic, vascular-targeted, photodynamically induced myocardial infarction  

PubMed Central

We describe a novel model of myocardial infarction (MI) in rats induced by percutaneous transthoracic low-energy laser-targeted photodynamic irradiation. The procedure does not require thoracotomy and represents a minimally invasive alternative to existing surgical models. Target cardiac area to be photodynamically irradiated was triangulated from the thoracic X-ray scans. The acute phase of MI was histopathologically characterized by the presence of extensive vascular occlusion, hemorrhage, loss of transversal striations, neutrophilic infiltration, and necrotic changes of cardiomyocytes. Consequently, damaged myocardium was replaced with fibrovascular and granulation tissue. The fibrotic scar in the infarcted area was detected by computer tomography imaging. Cardiac troponin I (cTnI), a specific marker of myocardial injury, was significantly elevated at 6 h (41 ± 6 ng/ml, n = 4, P < 0.05 vs. baseline) and returned to baseline after 72 h. Triphenyltetrazolium chloride staining revealed transmural anterolateral infarcts targeting 25 ± 3% of the left ventricle at day 1 with a decrease to 20 ± 3% at day 40 (n = 6 for each group, P < 0.01 vs. day 1). Electrocardiography (ECG) showed significant ST-segment elevation in the acute phase with subsequent development of a pathological Q wave and premature ventricular contractions in the chronic phase of MI. Vectorcardiogram analysis of spatiotemporal electrical signal transduction revealed changes in inscription direction, QRS loop morphology, and redistribution in quadrant areas. The photodynamically induced MI in n = 51 rats was associated with 12% total mortality. Histological findings, ECG abnormalities, and elevated cTnI levels confirmed the photosensitizer-dependent induction of MI after laser irradiation. This novel rodent model of MI might provide a platform to evaluate new diagnostic or therapeutic interventions. PMID:24213611

Pokreisz, Peter; Schnitzer, Jan E.

2013-01-01

72

Magnetic targeting enhances retrograde cell retention in a rat model of myocardial infarction  

PubMed Central

Introduction Retrograde coronary venous infusion is a promising delivery method for cellular cardiomyoplasty. Poor cell retention is the major obstacle to the establishment of this method as the preferred route for cell delivery. Here, we explored whether magnetic targeting could enhance retrograde cell retention in a rat model of myocardial infarction. Methods Rat mesenchymal stem cells were labeled with superparamagnetic oxide nanoparticles. The magnetic responsiveness of MSCs was observed while cells flowed through a tube that served as a model of blood vessels in a 0.6-Tesla magnetic field. In a Sprague–Dawley rat model of acute myocardial infarction, 1?×?106 magnetic mesenchymal stem cells were transjugularly injected into the left cardiac vein while a 0.6-Tesla magnet was placed above the heart. The cardiac retention of transplanted cells was assessed by using quantitative Y chromosome-specific polymerase chain reaction, cardiac magnetic resonance imaging, and optical imaging. Cardiac function was measured by using echocardiography, and histologic analyses of infarct morphology and angiogenesis were obtained. Results The flowing iron oxide-labeled mesenchymal stem cells were effectively attracted to the area where the magnet was positioned. Twenty-four hours after cellular retrocoronary delivery, magnetic targeting significantly increased the cardiac retention of transplanted cells by 2.73- to 2.87-fold. Histologic analyses showed that more transplanted cells were distributed in the anterior wall of the left ventricle. The enhanced cell engraftment persisted for at least 3 weeks, at which time, left ventricular remodeling was attenuated, and cardiac function benefit was improved. Conclusions These results suggest that magnetic targeting offers new perspectives for retrograde coronary venous delivery to enhance cell retention and subsequent functional benefit in heart diseases. PMID:24330751

2013-01-01

73

These authors contributed equally to this work Modeling Patient Response to Acute Myocardial Infarction: Implications for  

E-print Network

Patient Response to Acute Myocardial Infarction: Implications for a Tailored Technology-Based Program of decision-making in patients suffering from symptoms of acute myocardial infarction. In order to do so, we for two hours or more after symptom onset for acute myocardial infarction (AMI).1-4 This delay can

Cimino, James J.

74

Identification of Cardiac Infarctions from ECG-Measurements  

E-print Network

Identification of Cardiac Infarctions from ECG-Measurements DIPLOMARBEIT vorgelegt von Melanie.3 Ischemia and Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3 The Bidomain and Reparameterized FitzHugh-Nagumo Model . . . . . . . . . . . 9 3.4 Modeling Infarctions and the Complete Model

Münster, Westfälische Wilhelms-Universität

75

Original article Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction  

E-print Network

infarction model: Insight gained using metabolomic approaches Ning Li a , Jun-Yan Liu c , Valeriy Timofeyev inhibitors Myocardial infarction Epoxyeicosatrienoic acids Oxylipin profiling Myocardial infarction (MI

Hammock, Bruce D.

76

Fatal outcome after brain stem infarction related to bilateral vertebral artery occlusion - case report of a detrimental complication of cervical spine trauma  

PubMed Central

Background Vertebral artery injury (VAI) after blunt cervical trauma occurs more frequently than historically believed. The symptoms due to vertebral artery (VA) occlusion usually manifest within the first 24 hours after trauma. Misdiagnosed VAI or delay in diagnosis has been reported to cause acute deterioration of previously conscious and neurologically intact patients. Case presentation A 67 year-old male was involved in a motor vehicle crash (MVC) sustaining multiple injuries. Initial evaluation by the emergency medical response team revealed that he was alert, oriented, and neurologically intact. He was transferred to the local hospital where cervical spine computed tomography (CT) revealed several abnormalities. Distraction and subluxation was present at C5-C6 and a comminuted fracture of the left lateral mass of C6 with violation of the transverse foramen was noted. Unavailability of a spine specialist prompted the patient's transfer to an area medical center equipped with spine care capabilities. After arrival, the patient became unresponsive and neurological deficits were noted. His continued deterioration prompted yet another transfer to our Level 1 regional trauma center. A repeat cervical spine CT at our institution revealed significantly worsened subluxation at C5-C6. CT angiogram also revealed complete occlusion of bilateral VA. The following day, a repeat CT of the head revealed brain stem infarction due to bilateral VA occlusion. Shortly following, the patient was diagnosed with brain death and care was withdrawn. Conclusion Brain stem infarction secondary to bilateral VA occlusion following cervical spine trauma resulted in fatal outcome. Prompt imaging evaluation is necessary to assess for VAI in cervical trauma cases with facet joint subluxation/dislocation or transverse foramen fracture so that treatment is not delayed. Additionally, multiple transportation events are risk factors for worsening when unstable cervical injuries are present. Close attention to proper immobilization and neck position depending on the mechanism of injury is mandatory. PMID:21756312

2011-01-01

77

Sesamin attenuates neurotoxicity in mouse model of ischemic brain stroke.  

PubMed

Stroke is a severe neurological disorder characterized by the abrupt loss of blood circulation into the brain resulting into wide ranging brain and behavior abnormalities. The present study was designed to evaluate molecular mechanism by which sesamin (SES) induces neuroprotection in mouse model of ischemic stroke. The results of this study demonstrate that SES treatment (30 mg/kg bwt) significantly reduced infarction volume, lipid per-oxidation, cleaved-caspase-3 activation, and increased GSH activity following MCAO in adult male mouse. SES treatment also diminished iNOS and COX-2 protein expression, and significantly restored SOD activity and protein expression level in the ischemic cortex of the MCAO animals. Furthermore, SES treatment also significantly reduced inflammatory and oxidative stress markers including Iba1, Nox-2, Cox-2, peroxynitrite compared to placebo MCAO animals. Superoxide radical production, as studied by DHE staining method, was also significantly reduced in the ischemic cortex of SES treated compared to placebo MCAO animals. Likewise, downstream effects of superoxide free radicals i.e. MAPK/ERK and P38 activation was also significantly attenuated in SES treated compared to placebo MCAO animals. In conclusion, these results suggest that SES induces significant neuroprotection, by ameliorating many signaling pathways activated/deactivated following cerebral ischemia in adult mouse. PMID:25316624

Ahmad, Saif; Elsherbiny, Nehal M; Haque, Rizwanul; Khan, M Badruzzaman; Ishrat, Tauheed; Shah, Zahoor A; Khan, Mohammad M; Ali, Mehboob; Jamal, Arshad; Katare, Deepshikha Pande; Liou, Gregory I; Bhatia, Kanchan

2014-12-01

78

Reduced Brain Edema and Infarction Volume in Mice Lacking the Neuronal Isoform of Nitric Oxide Synthase After Transient MCA Occlusion  

Microsoft Academic Search

Infarct volume and edema were assessed after transient focal ischemia in mice lacking neuronal nitric oxide synthase (NOS) gene expression. With use of an 8–0 coated monofilament, the middle cerebral artery (MCA) of mutant (n = 32) and wild-type mice [SV-129 (n = 31), C57Black\\/6 (n = 18)] were occluded for 3 h and reperfused for up to 24 h.

Hideaki Hara; Paul L. Huang; Nariman Panahian; Mark C. Fishman; Michael A. Moskowitz

1996-01-01

79

Beneficial Effects of Schisandrin B on the Cardiac Function in Mice Model of Myocardial Infarction  

PubMed Central

The fruit of Schisandra chinensis has been used in the traditional Chinese medicine for thousands of years. Accumulating evidence suggests that Schisandrin B (Sch B) has cardioprotection effect on myocardial ischemia in vitro. However, it is unclear whether Sch B has beneficial effects on continuous myocardial ischemia in vivo. The aim of the present study was to investigate whether Sch B could improve cardiac function and attenuate myocardial remodeling after myocardial infarction (MI) in mice. Mice model of MI was established by permanent ligation of the left anterior descending (LAD) coronary artery. Then the MI mice were randomly treated with Sch B or vehicle alone. After treatment for 3 weeks, Sch B could increase survival rate, improve heart function and decrease infarct size compared with vehicle. Moreover, Sch B could down-regulate some inflammatory cytokines, activate eNOS pathway, inhibit cell apoptosis, and enhance cell proliferation. Further in vitro study on H9c2 cells showed similar effects of Sch B on prevention of hypoxia-induced inflammation and cell apoptosis. Taken together, our results demonstrate that Sch B can reduce inflammation, inhibit apoptosis, and improve cardiac function after ischemic injury. It represents a potential novel therapeutic approach for treatment of ischemic heart disease. PMID:24260217

Chen, Pengsheng; Pang, Sisi; Yang, Naiquan; Meng, Haoyu; Liu, Jia; Zhou, Ningtian; Zhang, Min; Xu, Zhihui; Gao, Wei; Chen, Bo; Tao, Zhengxian; Wang, Liansheng; Yang, Zhijian

2013-01-01

80

Ranolazine treatment for myocardial infarction? Effects on the development of necrosis, left ventricular function and arrhythmias in experimental models.  

PubMed

Ranolazine, an inhibitor of the late current of the cardiac action potential (late I(Na)), is a well established clinical treatment for chronic angina. The late INa in cardiac myocytes also plays an important role in the pathophysiology of acute myocardial ischemia and reperfusion, and thus is a potential therapeutic target to ameliorate consequences of myocardial infarction. In experimental animal models, ranolazine has been shown to reduce myocardial infarct size, improve left ventricular function, decrease ischemia/reperfusion-induced arrhythmias and improve outcome in heart failure. Here we focus specifically on data from in vivo animal studies of myocardial ischemia and reperfusion. PMID:25112450

Hale, Sharon L; Kloner, Robert A

2014-10-01

81

Erythropoietin Enhances the Angiogenic Potency of Autologous Bone Marrow Stromal Cells in a Rat Model of Myocardial Infarction  

Microsoft Academic Search

Background: Transplantation of marrow stromal cells (MSC) has been shown to improve heart perfusion and cardiac function after ischemia. Erythropoietin (EPO) is capable of inducing angiogenesis and inhibiting cell apoptosis. The aim of this study was to investigate the effect of EPO on the therapeutic potency of MSC transplantation in a rat model of myocardial infarction. Methods: MSC viability was

Dingguo Zhang; Fumin Zhang; Yuqing Zhang; Xiang Gao; Chuanfu Li; Wengzhu Ma; Kejiang Cao

2007-01-01

82

Traumatic brain injury using mouse models.  

PubMed

The use of mouse models in traumatic brain injury (TBI) has several advantages compared to other animal models including low cost of breeding, easy maintenance, and innovative technology to create genetically modified strains. Studies using knockout and transgenic mice demonstrating functional gain or loss of molecules provide insight into basic mechanisms of TBI. Mouse models provide powerful tools to screen for putative therapeutic targets in TBI. This article reviews currently available mouse models that replicate several clinical features of TBI such as closed head injuries (CHI), penetrating head injuries, and a combination of both. CHI may be caused by direct trauma creating cerebral concussion or contusion. Sudden acceleration-deceleration injuries of the head without direct trauma may also cause intracranial injury by the transmission of shock waves to the brain. Recapitulation of temporary cavities that are induced by high-velocity penetrating objects in the mouse brain are difficult to produce, but slow brain penetration injuries in mice are reviewed. Synergistic damaging effects on the brain following systemic complications are also described. Advantages and disadvantages of CHI mouse models induced by weight drop, fluid percussion, and controlled cortical impact injuries are compared. Differences in the anatomy, biomechanics, and behavioral evaluations between mice and humans are discussed. Although the use of mouse models for TBI research is promising, further development of these techniques is warranted. PMID:24493632

Zhang, Yi Ping; Cai, Jun; Shields, Lisa B E; Liu, Naikui; Xu, Xiao-Ming; Shields, Christopher B

2014-08-01

83

Autologous transplantation of arterial cells improves cardiac function in a rabbit model of infarcted myocardium.  

PubMed

Cellular cardiomyoplasty is a promising approach for the treatment of severe heart failure. However, the question which cell line is the best to use is still a matter of debate. In this study, we aimed to evaluate the efficacy of arterial media-intima cell suspension (AMICS) transplantation in rabbit myocardial infarct model. The study was divided into 2 groups: group A (the cell-treated group, n = 9) and group B (the medium injection group, n = 8). Group A was further divided into 2 subgroups as branch-1 (treated with unlabeled cells) and branch-2 (treated with iron-labeled cells). The experimental myocardial infarction (MI) was induced by ligation of left anterior descending coronary artery with a combination of cryoinjury. Ten days after the MI, cells obtained from autologous femoral arteries were injected into the injured myocardium of group A, while group B received an injection of only DMEM medium. Clinical, echocardiographic, and histopathologic evaluations were done. As compared to the ninth day values, echocardiography showed a significant improvement in systolic functions and left ventricular (LV) dimensions of the cell-treated group on the 30th day. In the heart biopsy sections of branch-1, the immunostained injected cells were observed to exist closely, suggesting an organization. Cells existing separately and lumen-like structure organizations stained positive with both smooth muscle cell (SMC) alpha-actin and Prussian Blue were also showed in the histological observation of branch-2. Autologous AMICS transplantation seems to be a feasible and efficacious method for cellular cardiomyoplasty in our rabbit model. PMID:19739969

Tokac, Mehmet; Aktan, Murad; Ak, Ahmet; Duman, Selcuk; Tokgozoglu, Lale; Aygul, Nazif; Paksoy, Yahya; Porat, Yael

2010-06-01

84

Development of a Closed Chest Model of Chronic Myocardial Infarction in Swine: Magnetic Resonance Imaging and Pathological Evaluation  

PubMed Central

Our aim was to develop an easy-to-induce, reproducible, and low mortality clinically relevant closed-chest model of chronic myocardial infarction in swine using intracoronary ethanol and characterize its evolution using MRI and pathology. We injected 3-4?mL of 100% ethanol into the mid-LAD of anesthetized swine. Heart function and infarct size were assessed serially using MRI. Pigs were euthanized on days 7, 30, and 90 (n = 5 at each timepoint). Postoperative MRI revealed compromised contractility and decreased ejection fraction, from 53.8% ± 6.32% to 43.79% ± 7.72% (P = 0.001). These values remained lower than baseline thorough the followup (46.54% ± 11.12%, 44.48% ± 7.77%, and 40.48% ± 6.40%, resp., P < 0.05). Progressive remodeling was seen in all animals. Infarcted myocardium decreased on the first 30 days (from 18.09% ± 7.26% to 9.9% ± 5.68%) and then stabilized (10.2% ± 4.21%). Pathology revealed increasing collagen content and fibrous organization over time, with a rim of preserved endocardial cells. In conclusion, intracoronary ethanol administration in swine consistently results in infarction. The sustained compromise in heart function and myocardial thinning over time indicate that the model may be useful for the preclinical evaluation of and training in therapeutic approaches to heart failure. PMID:24282645

Crisóstomo, Verónica; Maestre, Juan; Maynar, Manuel; Sun, Fei; Báez-Díaz, Claudia; Usón, Jesús; Sánchez-Margallo, Francisco M.

2013-01-01

85

New Strategies for Echocardiographic Evaluation of Left Ventricular Function in a Mouse Model of Long-Term Myocardial Infarction  

PubMed Central

Background The aim of this article is to present an optimized acquisition and analysis protocol for the echocardiographic evaluation of left ventricle (LV) remodeling in a mouse model of myocardial infarction (MI). Methodology 13 female DBA/2J mice underwent permanent occlusion of the left anterior descending (LAD) coronary artery leading to MI. Mice echocardiography was performed using a Vevo 770 (Visualsonics, Canada) before infarction, and 7, 14, 30, 60, 90 and 120 days after LAD ligation. LV systolic function was evaluated using different parameters, including the fractional area change (FAC%) computed in four high-temporal resolution B-mode short axis images taken at different ventricular levels, and in one parasternal long axis. Pulsed wave and tissue Doppler modes were used to evaluate the diastolic function and Tei Index for global cardiac function. The echocardiographic measurements of infarct size were validated histologically using collagen deposition labeled by Sirius red staining. All data was analyzed using Shapiro-Wilk and Student's t-tests. Principal Findings Our results reveal LV dilation resulting in marked remodeling an severe systolic dysfunction, starting seven days after MI (LV internal apical diameter, basal?=?2.82±0.24, 7d?=?3.49±0.42; p<0.001. End-diastolic area, basal?=?18.98±1.81, 7d?=?22.04±2.11; p<0.001). A strong statistically significant negative correlation exists between the infarct size and long-axis FAC% (r?=??0.946; R2?=?0.90; p<0.05). Moreover, the measured Tei Index values confirmed significant post-infarction impairment of the global cardiac function (basal?=?0.46±0.07, 7d?=?0.55±0.08, 14 d?=?0.57±0.06, 30 d?=?0.54±0.06, 60 d?=?0.54±0.07, 90 d?=?0.57±0.08; p<0.01). Conclusions/Significance In summary, we have performed a complete characterization of LV post-infarction remodeling in a DBA/2J mouse model of MI, using parameters adapted to the particular characteristics of the model In the future, this well characterized model will be used in both investigative and pharmacological studies that require accurate quantitative monitoring of cardiac recovery after myocardial infarction. PMID:22848568

Benavides-Vallve, Carolina; Corbacho, David; Iglesias-Garcia, Olalla; Pelacho, Beatriz; Albiasu, Edurne; Castaño, Sara; Muñoz-Barrutia, Arrate; Prosper, Felipe; Ortiz-de-Solorzano, Carlos

2012-01-01

86

Computational Modeling of Brain Dynamics during Repetitive Head Motions  

E-print Network

Computational Modeling of Brain Dynamics during Repetitive Head Motions Igor Szczyrba School motions in traumatic scenarios that are as- sociated with severe brain injuries. Our results are based on the linear Kelvin-Voigt brain injury model, which treats the brain matter as a viscoelastic solid, and on our

Burtscher, Martin

87

A model for lupus brain disease  

PubMed Central

Summary Systemic lupus erythematosus is an autoimmune disease characterized by antibodies that bind target autoantigens in multiple organs in the body. In peripheral organs, immune complexes engage the complement cascade, recruiting blood-borne inflammatory cells and initiating tissue inflammation. Immune complex-mediated activation of Fc receptors on infiltrating blood-borne cells and tissue resident cells amplifies an inflammatory cascade with resulting damage to tissue function, ultimately leading to tissue destruction. This pathophysiology appears to explain tissue injury throughout the body, except in the central nervous system. This review addresses a paradigm we have developed for autoantibody-mediated brain damage. This paradigm suggests that antibody-mediated brain disease does not depend on immune complex formation but rather on antibody-mediated alterations in neuronal activation and survival. Moreover, antibodies only access brain tissue when blood-brain barrier integrity is impaired, leading to a lack of concurrence of brain disease and tissue injury in other organs. We discuss the implications of this model for lupus and for identifying other antibodies that may contribute to brain disease. PMID:22725954

Diamond, Betty; Volpe, Bruce T.

2015-01-01

88

Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells.  

PubMed

Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury, but preclinical studies in large animal models are required to determine optimal cell preparation and delivery strategies to maximize functional benefits and to evaluate safety. Here, we utilized a porcine model of acute myocardial infarction (MI) to investigate the functional impact of intramyocardial transplantation of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells, in combination with a 3D fibrin patch loaded with insulin growth factor (IGF)-encapsulated microspheres. hiPSC-derived cardiomyocytes integrated into host myocardium and generated organized sarcomeric structures, and endothelial and smooth muscle cells contributed to host vasculature. Trilineage cell transplantation significantly improved left ventricular function, myocardial metabolism, and arteriole density, while reducing infarct size, ventricular wall stress, and apoptosis without inducing ventricular arrhythmias. These findings in a large animal MI model highlight the potential of utilizing hiPSC-derived cells for cardiac repair. PMID:25479750

Ye, Lei; Chang, Ying-Hua; Xiong, Qiang; Zhang, Pengyuan; Zhang, Liying; Somasundaram, Porur; Lepley, Mike; Swingen, Cory; Su, Liping; Wendel, Jacqueline S; Guo, Jing; Jang, Albert; Rosenbush, Daniel; Greder, Lucas; Dutton, James R; Zhang, Jianhua; Kamp, Timothy J; Kaufman, Dan S; Ge, Ying; Zhang, Jianyi

2014-12-01

89

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome  

PubMed Central

Background: To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Methods: Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Results: Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Conclusion: Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis. PMID:21915166

Naess, Halvor; Romi, Fredrik

2011-01-01

90

An experimental myocardial infarction model in the rat and its properties.  

PubMed

The photochemical reaction between rose bengal and light (540 nm) produces thrombotic occlusion in rat coronary artery. We have now developed an experimental myocardial infarction (MI) model by photochemically induced thrombosis (PIT) in rats and investigated the mechanisms responsible for the induction of MI. PIT in the coronary artery induced myocardial ischemia, which was determined by tissue oxygen tension (tpO2), and resulted in MI. Pretreatment with a thromboxane (TX) A2-receptor antagonist, vapiprost, prevented a decrease in myocardial tpO2 and markedly reduced the MI area, although vapiprost inhibited collagen-induced platelet aggregation by 30% ex vivo. An ADP-induced platelet aggregation inhibitor, clopidogrel, also reduced the MI area. In contrast to vapiprost, clopidogrel inhibited collagen-induced platelet aggregation by 90% ex vivo. Pretreatment with a 5-HT2-receptor antagonist, ketanserin, which did not inhibit collagen-induced platelet aggregation ex vivo, prevented the decrease in myocardial tpO2 and reduced the MI area. These results suggest that TXA2, 5-HT and ADP play a role in the induction of MI and that platelet aggregation and other factors induce ischemia in this model. PMID:7745845

Hirata, Y; Umemura, K; Uematsu, T; Nakashima, M

1995-01-01

91

Peri-infarct Blood-Brain Barrier Dysfunction Facilitates Induction of Spreading Depolarization Associated with Epileptiform Discharges  

PubMed Central

Recent studies showed that spreading depolarizations (SDs) occur abundantly in patients following ischemic stroke and experimental evidence suggests that SDs recruit tissue at risk into necrosis. We hypothesized that BBB opening with consequent alterations of the extracellular electrolyte composition and extravasation of albumin facilitates generation of SDs since albumin mediates an astrocyte transcriptional response with consequent disturbance of potassium and glutamate homeostasis. Here we show extravasation of Evans blue-albumin complex into the hippocampus following cortical photothrombotic stroke in the neighbouring neocortex. Using extracellular field potential recordings and exposure to serum electrolytes we observed spontaneous SDs in 80 % of hippocampal slices obtained from rats 24 h after cortical photothrombosis. Hippocampal exposure to albumin for 24 h through intraventricular application together with serum electrolytes lowered the threshold for the induction of SDs in most slices irrespective of the pathway of stimulation. Exposing acute slices from naive animals to albumin led also to a reduced SD threshold. In albumin-exposed slices the onset of SDs was usually associated with larger stimulus-induced accumulation of extracellular potassium, and preceded by epileptiform activity, which was also observed during the recovery phase of SDs. Application of ifenprodil (3?M), an NMDA-receptor type 2 B antagonist, blocked stimulus dependent epileptiform discharges and generation of SDs in slices from animals treated with albumin in-vivo. We suggest that BBB opening facilitates the induction of peri-infarct SDs through impaired homeostasis of K+. PMID:22782081

Lapilover, EG; Lippman, K.; Salar, S.; Maslarova, A.; Dreier, JP; Heinemann, U.; Friedman, A.

2012-01-01

92

Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model  

Microsoft Academic Search

BackgroundTherapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+\\/CD34+) genetically modified with VEGF plus PDGF genes (VIP).Methods and FindingsMyocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue

Hiranmoy Das; Jon C. George; Matthew Joseph; Manjusri Das; Nasreen Abdulhameed; Anna Blitz; Mahmood Khan; Ramasamy Sakthivel; Hai-Quan Mao; Brian D. Hoit; Periannan Kuppusamy; Vincent J. Pompili

2009-01-01

93

Theory and Implementation Of Small Brain Models James K. Peterson  

E-print Network

Theory and Implementation Of Small Brain Models James K. Peterson Department of Mathematical Abstract An outline of mechanisms that will allow the creation of small brain models is discussed. We.5 Modulation Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 6 Second

Peterson, James K

94

Modelling of Brain Consciousness based on Collaborative Adaptive Filters  

E-print Network

Modelling of Brain Consciousness based on Collaborative Adaptive Filters Ling Lia, , Yili Xiaa of Technology, Japan c Laboratory for Advanced Brain Signal Processing, RIKEN Brain Science Institute, Saitama method for the discrimination between discrete states of brain con- sciousness is proposed, achieved

Kent, University of

95

Modeling the Network Architecture of the Human Brain Olaf Sporns  

E-print Network

cell assemblies Macroscopic: Anatomically segregated brain regions and inter-regional pathways. BrainModeling the Network Architecture of the Human Brain Olaf Sporns Department of Psychological and Brain Sciences Indiana University, Bloomington, IN 47405 http://www.indiana.edu/~cortex , osporns

Bressler, Steven L.

96

Electromechanical feedback with reduced cellular connectivity alters electrical activity in an infarct injured left ventricle: a finite element model study  

PubMed Central

Myocardial infarction (MI) significantly alters the structure and function of the heart. As abnormal strain may drive heart failure and the generation of arrhythmias, we used computational methods to simulate a left ventricle with an MI over the course of a heartbeat to investigate strains and their potential implications to electrophysiology. We created a fully coupled finite element model of myocardial electromechanics consisting of a cellular physiological model, a bidomain electrical diffusion solver, and a nonlinear mechanics solver. A geometric mesh built from magnetic resonance imaging (MRI) measurements of an ovine left ventricle suffering from a surgically induced anteroapical infarct was used in the model, cycled through the cardiac loop of inflation, isovolumic contraction, ejection, and isovolumic relaxation. Stretch-activated currents were added as a mechanism of mechanoelectric feedback. Elevated fiber and cross fiber strains were observed in the area immediately adjacent to the aneurysm throughout the cardiac cycle, with a more dramatic increase in cross fiber strain than fiber strain. Stretch-activated channels decreased action potential (AP) dispersion in the remote myocardium while increasing it in the border zone. Decreases in electrical connectivity dramatically increased the changes in AP dispersion. The role of cross fiber strain in MI-injured hearts should be investigated more closely, since results indicate that these are more highly elevated than fiber strain in the border of the infarct. Decreases in connectivity may play an important role in the development of altered electrophysiology in the high-stretch regions of the heart. PMID:22058157

Guccione, Julius M.; Ratcliffe, Mark B.; Sundnes, Joakim S.

2012-01-01

97

Non-invasive estimation of myocardial infarction by means of a heart-model-based imaging approach: a simulation study.  

PubMed

In the study, a new myocardial infarction (MI) estimation method was developed for estimating MI in the three-dimensional myocardium by means of a heart-model-based inverse approach. The site and size of MI are estimated from body surface electrocardiograms by minimising multiple objective functions of the measured body surface potential maps (BSPMs) and the heart-model-generated BSPMs. Computer simulations were conducted to evaluate the performance of the developed method, using a single-site MI and dual-site MI protocols. The simulation results show that, for the single-site MI, the averaged spatial distance (SD) between the weighting centres of the 'true' and estimated MIs, and the averaged relative error (RE) between the numbers of the 'true' and estimated infarcted units are 3.0 +/- 0.6/3.6 +/- 0.6 mm and 0.11 +/- 0.02/0.14 +/- 0.02, respectively, when 5 microV/10 microV Gaussian white noise was added to the body surface potentials. For the dual-site MI, the averaged SD between the weighting centres of the 'true' and estimated MIs, and the averaged RE between the numbers of the 'true' and estimated infarcted units are 3.8 +/- 0.7/3.9 +/- 0.7mm and 0.12 +/- 0.02/0.14 +/- 0.03, respectively, when 5 microV/10 microV Gaussian white noise was added to the body surface potentials. The simulation results suggest the feasibility of applying the heart-model-based imaging approach to the estimation of myocardial infarction from body surface potentials. PMID:14977234

Li, G; He, B

2004-01-01

98

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker, in a porcine model of acute myocardial infarction.  

PubMed

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI. PMID:25552881

Sim, Doo Sun; Jeong, Myung Ho; Song, Ho Chun; Kim, Jahae; Chong, Ari; Bom, Hee Seung; Jeong, In Seok; Oh, Sang Gi; Kim, Jong Min; Park, Dae Sung; Kim, Jung Ha; Lim, Kyung Seob; Kim, Min Suk; Ryu, Shi Hyun; Kim, Hyun Kuk; Kim, Sung Soo; Jang, Su Young; Cho, Jae Yeong; Jeong, Hae Chang; Lee, Ki Hong; Park, Keun Ho; Yoon, Nam Sik; Yoon, Hyun Ju; Kim, Kye Hun; Hong, Young Joon; Park, Hyung Wook; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee

2015-01-01

99

Neurodynamical model of collective brain  

NASA Technical Reports Server (NTRS)

A dynamical system which mimics collective purposeful activities of a set of units of intelligence is introduced and discussed. A global control of the unit activities is replaced by the probabilistic correlations between them. These correlations are learned during a long term period of performing collective tasks, and are stored in the synaptic interconnections. The model is represented by a system of ordinary differential equations with terminal attractors and repellers, and does not contain any man-made digital devices.

Zak, Michail

1992-01-01

100

The Brain's Router: A Cortical Network Model of Serial Processing in the Primate Brain  

E-print Network

The Brain's Router: A Cortical Network Model of Serial Processing in the Primate Brain Ariel-task experiments in humans and non-human primates. Citation: Zylberberg A, Ferna´ndez Slezak D, Roelfsema PR in the Primate Brain. PLoS Comput Biol 6(4): e1000765. doi:10.1371/journal.pcbi.1000765 Editor: Karl J. Friston

Paris-Sud XI, Université de

101

Cognitive aging as an extension of brain development: A model linking learning, brain plasticity, and neurodegeneration  

E-print Network

of aging to delay and prevent mental illness must thus be a top priority for biomedical research. UntilReview Cognitive aging as an extension of brain development: A model linking learning, brain Differences in cognitive aging rates among mammals suggest that the pace of brain aging is genetically

de Magalhães, João Pedro

102

Intracardiac injection of matrigel induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model  

PubMed Central

Abstract Matrigel promotes angiogenesis in the myocardium from ischemic injury and prevents remodelling of the left ventricle. We assessed the therapeutic efficacy of intracardiac matrigel injection and matrigel-mediated stem cell homing in a rat myocardial infarction (MI) model. Following MI, matrigel (250 ?l) or phosphate-buffered solution (PBS) was delivered by intracardiac injection. Compared to the MI control group (MI-PBS), matrigel significantly improved left ventricular function (n= 11, P < 0.05) assessed by pressure–volume loops after 4 weeks. There is no significant difference in infarct size between MI-matrigel (MI-M; 21.48 ± 1.49%, n= 10) and MI-PBS hearts (20.98 ± 1.25%, n= 10). The infarct wall thickness of left ventricle is significantly higher (P < 0.01) in MI-M (0.72 ± 0.02 mm, n= 10) compared with MI-PBS (0.62 ± 0.02 mm, n= 10). MI-M hearts exhibited higher capillary density (border 130.8 ± 4.7 versus 115.4 ± 6.0, P < 0.05; vessels per high-power field [HPF; 400×], n= 6) than MI-PBS hearts. c-Kit+ stem cells (38.3 ± 5.3 versus 25.7 ± 1.5 c-Kit+ cells per HPF [630×], n= 5, P < 0.05) and CD34+ cells (13.0 ± 1.51 versus 5.6 ± 0.68 CD34+ cells per HPF [630×], n= 5, P < 0.01) were significantly more numerous in MI-M than in MI-PBS in the infarcted hearts (n= 5, P < 0.05). Intracardiac matrigel injection restores myocardial functions following MI, which may attribute to the improved recruitment of CD34+ and c-Kit+ stem cells. PMID:20477905

Ou, Lailiang; Li, Wenzhong; Zhang, Yue; Wang, Weiwei; Liu, Jun; Sorg, Heiko; Furlani, Dario; Gäbel, Ralf; Mark, Peter; Klopsch, Christian; Wang, Liang; Lützow, Karola; Lendlein, Andreas; Wagner, Klaus; Klee, Doris; Liebold, Andreas; Li, Ren-Ke; Kong, Deling; Steinhoff, Gustav; Ma, Nan

2011-01-01

103

The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction.  

PubMed

We recently described a murine embryonic stem cell (ESC) line engineered to express the activated Notch 4 receptor in a tetracycline (doxcycline; Dox) regulated fashion (tet-notch4 ESCs). Notch 4 induction in Flk1(+) hematopoietic and vascular progenitors from this line respecified them to a cardiovascular fate. We reasoned that these cells would be ideal for evaluating the contribution of the cardiomyocyte and vascular lineages to the functional improvement noted following stem cell transplantation in infarcted hearts. Flk-1(+) Tet-notch4 cells from d 3 embryoid bodies exposed to doxycycline (Dox(+)) were compared to uninduced (Dox(-)) Flk-1(+) cells. Mice underwent transplantation of 5 x 10(5) Dox(+) cells, Dox(-)cells, or an equal volume of serum-free medium after surgically induced myocardial infarction. The mean ejection fraction was 59 + or - 15, 46 + or - 17, and 39 + or - 13% in the Dox(+), Dox(-), and serum-free medium groups, respectively (P<0.05 for the differences among all 3 groups). Immunohistochemistry of hearts injected with Dox(+) grafts expressed myocardial and vascular markers, whereas grafts of Dox(-) cells expressed primarily vascular markers. We conclude that cardiovascular progenitors are more effective than vascular progenitors in improving function after myocardial infarction. The transplantation of appropriate cell types is critical for maximizing the benefit of cardiovascular cell therapy.-Adler, E. D., Chen, V. C., Bystrup, A., Kaplan, A. D., Giovannone, S., Briley-Saebo, K., Young, W., Kattman, S., Mani, V., Laflamme, M., Zhu, W.-Z., Fayad, Z., Keller, G. The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction. PMID:19940262

Adler, Eric D; Chen, Vincent C; Bystrup, Anne; Kaplan, Aaron D; Giovannone, Steven; Briley-Saebo, Karen; Young, Wilson; Kattman, Steve; Mani, Venkatesh; Laflamme, Michael; Zhu, Wei-Zhong; Fayad, Zahi; Keller, Gordon

2010-04-01

104

The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction  

PubMed Central

We recently described a murine embryonic stem cell (ESC) line engineered to express the activated Notch 4 receptor in a tetracycline (doxcycline; Dox) regulated fashion (tet-notch4 ESCs). Notch 4 induction in Flk1+ hematopoietic and vascular progenitors from this line respecified them to a cardiovascular fate. We reasoned that these cells would be ideal for evaluating the contribution of the cardiomyocyte and vascular lineages to the functional improvement noted following stem cell transplantation in infarcted hearts. Flk-1+ Tet-notch4 cells from d 3 embryoid bodies exposed to doxycycline (Dox+) were compared to uninduced (Dox?) Flk-1+ cells. Mice underwent transplantation of 5 × 105 Dox+ cells, Dox?cells, or an equal volume of serum-free medium after surgically induced myocardial infarction. The mean ejection fraction was 59 ± 15, 46 ± 17, and 39 ± 13% in the Dox+, Dox?, and serum-free medium groups, respectively (P<0.05 for the differences among all 3 groups). Immunohistochemistry of hearts injected with Dox+ grafts expressed myocardial and vascular markers, whereas grafts of Dox? cells expressed primarily vascular markers. We conclude that cardiovascular progenitors are more effective than vascular progenitors in improving function after myocardial infarction. The transplantation of appropriate cell types is critical for maximizing the benefit of cardiovascular cell therapy.—Adler, E. D., Chen, V. C., Bystrup, A., Kaplan, A. D., Giovannone, S., Briley-Saebo, K., Young, W., Kattman, S., Mani, V., Laflamme, M., Zhu, W.-Z., Fayad, Z., Keller, G. The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction. PMID:19940262

Adler, Eric D.; Chen, Vincent C.; Bystrup, Anne; Kaplan, Aaron D.; Giovannone, Steven; Briley-Saebo, Karen; Young, Wilson; Kattman, Steve; Mani, Venkatesh; Laflamme, Michael; Zhu, Wei-Zhong; Fayad, Zahi; Keller, Gordon

2010-01-01

105

Therapeutic application of adipose derived stem cells in acute myocardial infarction: lessons from animal models.  

PubMed

The majority of patients survive an acute myocardial infarction (AMI). Their outcome is negatively influenced by post-AMI events, such as loss of viable cardiomyocytes due to a post-AMI inflammatory response, eventually resulting in heart failure and/or death. Recent pre-clinical animal studies indicate that mesenchymal stem cells derived from adipose tissue (ASC) are new promising candidates that may facilitate cardiovascular regeneration in the infarcted myocardium. In this review we have compared all animal studies in which ASC were used as a therapy post-AMI and have focused on aspects that might be important for future successful clinical application of ASC. PMID:24577790

Naaijkens, B A; van Dijk, A; Kamp, O; Krijnen, P A J; Niessen, H W M; Juffermans, L J M

2014-06-01

106

Construction of Anatomically Correct Models of Mouse Brain Networks 1  

E-print Network

Construction of Anatomically Correct Models of Mouse Brain Networks 1 B. H. McCormick a, W. Koh a Y and Public Health, Texas A&M University, 4458 TAMU, College Station, TX 77843-4458 Abstract The Mouse Brain Web, a federated database, provides for the construction of anatomically correct models of mouse brain

Keyser, John

107

A novel cardiac muscle-derived biomaterial reduces dyskinesia and postinfarct left ventricular remodeling in a mouse model of myocardial infarction  

PubMed Central

Extracellular matrix (ECM) degradation after myocardial infarction (MI) leaves the myocardium structurally weakened and, as a result, susceptible to early infarct zone dyskinesia and left ventricular (LV) remodeling. While various cellular and biomaterial preparations have been transplanted into the infarct zone in hopes of improving post-MI LV remodeling, an allogeneic cardiac muscle-derived ECM extract has yet to be developed and tested in the setting of reperfused MI. We sought to determine the effects of injecting a novel cardiac muscle-derived ECM into the infarct zone on early dyskinesia and LV remodeling in a mouse model of MI. Cardiac muscle ECM was extracted from frozen mouse heart tissue by a protocol that enriches for basement membrane constituents. The extract was injected into the infarct zone immediately after ischemia/reperfusion injury (n = 6). Echocardiography was performed at baseline and at days 2, 7, 14, and 28 post-MI to assess 3D LV volumes and cardiac function, as compared to infarcted controls (n = 9). Early infarct zone dyskinesia was measured on day 2 post-MI using a novel metric, the dyskinesia index. End-systolic volume was significantly reduced in the ECM-treated group compared to controls by day 14. Ejection fraction and stroke volume were also significantly improved in the ECM-treated group. ECM-treated hearts showed a significant (P < 0.005) reduction in dyskinetic motion on day 2. Thus, using high-frequency ultrasound, it was shown that treatment with a cardiac-derived ECM preparation reduced early infarct zone dyskinesia and post-MI LV remodeling in a mouse model of reperfused MI. PMID:25825543

O'Connor, Daniel M; Naresh, Nivedita K; Piras, Bryan A; Xu, Yaqin; Smith, Robert S; Epstein, Frederick H; Hossack, John A; Ogle, Roy C; French, Brent A

2015-01-01

108

Modeling brain dynamics using computational neurogenetic approach  

PubMed Central

The paper introduces a novel computational approach to brain dynamics modeling that integrates dynamic gene–protein regulatory networks with a neural network model. Interaction of genes and proteins in neurons affects the dynamics of the whole neural network. Through tuning the gene–protein interaction network and the initial gene/protein expression values, different states of the neural network dynamics can be achieved. A generic computational neurogenetic model is introduced that implements this approach. It is illustrated by means of a simple neurogenetic model of a spiking neural network of the generation of local field potential. Our approach allows for investigation of how deleted or mutated genes can alter the dynamics of a model neural network. We conclude with the proposal how to extend this approach to model cognitive neurodynamics. PMID:19003458

Kasabov, Nikola

2008-01-01

109

Intermittent vagal nerve stimulation alters the electrophysiological properties of atrium in the myocardial infarction rat model.  

PubMed

Intermittent vagal nerve stimulation (VNS) has emerged as a potential therapy to treat cardiovascular diseases by delivering electrical stimulation to the vagus nerves. The purpose of this study was to investigate the electrophysiological changes in the atrium resulting from long-term intermittent VNS therapy in the chronic myocardial infarction (MI) rat model. MI was induced via left anterior descending coronary artery (LAD) ligation in male Sprague-Dawley rats, randomized into two groups: MI (implanted with nonfunctional VNS stimulators) and MI-VNS (implanted with functional VNS stimulators and received chronic intermittent VNS treatment) groups. Further, a sham group was used as control in which MI was not performed and received nonfunctional VNS stimulators. At 12 weeks, optical mapping of right atrium (RA) of sinus rhythm was performed. Our results demonstrated that chronic MI changed the electrical properties of the atrium action potentials and resulted in reduced action potential duration at 50% (APD50) and 80% (APD80) repolarization. Chronic right cervical VNS restored the APD back to healthy heart APD values. Additionally, APD heterogeneity index increased as a result of the chronic MI. Chronic VNS was not found to alter this increase. By calculating PR intervals from weekly ECG recordings of anaesthetized rats, we demonstrated that chronic MI and intermittent VNS did not affect the AV conduction time from the atria to the ventricles. From our study, we conclude the MI decreased the APD and increased APD spatial dispersion. VNS increased the APD back to healthy normal values but did change the APD spatial dispersion and the electrical conduction in the RA. PMID:25570272

Xueyi Xie; Lee, Steven W; Johnson, Christopher; Ippolito, Joseph; KenKnight, Bruce H; Tolkacheva, Elena G

2014-08-01

110

Hypericin as a marker for determination of myocardial viability in a rat model of myocardial infarction.  

PubMed

The aim of this study was to investigate the necrosis-avid agent hypericin as a potential indicator for determination of myocardial infarction (MI). Male Sprague-Dawley rats (n = 30) weighing 350 ± 20 g were subjected to acute reperfused MI. Animals were divided into four groups (n = 6), in which hypericin was intravenously injected at 0, 1, 2 and 5 mg kg(-1) respectively. One day after injection, rats were euthanized with their hearts excised for qualitative and quantitative studies by means of microscopic fluorescence examination to decide the dosage of hypericin. Another group was injected with hypericin at the decided dose and evaluated by fluorescence macroscopy in colocalization with triphenyltetrazoliumchloride (TTC) and histomorphology. Infarct-to-normal contrast ratio and relative infarct size were quantified. Hypericin-induced red fluorescence was significantly brighter in necrotic than in viable myocardium as proven by a six times higher mean fluorescence density. Mean MI area was 35.66 ± 22.88% by hypericin fluorescence and 32.73 ± 21.98% by TTC staining (R(2) = 0.9803). Global MI-volume was 34.56 ± 21.07% by hypericin and 35.11 ± 20.47% by TTC staining (R(2) = 0.9933). The results confirm that hypericin specifically labeled necrosis, and enhanced the imaging contrast between the infarcted and normal myocardium, suggesting its potential applications for the assessment of myocardial viability. PMID:24460608

Jiang, Cuihua; Li, Yue; Jiang, Xiao; Yao, Nan; Gao, Meng; Zhang, Xueli; Wang, Junying; Wang, Xiaoning; Sun, Ziping; Zhang, Jian; Ni, Yicheng

2014-01-01

111

Diffusion Based Modeling of Human Brain Response to External Stimuli  

E-print Network

Human brain response is the overall ability of the brain in analyzing internal and external stimuli in the form of transferred energy to the mind/brain phase-space and thus, making the proper decisions. During the last decade scientists discovered about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research there was less effort which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling of human EEG signal, as an alert state of overall human brain activity monitoring, due to receiving external stimuli, based on fractional diffusion equation. The results of this modeling show very good agreement with the real human EEG signal and thus, this model can be used as a strong representative of the human brain activity.

Namazi, Hamidreza

2012-01-01

112

Field theory model of brain extracellular matrix  

PubMed Central

The perineural net (PNN) is responsible for synaptic stabilization of adult brain. It plays an important role in brain signal processing and non-synaptic signal transfer as well [ 1]. Since it is composed of largely negatively charged chains of disaccharides, it can be easily affected by strong external electromagnetic field irradiated by high-energy particles passing brain tissues. One of the effects of such exposure is a cognitive impairment. Since outside of the Bragg peak area local electromagnetic field irradiation strong enough to affect on the PNN's dynamics, it is very important to understand PNN's behavior in locally strong electromagnetic fields. The presented work is devoted to PNN modeling in field theory framework. As a toy model of PNN, we consider fractal lattice with Ising and XY model applied. More precise study requires application of the quantum electrodynamics on the lattice. We study how local excitations can change phase state of the overall lattice and its finite clusters. For this propose, the partition function of the Ising model is calculated using Monte Carlo simulation [ 2]. The two-dimensional Serpinsky Carpet lattice is applied to approximate structure of the brain extracellular matrix. Order parameter is calculated for different levels of the self-similarity of the Serpinsky Carpet. It is shown that starting from the level = 3, the lattice with fractal structure has irreversible phase transition: phase state after restoration differs from the initial one. In Fig.  1, the calculation of the correlation length change due to the energy dissipation after a local impact is shown. The column shows correlation strength (from 0 to 1), the right axis shows the cluster size ratio to the whole lattice size in percentage. The initial lattice was totally correlated (100% of the lattice has correlation strength that equals 1). The left side of the picture corresponds the locally excited lattice with no correlation, the right side of the picture corresponds the lattice after the relaxation to the equilibrium state due to the energy dissipation. It can be clearly seen that the lattice is not correlated after the relaxation. Fig. 1.Correlation length change due to the energy dissipation. Conclusions Local impact changes the correlation length of the fractal lattice: after the restoration, the correlation length becomes short, thus signal processing on the lattice changes significantly. Thus, it can be considered as a good model to study of the extracellular matrix change due to local excitations of strong electromagnetic field.

Molochkov, Alexander; Goy, Vladimir; Tolstonogov, Anton

2014-01-01

113

Fluid-dynamics modelling of the human left ventricle with dynamic mesh for normal and myocardial infarction: preliminary study.  

PubMed

Pulsating blood flow patterns in the left ventricular (LV) were computed for three normal subjects and three patients after myocardial infarction (MI). Cardiac magnetic resonance (MR) images were obtained, segmented and transformed into 25 frames of LV for a computational fluid dynamics (CFD) study. Multi-block structure meshes were generated for 25 frames and 75 intermediate grids. The complete LV cycle was modelled by using ANSYS-CFX 12. The flow patterns and pressure drops in the LV chamber of this study provided some useful information on intra-LV flow patterns with heart diseases. PMID:22795507

Khalafvand, S S; Ng, E Y K; Zhong, L; Hung, T K

2012-08-01

114

The direct incorporation of perfusion defect information to define ischemia and infarction in a finite element model of the left ventricle.  

PubMed

This paper describes the process in which complex lesion geometries (specified by computer generated perfusion defects) are incorporated in the description of nonlinear finite element (FE) mechanical models used for specifying the motion of the left ventricle (LV) in the 4D extended cardiac torso (XCAT) phantom to simulate gated cardiac image data. An image interrogation process was developed to define the elements in the LV mesh as ischemic or infarcted based upon the values of sampled intensity levels of the perfusion maps. The intensity values were determined for each of the interior integration points of every element of the FE mesh. The average element intensity levels were then determined. The elements with average intensity values below a user-controlled threshold were defined as ischemic or infarcted depending upon the model being defined. For the infarction model cases, the thresholding and interrogation process were repeated in order to define a border zone (BZ) surrounding the infarction. This methodology was evaluated using perfusion maps created by the perfusion cardiac-torso (PCAT) phantom an extension of the 4D XCAT phantom. The PCAT was used to create 3D perfusion maps representing 90% occlusions at four locations (left anterior descending (LAD) segments 6 and 9, left circumflex (LCX) segment 11, right coronary artery (RCA) segment 1) in the coronary tree. The volumes and shapes of the defects defined in the FE mechanical models were compared with perfusion maps produced by the PCAT. The models were incorporated into the XCAT phantom. The ischemia models had reduced stroke volume (SV) by 18-59?ml. and ejection fraction (EF) values by 14-50% points compared to the normal models. The infarction models, had less reductions in SV and EF, 17-54?ml. and 14-45% points, respectively. The volumes of the ischemic/infarcted regions of the models were nearly identical to those volumes obtained from the perfusion images and were highly correlated (R2?=?0.99). PMID:25367177

Veress, Alexander I; Fung, George S K; Lee, Taek-Soo; Tsui, Benjamin M W; Kicska, Gregory A; Paul Segars, W; Gullberg, Grant T

2015-05-01

115

Animal models of traumatic brain injury  

PubMed Central

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in both civilian life and the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs, which were identified to be effective in animal TBI models, have all failed in phase II or phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies. PMID:23329160

Xiong, Ye; Mahmood, Asim; Chopp, Michael

2014-01-01

116

Cannabinoid CB2 receptor activation decreases cerebral infarction in a mouse focal ischemia/reperfusion model  

PubMed Central

Cannabinoid CB2 Receptor (CB2) activation has been shown to have immunomodulatory properties without psychotropic effects. The hypothesis of this study is that selective CB2 agonist treatment can attenuate cerebral ischemia/reperfusion injury. Selective CB2 agonists (O-3853, O-1966) were administered intravenously 1 h before transient middle cerebral artery occlusion (MCAO) or 10 mins after reperfusion in male mice. Leukocyte/endothelial interactions were evaluated before MCAO, 1 h after MCAO, and 24 h after MCAO via a closed cranial window. Cerebral infarct volume and motor function were determined 24 h after MCAO. Administration of the selective CB2 agonists significantly decreased cerebral infarction (30%) and improved motor function (P < 0.05) after 1 h MCAO followed by 23 h reperfusion in mice. Transient ischemia in untreated animals was associated with a significant increase in leukocyte rolling and adhesion on both venules and arterioles (P < 0.05), whereas the enhanced rolling and adhesion were attenuated by both selective CB2 agonists administered either at 1 h before or after MCAO (P < 0.05). CB2 activation is associated with a reduction in white blood cell rolling and adhesion along cerebral vascular endothelial cells, a reduction in infarct size, and improved motor function after transient focal ischemia. PMID:17245417

Zhang, Ming; Martin, Billy R; Adler, Martin W; Razdan, Raj K; Jallo, Jack I; Tuma, Ronald F

2009-01-01

117

Investigation into the optimal surgical conditions for coronary artery ligation for establishing a myocardial infarction model in mice  

PubMed Central

In the present study, the left anterior descending coronary arteries of mice under anesthesia were ligated, and the optimal surgical conditions for coronary artery ligation (CAL) in the establishment of a myocardial infarction (MI) mouse model were investigated. All mice that survived were sacrificed seven days subsequent to the successful surgery. Body weight, blood serum and heart tissues were obtained for further analysis or biochemical and histopathological examinations. The survival rate of the mice following the CAL procedure was 70%. The aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations in the serum of the experimental mice were significantly increased compared with those of the control mice, which reflected the enzyme release from the infarcted myocardial cells. Histopathological examination showed different degrees of MI in the heart tissues of the experimental mice. The results indicate that an MI model in mice may be successfully established using CAL under the surgical conditions utilized in the present study. These conditions were cost effective and the results may be replicated by laboratories that are less well-equipped. PMID:24137186

YUE, XIA; YU, HONGSHENG; LIN, XIALU; LIU, KUI; WANG, XIN; ZHOU, FEI; ZHAO, JINSHUN; ZOU, BAOBO

2013-01-01

118

Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition  

PubMed Central

Recent clinical data indicates that hemodynamic changes caused by cardiovascular diseases such as atherosclerosis, heart failure, and hypertension affect cognition. Yet, the underlying mechanisms of the resulting vascular cognitive impairment (VCI) are poorly understood. One reason for the lack of mechanistic insights in VCI is that research in dementia primarily focused on Alzheimer's disease models. To fill in this gap, we critically reviewed the published data and various models of VCI. Typical findings in VCI include reduced cerebral perfusion, blood–brain barrier alterations, white matter lesions, and cognitive deficits, which have also been reported in different cardiovascular mouse models. However, the tests performed are incomplete and differ between models, hampering a direct comparison between models and studies. Nevertheless, from the currently available data we conclude that a few existing surgical animal models show the key features of vascular cognitive decline, with the bilateral common carotid artery stenosis hypoperfusion mouse model as the most promising model. The transverse aortic constriction and myocardial infarction models may be good alternatives, but these models are as yet less characterized regarding the possible cerebral changes. Mixed models could be used to study the combined effects of different cardiovascular diseases on the deterioration of cognition during aging. PMID:23963364

Bink, Diewertje I; Ritz, Katja; Aronica, Eleonora; van der Weerd, Louise; Daemen, Mat JAP

2013-01-01

119

A mathematical model of brain glucose homeostasis  

Microsoft Academic Search

BACKGROUND: The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG) regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. METHODS: In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes,

Lu Gaohua; Hidenori Kimura

2009-01-01

120

Models of the Aging Brain Structure and Individual Decline  

PubMed Central

The aging brain’s structural development constitutes a spatiotemporal process that is accessible by MR-based computational morphometry. Here we introduce basic concepts and analytical approaches to quantify age-related differences and changes in neuroanatomical images of the human brain. The presented models first address the estimation of age trajectories, then we consider inter-individual variations of structural decline, using a repeated measures design. We concentrate our overview on preprocessed neuroanatomical images of the human brain to facilitate practical applications to diverse voxel- and surface-based structural markers. Together these methods afford analysis of aging brain structure in relation to behavioral, health, or cognitive parameters. PMID:22435060

Ziegler, Gabriel; Dahnke, Robert; Gaser, Christian

2012-01-01

121

Model-based autosegmentation of brain structures in the honeybee using statistical shape models  

E-print Network

Model-based autosegmentation of brain structures in the honeybee using statistical shape models K University of Berlin, 2 Zuse Institute, Berlin Surface-based brain atlases like the Honeybee Brain Atlas (www-Dimensional Average-Shape atlas of the honeybee brain and its applications. JCN 492(1):1-19. 2 Lamecker et.al. (2004

Andrzejak, Artur

122

Build-a-Brain Project : Students Design and Model the Brain of an Imaginary Animal  

NSDL National Science Digital Library

The brain is a truly fascinating structure! Although the brain is a single organ, it is very complex and has several regions, each having a specific function. In this fun-filled, "minds-on" lesson, students learn about the various regions of the brain and then build brains of imaginary animals using modeling dough and other art supplies in an inquiry based format. (See sidebar onpage 30, and Resources for a downloadable student handout on this topic as well as for other sites containing additional information and diagrams).

Archibald J. Fobbs Jr.

2006-01-01

123

Brain  

MedlinePLUS

... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

124

Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer-like brain amyloidosis  

Microsoft Academic Search

BACKGROUND: An increasing body of evidence implicates both brain inflammation and oxidative stress in the pathogenesis of Alzheimer's disease (AD). The relevance of their interaction in vivo, however, is unknown. Previously, we have shown that separate pharmacological targeting of these two components results in amelioration of the amyloidogenic phenotype of a transgenic mouse model of AD-like brain amyloidosis (Tg2576). METHODS:

Yuemang Yao; Cinzia Chinnici; Hanguan Tang; John Q Trojanowski; Domenico Praticò

2004-01-01

125

PET imaging of a collagen matrix reveals its effective injection and targeted retention in a mouse model of myocardial infarction.  

PubMed

Injectable biomaterials have shown promise for cardiac regeneration therapy. However, little is known regarding their retention and distribution upon application in vivo. Matrix imaging would be useful for evaluating these important properties. Herein, hexadecyl-4-[(18)F]fluorobenzoate ((18)F-HFB) and Qdot labeling was used to evaluate collagen matrix delivery in a mouse model of myocardial infarction (MI). At 1wk post-MI, mice received myocardial injections of (18)F-HFB- or Qdot-labeled matrix to assess its early retention and distribution (at 10min and 2h) by positron emission tomography (PET), or fluorescence imaging, respectively. PET imaging showed that the bolus of matrix at 10min redistributed evenly within the ischemic territory by 2h. Ex vivo biodistribution revealed myocardial matrix retention of ?65%, which correlated with PET results, but may be an underestimate since (18)F-HFB matrix labeling efficiency was ?82%. For covalently linked Qdots, labeling efficiency was ?96%. Ex vivo Qdot quantification showed that ?84% of the injected matrix was retained in the myocardium. Serial non-invasive PET imaging and validation by fluorescence imaging confirmed the effectiveness of the collagen matrix to be retained and redistributed within the infarcted myocardium. This study identifies matrix-targeted imaging as a promising modality for assessing the biodistribution of injectable biomaterials for application in the heart. PMID:25725551

Ahmadi, Ali; L Thorn, Stephanie; Alarcon, Emilio I; Kordos, Myra; Padavan, Donna T; Hadizad, Tayebeh; Cron, Greg O; Beanlands, Rob S; DaSilva, Jean N; Ruel, Marc; deKemp, Robert A; Suuronen, Erik J

2015-05-01

126

Translation of TRO40303 from myocardial infarction models to demonstration of safety and tolerance in a randomized Phase I trial  

PubMed Central

Background Although reperfusion injury has been shown to be responsible for cardiomyocytes death after an acute myocardial infarction, there is currently no drug on the market that reduces this type of injury. TRO40303 is a new cardioprotective compound that was shown to inhibit the opening of the mitochondrial permeability transition pore and reduce infarct size after ischemia-reperfusion in a rat model of cardiac ischemia-reperfusion injury. Methods In the rat model, the therapeutic window and the dose effect relationship were investigated in order to select the proper dose and design for clinical investigations. To evaluate post-ischemic functional recovery, TRO40303 was tested in a model of isolated rat heart. Additionally, TRO40303 was investigated in a Phase I randomized, double-blind, placebo controlled study to assess the safety, tolerability and pharmacokinetics of single intravenous ascending doses of the compound (0.5 to 13 mg/kg) in 72 healthy male, post-menopausal and hysterectomized female subjects at flow rates from 0.04 to 35 mL/min (EudraCT number: 2010-021453-39). This work was supported in part by the French Agence Nationale de la Recherche. Results In the vivo model, TRO40303 reduced infarct size by 40% at 1 mg/kg and by 50% at 3 and 10 mg/kg given by intravenous bolus and was only active when administered before reperfusion. Additionally, TRO40303 provided functional recovery and reduced oxidative stress in the isolated rat heart model. These results, together with pharmacokinetic based allometry to human and non-clinical toxicology data, were used to design the Phase I trial. All the tested doses and flow rates were well tolerated clinically. There were no serious adverse events reported. No relevant changes in vital signs, electrocardiogram parameters, laboratory tests or physical examinations were observed at any time in any dose group. Pharmacokinetics was linear up to 6 mg/kg and slightly ~1.5-fold, hyper-proportional from 6 to 13 mg/kg. Conclusions These data demonstrated that TRO40303 can be safely administered by the intravenous route in humans at doses expected to be pharmacologically active. These results allowed evaluating the expected active dose in human at 6 mg/kg, used in a Phase II proof-of-concept study currently ongoing. PMID:24507657

2014-01-01

127

S-values calculated from a tomographic head/brain model for brain imaging  

NASA Astrophysics Data System (ADS)

A tomographic head/brain model was developed from the Visible Human images and used to calculate S-values for brain imaging procedures. This model contains 15 segmented sub-regions including caudate nucleus, cerebellum, cerebral cortex, cerebral white matter, corpus callosum, eyes, lateral ventricles, lenses, lentiform nucleus, optic chiasma, optic nerve, pons and middle cerebellar peduncle, skull CSF, thalamus and thyroid. S-values for C-11, O-15, F-18, Tc-99m and I-123 have been calculated using this model and a Monte Carlo code, EGS4. Comparison of the calculated S-values with those calculated from the MIRD (1999) stylized head/brain model shows significant differences. In many cases, the stylized head/brain model resulted in smaller S-values (as much as 88%), suggesting that the doses to a specific patient similar to the Visible Man could have been underestimated using the existing clinical dosimetry.

Chao, Tsi-chian; Xu, X. George

2004-11-01

128

Diffusion Modeling in BrainSuite13 Justin P. Haldar  

E-print Network

Diffusion Modeling in BrainSuite13 Justin P. Haldar #12;Outline Introduction Diffusion in BrainSuite13 Diffusion Modeling Tracking Analysis Other Resources Conclusion 2 #12;Apparent Diffusion Coefficient Fractional Anisotropy Anomalous Exponent Kurtosis Motivation 3 Diffusion MRI provides unique

Leahy, Richard M.

129

Socioeconomic status, cognitive-emotional factors, and health status following myocardial infarction: testing the Reserve Capacity Model.  

PubMed

Health disparities by socioeconomic status (SES) exist for many outcomes, including patients' subjective health status after myocardial infarction (MI). The Reserve Capacity Model (RCM), a theoretical means to understand such disparities, was tested to examine the possible mediating effects of cognitive-emotional factors on the association between SES and health status. Data from 2,348 post-MI patients in PREMIER were used. Indicators of SES were collected during hospitalization via personal interviews, while participants completed measures of stress and reserves at 1 month, depressive symptoms at 6 months, and health status at 1 year through telephone interviews. Structural equation model results provide partial support for the RCM, as cognitive-emotional factors partially mediated the association between SES and mental health status. For physical health status, results supported direct rather than indirect effects of SES. Findings suggest psychosocial interventions with patients of low SES will have their greatest effects on appraisals of psychological health status. PMID:25022863

Bennett, Kymberley K; Buchanan, Donna M; Jones, Philip G; Spertus, John A

2015-02-01

130

Modeling Brain Resonance Phenomena Using a Neural Mass Model  

PubMed Central

Stimulation with rhythmic light flicker (photic driving) plays an important role in the diagnosis of schizophrenia, mood disorder, migraine, and epilepsy. In particular, the adjustment of spontaneous brain rhythms to the stimulus frequency (entrainment) is used to assess the functional flexibility of the brain. We aim to gain deeper understanding of the mechanisms underlying this technique and to predict the effects of stimulus frequency and intensity. For this purpose, a modified Jansen and Rit neural mass model (NMM) of a cortical circuit is used. This mean field model has been designed to strike a balance between mathematical simplicity and biological plausibility. We reproduced the entrainment phenomenon observed in EEG during a photic driving experiment. More generally, we demonstrate that such a single area model can already yield very complex dynamics, including chaos, for biologically plausible parameter ranges. We chart the entire parameter space by means of characteristic Lyapunov spectra and Kaplan-Yorke dimension as well as time series and power spectra. Rhythmic and chaotic brain states were found virtually next to each other, such that small parameter changes can give rise to switching from one to another. Strikingly, this characteristic pattern of unpredictability generated by the model was matched to the experimental data with reasonable accuracy. These findings confirm that the NMM is a useful model of brain dynamics during photic driving. In this context, it can be used to study the mechanisms of, for example, perception and epileptic seizure generation. In particular, it enabled us to make predictions regarding the stimulus amplitude in further experiments for improving the entrainment effect. PMID:22215992

Spiegler, Andreas; Knösche, Thomas R.; Schwab, Karin; Haueisen, Jens; Atay, Fatihcan M.

2011-01-01

131

Mathematical modeling of human brain physiological data  

NASA Astrophysics Data System (ADS)

Recently, a mathematical model of the basic physiological processes regulating the cerebral perfusion and oxygen supply was introduced [Jung , J. Math. Biol.JMBLAJ0303-681210.1007/s00285-005-0343-5 51, 491 (2005)]. Although this model correctly describes the interdependence of arterial blood pressure (ABP) and intracranial pressure (ICP), it fails badly when it comes to explaining certain abnormal correlations seen in about 80% of the recordings of ABP together with ICP and the partial oxygen pressure (TiPO2) of the neuronal tissue, taken at an intensive care unit during neuromonitoring of patients with a severe brain trauma. Such recordings occasionally show segments, where the mean arterial blood pressure is correlated with the partial oxygen pressure in tissue but anticorrelated with the intracranial pressure. The origin of such abnormal correlations has not been fully understood yet. Here, two extensions to the previous approach are proposed which can reproduce such abnormal correlations in simulations quantitatively. Furthermore, as the simulations are based on a mathematical model, additional insight into the physiological mechanisms from which such abnormal correlations originate can be gained.

Böhm, Matthias; Faltermeier, Rupert; Brawanski, Alexander; Lang, Elmar W.

2013-12-01

132

Application of peripheral-blood-derived endothelial progenitor cell for treating ischemia-reperfusion injury and infarction: a preclinical study in rat models  

PubMed Central

Background Our aim was to explore the therapeutic effects of peripheral blood-derived endothelial progenitor cells (PB-EPC) in cardiac ischemia-reperfusion infarction models in rats and in in vitro culture systems. Methods Rat models of ischemia reperfusion and myocardial infarction were developed using male, Sprague–Dawley rats. Cardiomyocyte and endothelial cell cultures were also established. Therapeutic effects of PB-EPCs were examined in vivo and in vitro in both models. Rats underwent either cardiac ischemia-reperfusion (n?=?40) or infarction (n?=?56) surgeries and were transplanted with genetically modified EPCs. Treatment efficacy in the ischemia-reperfusion group was measured by infarct size, myocardial contraction velocity, and myeloperoxidase activity after transplantation. Cardiomyocyte survival and endothelial cell apoptosis were investigated in vitro. Vascular growth-associated protein expression and cardiac function were evaluated in the myocardial infarction group by western blot and echocardiography, respectively. Results Infarct size and myeloperoxidase activity were significantly decreased in the ischemia-reperfusion group, whereas myocardial contractility was significantly increased in the EPC and T?4 groups compared with that in the control group. In contrast, no differences were found between EPC?+?shRNA T?4 and control groups. Rates of cardiomyocyte survival and endothelial cell apoptosis were significantly higher and lower, respectively, in the EPC and T?4 groups than in the control group, whereas no differences were found between the EPC?+?shRNA T?4 and control group. Four weeks after myocardial infarction, cardiac function was significantly better in the EPC group than in the control group. Expressions of PDGF, VEGF, and Flk-1 were significantly higher in EPC group than in control group. Conclusions Study findings suggest that PB-EPCs are able to protect cardiomyocytes from ischemia-reperfusion or infarction-induced damage via a T?4-mediated mechanism. EPCs may also provide protection through increased expression of proteins involved in mediating vascular growth. Autologous peripheral-blood-derived EPCs are readily available for efficient therapeutic use without the concerns of graft rejection. PMID:23452866

2013-01-01

133

Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models  

PubMed Central

Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cells were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibrillary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibrillary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibrillary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cells. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells. PMID:25206546

Qiao, Guanqun; Li, Qingquan; Peng, Gang; Ma, Jun; Fan, Hongwei; Li, Yingbin

2013-01-01

134

Volumetric Intraoperative Brain Deformation Compensation: Model Development and Phantom Validation  

PubMed Central

During neurosurgery, nonrigid brain deformation may affect the reliability of tissue localization based on preoperative images. To provide accurate surgical guidance in these cases, preoperative images must be updated to reflect the intraoperative brain. This can be accomplished by warping these preoperative images using a biomechanical model. Due to the possible complexity of this deformation, intraoperative information is often required to guide the model solution. In this paper, a linear elastic model of the brain is developed to infer volumetric brain deformation associated with measured intraoperative cortical surface displacement. The developed model relies on known material properties of brain tissue, and does not require further knowledge about intraoperative conditions. To provide an initial estimation of volumetric model accuracy, as well as determine the model’s sensitivity to the specified material parameters and surface displacements, a realistic brain phantom was developed. Phantom results indicate that the linear elastic model significantly reduced localization error due to brain shift, from >16 mm to under 5 mm, on average. In addition, though in vivo quantitative validation is necessary, preliminary application of this approach to images acquired during neocortical epilepsy cases confirms the feasibility of applying the developed model to in vivo data. PMID:22562728

DeLorenzo, Christine; Papademetris, Xenophon; Staib, Lawrence H.; Vives, Kenneth P.; Spencer, Dennis D.; Duncan, James S.

2012-01-01

135

77 FR 13578 - Disability and Rehabilitation Research Project; Traumatic Brain Injury Model Systems Centers  

Federal Register 2010, 2011, 2012, 2013, 2014

...Rehabilitation Research Project; Traumatic Brain Injury Model Systems Centers AGENCY: Office...Rehabilitation Research Project--Traumatic Brain Injury Model Systems Centers. CFDA Number...Projects (DRRPs) to serve as Traumatic Brain Injury Model Systems (TBIMS)...

2012-03-07

136

77 FR 34363 - Disability and Rehabilitation Research Projects and Centers Program; Traumatic Brain Injury Model...  

Federal Register 2010, 2011, 2012, 2013, 2014

...Projects and Centers Program; Traumatic Brain Injury Model Systems Centers AGENCY: Office...Research Project (DRRP)-- Traumatic Brain Injury Model Systems Centers. SUMMARY...notice announces a priority for Traumatic Brain Injury Model Systems (TBIMS)...

2012-06-11

137

On a Mathematical Model of Brain Activities  

SciTech Connect

The procedure of recognition can be described as follows: There is a set of complex signals stored in the memory. Choosing one of these signals may be interpreted as generating a hypothesis concerning an 'expexted view of the world'. Then the brain compares a signal arising from our senses with the signal chosen from the memory leading to a change of the state of both signals. Furthermore, measurements of that procedure like EEG or MEG are based on the fact that recognition of signals causes a certain loss of excited neurons, i.e. the neurons change their state from 'excited' to 'nonexcited'. For that reason a statistical model of the recognition process should reflect both--the change of the signals and the loss of excited neurons. A first attempt to explain the process of recognition in terms of quantum statistics was given. In the present note it is not possible to present this approach in detail. In lieu we will sketch roughly a few of the basic ideas and structures of the proposed model of the recognition process (Section). Further, we introduce the basic spaces and justify the choice of spaces used in this approach. A more elaborate presentation including all proofs will be given in a series of some forthcoming papers. In this series also the procedures of creation of signals from the memory, amplification, accumulation and transformation of input signals, and measurements like EEG and MEG will be treated in detail.

Fichtner, K.-H. [Friedrich Schiller Unversity Jena, Institute of Applied Mathematics, E.-Abbe-Platz 2, 07743 Jena (Germany); Fichtner, L. [Friedrich Schiller Unversity Jena, Institute of Psychology, Am Steiger 3, 07743 Jena (Germany); Freudenberg, W. [Brandenb. Techn. University Cottbus, Dep. of Mathematics, PO box 10 13 44, 03013 Cottbus (Germany); Ohya, M. [Tokyo University of Science, Department of Information Science, Noda City, Chiba 278-8510 (Japan)

2007-12-03

138

On a Mathematical Model of Brain Activities  

NASA Astrophysics Data System (ADS)

The procedure of recognition can be described as follows: There is a set of complex signals stored in the memory. Choosing one of these signals may be interpreted as generating a hypothesis concerning an "expexted view of the world". Then the brain compares a signal arising from our senses with the signal chosen from the memory leading to a change of the state of both signals. Furthermore, measurements of that procedure like EEG or MEG are based on the fact that recognition of signals causes a certain loss of excited neurons, i.e. the neurons change their state from "excited" to "nonexcited". For that reason a statistical model of the recognition process should reflect both—the change of the signals and the loss of excited neurons. A first attempt to explain the process of recognition in terms of quantum statistics was given in [1]. In the present note it is not possible to present this approach in detail. In lieu we will sketch roughly a few of the basic ideas and structures of the proposed model of the recognition process (Section). Further, we introduce the basic spaces and justify the choice of spaces used in this approach. A more elaborate presentation including all proofs will be given in a series of some forthcoming papers [2, 3]. In this series also the procedures of creation of signals from the memory, amplification, accumulation and transformation of input signals, and measurements like EEG and MEG will be treated in detail.

Fichtner, K.-H.; Fichtner, L.; Freudenberg, W.; Ohya, M.

2007-12-01

139

Experimental models of repetitive brain injuries  

Microsoft Academic Search

Repetitive traumatic brain injury (TBI) occurs in a significant portion of trauma patients, especially in specific populations, such as child abuse victims or athletes involved in contact sports (e.g. boxing, football, hockey, and soccer). A continually emerging hypothesis is that repeated mild injuries may cause cumulative damage to the brain, resulting in long-term cognitive dysfunction. The growing attention to this

John T. Weber

2007-01-01

140

Benefits of Standardizing the Treatment of Arrhythmias in the Sheep (Ovis aries) Model of Chronic Heart Failure after Myocardial Infarction  

PubMed Central

Large animal models of heart failure are essential in preclinical device testing. In sheep, catheter-based coil embolization of the left anterior descending and diagonal artery provides a minimally invasive and reproducible model of myocardial infarction (MI). Although widely used, this model has historically been plagued with a 30% mortality rate, both in the literature and in our own experience. Our study endeavored to decrease the mortality rate by targeting the most common cause of death, intractable arrhythmias, during creation of the ovine MI model. To this end, we evaluated 2 methods of managing perioperative antiarrhythmic therapy and cardiopulmonary resuscitation during model creation. The first group of sheep was managed at the discretion of the individual operator, whereas the second group was treated according to a standardized protocol that included mandatory pretreatment with amiodarone. Sheep experiencing life-threatening arrhythmias, most commonly ventricular fibrillation, were either resuscitated according to operator-driven instructions or the standardized protocol. By comparing these 2 treatment groups, we have shown that using a standardized protocol is advantageous in reducing mortality associated with the ovine MI model. Since implementing the standardized protocol, our laboratory has lowered the expected mortality rate to 10% during catheter-based induction of ovine MI and has greatly reduced the number of animals required for study needs. In addition, the standardized protocol has proven beneficial in training new staff members. By implementing this standardized method of model management, the outcomes of model creation have been optimized. PMID:23849412

Dardenne, Adrienne; Fernandez, Carlos; Wagner, Alyssa; Milewski, Krzysztof; Ordanes, Diane R; Mount, Patricia A; Cheng, Yanping; Yi, Geng-Hua; Conditt, Gerard B; Tellez, Armando; Kaluza, Greg L; Granada, Juan F; Feeney, William P

2013-01-01

141

Hydrogen sulfide protects the brain against ischemic reperfusion injury in a transient model of focal cerebral ischemia.  

PubMed

Hydrogen sulfide (H(2)S), a well-known toxic gas, is regarded as endogenous neuromodulator and plays multiple roles in the central nervous system under physiological and pathological states, especially in secondary neuronal injury. Recent studies have shown relatively high concentrations of hydrogen sulfide (H(2)S) in the brain and also cytoprotective effects of endogenous and exogenous H(2)S in models of in vitro and in vivo ischemic injury. H(2)S protects neurons by functioning as an anti-oxidant, anti-inflammatory, and anti-apoptotic mediator and by improving neurological function. Moreover, it protects neurons from glutamate toxicity. Therefore, the present study aimed to determine whether H(2)S provides protection in transient focal cerebral ischemia. Focal ischemia was induced by 60-min middle cerebral artery occlusion (MCAO), followed by 23-h reperfusion. Saline as a vehicle and NaHS (H(2)S donor; 1 and 5 mg) were intraperitoneally injected (IP) at the beginning of ischemia. Infarct volume, brain edema, and apoptosis were assessed 24 h after MCAO.Treatment with NaHS at doses of 1 and 5 mg markedly reduced total infarct volumes by 29 and 51 %, respectively (P?brain edema (P?brain injuries and postischemic cerebral edema in a dose-dependent manner likely through the blocking programmed cell death.We propose that H(2)S might be a promising therapeutic target for stroke, although more researches are necessary to take into account the potential therapeutic effects of H(2)S in stroke patients. PMID:24643521

Gheibi, Sevda; Aboutaleb, Nahid; Khaksari, Mehdi; Kalalian-Moghaddam, Hamid; Vakili, Abedin; Asadi, Yasin; Mehrjerdi, Fatemeh Zare; Gheibi, Azam

2014-10-01

142

A Novel Three-Phase Model of Brain Tissue Microstructure  

E-print Network

all depend on ECS integrity. Many pathological brain conditions are associated with changes in ECSA Novel Three-Phase Model of Brain Tissue Microstructure Jana L. Gevertz1 , Salvatore Torquato1 States of America, 3 Princeton Institute for the Science and Technology of Materials, Princeton

Torquato, Salvatore

143

Modeling Integration and Dissociation in Brain and Cognitive Development  

Microsoft Academic Search

Over the course of development, brain areas can become increasingly dissociated in their functions, or increasingly integrated. Computational models can provide insights into how and why these opposing effects happen. This paper presents a computational framework for understanding the specialization of brain functions across the hippocampus, neocortex, and basal ganglia. This framework is based on computational tradeoffs that arise in

Randall C. O'Reilly

144

Cardioprotection by L-glutamate during postischaemic reperfusion: reduced infarct size and enhanced glycogen resynthesis in a rat insulin-free heart model.  

PubMed

1. Previously, we found that administration of high-dose L-glutamate during postischaemic reperfusion improves haemodynamic recovery and enhances glycogen resynthesis. In the present study, we investigated whether the same effect occurs in an insulin-free model and whether glutamate administration reduces infarct size. Further, we studied whether the cardioprotective effect of glutamate depends on preserved glutamate transamination and K(ATP) channel activity. 2. In a rat isolated, insulin-free, perfused heart model, we compared the effects of administration of L-glutamate (10 mmol/L) during either 45 min no-flow regional ischaemia plus 120 min reperfusion or reperfusion alone on infarct size and left ventricular (LV) recovery. The effect of glutamate on glycogen metabolism was studied in a model of 30 min global no-flow ischaemia and 60 min reperfusion. In both models, the effects of inhibition of glutamate transamination and K(ATP) channel activity were examined by adding amino-oxyacetate (an aminotransferase inhibitor; 0.1 mmol/L) and glibenclamide (a K(ATP) blocker; 10 mmol/L), respectively. 3. Administration of L-glutamate reduced infarct size by 60% (P < 0.01) and improved postischaemic LV function (developed pressure and rate pressure product; P < 0.05). L-Glutamate increased glycogen content after 60 min reperfusion by 65% (P < 0.01). Amino-oxyacetate, as well as glibenclamide, abolished the glutamate-mediated reduction in infarct size, haemodynamic improvement and glycogen resynthesis during reperfusion. 4. In conclusion, L-glutamate administration from the start of postischaemic reperfusion exerts cardioprotective effects, including reduced infarct size, improved haemodynamic recovery and enhanced glycogen resynthesis. These effects depend on preserved transamination of glutamate and K(ATP) channel activity, but not on insulin administration. PMID:18346179

Kristiansen, Steen B; Løfgren, Bo; Støttrup, Nicolaj B; Kimose, Hans-Henrik; Nielsen-Kudsk, Jens E; Bøtker, Hans E; Nielsen, Torsten T

2008-08-01

145

The Virtual Brain Integrates Computational Modeling and Multimodal Neuroimaging  

PubMed Central

Abstract Brain function is thought to emerge from the interactions among neuronal populations. Apart from traditional efforts to reproduce brain dynamics from the micro- to macroscopic scales, complementary approaches develop phenomenological models of lower complexity. Such macroscopic models typically generate only a few selected—ideally functionally relevant—aspects of the brain dynamics. Importantly, they often allow an understanding of the underlying mechanisms beyond computational reproduction. Adding detail to these models will widen their ability to reproduce a broader range of dynamic features of the brain. For instance, such models allow for the exploration of consequences of focal and distributed pathological changes in the system, enabling us to identify and develop approaches to counteract those unfavorable processes. Toward this end, The Virtual Brain (TVB) (www.thevirtualbrain.org), a neuroinformatics platform with a brain simulator that incorporates a range of neuronal models and dynamics at its core, has been developed. This integrated framework allows the model-based simulation, analysis, and inference of neurophysiological mechanisms over several brain scales that underlie the generation of macroscopic neuroimaging signals. In this article, we describe how TVB works, and we present the first proof of concept. PMID:23442172

Schirner, Michael; McIntosh, Anthony R.; Jirsa, Viktor K.

2013-01-01

146

Zebrafish as an emerging model for studying complex brain disorders  

PubMed Central

The zebrafish (Danio rerio) is rapidly becoming a popular model organism in pharmacogenetics and neuropharmacology. Both larval and adult zebrafish are currently used to increase our understanding of brain function, dysfunction, and their genetic and pharmacological modulation. Here we review the developing utility of zebrafish in the analysis of complex brain disorders (including, for example, depression, autism, psychoses, drug abuse and cognitive disorders), also covering zebrafish applications towards the goal of modeling major human neuropsychiatric and drug-induced syndromes. We argue that zebrafish models of complex brain disorders and drug-induced conditions have become a rapidly emerging critical field in translational neuropharmacology research. PMID:24412421

Kalueff, Allan V.; Stewart, Adam Michael; Gerlai, Robert

2014-01-01

147

Controlling ferrofluid permeability across the blood–brain barrier model.  

PubMed

In the present study, an in vitro blood–brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood–brain barrier model was completed by examining the permeability of FITCDextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood–brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood–brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood–brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood–brain barrier (e.g. CPB). PMID:24457539

Shi, Di; Sun, Linlin; Mi, Gujie; Sheikh, Lubna; Bhattacharya, Soumya; Nayar, Suprabha; Webster, Thomas J

2014-02-21

148

Controlling ferrofluid permeability across the blood-brain barrier model  

NASA Astrophysics Data System (ADS)

In the present study, an in vitro blood-brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood-brain barrier model was completed by examining the permeability of FITC-Dextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood-brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood-brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood-brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood-brain barrier (e.g. CPB).

Shi, Di; Sun, Linlin; Mi, Gujie; Sheikh, Lubna; Bhattacharya, Soumya; Nayar, Suprabha; Webster, Thomas J.

2014-02-01

149

Echocardiographic assessment of coronary artery flow in normal canines and model dogs with myocardial infarction  

PubMed Central

This study was conducted to evaluate the usefulness of coronary arterial profiles from normal dogs (11 animals) and canines (six dogs) with experimental myocardial infarction (MI) induced by ligation of the left coronary artery (LCA). Blood velocity of the LCA and right coronary artery (RCA) were evaluated following transthoracic pulsed-wave Doppler echocardiography. The LCA was observed as an infundibular shape, located adjacent to the sinus of Valsalva. The RCA appeared as a tubular structure located 12 o'clock relative to the aorta. In normal dogs, the LCA and RCA mean peak diastolic velocities were 20.84 ± 3.24 and 19.47 ± 2.67 cm/sec, respectively. The LCA and RCA mean diastolic deceleration times were 0.91 ± 0.14 sec and 1.13 ± 0.20 sec, respectively. In dogs with MI, the LCA had significantly (p < 0.01) lower peak velocities (14.82 ± 1.61 cm/sec) than the RCA (31.61 ± 2.34 cm/sec). The RCA had a significantly (p < 0.01) rapid diastolic deceleration time (0.71 ± 0.06 sec) than that found in the LCA (1.02 ± 0.22 sec) of MI dogs. In conclusion, these profiles may serve as a differential factor for evaluating cardiomyopathy in dogs. PMID:23820197

Park, Nohwon; Kim, Jaehwan; Lee, Miyoung; Lee, Soyun; Song, Sunhye; Lee, Seungjun; Kim, Soyoung; Park, Yangwoo

2014-01-01

150

RESEARCH Open Access Repairing chronic myocardial infarction with  

E-print Network

RESEARCH Open Access Repairing chronic myocardial infarction with autologous mesenchymal stem cells) seeded on collagen-1 scaffold on the cardiac reconstruction in rat model of chronic myocardial infarction to control (64 ± 4% vs 49 ± 3% p = 0.02) and a reduced infarction. Contractile parameter dp/dtmax and dp

Paris-Sud XI, Université de

151

Generative Models of Brain Connectivity for Population Studies Archana Venkataraman  

E-print Network

Generative Models of Brain Connectivity for Population Studies by Archana Venkataraman S.B., Electrical Engineering, Massachusetts Institute of Technology (2006) M.Eng., Electrical Engineering, Massachusetts Institute of Technology (2007) Submitted to the Department of Electrical Engineering and Computer

Golland, Polina

152

Comparison of three rheological models of shear flow behavior studied on blood samples from post-infarction patients.  

PubMed

Quantitative analysis of blood viscosity was performed on the basis of mathematical models of non-Newtonian fluid shear flow behavior (Casson, Ree-Eyring and Quemada). A total of 100 blood samples were drawn from clinically stable survivors of myocardial infarction, treated with aspirin or acenocoumarol and controls to these drugs. Whole blood and plasma viscosity were measured at a broad range of shear rates using a rotary-oscillating viscometer Contraves LS40. Numerical analysis of the experimental data was carried out by means of linear (for Casson) and non-linear regression for the remaining models. In the evaluation of the results, both the fit quality and physical interpretation of the models' parameters were considered. The Quemada model fitted most precisely with the experimental findings and, despite the controversies concerning the relationship between in vivo tissue perfusion and in vitro rheological measurements, seemed to be a valuable method enhancing investigation possibilities of cardiovascular patients. Our results suggest that aspirin does not affect blood rheological properties, while acenocoumarol may slightly alter red cell deformability and rouleaux formation. PMID:17674068

Marcinkowska-Gapi?ska, Anna; Gapinski, Jacek; Elikowski, Waldemar; Jaroszyk, Feliks; Kubisz, Leszek

2007-09-01

153

Distributed parameters deterministic model for treatment of brain tumors using Galerkin  

E-print Network

is the blood brain barrier (BBB), which exists in the human brain as a desirable protection for the brain cellsDistributed parameters deterministic model for treatment of brain tumors using Galerkin finite, we present a distributed parameters deterministic model for treat- ment of brain tumors using

Hanson, Floyd B.

154

A dynamic phantom brain model for near-infrared spectroscopy  

Microsoft Academic Search

Describes the construction, fluid dynamics and optical properties of an in vitro model of the neonatal brain for testing near-infrared spectroscopy (NIRS) instruments. The brain model is a solid plastic structure containing a vascular network perfused with blood equilibrated with O2, N2 and CO2 in a closed circuit. The oxygenation state and haemoglobin concentration of the perfusate can be regulated

C. D. Kurth; Hanli Liu; W. S. Thayer; B. Chance

1995-01-01

155

A Large-Scale Model of the Functioning Brain  

Microsoft Academic Search

A central challenge for cognitive and systems neuroscience is to relate the incredibly complex behavior of animals to the equally complex activity of their brains. Recently described, large-scale neural models have not bridged this gap between neural activity and biological function. In this work, we present a 2.5-million-neuron model of the brain (called “Spaun”) that bridges this gap by exhibiting

Chris Eliasmith; Terrence C. Stewart; Xuan Choo; Trevor Bekolay; Travis DeWolf; Yichuan Tang; Daniel Rasmussen

2012-01-01

156

Rasagiline is neuroprotective in an experimental model of brain ischemia in the rat  

Microsoft Academic Search

Summary.  The neuroprotective effects of intravenous rasagiline were investigated in a rat model of stroke. Middle cerebral artery (MCA)\\u000a occlusion was performed in male rats and the short- (neurological severity score [NSS], infarct size), intermediate- (cognition)\\u000a and long-term (necrotic area) effects were assessed. A bolus (3?mg\\/kg) of rasagiline followed by a 3-h infusion (3?mg\\/kg\\/h),\\u000a initiated immediately after MCA occlusion, reduced infarct

Z. Speiser; A. Mayk; L. Litinetsky; T. Fine; A. Nyska; E. Blaugrund; S. Cohen

2007-01-01

157

Fluid-percussion–induced traumatic brain injury model in rats  

Microsoft Academic Search

Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Various attempts have been made to replicate clinical TBI using animal models. The fluid-percussion model (FP) is one of the oldest and most commonly used models of experimentally induced TBI. Both central (CFP) and lateral (LFP) variations of the model have been used. Developed initially for use in

Shruti V Kabadi; Genell D Hilton; Bogdan A Stoica; David N Zapple; Alan I Faden

2010-01-01

158

A cell culture model of the blood-brain barrier  

PubMed Central

Endothelial cells that make up brain capillaries and constitute the blood-brain barrier become different from peripheral endothelial cells in response to inductive factors found in the nervous system. We have established a cell culture model of the blood-brain barrier by treating brain endothelial cells with a combination of astrocyte-conditioned medium and agents that elevate intracellular cAMP. These cells form high resistance tight junctions and exhibit low rates of paracellular leakage and fluid-phase endocytosis. They also undergo a dramatic structural reorganization as they form tight junctions. Results from these studies suggest modes of manipulating the permeability of the blood-brain barrier, potentially providing the basis for increasing the penetration of drugs into the central nervous system. PMID:1661734

1991-01-01

159

Cerebral organoids model human brain development and microcephaly  

PubMed Central

The complexity of the human brain has made it difficult to study many brain disorders in model organisms, and highlights the need for an in vitro model of human brain development. We have developed a human pluripotent stem cell-derived 3D organoid culture system, termed cerebral organoid, which develops various discrete though interdependent brain regions. These include cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNAi and patient-specific iPS cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could explain the disease phenotype. Our data demonstrate that 3D organoids can recapitulate development and disease of even this most complex human tissue. PMID:23995685

Lancaster, Madeline A.; Renner, Magdalena; Martin, Carol-Anne; Wenzel, Daniel; Bicknell, Louise S.; Hurles, Matthew E.; Homfray, Tessa; Penninger, Josef M.; Jackson, Andrew P.; Knoblich, Juergen A.

2013-01-01

160

A Bayesian Model of Category-Specific Emotional Brain Responses  

PubMed Central

Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories—fear, anger, disgust, sadness, or happiness—is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490

Wager, Tor D.; Kang, Jian; Johnson, Timothy D.; Nichols, Thomas E.; Satpute, Ajay B.; Barrett, Lisa Feldman

2015-01-01

161

A bayesian model of category-specific emotional brain responses.  

PubMed

Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories-fear, anger, disgust, sadness, or happiness-is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490

Wager, Tor D; Kang, Jian; Johnson, Timothy D; Nichols, Thomas E; Satpute, Ajay B; Barrett, Lisa Feldman

2015-04-01

162

Biothermal Model of Patient and Automatic Control System of Brain Temperature for Brain Hypothermia Treatment  

NASA Astrophysics Data System (ADS)

Various surface-cooling apparatus such as the cooling cap, muffler and blankets have been commonly used for the cooling of the brain to provide hypothermic neuro-protection for patients of hypoxic-ischemic encephalopathy. The present paper is aimed at the brain temperature regulation from the viewpoint of automatic system control, in order to help clinicians decide an optimal temperature of the cooling fluid provided for these three types of apparatus. At first, a biothermal model characterized by dynamic ambient temperatures is constructed for adult patient, especially on account of the clinical practice of hypothermia and anesthesia in the brain hypothermia treatment. Secondly, the model is represented by the state equation as a lumped parameter linear dynamic system. The biothermal model is justified from their various responses corresponding to clinical phenomena and treatment. Finally, the optimal regulator is tentatively designed to give clinicians some suggestions on the optimal temperature regulation of the patient’s brain. It suggests the patient’s brain temperature could be optimally controlled to follow-up the temperature process prescribed by the clinicians. This study benefits us a great clinical possibility for the automatic hypothermia treatment.

Wakamatsu, Hidetoshi; Gaohua, Lu

163

3D Echo-Based Patient-Specific Computational Left Ventricle Models to Quantify Material Properties and Stress/Strain Differences between Ventricles with and without Infarct  

PubMed Central

Identifying ventricle material properties and its infarct area after heart attack noninvasively is of great important in clinical applications. An echo-based computational modeling approach was proposed to investigate left ventricle (LV) mechanical properties and stress conditions using patient-specific data. Echo data was acquired from one healthy volunteer (male, age: 58) and a male patient (age: 60) who had an acute inferior myocardial infarction one week before echo image acquisition. Standard echocardiograms were obtained using an ultrasound machine (E9, GE Mechanical Systems, Milwaukee, Wisconsin) with a 3V probe and data were segmented for model construction. Finite element models were constructed to obtain ventricle stress and strain conditions. A pre-shrink process was applied so that the model ventricle geometries under end-of-systole pressure matched in vivo data. Our results indicated that the modeling approach has the potential to be used to determine ventricle material properties. The equivalent Young’s modulus value from the healthy LV (LV1) was about 30% softer than that of the infarct LV (LV2) at end of diastole, but was about 100% stiffer than that of LV2 at end of systole. This can be explained as LV1 has more active contraction reflected by stiffness variations. Using averaged values, at end-systole, longitudinal curvature from LV2 was 164% higher than that from LV1. LV stress from LV2 was 82% higher than that from LV1. At end-diastole, L-curvature from LV2 was still 132% higher than that from LV1, while LV stress from LV2 was only 9% higher than that from LV1. Longitudinal curvature and stress showed the largest differences between the two ventricles, with the LV with infarct having higher longitudinal curvature and stress values. Large scale studies are needed to further confirm our findings. PMID:25663830

Fan, Rui; Yao, Jing; Yang, Chun; Xu, Di

2014-01-01

164

A hierarchical model of the evolution of human brain specializations  

PubMed Central

The study of information-processing adaptations in the brain is controversial, in part because of disputes about the form such adaptations might take. Many psychologists assume that adaptations come in two kinds, specialized and general-purpose. Specialized mechanisms are typically thought of as innate, domain-specific, and isolated from other brain systems, whereas generalized mechanisms are developmentally plastic, domain-general, and interactive. However, if brain mechanisms evolve through processes of descent with modification, they are likely to be heterogeneous, rather than coming in just two kinds. They are likely to be hierarchically organized, with some design features widely shared across brain systems and others specific to particular processes. Also, they are likely to be largely developmentally plastic and interactive with other brain systems, rather than canalized and isolated. This article presents a hierarchical model of brain specialization, reviewing evidence for the model from evolutionary developmental biology, genetics, brain mapping, and comparative studies. Implications for the search for uniquely human traits are discussed, along with ways in which conventional views of modularity in psychology may need to be revised. PMID:22723350

Barrett, H. Clark

2012-01-01

165

Development of a Model for Whole Brain Learning of Physiology  

ERIC Educational Resources Information Center

In this report, a model was developed for whole brain learning based on Curry's onion model. Curry described the effect of personality traits as the inner layer of learning, information-processing styles as the middle layer of learning, and environmental and instructional preferences as the outer layer of learning. The model that was developed…

Eagleton, Saramarie; Muller, Anton

2011-01-01

166

Comparison of two sulfonylureas with high and low myocardial K ATP channel affinity on myocardial infarct size and metabolism in a rat model of type 2 diabetes  

Microsoft Academic Search

Aims\\/hypothesis  Sulfonylureas (SUs) may impair outcome in patients with acute coronary syndrome. Most experimental studies of the myocardial\\u000a effects of SU treatment are performed in non-diabetic models. We compared the effect of two widely used SUs, glibenclamide\\u000a (gb) and gliclazide (gc), with high and low myocardial KATP channel affinity, respectively, at therapeutic concentrations on infarct size, left ventricular (LV) function and

S. B. Kristiansen; B. Løfgren; J. M. Nielsen; N. B. Støttrup; E. S. Buhl; J. E. Nielsen-Kudsk; T. T. Nielsen; J. Rungby; A. Flyvbjerg; H. E. Bøtker

2011-01-01

167

Action of acetylstrophanthidin on experimental myocardial infarction.  

NASA Technical Reports Server (NTRS)

An experimental animal model with acute myocardial infarction of a size insufficient to produce profound heart failure or shock was used to study the effects of acute infarction on digitalis tolerance and the hemodynamic changes produced by moderate and large doses of acetylstrophanthidin. With acute myocardial infarction, digitalis toxic arrhythmias could be precipitated with significantly lower doses of digitalis than in animals without myocardial infarction. There was no precise correlation between the size of infarction and the toxic dose of glycoside. Coronary artery ligation produced a stable but relatively depressed circulatory state, as evidenced by lowered cardiac output and stroke volume and elevated systemic vascular resistance and left atrial mean pressure. When digitalis was infused, the following significant changes were observed at nontoxic doses: (1) elevation of aortic and left ventricular pressures; (2) further decline in cardiac output; and (3) decreased left atrial mean pressure.

Nola, G. T.; Pope, S. E.; Harrison, D. C.

1972-01-01

168

Preventive and therapeutic effects of ginsenoside Rb1 for neural injury during cerebral infarction in rats.  

PubMed

To examine the preventive and therapeutic effects of ginsenoside Rb1 for neural injury during cerebral infarction, we used a middle cerebral artery occlusion (MCAO) model in rats to investigate the effects of ginsenoside Rb1 with Edaravone as a control. Ginsenoside Rb1 was given to the rats by intragastric administration either before or after the MCAO surgery to study its preventive and therapeutic effects. Ginsenoside Rb1-treated rats had a smaller infarct volume than the positive control. Interleukin-1 (IL-1), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-? (TNF-?), neurofilament (NF) and growth associated protein-43 (GAP-43) were measured to determine brain damage and the recovery of nerves. These findings suggest that ginsenoside Rb1 has neuroprotective effects in rats, and the protection efficiency is higher than Edaravone. The protective mechanism is different from Edaravone. The preventive ability of ginsenoside Rb1 is higher than its repair ability in neuroprotection in vivo. PMID:23548124

Jiang, Zhou; Wang, Yuhui; Zhang, Xiaoyun; Peng, Tao; Lu, Yun; Leng, Jianchun; Xie, Quan

2013-01-01

169

5?-Adenosine Monophosphate-Induced Hypothermia Attenuates Brain Ischemia/Reperfusion Injury in a Rat Model by Inhibiting the Inflammatory Response  

PubMed Central

Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5?-adenosine monophosphate (5?-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5?-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5?-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.

Miao, Yi-Feng; Wu, Hui; Yang, Shao-Feng; Dai, Jiong; Qiu, Yong-Ming; Tao, Zhen-Yi; Zhang, Xiao-Hua

2015-01-01

170

Mathematical framework for large-scale brain network modeling in The Virtual Brain.  

PubMed

In this article, we describe the mathematical framework of the computational model at the core of the tool The Virtual Brain (TVB), designed to simulate collective whole brain dynamics by virtualizing brain structure and function, allowing simultaneous outputs of a number of experimental modalities such as electro- and magnetoencephalography (EEG, MEG) and functional Magnetic Resonance Imaging (fMRI). The implementation allows for a systematic exploration and manipulation of every underlying component of a large-scale brain network model (BNM), such as the neural mass model governing the local dynamics or the structural connectivity constraining the space time structure of the network couplings. Here, a consistent notation for the generalized BNM is given, so that in this form the equations represent a direct link between the mathematical description of BNMs and the components of the numerical implementation in TVB. Finally, we made a summary of the forward models implemented for mapping simulated neural activity (EEG, MEG, sterotactic electroencephalogram (sEEG), fMRI), identifying their advantages and limitations. PMID:25592995

Sanz-Leon, Paula; Knock, Stuart A; Spiegler, Andreas; Jirsa, Viktor K

2015-05-01

171

An Anthelmintic Drug, Pyrvinium Pamoate, Thwarts Fibrosis and Ameliorates Myocardial Contractile Dysfunction in a Mouse Model of Myocardial Infarction  

PubMed Central

Metabolic adaptation to limited supplies of oxygen and nutrients plays a pivotal role in health and disease. Heart attack results from insufficient delivery of oxygen and nutrients to the heart, where cardiomyocytes die and cardiac fibroblasts proliferate – the latter causing scar formation, which impedes regeneration and impairs contractility of the heart. We postulated that cardiac fibroblasts survive metabolic stress by adapting their intracellular metabolism to low oxygen and nutrients, and impeding this metabolic adaptation would thwart their survival and facilitate the repair of scarred heart. Herein, we show that an anthelmintic drug, Pyrvinium pamoate, which has been previously shown to compromise cancer cell survival under glucose starvation condition, also disables cardiac fibroblast survival specifically under glucose deficient condition. Furthermore, Pyrvinium pamoate reduces scar formation and improves cardiac contractility in a mouse model of myocardial infarction. As Pyrvinium pamoate is an FDA-approved drug, our results suggest a therapeutic use of this or other related drugs to repair scarred heart and possibly other organs. PMID:24223934

Murakoshi, Motoaki; Saiki, Kyohei; Urayama, Kyoji; Sato, Thomas N.

2013-01-01

172

Corticonic models of brain mechanisms underlying cognition and intelligence  

NASA Astrophysics Data System (ADS)

The concern of this review is brain theory or more specifically, in its first part, a model of the cerebral cortex and the way it: (a) interacts with subcortical regions like the thalamus and the hippocampus to provide higher-level-brain functions that underlie cognition and intelligence, (b) handles and represents dynamical sensory patterns imposed by a constantly changing environment, (c) copes with the enormous number of such patterns encountered in a lifetime by means of dynamic memory that offers an immense number of stimulus-specific attractors for input patterns (stimuli) to select from, (d) selects an attractor through a process of “conjugation” of the input pattern with the dynamics of the thalamo-cortical loop, (e) distinguishes between redundant (structured) and non-redundant (random) inputs that are void of information, (f) can do categorical perception when there is access to vast associative memory laid out in the association cortex with the help of the hippocampus, and (g) makes use of “computation” at the edge of chaos and information driven annealing to achieve all this. Other features and implications of the concepts presented for the design of computational algorithms and machines with brain-like intelligence are also discussed. The material and results presented suggest, that a Parametrically Coupled Logistic Map network (PCLMN) is a minimal model of the thalamo-cortical complex and that marrying such a network to a suitable associative memory with re-entry or feedback forms a useful, albeit, abstract model of a cortical module of the brain that could facilitate building a simple artificial brain. In the second part of the review, the results of numerical simulations and drawn conclusions in the first part are linked to the most directly relevant works and views of other workers. What emerges is a picture of brain dynamics on the mesoscopic and macroscopic scales that gives a glimpse of the nature of the long sought after brain code underlying intelligence and other higher level brain functions.

Farhat, Nabil H.

173

Modeling the Developing Drosophila Brain: Rationale, Technique, and Application  

NSDL National Science Digital Library

Digital three-dimensional models, besides representing helpful didactic tools, play an important role in the analysis of brain function and development. The fundamental idea of this approach is that patterns of neural connectivity and activity, pathological lesions, or gene expression are transferred into a single in silico structure: the digital atlas model. This article focuses on recent and ongoing work to build digital models of the developing Drosophila brain, which is formed by an invariant set of approximately 100 neural lineages. Lineages represent key elements in the emerging models of the fly brain: aside from their common origin, which is reflected in the shared expression of numerous developmental control genes, neurons belonging to a given lineage share many morphological characters, including axonal projection and dendritic arborization.

Volker Hartenstein and colleagues (University of California at Los Angeles; )

2008-10-01

174

Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study  

PubMed Central

Background In acute stage of cerebral infarction, MRI indices (rDWI & rADC) deteriorate during the first 3-7 days after the ictus and then gradually normalize in approximately 10 days (pseudonormalization time), although the tissue is already infarcted. Since effective treatments improve these indices significantly and in less than the natural pseudonormalization time, a combined analysis of these changes provides an opportunity for objective evaluation on the effectiveness of various treatments for cerebral infarction. Hydroxyl radicals are highly destructive to the tissue and aggravate cerebral infarction. We treated brainstem infarction patients in acute stage with hydroxyl radical scavengers (Edaravone and hydrogen) by intravenous administration and evaluated the effects of the treatment by a serial observation and analysis of these MRI indices. The effects of the treatment were evaluated and compared in two groups, an Edaravone alone group and a combined group with Edaravone and hydrogen, in order to assess beneficial effects of addition of hydrogen. Methods The patients were divided in Edaravone only group (E group. 26 patients) and combined treatment group with Edaravone and hydrogen enriched saline (EH group. 8 patients). The extent of the initial hump of rDWI, the initial dip of rADC and pseudo-normalization time were determined in each patient serially and averages of these data were compared in these two groups and also with the natural course in the literatures. Results The initial hump of rDWI reached 2.0 in the E group which was better than 2.5 of the natural course but was not as good as 1.5 of the EH group. The initial dip of rADC was 0.6 in the E group which was close to the natural course but worse than 0.8 of the EH group. Pseudonormalization time of rDWI and rADC was 9 days only in EH group but longer in other groups. Addition of hydrogen caused no side effects. Conclusions Administration of hydroxyl radical scavengers in acute stage of brainstem infarction improved MRI indices against the natural course. The effects were more obvious and significant in the EH group. These findings may imply the need for more frequent daily administration of hydroxyl scavenger, or possible additional hydrogen effects on scavenger mechanisms. PMID:22146068

2011-01-01

175

Realistic modeling of neurons and networks: towards brain simulation  

PubMed Central

Summary Realistic modeling is a new advanced methodology for investigating brain functions. Realistic modeling is based on a detailed biophysical description of neurons and synapses, which can be integrated into microcircuits. The latter can, in turn, be further integrated to form large-scale brain networks and eventually to reconstruct complex brain systems. Here we provide a review of the realistic simulation strategy and use the cerebellar network as an example. This network has been carefully investigated at molecular and cellular level and has been the object of intense theoretical investigation. The cerebellum is thought to lie at the core of the forward controller operations of the brain and to implement timing and sensory prediction functions. The cerebellum is well described and provides a challenging field in which one of the most advanced realistic microcircuit models has been generated. We illustrate how these models can be elaborated and embedded into robotic control systems to gain insight into how the cellular properties of cerebellar neurons emerge in integrated behaviors. Realistic network modeling opens up new perspectives for the investigation of brain pathologies and for the neurorobotic field. PMID:24139652

D’Angelo, Egidio; Solinas, Sergio; Garrido, Jesus; Casellato, Claudia; Pedrocchi, Alessandra; Mapelli, Jonathan; Gandolfi, Daniela; Prestori, Francesca

176

MR image denoising method for brain surface 3D modeling  

NASA Astrophysics Data System (ADS)

Three-dimensional (3D) modeling of medical images is a critical part of surgical simulation. In this paper, we focus on the magnetic resonance (MR) images denoising for brain modeling reconstruction, and exploit a practical solution. We attempt to remove the noise existing in the MR imaging signal and preserve the image characteristics. A wavelet-based adaptive curve shrinkage function is presented in spherical coordinates system. The comparative experiments show that the denoising method can preserve better image details and enhance the coefficients of contours. Using these denoised images, the brain 3D visualization is given through surface triangle mesh model, which demonstrates the effectiveness of the proposed method.

Zhao, De-xin; Liu, Peng-jie; Zhang, De-gan

2014-11-01

177

Dietary Soy May Not Confound Acute Experimental Stroke Infarct Volume Outcomes In Ovariectomized Female Rats  

PubMed Central

Estrogen administration can alter experimental stroke outcomes. Soy as a source of phytoestrogens may therefore modulate responses in “estrogen-sensitive” stroke models, thus potentially confounding results. We evaluated the effects of dietary soy on acute infarct volumes in a pilot study using a rat focal stroke model. We hypothesized that ovariectomized (OVX) rats fed a soy-rich diet would have smaller acute infarct volumes than rats fed a soy-free diet. OVX rats were randomly assigned to a soy-free (n=6) or a soy-rich (n=6) diet for 4 weeks and weighed weekly. Following the dietary trial, rats underwent 2 hours of middle cerebral artery occlusion (MCAO). Mean arterial blood pressure, rectal and temporalis muscle temperatures, arterial blood gases, and blood glucose were recorded peri-ischemia. Rats were euthanized 22 hours following 2 hours of MCAO. Brains were stained with 2,3,5-triphenyl tetrazolium chloride for acute infarct volume analysis. Uterine weight and histology were also evaluated as additional internal estrogen-sensitive controls. Rats on the soy-free diet had greater gains in body weight (259±6% baseline body weight) than rats on the soy-rich diet (238±4% baseline body weight). No differences were seen in uterine weight and histology, peri-ischemic physiological parameters, and infarct volumes between the treatment groups. Results of this pilot study suggest that the dietary soy level tested may not alter acute infarct volumes in ischemic female rat brain. More studies addressing the potential confounding effects of dietary soy in “estrogen-sensitive” stroke models are needed if investigators are to make informed choices regarding diets used in experimental stroke research. PMID:20147341

Prongay, Kamm D.; Lewis, Anne D.; Hurn, Patricia D.; Murphy, Stephanie J.

2009-01-01

178

Adoptive Transfer of Myelin Basic Protein-Tolerized Splenocytes to Naive Animals Reduces Infarct Size A Role for Lymphocytes in Ischemic Brain Injury?  

Microsoft Academic Search

Background and Purpose—Breakdown of the blood-brain barrier during stroke allows central nervous system antigens to leak into the systemic circulation and allows circulating leukocytes access to the brain. Encounter of central nervous system antigens by the peripheral immune system can be capitalized on to modulate the postischemic inflammatory response and potentially improve outcome from stroke. Methods—Male Lewis rats were tolerized

Kyra Becker; Darin Kindrick; Richard McCarron; John Hallenbeck; Robert Winn

179

Reperfusion therapy with low-dose insulin or insulin-like growth factor 2; myocardial function and infarct size in a porcine model of ischaemia and reperfusion.  

PubMed

In an open-chest porcine model, we examined whether myocardial pharmacological conditioning at the time of reperfusion with low-dose insulin or insulin-like growth factor 2 (IGF2), not affecting serum glucose levels, could reduce infarct size and improve functional recovery. Two groups of anaesthetized pigs with either 60 or 40 min. of left anterior descending artery occlusion (total n = 42) were randomized to receive either 0.9% saline, insulin or IGF2 infusion for 15 min., starting 5 min. before a 180-min. reperfusion period. Repeated fluorescent microsphere injections were used to confirm ischaemia and reperfusion. Area at risk and infarct size was determined with Evans blue and triphenyltetrazolium chloride staining. Local myocardial function was evaluated with multi-layer radial tissue Doppler strain and speckle-tracking strain from epicardial echocardiography. Western blotting and TUNEL staining were performed to explore apoptosis. Infarct size did not differ between treatment groups and was 56.7 ± 6.8%, 49.7 ± 9.6%, 56.2 ± 8.0% of area at risk for control, insulin and IGF2 group, respectively, in the 60-min. occlusion series. Corresponding values were 45.6 ± 6.0%, 48.4 ± 7.2% and 34.1 ± 5.8% after 40-min. occlusion. Global and local cardiac function did not differ between treatment groups. No differences related to treatment could be found in myocardial tissue cleaved caspase-3 content or the degree of TUNEL staining. Reperfusion therapy with low-dose insulin or with IGF2 neither reduced infarct size nor improved function in reperfused myocardium in this in vivo porcine model. PMID:24751184

Salminen, Pirjo-Riitta; Dahle, Geir Olav; Moen, Christian Arvei; Wergeland, Anita; Jonassen, Anne Kristin; Haaverstad, Rune; Matre, Knut; Grong, Ketil

2014-11-01

180

Reperfusion Therapy with Low-Dose Insulin or Insulin-Like Growth Factor 2; Myocardial Function and Infarct Size in a Porcine Model of Ischaemia and Reperfusion  

PubMed Central

In an open-chest porcine model, we examined whether myocardial pharmacological conditioning at the time of reperfusion with low-dose insulin or insulin-like growth factor 2 (IGF2), not affecting serum glucose levels, could reduce infarct size and improve functional recovery. Two groups of anaesthetized pigs with either 60 or 40 min. of left anterior descending artery occlusion (total n = 42) were randomized to receive either 0.9% saline, insulin or IGF2 infusion for 15 min., starting 5 min. before a 180-min. reperfusion period. Repeated fluorescent microsphere injections were used to confirm ischaemia and reperfusion. Area at risk and infarct size was determined with Evans blue and triphenyltetrazolium chloride staining. Local myocardial function was evaluated with multi-layer radial tissue Doppler strain and speckle-tracking strain from epicardial echocardiography. Western blotting and TUNEL staining were performed to explore apoptosis. Infarct size did not differ between treatment groups and was 56.7 ± 6.8%, 49.7 ± 9.6%, 56.2 ± 8.0% of area at risk for control, insulin and IGF2 group, respectively, in the 60-min. occlusion series. Corresponding values were 45.6 ± 6.0%, 48.4 ± 7.2% and 34.1 ± 5.8% after 40-min. occlusion. Global and local cardiac function did not differ between treatment groups. No differences related to treatment could be found in myocardial tissue cleaved caspase-3 content or the degree of TUNEL staining. Reperfusion therapy with low-dose insulin or with IGF2 neither reduced infarct size nor improved function in reperfused myocardium in this in vivo porcine model. PMID:24751184

Salminen, Pirjo-Riitta; Dahle, Geir Olav; Moen, Christian Arvei; Wergeland, Anita; Jonassen, Anne Kristin; Haaverstad, Rune; Matre, Knut; Grong, Ketil

2014-01-01

181

Kidney Modeling molecular dockingBrain Analysis Visualization  

E-print Network

1 Researcher Kidney Modeling molecular dockingBrain Analysis Visualization e-Research Platform User Environment Globus Condor Alchemi UNICORE XGrid PBS ResearcherResearcher Kidney Modeling molecular docking Computer Servers Virtual Organization Grid Host Environment Globus Condor Alchemi UNICORE XGrid PBS Kidney

Melbourne, University of

182

Creating Physical 3D Stereolithograph Models of Brain and Skull  

PubMed Central

The human brain and skull are three dimensional (3D) anatomical structures with complex surfaces. However, medical images are often two dimensional (2D) and provide incomplete visualization of structural morphology. To overcome this loss in dimension, we developed and validated a freely available, semi-automated pathway to build 3D virtual reality (VR) and hand-held, stereolithograph models. To evaluate whether surface visualization in 3D was more informative than in 2D, undergraduate students (n?=?50) used the Gillespie scale to rate 3D VR and physical models of both a living patient-volunteer's brain and the skull of Phineas Gage, a historically famous railroad worker whose misfortune with a projectile tamping iron provided the first evidence of a structure-function relationship in brain. Using our processing pathway, we successfully fabricated human brain and skull replicas and validated that the stereolithograph model preserved the scale of the VR model. Based on the Gillespie ratings, students indicated that the biological utility and quality of visual information at the surface of VR and stereolithograph models were greater than the 2D images from which they were derived. The method we developed is useful to create VR and stereolithograph 3D models from medical images and can be used to model hard or soft tissue in living or preserved specimens. Compared to 2D images, VR and stereolithograph models provide an extra dimension that enhances both the quality of visual information and utility of surface visualization in neuroscience and medicine. PMID:17971879

Kelley, Daniel J.; Farhoud, Mohammed; Meyerand, M. Elizabeth; Nelson, David L.; Ramirez, Lincoln F.; Dempsey, Robert J.; Wolf, Alan J.; Alexander, Andrew L.; Davidson, Richard J.

2007-01-01

183

Regulatory effect of Dimethyl Sulfoxide (DMSO) on astrocytic reactivity in a murine model of cerebral infarction by arterial embolization  

PubMed Central

Introduction: The pathophysiology of cerebral ischemia is essential for early diagnosis, neurologic recovery, the early onset of drug treatment and the prognosis of ischemic events. Experimental models of cerebral ischemia can be used to evaluate the cellular response phenomena and possible neurological protection by drugs. Objective: To characterize the cellular changes in the neuronal population and astrocytic response by the effect of Dimethyl Sulfoxide (DMSO) on a model of ischemia caused by cerebral embolism. Methods: Twenty Wistar rats were divided into four groups (n= 5). The infarct was induced with ?-bovine thrombin (40 NIH/Unit.). The treated group received 90 mg (100 ?L) of DMSO in saline (1:1 v/v) intraperitoneally for 5 days; ischemic controls received only NaCl (placebo) and two non-ischemic groups (simulated) received NaCl and DMSO respectively. We evaluated the neuronal (anti-NeuN) and astrocytic immune-reactivity (anti-GFAP). The results were analyzed by densitometry (NIH Image J-Fiji 1.45 software) and analysis of variance (ANOVA) with the Graph pad software (Prism 5). Results: Cerebral embolism induced reproducible and reliable lesions in the cortex and hippocampus (CA1)., similar to those of focal models. DMSO did not reverse the loss of post-ischemia neuronal immune-reactivity, but prevented the morphological damage of neurons, and significantly reduced astrocytic hyperactivity in the somato-sensory cortex and CA1 (p <0.001). Conclusions: The regulatory effect of DMSO on astrocyte hyperreactivity and neuronal-astroglial cytoarchitecture , gives it potential neuroprotective properties for the treatment of thromboembolic cerebral ischemia in the acute phase. PMID:24892319

Rengifo Valbuena, Carlos Augusto; Ávila Rodríguez, Marco Fidel; Céspedes Rubio, Angel

2013-01-01

184

Xenon contrast CT-CBF scanning of the brain differentiates normal age-related changes from multi-infarct dementia and senile dementia of Alzheimer type  

SciTech Connect

Local cerebral blood flow (LCBF) and partition coefficients (L lambda) were measured during inhalation of stable xenon gas with serial CT scanning among normal volunteers (N . 15), individuals with multi-infarct dementia (MID, N . 10), and persons with senile dementia of Alzheimer type (SDAT, N . 8). Mean gray matter flow values were reduced in both MID and SDAT. Age-related declines in LCBF values in normals were marked in frontal cortex and basal ganglia. LCBF values were decreased beyond normals in frontal and temporal cortices and thalamus in MID and SDAT, in basal ganglia only in MID. Unlike SDAT and age-matched normals, L lambda values were reduced in fronto-temporal cortex and thalamus in MID. Multifocal nature of lesions in MID was apparent. Coefficients of variation for LCBFs were greater in MID compared with SDAT and/or age-matched normals.

Tachibana, H.; Meyer, J.S.; Okayasu, H.; Shaw, T.G.; Kandula, P.; Rogers, R.L.

1984-07-01

185

The brain renin-angiotensin-aldosterone system: a major mechanism for sympathetic hyperactivity and left ventricular remodeling and dysfunction after myocardial infarction.  

PubMed

Following a myocardial infarction (MI), increases in plasma angiotensin II may activate central nervous system (CNS) pathways and thereby peripheral mechanisms (eg, sympathetic activity and the circulating/cardiac renin-angiotensin-aldosterone system ). Plasma angiotensin II may directly activate CNS pathways through the subfornical organ and chronically enhance activity by way of a neuromodulatory system. The latter involves an increase in CNS aldosterone-causing "ouabain" release (eg, from magnocellular neurons of the supraoptic and paraventricular nuclei). "Ouabain" may lower membrane potential, thereby enhancing activity of angiotensinergic pathways. The resulting increases in sympathetic activity, and circulating/cardiac RAAS contributes to progressive left ventricular remodeling and dysfunction after MI and can be largely prevented by central administration of a blocker for any of the components of this neuromodulatory system. These new insights into the crucial role of the CNS may lead to new therapeutic approaches for the prevention of heart failure after MI with minimal peripheral adverse effects. PMID:19486591

Huang, Bing S; Leenen, Frans H H

2009-06-01

186

Task-specific functional brain geometry from model maps.  

PubMed

In this paper we propose model maps to derive and represent the intrinsic functional geometry of a brain from functional magnetic resonance imaging (fMRI) data for a specific task. Model maps represent the coherence of behavior of individual fMRI-measurements for a set of observations, or a time sequence. The maps establish a relation between individual positions in the brain by encoding the blood oxygen level dependent (BOLD) signal over a time period in a Markov chain. They represent this relation by mapping spatial positions to a new metric space, the model map. In this map the Euclidean distance between two points relates to the joint modeling behavior of their signals and thus the co-dependencies of the corresponding signals. The map reflects the functional as opposed to the anatomical geometry of the brain. It provides a quantitative tool to explore and study global and local patterns of resource allocation in the brain. To demonstrate the merit of this representation, we report quantitative experimental results on 29 fMRI time sequences, each with sub-sequences corresponding to 4 different conditions for two groups of individuals. We demonstrate that drug abusers exhibit lower differentiation in brain interactivity between baseline and reward related tasks, which could not be quantified until now. PMID:18979834

Langs, Georg; Samaras, Dimitris; Paragios, Nikos; Honorio, Jean; Alia-Klein, Nelly; Tomasi, Dardo; Volkow, Nora D; Goldstein, Rita Z

2008-01-01

187

Hyper- and Viscoelastic Modeling of Needle and Brain Tissue Interaction  

PubMed Central

Deep needle insertion into brain is important for both diagnostic and therapeutic clinical interventions. We have developed an automated system for robotically steering flexible needles within the brain to improve targeting accuracy. In this work, we have developed a finite element needle-tissue interaction model that allows for the investigation of safe parameters for needle steering. The tissue model implemented contains both hyperelastic and viscoelastic properties to simulate the instantaneous and time-dependent responses of brain tissue. Several needle models were developed with varying parameters to study the effects of the parameters on tissue stress, strain and strain rate during needle insertion and rotation. The parameters varied include needle radius, bevel angle, bevel tip fillet radius, insertion speed, and rotation speed. The results will guide the design of safe needle tips and control systems for intracerebral needle steering. PMID:25571492

Lehocky, Craig A.; Shi, Yixing; Riviere, Cameron N.

2014-01-01

188

Mitochondrially targeted Endonuclease III has a powerful anti-infarct effect in an in vivo rat model of myocardial ischemia/reperfusion.  

PubMed

Recent reports indicate that elevating DNA glycosylase/AP lyase repair enzyme activity offers marked cytoprotection in cultured cells and a variety of injury models. In this study, we measured the effect of EndoIII, a fusion protein construct that traffics Endonuclease III, a DNA glycosylase/AP lyase, to the mitochondria, on infarct size in a rat model of myocardial ischemia/reperfusion. Open-chest, anesthetized rats were subjected to 30 min of occlusion of a coronary artery followed by 2 h of reperfusion. An intravenous bolus of EndoIII, 8 mg/kg, just prior to reperfusion reduced infarct size from 43.8 ± 1.4% of the risk zone in control animals to 24.0 ± 1.3% with no detectable hemodynamic effect. Neither EndoIII's vehicle nor an enzymatically inactive EndoIII mutant (K120Q) offered any protection. The magnitude of EndoIII's protection was comparable to that seen with the platelet aggregation inhibitor cangrelor (25.0 ± 1.8% infarction of risk zone). Because loading with a P2Y12 receptor blocker to inhibit platelets is currently the standard of care for treatment of acute myocardial infarction, we tested whether EndoIII could further reduce infarct size in rats treated with a maximally protective dose of cangrelor. The combination reduced infarct size to 15.1 ± 0.9% which was significantly smaller than that seen with either cangrelor or EndoIII alone. Protection from cangrelor but not EndoIII was abrogated by pharmacologic blockade of phosphatidylinositol-3 kinase or adenosine receptors indicating differing cellular mechanisms. We hypothesized that EndoIII protected the heart from spreading necrosis by preventing the release of proinflammatory fragments of mitochondrial DNA (mtDNA) into the heart tissue. In support of this hypothesis, an intravenous bolus at reperfusion of deoxyribonuclease I (DNase I) which should degrade any DNA fragments escaping into the extracellular space was as protective as EndoIII. Furthermore, the combination of EndoIII and DNase I produced additive protection. While EndoIII would maintain mitochondrial integrity in many of the ischemic cardiomyocytes, DNase I would further prevent mtDNA released from those cells that EndoIII could not save from propagating further necrosis. Thus, our mtDNA hypothesis would predict additive protection. Finally to demonstrate the toxicity of mtDNA, isolated hearts were subjected to 15 min of global ischemia. Infarct size doubled when the coronary vasculature was filled with mtDNA fragments during the period of global ischemia. To our knowledge, EndoIII and DNase are the first agents that can both be given at reperfusion and add to the protection of a P2Y12 blocker, and thus should be effective in today's patient with acute myocardial infarction. PMID:25595210

Yang, Xi-Ming; Cui, Lin; White, James; Kuck, Jamie; Ruchko, Mykhaylo V; Wilson, Glenn L; Alexeyev, Mikhail; Gillespie, Mark N; Downey, James M; Cohen, Michael V

2015-03-01

189

Resolving Structural Variability in Network Models and the Brain  

PubMed Central

Large-scale white matter pathways crisscrossing the cortex create a complex pattern of connectivity that underlies human cognitive function. Generative mechanisms for this architecture have been difficult to identify in part because little is known in general about mechanistic drivers of structured networks. Here we contrast network properties derived from diffusion spectrum imaging data of the human brain with 13 synthetic network models chosen to probe the roles of physical network embedding and temporal network growth. We characterize both the empirical and synthetic networks using familiar graph metrics, but presented here in a more complete statistical form, as scatter plots and distributions, to reveal the full range of variability of each measure across scales in the network. We focus specifically on the degree distribution, degree assortativity, hierarchy, topological Rentian scaling, and topological fractal scaling—in addition to several summary statistics, including the mean clustering coefficient, the shortest path-length, and the network diameter. The models are investigated in a progressive, branching sequence, aimed at capturing different elements thought to be important in the brain, and range from simple random and regular networks, to models that incorporate specific growth rules and constraints. We find that synthetic models that constrain the network nodes to be physically embedded in anatomical brain regions tend to produce distributions that are most similar to the corresponding measurements for the brain. We also find that network models hardcoded to display one network property (e.g., assortativity) do not in general simultaneously display a second (e.g., hierarchy). This relative independence of network properties suggests that multiple neurobiological mechanisms might be at play in the development of human brain network architecture. Together, the network models that we develop and employ provide a potentially useful starting point for the statistical inference of brain network structure from neuroimaging data. PMID:24675546

Klimm, Florian; Bassett, Danielle S.; Carlson, Jean M.; Mucha, Peter J.

2014-01-01

190

Resolving structural variability in network models and the brain.  

PubMed

Large-scale white matter pathways crisscrossing the cortex create a complex pattern of connectivity that underlies human cognitive function. Generative mechanisms for this architecture have been difficult to identify in part because little is known in general about mechanistic drivers of structured networks. Here we contrast network properties derived from diffusion spectrum imaging data of the human brain with 13 synthetic network models chosen to probe the roles of physical network embedding and temporal network growth. We characterize both the empirical and synthetic networks using familiar graph metrics, but presented here in a more complete statistical form, as scatter plots and distributions, to reveal the full range of variability of each measure across scales in the network. We focus specifically on the degree distribution, degree assortativity, hierarchy, topological Rentian scaling, and topological fractal scaling--in addition to several summary statistics, including the mean clustering coefficient, the shortest path-length, and the network diameter. The models are investigated in a progressive, branching sequence, aimed at capturing different elements thought to be important in the brain, and range from simple random and regular networks, to models that incorporate specific growth rules and constraints. We find that synthetic models that constrain the network nodes to be physically embedded in anatomical brain regions tend to produce distributions that are most similar to the corresponding measurements for the brain. We also find that network models hardcoded to display one network property (e.g., assortativity) do not in general simultaneously display a second (e.g., hierarchy). This relative independence of network properties suggests that multiple neurobiological mechanisms might be at play in the development of human brain network architecture. Together, the network models that we develop and employ provide a potentially useful starting point for the statistical inference of brain network structure from neuroimaging data. PMID:24675546

Klimm, Florian; Bassett, Danielle S; Carlson, Jean M; Mucha, Peter J

2014-03-01

191

Salubrinal protects cardiomyocytes against apoptosis in a rat myocardial infarction model via suppressing the dephosphorylation of eukaryotic translation initiation factor 2?.  

PubMed

The aim of the present study was to examine the role of eIF2? in cardiomyocyte apoptosis and evaluate the cardioprotective role of salubrinal in a rat myocardial infarction (MI) model. Rat left anterior descending coronary arteries were ligated and the classical proteins involved in the endoplasmic reticulum stress (ERS)?induced apoptotic pathway were analyzed using quantitative polymerase chain reaction and western blot analysis. Salubrinal was administered to the rats and cardiomyocyte apoptosis and infarct size were evaluated by a specific staining method. Compared with the sham surgery group, the rate of cardiomyocyte apoptosis in the MI group was increased with the development of the disease. It was also demonstrated that the mRNA and protein levels of GRP78, caspase?12, CHOP and the protein expression of p?eIF2? were increased in the MI group. Furthermore, the results showed that treatment with salubrinal can decrease cardiomyocyte apoptosis and infarct size by increasing eIF2? phosphorylation and decreasing the expression of caspase?12 and CHOP. The present study suggests that salubrinal protects against ER stress?induced rat cadiomyocyte apoptosis via suppressing the dephosphorylation of eIF2? in the ERS-associated pathway. PMID:25816071

Li, Rui-Jun; He, Kun-Lun; Li, Xin; Wang, Li-Li; Liu, Chun-Lei; He, Yun-Yun

2015-07-01

192

Magnetic Resonance Imaging of Acute Reperfused Myocardial Infarction: Intraindividual Comparison of ECIII-60 and Gd-DTPA in a Swine Model  

SciTech Connect

Purpose. To compare a necrosis-avid contrast agent (NACA) bis-Gd-DTPA-pamoic acid derivative (ECIII-60) after intracoronary delivery with an extracellular agent Gd-DTPA after intravenous injection on magnetic resonance imaging (MRI) in a swine model of acute reperfused myocardial infarction (MI). Methods. Eight pigs underwent 90 min of transcatheter coronary balloon occlusion and 60 min of reperfusion. After intravenous injection of Gd-DTPA at a dose of 0.2 mmol/kg, all pigs were scanned with T1-weighted MRI until the delayed enhancement of MI disappeared. Then they were intracoronarily infused with ECIII-60 at 0.0025 mmol/kg and imaged for 5 hr. Signal intensity, infarct-over-normal contrast ratio and relative infarct size were quantified, compared, and correlated with the results of postmortem MRI and triphenyltetrazolium chloride (TTC) histochemical staining. Results. A contrast ratio over 3.0 was induced by both Gd-DTPA and ECIII-60. However, while the delayed enhancement with Gd-DTPA virtually vanished in 1 hr, ECIII-60 at an 80x smaller dose depicted the MI accurately over 5 hr as proven by ex vivo MRI and TTC staining. Conclusion. Both Gd-DTPA and ECIII-60 strongly enhanced acute MI. Comparing with fading contrast in a narrow time window with intravenous Gd-DTPA, intracoronary ECIII-60 persistently demarcated the acute MI, indicating a potential method for postprocedural assessment of myocardial viability after coronary interventions.

Jin Jiyang; Teng Gaojun [Zhongda Hospital of Southeast University, Department of Radiology (China); Feng Yi; Wu Yanping [Zhongda Hospital of Southeast University, Department of Cardiology (China); Jin Qindi [Zhongda Hospital of Southeast University, Department of Radiology (China); Wang Yu [Zhongda Hospital of Southeast University, Department of Cardiology (China); Wang Zhen [Zhongda Hospital of Southeast University, Department of Anaesthesiology (China); Lu Qin [Zhongda Hospital of Southeast University, Department of Radiology (China); Jiang Yibo [Zhongda Hospital of Southeast University, Department of Cardiology (China); Wang Shengqi; Chen Feng [Zhongda Hospital of Southeast University, Department of Radiology (China); Marchal, Guy; Ni Yicheng [University Hospitals, University of Leuven, Department of Radiology (Belgium)], E-mail: yicheng.ni@med.kuleuven.ac.be

2007-04-15

193

Cardioprotective activity of placental growth factor in a rat model of acute myocardial infarction: nanoparticle-based delivery versus direct myocardial injection  

PubMed Central

Background To comparatively evaluate the cardioprotective activity of placental growth factor (PGF) delivered through direct injection and a nanoparticle-based system respectively and to study the underlying mechanisms in a rat model of acute myocardial infarction (AMI). Methods Poly lactic-co-glycolic acid (PLGA)-based PGF-carrying nanoparticles (PGF-PLGANPs) were created. The mean size and morphology of particles were analyzed with particle size analyzer and transmission electronic microscopy (TEM). Encapsulation efficiency and sustained-release dose curve were analyzed by ELISA. Sprague-Dawley rats were randomized into four groups (n?=?10). While animals in the first group were left untreated as controls, those in the other 3 groups underwent surgical induction of AMI, followed by treatment with physiological saline, PGF, and PGF-PLGANPs, respectively. Cardiac function was evaluated by transthoracic echocardiography at 4 weeks after treatment. At 6 weeks, rats were sacrificed, infarction size was analyzed with Masson trichrome staining, and protein contents of TIMP-2, MT1-MMP and MMP-2 at the infarction border were determined by immunohistochemistry and western blotting analysis. Results PGF was released for at least 15 days, showing successful preparation of PGF-PLGANPs. Coronary artery ligation successfully induced AMI. Compared to physiological saline control, PGF, injected to the myocardium either as a nude molecule or in a form of nanoparticles, significantly reduced infarction size, improved cardiac function, and elevated myocardial expression of TIMP-2, MT1-MMP, and MMP-2 (P?

2014-01-01

194

Characterizing and Differentiating Brain State Dynamics via Hidden Markov Models.  

PubMed

Functional connectivity measured from resting state fMRI (R-fMRI) data has been widely used to examine the brain's functional activities and has been recently used to characterize and differentiate brain conditions. However, the dynamical transition patterns of the brain's functional states have been less explored. In this work, we propose a novel computational framework to quantitatively characterize the brain state dynamics via hidden Markov models (HMMs) learned from the observations of temporally dynamic functional connectomics, denoted as functional connectome states. The framework has been applied to the R-fMRI dataset including 44 post-traumatic stress disorder (PTSD) patients and 51 normal control (NC) subjects. Experimental results show that both PTSD and NC brains were undergoing remarkable changes in resting state and mainly transiting amongst a few brain states. Interestingly, further prediction with the best-matched HMM demonstrates that PTSD would enter into, but could not disengage from, a negative mood state. Importantly, 84 % of PTSD patients and 86 % of NC subjects are successfully classified via multiple HMMs using majority voting. PMID:25331991

Ou, Jinli; Xie, Li; Jin, Changfeng; Li, Xiang; Zhu, Dajiang; Jiang, Rongxin; Chen, Yaowu; Zhang, Jing; Li, Lingjiang; Liu, Tianming

2014-10-21

195

Animal models of brain maldevelopment induced by cycad plant genotoxins.  

PubMed

Cycads are long-lived tropical and subtropical plants that contain azoxyglycosides (e.g., cycasin, macrozamin) and neurotoxic amino acids (notably ?-N-methylamino-l-alanine l-BMAA), toxins that have been implicated in the etiology of a disappearing neurodegenerative disease, amyotrophic lateral sclerosis and parkinsonism-dementia complex that has been present in high incidence among three genetically distinct populations in the western Pacific. The neuropathology of amyotrophic lateral sclerosis/parkinsonism-dementia complex includes features suggestive of brain maldevelopment, an experimentally proven property of cycasin attributable to the genotoxic action of its aglycone methylazoxymethanol (MAM). This property of MAM has been exploited by neurobiologists as a tool to study perturbations of brain development. Depending on the neurodevelopmental stage, MAM can induce features in laboratory animals that model certain characteristics of epilepsy, schizophrenia, or ataxia. Studies in DNA repair-deficient mice show that MAM perturbs brain development through a DNA damage-mediated mechanism. The brain DNA lesions produced by systemic MAM appear to modulate the expression of genes that regulate neurodevelopment and contribute to neurodegeneration. Epigenetic changes (histone lysine methylation) have also been detected in the underdeveloped brain after MAM administration. The DNA damage and epigenetic changes produced by MAM and, perhaps by chemically related substances (e.g., nitrosamines, nitrosoureas, hydrazines), might be an important mechanism by which early-life exposure to genotoxicants can induce long-term brain dysfunction. PMID:24339036

Kisby, Glen E; Moore, Holly; Spencer, Peter S

2013-12-01

196

Animal Models of Brain Maldevelopment Induced by Cycad Plant Genotoxins  

PubMed Central

Cycads are long-lived tropical and subtropical plants that contain azoxyglycosides (e.g., cycasin, macrozamin) and neurotoxic amino acids (notably ?-N-methylamino-L-alanine L-BMAA), toxins that have been implicated in the etiology of a disappearing neurodegenerative disease, amyotrophic lateral sclerosis and parkinsonism-dementia complex that has been present in high incidence among three genetically distinct populations in the western Pacific. The neuropathology of amyotrophic lateral sclerosis/parkinsonism-dementia complex includes features suggestive of brain maldevelopment, an experimentally proven property of cycasin attributable to the genotoxic action of its aglycone methylazoxymethanol (MAM). This property of MAM has been exploited by neurobiologists as a tool to study perturbations of brain development. Depending on the neurodevelopmental stage, MAM can induce features in laboratory animals that model certain characteristics of epilepsy, schizophrenia, or ataxia. Studies in DNA repair-deficient mice show that MAM perturbs brain development through a DNA damage-mediated mechanism. The brain DNA lesions produced by systemic MAM appear to modulate the expression of genes that regulate neurodevelopment and contribute to neurodegeneration. Epigenetic changes (histone lysine methylation) have also been detected in the underdeveloped brain after MAM administration. The DNA damage and epigenetic changes produced by MAM and, perhaps by chemically related substances (e.g., nitrosamines, nitrosoureas, hydrazines), might be an important mechanism by which early-life exposure to genotoxicants can induce long-term brain dysfunction. PMID:24339036

Kisby, Glen E.; Moore, Holly; Spencer, Peter S.

2014-01-01

197

Rao, Olshausen and Lewicki: Probabilistic Models of the Brain 2001/05/02 19:33 Probabilistic Models of the Brain  

E-print Network

Rao, Olshausen and Lewicki: Probabilistic Models of the Brain 2001/05/02 19:33 Probabilistic Models of the Brain: Perception and Neural Function Edited by Rajesh P. N. Rao Bruno A. Olshausen Michael S. Lewicki Cataloging-in-Publication Data Statistical Theories of the Brain / Edited by Rajesh P. N. Rao, Bruno A

Jepson, Allan D.

198

JAMA Patient Page: Myocardial Infarction  

MedlinePLUS

... the American Medical Association JAMA PATIENT PAGE Myocardial Infarction M yocardial infarction , also known as a heart attack, can strike without warning. A myocardial infarction occurs when blood supply to a part of ...

199

Characterisation and modelling of brain tissue for surgical simulation.  

PubMed

Interactive surgical simulators capable of providing a realistic visual and haptic feedback to users are a promising technology for medical training and surgery planification. However, modelling the physical behaviour of human organs and tissues for surgery simulation remains a challenge. On the one hand, this is due to the difficulty to characterise the physical properties of biological soft tissues. On the other hand, the challenge still remains in the computation time requirements of real-time simulation required in interactive systems. Real-time surgical simulation and medical training must employ a sufficiently accurate and simple model of soft tissues in order to provide a realistic haptic and visual response. This study attempts to characterise the brain tissue at similar conditions to those that take place on surgical procedures. With this aim, porcine brain tissue is characterised, as a surrogate of human brain, on a rotational rheometer at low strain rates and large strains. In order to model the brain tissue with an adequate level of accuracy and simplicity, linear elastic, hyperelastic and quasi-linear viscoelastic models are defined. These models are simulated using the ABAQUS finite element platform and compared with the obtained experimental data. PMID:25676499

Mendizabal, A; Aguinaga, I; Sánchez, E

2015-05-01

200

Computational modeling of an endovascular approach to deep brain stimulation  

NASA Astrophysics Data System (ADS)

Objective. Deep brain stimulation (DBS) therapy currently relies on a transcranial neurosurgical technique to implant one or more electrode leads into the brain parenchyma. In this study, we used computational modeling to investigate the feasibility of using an endovascular approach to target DBS therapy. Approach. Image-based anatomical reconstructions of the human brain and vasculature were used to identify 17 established and hypothesized anatomical targets of DBS, of which five were found adjacent to a vein or artery with intraluminal diameter ?1 mm. Two of these targets, the fornix and subgenual cingulate white matter (SgCwm) tracts, were further investigated using a computational modeling framework that combined segmented volumes of the vascularized brain, finite element models of the tissue voltage during DBS, and multi-compartment axon models to predict the direct electrophysiological effects of endovascular DBS. Main results. The models showed that: (1) a ring-electrode conforming to the vessel wall was more efficient at neural activation than a guidewire design, (2) increasing the length of a ring-electrode had minimal effect on neural activation thresholds, (3) large variability in neural activation occurred with suboptimal placement of a ring-electrode along the targeted vessel, and (4) activation thresholds for the fornix and SgCwm tracts were comparable for endovascular and stereotactic DBS, though endovascular DBS was able to produce significantly larger contralateral activation for a unilateral implantation. Significance. Together, these results suggest that endovascular DBS can serve as a complementary approach to stereotactic DBS in select cases.

Teplitzky, Benjamin A.; Connolly, Allison T.; Bajwa, Jawad A.; Johnson, Matthew D.

2014-04-01

201

Modelling brain emergent behaviours through coevolution of neural agents.  

PubMed

Recently, many research efforts focus on modelling partial brain areas with the long-term goal to support cognitive abilities of artificial organisms. Existing models usually suffer from heterogeneity, which constitutes their integration very difficult. The present work introduces a computational framework to address brain modelling tasks, emphasizing on the integrative performance of substructures. Moreover, implemented models are embedded in a robotic platform to support its behavioural capabilities. We follow an agent-based approach in the design of substructures to support the autonomy of partial brain structures. Agents are formulated to allow the emergence of a desired behaviour after a certain amount of interaction with the environment. An appropriate collaborative coevolutionary algorithm, able to emphasize both the speciality of brain areas and their cooperative performance, is employed to support design specification of agent structures. The effectiveness of the proposed approach is illustrated through the implementation of computational models for motor cortex and hippocampus, which are successfully tested on a simulated mobile robot. PMID:15990275

Maniadakis, Michail; Trahanias, Panos

2006-06-01

202

Brain atlas of an emerging teleostean model: Nothobranchius furzeri.  

PubMed

Nothobranchius furzeri has emerged as a new fish model for neurobiological and age research over recent years, due to the exceptionally short lifespan, age-dependent cognitive/behavioral decline, expression of age-related biomarkers. The growing interest in this teleost has raised the need to construct an atlas of the whole brain of N. furzeri. The study has been carried out on adult specimens belonging to the long lived strain, originating from Mozambique and named MZM 04/10. In the atlas, the external features of brain, images of sections stained with luxol fast bleu/violet and schematic drawings of the most representative sections are showed. The identification and description of brain structures has been carried out on methodological and hodological studies. Comparative analyses have revealed remarkable and peculiar neuroanatomical characteristics of N. furzeri brain architecture. Thus, a comprehensive whole brain atlas of N. furzeri has been constructed aiming to provide a baseline for structural and functional future experiments on this emerging model organism. PMID:23408644

D'angelo, Livia

2013-04-01

203

Infarct volume prediction using apparent diffusion coefficient maps during middle cerebral artery occlusion and soon after reperfusion in the rat.  

PubMed

Middle cerebral artery occlusion (MCAO) in rodents causes brain infarctions of variable sizes that depend on multiple factors, particularly in models of ischemia/reperfusion. This is a major problem for infarct volume comparisons between different experimental groups since unavoidable variability can induce biases in the results and imposes the use of large number of subjects. MRI can help to minimize these difficulties by ensuring that the severity of ischemia is comparable between groups. Furthermore, several studies showed that infarct volumes can be predicted with MRI data obtained soon after ischemia onset. However, such predictive studies require multiparametric MRI acquisitions that cannot be routinely performed, and data processing using complex algorithms that are often not available. The aim here was to provide a simplified method for infarct volume prediction using apparent diffusion coefficient (ADC) data in a model of transient MCAO in rats. ADC images were obtained before, during MCAO and after 60 min of reperfusion. Probability histograms were generated using ADC data obtained either during MCAO, after reperfusion, or both combined. The results were compared to real infarct volumes, i.e.T2 maps obtained at day 7. Assessment of the performance of the estimations showed better results combining ADC data obtained during occlusion and at reperfusion. Therefore, ADC data alone can provide sufficient information for a reasonable prediction of infarct volume if the MRI information is obtained both during the occlusion and soon after reperfusion. This approach can be used to check whether drug administration after MRI acquisition can change infarct volume prediction. PMID:25128601

Tudela, Raúl; Soria, Guadalupe; Pérez-De-Puig, Isabel; Ros, Domènec; Pavía, Javier; Planas, Anna M

2014-10-01

204

Magnetic Resonance Imaging in Experimental Models of Brain Disorders  

Microsoft Academic Search

This review gives an overview of the application of magnetic resonance imaging (MRI) in experimental models of brain disorders. MRI is a noninvasive and versatile imaging modality that allows longitudinal and three-dimensional assessment of tissue morphology, metabolism, physiology, and function. MRI can be sensitized to proton density, T1, T2, susceptibility contrast, magnetization transfer, diffusion, perfusion, and flow. The combination of

Rick M. Dijkhuizen; Klaas Nicolay

2003-01-01

205

The musician's brain as a model of neuroplasticity  

Microsoft Academic Search

Studies of experience-driven neuroplasticity at the behavioural, ensemble, cellular and molecular levels have shown that the structure and significance of the eliciting stimulus can determine the neural changes that result. Studying such effects in humans is difficult, but professional musicians represent an ideal model in which to investigate plastic changes in the human brain. There are two advantages to studying

Eckart Altenmüller; Lutz Jäncke; Thomas F. Münte

2002-01-01

206

A model for intratumoural chemotherapy in the rat brain  

Microsoft Academic Search

Summary To achieve the best reproducibility in rat brain tumour models several injection techniques have been used. Although stereotactic cell injections have proved to be effective and reliable, they are expensive and time consuming. A new permanently implanted device is presented here. It allows precise cell delivery for best tumour reproducibility, and it can be left in place for future

M. Saini; F. Roser; M. Samii; M. Bellinzona

2004-01-01

207

Orthotopic models of pediatric brain tumors in zebrafish.  

PubMed

High-throughput screens (HTS) of compound toxicity against cancer cells can identify thousands of potential new drug-leads. But only limited numbers of these compounds can progress to expensive and labor-intensive efficacy studies in mice, creating a 'bottle neck' in the drug development pipeline. Approaches that triage drug-leads for further study are greatly needed. Here we provide an intermediary platform between HTS and mice by adapting mouse models of pediatric brain tumors to grow as orthotopic xenografts in the brains of zebrafish. Freshly isolated mouse ependymoma, glioma and choroid plexus carcinoma cells expressing red fluorescence protein were conditioned to grow at 34?°C. Conditioned tumor cells were then transplanted orthotopically into the brains of zebrafish acclimatized to ambient temperatures of 34?°C. Live in vivo fluorescence imaging identified robust, quantifiable and reproducible brain tumor growth as well as spinal metastasis in zebrafish. All tumor xenografts in zebrafish retained the histological characteristics of the corresponding parent mouse tumor and efficiently recruited fish endothelial cells to form a tumor vasculature. Finally, by treating zebrafish harboring ERBB2-driven gliomas with an appropriate cytotoxic chemotherapy (5-fluorouracil) or tyrosine kinase inhibitor (erlotinib), we show that these models can effectively assess drug efficacy. Our data demonstrate, for the first time, that mouse brain tumors can grow orthotopically in fish and serve as a platform to study drug efficacy. As large cohorts of brain tumor-bearing zebrafish can be generated rapidly and inexpensively, these models may serve as a powerful tool to triage drug-leads from HTS for formal efficacy testing in mice. PMID:24747973

Eden, C J; Ju, B; Murugesan, M; Phoenix, T N; Nimmervoll, B; Tong, Y; Ellison, D W; Finkelstein, D; Wright, K; Boulos, N; Dapper, J; Thiruvenkatam, R; Lessman, C A; Taylor, M R; Gilbertson, R J

2015-03-26

208

Hierarchical Models in the Brain Karl Friston*  

E-print Network

linear model for static data to generalised convolution models, with system noise, for nonlinear time be formulated as a simple neural network and may provide a useful metaphor for inference and learning of the inversion lends itself to a relatively simple neural network implementation that shares many formal

Pillow, Jonathan

209

Neurodynamic models of brain in psychiatry Walter J Freeman. M.D.  

E-print Network

: Brain theory and psychiatry Abstract The history of brain theory is described in terms of three kinds_ _ Neurodynamic models of brain in psychiatry Walter J Freeman. M.D. Neuropsychopharmacology 28, S review of the historical emergence of brain theory Psychiatry has two deep roots, one in the experiences

Freeman, Walter J.

210

Segmentation of ventricles in brain CT images using Gaussian Mixture Model method  

Microsoft Academic Search

In this paper, a segmentation method using Gaussian mixture model (GMM) combined with template match is proposed for analysis of brain CT images. The specific aim of this method is to extract ventricles from brain CT images. These can then be used for automated detection of the midline shift in brain. In the method, different types of brain tissue, of

Wenan Chen; Kayvan Najarian

2009-01-01

211

Models in search of a brain  

Microsoft Academic Search

Mental localization efforts tend to stress the where more than the what. We argue that the proper targets for localization\\u000a are well-specified cognitive models. We make this case by relating an existing cognitive model of category learning to a learning\\u000a circuit involving the hippocampus, perirhinal, and prefrontal cortices. Results from groups varying in function along this\\u000a circuit (e.g., infants, amnesics,

Bradley C. Love; Todd M. Gureckis

2007-01-01

212

Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction  

PubMed Central

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo. With the advent of genetic modifications to the whole organism or the myocardium and an array of biological and/or synthetic materials, there is great potential for any combination of these to assuage the extent of acute ischemic injury and impede the onset of heart failure pursuant to myocardial remodeling. Here we present the methods and materials used to reliably perform this microsurgery and the modifications involved for temporary (with reperfusion) or permanent coronary artery occlusion studies as well as intramyocardial injections. The effects on the heart that can be seen during the procedure and at the termination of the experiment in addition to histological evaluation will verify efficacy. Briefly, surgical preparation involves anesthetizing the mice, removing the fur on the chest, and then disinfecting the surgical area. Intratracheal intubation is achieved by transesophageal illumination using a fiber optic light. The tubing is then connected to a ventilator. An incision made on the chest exposes the pectoral muscles which will be cut to view the ribs. For ischemia/reperfusion studies, a 1 cm piece of PE tubing placed over the heart is used to tie the ligature to so that occlusion/reperfusion can be customized. For intramyocardial injections, a Hamilton syringe with sterile 30gauge beveled needle is used. When the myocardial manipulations are complete, the rib cage, the pectoral muscles, and the skin are closed sequentially. Line block analgesia is effected by 0.25% marcaine in sterile saline which is applied to muscle layer prior to closure of the skin. The mice are given a subcutaneous injection of saline and placed in a warming chamber until they are sternally recumbent. They are then returned to the vivarium and housed under standard conditions until the time of tissue collection. At the time of sacrifice, the mice are anesthetized, the heart is arrested in diastole with KCl or BDM, rinsed with saline, and immersed in fixative. Subsequently, routine procedures for processing, embedding, sectioning, and histological staining are performed. Nonsurgical intubation of a mouse and the microsurgical manipulations described make this a technically challenging model to learn and achieve reproducibility. These procedures, combined with the difficulty in performing consistent manipulations of the ligature for timed occlusion(s) and reperfusion or intramyocardial injections, can also affect the survival rate so optimization and consistency are critical. PMID:21673649

Virag, Jitka A.I.; Lust, Robert M.

2011-01-01

213

Antidepressant fluvoxamine reduces cerebral infarct volume and ameliorates sensorimotor dysfunction in experimental stroke.  

PubMed

The sigma-1 receptor has been reported to be associated with diverse biological activities including cellular differentiation, neuroplasticity, neuroprotection, and cognitive functioning of the brain. Fluvoxamine, one of the currently known antidepressants, is a sigma-1 receptor agonist; its effectiveness in treating acute cerebral ischemia has not been reported. We studied the in-vivo effects of this compound using an animal model of focal cerebral ischemia. Forty male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion and assigned to five treatment groups (n=8 each). Postischemic neurological deficits and infarct volume were determined 24 h after stroke-inducing surgery. Significant reductions in infarct volume (total and cortical) were found in group 2 (fluvoxamine 20 mg/kg given 6 h before and immediately after ischemic onset) and group 3 (fluvoxamine given immediately after ischemic onset and 2 h later) compared with controls. Fluvoxamine induced significant amelioration of sensorimotor dysfunction, as indicated by the scores of forelimb and hindlimb placing tests. Moreover, NE-100, a selective sigma-1 receptor antagonist, completely blocked the neuroprotective effect of fluvoxamine. The present findings suggest that the sigma-1 receptor agonist fluvoxamine reduces infarct volume and ameliorates neurological impairment even on postischemic treatment. From the clinical viewpoint, fluvoxamine may be a promising new therapeutic approach for cerebral infarction. PMID:24709917

Sato, Shinsuke; Kawamata, Takakazu; Kobayashi, Tomonori; Okada, Yoshikazu

2014-07-01

214

Structural connectivity based whole brain modelling in epilepsy.  

PubMed

Epilepsy is a neurological condition characterised by the recurrence of seizures. During seizures multiple brain areas can behave abnormally. Rather than considering each abnormal area in isolation, one can consider them as an interconnected functional 'network'. Recently, there has been a shift in emphasis to consider epilepsy as a disorder involving more widespread functional brain networks than perhaps was previously thought. The basis for these functional networks is proposed to be the static structural brain network established through the connectivity of the white matter. Additionally, it has also been argued that time varying aspects of epilepsy are of crucial importance and as such computational models of these dynamical properties have recently advanced. We describe how dynamic computer models can be combined with static human in vivo connectivity obtained through diffusion weighted magnetic resonance imaging. We predict that in future the use of these two methods in concert will lead to predictions for optimal surgery and brain stimulation sites for epilepsy and other neurological disorders. PMID:25149109

Taylor, Peter Neal; Kaiser, Marcus; Dauwels, Justin

2014-10-30

215

Dynamic Bayesian network modeling for longitudinal brain morphometry.  

PubMed

Identifying interactions among brain regions from structural magnetic-resonance images presents one of the major challenges in computational neuroanatomy. We propose a Bayesian data-mining approach to the detection of longitudinal morphological changes in the human brain. Our method uses a dynamic Bayesian network to represent evolving inter-regional dependencies. The major advantage of dynamic Bayesian network modeling is that it can represent complicated interactions among temporal processes. We validated our approach by analyzing a simulated atrophy study, and found that this approach requires only a small number of samples to detect the ground-truth temporal model. We further applied dynamic Bayesian network modeling to a longitudinal study of normal aging and mild cognitive impairment--the Baltimore Longitudinal Study of Aging. We found that interactions among regional volume-change rates for the mild cognitive impairment group are different from those for the normal-aging group. PMID:21963916

Chen, Rong; Resnick, Susan M; Davatzikos, Christos; Herskovits, Edward H

2012-02-01

216

An extension Gaussian mixture model for brain MRI segmentation.  

PubMed

The segmentation of brain magnetic resonance (MR) images into gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) has been an intensive studied area in the medical image analysis community. The Gaussian mixture model (GMM) is one of the most commonly used model to represent the intensity of different tissue types. However, as a histogram-based model, the spatial relationship between pixels is discarded in the GMM, making it sensitive to noise. Herein we present a new framework which aims to incorporate spatial information into the standard GMM, where each pixel is assigned its individual prior by leveraging its neighborhood information. Expectation maximization (EM) is modified to estimate the parameters of the proposed method. The method is validated on both synthetic and real brain MR images, showing its effectiveness in the segmentation task. PMID:25571044

Song, Yantao; Ji, Zexuan; Sun, Quansen

2014-01-01

217

Homing of Neural Stem Cells From the Venous Compartment Into a Brain Infarct Does Not Involve Conventional Interactions With Vascular Endothelium  

PubMed Central

Human neural stem cells (hNSCs) hold great potential for treatment of a wide variety of neurodegenerative and neurotraumatic conditions. Heretofore, administration has been through intracranial injection or implantation of cells. Because neural stem cells are capable of migrating to the injured brain from the intravascular space, it seemed feasible to administer them intravenously if their ability to circumvent the blood-brain barrier was enhanced. In the present studies, we found that interactions of hNSCs in vitro on the luminal surface of human umbilical vein endothelial cells was enhanced following enforced expression of cutaneous lymphocyte antigen on cell surface moieties by incubation of hNSCs with fucosyltransferase VI and GDP-fucose (fhNSCs). Interestingly, ex vivo fucosylation of hNSCs not only did not improve the cells homing into the brain injured by stroke following intravenous administration but also increased mortality of rats compared with the nonfucosylated hNSC group. Efforts to explain these unexpected findings using a three-dimensional flow chamber device revealed that transmigration of fhNSCs (under conditions of physiological shear stress) mediated by stromal cell-derived factor 1? was significantly decreased compared with controls. Further analysis revealed that hNSCs poorly withstand physiological shear stress, and their ability is further decreased following fucosylation. In addition, fhNSCs demonstrated a higher frequency of cellular aggregate formation as well as a tendency for removal of fucose from the cell surface. In summary, our findings suggest that the behavior of hNSCs in circulation is different from that observed with other cell types and that, at least for stroke, intravenous administration is a suboptimal route, even when the in vitro rolling ability of hNSCs is optimized by enforced fucosylation. PMID:24396034

Goncharova, Valentina; Das, Shreyasi; Niles, Walter; Schraufstatter, Ingrid; Wong, Aaron K.; Povaly, Tatiana; Wakeman, Dustin; Miller, Leonard

2014-01-01

218

Homing of neural stem cells from the venous compartment into a brain infarct does not involve conventional interactions with vascular endothelium.  

PubMed

Human neural stem cells (hNSCs) hold great potential for treatment of a wide variety of neurodegenerative and neurotraumatic conditions. Heretofore, administration has been through intracranial injection or implantation of cells. Because neural stem cells are capable of migrating to the injured brain from the intravascular space, it seemed feasible to administer them intravenously if their ability to circumvent the blood-brain barrier was enhanced. In the present studies, we found that interactions of hNSCs in vitro on the luminal surface of human umbilical vein endothelial cells was enhanced following enforced expression of cutaneous lymphocyte antigen on cell surface moieties by incubation of hNSCs with fucosyltransferase VI and GDP-fucose (fhNSCs). Interestingly, ex vivo fucosylation of hNSCs not only did not improve the cells homing into the brain injured by stroke following intravenous administration but also increased mortality of rats compared with the nonfucosylated hNSC group. Efforts to explain these unexpected findings using a three-dimensional flow chamber device revealed that transmigration of fhNSCs (under conditions of physiological shear stress) mediated by stromal cell-derived factor 1? was significantly decreased compared with controls. Further analysis revealed that hNSCs poorly withstand physiological shear stress, and their ability is further decreased following fucosylation. In addition, fhNSCs demonstrated a higher frequency of cellular aggregate formation as well as a tendency for removal of fucose from the cell surface. In summary, our findings suggest that the behavior of hNSCs in circulation is different from that observed with other cell types and that, at least for stroke, intravenous administration is a suboptimal route, even when the in vitro rolling ability of hNSCs is optimized by enforced fucosylation. PMID:24396034

Goncharova, Valentina; Das, Shreyasi; Niles, Walter; Schraufstatter, Ingrid; Wong, Aaron K; Povaly, Tatiana; Wakeman, Dustin; Miller, Leonard; Snyder, Evan Y; Khaldoyanidi, Sophia K

2014-02-01

219

Accurate and robust extraction of brain regions using a deformable model based on radial basis functions.  

PubMed

Brain extraction from head magnetic resonance (MR) images is a classification problem of segmenting image volumes into brain and non-brain regions. It is a difficult task due to the convoluted brain surface and the inapparent brain/non-brain boundaries in images. This paper presents an automated, robust, and accurate brain extraction method which utilizes a new implicit deformable model to well represent brain contours and to segment brain regions from MR images. This model is described by a set of Wendland's radial basis functions (RBFs) and has the advantages of compact support property and low computational complexity. Driven by the internal force for imposing the smoothness constraint and the external force for considering the intensity contrast across boundaries, the deformable model of a brain contour can efficiently evolve from its initial state toward its target by iteratively updating the RBF locations. In the proposed method, brain contours are separately determined on 2D coronal and sagittal slices. The results from these two views are generally complementary and are thus integrated to obtain a complete 3D brain volume. The proposed method was compared to four existing methods, Brain Surface Extractor, Brain Extraction Tool, Hybrid Watershed Algorithm, and Model-based Level Set, by using two sets of MR images as well as manual segmentation results obtained from the Internet Brain Segmentation Repository. Our experimental results demonstrated that the proposed approach outperformed these four methods when jointly considering extraction accuracy and robustness. PMID:19467263

Liu, Jia-Xiu; Chen, Yong-Sheng; Chen, Li-Fen

2009-10-15

220

Experimental myocardial infarction  

PubMed Central

Compliance of the infarcted left ventricle was studied in dogs 3-5 days after occlusion of the left anterior descending coronary artery. Compliance was assessed from postmortem pressure-volume curves and from pressure-length measurements (mercury-in-silastic segment length gauges) made both in vivo and postmortem. Postmortem pressure-volume curves showed reduced compliance compared to sham-operated animals. Postmortem pressure-length curves of infarcted and adjacent normal myocardium indicated that the diminished total compliance could be attributed to an increase in stiffness of the infarcted area. This was confirmed by in vivo end-diastolic pressure-length changes produced by transient aortic occlusion. The infarcted area was akinetic, showing neither contraction nor aneurysmal bulging. In addition, anesthetized dogs with infarcts, when compared with sham-operated animals, had similar left ventricular end-diastolic volumes (indicator dilution method), but higher left ventricular end-diastolic pressures. Taken with previous observations, which show that systolic aneurysmal bulging is uniformly present at the onset of ischemia, these results indicate that stiffening of the ischemic myocardium occurs during the first 5 days after infarction, and show that elevation of left ventricular filling pressure does not necessarily signify ventricular dilatation. The results also suggest a mechanism whereby ventricular performance may improve during recovery from acute myocardial infarction. Images PMID:4914678

Hood, William B.; Bianco, Jesus A.; Kumar, Raj; Whiting, Richard B.

1970-01-01

221

Neuronal regeneration in a zebrafish model of adult brain injury  

PubMed Central

SUMMARY Neural stem cells in the subventricular zone (SVZ) of the adult mammalian forebrain are a potential source of neurons for neural tissue repair after brain insults such as ischemic stroke and traumatic brain injury (TBI). Recent studies show that neurogenesis in the ventricular zone (VZ) of the adult zebrafish telencephalon has features in common with neurogenesis in the adult mammalian SVZ. Here, we established a zebrafish model to study injury-induced neurogenesis in the adult brain. We show that the adult zebrafish brain possesses a remarkable capacity for neuronal regeneration. Telencephalon injury prompted the proliferation of neuronal precursor cells (NPCs) in the VZ of the injured hemisphere, compared with in the contralateral hemisphere. The distribution of NPCs, viewed by BrdU labeling and ngn1-promoter-driven GFP, suggested that they migrated laterally and reached the injury site via the subpallium and pallium. The number of NPCs reaching the injury site significantly decreased when the fish were treated with an inhibitor of ?-secretase, a component of the Notch signaling pathway, suggesting that injury-induced neurogenesis mechanisms are at least partly conserved between fish and mammals. The injury-induced NPCs differentiated into mature neurons in the regions surrounding the injury site within a week after the injury. Most of these cells expressed T-box brain protein (Tbr1), suggesting they had adopted the normal neuronal fate in this region. These results suggest that the telencephalic VZ contributes to neural tissue recovery following telencephalic injury in the adult zebrafish, and that the adult zebrafish is a useful model for regenerative medicine. PMID:22028327

Kishimoto, Norihito; Shimizu, Kohei; Sawamoto, Kazunobu

2012-01-01

222

Iron Deposition following Chronic Myocardial Infarction as a Substrate for Cardiac Electrical Anomalies: Initial Findings in a Canine Model  

PubMed Central

Purpose Iron deposition has been shown to occur following myocardial infarction (MI). We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies. Methods Two groups of dogs (ex-vivo (n?=?12) and in-vivo (n?=?10)) were studied at 16 weeks post MI. Hearts of animals from ex-vivo group were explanted and sectioned into infarcted and non-infarcted segments. Impedance spectroscopy was used to derive electrical permittivity () and conductivity (). Mass spectrometry was used to classify and characterize tissue sections with (IRON+) and without (IRON-) iron. Animals from in-vivo group underwent cardiac magnetic resonance imaging (CMR) for estimation of scar volume (late-gadolinium enhancement, LGE) and iron deposition (T2*) relative to left-ventricular volume. 24-hour electrocardiogram recordings were obtained and used to examine Heart Rate (HR), QT interval (QT), QT corrected for HR (QTc) and QTc dispersion (QTcd). In a fraction of these animals (n?=?5), ultra-high resolution electroanatomical mapping (EAM) was performed, co-registered with LGE and T2* CMR and were used to characterize the spatial locations of isolated late potentials (ILPs). Results Compared to IRON- sections, IRON+ sections had higher, but no difference in. A linear relationship was found between iron content and (p<0.001), but not (p?=?0.34). Among two groups of animals (Iron (<1.5%) and Iron (>1.5%)) with similar scar volumes (7.28%±1.02% (Iron (<1.5%)) vs 8.35%±2.98% (Iron (>1.5%)), p?=?0.51) but markedly different iron volumes (1.12%±0.64% (Iron (<1.5%)) vs 2.47%±0.64% (Iron (>1.5%)), p?=?0.02), QT and QTc were elevated and QTcd was decreased in the group with the higher iron volume during the day, night and 24-hour period (p<0.05). EAMs co-registered with CMR images showed a greater tendency for ILPs to emerge from scar regions with iron versus without iron. Conclusion The electrical behavior of infarcted hearts with iron appears to be different from those without iron. Iron within infarcted zones may evolve as an arrhythmogenic substrate in the post MI period. PMID:24066038

Wang, Xunzhang; Yang, Hsin-Jung; Tang, Richard L. Q.; Thajudeen, Anees; Shehata, Michael; Amorn, Allen M.; Liu, Enzhao; Stewart, Brian; Bennett, Nathan; Harlev, Doron; Tsaftaris, Sotirios A.; Jackman, Warren M.; Chugh, Sumeet S.; Dharmakumar, Rohan

2013-01-01

223

Omental Infarction Mimicking Cholecystitis  

PubMed Central

Omental infarction can be difficult to diagnose preoperatively as imaging may be inconclusive and patients often present in a way that suggests a more common surgical pathology such as appendicitis. Here, a 40-year-old Caucasian man presented to casualty with shortness of breath and progressive right upper abdominal pain, accompanied with right shoulder and neck pain. Exploratory laparoscopy was eventually utilised to diagnose an atypical form of omental infarction that mimics cholecystitis. The vascular supply along the long axis of the segment was occluded initiating necrosis. In this case, the necrotic segment was adherent with the abdominal wall, a pathology not commonly reported in cases of omental infarction. PMID:25737796

Smolilo, David; Lewis, Benjamin C.; Yeow, Marina; Watson, David I.

2015-01-01

224

Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model.  

PubMed

The transplantation of adipose tissue-derived stem cells (ADSCs) improves cardiac contractility after myocardial infarction (MI); however, little is known about the electrophysiological consequences of transplantation. The purpose of this study was to clarify whether the transplantation of ADSCs increases or decreases the incidence of ventricular tachyarrhythmias (VT) in a rat model of MI. MI was induced experimentally by permanent occlusion of the left anterior descending artery of Lewis rats. ADSCs were harvested from GFP-transgenic rats, and were cultured until passage four. ADSCs (10×10(6)) resuspended in 100?L saline or pro-survival cocktail (PSC), which enhances cardiac graft survival, were injected directly into syngeneic rat hearts 1week after MI. The recipients of ADSCs suspended in PSC had a larger graft area compared with those receiving ASDCs suspended in saline at 1week post-transplantation (number of graft cells/section: 148.7±10.6 vs. 22.4±3.4, p<0.05, n=5/group). Thereafter, all ADSC recipients were transplanted with ASDCs in PSC. ADSCs were transplanted into infarcted hearts, and the mechanical and electrophysiological functions were assessed. Echocardiography revealed that ADSC recipients had improved contractile function compared with those receiving PSC vehicle (fractional shortening: 21.1±0.9 vs. 14.1±1.2, p<0.05, n?12/group). Four weeks post-transplantation, VT was induced via in vivo programmed electrical stimulation. The recipients of ADSCs showed a significantly lower incidence of induced VT compared with the control (31.3% vs. 83.3%, p<0.05, n?12/group). To understand the electrical activity following transplantation, we performed ex vivo optical mapping using a voltage sensitive dye, and found that ADSC transplantation decreased conduction velocity and its dispersion in the peri-infarct area. These results suggest that ADSC transplantation improved cardiac mechanical and electrophysiological functions in subacute MI. PMID:25724725

Gautam, Milan; Fujita, Daiki; Kimura, Kazuhiro; Ichikawa, Hinako; Izawa, Atsushi; Hirose, Masamichi; Kashihara, Toshihide; Yamada, Mitsuhiko; Takahashi, Masafumi; Ikeda, Uichi; Shiba, Yuji

2015-04-01

225

Self-organization in a simple brain model  

SciTech Connect

Simulations on a simple model of the brain are presented. The model consists of a set of randomly connected neurons. Inputs and outputs are also connected randomly to a subset of neurons. For each input there is a set of output neurons which must fire in order to achieve success. A signal giving information as to whether or not the action was successful is fed back to the brain from the environment. The connections between firing neurons are strengthened or weakened according to whether or not the action was successful. The system learns, through a self-organization process, to react intelligently to input signals, i.e. it learns to quickly select the correct output for each input. If part of the network is damaged, the system relearns the correct response after a training period.

Stassinopoulos, D.; Bak, P. [Brookhaven National Lab., Upton, NY (United States). Dept. of Physics; Alstroem, P. [Niels Bohr Inst., Copenhagen (Denmark). Dept. of Physics

1994-03-10

226

A model for genomic imprinting in the social brain: juveniles.  

PubMed

What are imprinted genes doing in the adult brain? Genomic imprinting is when a gene's expression depends upon parent of origin. According to the prevailing view, the "kinship theory" of genomic imprinting, this effect is driven by evolutionary conflicts between genes inherited via sperm versus egg. This theory emphasizes conflicts over the allocation of maternal resources, and focuses upon genes that are expressed in the placenta and infant brain. However, there is growing evidence that imprinted genes are also expressed in the juvenile and adult brain, after cessation of parental care. These genes have recently been suggested to underpin neurological disorders of the social brain such as psychosis and autism. Here we advance the kinship theory by developing an evolutionary model of genomic imprinting for social behavior beyond the nuclear family. We consider the role of demography and mating system, emphasizing the importance of sex differences in dispersal and variance in reproductive success. We predict that, in hominids and birds, altruism will be promoted by paternally inherited genes and egoism will be promoted by maternally inherited genes. In nonhominid mammals we predict more diversity, with some mammals showing the same pattern and other showing the reverse. We discuss the implications for the evolution of psychotic and autistic spectrum disorders in human populations with different social structures. PMID:20394663

Ubeda, Francisco; Gardner, Andy

2010-09-01

227

Cultured Brain Microvessel Endothelial Cells as In Vitro Models of the Blood-Brain Barrier  

E-print Network

to absorption of peptides. Pharm Weekbl [Sci] 10:38-39, 1988. Kempski, 0.; Villacara, A.; Spatz, M.; Dodson, R.F.; Corn, C.; Merkel, N.; and Bembry, J. Cerebromicrovascular endothelial permeability: In vitro studies. Acta Neuropathol (Berl) 74:329-334, 1987... cells for drug transport and metabolism studies. Pharm Res 7:435-451, 1990. Audus, K.L., and Borchardt, R.T. Characterization of an in vitro blood-brain barrier model system for studying drug transport and metabolism. Pharm Res 3:81-87, 1986a. Audus, K...

Takakura, Yoshinobu; Audus, Kenneth L.; Borchardt, Ronald T.

1992-01-01

228

Information transfer of an Ising model on a brain network  

E-print Network

We implement the Ising model on an anatomical connectivity matrix describing the brain at a coarse scale. We find that the critical state of the model is also characterized by the maximal amount of total information transfer among variables and exhibits signature of the law of diminishing marginal returns, some nodes showing disparity between incoming and outgoing information. Our results extend the recent analysis of dynamical oscillators models on the connectome structure, taking into account lagged and directional influences, concentrating on the nodes that are more prone to became bottlenecks of information.

Marinazzo, Daniele; Wu, Guorong; Angelini, Leonardo; Cortes, Jesus M; Stramaglia, Sebastiano

2013-01-01

229

An improved dosimetric model of the head and brain  

E-print Network

. . Introduction . Particle Interactions with Matter in EGS4 . The EGS4 Code The PRESTA Version of EGS4 . . . . 37 . 37 . . . 38 . . . . . 40 . 43 CHAPTER Page VI THE NEW DOSIMETRIC MODEL FOR THE BRAIN AND HEAD . . . . , . , 47 Introduction... (electrons or positrons origmating in the nucleus), gamma-rays (photons originatmg in the nucleus), x-rays (photons resultmg from transitions among the atomic electrons), conversion electrons (atomic electrons ejected as an alternative to gmnma...

Bouchet, Lionel Gerard

1995-01-01

230

Validation of Contrast-Enhanced MRI to Monitor Regenerative Efficacy after Cell Therapy in a Porcine Model of Convalescent Myocardial Infarction  

PubMed Central

Background Magnetic Resonance Imaging (MRI) in the CADUCEUS trial revealed that cardiosphere-derived cells (CDCs) decrease scar size and increase viable myocardium post-myocardial infarction (MI), but MRI has not been validated as an index of regeneration after cell therapy. We tested the validity of contrast-enhanced MRI in quantifying scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. Methods and Results Yucatan minipigs underwent induction of MI and 2-3 weeks later were randomized to receive intracoronary infusion of 12.5×106 mismatched allogeneic CDCs or vehicle. Allogeneic CDCs induced mild local mononuclear infiltration but no systemic immunogenicity. MRI revealed that allogeneic CDCs attenuated remodeling, improved global and regional function, decreased scar size and increased viable myocardium compared to placebo 2 months post-treatment. Extensive histological analysis validated quantitatively the MRI measurements of scar size, scar mass and viable mass. CDCs neither altered gadolinium contrast myocardial kinetics, nor induced changes in vascular density or architecture in viable and scarred myocardium. Histology demonstrated that CDCs lead to cardiomyocyte hyperplasia in the border zone, consistent with the observed stimulation of endogenous regenerative mechanisms (cardiomyocyte cycling, upregulation of endogenous progenitors, angiogenesis). Conclusions Contrast-enhanced MRI accurately measures scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. MRI represents a useful tool for assessing dynamic changes in the infarct and monitoring regenerative efficacy. PMID:24061088

Malliaras, Konstantinos; Smith, Rachel R.; Kanazawa, Hideaki; Yee, Kristine; Seinfeld, Jeffrey; Tseliou, Eleni; Dawkins, James F.; Kreke, Michelle; Cheng, Ke; Luthringer, Daniel; Ho, Chak-Sum; Blusztajn, Agnieszka; Valle, Ileana; Chowdhury, Supurna; Makkar, Raj R.; Dharmakumar, Rohan; Li, Debiao; Marbán, Linda; Marbán, Eduardo

2014-01-01

231

An overview on development and application of an experimental platform for quantitative cardiac imaging research in rabbit models of myocardial infarction  

PubMed Central

To exploit the advantages of using rabbits for cardiac imaging research and to tackle the technical obstacles, efforts have been made under the framework of a doctoral research program. In this overview article, by cross-referencing the current literature, we summarize how we have developed a preclinical cardiac research platform based on modified models of reperfused myocardial infarction (MI) in rabbits; how the in vivo manifestations of cardiac imaging could be closely matched with those ex vivo macro- and microscopic findings; how these imaging outcomes could be quantitatively analyzed, validated and demonstrated; and how we could apply this cardiac imaging platform to provide possible solutions to certain lingering diagnostic and therapeutic problems in experimental cardiology. In particular, tissue components in acute cardiac ischemia have been stratified and characterized, post-infarct lipomatous metaplasia (LM) as a common but hardly illuminated clinical pathology has been identified in rabbit models, and a necrosis avid tracer as well as an anti-ischemic drug have been successfully assessed for their potential utilities in clinical cardiology. These outcomes may interest the researchers in the related fields and help strengthen translational research in cardiovascular diseases. PMID:25392822

Feng, Yuanbo; Bogaert, Jan; Oyen, Raymond

2014-01-01

232

Small synthetic hyaluronan disaccharides afford neuroprotection in brain ischemia-related models.  

PubMed

High molecular weight (HMW) glycosaminoglycanes of the extracellular matrix have been implicated in tissue repair. The aim of this study was to evaluate if small synthetic hyaluronan disaccharides with different degrees of sulfation (methyl 2-acetamido-2-deoxy-3-O-(?-d-glucopyranosyluronic acid)-O-sulfo-?-d-glucopyranoside, sodium salt (di0S), methyl 2-acetamido-2-deoxy-3-O-(?-d-glucopyranosyluronic acid)-6-di-O-sulfo-?-d-glucopyranoside, disodium salt (di6S) and methyl 2-acetamido-2-deoxy-3-O-(?-d-glucopyranosyluronic acid)-4,6-di-O-sulfo-?-d-glucopyranoside, trisodium salt (di4,6S)) could improve cell survival in in vitro and in vivo brain ischemia-related models. Rat hippocampal slices subjected to oxygen and glucose deprivation and a photothrombotic stroke model in mice were used. The three hyaluran disaccharides, incubated during the oxygen and glucose deprivation (15min) and re-oxygenation periods (120min), reduced cell death of hippocampal slices measured as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction, being the most potent di4,6S; in contrast, high molecular hyaluronan was ineffective. The protective actions of di4,6S against oxygen and glucose deprivation were related to activation of the PI3K/Akt survival pathway, reduction of p65 translocation to the nucleus, inhibition of inducible nitric oxide oxidase induction and reactive oxygen species production, and to an increase in glutathione levels. Administered 1h post-stroke, di4,6S reduced cerebral infarct size and improved motor activity in the beam walk test. In conclusion, di4,6S affords neuroprotection in in vitro and in vivo models of ischemic neuronal damage. Our results suggest that its neuroprotective effect could be exerted through its capability to reduce oxidative stress during ischemia. Its small molecular size makes it a more potential druggable drug to target the brain as compared with its HMW parent compound hyaluronan. PMID:24486437

Egea, J; Parada, E; Gómez-Rangel, V; Buendia, I; Negredo, P; Montell, E; Ruhí, R; Vergés, J; Roda, J M; García, A G; López, M G

2014-04-18

233

Avoiding Boltzmann Brain domination in holographic dark energy models  

E-print Network

In a spatially infinite and eternal universe approaching ultimately a de Sitter (or quasi-de Sitter) regime, structure can form by thermal fluctuations as such a space is thermal. The models of Dark Energy invoking holographic principle fit naturally into such a category, and spontaneous formation of isolated brains in otherwise empty space seems the most perplexing, creating the paradox of Boltzmann Brains (BB). It is thus appropriate to ask if such models can be made free from domination by Boltzmann Brains. Here we consider only the simplest model, but adopt both the local and the global viewpoint in the description of the Universe. In the former case, we find that if a parameter $c$, which modulates the Dark Energy density, lies outside the exponentially narrow strip around the most natural $c = 1$ line, the theory is rendered BB-safe. In the later case, the bound on $c$ is exponentially stronger, and seemingly at odds with those bounds on $c$ obtained from various observational tests.

R. Horvat

2015-02-23

234

Avoiding Boltzmann Brain domination in holographic dark energy models  

E-print Network

In a spatially infinite and eternal universe approaching ultimately a de Sitter (or quasi-de Sitter) regime, structure can form by thermal fluctuations as such a space is thermal. The models of Dark Energy invoking holographic principle fit naturally into such a category, and spontaneous formation of isolated brains in otherwise empty space seems the most perplexing, creating the paradox of Boltzmann Brains (BB). It is thus appropriate to ask if such models can be made free from domination by Boltzmann Brains. Here we consider only the simplest model, but adopt both the local and the global viewpoint in the description of the Universe. In the former case, we find that if a parameter $c$, which modulates the Dark Energy density, lies outside the exponentially narrow strip around the most natural $c = 1$ line, the theory is rendered BB-safe. In the later case, the bound on $c$ is exponentially stronger, and seemingly at odds with those bounds on $c$ obtained from various observational tests.

Horvat, R

2015-01-01

235

Design and Integration of Partial Brain Models Using Hierarchical Cooperative CoEvolution  

E-print Network

Design and Integration of Partial Brain Models Using Hierarchical Cooperative CoEvolution Michail and integrating brain-inspired artificial cognitive sys- tems. Specifically, we introduce a new computational framework for modelling partial brain areas following a coevolutionary agent-based approach. Properly for

Trahanias, Panos

236

Categories and Functional Units: An Infinite Hierarchical Model for Brain Activations  

E-print Network

Categories and Functional Units: An Infinite Hierarchical Model for Brain Activations Danial present a model that describes the structure in the responses of different brain areas to a set of stimuli encodes the relationship between brain activations and fMRI time courses. A variational inference

Golland, Polina

237

Predictive Modeling of fMRI Brain States using Functional Canonical Correlation Analysis  

E-print Network

Predictive Modeling of fMRI Brain States using Functional Canonical Correlation Analysis S Abstract. We present a novel method for predictive modeling of human brain states from functional for prediction of naturalistic stimuli from unknown fMRI data shows that the method nds highly predictive brain

Smeulders, Arnold

238

MODELING INTRACRANIAL FLUID FLOWS AND VOLUMES DURING TRAUMATIC BRAIN INJURY TO BETTER UNDERSTAND PRESSURE  

E-print Network

MODELING INTRACRANIAL FLUID FLOWS AND VOLUMES DURING TRAUMATIC BRAIN INJURY TO BETTER UNDERSTAND treatment options for elevated ICP during traumatic brain injury (TBI). The model uses fluid volumes mechanisms that are activated during TBI. Keywords--intracranial pressure (ICP), traumatic brain injury (TBI

239

A Weighted Multi-Sequence Markov Model For Brain Lesion Segmentation  

E-print Network

A Weighted Multi-Sequence Markov Model For Brain Lesion Segmentation F. Forbes, S. Doyle D. Garcia brain lesions. It is based on an augmented multi-sequence hidden Markov model that in- cludes additional of multiple sclerosis and stroke lesions shows promising results. 1 Introduction Magnetic Resonance (MR) brain

Paris-Sud XI, Université de

240

Finite element decomposition and grid generation for brain modeling and visualization  

E-print Network

Numerical grid generation is used to provide a framework for brain and neuron visualization. Smoothing spline surfaces are fit to contour data to generate 3D solid model reconstruction of brain tissues. Finite element methods are then used...

Batte, David Allan

1997-01-01

241

Experimental myocardial infarction  

PubMed Central

Acute myocardial infarction causes depression of left ventricular function, but the capacity of the ventricle to recover from such an injury remains unknown. This problem was explored by measuring left ventricular function in eight intact conscious dogs before, 1 hr after, and again 6-8 days after myocardial infarction. Acute myocardial infarction was produced using a technique which entails gradual inflation over an average period of 1 hr of a balloon cuff previously implanted around the left anterior descending coronary artery. Occurrence of anterior wall infarction was detected electrocardiographically and later confirmed by postmortem examination. Left ventricular function was evaluated from the relationship between left ventricular developed pressure (left ventricular peak systolic pressure minus left ventricular end-diastolic pressure) and left ventricular end-diastolic pressure during transient aortic occlusion with a balloon catheter. Left ventricular function curves were obtained by plotting left ventricular-developed pressure at increasing left ventricular end-diastolic pressures up to 50 mm Hg. Acute myocardial infarction caused marked depression of left ventricular function measured 1 hr after onset of infarction, but 1 wk later all eight animals showed improvement with return of function toward the control levels. A small but significant descending limb was noted at left ventricular end-diastolic pressures above 35 mm Hg. Quantitatively, the descending limb was similar before, 1 hr after, and 1 wk after myocardial infarction. Hemodynamic data revealed evidence of left ventricular failure in all animals, but variability in individual hemodynamic parameters was noted. The data indicate that the marked depression of left ventricular function observed immediately after experimental acute myocardial infarction undergoes considerable resolution within 1 wk, but that functional recovery remains incomplete. PMID:5409808

Kumar, Raj; Hood, William B.; Joison, Julio; Norman, John C.; Abelmann, Walter H.

1970-01-01

242

Ibudilast, a phosphodiesterase inhibitor with anti-inflammatory activity, protects against ischemic brain injury in rats  

Microsoft Academic Search

Ibudilast, a non-selective phosphodiesterase inhibitor, is clinically used in patients with stroke or dizziness. However, whether the compound exerts a beneficial effect on acute ischemic stroke remains to be established. We used a rat model of transient focal cerebral ischemia using middle cerebral artery occlusion (MCAO) and reperfusion, and explored the effects of ibudilast on infarction size, brain edema, atrophy,

Joo-Yong Lee; Eunsil Cho; Young Eun Ko; Inki Kim; Kyung Jin Lee; Sun U. Kwon; Dong-Wha Kang; Jong S. Kim

243

Fluid-percussion–induced traumatic brain injury model in rats  

PubMed Central

Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Various attempts have been made to replicate clinical TBI using animal models. The fluid-percussion model (FP) is one of the oldest and most commonly used models of experimentally induced TBI. Both central (CFP) and lateral (LFP) variations of the model have been used. Developed initially for use in larger species, the standard FP device was adapted more than 20 years ago to induce consistent degrees of brain injury in rodents. Recently, we developed a microprocessor-controlled, pneumatically driven instrument, micro-FP (MFP), to address operational concerns associated with the use of the standard FP device in rodents. We have characterized the MFP model with regard to injury severity according to behavioral and histological outcomes. In this protocol, we review the FP models and detail surgical procedures for LFP. The surgery involves tracheal intubation, craniotomy and fixation of Luer fittings, and induction of injury. The surgical procedure can be performed within 45–50 min. PMID:20725070

Kabadi, Shruti V.; Hilton, Genell D.; Stoica, Bogdan A.; Zapple, David N.; Faden, Alan I.

2013-01-01

244

Simulation model for contrast agent dynamics in brain perfusion scans.  

PubMed

Standardization efforts are currently under way to reduce the heterogeneity of quantitative brain perfusion methods. A brain perfusion simulation model is proposed to generate test data for an unbiased comparison of these methods. This model provides realistic simulated patient data and is independent of and different from any computational method. The flow of contrast agent solute and blood through cerebral vasculature with disease-specific configurations is simulated. Blood and contrast agent dynamics are modeled as a combination of convection and diffusion in tubular networks. A combination of a cerebral arterial model and a microvascular model provides arterial-input and time-concentration curves for a wide range of flow and perfusion statuses. The model is configured to represent an embolic stroke in one middle cerebral artery territory and provides physiologically plausible vascular dispersion operators for major arteries and tissue contrast agent retention functions. These curves are fit to simpler template curves to allow the use of the simulation results in multiple validation studies. A gamma-variate function with fit parameters is proposed as the vascular dispersion operator, and a combination of a boxcar and exponential decay function is proposed as the retention function. Such physiologically plausible operators should be used to create test data that better assess the strengths and the weaknesses of various analysis methods. PMID:20572155

Bredno, Jörg; Olszewski, Mark E; Wintermark, Max

2010-07-01

245

Serial in vivo positive contrast MRI of iron oxide-labeled embryonic stem cell-derived cardiac precursor cells in a mouse model of myocardial infarction.  

PubMed

Myocardial regeneration with stem-cell transplantation is a possible treatment option to reverse deleterious effects that occur after myocardial infarction. Since little is known about stem cell survival after transplantation, developing techniques for "tracking" cells would be desirable. Iron-oxide-labeled stem cells have been used for in vivo tracking using MRI but produce negative contrast images that are difficult to interpret. The aim of the current study was to test a positive contrast MR technique using reduced z-gradient rephasing (GRASP) to aid in dynamically tracking stem cells in an in vivo model of mouse myocardial infraction. Ferumoxides and protamine sulfate were complexed and used to magnetically label embryonic stem cell-derived cardiac-precursor-cells (ES-CPCs). A total of 500,000 ES-CPCs were injected in the border zone of infarcted mice and MR imaging was performed on a 9.4T scanner using T(2)*-GRE sequences (negative contrast) and positive contrast GRASP technique before, 24 hours, and 1 week after ES-CPC implantation. Following imaging, mice were sacrificed for histology and Perl's staining was used to confirm iron within myocardium. Good correlation was observed between signal loss seen on conventional T(2)* images, bright areas on GRASP, and the presence of iron on histology. This demonstrated the feasibility of in vivo stem cell imaging with positive contrast MRI. PMID:18581415

Mani, Venkatesh; Adler, Eric; Briley-Saebo, Karen C; Bystrup, Anne; Fuster, Valentin; Keller, Gordon; Fayad, Zahi A

2008-07-01

246

The animat: new frontiers in whole brain modeling.  

PubMed

The researchers at Boston University (BU)'s Neuromorphics Laboratory, part of the National Science Foundation (NSF)-sponsored Center of Excellence for Learning in Education, Science, and Technology (CELEST), are working in collaboration with the engineers and scientists at Hewlett-Packard (HP) to implement neural models of intelligent processes for the next generation of dense, low-power, computer hardware that will use memristive technology to bring data closer to the processor where computation occurs. The HP and BU teams are jointly designing an optimal infrastructure, simulation, and software platform to build an artificial brain. The resulting Cog Ex Machina (Cog) software platform has been successfully used to implement a large-scale, multicomponent brain system that is able to simulate some key rat behavioral results in a virtual environment and has been applied to control robotic platforms as they learn to interact with their environment. PMID:22344952

Ames, Heather; Mingolla, Ennio; Sohail, Aisha; Chandler, Benjamin; Gorchetchnikov, Anatoli; Leveille, Jasmin; Livitz, Gennady; Versace, Massimiliano

2012-01-01

247

High-strain-rate brain injury model using submerged acute rat brain tissue slices.  

PubMed

Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3?psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6?h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads. PMID:21970544

Sarntinoranont, Malisa; Lee, Sung J; Hong, Yu; King, Michael A; Subhash, Ghatu; Kwon, Jiwoon; Moore, David F

2012-01-20

248

Experimental Models of Brain Ischemia: A Review of Techniques, Magnetic Resonance Imaging, and Investigational Cell-Based Therapies  

PubMed Central

Stroke continues to be a significant cause of death and disability worldwide. Although major advances have been made in the past decades in prevention, treatment, and rehabilitation, enormous challenges remain in the way of translating new therapeutic approaches from bench to bedside. Thrombolysis, while routinely used for ischemic stroke, is only a viable option within a narrow time window. Recently, progress in stem cell biology has opened up avenues to therapeutic strategies aimed at supporting and replacing neural cells in infarcted areas. Realistic experimental animal models are crucial to understand the mechanisms of neuronal survival following ischemic brain injury and to develop therapeutic interventions. Current studies on experimental stroke therapies evaluate the efficiency of neuroprotective agents and cell-based approaches using primarily rodent models of permanent or transient focal cerebral ischemia. In parallel, advancements in imaging techniques permit better mapping of the spatial-temporal evolution of the lesioned cortex and its functional responses. This review provides a condensed conceptual review of the state of the art of this field, from models and magnetic resonance imaging techniques through to stem cell therapies. PMID:24600434

Canazza, Alessandra; Minati, Ludovico; Boffano, Carlo; Parati, Eugenio; Binks, Sophie

2013-01-01

249

Experimental myocardial infarction  

PubMed Central

Use of digitalis in myocardial infarction is controversial. To determine the efficacy and toxic threshold, serial infusions of 3 ?g/kg per min of acetyl-strophanthidin were given to six intact conscious dogs 24 hr before and 1 hr, 2 days, and 7 days after myocardial infarction induced by inflation of a balloon cuff implanted on the left anterior descending coronary artery. Within 1 hr after myocardial infarction, heart rate increased by 28%. Left ventricular end-diastolic pressure increased from 7 to 20 mm Hg, and stroke volume decreased by 25%. At this time acetylstrophanthidin caused no beneficial hemodynamic change, 1 wk later, the heart rate and left ventricular end-diastolic pressure had declined toward normal but remained elevated. At this time, acetylstrophanthidin lowered left ventricular end-diastolic pressure by 25%, and increased the stroke volume and cardiac output by 25% and 21% respectively, without any change in heart rate or aortic pressure. Tolerance to acetylstrophanthidin, defined as appearance of ventricular tachycardia, declined the 1st hr after myocardial infarction by 24% (P<0.05) from the control level of 43 ±4 ?g/kg (SEM), but subsequently returned to control. Thus, immediately after myocardial infarction, tolerance to acetylstrophanthidin was reduced, and left ventricular failure was not ameliorated. 1 wk later in the healing phase of myocardial infarction, tolerance to acetylstrophanthidin returned to normal and left ventricular performance was improved by this drug. The study suggests a limited therapeutic role for digitalis in the treatment of left ventricular failure in the acute phase immediately after myocardial infarction, but beneficial effects may occur in the healing phase 1 wk later. PMID:5411786

Kumar, Raj; Hood, William B.; Joison, Julio; Gilmour, David P.; Norman, John C.; Abelmann, Walter H.

1970-01-01

250

Feasibility Study of Using Ultrasound Stimulation to Enhancing Blood-Brain Barrier Disruption in a Brain Tumor Model  

Microsoft Academic Search

The purpose of this study is to demonstrate the feasibility of using ultrasound induced BBB-disruption technology to enhance\\u000a brain-permeable area in a brain tumor model for the enhancement of brain-tumor drug delivery. In our system setup, either\\u000a 28-kHz non-focused ultrasound or 400-kHz focused ultrasound was used. To examine this, SD rats (n = 14) with C-6 Cell been\\u000a intestinally implanted

C. H. Pan; C. Y. Ting; C. Y. Huang; P. Y. Chen; K. C. Wei; H. L. Liu

251

A model for intratumoural chemotherapy in the rat brain.  

PubMed

To achieve the best reproducibility in rat brain tumour models several injection techniques have been used. Although stereotactic cell injections have proved to be effective and reliable, they are expensive and time consuming. A new permanently implanted device is presented here. It allows precise cell delivery for best tumour reproducibility, and it can be left in place for future injections at the exact same location, such as intratumoural chemotherapy. A Teflon tube was mounted on a disc, inserted into the rat brain and sealed to the skull. The device was tested in two rat strains (Wistar and New Zealand Nude rats) with two different glioma cell lines (9L and C6). Rats were treated with placebo to determine if repeated treatments had an effect on the device placement, or if device-related morbidity was induced. Analysis of brain sections showed that the device path was always within the tumour. The device never moved or came off the scalp. Both Wistar rats and NZ nude rats tolerated the device well. No morbidity or mortality was observed, regardless of the presence of the device; no infections were seen. Biocompatible, non-irritating and well tolerated, such a device can be used for reproducible tumour cell injections and repeated intralesional delivery of drugs. PMID:15197617

Saini, M; Roser, F; Samii, M; Bellinzona, M

2004-07-01

252

Usefulness of MRI to differentiate between temporary and long-term coronary artery occlusion in a minimally invasive model of experimental myocardial infarction.  

PubMed

The surgical technique employed to determine an experimental ischemic damage is a major factor in the subsequent process of myocardial scar development. We set out to establish a minimally invasive porcine model of myocardial infarction using cardiac contrast-enhanced magnetic resonance imaging (ce-MRI) as the basic diagnostic tool. Twenty-seven domestic pigs were randomized to either temporary or permanent occlusion of the left anterior descending artery (LAD). Temporary occlusion was achieved by inflation of a percutaneous balloon in the left anterior descending artery directly beyond the second diagonal branch. Occlusion was maintained for 30 or 45 min, followed by reperfusion. Permanent occlusion was achieved via thrombin injection. Thirteen animals died peri- or postinterventionally due to arrhythmias. Fourteen animals survived the 30-min ischemia (four animals; group 1), the 45-min ischemia (six animals; group 2), or the permanent occlusion (4 animals; group 3). Coronary angiography and ce-MRI were performed 8 weeks after coronary occlusion to document the coronary flow grade and the size of myocardial scar tissue. The LAD was patent in all animals in groups 1 and 2, with normal TIMI flow; in group 3 animals, the LAD was totally occluded. Fibrosis of the left ventricle in group 1 (4.9 +/- 4.4%; p = 0.008) and group 2 (9.4 +/- 2.9%; p = 0.05) was significantly lower than in group 3 (14.5 +/- 3.9%). Wall thickness of the ischemic area was significantly lower in group 3 versus group 1 and group 2 (2.9 +/- 0.3, 5.9 +/- 0.7, and 6.1 +/- 0.7 mm; p = 0.005). The extent of late enhancement of the left ventricle was also significantly higher in group 3 (16.9 +/- 2.1%) compared to group 1 (5.3 +/- 5.4%; p = 0.003) and group 2 (9.7 +/- 3.4%, p = 0.013). In conclusion, the present model of minimally invasive infarction coupled with ce-MRI may represent a useful alternative to the open chest model for studies of myocardial infarction and scar development. PMID:19472001

Abegunewardene, Nico; Vosseler, Markus; Gori, Tommaso; Hoffmann, Nico; Schmidt, Kai-Helge; Becker, Dietmar; Kreitner, Karl-Friedrich; Petersen, Steffen E; Schreiber, Laura M; Horstick, Georg; Münzel, Thomas

2009-09-01

253

A rodent model of mild traumatic brain blast injury.  

PubMed

One of the criteria defining mild traumatic brain injury (mTBI) in humans is a loss of consciousness lasting for less than 30 min. mTBI can result in long-term impairment of cognition and behavior. In rats, the length of time it takes a rat to right itself after injury is considered to be an analog for human return to consciousness. This study characterized a rat mild brain blast injury (mBBI) model defined by a righting response reflex time (RRRT) of more than 4 min but less than 10 min. Assessments of motor coordination relying on beam-balance and foot-fault assays and reference memory showed significant impairment in animals exposed to mBBI. This study's hypothesis is that there are inflammatory outcomes to mTBI over time that cause its deleterious effects. For example, mBBI significantly increased brain levels of interleukin (IL)-1? and tumor necrosis factor-? (TNF?) protein. There were significant inflammatory responses in the cortex, hippocampus, thalamus, and amygdala 6 hr after mBBI, as evidenced by increased levels of the inflammatory markers associated with activation of microglia and macrophages, ionized calcium binding adaptor 1 (IBA1), impairment of the blood-brain barrier, and significant neuronal losses. There were significant increases in phosphorylated Tau (p-Tau) levels, a putative precursor to the development of neuroencephalopathy, as early as 6 hr after mBBI in the cortex and the hippocampus but not in the thalamus or the amygdala. There was an apparent correlation between RRRTs and p-Tau protein levels but not IBA1. These results suggest potential therapies for mild blast injuries via blockade of the IL-1? and TNF? receptors. © 2014 Wiley Periodicals, Inc. PMID:25410497

Perez-Polo, J R; Rea, H C; Johnson, K M; Parsley, M A; Unabia, G C; Xu, G-Y; Prough, D; DeWitt, D S; Spratt, H; Hulsebosch, C E

2015-04-01

254

Modeling the Impact of Lesions in the Human Brain  

Microsoft Academic Search

Lesions of anatomical brain networks result in functional disturbances of brain systems and behavior which depend sensitively, often unpredictably, on the lesion site. The availability of whole-brain maps of structural connections within the human cerebrum and our increased understanding of the physiology and large-scale dynamics of cortical networks allow us to investigate the functional consequences of focal brain lesions in

Jeffrey Alstott; Michael Breakspear; Patric Hagmann; Leila Cammoun; Olaf Sporns

2009-01-01

255

Kinematic analysis of left ventricular deformation in myocardial infarction using magnetic resonance cardiac tagging  

Microsoft Academic Search

The Magnetic Resonance (MR) tagging technique provides detailed information about 2D motion in the plane of observation. Interpretation of this information as a reflection of the 3D motion of the entire cardiac wall is a major problem. In finite element models of the mechanics of the infarcted heart, an infarcted region causes motional asymmetry, extending far beyond the infarct boundary.

Frank W. L. Aelen; Theo Arts; Dave G. M. Sanders; Guillaume R. P. Thelissen; Frits W. Prinzen; Robert S. Reneman

1999-01-01

256

Brief Communication Transplantation of embryonic stem cells into the infarcted mouse heart  

E-print Network

Brief Communication Transplantation of embryonic stem cells into the infarcted mouse heart) cells following myocardial infarction (MI) in animal models is beneficial; however, the mechanism by eGFP or b-galactosidase-positive cells in the infarct region without evidence for tumor formation

Kamp, Tim

257

In Vivo Magnetic Resonance Imaging of Mesenchymal Stem Cells in Myocardial Infarction  

E-print Network

In Vivo Magnetic Resonance Imaging of Mesenchymal Stem Cells in Myocardial Infarction Dara L-MSCs) in a swine myocardial infarction (MI) model. Methods and Results--Adult farm pigs (n 5) were subjected correlated with histology. Contrast-enhanced MRI demonstrated successful injection in the infarct and serial

Atalar, Ergin

258

POSTER PRESENTATION Open Access Multistability in large scale models of brain  

E-print Network

POSTER PRESENTATION Open Access Multistability in large scale models of brain activity Mathieu in the brain at rest, reveal several large-scale functional net- works, presumably involved in different brain functions. In parallel, structural networks obtained by Diffusion Spectrum Imaging ("connectome") identify

Paris-Sud XI, Université de

259

SEGMENTATION OF PATIENT SPECIFIC MEG/EEG SKULL, SCALP, AND BRAIN MODELS FROM MRI  

E-print Network

SEGMENTATION OF PATIENT SPECIFIC MEG/EEG SKULL, SCALP, AND BRAIN MODELS FROM MRI Belma Dogdas California, LA, CA 90089-2564 ABSTRACT We present an automated method for segmenting skull, scalp, and brain and morphology to produce a scalp mask. The brain and scalp masks provide boundaries between which the skull must

Leahy, Richard M.

260

Aligning context-based statistical models of language with brain activity during reading  

E-print Network

Aligning context-based statistical models of language with brain activity during reading Leila for incoming words given the context. On the other hand, brain imaging studies have sug- gested that during reading, the brain (a) continu- ously builds a context from the successive words and every time

Knight, Kevin

261

INCORPORATION OF A LANGUAGE MODEL INTO A BRAIN COMPUTER INTERFACE BASED SPELLER THROUGH HMMs  

E-print Network

of establishing direct communication pathways between the brain and external devices. The primary motivationINCORPORATION OF A LANGUAGE MODEL INTO A BRAIN COMPUTER INTERFACE BASED SPELLER THROUGH HMMs Ã?ada, 34956 Istanbul, Turkey ABSTRACT Brain computer interface (BCI) research deals with the problem

Yanikoglu, Berrin

262

A computational model for signaling pathways in bounded small-world networks corresponding to brain size  

E-print Network

A computational model for signaling pathways in bounded small-world networks corresponding to brain the number of neurons in the human brain, found that the length of simulated signaling pathway can by I. Bojak Available online 22 August 2011 Keywords: Small-world Brain Network Neuro-inspired a b

Hong, Dawei

263

ANALYZING IMAGING BIOMARKERS FOR TRAUMATIC BRAIN INJURY USING 4D MODELING OF LONGITUDINAL MRI  

E-print Network

ANALYZING IMAGING BIOMARKERS FOR TRAUMATIC BRAIN INJURY USING 4D MODELING OF LONGITUDINAL MRI Bo and treatment efficacy in patients with traumatic brain injury (TBI). To our knowledge, the identification, School of Computing, Brain Injury Research Center, University of Utah University of California at Los

Gerig, Guido

264

Brain glucose metabolism in an animal model of depression.  

PubMed

An increasing number of data support the involvement of disturbances in glucose metabolism in the pathogenesis of depression. We previously reported that glucose and glycogen concentrations in brain structures important for depression are higher in a prenatal stress model of depression when compared with control animals. A marked rise in the concentrations of these carbohydrates and glucose transporters were evident in prenatally stressed animals subjected to acute stress and glucose loading in adulthood. To determine whether elevated levels of brain glucose are associated with a change in its metabolism in this model, we assessed key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase), products of glycolysis, i.e., pyruvate and lactate, and two selected enzymes of the tricarboxylic acid cycle (pyruvate dehydrogenase and ?-ketoglutarate dehydrogenase) in the hippocampus and frontal cortex. Additionally, we assessed glucose-6-phosphate dehydrogenase activity, a key enzyme in the pentose phosphate pathway (PPP). Prenatal stress increased the levels of phosphofructokinase, an important glycolytic enzyme, in the hippocampus and frontal cortex. However, prenatal stress had no effect on hexokinase or pyruvate kinase levels. The lactate concentration was elevated in prenatally stressed rats in the frontal cortex, and pyruvate levels remained unchanged. Among the tricarboxylic acid cycle enzymes, prenatal stress decreased the level of pyruvate dehydrogenase in the hippocampus, but it had no effect on ?-ketoglutarate dehydrogenase. Like in the case of glucose and its transporters, also in the present study, differences in markers of glucose metabolism between control animals and those subjected to prenatal stress were not observed under basal conditions but in rats subjected to acute stress and glucose load in adulthood. Glucose-6-phosphate dehydrogenase activity was not reduced by prenatal stress but was found to be even higher in animals exposed to all experimental conditions, i.e., prenatal stress, acute stress, and glucose administration. Our data indicate that glycolysis is increased and the Krebs cycle is decreased in the brain of a prenatal stress animal model of depression. PMID:25819664

Detka, J; Kurek, A; Kucharczyk, M; G?ombik, K; Basta-Kaim, A; Kubera, M; Laso?, W; Budziszewska, B

2015-06-01

265

Mesenchymal Stem Cell Transplantation Enhancement in Myocardial Infarction Rat Model under Ultrasound Combined with Nitric Oxide Microbubbles  

PubMed Central

Objective This study evaluated the effects of ultrasound combined with the homemade nitric oxide (NO) micro-bubble destruction on the in vitro proliferation, apoptosis, and migration of mesenchymal stem cells (MSCs). Furthermore, we studied whether or not irradiation of the NO micro-bubble combined with bone-marrow derived MSC infusion had a better effect on treating myocardial infarction. The possible mechanism of MSC delivery into the infarcted myocardium was also investigated. Methods The murine bone marrow-derived MSCs were isolated, cultured, irradiated, and combined with different concentrations of NO microbubbles. MTT proliferation assay, annexin V-FITC apoptosis detection, migration assay, and RT-PCR were performed 24 h after the irradiation. The NO micro-bubbles was a intravenously injected, followed by the infusion of MSCs, which were labeled by CM-Dil. Myocardium was harvested 48 h later and the distribution of MSCs was observed by laser scanning confocal microscope after frozen sectioning. Echocardiography, histological examination, RT-PCR, and western blotting were performed four weeks after the cell transplantation. Results Ultrasound combined with 1:70 NO micro-bubbles had no significant impact on the proliferation or apoptosis of MSCs. Transwell chamber findings demonstrated that MSCs migrated more efficiently in group that underwent ultrasound combined with 1:70 NO micro-bubbles. The Real-time PCR results indicated that the expression of CXCR4 was much higher in the group undergoing ultrasound combined with 1:70 NO micro-bubbles. The normalized fluorescence intensity greatly increased in the group of US+NO micro-bubbles and the cardiac function was also markedly improved. Immunohistochemical staining showed that the capillary density was much greater in the group of US+NO micro-bubbles as compared to that of the other groups. RT-PCR and western blotting also revealed a higher SDF-1 and VEGF expression in the group of US+NO micro-bubbles. Conclusions NO micro-bubbles could be used in the cell transplantation, which efficiently promoted the MSC homing into the infarcted myocardium. PMID:24244646

Tong, Jiayi; Ding, Jiandong; Shen, Xiangbo; Chen, Long; Bian, Yeping; Ma, Genshan; Yao, Yuyu; Yang, Fang

2013-01-01

266

Using Data-Driven Model-Brain Mappings to Constrain Formal Models of Cognition  

PubMed Central

In this paper we propose a method to create data-driven mappings from components of cognitive models to brain regions. Cognitive models are notoriously hard to evaluate, especially based on behavioral measures alone. Neuroimaging data can provide additional constraints, but this requires a mapping from model components to brain regions. Although such mappings can be based on the experience of the modeler or on a reading of the literature, a formal method is preferred to prevent researcher-based biases. In this paper we used model-based fMRI analysis to create a data-driven model-brain mapping for five modules of the ACT-R cognitive architecture. We then validated this mapping by applying it to two new datasets with associated models. The new mapping was at least as powerful as an existing mapping that was based on the literature, and indicated where the models were supported by the data and where they have to be improved. We conclude that data-driven model-brain mappings can provide strong constraints on cognitive models, and that model-based fMRI is a suitable way to create such mappings. PMID:25747601

Borst, Jelmer P.; Nijboer, Menno; Taatgen, Niels A.; van Rijn, Hedderik; Anderson, John R.

2015-01-01

267

Using data-driven model-brain mappings to constrain formal models of cognition.  

PubMed

In this paper we propose a method to create data-driven mappings from components of cognitive models to brain regions. Cognitive models are notoriously hard to evaluate, especially based on behavioral measures alone. Neuroimaging data can provide additional constraints, but this requires a mapping from model components to brain regions. Although such mappings can be based on the experience of the modeler or on a reading of the literature, a formal method is preferred to prevent researcher-based biases. In this paper we used model-based fMRI analysis to create a data-driven model-brain mapping for five modules of the ACT-R cognitive architecture. We then validated this mapping by applying it to two new datasets with associated models. The new mapping was at least as powerful as an existing mapping that was based on the literature, and indicated where the models were supported by the data and where they have to be improved. We conclude that data-driven model-brain mappings can provide strong constraints on cognitive models, and that model-based fMRI is a suitable way to create such mappings. PMID:25747601

Borst, Jelmer P; Nijboer, Menno; Taatgen, Niels A; van Rijn, Hedderik; Anderson, John R

2015-01-01

268

Melanoma Cells Homing to the Brain: An In Vitro Model  

PubMed Central

We developed an in vitro contact through-feet blood brain barrier (BBB) model built using type IV collagen, rat astrocytes, and human umbilical vein endothelial cells (HUVECs) cocultured through Transwell porous polycarbonate membrane. The contact between astrocytes and HUVECs was demonstrated by electron microscopy: astrocytes endfeet pass through the 8.0??m pores inducing HUVECs to assume a cerebral phenotype. Using this model we evaluated transmigration of melanoma cells from two different patients (M1 and M2) selected among seven melanoma primary cultures. M2 cells showed a statistically significant higher capability to pass across the in vitro BBB model, compared to M1. Expression of adhesion molecules was evaluated by flow cytometry: a statistically significant increased expression of MCAM, ?v?3, and CD49b was detected in M1. PCR array data showed that M2 had a higher expression of several matrix metalloproteinase proteins (MMPs) compared to M1. Specifically, data suggest that MMP2 and MMP9 could be directly involved in BBB permeability and that brain invasion by melanoma cells could be related to the overexpression of many MMPs. Future studies will be necessary to deepen the mechanisms of central nervous system invasion. PMID:25692137

Rizzo, A.; Vasco, C.; Girgenti, V.; Fugnanesi, V.; Calatozzolo, C.; Canazza, A.; Salmaggi, A.; Rivoltini, L.; Morbin, M.; Ciusani, E.

2015-01-01

269

Melanoma cells homing to the brain: an in vitro model.  

PubMed

We developed an in vitro contact through-feet blood brain barrier (BBB) model built using type IV collagen, rat astrocytes, and human umbilical vein endothelial cells (HUVECs) cocultured through Transwell porous polycarbonate membrane. The contact between astrocytes and HUVECs was demonstrated by electron microscopy: astrocytes endfeet pass through the 8.0??m pores inducing HUVECs to assume a cerebral phenotype. Using this model we evaluated transmigration of melanoma cells from two different patients (M1 and M2) selected among seven melanoma primary cultures. M2 cells showed a statistically significant higher capability to pass across the in vitro BBB model, compared to M1. Expression of adhesion molecules was evaluated by flow cytometry: a statistically significant increased expression of MCAM, ?v?3, and CD49b was detected in M1. PCR array data showed that M2 had a higher expression of several matrix metalloproteinase proteins (MMPs) compared to M1. Specifically, data suggest that MMP2 and MMP9 could be directly involved in BBB permeability and that brain invasion by melanoma cells could be related to the overexpression of many MMPs. Future studies will be necessary to deepen the mechanisms of central nervous system invasion. PMID:25692137

Rizzo, A; Vasco, C; Girgenti, V; Fugnanesi, V; Calatozzolo, C; Canazza, A; Salmaggi, A; Rivoltini, L; Morbin, M; Ciusani, E

2015-01-01

270

Neuroprotective effects of crocin on the histopathological alterations following brain ischemia-reperfusion injury in rat  

PubMed Central

Objective(s): Some histopathological alterations take place in the ischemic regions following brain ischemia. Recent studies have demonstrated some neuroprotective roles of crocin in different models of experimental cerebral ischemia. Here, we investigated the probable neuroprotective effects of crocin on the brain infarction and histopathological changes after transient model of focal cerebral ischemia. Materials and Methods: Experiment was performed in four groups of rats (each group; n=8), sham, control ischemia and ischemia treated rats. Transient focal cerebral ischemia was induced by 80 min middle cerebral artery occlusion (MCAO) followed by 24 hr reperfusion. Crocin, at doses 50 and 80 mg/kg, was injected at the beginning of ischemia (IP injection). Neurologic outcome (Neurological Deficit Score, NDS scale), infarct volume (TTC staining) and histological studies were assessed 24 hr after termination of MCAO. Results: Treatment with crocin, at doses 50 and 80 mg/kg, significantly reduced the cortical infarct volume by 48% and 60%, and also decreased striatal infarct volume by 45% and75%, respectively. Crocin at two different doses significantly improved the NDS of ischemic rats. At histological evaluation, crocin, at dose 80 mg/kg more than 50 mg/kg, decreased the number of eosinophilic (prenecrotic) neurons and reduced the fiber demyelination and axonal damage in ischemic regions. Conclusion: Our findings indicated that crocin effectively reduces brain ischemia-induced injury and improves neurological outcomes. Crocin also is a potent neuroprotective factor that can be able to prevent histopathological alterations following brain ischemia. PMID:25691932

Sarshoori, Javad Raouf; Asadi, Mohammad Hossien; Mohammadi, Mohammad Taghi

2014-01-01

271

Natural Genetic Variation of Integrin Alpha L (Itgal) Modulates Ischemic Brain Injury in Stroke  

PubMed Central

During ischemic stroke, occlusion of the cerebrovasculature causes neuronal cell death (infarction), but naturally occurring genetic factors modulating infarction have been difficult to identify in human populations. In a surgically induced mouse model of ischemic stroke, we have previously mapped Civq1 to distal chromosome 7 as a quantitative trait locus determining infarct volume. In this study, genome-wide association mapping using 32 inbred mouse strains and an additional linkage scan for infarct volume confirmed that the size of the infarct is determined by ancestral alleles of the causative gene(s). The genetically isolated Civq1 locus in reciprocal recombinant congenic mice refined the critical interval and demonstrated that infarct size is determined by both vascular (collateral vessel anatomy) and non-vascular (neuroprotection) effects. Through the use of interval-specific SNP haplotype analysis, we further refined the Civq1 locus and identified integrin alpha L (Itgal) as one of the causative genes for Civq1. Itgal is the only gene that exhibits both strain-specific amino acid substitutions and expression differences. Coding SNPs, a 5-bp insertion in exon 30b, and increased mRNA and protein expression of a splice variant of the gene (Itgal-003, ENSMUST00000120857), all segregate with infarct volume. Mice lacking Itgal show increased neuronal cell death in both ex vivo brain slice and in vivo focal cerebral ischemia. Our data demonstrate that sequence variation in Itgal modulates ischemic brain injury, and that infarct volume is determined by both vascular and non-vascular mechanisms. PMID:24130503

Keum, Sehoon; Lee, Han Kyu; Chu, Pei-Lun; Kan, Matthew J.; Huang, Min-Nung; Gallione, Carol J.; Gunn, Michael D.; Lo, Donald C.; Marchuk, Douglas A.

2013-01-01

272

Agraphia caused by acute right parietal infarction.  

PubMed

Injury in the dominant language hemisphere typically leads to agraphia, however we report a patient with agraphia after injury to the right angular gyrus. A 71-year-old Korean woman presented with the complaint of an inability to write for the last 7days. The patient had been illiterate for most of her life, but had started learning to write Hangul, the Korean alphabet, at a welfare center 3years ago. On language screening she was unable to write although she could read, and other language functions showed no abnormalities. Brain MRI showed acute infarction in the right angular gyrus. Her writing patterns displayed features of surface agraphia, indicative of phoneme-to-grapheme conversion with phonetic writing of targets. Additionally, she manifested visual errors. A functional MRI indicated that her left hemisphere was language dominant. This patient experienced agraphia resulting from pure impairment of visuo-constructive function after acute infarction in the right angular gyrus. PMID:25564267

Lee, Manyong; Suh, Mee Kyung; Lee, Myung Hyun; Lee, Jin Soo; Moon, So Young

2015-04-01

273

AICAR-dependent AMPK Activation Improves Scar Formation in the Aged Heart in a Murine Model of Reperfused Myocardial Infarction  

PubMed Central

We have demonstrated that scar formation after myocardial infarction (MI) is associated with an endogenous pool of CD44posCD45neg multipotential mesenchymal stem cells (MSC). MSC differentiate into fibroblasts secreting collagen that forms a scar and mature into myofibroblasts that express alpha smooth muscle actin (?-SMA) that stabilizes the scar. In the aging mouse, cardiac repair after MI is associated with impaired differentiation of MSC; MSC derived from aged hearts form dysfunctional fibroblasts that deposit less collagen in response to transforming growth factor beta-1 (TGF-?1) and poorly mature into myofibroblasts. We found in vitro that the defect in myofibroblast maturation can be remedied by AICAR, which activates non-canonical TGF-? signaling through AMP-activated protein kinase (AMPK). In the present study, we injected aged mice with AICAR and subjected them to 1h occlusion of the left anterior descending artery (LAD) and then reperfusion for up to 30 days. AICAR-dependent AMPK signaling led to mobilization of an endogenous CD44posCD45neg MSC and its differentiation towards fibroblasts and myofibroblasts in the infarct. This was accompanied by enhanced collagen deposition and collagen fiber maturation in the scar. The AICAR-treated group has demonstrated reduced adverse remodeling as indicated by improved apical end diastolic dimension but no changes in ejection fraction and cardiac output were observed. We concluded that these data indicate the novel, previously not described role of AMPK in the post-MI scar formation. These findings can potentially lead to a new therapeutic strategy for prevention of adverse remodeling in the aging heart. PMID:23871790

Cieslik, Katarzyna A.; Taffet, George E.; Crawford, Jeffrey R.; Trial, JoAnn; Osuna, Patricia Mejia; Entman, Mark L.

2013-01-01

274

Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.  

PubMed

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems. PMID:24499315

Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

2014-03-25

275

Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest  

PubMed Central

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer–drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems. PMID:24499315

2015-01-01

276

Multispectral optoacoustic tomography of myocardial infarction  

PubMed Central

Objectives To investigate the feasibility of a high resolution optical imaging strategy for myocardial infarction. Background Near-infrared approaches to imaging cardiovascular disease enable visualization of disease-associated biological processes in vivo. However, even at the scale of small animals, the strong scattering of light prevents high resolution imaging after the first 1–2 mm of tissue, leading to degraded signal localization. Methods Multispectral optoacoustic tomography (MSOT) was used to non-invasively image myocardial infarction (MI) in a murine model of coronary artery ligation at resolutions not possible with current deep-tissue optical imaging methods. Post-MI imaging was based on resolving the spectral absorption signature of a dendritic polyglycerol sulfate-based (dPGS) near-infrared imaging agent targeted to P- and L-selectin. Results In vivo imaging succeeded in detection of the agent in the injured myocardium after intravenous injection. The high anatomic resolution (<200 ?m) achieved by the described method allowed signals originating in the infarcted heart to be distinguished from uptake in adjacent regions. Histological analysis found dPGS signal in infarcted areas, originating from leukocytes and endothelial cells. Conclusions MSOT imaging of myocardial infarction provides non-invasive visualization of optical contrast with a high spatial resolution that is not degraded by the scattering of light. PMID:25327410

Taruttis, Adrian; Wildgruber, Moritz; Kosanke, Katja; Beziere, Nicolas; Licha, Kai; Haag, Rainer; Aichler, Michaela; Walch, Axel; Rummeny, Ernst; Ntziachristos, Vasilis

2012-01-01

277

Focal brain trauma in the cryogenic lesion model in mice.  

PubMed

The method to induce unilateral cryogenic lesions was first described in 1958 by Klatzo. We describe here an adaptation of this model that allows reliable measurement of lesion volume and vasogenic edema by 2, 3, 5-triphenyltetrazolium chloride-staining and Evans blue extravasation in mice. A copper or aluminium cylinder with a tip diameter of 2.5 mm is cooled with liquid nitrogen and placed on the exposed skull bone over the parietal cortex (coordinates from bregma: 1.5 mm posterior, 1.5 mm lateral). The tip diameter and the contact time between the tip and the parietal skull determine the extent of cryolesion. Due to an early damage of the blood brain barrier, the cryogenic cortical injury is characterized by vasogenic edema, marked brain swelling, and inflammation. The lesion grows during the first 24 hours, a process involving complex interactions between endothelial cells, immune cells, cerebral blood flow, and the intracranial pressure. These contribute substantially to the damage from the initial injury. The major advantage of the cryogenic lesion model is the circumscribed and highly reproducible lesion size and location. PMID:22480252

Raslan, Furat; Albert-Weißenberger, Christiane; Ernestus, Ralf-Ingo; Kleinschnitz, Christoph; Sirén, Anna-Leena

2012-01-01

278

Focal brain trauma in the cryogenic lesion model in mice  

PubMed Central

The method to induce unilateral cryogenic lesions was first described in 1958 by Klatzo. We describe here an adaptation of this model that allows reliable measurement of lesion volume and vasogenic edema by 2, 3, 5-triphenyltetrazolium chloride-staining and Evans blue extravasation in mice. A copper or aluminium cylinder with a tip diameter of 2.5 mm is cooled with liquid nitrogen and placed on the exposed skull bone over the parietal cortex (coordinates from bregma: 1.5 mm posterior, 1.5 mm lateral). The tip diameter and the contact time between the tip and the parietal skull determine the extent of cryolesion. Due to an early damage of the blood brain barrier, the cryogenic cortical injury is characterized by vasogenic edema, marked brain swelling, and inflammation. The lesion grows during the first 24 hours, a process involving complex interactions between endothelial cells, immune cells, cerebral blood flow, and the intracranial pressure. These contribute substantially to the damage from the initial injury. The major advantage of the cryogenic lesion model is the circumscribed and highly reproducible lesion size and location. PMID:22480252

2012-01-01

279

A mathematical model for brain tumor response to radiation therapy  

PubMed Central

Gliomas are highly invasive primary brain tumors, accounting for nearly 50% of all brain tumors (Alvord and Shaw in The pathology of the aging human nervous system. Lea & Febiger, Philadelphia, pp 210–281, 1991). Their aggressive growth leads to short life expectancies, as well as a fairly algorithmic approach to treatment: diagnostic magnetic resonance image (MRI) followed by biopsy or surgical resection with accompanying second MRI, external beam radiation therapy concurrent with and followed by chemotherapy, with MRIs conducted at various times during treatment as prescribed by the physician. Swanson et al. (Harpold et al. in J Neuropathol Exp Neurol 66:1–9, 2007) have shown that the defining and essential characteristics of gliomas in terms of net rates of proliferation (?) and invasion (D) can be determined from serial MRIs of individual patients. We present an extension to Swanson’s reaction-diffusion model to include the effects of radiation therapy using the classic linear-quadratic radiobiological model (Hall in Radiobiology for the radiologist. Lippincott, Philadelphia, pp 478–480, 1994) for radiation efficacy, along with an investigation of response to various therapy schedules and dose distributions on a virtual tumor (Swanson et al. in AACR annual meeting, Los Angeles, 2007). PMID:18815786

Rockne, R.; Alvord, E. C.; Rockhill, J. K.

2013-01-01

280

Avian Egg Latebra as Brain Tissue Water Diffusion Model  

PubMed Central

Purpose Simplified models of non-monoexponential diffusion signal decay are of great interest to study the basic constituents of complex diffusion behaviour in tissues. The latebra, a unique structure uniformly present in the yolk of avian eggs, exhibits a non-monoexponential diffusion signal decay. This model is more complex than simple phantoms based on differences between water and lipid diffusion, but is also devoid of microscopic structures with preferential orientation or perfusion effects. Methods Diffusion scans with multiple b-values were performed on a clinical 3 Tesla system in raw and boiled chicken eggs equilibrated to room temperature. Diffusion encoding was applied over the ranges 5–5,000 and 5–50,000 s/mm2. A low read-out bandwidth and chemical shift was used for reliable lipid/water separation. Signal decays were fitted with exponential functions. Results The latebra, when measured over the 5–5,000 s/mm2 range, exhibited independent of preparation clearly biexponential diffusion, with diffusion parameters similar to those typically observed in in-vivo human brain. For the range 5–50,000 s/mm2 there was evidence of a small third, very slow diffusing water component. Conclusion The latebra of the avian egg contains membrane structures, which may explain a deviation from a simple monoexponential diffusion signal decay, which is remarkably similar to the deviation observed in brain tissue. PMID:24105853

Maier, Stephan E.; Mitsouras, Dimitris; Mulkern, Robert V.

2013-01-01

281

A better mild traumatic brain injury model in the rat.  

PubMed

The primary pathology associated with mild -traumatic brain injury (TBI) is selective axonal injury, which may characterize the vast majority of blast-induced TBIs. Axonal injuries in cases of mild TBI have been considered to be the main factors responsible for the long-lasting memory or attentional impairment in affected subjects. Among these axonal injuries, recent attention has been focused on the cingulum bundle (CB). Furthermore, recent studies with diffusion tensor MR imaging have shown the presence of injuries of the CB in cases of mild TBI in humans. This study aimed to provide a better laboratory model of mild TBI.Sprague-Dawley rats were subjected to mild TBI using laser-induced shock waves (LISW) (sham, 0.5 J/cm(2), or 1.0 J/cm(2); n = 4 per group). Bodian-stained brain sections 14 days after LISW at 0.5 J/cm(2) or 1.0 J/cm(2) showed a decrease in the CB axonal density compared with the sham group, whereas there were no differences in the axonal density of the corpus callosum.The present study shows that this model is capable of reproducing the histological changes associated with mild TBI. PMID:23564112

Takeuchi, Satoru; Nawashiro, Hiroshi; Sato, Shunichi; Kawauchi, Satoko; Nagatani, Kimihiro; Kobayashi, Hiroaki; Otani, Naoki; Osada, Hideo; Wada, Kojiro; Shima, Katsuji

2013-01-01

282

Bayesian network models in brain functional connectivity analysis.  

PubMed

Much effort has been made to better understand the complex integration of distinct parts of the human brain using functional magnetic resonance imaging (fMRI). Altered functional connectivity between brain regions is associated with many neurological and mental illnesses, such as Alzheimer and Parkinson diseases, addiction, and depression. In computational science, Bayesian networks (BN) have been used in a broad range of studies to model complex data set in the presence of uncertainty and when expert prior knowledge is needed. However, little is done to explore the use of BN in connectivity analysis of fMRI data. In this paper, we present an up-to-date literature review and methodological details of connectivity analyses using BN, while highlighting caveats in a real-world application. We present a BN model of fMRI dataset obtained from sixty healthy subjects performing the stop-signal task (SST), a paradigm widely used to investigate response inhibition. Connectivity results are validated with the extant literature including our previous studies. By exploring the link strength of the learned BN's and correlating them to behavioral performance measures, this novel use of BN in connectivity analysis provides new insights to the functional neural pathways underlying response inhibition. PMID:24319317

Ide, Jaime S; Zhang, Sheng; Li, Chiang-Shan R

2014-01-01

283

A mouse model of human repetitive mild traumatic brain injury  

PubMed Central

A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an impact to the cranium of an unrestrained subject allowing rapid acceleration of the free-moving head and torso, an essential characteristic known to be important for concussive injury in humans, and a factor that is missing from existing animal models of TBI. Our method does not require scalp incision, emplacement of protective skull helmets or surgery and the procedure can be completed in 1-2 minutes. Mice spontaneously recover the righting reflex and show no evidence of seizures, paralysis or impaired behavior. Skull fractures and intracranial bleeding are very rare. Minor deficits in motor coordination and locomotor hyperactivity recover over time. Histological analyses reveal mild astrocytic reactivity (increased expression of GFAP) and increased phospho-tau but a lack of blood-brain-barrier disruption, edema and microglial activation. This new animal model is simple and cost-effective and will facilitate characterization of the neurobiological and behavioral consequences of rmTBI. It is also ideal for high throughput screening of potential new therapies for mild concussive injuries as experienced by athletes and military personnel. PMID:21930157

Kane, Michael J.; Pérez, Mariana Angoa; Briggs, Denise I.; Viano, David C.; Kreipke, Christian W.; Kuhn, Donald M.

2011-01-01

284

The effects of N-methyl-N-nitrosourea and azoxymethane on focal cerebral infarction and the expression of p53, p21 proteins.  

PubMed

If the activity of pro-apoptotic genes can be down-regulated by certain chemicals, cells may be protected from apoptosis. To test this hypothesis in a cerebral infarction model, we used N-methyl-N-nitrosourea (MNU) and azoxymethane (AOM), which were approved gene-modulating chemicals. A focal cerebral infarction was created by coagulation of the right middle cerebral artery and ipsilateral common carotid artery (CCA) and simultaneous transient occlusion of the contralateral CCA for 30 min in 25 adult Sprague-Dawley rats that were sacrificed 24 h later. In one group (n=7), MNU (5 mg/kg) was injected intravenously 30 min before initiation of ischemia. In another group (n=7), AOM (15 mg/kg) was administered intraperitoneally before 24 h of ischemia. The infarction volumes were checked and the brains were stained for p53 and p21 proteins. The width in micrometers of the peri-infarct area containing p53 or p21 protein-positive cells, and the number of p53 or p21 protein-positive cells (cells/HPF) were measured at an adjacent peri-infarct area. The AOM-treated group showed a significantly reduced infarction volume (by 42.5%, p<0.001), a significantly greater number of p53 positive cells (by 12.0%, p<0. 05), and a significantly wider p53 protein-positive area (by 15.6%, p<0.01) than the untreated group. AOM did not show any influence on the expression pattern of the p21 protein. MNU had no effect in the expression of p53 or p21 proteins. As a result, we concluded that AOM revealed a protective effect in ischemia by suppressing the pro-apoptotic activity of the p53 gene. Safer chemicals that can modulate apoptotic genes, if any, will provide a new therapeutic modality for cerebral infarction. PMID:10677604

Park, S W; Kim, Y B; Hwang, S N; Choi, D Y; Kwon, J T; Min, B K; Suk, J S

2000-02-14

285

Modeling the brain-pituitary-gonad axis in salmon  

SciTech Connect

To better understand the complexity of the brain-pituitary-gonad axis (BPG) in fish, we developed a biologically based pharmacodynamic model capable of accurately predicting the normal functioning of the BPG axis in salmon. This first-generation model consisted of a set of 13 equations whose formulation was guided by published values for plasma concentrations of pituitary- (FSH, LH) and ovary- (estradiol, 17a,20b-dihydroxy-4-pregnene-3-one) derived hormones measured in Coho salmon over an annual spawning period. In addition, the model incorporated pertinent features of previously published mammalian models and indirect response pharmacodynamic models. Model-based equations include a description of gonadotropin releasing hormone (GnRH) synthesis and release from the hypothalamus, which is controlled by environmental variables such as photoperiod and water temperature. GnRH stimulated the biosynthesis of mRNA for FSH and LH, which were also influenced by estradiol concentration in plasma. The level of estradiol in the plasma was regulated by the oocytes, which moved along a maturation progression. Estradiol was synthesized at a basal rate and as oocytes matured, stimulation of its biosynthesis occurred. The BPG model can be integrated with toxico-genomic, -proteomic data, allowing linkage between molecular based biomarkers and reproduction in fish.

Kim, Jonghan; Hayton, William L.; Schultz, Irv R.

2006-08-24

286

Effect of the serotonin antagonist ketanserin on the hemodynamic and morphological consequences of thrombotic infarction  

SciTech Connect

The effect of the serotonin (5-hydroxytryptamine, 5-HT) antagonist ketanserin on the remote hemodynamic consequences of thrombotic brain infarction was studied in rats. Treated rats received an injection of 1 mg/kg ketanserin 30 min before and 1 h following photochemically induced cortical infarction. Local CBF (LCBF) was assessed autoradiographically with ({sup 14}C)iodoantipyrine 4 h following infarction, and chronic infarct size was documented at 5 days. Thrombotic infarction led to significant decreases in LCBF within noninfarcted cortical regions. For example, mean LCBF was decreased to 63, 55, and 65% of control (nontreated normal rats) in ipsilateral frontal, lateral, and auditory cortices, respectively. In rats treated with ketanserin, significant decreases in LCBF were not documented within remote cortical areas compared with controls. In contrast to these hemodynamic effects, morphological analysis of chronic infarct size demonstrated no differences in infarct volume between treated (27 +/- 3 mm3) and nontreated (27 +/- 6 mm3) rats. These data are consistent with the hypothesis that 5-HT is involved in the widespread hemodynamic consequences of experimentally induced thrombotic infarction. Remote hemodynamic consequences of acute infarction can be inhibited without altering final infarct size.

Dietrich, W.D.; Busto, R.; Ginsberg, M.D. (Univ. of Miami School of Medicine, FL (USA))

1989-12-01

287

Fast, Sequence Adaptive Parcellation of Brain MR Using Parametric Models  

PubMed Central

In this paper we propose a method for whole brain parcellation using the type of generative parametric models typically used in tissue classification. Compared to the non-parametric, multi-atlas segmentation techniques that have become popular in recent years, our method obtains state-of-the-art segmentation performance in both cortical and subcortical structures, while retaining all the benefits of generative parametric models, including high computational speed, automatic adaptiveness to changes in image contrast when different scanner platforms and pulse sequences are used, and the ability to handle multi-contrast (vector-valued intensities) MR data. We have validated our method by comparing its segmentations to manual delineations both within and across scanner platforms and pulse sequences, and show preliminary results on multi-contrast test-retest scans, demonstrating the feasibility of the approach. PMID:24505732

Puonti, Oula; Iglesias, Juan Eugenio; Van Leemput, Koen

2014-01-01

288

Migration of bone marrow-derived cells and improved perfusion after treatment with erythropoietin in a murine model of myocardial infarction  

PubMed Central

Abstract Erythropoietin (EPO) was shown to have protective effects after myocardial infarction (MI) by neovascularization and antiapoptotic mechanisms. Beside direct receptor-dependent mechanisms, mobilization and homing of bone marrow-derived cells (BMCs) may play a pivotal role in this regard. In this study, we intended to track different subpopulations of BMCs and to assess serially myocardial perfusion changes in EPO-treated mice after MI. To allow tracking of BMCs, we used a chimeric mouse model. Therefore, mice (C57BL/6J) were sublethally irradiated, and bone marrow (BM) from green fluorescent protein transgenic mice was transplanted. Ten weeks later coronary artery ligation was performed to induce MI. EPO was injected for 3 days with a total dose of 5000 IU/kg. Subpopulations (CD31, c-kit, CXCR-4 and Sca-1) of EGFP+ cells were studied in peripheral blood, bone marrow and hearts by flow cytometry. Myocardial perfusion was serially investigated in vivo by pinhole single-photon emission computed tomography (SPECT) at days 6 and 30 after MI. EPO-treated animals revealed an enhanced mobilization of BMCs into peripheral blood. The numbers of these cells in BM remained unchanged. Homing of all BMCs subpopulations to the ischaemic myocardium was significantly increased in EPO-treated mice. Among the investigated subpopulations, EPO predominantly affected migration of CXCR-4+ (4.3-fold increase). Repetitively SPECT analyses revealed a reduction of perfusion defects after EPO treatment over time. Our study shows that EPO treatment after MI enhances the migration capacity of BMCs into ischaemic tissue, which may attribute to an improved perfusion and reduced size of infarction, respectively. PMID:21362129

Brunner, Stefan; Huber, Bruno C; Weinberger, Tobias; Vallaster, Marcus; Wollenweber, Tim; Gerbitz, Armin; Hacker, Marcus; Franz, Wolfgang-Michael

2012-01-01

289

Suppression of poly (ADP-ribose) polymerase activation by 3-aminobenzamide in a rat model of myocardial infarction: long-term morphological and functional consequences  

PubMed Central

Recent studies demonstrated that inhibition or genetic inactivation of the enzyme poly (ADP-ribose) polymerase (PARP) is beneficial in myocardial reperfusion injury. PARP activation in the reperfused myocardium has been assumed, but not directly demonstrated. Furthermore, the issue whether pharmacological PARP inhibition affords long-term functional benefit in the reperfused myocardium has not been explored. These questions were addressed in the present study. In a rat model of myocardial ischemia (1?h) and reperfusion (up to 24?h), there was a marked and significant activation of PARP in the ischemic borderzone, as determined by poly(ADP-ribose) (PAR) immunohistochemistry. PAR localized to the nuclei of myocytes and infiltrating mononuclear cells. In the core of the infarction, necrotic tissues and diffuse PAR staining were observed. PARP activation remained markedly detectable 24?h after reperfusion. The PARP inhibitor 3-aminobenzamide (20?mg?kg?1 intraperitoneally 10?min before reperfusion, and every 2?h thereafter for 6?h) markedly reduced the activation of the enzyme in myocytes. 3-aminobenzamide significantly protected against myocardial morphological and functional alterations at 24?h post-reperfusion. Notably, infarct size was reduced, circulating creatine kinase activity was attenuated, and myocardial contractility (dP dt?1) was restored by 3-aminobenzamide. Our results demonstrate a significant and prolonged activation of PARP in the reperfused myocardium, localizing to the necrotic area and the ischaemic borderzone. Furthermore, the studies demonstrate that PARP inhibition affords long-term beneficial morphological and functional effects in the reperfused myocardium. These data strengthen the notion that pharmacological PARP inhibition is a viable novel experimental approach for protection against myocardial reperfusion injury. PMID:11498530

Liaudet, Lucas; Szabó, Éva; Timashpolsky, Leonid; Virág, László; Cziráki, Attila; Szabó, Csaba

2001-01-01

290

Language Model Applications to Spelling with Brain-Computer Interfaces  

PubMed Central

Within the Ambient Assisted Living (AAL) community, Brain-Computer Interfaces (BCIs) have raised great hopes as they provide alternative communication means for persons with disabilities bypassing the need for speech and other motor activities. Although significant advancements have been realized in the last decade, applications of language models (e.g., word prediction, completion) have only recently started to appear in BCI systems. The main goal of this article is to review the language model applications that supplement non-invasive BCI-based communication systems by discussing their potential and limitations, and to discern future trends. First, a brief overview of the most prominent BCI spelling systems is given, followed by an in-depth discussion of the language models applied to them. These language models are classified according to their functionality in the context of BCI-based spelling: the static/dynamic nature of the user interface, the use of error correction and predictive spelling, and the potential to improve their classification performance by using language models. To conclude, the review offers an overview of the advantages and challenges when implementing language models in BCI-based communication systems when implemented in conjunction with other AAL technologies. PMID:24675760

Mora-Cortes, Anderson; Manyakov, Nikolay V.; Chumerin, Nikolay; Van Hulle, Marc M.

2014-01-01

291

Computational modeling of the brain limbic system and its application in control engineering  

E-print Network

of this thesis, Chapter IV, shows the utilization of the Brain Emotional Learning (BEL) model in different applications of control and signal fusion systems. The main effort is focused on applying the model to control systems where the model acts...

Shahmirzadi, Danial

2005-11-01

292

Modeling brain circuitry over a wide range of scales  

PubMed Central

If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM) see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important. In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation.

Fua, Pascal; Knott, Graham W.

2015-01-01

293

A Model for Diffusion in White Matter in the Brain  

PubMed Central

Diffusion of molecules in brain and other tissues is important in a wide range of biological processes and measurements ranging from the delivery of drugs to diffusion-weighted magnetic resonance imaging. Diffusion tensor imaging is a powerful noninvasive method to characterize neuronal tissue in the human brain in vivo. As a first step toward understanding the relationship between the measured macroscopic apparent diffusion tensor and underlying microscopic compartmental geometry and physical properties, we treat a white matter fascicle as an array of identical thick-walled cylindrical tubes arranged periodically in a regular lattice and immersed in an outer medium. Both square and hexagonal arrays are considered. The diffusing molecules may have different diffusion coefficients and concentrations (or densities) in different domains, namely within the tubes' inner core, membrane, myelin sheath, and within the outer medium. Analytical results are used to explore the effects of a large range of microstructural and compositional parameters on the apparent diffusion tensor and the degree of diffusion anisotropy, allowing the characterization of diffusion in normal physiological conditions as well as changes occurring in development, disease, and aging. Implications for diffusion tensor imaging and for the possible in situ estimation of microstructural parameters from diffusion-weighted MR data are discussed in the context of this modeling framework. PMID:16100258

Sen, Pabitra N.; Basser, Peter J.

2005-01-01

294

EXPERIMENTAL DETERMINATION of HEAT RISE and SAR OCCURRED by 900 MHz EM RADIATION ON HUMAN BRAIN by USING BRAIN PHANTOM MODEL  

Microsoft Academic Search

In this study, heat rise in brain tissue on 900 MHz radiation has been investigated by using phantom model of human brain. Brain equivalent tissue, by considering various exposure possibilities at 900 MHz has been exposed to RFR (Radio Frequency Radiation) at certain periods. When RFR were used, results of heat rise have been logged to computer. Eventually, for human

A. ?ükrü ONURAL

2004-01-01

295

Computational modeling of pedunculopontine nucleus deep brain stimulation  

NASA Astrophysics Data System (ADS)

Objective. Deep brain stimulation (DBS) near the pedunculopontine nucleus (PPN) has been posited to improve medication-intractable gait and balance problems in patients with Parkinson's disease. However, clinical studies evaluating this DBS target have not demonstrated consistent therapeutic effects, with several studies reporting the emergence of paresthesia and oculomotor side effects. The spatial and pathway-specific extent to which brainstem regions are modulated during PPN-DBS is not well understood. Approach. Here, we describe two computational models that estimate the direct effects of DBS in the PPN region for human and translational non-human primate (NHP) studies. The three-dimensional models were constructed from segmented histological images from each species, multi-compartment neuron models and inhomogeneous finite element models of the voltage distribution in the brainstem during DBS. Main Results. The computational models predicted that: (1) the majority of PPN neurons are activated with -3 V monopolar cathodic stimulation; (2) surgical targeting errors of as little as 1 mm in both species decrement activation selectivity; (3) specifically, monopolar stimulation in caudal, medial, or anterior PPN activates a significant proportion of the superior cerebellar peduncle (up to 60% in the human model and 90% in the NHP model at -3 V) (4) monopolar stimulation in rostral, lateral or anterior PPN activates a large percentage of medial lemniscus fibers (up to 33% in the human model and 40% in the NHP model at -3 V) and (5) the current clinical cylindrical electrode design is suboptimal for isolating the modulatory effects to PPN neurons. Significance. We show that a DBS lead design with radially-segmented electrodes may yield improved functional outcome for PPN-DBS.

Zitella, Laura M.; Mohsenian, Kevin; Pahwa, Mrinal; Gloeckner, Cory; Johnson, Matthew D.

2013-08-01

296

Computational modeling of pedunculopontine nucleus deep brain stimulation  

PubMed Central

Objective Deep brain stimulation (DBS) near the pedunculopontine nucleus (PPN) has been posited to improve medication-intractable gait and balance problems in patients with Parkinson’s disease. However, clinical studies evaluating this DBS target have not demonstrated consistent therapeutic effects, with several studies reporting the emergence of paresthesia and oculomotor side effects. The spatial and pathway-specific extent to which brainstem regions are modulated during PPN-DBS is not well understood. Approach Here, we describe two computational models that estimate the direct effects of DBS in the PPN region for human and translational non-human primate (NHP) studies. The three-dimensional models were constructed from segmented histological images from each species, multi-compartment neuron models, and inhomogeneous finite element models of the voltage distribution in the brainstem during DBS. Main Results The computational models predicted that: 1) the majority of PPN neurons are activated with ?3V monopolar cathodic stimulation; 2) surgical targeting errors of as little as 1 mm in both species decrement activation selectivity; 3) specifically, monopolar stimulation in caudal, medial, or anterior PPN activates a significant proportion of the superior cerebellar peduncle (up to 60% in the human model and 90% in the NHP model at -3V); 4) monopolar stimulation in rostral, lateral, or anterior PPN activates a large percentage of medial lemniscus fibers (up to 33% in the human model and 40% in the NHP model at ?3V); and, 5) the current clinical cylindrical electrode design is suboptimal for isolating the modulatory effects to PPN neurons. Significance We show that a DBS lead design with radially-segmented electrodes may yield improved functional outcome for PPN-DBS. PMID:23723145

Zitella, Laura M.; Mohsenian, Kevin; Pahwa, Mrinal; Gloeckner, Cory; Johnson, Matthew D.

2013-01-01

297

Tongxinluo Improves Cardiac Function and Ameliorates Ventricular Remodeling in Mice Model of Myocardial Infarction through Enhancing Angiogenesis  

PubMed Central

Background. Myocardial infarction (MI) is a major cause of morbidity and mortality in the world. Tongxinluo (TXL) is a traditional Chinese compound prescription which has cardioprotective functions. The present study was aimed to determine the effect of TXL on postischemic cardiac dysfunction and cardiac remodeling and to elucidate the underlying mechanisms. Methods and Results. MI was performed by ligation of left anterior descending coronary artery (LAD) in male adult mice. Mice were randomly divided into four groups: (1) sham group (Sham); (2) MI-control group (Control); (3) MI-low dose TXL group (TXL-L); and (4) MI-high dose TXL (TXL-H) group. Compared with the control group, TXL treatment restored cardiac function, increased revascularization, attenuated cardiomyocyte apoptosis, and reduced interstitial fibrosis. TXL treatment increased the phosphorylation of Akt, extracellular signal regulated kinase (ERK), and endothelial nitric oxide synthase (eNOS); the expression of phosphatidylinositol3-kinase (PI3K), hypoxia-inducible factors 1? (HIF-1?), and vascular endothelial growth factor (VEGF); and the DNA binding activity of HIF-1? after MI. Conclusion. TXL may improve cardiac function and ameliorate cardiac remodeling by increasing neovascularization through enhancing the phosphorylation of Akt and ERK, the expression and activity of HIF-1?, and the protein level of VEGF and p-eNOS. PMID:24069057

Bai, Wen-Wu; Xing, Yi-Fan; Wang, Bo; Lu, Xiao-Ting; Wang, Ying-Bin; Sun, Yuan-Yuan; Liu, Xiao-Qiong; Guo, Tao; Zhao, Yu-Xia

2013-01-01

298

An Angiotensin Receptor Blocker Prevents Arrhythmogenic Left Atrial Remodeling in a Rat Post Myocardial Infarction Induced Heart Failure Model  

PubMed Central

This study investigated the role of angiotensin II receptor blocker in atrial remodeling in rats with atrial fibrillation (AF) induced by a myocardial infarction (MI). MIs were induced by a ligation of the left anterior descending coronary artery. Two days after, the rats in the losartan group were given losartan (10 mg/kg/day for 10 weeks). Ten weeks later, echocardiography and AF induction studies were conducted. Ejection fraction was significantly lower in the MI rats. Fibrosis analysis revealed much increased left atrial fibrosis in the MI group than sham (2.22 ± 0.66% vs 0.25 ± 0.08%, P = 0.001) and suppression in the losartan group (0.90 ± 0.27%, P 0.001) compared with the MI group. AF inducibility was higher in the MI group than sham (39.4 ± 43.0% vs 2.0 ± 6.3%, P = 0.005) and significantly lower in losartan group (12.0 ± 31.6%, P = 0.029) compared with the MI. The left atrial endothelial nitric oxide synthase (NOS) and sarco/endoplasmic reticulum Ca2+-ATPase levels were lower in the MI group and higher in the losartan group significantly. The atrial inducible NOS and sodium-calcium exchanger levels were higher in the MI and lower in the losartan group significantly. Losartan disrupts collagen fiber formation and prevents the alteration of the tissue eNOS and iNOS levels, which prevent subsequent AF induction. PMID:23678261

Kim, Hyun-Su; No, Chi-Wan; Goo, Sang-Ho

2013-01-01

299

Long-lasting neuroprotection and neurological improvement in stroke models with new, potent and brain permeable inhibitors of poly(ADP-ribose) polymerase  

PubMed Central

BACKGROUND AND PURPOSES Thienyl-isoquinolone (TIQ-A) is a relatively potent PARP inhibitor able to reduce post-ischaemic neuronal death in vitro. Here we have studied, in different stroke models in vivo, the neuroprotective properties of DAMTIQ and HYDAMTIQ, two TIQ-A derivatives able to reach the brain and to inhibit PARP-1 and PARP-2. EXPERIMENTAL APPROACH Studies were carried out in (i) transient (2 h) middle cerebral artery occlusion (tMCAO), (ii) permanent MCAO (pMCAO) and (iii) electrocoagulation of the distal portion of MCA in conjunction with transient (90 min) bilateral carotid occlusion (focal cortical ischaemia). KEY RESULTS In male rats with tMCAO, HYDAMTIQ (0.1–10 mg·kg?1) injected i.p. three times, starting 4 h after MCAO, reduced infarct volumes by up to 70%, reduced the loss of body weight by up to 60% and attenuated the neurological impairment by up to 40%. In age-matched female rats, HYDAMTIQ also reduced brain damage. Protection, however, was less pronounced than in the male rats. In animals with pMCAO, HYDAMTIQ administered 30 min after MCAO reduced infarct volumes by approximately 40%. In animals with focal cortical ischaemia, HYDAMTIQ treatment decreased post-ischaemic accumulation of PAR (the product of PARP activity) and the presence of OX42-positive inflammatory cells in the ischaemic cortex. It also reduced sensorimotor deficits for up to 90 days after MCAO. CONCLUSION AND IMPLICATIONS Our results show that HYDAMTIQ is a potent PARP inhibitor that conferred robust neuroprotection and long-lasting improvement of post-stroke neurological deficits. PMID:21913897

Moroni, F; Cozzi, A; Chiarugi, A; Formentini, L; Camaioni, E; Pellegrini-Giampietro, DE; Chen, Y; Liang, S; Zaleska, MM; Gonzales, C; Wood, A; Pellicciari, R

2012-01-01

300

Longitudinal monitoring adipose-derived stem cell survival by PET imaging hexadecyl-4-¹²?I-iodobenzoate in rat myocardial infarction model.  

PubMed

This study aims to monitor how the change of cell survival of transplanted adipose-derived stem cells (ADSCs) responds to myocardial infarction (MI) via the hexadecyl-4-(124)I-iodobenzoate ((124)I-HIB) mediated direct labeling method in vivo. Stem cells have shown the potential to improve cardiac function after MI. However, monitoring of the fate of transplanted stem cells at target sites is still unclear. Rat ADSCs were labeled with (124)I-HIB, and radiolabeled ADSCs were transplanted into the myocardium of normal and MI model. In the group of (124)I-HIB-labeled ADSC transplantation, in vivo imaging was performed using small-animal positron emission tomography (PET)/computed tomography (CT) for 9 days. Twenty-one days post-transplantation, histopathological analysis and apoptosis assay were performed. ADSC viability and differentiation were not affected by (124)I-HIB labeling. In vivo tracking of the (124)I-HIB-labeled ADSCs was possible for 9 and 3 days in normal and MI model, respectively. Apoptosis of transplanted cells increased in the MI model compared than that in normal model. We developed a direct labeling agent, (124)I-HIB, and first tried to longitudinally monitor transplanted stem cell to MI. This approach may provide new insights on the roles of stem cell monitoring in living bodies for stem cell therapy from pre-clinical studies to clinical trials. PMID:25446095

Kim, Min Hwan; Woo, Sang-Keun; Lee, Kyo Chul; An, Gwang Il; Pandya, Darpan; Park, Noh Won; Nahm, Sang-Soep; Eom, Ki Dong; Kim, Kwang Il; Lee, Tae Sup; Kim, Chan Wha; Kang, Joo Hyun; Yoo, Jeongsoo; Lee, Yong Jin

2015-01-01

301

Multicolor Fluorescence Imaging of Traumatic Brain Injury in a Cryolesion Mouse Model  

PubMed Central

Traumatic brain injury is characterized by initial tissue damage, which then can lead to secondary processes such as cell death and blood-brain-barrier disruption. Clinical and preclinical studies of traumatic brain injury typically employ anatomical imaging techniques and there is a need for new molecular imaging methods that provide complementary biochemical information. Here, we assess the ability of a targeted, near-infrared fluorescent probe, named PSS-794, to detect cell death in a brain cryolesion mouse model that replicates certain features of traumatic brain injury. In short, the model involves brief contact of a cold rod to the head of a living, anesthetized mouse. Using noninvasive whole-body fluorescence imaging, PSS-794 permitted visualization of the cryolesion in the living animal. Ex vivo imaging and histological analysis confirmed PSS-794 localization to site of brain cell death. The nontargeted, deep-red Tracer-653 was validated as a tracer dye for monitoring blood-brain-barrier disruption, and a binary mixture of PSS-794 and Tracer-653 was employed for multicolor imaging of cell death and blood-brain-barrier permeability in a single animal. The imaging data indicates that at 3 days after brain cryoinjury the amount of cell death had decreased significantly, but the integrity of the blood-brain-barrier was still impaired; at 7 days, the blood-brain-barrier was still three times more permeable than before cryoinjury. PMID:22860222

2012-01-01

302

In vivo amino acid transport of subacute and chronic cerebral infarction evaluated by 12-18F-phenylalanine  

SciTech Connect

On the basis of previous validation of kinetic two-compartment model and the determination of normal values of three parameters (k{sub 1}:influx rate constant, k{sub 2}:outflux rate constant, Vd:distribution volume), PET measurements of in vivo amino acid transport from blood to brain using L-(2-18F)-fluorophenylalanine ({sup 18}F-Phe) were undergone in the patients with cerebral infarction. The purposes of this study are to evaluate the alteration of amino acid transport in subacute and chronic stage of cerebral infarction and to compare with cerebral blood flow (CBF) and oxygen metabolism. Dynamic {sup 18}F-Phe PET studies for 50 minutes were performed in 7 patients with cerebral infarction. The input function was obtained by 27 points of arterial sampling. In all patients, measurements of CBF, cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO{sub 2}), and oxygen extraction fraction (OEF) were made on the same day of {sup 18}F-Phe PET measurement. Each patient was studied twice, within 2 weeks of the onset and 3 months later. Weighted integration technique with table look-up method was applied for the reconstruction of parametric images of {sup 18}F-Phe and ROI analysis of k{sub 1}, k{sub 2}, and Vd. In subacute stage, significant reduction of k{sub 2} value in infarct area was observed when compared to that in periinfarct area (p<0.05) and in normal cortices (p<0.001). k{sub 1} value in this stage showed only slightly decrease in infarct area, therefore, Vd value in infarct area increased significantly compared to normal cortices (p<0.001). In chronic stage, both k{sub 1} and k{sub 2} values in infarct area were significantly lower than that in normal cortices (p<0.001), and corresponding Vd value reduced to normal level. Correlativity between kinetic parameters of {sup 18}F-Phe and CBF or oxygen metabolism was not observed both in subacute and chronic stage of infarction.

Shimosegawa, E.; Miura, S.; Murakami, M. [Research Institute for Brain & Blood Vessels, Akita (Japan)] [and others

1994-05-01

303

Spatial disorientation in right-hemisphere infarction.  

PubMed Central

Spatial orientation was tested with the rod orientation test. The subjects were 40 normal controls and 68 brain-damaged patients with cerebral infarcts. Patients in whom the lesion included the post-rolandic region of the right hemisphere performed worse than controls or patients with lesions at other sites. Patients with an exclusively postrolandic (usually occipital) lesion showed higher error rates than patients with a combined prerolandic and postrolandic lesion, but only for the visual part of the test. These patients were re-examined one year after the stroke. Most of them showed an incomplete recovery of spatial function. PMID:7119828

Meerwaldt, J D; van Harskamp, F

1982-01-01

304

Short-term pretreatment with atorvastatin attenuates left ventricular dysfunction, reduces infarct size and apoptosis in acute myocardial infarction rats  

PubMed Central

Background: Atorvastatin showed a number of cardiovascular benefits, however, the role and underlying molecular mechanisms of short-term atorvastatin-mediated protection remain unclear. Methods: 30 rats were randomly divided into 3 groups: sham group, acute myocardial infarction model group and atorvastatin group. The rats of acute myocardial infarction model were established by ligation of the left anterior descending of coronary arteries. Before surgery, rats in the atorvastatin group received 20 mg/kg/d atorvastatin for 7 days in atorvastatin group. After 4 hours of model established, changes in hemodynamics parameters were recorded and myocardial infarct size was achieved by Evans blue-TTC staining. Myocardium apoptosis was evaluated by TUNEL. The expression of FAS, FAS-L, Bcl-2, Bax, p-BAD, Caspase-8 and Caspase-3 in myocardium were examined by Western blot. Results: In the atorvastatin group, left ventricular function was elevated and infarct size was decreased compared with the model group. Moreover, in the atorvastatin group, the cell apoptosis index was reduced in response to myocardial infarction. The expressions of Bcl-2 were increased and Bax, p-BAD, Fas, Fas-L, caspase-8 and caspase-3 in myocardium were decreased in atorvastatin group. Conclusions: Short-term atorvastatin pretreatment restored left ventricular function and limited infarct size in acute myocardial infarction, which were associated with reduction of the apoptosis in myocardium through Bcl-2 and Fas pathway. PMID:25663976

Chen, Tie-Long; Zhu, Guang-Li; He, Xiao-Long; Wang, Jian-An; Wang, Yu; Qi, Guo-An

2014-01-01

305

In Search of Functional Specificity in the Brain: Generative Models for Group fMRI Data  

E-print Network

In Search of Functional Specificity in the Brain: Generative Models for Group fMRI Data by Danial #12;2 #12;3 In Search of Functional Specificity in the Brain: Generative Models for Group fMRI Data an exploratory framework for design and analysis of fMRI studies. In our framework, the experimenter presents

Golland, Polina

306

Probing the brain’s white matter with diffusion MRI and a tissue dependent diffusion model   

E-print Network

While diffusion MRI promises an insight into white matter microstructure in vivo, the axonal pathways that connect different brain regions together can only partially be segmented using current methods. Here we present ...

Piatkowski, Jakub Przemyslaw

2014-06-27

307

Cardiac Function in a Long-Term Follow-Up Study of Moderate and Severe Porcine Model of Chronic Myocardial Infarction  

PubMed Central

Background. Novel therapies need to be evaluated in a relevant large animal model that mimics the clinical course and treatment in a reasonable time frame. To reliably assess therapeutic efficacy, knowledge regarding the translational model and the course of disease is needed. Methods. Landrace pigs were subjected to a transient occlusion of the proximal left circumflex artery (LCx) (n = 6) or mid-left anterior descending artery (LAD) (n = 6) for 150?min. Cardiac function was evaluated before by 2D echocardiography or 3D echocardiography and pressure-volume loop analysis. At 12 weeks of follow-up the heart was excised for histological analysis and infarct size calculations. Results. Directly following AMI, LVEF was severely reduced compared to baseline in the LAD group (?17.1 ± 1.6%, P = 0.009) compared to only a moderate reduction in the LCx group (?5.9 ± 1.5%, P = 0.02) and this effect remained unchanged during 12 weeks of follow-up. Conclusion. Two models of chronic MI, representative for different patient groups, can reproducibly be created through clinically relevant ischemia-reperfusion of the mid-LAD and proximal LCx.

de Jong, Renate; van Hout, Gerardus P. J.; Houtgraaf, Jaco H.; Takashima, S.; Pasterkamp, Gerard; Hoefer, Imo; Duckers, Henricus J.

2015-01-01

308

Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model  

PubMed Central

The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [18F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [18F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33–35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC–associated [18F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [18F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI. PMID:21912635

Marini, Frank C.; Silva, Guilherme V.; Zheng, Yi; Baimbridge, Fred; Quan, Xin; Fernandes, Marlos R.; Gahremanpour, Amir; Young, Daniel; Paolillo, Vincenzo; Mukhopadhyay, Uday; Borne, Agatha T.; Uthamanthil, Rajesh; Brammer, David; Jackson, James; Decker, William K.; Najjar, Amer M.; Thomas, Michael W.; Volgin, Andrei; Rabinovich, Brian; Soghomonyan, Suren; Jeong, Hwan-Jeong; Rios, Jesse M.; Steiner, David; Robinson, Simon; Mawlawi, Osama; Pan, Tinsu; Stafford, Jason; Kundra, Vikas; Li, Chun; Alauddin, Mian M.; Willerson, James T.; Shpall, Elizabeth; Gelovani, Juri G.

2011-01-01

309

A detailed method for preparation of a functional and flexible blood–brain barrier model using porcine brain endothelial cells?  

PubMed Central

The blood–brain barrier (BBB) is formed by the endothelial cells of cerebral microvessels and forms the critical interface regulating molecular flux between blood and brain. It contributes to homoeostasis of the microenvironment of the central nervous system and protection from pathogens and toxins. Key features of the BBB phenotype are presence of complex intercellular tight junctions giving a high transendothelial electrical resistance (TEER), and strongly polarised (apical:basal) localisation of transporters and receptors. In vitro BBB models have been developed from primary culture of brain endothelial cells of several mammalian species, but most require exposure to astrocytic factors to maintain the BBB phenotype. Other limitations include complicated procedures for isolation, poor yield and batch-to-batch variability. Some immortalised brain endothelial cell models have proved useful for transport studies but most lack certain BBB features and have low TEER. We have developed an in vitro BBB model using primary cultured porcine brain endothelial cells (PBECs) which is relatively simple to prepare, robust, and reliably gives high TEER (mean?800 ? cm2); it also shows good functional expression of key tight junction proteins, transporters, receptors and enzymes. The model can be used either in monoculture, for studies of molecular flux including permeability screening, or in co-culture with astrocytes when certain specialised features (e.g. receptor-mediated transcytosis) need to be maximally expressed. It is also suitable for a range of studies of cell:cell interaction in normal physiology and in pathology. The method for isolating and growing the PBECs is given in detail to facilitate adoption of the model. This article is part of a Special Issue entitled Companion Paper. PMID:23603406

Patabendige, Adjanie; Skinner, Robert A.; Morgan, Louise; Joan Abbott, N.

2013-01-01

310

A comparative study of theoretical graph models for characterizing structural networks of human brain.  

PubMed

Previous studies have investigated both structural and functional brain networks via graph-theoretical methods. However, there is an important issue that has not been adequately discussed before: what is the optimal theoretical graph model for describing the structural networks of human brain? In this paper, we perform a comparative study to address this problem. Firstly, large-scale cortical regions of interest (ROIs) are localized by recently developed and validated brain reference system named Dense Individualized Common Connectivity-based Cortical Landmarks (DICCCOL) to address the limitations in the identification of the brain network ROIs in previous studies. Then, we construct structural brain networks based on diffusion tensor imaging (DTI) data. Afterwards, the global and local graph properties of the constructed structural brain networks are measured using the state-of-the-art graph analysis algorithms and tools and are further compared with seven popular theoretical graph models. In addition, we compare the topological properties between two graph models, namely, stickiness-index-based model (STICKY) and scale-free gene duplication model (SF-GD), that have higher similarity with the real structural brain networks in terms of global and local graph properties. Our experimental results suggest that among the seven theoretical graph models compared in this study, STICKY and SF-GD models have better performances in characterizing the structural human brain network. PMID:24369454

Li, Xiaojin; Hu, Xintao; Jin, Changfeng; Han, Junwei; Liu, Tianming; Guo, Lei; Hao, Wei; Li, Lingjiang

2013-01-01

311

Traumatic Brain Injury – Modeling Neuropsychiatric Symptoms in Rodents  

PubMed Central

Each year in the US, ?1.5 million people sustain a traumatic brain injury (TBI). Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and motor deficits, cognitive impairments including problems with memory, learning, and attention, and neuropsychiatric symptoms such as depression, anxiety, irritability, aggression, and suicidal rumination. Although partially associated with the site and severity of injury, the biological mechanisms associated with many of these symptoms – and why some patients experience differing assortments of persistent maladies – are largely unknown. The use of animal models is a promising strategy for elucidation of the mechanisms of impairment and treatment, and learning, memory, sensory, and motor tests have widespread utility in rodent models of TBI and psychopharmacology. Comparatively, behavioral tests for the evaluation of neuropsychiatric symptomatology are rarely employed in animal models of TBI and, as determined in this review, the results have been inconsistent. Animal behavioral studies contribute to the understanding of the biological mechanisms by which TBI is associated with neurobehavioral symptoms and offer a powerful means for pre-clinical treatment validation. Therefore, further exploration of the utility of animal behavioral tests for the study of injury mechanisms and therapeutic strategies for the alleviation of emotional symptoms are relevant and essential. PMID:24109476

Malkesman, Oz; Tucker, Laura B.; Ozl, Jessica; McCabe, Joseph T.

2013-01-01

312

Acute myocardial infarct scintigraphy with infarct-avid radiotracers  

SciTech Connect

The selective uptake of radiopharmaceuticals by acutely infarcted myocardium has emerged as an independent, noninvasive technique to aid in the detection, localization, and quantification of myocardial necrosis.

Wynne, J.; Holman, B.L.

1980-01-01

313

Examination of Blood-Brain Barrier (BBB) Integrity In A Mouse Brain Tumor Model  

PubMed Central

The present study evaluates, both functionally and biochemically, brain tumor-induced alterations in brain capillary endothelial cells. Brain tumors were induced in Balb/c mice via intracranial injection of Lewis Lung carcinoma (3LL) cells into the right hemisphere of the mouse brain using stereotaxic apparatus. Blood-brain barrier (BBB) permeability was assessed at various stages of tumor development, using both radiolabeled tracer permeability and magnetic resonance imaging (MRI) with gadolinium diethylene-triamine-pentaacetate contrast enhancement (Gad-DTPA). The expression of the drug efflux transporter, P-glycoprotein (P-gp), in the BBB at various stages of tumor development was also evaluated by Western blot and immunohistochemistry. Median mouse survival following tumor cell injection was 17 days. The permeability of the BBB to 3H-mannitol was similar in both brain hemispheres at 7 and 10 days post-injection. By day 15, there was a 2-fold increase in 3H-mannitol permeability in the tumor bearing hemispheres compared to the non-tumor hemispheres. Examination of BBB permeability with Gad-DTPA contrast enhanced MRI indicated cerebral vascular permeability changes were confined to the tumor area. The permeability increase observed at the later stages of tumor development correlated with an increase in cerebral vascular volume suggesting angiogenesis within the tumor bearing hemisphere. Furthermore, the Gad-DPTA enhancement observed within the tumor area was significantly less than Gad-DPTA enhancement within the circumventricular organs not protected by the BBB. Expression of P-gp in both the tumor bearing and non-tumor bearing portions of the brain appeared similar at all time points examined. These studies suggest that although BBB integrity is altered within the tumor site at later stages of development, the BBB is still functional and limiting in terms of solute and drug permeability in and around the tumor. PMID:23184143

On, Ngoc; Mitchell, Ryan; Savant, Sanjot D.; Bachmeier, Corbin. J.; Hatch, Grant M.; Miller, Donald W.

2013-01-01

314

Examination of blood-brain barrier (BBB) integrity in a mouse brain tumor model.  

PubMed

The present study evaluates, both functionally and biochemically, brain tumor-induced alterations in brain capillary endothelial cells. Brain tumors were induced in Balb/c mice via intracranial injection of Lewis Lung carcinoma cells into the right hemisphere of the mouse brain using stereotaxic apparatus. Blood-brain barrier (BBB) permeability was assessed at various stages of tumor development, using both radiolabeled tracer permeability and magnetic resonance imaging with gadolinium diethylene-triamine-pentaacetate contrast enhancement (Gad-DTPA). The expression of the drug efflux transporter, P-glycoprotein (P-gp), in the BBB at various stages of tumor development was also evaluated by Western blot and immunohistochemistry. Median mouse survival following tumor cell injection was 17 days. The permeability of the BBB to (3)H-mannitol was similar in both brain hemispheres at 7 and 10 days post-injection. By day 15, there was a twofold increase in (3)H-mannitol permeability in the tumor bearing hemispheres compared to the non-tumor hemispheres. Examination of BBB permeability with Gad-DTPA contrast enhanced MRI indicated cerebral vascular permeability changes were confined to the tumor area. The permeability increase observed at the later stages of tumor development correlated with an increase in cerebral vascular volume suggesting angiogenesis within the tumor bearing hemisphere. Furthermore, the Gad-DPTA enhancement observed within the tumor area was significantly less than Gad-DPTA enhancement within the circumventricular organs not protected by the BBB. Expression of P-gp in both the tumor bearing and non-tumor bearing portions of the brain appeared similar at all time points examined. These studies suggest that although BBB integrity is altered within the tumor site at later stages of development, the BBB is still functional and limiting in terms of solute and drug permeability in and around the tumor. PMID:23184143

On, Ngoc H; Mitchell, Ryan; Savant, Sanjot D; Bachmeier, Corbin J; Hatch, Grant M; Miller, Donald W

2013-01-01

315

Immunological considerations of modern animal models of malignant primary brain tumors  

E-print Network

an animal brain tumor model and its response to therapy withanimal hosts for the purpose of developing immune based therapies,animals is essential prior to using these models to evaluate immune based therapies.

2009-01-01

316

Approaches to Modelling the Dynamical Activity of Brain Function Based on the Electroencephalogram  

NASA Astrophysics Data System (ADS)

The brain is arguably the quintessential complex system as indicated by the patterns of behaviour it produces. Despite many decades of concentrated research efforts, we remain largely ignorant regarding the essential processes that regulate and define its function. While advances in functional neuroimaging have provided welcome windows into the coarse organisation of the neuronal networks that underlie a range of cognitive functions, they have largely ignored the fact that behaviour, and by inference brain function, unfolds dynamically. Modelling the brain's dynamics is therefore a critical step towards understanding the underlying mechanisms of its functioning. To date, models have concentrated on describing the sequential organisation of either abstract mental states (functionalism, hard AI) or the objectively measurable manifestations of the brain's ongoing activity (rCBF, EEG, MEG). While the former types of modelling approach may seem to better characterise brain function, they do so at the expense of not making a definite connection with the actual physical brain. Of the latter, only models of the EEG (or MEG) offer a temporal resolution well matched to the anticipated temporal scales of brain (mental processes) function. This chapter will outline the most pertinent of these modelling approaches, and illustrate, using the electrocortical model of Liley et al, how the detailed application of the methods of nonlinear dynamics and bifurcation theory is central to exploring and characterising their various dynamical features. The rich repertoire of dynamics revealed by such dynamical systems approaches arguably represents a critical step towards an understanding of the complexity of brain function.

Liley, David T. J.; Frascoli, Federico

317

Ex vivo Evans blue assessment of the blood brain barrier in three breast cancer brain metastasis models  

PubMed Central

The limited entry of anticancer drugs into the central nervous system represents a special therapeutic challenge for patients with brain metastases and is primarily due to the blood brain barrier (BBB). Albumin-bound Evans blue (EB) dye is too large to cross the BBB but can grossly stain tissue blue when the BBB is disrupted. The course of tumor development and the integrity of the BBB were studied in three preclinical breast cancer brain metastasis (BCBM) models. A luciferase-transduced braintropic clone of MDA-231 cell line was used. Nude mice were subjected to stereotactic intracerebral inoculation, mammary fat pad-derived tumor fragment implantation, or carotid artery injections. EB was injected 30 min prior to euthanasia at various timepoints for each of the BCBM model animals. Serial bioluminescent imaging demonstrated exponential tumor growth in all models. Carotid BCBM appeared as diffuse multifocal cell clusters. EB aided the localization of metastases ex vivo. Tumor implants stained blue at 7 days whereas gross staining was not evident until day 14 in the stereotactic model and day 28 for the carotid model. EB assessment of the integrity of the BBB provides useful information relevant to drug testing in preclinical BCBM models. PMID:24510011

Do, John; Foster, Deshka; Renier, Corinne; Vogel, Hannes; Rosenblum, Sahar; Doyle, Timothy C.; Tse, Victor

2015-01-01

318

Towards Stratifying Ischemic Components by Cardiac MRI and Multifunctional Stainings in a Rabbit Model of Myocardial Infarction  

PubMed Central

Objectives: We sought to identify critical components of myocardial infarction (MI) including area at risk (AAR), MI-core and salvageable zone (SZ) by using cardiac magnetic resonance imaging (cMRI) and multifunctional stainings in rabbits. Materials and Methods: Fifteen rabbits received 90-min coronary artery (CA) ligation and reopening to induce reperfused MI. First-pass perfusion weighted imaging (PWI90') was performed immediately before CA reperfusion. Necrosis avid dye Evans blue (EB) was intravenously injected for later MI-core detection. One-day later, cMRI with T2-weighted imaging (T2WI), PWI24h and delayed enhancement (DE) T1WI was performed at a 3.0T clinical scanner. The heart was excised and CA was re-ligated with aorta infused by red-iodized-oil (RIO). The heart was sliced into 3-mm sections for digital radiography (DR), histology and planimetry with myocardial salvage index (MSI) and perfusion density rate (PDR) calculated. Results: There was no significant difference between MI-cores defined by DE-T1WI and EB-staining (31.13±8.55% vs 29.80±7.97%; p=0.74). The AAR was defined similarly by PWI90' (39.93±9.51%), RIO (38.82±14.41%) and DR (38.17±15.98%), underestimated by PWI24h (36.44±5.31%), but overestimated (p<0.01) by T2WI (56.93±8.87%). Corresponding MSI turned out to be 24.17±9.5% (PWI90'), 21.97±9.41% (DR) and 22.68±9.65% (RIO), which were significantly (p<0.01) higher and lower than that with PWI24h (15.15±7.34%) and T2WI (45.52±7.5%) respectively. The PDR differed significantly (p<0.001) between normal myocardium (350.6±33.1%) and the AAR (31.2±15%), suggesting 11-times greater blood perfusion in normal myocardium over the AAR. Conclusion: The introduced rabbit platform and new staining techniques together with the use of a 3.0T clinical scanner for cMRI enabled visualization of MI components and may contribute to translational cardiac imaging research for improved theranostic management of ischemic heart disease. PMID:24396513

Feng, Yuanbo; Chen, Feng; Ma, Zhanlong; Dekeyzer, Frederik; Yu, Jie; Xie, Yi; Cona, Marlein Miranda; Oyen, Raymond; Ni, Yicheng

2014-01-01

319

A Drosophila model of closed head traumatic brain injury  

PubMed Central

Traumatic brain injury (TBI) is a substantial health issue worldwide, yet the mechanisms responsible for its complex spectrum of pathologies remains largely unknown. To investigate the mechanisms underlying TBI pathologies, we developed a model of TBI in Drosophila melanogaster. The model allows us to take advantage of the wealth of experimental tools available in flies. Closed head TBI was inflicted with a mechanical device that subjects flies to rapid acceleration and deceleration. Similar to humans with TBI, flies with TBI exhibited temporary incapacitation, ataxia, activation of the innate immune response, neurodegeneration, and death. Our data indicate that TBI results in death shortly after a primary injury only if the injury exceeds a certain threshold and that age and genetic background, but not sex, substantially affect this threshold. Furthermore, this threshold also appears to be dependent on the same cellular and molecular mechanisms that control normal longevity. This study demonstrates the potential of flies for providing key insights into human TBI that may ultimately provide unique opportunities for therapeutic intervention. PMID:24127584

Katzenberger, Rebeccah J.; Loewen, Carin A.; Wassarman, Douglas R.; Petersen, Andrew J.; Ganetzky, Barry; Wassarman, David A.

2013-01-01

320

The Pediatric Acquired Brain Injury Community Outreach Program (PABICOP) - an innovative comprehensive model of care for children and youth with an acquired brain injury.  

PubMed

The Pediatric Acquired Brain Injury Community Outreach Program - an innovative, comprehensive model of care for children and youth with an acquired brain injury is described. The background to the formation of the idea is delineated and the current function of the model given. Future directions are discussed. The program addresses the needs and issues of children and youth with an acquired brain injury and their families. Subsequent literature supports the concept of care that this program espouses. PMID:15502254

Gillett, Jane

2004-01-01

321

Modeling localized delivery of Doxorubicin to the brain following focused ultrasound enhanced blood-brain barrier permeability  

NASA Astrophysics Data System (ADS)

Doxorubicin (Dox) is a well-established chemotherapeutic agent, however it has limited efficacy in treating brain malignancies due to the presence of the blood-brain barrier (BBB). Recent preclinical studies have demonstrated that focused ultrasound induced BBB disruption (BBBD) enables efficient delivery of Dox to the brain. For future treatment planning of BBBD-based drug delivery, it is crucial to establish a mathematical framework to predict the effect of transient BBB permeability enhancement on the spatiotemporal distribution of Dox at the targeted area. The constructed model considers Dox concentrations within three compartments (plasma, extracellular, intracellular) that are governed by various transport processes (e.g. diffusion in interstitial space, exchange across vessel wall, clearance by cerebral spinal fluid, uptake by brain cells). By examining several clinical treatment aspects (e.g. sonication scheme, permeability enhancement, injection mode), our simulation results support the experimental findings of optimal interval delay between two consecutive sonications and therapeutically-sufficient intracellular concentration with respect to transfer constant Ktrans range of 0.01–0.03?min?1. Finally, the model suggests that infusion over a short duration (20–60?min) should be employed along with single-sonication or multiple-sonication at 10?min interval to ensure maximum delivery to the intracellular compartment while attaining minimal cardiotoxicity via suppressing peak plasma concentration.

Nhan, Tam; Burgess, Alison; Lilge, Lothar; Hynynen, Kullervo

2014-10-01

322

Modelling the anesthetized brain with ensembles of neuronal and astrocytic oscillators  

NASA Astrophysics Data System (ADS)

We propose a minimalistic model of the anesthetized brain in order to study the generation of rhythms observed in electroencephalograms (EEGs) recorded from anesthetized humans. We propose that non-neuronal brain cells-astrocytes-play an important role in brain dynamics and that oscillation-based models may provide a simple way to study such dynamics. The model is capable of replicating the main features (i.e. slow and alpha oscillations) observed in EEGs. In addition, this model suggests that astrocytes are integral to the generation of slow EEG (˜0.7 Hz) rhythms. By including astrocytes in the model we take a first step towards investigating the interaction of the brain and cardiovasular system which are primarily connected via astrocytes. The model also illustrates that rich nonlinear dynamics can arise from basic oscillatory "building blocks" and therefore complex systems may be modelled in an uncomplicated way.

Hansard, T.; Hale, A. C.; Stefanovska, A.

2013-01-01

323

Brain Complexity: Analysis, Models and Limits of Understanding  

E-print Network

the operational principles of organisms and brains to develop alternative, biologically inspired comput- ing are mentioned indicating that the con- cept of the basic uniformity of the cortex is untenable. The claim is dis new computing systems based on information processing principles derived from the working of the brain

Schierwagen, Andreas

324

Quantitative genetic modeling of variation in human brain morphology  

Microsoft Academic Search

The degree to which individual variation in brain structure in humans is genetically or environmentally determined is as yet not well understood. We studied the brains of 54 monozygotic (33 male, 21 female) and 58 dizygotic (17 male, 20 female, 21 opposite sex) pairs of twins and 34 of their full siblings (19 male, 15 female) by means of high

W. F. C. Baare; H. E. Hulshoff-Poll; Dorret I. Boomsma; Daniëlle Posthuma; Geus de E. J. C; H. G. Snack; Haren van N. E. M; Oel van C. J; René S. Kahn

2001-01-01

325

Post-insult valproate treatment potentially improved functional recovery in patients with acute middle cerebral artery infarction  

PubMed Central

Animal stroke models suggest that valproate has multiple neuroprotective mechanisms against ischemic brain damage. This study investigated whether valproate improves functional recovery in patients with acute middle cerebral artery (MCA) infarction. This was an open-label controlled trial. Three to 24 hours after acute MCA infarction, patients were assigned to either the valproate group (n = 17) or the non-valproate group (n = 17). The valproate group received intravenous valproate (400 mg) at enrollment, and then every 12 hours for three days, followed by oral valproate (500 mg) every 12 hours for three months. Neurological function, laboratory data, and brain magnetic resonance imaging were examined at stroke onset, and at two-week and three-month follow-up. No significant differences were observed between the groups with regard to demographics or baseline characteristics. All patients were elderly, had a high pretreatment score on the NIH stroke scale (NIHSS), and slow stroke lesion growth with a final large infarct volume at two-week follow-up. At the three-month follow-up, functional outcome between pre- and post-treatment had improved significantly in the valproate group (NIHSS, p = 0.004; modified Rankin scale (mRS), p = 0.007; Barthel index (BI), p = 0.001). No such improvement was noted in the NIHSS or mRS for the non-valproate group, though mild improvement was seen on the BI (p = 0.022). This open-label trial is the first to demonstrate that valproate treatment markedly improves functional outcome in patients with acute MCA infarction. PMID:25628792

Lee, Jiunn-Tay; Chou, Chung-Hsing; Cho, Nai-Yu; Sung, Yueh-Feng; Yang, Fu-Chi; Chen, Cheng-Yu; Lai, Yu-Hua; Chiang, Chun-I; Chu, Chi-Ming; Lin, Jiann-Chyun; Hsu, Yaw-Don; Hong, Jau-Shyong; Peng, Giia-Sheun; Chuang, De-Maw

2014-01-01

326

NeuroGPS: automated localization of neurons for brain circuits using L1 minimization model  

PubMed Central

Drawing the map of neuronal circuits at microscopic resolution is important to explain how brain works. Recent progresses in fluorescence labeling and imaging techniques have enabled measuring the whole brain of a rodent like a mouse at submicron-resolution. Considering the huge volume of such datasets, automatic tracing and reconstruct the neuronal connections from the image stacks is essential to form the large scale circuits. However, the first step among which, automated location the soma across different brain areas remains a challenge. Here, we addressed this problem by introducing L1 minimization model. We developed a fully automated system, NeuronGlobalPositionSystem (NeuroGPS) that is robust to the broad diversity of shape, size and density of the neurons in a mouse brain. This method allows locating the neurons across different brain areas without human intervention. We believe this method would facilitate the analysis of the neuronal circuits for brain function and disease studies. PMID:23546385

Quan, Tingwei; Zheng, Ting; Yang, Zhongqing; Ding, Wenxiang; Li, Shiwei; Li, Jing; Zhou, Hang; Luo, Qingming; Gong, Hui; Zeng, Shaoqun

2013-01-01

327

Allostasis and the Human Brain: Integrating Models of Stress from the Social and Life Sciences  

ERIC Educational Resources Information Center

We draw on the theory of allostasis to develop an integrative model of the current stress process that highlights the brain as a dynamically adapting interface between the changing environment and the biological self. We review evidence that the core emotional regions of the brain constitute the primary mediator of the well-established association…

Ganzel, Barbara L.; Morris, Pamela A.; Wethington, Elaine

2010-01-01

328

Model-based 3-D segmentation of multiple sclerosis lesions in magnetic resonance brain images  

Microsoft Academic Search

Human investigators instinctively segment medical images into their anatomical components, drawing upon prior knowledge of anatomy to overcome image artifacts, noise, and lack of tissue contrast. The authors describe: 1) the development and use of a brain tissue probability model for the segmentation of multiple sclerosis (MS) lesions in magnetic resonance (MR) brain images, and 2) an empirical comparison of

Micheline Kamber; Rajjan Shinghal; D. L. Collins; Gordon S. Francis; Alan C. Evans

1995-01-01

329

Using Structural Equation Modeling to Assess Functional Connectivity in the Brain: Power and Sample Size Considerations  

ERIC Educational Resources Information Center

The present study assessed the impact of sample size on the power and fit of structural equation modeling applied to functional brain connectivity hypotheses. The data consisted of time-constrained minimum norm estimates of regional brain activity during performance of a reading task obtained with magnetoencephalography. Power analysis was first…

Sideridis, Georgios; Simos, Panagiotis; Papanicolaou, Andrew; Fletcher, Jack

2014-01-01

330

Quantitative genetic modeling of regional brain volumes and cognitive performance in older male  

E-print Network

reserved. Keywords: Quantitative genetic modeling; Regional brain volumes; Male twins * Corresponding environmental from genetic effects. Such comparisons have been conducted previously in selected samples of twins supported recently by several studies of brain morphology in younger twins and their siblings, where genetic

California at Davis, University of

331

Material Modeling and Development of a Realistic Dummy Testing Blast Induced Traumatic Brain Injury  

E-print Network

occurrence rate of traumatic brain injury (TBI) ­ 1.4 million people in US per year ­ 50,000 deaths ­ 235 Brain Injury S. G. M. Hossain1, C. A. Nelson1, T. Boulet2, M. Arnoult2, L. Zhang2, A. Holmberg2, J. HeinMaterial Modeling and Development of a Realistic Dummy Head for Testing Blast Induced Traumatic

Farritor, Shane

332

ORIGINAL ARTICLE Assessing a signal model and identifying brain activity from fMRI  

E-print Network

ORIGINAL ARTICLE Assessing a signal model and identifying brain activity from fMRI data-Verlag 2008 Abstract One of the major challenges of functional magnetic resonance imaging (fMRI) data analysis brain activity from fMRI data. We perform three tasks: (a) Estimating noise level from experimental fMRI

Gao, Jianbo

333

Early cognitive status and productivity outcome after traumatic brain injury: Findings from the TBI Model Systems  

Microsoft Academic Search

Sherer M, Sander AM, Nick TG, High WM Jr, Malec JF, Rosenthal M. Early cognitive status and productivity outcome after traumatic brain injury: findings from the TBI Model Systems. Arch Phys Med Rehabil 2002;83:183-92. Objective: To evaluate the contribution of early cognitive assessment to the prediction of productivity outcome after traumatic brain injury (TBI) adjusted for severity of injury, demographic

Mark Sherer; Angelle M. Sander; Todd G. Nick; Walter M. High; James F. Malec; Mitchell Rosenthal

2002-01-01

334

Constrained Gaussian mixture model framework for automatic segmentation of MR brain images  

Microsoft Academic Search

An automated algorithm for tissue segmentation of noisy, low contrast magnetic resonance (MR) images of the brain is presented. A mixture model composed of a large number of Gaussians is used to represent the brain image. Each tissue is represented by a large number of Gaussian components to capture the complex tissue spatial layout. The intensity of a tissue is

Hayit Greenspan; Amit Ruf; Jacob Goldberger

2006-01-01

335

Brain Effective Connectivity Modeling for Alzheimer's Disease by Sparse Gaussian Bayesian Network  

E-print Network

Brain Effective Connectivity Modeling for Alzheimer's Disease by Sparse Gaussian Bayesian Network, 85287 2 Banner Alzheimer's Institute, Banner Good Samaritan Medical Center, Phoenix, AZ, 85006 ABSTRACT Recent studies have shown that Alzheimer's disease (AD) is related to alteration in brain connectivity

Li, Jing

336

MESENCHYMAL STEM CELL DELIVERY INTO RAT INFARCTED MYOCARDIUM USING A POROUS POLYSACCHARIDE-BASED SCAFFOLD: A QUANTITATIVE  

E-print Network

1 MESENCHYMAL STEM CELL DELIVERY INTO RAT INFARCTED MYOCARDIUM USING A POROUS POLYSACCHARIDE myocardial infarction model. Cellular engraftment was measured by quantitative RT-PCR using MSCs previously in the peri-infarct area, mainly phenotypically consistent with immature MSCs. Functional assessment

Paris-Sud XI, Université de

337

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model  

Microsoft Academic Search

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to

Loren E. Glover; Naoki Tajiri; Tsz Lau; Yuji Kaneko; Harry van Loveren; Cesario V. Borlongan

2012-01-01

338

System Dynamics Modeling in the Evaluation of Delays of Care in ST-Segment Elevation Myocardial Infarction Patients within a Tiered Health System  

PubMed Central

Background Mortality rates amongst ST segment elevation myocardial infarction (STEMI) patients remain high, especially in developing countries. The aim of this study was to evaluate the factors related with delays in the treatment of STEMI patients to support a strategic plan toward structural and personnel modifications in a primary hospital aligning its process with international guidelines. Methods and Findings The study was conducted in a primary hospital localized in Foz do Iguaçu, Brazil. We utilized a qualitative and quantitative integrated analysis including on-site observations, interviews, medical records analysis, Qualitative Comparative Analysis (QCA) and System Dynamics Modeling (SD). Main cause of delays were categorized into three themes: a) professional, b) equipment and c) transportation logistics. QCA analysis confirmed four main stages of delay to STEMI patient’s care in relation to the ‘Door-in-Door-out’ time at the primary hospital. These stages and their average delays in minutes were: a) First Medical Contact (From Door-In to the first contact with the nurse and/or physician): 7 minutes; b) Electrocardiogram acquisition and review by a physician: 28 minutes; c) ECG transmission and Percutaneous Coronary Intervention Center team feedback time: 76 minutes; and d) Patient’s Transfer Waiting Time: 78 minutes. SD baseline model confirmed the system’s behavior with all occurring delays and the need of improvements. Moreover, after model validation and sensitivity analysis, results suggested that an overall improvement of 40% to 50% in each of these identified stages would reduce the delay. Conclusions This evaluation suggests that investment in health personnel training, diminution of bureaucracy, and management of guidelines might lead to important improvements decreasing the delay of STEMI patients’ care. In addition, this work provides evidence that SD modeling may highlight areas where health system managers can implement and evaluate the necessary changes in order to improve the process of care. PMID:25079362

de Andrade, Luciano; Lynch, Catherine; Carvalho, Elias; Rodrigues, Clarissa Garcia; Vissoci, João Ricardo Nickenig; Passos, Guttenberg Ferreira; Pietrobon, Ricardo; Nihei, Oscar Kenji; de Barros Carvalho, Maria Dalva

2014-01-01

339

Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model  

SciTech Connect

The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixed in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.

Yang, SH. [Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth TX 76107 (United States); Ballmann, C.; Quarles, C. A. [Department of Astronomy and Physics, Texas Christian University, TCU Box 298840, Fort Worth TX 76129 (United States)

2009-03-10

340

3D brain atlas reconstructor service--online repository of three-dimensional models of brain structures.  

PubMed

Brain atlases are important tools of neuroscience. Traditionally prepared in paper book format, more and more commonly they take digital form which extends their utility. To simplify work with different atlases, to lay the ground for developing universal tools which could abstract from the origin of the atlas, efforts are being made to provide common interfaces to these atlases. 3D Brain Atlas Reconstructor service (3dBARs) described here is a repository of digital representations of different brain atlases in CAF format which we recently proposed and a repository of 3D models of brain structures. A graphical front-end is provided for creating and viewing the reconstructed models as well as the underlying 2D atlas data. An application programming interface (API) facilitates programmatic access to the service contents from other websites. From a typical user's point of view, 3dBARs offers an accessible way to mine publicly available atlasing data with a convenient browser based interface, without the need to install extra software. For a developer of services related to brain atlases, 3dBARs supplies mechanisms for enhancing functionality of other software. The policy of the service is to accept new datasets as delivered by interested parties and we work with the researchers who obtain original data to make them available to the neuroscience community at large. The functionality offered by the 3dBARs situates it at the core of present and future general atlasing services tying it strongly to the global atlasing neuroinformatics infrastructure. PMID:23943281

Majka, Piotr; Kowalski, Jakub M; Chlodzinska, Natalia; Wójcik, Daniel K

2013-10-01

341

A model for genomic imprinting in the social brain: elders.  

PubMed

Genomic imprinting refers to the process whereby genes are silenced when inherited via sperm or egg. The most widely accepted theory for the evolution of genomic imprinting-the kinship theory-argues that conflict between maternally inherited and paternally inherited genes over phenotypes with asymmetric effects on matrilineal and patrilineal kin results in self-imposed silencing of one of the copies. This theory was originally developed in the context of fitness interactions within nuclear families, to understand intragenomic conflict in the embryo and infant, but it has recently been extended to encompass interactions within wider social groups, to understand intragenomic conflict over the social behavior of juveniles and adults. Here, we complete our model of genomic imprinting in the social brain by considering age-specific levels of expression in a society were generations overlap, to determine how intragenomic conflict plays out in older age. We determine the role of sex bias in juvenile dispersal, reproductive success, and adult mortality in mediating the direction and intensity of conflict over the competing demands of parental and communal care as the individual ages. We discover that sex-specific asymmetries in these demographic parameters result in intragenomic conflict at early age but this conflict gradually decays with age. Although individuals are riven by internal conflict in their youth and middle age, they put their demons to rest in later life. PMID:22519791

Úbeda, Francisco; Gardner, Andy

2012-05-01

342

Highlighting the Structure-Function Relationship of the Brain with the Ising Model and Graph Theory  

PubMed Central

With the advent of neuroimaging techniques, it becomes feasible to explore the structure-function relationships in the brain. When the brain is not involved in any cognitive task or stimulated by any external output, it preserves important activities which follow well-defined spatial distribution patterns. Understanding the self-organization of the brain from its anatomical structure, it has been recently suggested to model the observed functional pattern from the structure of white matter fiber bundles. Different models which study synchronization (e.g., the Kuramoto model) or global dynamics (e.g., the Ising model) have shown success in capturing fundamental properties of the brain. In particular, these models can explain the competition between modularity and specialization and the need for integration in the brain. Graphing the functional and structural brain organization supports the model and can also highlight the strategy used to process and organize large amount of information traveling between the different modules. How the flow of information can be prevented or partially destroyed in pathological states, like in severe brain injured patients with disorders of consciousness or by pharmacological induction like in anaesthesia, will also help us to better understand how global or integrated behavior can emerge from local and modular interactions. PMID:25276772

Das, T. K.; Abeyasinghe, P. M.; Crone, J. S.; Sosnowski, A.; Laureys, S.; Owen, A. M.; Soddu, A.

2014-01-01

343

Assessment of Myocardial Infarction by Cardiac Magnetic Resonance Imaging and Long-Term Mortality  

PubMed Central

Background Cardiac magnetic resonance imaging provides detailed anatomical information on infarction. However, few studies have investigated the association of these data with mortality after acute myocardial infarction. Objective To study the association between data regarding infarct size and anatomy, as obtained from cardiac magnetic resonance imaging after acute myocardial infarction, and long-term mortality. Methods A total of 1959 reports of “infarct size” were identified in 7119 cardiac magnetic resonance imaging studies, of which 420 had clinical and laboratory confirmation of previous myocardial infarction. The variables studied were the classic risk factors – left ventricular ejection fraction, categorized ventricular function, and location of acute myocardial infarction. Infarct size and acute myocardial infarction extent and transmurality were analyzed alone and together, using the variable named “MET-AMI”. The statistical analysis was carried out using the elastic net regularization, with the Cox model and survival trees. Results The mean age was 62.3 ± 12 years, and 77.3% were males. During the mean follow-up of 6.4 ± 2.9 years, there were 76 deaths (18.1%). Serum creatinine, diabetes mellitus and previous myocardial infarction were independently associated with mortality. Age was the main explanatory factor. The cardiac magnetic resonance imaging variables independently associated with mortality were transmurality of acute myocardial infarction (p = 0.047), ventricular dysfunction (p = 0.0005) and infarcted size (p = 0.0005); the latter was the main explanatory variable for ischemic heart disease death. The MET-AMI variable was the most strongly associated with risk of ischemic heart disease death (HR: 16.04; 95%CI: 2.64-97.5; p = 0.003). Conclusion The anatomical data of infarction, obtained from cardiac magnetic resonance imaging after acute myocardial infarction, were independently associated with long-term mortality, especially for ischemic heart disease death.

Petriz, João Luiz Fernandes; Gomes, Bruno Ferraz de Oliveira; Rua, Braulio Santos; Azevedo, Clério Francisco; Hadlich, Marcelo Souza; Mussi, Henrique Thadeu Periard; Taets, Gunnar de Cunto; do Nascimento, Emília Matos; Pereira, Basílio de Bragança; e Silva, Nelson Albuquerque de Souza

2015-01-01

344

Assessment of Myocardial Infarction by Cardiac Magnetic Resonance Imaging and Long-Term Mortality.  

PubMed

Background: Cardiac magnetic resonance imaging provides detailed anatomical information on infarction. However, few studies have investigated the association of these data with mortality after acute myocardial infarction. Objective: To study the association between data regarding infarct size and anatomy, as obtained from cardiac magnetic resonance imaging after acute myocardial infarction, and long-term mortality. Methods: A total of 1959 reports of "infarct size" were identified in 7119 cardiac magnetic resonance imaging studies, of which 420 had clinical and laboratory confirmation of previous myocardial infarction. The variables studied were the classic risk factors - left ventricular ejection fraction, categorized ventricular function, and location of acute myocardial infarction. Infarct size and acute myocardial infarction extent and transmurality were analyzed alone and together, using the variable named "MET-AMI". The statistical analysis was carried out using the elastic net regularization, with the Cox model and survival trees. Results: The mean age was 62.3 ± 12 years, and 77.3% were males. During the mean follow-up of 6.4 ± 2.9 years, there were 76 deaths (18.1%). Serum creatinine, diabetes mellitus and previous myocardial infarction were independently associated with mortality. Age was the main explanatory factor. The cardiac magnetic resonance imaging variables independently associated with mortality were transmurality of acute myocardial infarction (p = 0.047), ventricular dysfunction (p = 0.0005) and infarcted size (p = 0.0005); the latter was the main explanatory variable for ischemic heart disease death. The MET-AMI variable was the most strongly associated with risk of ischemic heart disease death (HR: 16.04; 95%CI: 2.64-97.5; p = 0.003). Conclusion: The anatomical data of infarction, obtained from cardiac magnetic resonance imaging after acute myocardial infarction, were independently associated with long-term mortality, especially for ischemic heart disease death. PMID:25424161

Petriz, João Luiz Fernandes; Gomes, Bruno Ferraz de Oliveira; Rua, Braulio Santos; Azevedo, Clério Francisco; Hadlich, Marcelo Souza; Mussi, Henrique Thadeu Periard; Taets, Gunnar de Cunto; Nascimento, Emília Matos do; Pereira, Basílio de Bragança; Silva, Nelson Albuquerque de Souza E

2014-11-21

345

T cell-derived interleukin (IL)-21 promotes brain injury following stroke in mice.  

PubMed

T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell-derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21-deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4(+) T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4(+) T cells in the area surrounding acute stroke lesions, suggesting that IL-21-mediated brain injury may be relevant to human stroke. PMID:24616379

Clarkson, Benjamin D S; Ling, Changying; Shi, Yejie; Harris, Melissa G; Rayasam, Aditya; Sun, Dandan; Salamat, M Shahriar; Kuchroo, Vijay; Lambris, John D; Sandor, Matyas; Fabry, Zsuzsanna

2014-04-01

346

Generative models of brain connectivity for population studies  

E-print Network

Connectivity analysis focuses on the interaction between brain regions. Such relationships inform us about patterns of neural communication and may enhance our understanding of neurological disorders. This thesis proposes ...

Venkataraman, Archana, Ph. D. Massachusetts Institute of Technology

2012-01-01

347

Computational modeling of primary blast effects on the human brain  

E-print Network

Since the beginning of the military conflicts in Iraq and Afghanistan, there have been over 250,000 diagnoses of traumatic brain injury (TBI) in the U.S. military, with the majority of incidents caused by improvised explosive ...

Nyein, Michelle K. (Michelle Kyaw)

2013-01-01

348

Quantitative Imaging Methods for the Development and Validation of Brain Biomechanics Models  

PubMed Central

Rapid deformation of brain tissue in response to head impact or acceleration can lead to numerous pathological changes, both immediate and delayed. Modeling and simulation hold promise for illuminating the mechanisms of traumatic brain injury (TBI) and for developing preventive devices and strategies. However, mathematical models have predictive value only if they satisfy two conditions. First, they must capture the biomechanics of the brain as both a material and a structure, including the mechanics of brain tissue and its interactions with the skull. Second, they must be validated by direct comparison with experimental data. Emerging imaging technologies and recent imaging studies provide important data for these purposes. This review describes these techniques and data, with an emphasis on magnetic resonance imaging approaches. In combination, these imaging tools promise to extend our understanding of brain biomechanics and improve our ability to study TBI in silico. PMID:22655600

Bayly, Philip V.; Clayton, Erik H.; Genin, Guy M.

2013-01-01

349

Novel Brain Arteriovenous Malformation Mouse Models for Type 1 Hereditary Hemorrhagic Telangiectasia  

PubMed Central

Endoglin (ENG) is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have a higher prevalence of brain arteriovenous malformation (AVM) than the general population and patients with other HHT subtypes. The pathogenesis of brain AVM in HHT1 patients is currently unknown and no specific medical therapy is available to treat patients. Proper animal models are crucial for identifying the underlying mechanisms for brain AVM development and for testing new therapies. However, creating HHT1 brain AVM models has been quite challenging because of difficulties related to deleting Eng-floxed sequence in Eng2fl/2fl mice. To create an HHT1 brain AVM mouse model, we used several Cre transgenic mouse lines to delete Eng in different cell-types in Eng2fl/2fl mice: R26CreER (all cell types after tamoxifen treatment), SM22?-Cre (smooth muscle and endothelial cell) and LysM-Cre (lysozyme M-positive macrophage). An adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF) was injected into the brain to induce focal angiogenesis. We found that SM22?-Cre-mediated Eng deletion in the embryo caused AVMs in the postnatal brain, spinal cord, and intestines. Induction of Eng deletion in adult mice using R26CreER plus local VEGF stimulation induced the brain AVM phenotype. In both models, Eng-null endothelial cells were detected in the brain AVM lesions, and formed mosaicism with wildtype endothelial cells. However, LysM-Cre-mediated Eng deletion in the embryo did not cause AVM in the postnatal brain even after VEGF stimulation. In this study, we report two novel HHT1 brain AVM models that mimic many phenotypes of human brain AVM and can thus be used for studying brain AVM pathogenesis and testing new therapies. Further, our data indicate that macrophage Eng deletion is insufficient and that endothelial Eng homozygous deletion is required for HHT1 brain AVM development. PMID:24520391

Choi, Eun-Jung; Chen, Wanqiu; Jun, Kristine; Arthur, Helen M.; Young, William L.; Su, Hua

2014-01-01

350

Optically enhanced blood-brain-barrier crossing of plasmonic-active nanoparticles in preclinical brain tumor animal models  

NASA Astrophysics Data System (ADS)

Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables monitoring of the therapeutic process in each individual. Such a concept dubbed "theranostics" potentiates translational research and improves precision medicine. One particular challenging application of theranostics involves imaging and controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound), however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation. Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold nanoparticle in future brain tumor imaging and therapy.

Yuan, Hsiangkuo; Wilson, Christy M.; Li, Shuqin; Fales, Andrew M.; Liu, Yang; Grant, Gerald; Vo-Dinh, Tuan

2014-02-01

351

Fluorodeoxyglucose /sup 18/F scan in Alzheimer's disease and multi-infarct dementia  

SciTech Connect

Patients with Alzheimer's disease and multi-infarct dementia were studied with scans using fluorodeoxyglucose tagged with fluorine 18. The rates of glucose metabolism were calculated. Patients with Alzheimer's dementia showed decreased metabolism in all areas of the brain but with preferential sparing of the primary motor and sensory cortex. Patients with multi-infarct dementia also had global reductions in glucose metabolic rates when compared with normal control subjects, but the areas of hypometabolism were focal and asymmetric.

Benson, D.F.; Kuhl, D.E.; Hawkins, R.A.; Phelps, M.E.; Cummings, J.L.; Tsai, S.Y.

1983-11-01

352

Ventricular remodeling and infarct expansion.  

PubMed

Infarct expansion, defined as an alteration in the ventricular topography due to thinning and lengthening of the infarcted segment, develops within the first few hours of the acute symptoms, mostly in patients with a large, transmural, anterior myocardial infarction. Shape changes, peculiar to risk region location and due to disparity in regional ventricular architecture, could be posited as the first step in the process of infarct expansion, with various cellular mechanisms contributing to subsequent continued early and late ventricular dilation. Because the increase in left ventricular volume is expected to be linearly dependent on the extent of the infarction, limiting infarct size, by thrombolysis, would proportionally reduce enlargement of the cavity. The effect of thrombolysis on left ventricular volume, however, seems not to be completely accounted for by the lessening effect of reperfusion on infarct size, because data suggest a restraining effect of reperfusion on the process of ventricular dilation in addition to the lessening effect on infarct size. If this turns out to be true, then the achievement of a patent vessel even beyond the time period when that patency may be expected to salvage myocardium would be further justified. Theoretical predictions substantiate the potential effectiveness in restraining ventricular dilation of stiffening of the necrotic region alone, independently of myocardial salvage in infarcted patients. The process of progressive ventricular dilation involves not only a primary alteration in function of the infarcted region, but also a time-dependent secondary change in the noninfarcted tissue itself, finalized to restore stroke volume despite a persistently depressed ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8279368

Zardini, P; Marino, P; Golia, G; Anselmi, M; Castelli, M

1993-12-16

353

Life-time and hierarchy of memory in the dissipative quantum model of brain  

E-print Network

Some recent developments of the dissipative quantum model of brain arereported. In particular, the time-dependent frequency case is considered withits implications on the different life-times of the collective modes.

Alfinito, E; Alfinito, Eleonora; Vitiello, Giuseppe

1999-01-01

354

Life-time and hierarchy of memory in the dissipative quantum model of brain  

E-print Network

Some recent developments of the dissipative quantum model of brain are reported. In particular, the time-dependent frequency case is considered with its implications on the different life-times of the collective modes.

Eleonora Alfinito; Giuseppe Vitiello

1999-12-30

355

Repurposed Experimental Cancer Drug Restores Brain Function in Mouse Models of Alzheimer's Disease  

MedlinePLUS

... Americans have Alzheimer’s disease, which causes clumps of amyloid beta protein to build up in the brain, and ... mechanisms. In a mouse model of Alzheimer’s disease, amyloid beta clusters (red) build up among neurons (green) in ...

356

A Computational Model for Lesion Dynamics in Multiple Sclerosis of the Brain  

E-print Network

A Computational Model for Lesion Dynamics in Multiple Sclerosis of the Brain Krishna Mohan, T. R of Pharmaceutical Sciences, State University of New York, Buffalo, NY 14260-1200, USA 1 Abstract Multiple sclerosis

Sen, Surajit

357

Brain Shift Correction Based on a Boundary Element Biomechanical Model with Different  

E-print Network

of updating the whole image data with intraoperative CT or MR scanners. It has the advantage that the image [6,7]. Paulsen et al. [6] modeled the brain as an elastic body with an interstitial fluid, while solv

Frey, Pascal

358

Psychosis post corona radiata and lentiform nucleus infarction.  

PubMed

Complications of stroke can include neuropsychiatric symptoms. However, post-stroke psychosis is rare. We report a case where an acute presentation of psychosis, depression and fluctuating cognitive impairment in a middle-aged man turned out to be related to a silent brain infarction. The patient had a background of poorly controlled type 2 diabetes mellitus with glycated haemoglobin level of 9.0-11.0%, hypertension and ischaemic heart disease. His CT brain results showed multifocal infarct with hypodensities at bilateral lentiform nucleus and bilateral corona radiata. His strong genetic predisposition of psychosis and a history of brief psychotic disorder with complete remission 3?years prior to the current presentation might possibly contribute to his post-stroke atypical neuropsychiatric presentation, and posed diagnostic challenges. He showed marked improvement with risperidone 6?mg nocte, chlorpromazine 50?mg nocte and fluvoxamine of 200?mg nocte. The need of comprehensive treatments to modify his stroke risk factors was addressed. PMID:25837653

Abang Abdullah, Khadijah Hasanah; Mohamed Saini, Suriati; Sharip, Shalisah; Abdul Rahman, Abdul Hamid

2015-01-01

359

Mechanical response of a head injury model with viscoelastic brain tissue  

Microsoft Academic Search

Head injury models in two geometries with pulse loading were investigated to study the phenomenon of wave propagation in viscoelastic\\u000a brain tissue. One-dimensional and two-dimensional Lagrangian finite-difference computer formulations were used. The brain\\u000a material was modeled both as a perfect fluid and as a viscoelastic material. A geometric description of the head was obtained\\u000a from a human skull. The material

KRISHAN K. WAttI; Howard C. Merchant

1977-01-01

360

A developmental ontology for the mammalian brain based on the prosomeric model.  

PubMed

In the past, attempts to create a hierarchical classification of brain structures (an ontology) have been limited by the lack of adequate data on developmental processes. Recent studies on gene expression during brain development have demonstrated the true morphologic interrelations of different parts of the brain. A developmental ontology takes into account the progressive rostrocaudal and dorsoventral differentiation of the neural tube, and the radial migration of derivatives from progenitor areas, using fate mapping and other experimental techniques. In this review, we used the prosomeric model of brain development to build a hierarchical classification of brain structures based chiefly on gene expression. Because genomic control of neural morphogenesis is remarkably conservative, this ontology should prove essentially valid for all vertebrates, aiding terminological unification. PMID:23871546

Puelles, Luis; Harrison, Megan; Paxinos, George; Watson, Charles

2013-10-01

361

Relative Roles of CD90 and c?Kit to the Regenerative Efficacy of Cardiosphere?Derived Cells in Humans and in a Mouse Model of Myocardial Infarction  

PubMed Central

Background The regenerative potential of cardiosphere?derived cells (CDCs) for ischemic heart disease has been demonstrated in mice, rats, pigs, and a recently completed clinical trial (CADUCEUS). CDCs are CD105+ stromal cells of intrinsic cardiac origin, but the antigenic characteristics of the active fraction remain to be defined. CDCs contain a small minority of c?kit+ cells, which have been argued to be cardiac progenitors, and a variable fraction of CD90+ cells whose bioactivity is unclear. Methods We performed a retrospective analysis of data from the CADUCEUS trial and a prospective mouse study to elucidate the roles of c?kit+ and CD90+ cells in human CDCs. Here, we show, surprisingly, that c?kit expression has no relationship to CDCs' therapeutic efficacy in humans, and depletion of c?kit+ cells does not undermine the structural and functional benefits of CDCs in a mouse model of myocardial infarction (MI). In contrast, CD90 expression negatively correlates with the therapeutic benefit of CDCs in humans (ie, higher CD90 expression associated with lower efficacy). Depletion of CD90+ cells augments the functional potency of CDCs in murine MI. CD90? CDCs secrete lower levels of inflammatory cytokines and can differentiate into cardiomyocytes in vitro and in vivo. Conclusion The majority population of CDCs (CD105+/CD90?/c?kit?) constitutes the active fraction, both in terms of therapeutic efficacy and in the ability to undergo cardiomyogenic differentiation. The c?kit+ fraction is neither necessary for, nor contributory to, the regenerative efficacy of CDCs. PMID:25300435

Cheng, Ke; Ibrahim, Ahmed; Hensley, M. Taylor; Shen, Deliang; Sun, Baiming; Middleton, Ryan; Liu, Weixin; Smith, Rachel R.; Marbán, Eduardo

2014-01-01

362

Postoperative cerebral venous infarction  

PubMed Central

Background: Postoperative cerebral venous infarction (POCVI) is not an uncommon complication in cranial surgeries. However, literature is sparse on the epidemiology and management of postoperative venous infarcts. Aims and Objectives: The aim was to study the incidence and clinico-radiological course of POCVI in patients in a tertiary level neurosurgical unit and compare the outcome between pediatric and adult patients following POCVI. Materials and Methods: In this prospective study carried out over an 8 month period, consecutive patients undergoing elective major cranial surgeries were monitored neurologically and with serial computed tomography (CT) of the head for POCVI in the postoperative period. All patients had at least one CT head done within 24 hours of surgery. Diagnosis of hemorrhagic POCVI was based on the presence of subcortical, multifocal hyperdensities with irregular margins and or low density areas in the perioperative fields. Nonhemorrhagic POCVI was diagnosed if CT showed a localized hypodensity poorly demarcated in the subcortical white matter with/without mass effect, along with the presence of fresh neurological deficits. Observations and Results: A total of 376 patients were enrolled in the study period. Of these, 26 (7%) developed POCVI. The male: female ratio was 1.2:1 and age ranged from 6 to 68 years with 12 (46%) being under the age of 18 years. Sixteen (61%) patients developed hemorrhagic POCVI and 10 (39%) patients developed nonhemorrhagic POCVI. The mean time to POCVI detection was 72 hours (range 24–144 hours). Seventeen (66%) patients were managed conservatively, and nine (34%) patients underwent decompressive craniectomy as an additional procedure for management of POCVI. In five patients (all with hemorrhagic POCVI), the infarction was an incidental finding. Of the 21 patients with symptomatic POCVI, 13 (61.9%) patients improved neurologically and were discharged with residual deficits. Two (9.5%) showed no neurological improvement till discharge, and 6 (28.5%) died during the hospital stay following POCVI. Conclusions: Children constitute a significant population (46% in our study) of the patients who develop POCVI with poor outcome similar to that seen in adult patients.

Agrawal, Deepak; Naik, Vikas

2015-01-01

363

MRI as a tool to study brain structure from mouse models for mental retardation  

NASA Astrophysics Data System (ADS)

Nowadays, transgenic mice are a common tool to study brain abnormalities in neurological disorders. These studies usually rely on neuropathological examinations, which have a number of drawbacks, including the risk of artefacts introduced by fixation and dehydration procedures. Here we present 3D Fast Spin Echo Magnetic Resonance Imaging (MRI) in combination with 2D and 3D segmentation techniques as a powerful tool to study brain anatomy. We set up MRI of the brain in mouse models for the fragile X syndrome (FMR1 knockout) and Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus (CRASH) syndrome (L1CAM knockout). Our major goal was to determine qualitative and quantitative differences in specific brain structures. MRI of the brain of fragile X and CRASH patients has revealed alterations in the size of specific brain structures, including the cerebellar vermis and the ventricular system. In the present MRI study of the brain from fragile X knockout mice, we have measured the size of the brain, cerebellum and 4th ventricle, which were reported as abnormal in human fragile X patients, but found no evidence for altered brain regions in the mouse model. In CRASH syndrome, the most specific brain abnormalities are vermis hypoplasia and abnormalities of the ventricular system with some degree of hydrocephalus. With the MRI study of L1CAM knockout mice we found vermis hypoplasia, abnormalities of the ventricular system including dilatation of the lateral and the 4th ventricles. These subtle abnormalities were not detected upon standard neuropathological examination. Here we proved that this sensitive MRI technique allows to measure small differences which can not always be detected by means of pathology.

Verhoye, Marleen; Sijbers, Jan; Kooy, R. F.; Reyniers, E.; Fransen, E.; Oostra, B. A.; Willems, Peter; Van der Linden, Anne-Marie

1998-07-01

364

Crataegus special extract WS® 1442 improves cardiac function and reduces infarct size in a rat model of prolonged coronary ischemia and reperfusion  

Microsoft Academic Search

In Germany, hydroalcoholic extracts from hawthorn (Crataegus spp.) leaves with flowers are approved drugs for the treatment of mild forms of heart insufficiency. Besides cardiotonic effects these herbal remedies have been shown to possess cardioprotective properties. We now evaluated if treatment of rats with the Crataegus special extract WS® 1442 also improves cardiac function and prevents myocardial infarction during prolonged

Maris Veveris; Egon Koch; Shyam S Chatterjee

2004-01-01

365

Expression of brain adiponectin in a murine model of transient cerebral ischemia  

PubMed Central

Objective: Adiponectin is a hormone that is mainly secreted by fat cells. Adiponectin has anti-inflammatory and anti-atherosclerotic effects, and a protective effect against ischemic brain injury, but the level of expression of adiponectin in brain tissue is unknown. In the current study, a mouse model of transient cerebral ischemia was used to determine the level of expression of adiponectin in ischemic brain tissue. Methods: Sixty CD-1 mice underwent transient middle cerebral artery occlusion. The level of expression of adiponectin in mouse brain tissues 1 hour, 4 hours, 1 day, 3 days, and 7 days, after cerebral ischemia/reperfusion injury were determined using a real-time quantitative polymerase chain reaction, Western blot, and immunohistochemistry. Results: The level of expression of adiponectin in mouse ischemic brain tissues increased after cerebral ischemia/reperfusion injury and was higher in the central area of ischemia than in the peripheral area. The level of expression of adiponectin occurred only in vascular endothelial cells. There was no significant change in the level of expression of adiponectin mRNA in brain tissue pre- and post-ischemia/reperfusion injury. Conclusion: After cerebral ischemia/reperfusion injury, adiponectin accumulated in the vascular endothelial cells of ischemic brain tissues, and non-endogenous adiponectin was generated. Circulating adiponectin accumulated in ischemic brain tissues through its role in adhering to damaged vascular endothelial cells. PMID:25550990

Shen, Lin-Hui; Miao, Jie; Zhao, Ya-Jie; Zhao, Yong-Ju; Liang, Wei

2014-01-01

366

Comparative study of iodine-123-labeled hypericin and (99m)Tc-labeled hexakis [2-methoxy isobutyl isonitrile] in a rabbit model of myocardial infarction.  

PubMed

Identification of myocardial infarction (MI) by imaging is critical for clinical management of ischemic heart disease. Iodine-123-labeled hypericin (¹²³I-Hyp) is a new potent infarct avid agent. We sought to compare target selectivity and organ distribution between ¹²³I-Hyp and the myocardial perfusion agent, technetium-99m-labeled hexakis [2-methoxy isobutyl isonitrile] ((99m)Tc-Sestamibi) in rabbits with acute MI. Hypericin was radiolabeled with I using iodogen as oxidant, and (99m)Tc-Sestamibi was prepared from a commercial kit and radioactive sodium pertechnetate. Rabbits (n = 6) with 24-hour-old MI received ¹²³I-Hyp intravenously and received (99m)Tc-Sestamibi 9 hours later. They were studied by dual-isotope simultaneous acquisition micro single photon emission computed tomography/computed tomography (DISA-?SPECT/CT), tissue gamma counting (TGC), autoradiography, and histology. After purification, ¹²³I-Hyp was obtained with radiochemical purity around 99%. DISA-?SPECT/CT images showed ¹²³I-Hyp retention in infarcted but not in normal myocardium. By TGC, accumulation values reached 1.175 ± 0.096 percentage of injected dose per gram (%ID/g) and 0.028 ± 0.007%ID/g in infarcted myocardium and normal myocardium with high tracer concentration in liver, intestines, and gallbladder. (99m)Tc-Sestamibi was prepared with radiochemical purity over 95%. DISA-?SPECT/CT showed no accumulation in MI and high initial radioactivity levels in normal myocardium that were rapidly cleared as confirmed by TGC (0.011 ± 0.003%ID/g). Liver and intestines were clearly visualized. By TGC, gallbladder and kidneys show moderate (99m)Tc-Sestamibi uptake. The selectivity of ¹²³I-Hyp for infarcted myocardium and (99m)Tc-Sestamibi for normal myocardium was confirmed. ¹²³I-Hyp distribution in rabbits is characterized by hepatobiliary excretion. (99m)Tc-Sestamibi undergoes hepatorenal elimination. PMID:23714775

Cona, Marlein M; Feng, Yuanbo; Li, Yue; Chen, Feng; Vunckx, Kathleen; Zhou, Lin; Van Slambrouck, Katrien; Rezaei, Ahmadreza; Gheysens, Olivier; Nuyts, Johan; Verbruggen, Alfons; Oyen, Raymond; Ni, Yicheng

2013-09-01

367

Nitroglycerin Use in Myocardial Infarction Patients: Risks and Benefits  

PubMed Central

Acute myocardial infarction and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin remains a first-line treatment for angina pectoris and acute myocardial infarction. Nitroglycerin achieves its benefit by giving rise to nitric oxide, which causes vasodilation and increases blood flow to the myocardium. However, continuous delivery of nitroglycerin results in tolerance, limiting the use of this drug. Nitroglycerin tolerance is due, at least in part, to inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme that converts nitroglycerin to the vasodilator, nitric oxide. We have recently found that, in addition to nitroglycerin’s effect on the vasculature, sustained treatment with nitroglycerin negatively affects cardiomyocyte viability following ischemia, thus resulting in increased infarct size in a myocardial infarction model in animals. Co-administration of Alda-1, an activator of ALDH2, with nitroglycerin improves metabolism of reactive aldehyde adducts and prevents the nitroglycerin-induced increase in cardiac dysfunction following myocardial infarction. In this review, we describe the molecular mechanisms associated with the benefits and risks of nitroglycerin administration in myocardial infarction. (167 of 200). PMID:22040938

Ferreira, Julio C.B.; Mochly-Rosen, Daria

2012-01-01

368

Research Article Whitening of Background Brain Activity via Parametric Modeling  

Microsoft Academic Search

Several signal subspace techniques have been recently suggested for the extraction of the visual evoked potential signals from brain background colored noise. The majority of these techniques assume the background noise as white, and for colored noise, it is sug- gested to be whitened, without further elaboration on how this might be done. In this paper, we investigate the whitening

Nidal Kamel; Andrews Samraj; Arash Mousavi

2007-01-01

369

Brain Korea 21 Phase II: A New Evaluation Model. Monograph  

ERIC Educational Resources Information Center

In the late 1990s, the Korea Ministry of Education and Human Resources, in response to concern over the relatively low standing of the nation's universities and researchers, launched the Brain Korea 21 program BK21). BK21 seeks to make Korean research universities globally competitive and to produce more high-quality researchers in Korea. It…

Seong, Somi; Popper, Steven W.; Goldman, Charles A.; Evans, David K.

2008-01-01

370

Long-term reorganization of structural brain networks in a rabbit model of intrauterine growth restriction.  

PubMed

Characterization of brain changes produced by intrauterine growth restriction (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This condition affects 5-10% of all pregnancies and is associated with a wide range of neurodevelopmental disorders. Better understanding of the brain reorganization produced by IUGR opens a window of opportunity to find potential imaging biomarkers in order to identify the infants with a high risk of having neurodevelopmental problems and apply therapies to improve their outcomes. Structural brain networks obtained from diffusion magnetic resonance imaging (MRI) is a promising tool to study brain reorganization and to be used as a biomarker of neurodevelopmental alterations. In the present study this technique is applied to a rabbit animal model of IUGR, which presents some advantages including a controlled environment and the possibility to obtain high quality MRI with long acquisition times. Using a Q-Ball diffusion model, and a previously published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14 control rabbits at 70 days of age (equivalent to pre-adolescence human age) were obtained. The analysis of graph theory features showed a decreased network infrastructure (degree and binary global efficiency) associated with IUGR condition and a set of generalized fractional anisotropy (GFA) weighted measures associated with abnormal neurobehavior. Interestingly, when assessing the brain network organization independently of network infrastructure by means of normalized networks, IUGR showed increased global and local efficiencies. We hypothesize that this effect could reflect a compensatory response to reduced infrastructure in IUGR. These results present new evidence on the long-term persistence of the brain reorganization produced by IUGR that could underlie behavioral and developmental alterations previously described. The described changes in network organization have the potential to be used as biomarkers to monitor brain changes produced by experimental therapies in IUGR animal model. PMID:24943271

Batalle, Dafnis; Muñoz-Moreno, Emma; Arbat-Plana, Ariadna; Illa, Miriam; Figueras, Francesc; Eixarch, Elisenda; Gratacos, Eduard

2014-10-15

371

Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model  

PubMed Central

In earlier studies insects were proposed as suitable models for vertebrate blood–brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain barrier of the desert locust (Schistocerca gregaria). In an in vivo study on the locust, we found an increased uptake of the two well-known Pgp substrates, rhodamine 123 and loperamide after co-administration with the Pgp inhibitors cyclosporine A or verapamil. Furthermore, ex vivo studies on isolated locust brains demonstrated differences in permeation of high and low permeability compounds. The vertebrate Pgp inhibitor verapamil did not affect the uptake of passively diffusing compounds but significantly increased the brain uptake of Pgp substrates in the ex vivo model. In addition, studies at 2°C and 30°C showed differences in brain uptake between Pgp-effluxed and passively diffusing compounds. The transcriptome data show a high degree of sequence identity of the locust Pgp transporter protein sequences to the human Pgp sequence (37%), as well as the presence of conserved domains. As in vertebrates, the locust brain–barrier function is morphologically confined to one specific cell layer and by using a whole-brain ex vivo drug exposure technique our locust model may retain the major cues that maintain and modulate the physiological function of the brain barrier. We show that the locust model has the potential to act as a robust and convenient model for assessing BBB permeability in early drug discovery. PMID:25505597

Andersson, Olga; Badisco, Liesbeth; Hansen, Ane Håkansson; Hansen, Steen Honoré; Hellman, Karin; Nielsen, Peter Aadal; Olsen, Line Rørbæk; Verdonck, Rik; Abbott, N Joan; Vanden Broeck, Jozef; Andersson, Gunnar

2014-01-01

372

MR-guided transcranial brain HIFU in small animal models  

NASA Astrophysics Data System (ADS)

Recent studies have demonstrated the feasibility of transcranial high-intensity focused ultrasound (HIFU) therapy in the brain using adaptive focusing techniques. However, the complexity of the procedures imposes provision of accurate targeting, monitoring and control of this emerging therapeutic modality in order to ensure the safety of the treatment and avoid potential damaging effects of ultrasound on healthy tissues. For these purposes, a complete workflow and setup for HIFU treatment under magnetic resonance (MR) guidance is proposed and implemented in rats. For the first time, tissue displacements induced by the acoustic radiation force are detected in vivo in brain tissues and measured quantitatively using motion-sensitive MR sequences. Such a valuable target control prior to treatment assesses the quality of the focusing pattern in situ and enables us to estimate the acoustic intensity at focus. This MR-acoustic radiation force imaging is then correlated with conventional MR-thermometry sequences which are used to follow the temperature changes during the HIFU therapeutic session. Last, pre- and post-treatment magnetic resonance elastography (MRE) datasets are acquired and evaluated as a new potential way to non-invasively control the stiffness changes due to the presence of thermal necrosis. As a proof of concept, MR-guided HIFU is performed in vitro in turkey breast samples and in vivo in transcranial rat brain experiments. The experiments are conducted using a dedicated MR-compatible HIFU setup in a high-field MRI scanner (7 T). Results obtained on rats confirmed that both the MR localization of the US focal point and the pre- and post-HIFU measurement of the tissue stiffness, together with temperature control during HIFU are feasible and valuable techniques for efficient monitoring of HIFU in the brain. Brain elasticity appears to be more sensitive to the presence of oedema than to tissue necrosis.

Larrat, B.; Pernot, M.; Aubry, J.-F.; Dervishi, E.; Sinkus, R.; Seilhean, D.; Marie, Y.; Boch, A.-L.; Fink, M.; Tanter, M.

2010-01-01

373

Effects of Buyang Huanwu Decoction on Ventricular Remodeling and Differential Protein Profile in a Rat Model of Myocardial Infarction  

PubMed Central

Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from “Correction on Errors in Medical Classics” in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18?g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF. PMID:23049607

Zhou, Ying Chun; Liu, Bin; Li, Ying Jia; Jing, Lin Lin; Wen, Ge; Tang, Jing; Xu, Xin; Lv, Zhi Ping; Sun, Xue Gang

2012-01-01

374

A sticky weighted regression model for time-varying resting-state brain connectivity estimation.  

PubMed

Despite recent progress on brain connectivity modeling using neuroimaging data such as fMRI, most current approaches assume that brain connectivity networks have time-invariant topology/coefficients. This is clearly problematic as the brain is inherently nonstationary. Here, we present a time-varying model to investigate the temporal dynamics of brain connectivity networks. The proposed method allows for abrupt changes in network structure via a fused least absolute shrinkage and selection operator (LASSO) scheme, as well as recovery of time-varying networks with smoothly changing coefficients via a weighted regression technique. Simulations demonstrate that the proposed method yields improved accuracy on estimating time-dependent connectivity patterns when compared to a static sparse regression model or a weighted time-varying regression model. When applied to real resting-state fMRI datasets from Parkinson's disease (PD) and control subjects, significantly different temporal and spatial patterns were found to be associated with PD. Specifically, PD subjects demonstrated reduced network variability over time, which may be related to impaired cognitive flexibility previously reported in PD. The temporal dynamic properties of brain connectivity in PD subjects may provide insights into brain dynamics associated with PD and may serve as a potential biomarker in future studies. PMID:25252272

Liu, Aiping; Chen, Xun; McKeown, Martin J; Wang, Z Jane

2015-02-01

375

Dynamics of blood flow and oxygenation changes during brain activation: The balloon model  

Microsoft Academic Search

A biomechanical model is presented for the dynamic changes in deoxyhemoglobin content during brain activation. The model incorporates the conflicting effects of dynamic changes in both blood oxygenation and blood volume. Calcu- lations based on the model show pronounced transients in the deoxyhemoglobin content and the blood\\

Richard B. Buxton; Eric C. Wong; Lawrence R. Frank

1998-01-01

376

The Brain-Targeted Teaching Model for 21st-Century Schools  

ERIC Educational Resources Information Center

"The Brain-Targeted Teaching Model for 21st-Century Schools" serves as a bridge between research and practice by providing a cohesive, proven, and usable model of effective instruction. Compatible with other professional development programs, this model shows how to apply relevant research from educational and cognitive neuroscience to classroom…

Hardiman, Mariale

2012-01-01

377

Pharmacokinetic Modeling of Non-Linear Brain Distribution of Fluvoxamine in the Rat  

Microsoft Academic Search

Introduction  A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine.\\u000a \\u000a \\u000a \\u000a Materials and methods  Rats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1,\\u000a 3.7 or 7.3 mg.kg?1 of fluvoxamine.\\u000a \\u000a \\u000a \\u000a Analysis  With increasing dose a disproportional increase in brain concentrations was observed. The kinetics of brain distribution was\\u000a estimated

Marian Geldof; Jan Freijer; Ludy van Beijsterveldt; Meindert Danhof

2008-01-01

378

Modeling invasion of brain tissue by glioblastoma cells: ECM alignment and motility  

NASA Astrophysics Data System (ADS)

A key stage in the development of highly malignant brain tumors (Glioblastoma Multiforme) is invasion of normal brain tissue by motile cells moving through a crowded, complex environment. Evidence from in vitro experiments suggests the cell motion is accompanied by considerable deformation and alignment of the extra-cellular matrix (ECM) of the brain. In the case of breast cancer, alignment effects of this sort have been seen in vivo. We have modeled features of this system including stress confinement in the non-linear elasticity of the ECM and contact guidance of the cell motion.

Sander, L. M.

2013-03-01

379

Small intestinal ischemia and infarction  

MedlinePLUS

... the bowel are reconnected. In some cases, a colostomy or ileostomy is needed. The blockage of arteries ... Intestinal infarction may require a colostomy or ileostomy, which may be ... is common in these cases. People who have a large amount ...

380

Phosphodiesterase type 5 inhibitor Tadalafil increases Rituximab treatment efficacy in a mouse brain lymphoma model.  

PubMed

The treatment efficacy of Rituximab on lymphoma as an immunotherapeutic approach is confirmed, but this treatment has limited penetration through the brain micro vessels. Such limitation significantly attenuates the efficacy of systemic administration of this antibody on brain lymphomas. We aimed to confirm that Tadalafil, a long-acting phosphodiesterase type 5 inhibitor, could increase microvascular permeability and Rituximab treatment efficacy in brain lymphomas. We established a mouse brain lymphoma model by planting human-derived lymphoma cell line Raji into brain parenchyma of mice using stereotaxic techniques. After 16 days, 7.0 T magnetic resonance imaging was performed to confirm the presence of the mass. The mice were observed under near-infrared fluorescence after intravenous injection of fluorescence-labeled Rituximab. Evans Blue was used as probe to detect the microvascular permeability of brain lymphomas after Tadalafil administration. Starting from 4 days after implantation, the mice were administered different treatments. Survival analysis of brain lymphoma-loaded mice was performed. Evans Blue detection showed that Tadalafil administration could increase brain vascular permeability in the tumor-bearing group compared with control mice. Rituximab treatment prolonged the survival time of mice compared with the untreated control group (mean 25.75 vs. 20.8 days, p < 0.05). Tadalafil with Rituximab treatment resulted in the longest survival time (29 days, p < 0.05). Rituximab may be a promising therapeutic agent for the treatment of brain lymphoma. Tadalafil can enhance Rituximab treatment efficacy by improving the microvascular permeability in mice brain lymphoma. PMID:25524816

Wang, Rong; Chen, Wenli; Zhang, Qiang; Liu, Yong; Qiao, Xiaoyun; Meng, Kui; Mao, Ying

2015-03-01

381

In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia  

PubMed Central

The use of theranostics in neurosciences has been rare to date because of the limitations imposed on the free delivery of substances to the brain by the blood-brain barrier. Here we report the development of a theranostic system for the treatment of stroke, a leading cause of death and disability in developed countries. We first performed a series of proteomic, immunoblotting and immunohistological studies to characterize the expression of molecular biomarkers for the so-called peri-infarct tissue, a key region of the brain for stroke treatment. We confirmed that the HSP72 protein is a suitable biomarker for the peri-infarct region, as it is selectively expressed by at-risk tissue for up to 7 days following cerebral ischemia. We also describe the development of anti-HSP72 vectorized stealth immunoliposomes containing imaging probes to make them traceable by conventional imaging techniques (fluorescence and MRI) that were used to encapsulate a therapeutic agent (citicoline) for the treatment of cerebral ischemia. We tested the molecular recognition capabilities of these nano-platforms in vitro together with their diagnostic and therapeutic properties in vivo, in an animal model of cerebral ischemia. Using MRI, we found that 80% of vectorized liposomes were located on the periphery of the ischemic lesion, and animals treated with citicoline encapsulated on these liposomes presented lesion volumes up to 30% smaller than animals treated with free (non-encapsulated) drugs. Our results show the potential of nanotechnology for the development of effective tools for the treatment of neurological diseases. PMID:24396517

Agulla, Jesús; Brea, David; Campos, Francisco; Sobrino, Tomás; Argibay, Bárbara; Al-Soufi, Wajih; Blanco, Miguel; Castillo, José; Ramos-Cabrer, Pedro

2014-01-01

382

Improving low-dose blood-brain barrier permeability quantification using sparse high-dose induced prior for Patlak model  

E-print Network

Improving low-dose blood-brain barrier permeability quantification using sparse high-dose induced, New York, NY, USA Abstract Blood-brain barrier permeability (BBBP) measurements extracted from-brain barrier permeability; Patlak model; radiation dose reduction 1. Introduction As the first leading cause

Chen, Tsuhan

383

Off-center spherical model for dosimetry calculations in chick brain tissue  

SciTech Connect

This paper presents calculations for the electric field and absorbed power density distribution in chick brain tissue inside a test tube, using an off-center spherical model. It is shown that the off-center spherical model overcomes many of the limitations of the concentric spherical model, and permits a more realistic modeling of the brain tissue as it sits in the bottom of the test tube surrounded by buffer solution. The effect of the unequal amount of buffer solution above the upper and below the lower surfaces of the brain is analyzed. The field distribution is obtained in terms of a rapidly converging series of zonal harmonics. A method that permits the expansion of spherical harmonics about an off-center origin in terms of spherical harmonics at the origin is developed to calculate in closed form the electric field distribution. Numerical results are presented for the absorbed power density distribution at a carrier frequency of 147 MHz. It is shown that the absorbed power density increases toward the bottom of the brain surface. Scaling relations are developed by keeping the electric field intensity in the brain tissue the same at two different frequencies. Scaling relations inside, as well as outside, the brain surface are given. The scaling relation distribution is calculated as a function of position, and compared to the scaling relations obtained in the concentric spherical model. It is shown that the off-center spherical model yields scaling ratios in the brain tissue that lie between the extreme values predicted by the concentric and isolated spherical models.

Gonzalez, G.; Nearing, J.C.; Spiegel, R.J.; Joines, W.T.

1986-01-01

384

Agent-based brain modeling by means of hierarchical cooperative coevolution.  

PubMed

We address the development of brain-inspired models that will be embedded in robotic systems to support their cognitive abilities. We introduce a novel agent-based coevolutionary computational framework for modeling assemblies of brain areas. Specifically, self-organized agent structures are employed to represent brain areas. In order to support the design of agents, we introduce a hierarchical cooperative coevolutionary (HCCE) scheme that effectively specifies the structural details of autonomous, yet cooperating system components. The design process is facilitated by the capability of the HCCE-based design mechanism to investigate the performance of the model in lesion conditions. Interestingly, HCCE also provides a consistent mechanism to reconfigure (if necessary) the structure of agents, facilitating follow-up modeling efforts. Implemented models are embedded in a simulated robot to support its behavioral capabilities, also demonstrating the validity of the proposed computational framework. PMID:19239349

Maniadakis, Michail; Trahanias, Panos

2009-01-01

385

Acute care of myocardial infarction.  

PubMed Central

Patients with acute myocardial infarct (AMI) need rapid diagnosis and prompt initiation of thrombolytic therapy. Patients with suspected cardiac ischemia must receive a coordinated team response by the emergency room staff including rapid electrocardiographic analysis and a quick but thorough history and physical examination to diagnose AMI. Thrombolysis and adjunct therapies should be administered promptly when indicated. The choice of thrombolytics is predicated by the location of the infarct. PMID:8754702

Gutman, M. B.; Lee, T. F.; Gin, K.; Ho, K.

1996-01-01

386

Segmentation of Brain MR Images through a Hidden Markov Random Field Model and the Expectation Maximization Algorithm  

Microsoft Academic Search

The finite mixture (FM) model is the most commonly used model for statistical segmentation of brain magnetic reso- nance (MR) images because of its simple mathematical form and the piecewise constant nature of ideal brain MR images. However, being a histogram-based model, the FM has an intrinsic limita- tion—no spatial information is taken into account. This causes the FM model

Yongyue Zhang; Michael Brady; Stephen M. Smith

2001-01-01

387

[Hemorrhagic infarction following cerebral vasospasm].  

PubMed

Among 528 cases with ruptured aneurysm, 10 cases (1.9%) developed hemorrhagic infarction following vasospasm. There was no obvious relationship between the occurrence and location of aneurysm and the neurological grade on admission. Hemorrhagic infarction occurred from day 9 to 25 (mean day 16) after aneurysmal rupture, and the major neurological symptoms were aggravation of consciousness level, which appeared in 6 cases. On the CT scans of the hemorrhagic infarction following vasospasm, nine cases revealed heterogeneous hemorrhage as assembled of spotty or linear hemorrhages within the ischemic infarction, and 5 cases had massive hemorrhagic infarction in size with mass effect. Although surgical therapy for 2 cases and conservative therapy for 8 cases were performed, the results were unfavorable; ie, 2 cases were good, 5 fair or poor, and 3 died. Especially, 5 cases with massive hemorrhagic infarction obviously resulted in poor prognosis. In our series, induced hypertension therapy for vasospasm was considered as a risk factor. In conclusion, it is necessary to avoid induced hypertension therapy in the remission stage of vasospasm and serial SPECT study might be recommended as a useful prospective method estimating the vasospasm. PMID:2605044

Andoh, T; Imao, Y; Nishimura, Y; Sakai, N; Yamada, H

1989-10-01

388

Learning Computational Models of Video Memorability from fMRI Brain Imaging.  

PubMed

Generally, various visual media are unequally memorable by the human brain. This paper looks into a new direction of modeling the memorability of video clips and automatically predicting how memorable they are by learning from brain functional magnetic resonance imaging (fMRI). We propose a novel computational framework by integrating the power of low-level audiovisual features and brain activity decoding via fMRI. Initially, a user study experiment is performed to create a ground truth database for measuring video memorability and a set of effective low-level audiovisual features is examined in this database. Then, human subjects' brain fMRI data are obtained when they are watching the video clips. The fMRI-derived features that convey the brain activity of memorizing videos are extracted using a universal brain reference system. Finally, due to the fact that fMRI scanning is expensive and time-consuming, a computational model is learned on our benchmark dataset with the objective of maximizing the correlation between the low-level audiovisual features and the fMRI-derived features using joint subspace learning. The learned model can then automatically predict the memorability of videos without fMRI scans. Evaluations on publically available image and video databases demonstrate the effectiveness of the proposed framework. PMID:25314715

Han, Junwei; Chen, Changyuan; Shao, Ling; Hu, Xintao; Han, Jungong; Liu, Tianming

2014-10-01

389

A novel model for brain iron uptake: introducing the concept of regulation.  

PubMed

Neurologic disorders such as Alzheimer's, Parkinson's disease, and Restless Legs Syndrome involve a loss of brain iron homeostasis. Moreover, iron deficiency is the most prevalent nutritional concern worldwide with many associated cognitive and neural ramifications. Therefore, understanding the mechanisms by which iron enters the brain and how those processes are regulated addresses significant global health issues. The existing paradigm assumes that the endothelial cells (ECs) forming the blood-brain barrier (BBB) serve as a simple conduit for transport of transferrin-bound iron. This concept is a significant oversimplification, at minimum failing to account for the iron needs of the ECs. Using an in vivo model of brain iron deficiency, the Belgrade rat, we show the distribution of transferrin receptors in brain microvasculature is altered in luminal, intracellular, and abluminal membranes dependent on brain iron status. We used a cell culture model of the BBB to show the presence of factors that influence iron release in non-human primate cerebrospinal fluid and conditioned media from astrocytes; specifically apo-transferrin and hepcidin were found to increase and decrease iron release, respectively. These data have been integrated into an interactive model where BBB ECs are central in the regulation of cerebral iron metabolism. PMID:25315861

Simpson, Ian A; Ponnuru, Padmavathi; Klinger, Marianne E; Myers, Roland L; Devraj, Kavi; Coe, Christopher L; Lubach, Gabriele R; Carruthers, Anthony; Connor, James R

2015-01-01

390

Biomechanical modeling of decompressive craniectomy in traumatic brain injury  

Microsoft Academic Search

\\u000a Background Decompressive craniectomy is the final phase in the graded scheme of critical care management of refractory raised intracranial\\u000a pressure following severe traumatic brain injury. We aim to define the optimal size for decompressive craniectomy so that\\u000a a good balance is achieved between reduction of raised ICP and the extent of trans-calvarial herniation. Provision of such\\u000a quantitative data will also

Chun Ping Gao; Beng Ti Ang

391

Modeling and estimation of single evoked brain potential components  

Microsoft Academic Search

Presents a novel approach to solving the single-trial evoked-potential estimation problem. Recognizing that different components of an evoked potential complex may originate from different functional brain sites and can be distinguished according to their respective latencies and amplitudes, the authors propose an estimation approach based on identification of evoked potential components on a single-trial basis. The estimation process is performed

Daniel H. Lange; Hillel Pratt; Gideon F. Inbar

1997-01-01

392

Mechanisms of erythropoietin-induced brain protection in neonatal hypoxia-ischemia rat model.  

PubMed

Erythropoietin, a hemotopoietic growth factor, has brain protective actions. This study investigated the mechanisms of Recombinant Human EPO (rhEPO)-induced brain protection in neonates. An established rat hypoxia-ischemia model was used by ligation of the right common carotid artery of 7-day-old pups, followed by 90 minute of hypoxia (8% 02 and 92% N2) at 37 degrees C. Animals were divided into three groups: control, hypoxia-ischemia, and hypoxia-ischemia plus rhEPO treatment. In rhEPO treated pups, 300 units rhEPO was administered intraperitoneally 24 hours before hypoxia. rhEPO treatment (300 units) was administered daily for an additional 2 days. ELISA and immunohistochemistry examined the expression of EPO and EPOR. Brain weight, morphology, TUNEL assay, and DNA laddering evaluated brain protection. rhEPO abolished mortality (from 19% to 0%) during hypoxia insult, increased brain weight from 52% to 88%, reduced DNA fragmentation, and decreased TUNEL-positive cells. Real-time RT-PCR, Western blot, and immunohistochemistry revealed an enhanced expression of heat shock protein 27 (HSP27) in ischemic brain hemisphere. Double labeling of TUNEL with HSP27 showed most HSP27 positive cells were negative to TUNEL staining. rhEPO reduces brain injury, especially apoptotic cell death after neonatal hypoxia-ischemia, partially mediated by the activation of HSP27. PMID:14747752

Sun, Yun; Zhou, Changman; Polk, Paula; Nanda, Anil; Zhang, John H

2004-02-01

393

Core modular blood and brain biomarkers in social defeat mouse model for post traumatic stress disorder  

PubMed Central

Background Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects a substantial portion of combat veterans and poses serious consequences to long-term health. Consequently, the identification of diagnostic and prognostic blood biomarkers for PTSD is of great interest. Previously, we assessed genome-wide gene expression of seven brain regions and whole blood in a social defeat mouse model subjected to various stress conditions. Results To extract biological insights from these data, we have applied a new computational framework for identifying gene modules that are activated in common across blood and various brain regions. Our results, in the form of modular gene networks that highlight spatial and temporal biological functions, provide a systems-level molecular description of response to social stress. Specifically, the common modules discovered between the brain and blood emphasizes molecular transporters in the blood-brain barrier, and the associated genes have significant overlaps with known blood signatures for PTSD, major depression, and bipolar disease. Similarly, the common modules specific to the brain highlight the components of the social defeat stress response (e.g., fear conditioning pathways) in each brain sub-region. Conclusions Many of the brain-specific genes discovered are consistent with previous independent studies of PTSD or other mental illnesses. The results from this study further our understanding of the mechanism of stress response and contribute to a growing list of diagnostic biomarkers for PTSD. PMID:23962043

2013-01-01

394

Behavioral abnormalities of fetal growth retardation model rats with reduced amounts of brain proteoglycans.  

PubMed

Fetal growth retardation (FGR) is a critical problem in the neonatal period, because a substantial population of infants born with FGR go on to develop various developmental disorders. In the present study, we produced FGR model rats by continuous administration of a synthetic thromboxane A2 analogue (STA2) to pregnant rats. The FGR pups exhibited a significant delay in postnatal neurological development. Moreover, behavioral analyses revealed the presence of a learning disability in juvenile FGR male rats. To investigate the mechanism underlying the neurological disorders, histological and biochemical analyses of the brain of FGR rats were performed. The density of neurons in the cortical plate of an FGR brain was low compared with the brains of a similarly aged, healthy rat. Consistent with this finding, the density of TUNEL-positive cells was higher in the cortical plate of FGR brains. Western blot analyses showed that the levels of three brain-specific chondroitin sulfate proteoglycans (CSPGs), neurocan, phosphacan, and neuroglycan C, were all significantly reduced in the brain of neonatal FGR rats compared with those of the control. The reduction of CSPG-levels and morphological changes in the brain may be relevant to neurological dysfunction in FGR. PMID:19393646

Saito, Akiko; Matsui, Fumiko; Hayashi, Kanako; Watanabe, Kimi; Ichinohashi, Yuko; Sato, Yoshiaki; Hayakawa, Masahiro; Kojima, Seiji; Oohira, Atsuhiko

2009-09-01

395

Mathematical Modeling of Human Glioma Growth Based on Brain Topological Structures: Study of Two Clinical Cases  

PubMed Central

Gliomas are the most common primary brain tumors and yet almost incurable due mainly to their great invasion capability. This represents a challenge to present clinical oncology. Here, we introduce a mathematical model aiming to improve tumor spreading capability definition. The model consists in a time dependent reaction-diffusion equation in a three-dimensional spatial domain that distinguishes between different brain topological structures. The model uses a series of digitized images from brain slices covering the whole human brain. The Talairach atlas included in the model describes brain structures at different levels. Also, the inclusion of the Brodmann areas allows prediction of the brain functions affected during tumor evolution and the estimation of correlated symptoms. The model is solved numerically using patient-specific parametrization and finite differences. Simulations consider an initial state with cellular proliferation alone (benign tumor), and an advanced state when infiltration starts (malign tumor). Survival time is estimated on the basis of tumor size and location. The model is used to predict tumor evolution in two clinical cases. In the first case, predictions show that real infiltrative areas are underestimated by current diagnostic imaging. In the second case, tumor spreading predictions were shown to be more accurate than those derived from previous models in the literature. Our results suggest that the inclusion of differential migration in glioma growth models constitutes another step towards a better prediction of tumor infiltration at the moment of surgical or radiosurgical target definition. Also, the addition of physiological/psychological considerations to classical anatomical models will provide a better and integral understanding of the patient disease at the moment of deciding therapeutic options, taking into account not only survival but also life quality. PMID:22761843

Suarez, Cecilia; Maglietti, Felipe; Colonna, Mario; Breitburd, Karina; Marshall, Guillermo

2012-01-01

396

Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome  

PubMed Central

Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting almost exclusively females, caused in the overwhelming majority of the cases by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). High circulating levels of oxidative stress (OS) markers in patients suggest the involvement of OS in the RTT pathogenesis. To investigate the occurrence of oxidative brain damage in Mecp2 mutant mouse models, several OS markers were evaluated in whole brains of Mecp2-null (pre-symptomatic, symptomatic, and rescued) and Mecp2-308 mutated (pre-symptomatic and symptomatic) mice, and compared to those of wild type littermates. Selected OS markers included non-protein-bound iron, isoprostanes (F2-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes) and 4-hydroxy-2-nonenal protein adducts. Our findings indicate that oxidative brain damage 1) occurs in both Mecp2-null (both ?/y and stop/y) and Mecp2-308 (both 308/y males and 308/+ females) mouse models of RTT; 2) precedes the onset of symptoms in both Mecp2-null and Mecp2-308 models; and 3) is rescued by Mecp2 brain specific gene reactivation. Our data provide direct evidence of the link between Mecp2 deficiency, oxidative stress and RTT pathology, as demonstrated by the rescue of the brain oxidative homeostasis following brain-specifically Mecp2-reactivated mice. The present study indicates that oxidative brain damage is a previously unrecognized hallmark feature of murine RTT, and suggests that Mecp2 is involved in the protection of the brain from oxidative stress. PMID:24769161

De Felice, Claudio; Della Ragione, Floriana; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Ciccoli, Lucia; Scalabrì, Francesco; Marracino, Federico; Madonna, Michele; Belmonte, Giuseppe; Ricceri, Laura; De Filippis, Bianca; Laviola, Giovanni; Valacchi, Giuseppe; Durand, Thierry; Galano, Jean-Marie; Oger, Camille; Guy, Alexandre; Bultel-Poncé, Valérie; Guy, Jacky; Filosa, Stefania; Hayek, Joussef; D'Esposito, Maurizio

2014-01-01

397

Near Real-Time Computer Assisted Surgery for Brain Shift Correction Using Biomechanical Models  

PubMed Central

Conventional image-guided neurosurgery relies on preoperative images to provide surgical navigational information and visualization. However, these images are no longer accurate once the skull has been opened and brain shift occurs. To account for changes in the shape of the brain caused by mechanical (e.g., gravity-induced deformations) and physiological effects (e.g., hyperosmotic drug-induced shrinking, or edema-induced swelling), updated images of the brain must be provided to the neuronavigation system in a timely manner for practical use in the operating room. In this paper, a novel preoperative and intraoperative computational processing pipeline for near real-time brain shift correction in the operating room was developed to automate and simplify the processing steps. Preoperatively, a computer model of the patient’s brain with a subsequent atlas of potential deformations due to surgery is generated from diagnostic image volumes. In the case of interim gross changes between diagnosis, and surgery when reimaging is necessary, our preoperative pipeline can be generated within one day of surgery. Intraoperatively, sparse data measuring the cortical brain surface is collected using an optically tracked portable laser range scanner. These data are then used to guide an inverse modeling framework whereby full volumetric brain deformations are reconstructed from precomputed atlas solutions to rapidly match intraoperative cortical surface shift measurements. Once complete, the volumetric displacement field is used to update, i.e., deform, preoperative brain images to their intraoperative shifted state. In this paper, five surgical cases were analyzed with respect to the computational pipeline and workflow timing. With respect to postcortical surface data acquisition, the approximate execution time was 4.5 min. The total update process which included positioning the scanner, data acquisition, inverse model processing, and image deforming was ~11–13 min. In addition, easily implemented hardware, software, and workflow processes were identified for improved performance in the near future.

SUN, KAY; PHEIFFER, THOMAS S.; SIMPSON, AMBER L.; WEIS, JARED A.; THOMPSON, REID C.; MIGA, MICHAEL I.

2014-01-01

398

Exogenously induced brain activation regulates neuronal activity by top-down modulation: conceptualized model for electrical brain stimulation.  

PubMed

Physiological and exogenous factors are able to adjust sensory processing by modulating activity at different levels of the nervous system hierarchy. Accordingly, transcranial direct current stimulation (tDCS) may use top-down mechanisms to control the access for incoming information along the neuroaxis. To test the hypothesis that brain activation induced by tCDS is able to initiate top-down modulation and that chronic stress disrupts this effect, 60-day-old male Wistar rats (n = 78) were divided into control; control + tDCS; control + sham-tDCS; stress; stress + tDCS; and stress + sham-tDCS. Chronic stress was induced using a restraint stress model for 11 weeks, and then, the treatment was applied over 8 days. BDNF levels were used to assess neuronal activity at spinal cord, brainstem, and hippocampus. Mechanical pain threshold was assessed by von Frey test immediately and 24 h after the last tDCS-intervention. tDCS was able to decrease BDNF levels in the structures involved in the descending systems (spinal cord and brainstem) only in unstressed animals. The treatment was able to reverse the stress-induced allodynia and to increase the pain threshold in unstressed animals. Furthermore, there was an inverse relation between pain sensitivity and spinal cord BDNF levels. Accordingly, we propose the addition of descending systems in the current brain electrical modulation model. PMID:25665871

Spezia Adachi, Lauren Naomi; Quevedo, Alexandre Silva; de Souza, Andressa; Scarabelot, Vanessa Leal; Rozisky, Joanna Ripoll; de Oliveira, Carla; Marques Filho, Paulo Ricardo; Medeiros, Liciane Fernandes; Fregni, Felipe; Caumo, Wolnei; Torres, Iraci L S

2015-05-01

399

Positron emission tomography imaging of CD105 expression in a rat myocardial infarction model with 64Cu-NOTA-TRC105  

PubMed Central

Biological changes following myocardial infarction (MI) lead to increased secretion of angiogenic factors that subsequently stimulate the formation of new blood vessels as a compensatory mechanism to reverse ischemia. The goal of this study was to assess the role of CD105 expression during MI-induced angiogenesis by positron emission tomography (PET) imaging using 64Cu-labeled TRC105, an anti-CD105 monoclonal antibody. MI was induced by ligation of the left anterior descending (LAD) artery in female rats. Echocardiography and 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET scans were performed on post-operative day 3 to confirm the presence of MI in the infarct group and intact heart in the sham group, respectively. Ischemia-induced angiogenesis was non-invasively monitored with 64Cu-NOTA-TRC105 (an extensively validated PET tracer in our previous studies) PET on post-operative days 3, 10, and 17. Tracer uptake in the infarct zone was highest on day 3 following MI, which was significantly higher than that in the sham group (1.41 ± 0.45 %ID/g vs 0.57 ± 0.07 %ID/g; n=3, p<0.05). Subsequently, tracer uptake in the infarct zone decreased over time to the background level on day 17, whereas tracer uptake in the heart of sham rats remained low at all time points examined. Histopathology documented increased CD105 expression following MI, which corroborated in vivo findings. This study indicated that PET imaging of CD105 can be a useful tool for MI-rela