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1

Severity of leukoaraiosis determines clinical phenotype after brain infarction  

PubMed Central

Objective: To determine whether the extent of leukoaraiosis, a composite marker of baseline brain integrity, differed between patients with TIA with diffusion-weighted imaging (DWI) evidence of infarction (transient symptoms with infarction [TSI]) and patients with ischemic stroke. Methods: Leukoaraiosis volume on MRI was quantified in a consecutive series of 153 TSI and 354 ischemic stroke patients with comparable infarct volumes on DWI. We explored the relationship between leukoaraiosis volume and clinical phenotype (TIA or ischemic stroke) using a logistic regression model. Results: Patients with TSI tended to be younger (median age 66 vs 69 years, p = 0.062) and had smaller median normalized leukoaraiosis volume (1.2 mL, interquartile range [IQR] 0.2–4.7 mL vs 3.5 mL, IQR 1.2–8.6 mL, p < 0.001). In multivariable analysis controlling for age, stroke risk factors, etiologic stroke mechanism, infarct volume, and infarct location, increasing leukoaraiosis volume remained associated with ischemic stroke (odds ratio 1.05 per mL, 95%confidence interval 1.02–1.09, p = 0.004), along with infarct volume and infarct location. Conclusion: The probability of ischemic stroke rather than TSI increases with increasing leukoaraiosis volume, independent of infarct size and location. Our findings support the concept that the integrity of white matter tracts connecting different parts of the brain could contribute to whether or not patients develop TSI or ischemic stroke in an event of brain infarction. PMID:21700580

Arsava, E.M.; Bayrlee, A.; Vangel, M.; Rost, N.S.; Rosand, J.; Furie, K.L.; Sorensen, A.G.

2011-01-01

2

[Molecular mechanism of brain infarction].  

PubMed

Through many experimental brain ischemia studies, it has been suggested that all of the cellular elements in the central nervous system show dynamic stress responses depending on the degree of environmental changes induced by ischemia and reperfusion. In this symposium, first we reviewed the pathogenic role of microvascular stasis (i.e., secondary ischemia) caused by the primary ischemic event and demonstrated the important role of cell adhesion molecules through the experiments using ICAM-1 knock-out mouse as a model of brain ischemia/reperfusion. Next, we discussed the ischemia-induced neuronal cell responses in relation to the apoptosis-like selective neuronal death and the induction of adopted stress responses including stress protein synthesis and 'ischemic tolerance' phenomenon. A variety of stress proteins induced by ischemic stress have been reviewed in relation to their pathophysiological roles in the ischemic brain. Finally, we reviewed the important pathogenic roles of endoplasmic reticulum (ER) stress as well as adaptive responses of ubiquitin-proteasome system in ischemia-induced neuronal cell death. For the development of a novel therapeutic agent against ischemic stroke, it is quite important to clarify both the negative and positive cellular responses induced by brain ischemia/reperfusion. PMID:15152495

Matsumoto, Masayasu; Yamashita, Hiroshi; Kitagawa, Kazuo; Kohriyama, Tatsuo

2003-11-01

3

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

4

CONCURRENT ACUTE BRAIN INFARCTS IN PATIENTS WITH MONOCULAR VISUAL LOSS  

PubMed Central

Objective Embolism from a proximal source to the retinal circulation could be a sign of embolism from the same source to the hemispheric circulation. We sought to determine the frequency of acute brain infarcts on diffusion-weighted imaging (DWI) in patients with monocular visual loss of presumed ischemic origin (MVL). Methods We retrospectively studied 129 consecutive patients with MVL secondary to retinal ischemia. All patients underwent DWI, comprehensive ophthalmologic and neurologic examination, and diagnostic evaluations for the underlying etiology. Statistical analyses explored univariable and multivariable predictors of DWI evidence of acute brain infarcts. Results DWI revealed concurrent acute brain infarct(s) in 31 of the 129 patients (24%). The probability of positive DWI was higher in embolic versus non-embolic MVL (28% vs. 8%, p=0.04), in MVL characterized by permanent visual loss versus transient symptoms (33% vs. 18%, p=0.04), and in MVL associated with concurrent hemispheric symptoms versus isolated MVL (53% vs. 20%, p<0.01). Patients with positive DWI were more likely to harbor a major underlying etiology as compared to those with normal DWI (OR 3.7, 95% CI 1.5–9.4). Interpretation This study demonstrates that MVL does not always represent an isolated disease of the retina; approximately one out of every four patients with MVL demonstrates acute brain infarcts on DWI. Since patients with concurrent brain infarcts are more likely to exhibit a cardiac or vascular source of embolism, imaging evidence of brain injury in patients with MVL may be a useful marker to guide the timing and extent of the diagnostic examinations. PMID:22926859

Helenius, Johanna; Arsava, E. Murat; Goldstein, Joshua N.; Cestari, Dean M.; Buonanno, Ferdinando S.; Rosen, Bruce R.; Ay, Hakan

2012-01-01

5

Automatic segmentation of brain infarction in diffusion-weighted MR images  

NASA Astrophysics Data System (ADS)

It is important to detect the site and size of infarction volume in stroke patients. An automatic method for segmenting brain infarction lesion from diffusion weighted magnetic resonance (MR) images of patients has been developed. The method uses an integrated approach which employs image processing techniques based on anisotropic filters and atlas-based registration techniques. It is a multi-stage process, involving first images preprocessing, then global and local registration between the anatomical brain atlas and the patient, and finally segmentation of infarction volume based on region splitting and merging and multi-scale adaptive statistical classification. The proposed multi-scale adaptive statistical classification model takes into account spatial, intensity gradient, and contextual information of the anatomical brain atlas and the patient. Application of the method to diffusion weighted imaging (DWI) scans of twenty patients with clinically determined infarction was carried out. It shows that the method got a satisfied segmentation even in the presence of radio frequency (RF) inhomogeneities. The results were compared with lesion delineations by human experts, showing the identification of infarction lesion with accuracy and reproducibility.

Li, Wu; Tian, Jie

2003-05-01

6

INCREASED BLOOD BRAIN BARRIER PERMEABILITY ON PERFUSION CT MIGHT PREDICT MALIGNANT MIDDLE CEREBRAL ARTERY INFARCTION  

PubMed Central

Background and Purpose Perfusion computerized tomography (PCT) has been used to assess the extent of blood brain barrier (BBB) breakdown. The purpose of this study was to determine the predictive value of (BBB) permeability (BBBP) measured using PCT for development of malignant middle cerebral artery infarction (MMCA) requiring hemicraniectomy (HC). Methods We retrospectively identified patients from our stroke registry that had MCA infarction and were evaluated with admission PCT. BBBP and cerebral blood volume (CBV) maps were generated and infarct volumes calculated. Clinical and radiographic characteristics were compared between those who underwent HC versus those who did not undergo hemicraniectomy (NHC). Results 122 patients (12 (HC), 110 (NHC)) were identified. 12 patients who underwent HC had developed edema, midline shift or infarct expansion. Infarct permeability area (IParea), infarct CBV area (ICBVarea), and infarct volumes were significantly different (p<0.018, p<0.0211, p<0.0001, p<0.0014) between HC and NHC groups. Age (p=0.03) and admission National Institutes of Health Stroke Scale (NIHSS) (p=0.0029) were found to be independent predictors for HC. Using logistic regression modeling, there was an association between increased IParea and HC. The odds ratio for HC based on a 5, 10, 15 or 20 cm2 increase in IParea were 1.179, 1.390, 1.638 or 1.932, respectively (95% CI 1.035-1.343, 1.071-1.804, 1.108-2.423, 1.146-3.255). Conclusion Increased IParea is associated with an increased likelihood for undergoing HC. Since early HC for MMCA has been associated with better outcomes, the IParea on admission PCT might be a useful tool to predict MMCA and need for HC. PMID:20847316

Bektas, Hesna; Wu, Tzu-Ching; Kasam, Mallikarjunarao; Harun, Nusrat; Sitton, Clark W; Grotta, James C; Savitz, Sean I

2012-01-01

7

Atrial fibrillation is associated with reduced brain volume and cognitive function independent of cerebral infarcts  

PubMed Central

Background and Purpose Atrial fibrillation (AF) has been associated with cognitive decline independant of stroke, suggesting additional effects of AF on the brain. We aimed to assess the association between AF and brain function and structure in a general elderly population. Methods This is a cross-sectional analysis on 4251 non-demented participants (mean age 76 ± 5 years) in the population-based AGES-Reykjavik Study. Medical record data were collected on the presence, subtype and time from first diagnosis of AF; 330 participants had AF. Brain volume measurements, adjusted for intracranial volume, and presence of cerebral infarcts were determined with MRI. Memory, speed of processing and executive function composites were calculated from a cognitive test battery. In a multivariable linear regression model, adjustments were made for demographic, cardiovascular risk factors and cerebral infarcts. Results Participants with AF had lower total brain volume compared to those without AF (p<0.001). The association was stronger with persistent/permanent than paroxysmal AF and with increased time from the first diagnosis of the disease. Of the brain tissue volumes, AF was associated with lower volume of gray and white matter (p<0.001 and p=0.008 respectively) but not of white matter hyperintesities (p=0.49). Participants with AF scored lower on tests on memory. Conclusions AF is associated with smaller brain volume and the association is stronger with increasing burden of the arrhythmia. These findings suggest that AF has a cumulative negative effect on the brain independent of cerebral infarcts. PMID:23444303

Stefansdottir, Hrafnhildur; Arnar, David O.; Aspelund, Thor; Sigurdsson, Sigurdur; Jonsdottir, Maria K.; Hjaltason, Haukur; Launer, Lenore J.; Gudnason, Vilmundur

2013-01-01

8

Multiple Brain Infarcts: Clinical and Neuroimaging Patterns Using Diffusion-Weighted Magnetic Resonance  

Microsoft Academic Search

The capability of diffusion-weighted (DW) magnetic resonance imaging (MRI) to identify very early ischemic brain injury better than conventional MRI is well known. This technique, which successfully discriminates acute from old infarcts, is particularly useful in patients with multiple brain infarcts (MBI). Among 142 patients with acute stroke consecutively admitted to our primary care center, we selected 43 patients with

M. Altieri; R. J. Metz; C. Müller; P. Maeder; R. Meuli; J. Bogousslavsky

1999-01-01

9

Peripheral oxidative biomarkers constitute a valuable indicator of the severity of oxidative brain damage in acute cerebral infarction.  

PubMed

Oxidative stress contributes to post-ischemic brain damage. We assessed the correlation between plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, and progressive brain damage in rats subjected to transient or permanent ischemia. Male Wistar rats were subjected to permanent- and 0.5-, 1-, 2-h middle cerebral artery occlusion (MCAO). At various times thereafter, the infarct volume, 8-OHdG levels in plasma and brain tissue, DNA fragmentation, and immunohistochemical observations on their brains were recorded and compared. At 12 h after 2-h MCAO-reperfusion, the cortical infarct volume was increased; it peaked at 24 h. DNA degeneration expanded from the caudate putamen into the cortical region at 12 h. 8-OHdG-containing cells in the cortical infarct zone were observed at 12 h, the number of 8-OHdG-positive cells was highest at 24 h and they co-localized with DNA single-strand breaks. Plasma 8-OHdG significantly increased at 12 h, and peaked at 24 h after reperfusion (1.1+/-0.7 ng/ml (mean+/-S.D.); controls 0.3+/-0.1; p<0.01). This increase was in step with increased infarct volume, DNA degradation, and reflected immunohistochemical findings in the cortical region but not the caudate putamen. In the permanent MCAO model, plasma 8-OHdG levels were associated with the brain contents of 8-OHdG. Plasma 8-OHdG and the cortical infarct volume were lower in the 0.5- and 1-h than the 2-h MCAO model. Our findings suggest that 8-OHdG as a peripheral biomarker may be an indicator of oxidative brain damage in acute cerebral infarction. PMID:15464743

Liu, Hao; Uno, Masaaki; Kitazato, Keiko T; Suzue, Atsuhiko; Manabe, Shiji; Yamasaki, Hiroyuki; Shono, Masayuki; Nagahiro, Shinji

2004-10-29

10

Prolonged Exposure to Isoflurane Ameliorates Infarction Severity in the Rat Pup Model of Neonatal Hypoxia-Ischemia  

Microsoft Academic Search

The neonatal hypoxia-ischemia rat model referred to as the Rice–Vannucci model is extensively used to study perinatal hypoxia-ischemia\\u000a and child brain injury. One of the major weaknesses of this model is its inconsistency of brain infarction among animals.\\u000a We hypothesize that the inconsistency of infarction is caused by prolonged operation time and therefore isoflurane exposure.\\u000a Neonatal hypoxia-ischemia was induced in

Hank Chen; Michael Burris; Adrain Fajilan; Fred Spagnoli; John H. Zhang; Jiping Tang

11

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

12

Model-Based Design of Mechanical Therapies for Myocardial Infarction  

PubMed Central

The mechanical properties of healing myocardial infarcts are a critical determinant of pump function and the transition to heart failure. Recent reports suggest that modifying infarct mechanical properties can improve function and limit ventricular remodeling. However, little attempt has been made to identify the specific infarct material properties that would optimize left ventricular (LV) function. We utilized a finite-element model of a large anteroapical infarct in a dog heart to explore a wide range of infarct mechanical properties. Isotropic stiffening of the infarct reduced end-diastolic (EDV) and end-systolic (ESV) volumes, improved LV contractility, but had little effect on stroke volume. A highly anisotropic infarct, with high longitudinal stiffness but low circumferential stiffness coefficients, produced the best stroke volume by increasing diastolic filling, without affecting contractility or ESV. Simulated infarcts in two different locations displayed different transmural strain patterns. Our results suggest that there is a general trade-off between acutely reducing LV size and acutely improving LV pump function, that isotropically stiffening the infarct is not the only option of potential therapeutic interest, and that customizing therapies for different infarct locations may be important. Our model results should provide guidance for design and development of therapies to improve LV function by modifying infarct mechanical properties. PMID:21088945

Fomovsky, Gregory M.; Macadangdang, Jesse R.; Ailawadi, Gorav; Holmes, Jeffrey W.

2012-01-01

13

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

14

Predictors of Life-Threatening Brain Edema in Middle Cerebral Artery Infarction  

Microsoft Academic Search

Background: We performed a systematic review to identify predictors of the development of life-threatening brain edema in patients with middle cerebral artery infarction. Methods: We searched Medline from January 1966 and Embase from January 1974 to April 2007 for cohort and case-control studies on predictors of life-threatening edema in patients with middle cerebral artery infarction. Crude data were used to

Jeannette Hofmeijer; Ale Algra; L. Jaap Kappelle; H. Bart van der Worp

2008-01-01

15

Genome-wide Association Studies of MRI-defined Brain Infarcts: Meta-analysis from the CHARGE Consortium  

PubMed Central

Background Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI-infarct, in persons without histories of transient ischemic attack or stroke. We performed meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Methods Using 2.2 million genotyped and imputed SNPs, each study performed cross-sectional genome-wide association analysis of MRI-infarct using age and sex-adjusted logistic regression models. Study-specific findings were combined in an inverse-variance weighted meta-analysis, including 9401 participants with mean age 69.7, 19.4% of whom had ?1 MRI-infarct. Results The most significant association was found with rs2208454 (minor allele frequency: 20%), located in intron 3 of MACRO Domain Containing 2 gene and in the downstream region of Fibronectin Leucine Rich Transmembrane Protein 3 gene. Each copy of the minor allele was associated with lower risk of MRI-infarcts: odds ratio=0.76, 95% confidence interval=0.68–0.84, p=4.64×10?7. Highly suggestive associations (p<1.0×10?5) were also found for 22 other SNPs in linkage disequilibrium (r2>0.64) with rs2208454. The association with rs2208454 did not replicate in independent samples of 1822 white and 644 African-American participants, although 4 SNPs within 200kb from rs2208454 were associated with MRI-infarcts in African-American sample. Conclusions This first community-based, genome-wide association study on covert MRI-infarcts uncovered novel associations. Although replication of the association with top SNP failed, possibly due to insufficient power, results in the African American sample are encouraging, and further efforts at replication are needed. PMID:20044523

Debette, Stephanie; Bis, Joshua C.; Fornage, Myriam; Schmidt, Helena; Ikram, M. Arfan; Sigurdsson, Sigurdur; Heiss, Gerardo; Struchalin, Maksim; Smith, Albert V.; van der Lugt, Aad; DeCarli, Charles; Lumley, Thomas; Knopman, David S.; Enzinger, Christian; Eiriksdottir, Gudny; Koudstaal, Peter J.; DeStefano, Anita L.; Psaty, Bruce M.; Dufouil, Carole; Catellier, Diane J.; Fazekas, Franz; Aspelund, Thor; Aulchenko, Yurii S.; Beiser, Alexa; Rotter, Jerome I.; Tzourio, Christophe; Shibata, Dean K.; Tscherner, Maria; Harris, Tamara B.; Rivadeneira, Fernando; Atwood, Larry D.; Rice, Kenneth; Gottesman, Rebecca F.; van Buchem, Mark A.; Uitterlinden, Andre G.; Kelly-Hayes, Margaret; Cushman, Mary; Zhu, Yicheng; Boerwinkle, Eric; Gudnason, Vilmundur; Hofman, Albert; Romero, Jose R.; Lopez, Oscar; van Duijn, Cornelia M.; Au, Rhoda; Heckbert, Susan R.; Wolf, Philip A.; Mosley, Thomas H.; Seshadri, Sudha; Breteler, Monique M.B.; Schmidt, Reinhold; Launer, Lenore J.; Longstreth, WT

2010-01-01

16

Nicardipine in models of myocardial infarction  

PubMed Central

1 In a dog model of partial myocardial ischaemia, superimposed ST segment elevations in epicardial ECGs were inhibited by nicardipine over a cumulative i.v. dose range of 1-20 ?g kg-1. 2 Over the cumulative i.v. dose range of 0.5-166.5 ?g kg-1, nicardipine had little overall effect on gross cardiac conduction, at spontaneous heart rate. 3 Dogs that received oral 1-2 mg kg-1 nicardipine daily for 16 weeks and then survived 1 week occlusion of the left anterior descending coronary artery (LAD) developed a superior coronary collateral circulation compared with untreated animals. 4 Nicardipine given by three different dosing schedules to baboons markedly limited myocardial infarction over a 6 h period of LAD occlusion. 5 Compared with a group of completely untreated dogs, there was protection of the myocardium in the animals given nicardipine that survived 3 months occlusion of the LAD. ImagesFigure 7 PMID:4027150

Alps, B. J.; Calder, C.; Wilson, A.

1985-01-01

17

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

18

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

19

Imaging diagnosis--magnetic resonance imaging findings in a dog with sequential brain infarction.  

PubMed

An adult greyhound was evaluated on three occasions for acute, intracranial neurologic signs. Based on magnetic resonance (MR) imaging, there were T2-hyperintense and T1-hypointense, noncontrast enhancing lesions in the cerebellum, and brain stem. Using diffusion-weighted imaging (DWI), the lesions were characterized initially by restricted water diffusion. The presumptive diagnosis on each occasion was acute ischemic cerebrovascular accident leading to infarction. This allowed us to characterize the changes in appearance of infarcted neural tissue on the standard MR sequences over time, and to confirm that the DWI could be successfully used in low-field imaging. © 2012 Veterinary Radiology & Ultrasound. PMID:22731883

Major, Alison C; Caine, Abby; Rodriguez, Sue B; Cherubini, Giunio B

2012-01-01

20

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.

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

2014-01-01

21

Scattered Brain Infarct Pattern on Diffusion-Weighted Magnetic Resonance Imaging in Patients with Acute Ischemic Stroke  

Microsoft Academic Search

Background and Purpose: Infarct patterns on brain imaging contribute to the etiologic classification of ischemic stroke. However, the association of specific subtypes of infarcts and etiologic mechanisms is often weak, and acute lesions are frequently missed on initial computed tomography (CT). Diffusion-weighted imaging (DWI) is superior in visualizing acute ischemic lesions as compared to CT and conventional magnetic resonance imaging

Hans-Christian Koennecke; Johannes Bernarding; Jürgen Braun; Andreas Faulstich; Chris Hofmeister; Roland Nohr; Stefanie Leistner; Peter Marx

2001-01-01

22

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

23

Strategic infarcts in vascular dementia. A clinical and brain imaging experience.  

PubMed

The mechanisms of dementia resulting from small deep infarctions are incompletely understood. The thesis underlying the concept of "multi-infarct dementia" is that multiple lesions have a synergistic effect on mental functions, resulting in dementia irrespective of specific location or volume. In this report, we summarize our experience with six patients reported previously along with additional patients examined subsequently, whose clinical features and brain imaging findings allow an alternative formulation for dementia resulting from lacunar stroke. The six initial patients presented with an abrupt change in behavior after acute infarction involving the inferior genu of the internal capsule documented by computed tomography (CT) and magnetic resonance imaging (MRI). The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia were evident in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients using 133xenon regional cerebral blood flow (rCBF) and single photon emission computed tomography (SPECT) showed focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. Perfusion was also defective in the medial and laterial temporal cortex. Important pathways of the limbic system traverse the inferior capsule in the region of the genu. Corticothalamic and thalamocortical fibers form the thalamic peduncles which detach from the internal capsule and enter the thalamus at its rostral and caudal poles and along its dorsal surface. The anterior thalamic peduncle, conveys reciprocal connections between the dorsomedial nucleus and the cingulate gyrus, as well as the prefrontal and orbitofrontal cortex. The inferior thalamic peduncle carries fibers which connect the thalamus with orbitofrontal, insular, and temporal cortex, as well as the amygdala via the ansa peduncularis to the ventral amygdalofugal pathway. Thus, damage to one or both white-matter tracts may occur with infarctions in the region of the inferior genu, causing striking frontal behavioral effects and memory loss in our patients associated with functional deactivation of the ipsilateral frontal and temporal cortex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7763329

Tatemichi, T K; Desmond, D W; Prohovnik, I

1995-03-01

24

Cellular prion protein is increased in the plasma and peri-infarcted brain tissue after acute stroke.  

PubMed

The physiologic properties of the normal cellular prion protein (PrP(C)) have not been established fully, although recent evidence showed its upregulation in cerebral ischaemia. Using patients, animal models, and in vitro studies we aimed to identify in detail the expression and localization of PrP(C) in ischemic stroke. Patients in acute phase of ischaemic stroke had increased plasma levels of circulating PrP(C) as compared to healthy age- and gender-matched controls (3.1 +/- 1.4 vs. 1.9 +/- 0.7 ng/ml, P = 0.002). Immunohistochemistry showed increased expression of PrP(C) in the soma of peri-infarcted neurones as well as in the endothelial cells (EC) of micro-vessels and inflammatory cells in peri-infarcted brain tissue from patients who survived for 2-34 days after an initial stroke. The same pattern was repeated 1-48 hr after MCAO. RT-PCR showed increased gene expression of PrP(C) by human foetal neurons (HFN) after 12 hr of oxygen glucose deprivation (OGD), which remained increased after 24 hr reperfusion. Western blotting confirmed that protein expression was similarly upregulated, and fluorescent labeling showed a notable increase in peri-nuclear and axonal PrP(C) staining intensity. Increased plasma PrP(C) seems to reflect endogenous expression in acute stroke-affected brain tissue. Increased cellular expression in peri-infarcted regions may influence hypoxia-induced cell damage, although the effects on EC survival and angiogenesis remain to be elucidated. PMID:17149767

Mitsios, Nicholas; Saka, Mohamad; Krupinski, Jerzy; Pennucci, Roberta; Sanfeliu, Coral; Miguel Turu, Marta; Gaffney, John; Kumar, Pat; Kumar, Shant; Sullivan, Matthew; Slevin, Mark

2007-02-15

25

Higher Serum Triglyceride Level in Patients with Acute Ischemic Stroke Is Associated with Lower Infarct Volume on CT Brain Scans  

Microsoft Academic Search

We investigated the relationship between serum triglyceride level and acute ischemic stroke severity using infarct volume on CT brain scans as a marker. A total of 121 consecutive acute ischemic stroke patients (53 males and 68 females, age 47–93 years) with anterior circulation (75%), posterior circulation (9%) or lacunar infarcts (16%) were examined. All patients were admitted within 24 h

Slaven Pikija; Vladimir Trkulja; Nedeljko Sokol

2006-01-01

26

Are acute infarcts the cause of leukoaraiosis? Brain mapping for 16 consecutive weeks.  

PubMed

Neuroimaging of older adults commonly reveals abnormality (leukoaraiosis) in the cerebral white matter. Studies have established that extensive leukoaraiosis predicts dementia and disability, but the pathogenesis of leukoaraiosis remains unclear. We recruited 5 patients with leukoaraiosis and performed magnetic resonance mapping of the brain for 16 consecutive weeks. We observed tiny lesions arising de novo in the cerebral white matter. These lesions were clinically silent. They had the signature features of acute ischemic stroke. With time, the characteristics of these lesions approached those of pre-existing leukoaraiosis. Together, these findings suggest that tiny silent acute infarcts are a cause of leukoaraiosis. Ann Neurol 2014;76:899-904. PMID:25283088

Conklin, John; Silver, Frank L; Mikulis, David J; Mandell, Daniel M

2014-12-01

27

Changes in neuropeptide Y protein expression following photothrombotic brain infarction and epileptogenesis.  

PubMed Central

This study characterized morphological changes in the cortex and hippocampus of Sprague-Dawley rats following photothrombotic infarction and epileptogenesis with emphasis on the distribution of neuropeptide Y (NPY) expression. Animals were lesioned in the left sensorimotor cortex and compared with age-matched naïve and sham-operated controls by immunohistochemical techniques at 1, 3, 7, and 180 days post-lesioning (DPL). NPY immunostaining was assessed by light microscopy and quantified by the optical fractionator technique using unbiased stereological methods. At 1, 3, and 7 DPL, the number of NPY-positive somata in the lesioned cortex was increased significantly compared to controls and the contralateral cortex. At 180 DPL, lesioned epileptic animals with frequent seizure activity demonstrated significant increases of NPY expression in the cortex, CA1, CA3, hilar interneurons, and granule cells of the dentate gyrus. In addition to NPY immunostaining, neuronal degeneration, cell death/cell loss, and astroglial response were assessed with cell-specific markers. Nissl and NeuN staining showed reproducible infarctions at each investigated time point. FJB-positive somata were most abundant in the infarct core at 1 DPL, decreased markedly at 3 DPL, and virtually absent by 7 DPL. Activated astroglia were detected in the cortex and hippocampus following lesioning and the development of seizure activity. In summary, NPY protein expression and morphological changes following cortical photothrombosis were time-, region- and pathologic state-dependent. Alterations in NPY expression may reflect reactive or compensatory responses of the rat brain to acute infarction and to the development and expression of epileptic seizures. PMID:17123484

Kharlamov, Elena A.; Kharlamov, Alexander; Kelly, Kevin M.

2007-01-01

28

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

29

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

30

A novel embolic stroke model resembling lacunar infarction following proximal middle cerebral artery occlusion in beagle dogs.  

PubMed

It is estimated that lacunar infarcts account for 25% of all ischemic strokes, but its exact etiology is still on debating. The existing controversies include whether the embolisms can indeed cause lacunar stroke in humans or animal models. We hypothesized that lacunar infarction can be induced by the proximal middle cerebral artery (MCA) segmental occlusion involving the orifices of lenticulostriate arteries in animal models, which have abundant distal cerebral collateral anastomosis. Our work here establishes a proximal MCA occlusion model using thrombi (autologous blood clots about 1.7 mm in diameter and 5 mm in length) in 8 beagle dogs, evaluates the progression of ischemic lesions at 30 min interval within 6 h after embolization using the diffusion weighted imaging (DWI), and discusses the potential mechanisms of lacunar infarction. Our results indicate that the left proximal MCAs can be successfully occluded in all dogs using interventional single-thrombus method. The small solitary or multiple ischemic lesions shown in DWI were observed in the deep brain area, with the mean detecting time of 1.21 ± 0.45 h using DWI and diameter of 6.62 ± 0.60mm in 6h-DWI after procedure. In conclusion, our method established an ischemic model which can recapitulate the radiologic and histologic changes in lacunar infarcts, suggesting that emboli can cause lacunar infarcts in animal model. PMID:22722089

Liu, Sheng; Hu, Wei-Xing; Zu, Qing-Quan; Lu, Shan-Shan; Xu, Xiao-Quan; Sun, Lei; Zhou, Wei-Zhong; Shi, Hai-Bin

2012-07-30

31

The epidemiology of silent brain infarction: a systematic review of population-based cohorts  

PubMed Central

Background Cerebral infarction is a commonly observed radiological finding in the absence of corresponding, clinical symptomatology, the so-called silent brain infarction (SBI). SBIs are a relatively new consideration as improved imaging has facilitated recognition of their occurrence. However, the true incidence, prevalence and risk factors associated with SBI remain controversial. Methods Systematic searches of the Medline and EMBASE databases from 1946 to December 2013 were performed to identify original studies of population-based adult cohorts derived from community surveys and routine health screening that reported the incidence and prevalence of magnetic resonance imaging (MRI)-determined SBI. Results The prevalence of SBI ranges from 5% to 62% with most studies reported in the 10% to 20% range. Longitudinal studies suggest an annual incidence of between 2% and 4%. A strong association was seen to exist between epidemiological estimates of SBI and age of the population assessed. Hypertension, carotid stenosis, chronic kidney disease and metabolic syndrome all showed a strong association with SBI. Heart failure, coronary artery disease, hyperhomocysteinemia and obstructive sleep apnea are also likely of significance. However, any association between SBI and gender, ethnicity, tobacco or alcohol consumption, obesity, dyslipidemia, atrial fibrillation and diabetes mellitus remains unclear. Conclusions SBI is a remarkably common phenomenon and endemic among older people. This systematic review supports the association of a number of traditional vascular risk factors, but also highlights disparities between clinically apparent and silent strokes, potentially suggesting important differences in pathophysiology and warranting further investigation. PMID:25012298

2014-01-01

32

Continuous EEG monitoring for the detection of seizures in traumatic brain injury, infarction, and intracerebral hemorrhage: "to detect and protect".  

PubMed

Brain injury results in a primary pathophysiologic response that enables the brain to have seizures. Seizures occur frequently after traumatic and nontraumatic intracerebral bleeding. These seizures can be nonconvulsive, and if one does not monitor for seizures, one will not know they are occurring. The use of continuous EEG monitoring (cEEG) to detect brain arrhythmias after a primary insult, much in way that cardiac arrhythmias are detected after myocardial infarction, can influence treatment decisions and mitigate some of the pathophysiologic natural history of brain injuries. Seizures after brain injury worsen clinical outcome and need to be treated. In summary, cEEG is a valuable clinical instrument "to detect and protect," i.e., to detect seizures and protect the brain from seizure-related injury in critically ill patients, whose brains are often in a particularly vulnerable state. PMID:15805809

Vespa, Paul

2005-04-01

33

Myocardial infarction and intramyocardial injection models in swine  

PubMed Central

Sustainable and reproducible large animal models that closely replicate the clinical sequelae of myocardial infarction (MI) are important for the translation of basic science research into bedside medicine. Swine are well accepted by the scientific community for cardiovascular research, and they represent an established animal model for preclinical trials for US Food and Drug Administration (FDA) approval of novel therapies. Here we present a protocol for using porcine models of MI created with a closed-chest coronary artery occlusion-reperfusion technique. This creates a model of MI encompassing the anteroapical, lateral and septal walls of the left ventricle. This model infarction can be easily adapted to suit individual study design and enables the investigation of a variety of possible interventions. This model is therefore a useful tool for translational research into the pathophysiology of ventricular remodeling and is an ideal testing platform for novel biological approaches targeting regenerative medicine. This model can be created in approximately 8–10 h. PMID:22790084

McCall, Frederic C; Telukuntla, Kartik S; Karantalis, Vasileios; Suncion, Viky Y; Heldman, Alan W; Mushtaq, Muzammil; Williams, Adam R; Hare, Joshua M

2014-01-01

34

Late-onset Depression in the Absence of Stroke: Associated with Silent Brain Infarctions, Microbleeds and Lesion Locations  

PubMed Central

Background: Late-onset depression (LOD) is a frequent mood disorder among elderly. Previous studies have proved that LOD is associated with cerebral silent lesions especially white matter lesions (WML) and yielded the “vascular depression” hypothesis to explain the pathogenesis of LOD. However, there were relatively few studies about the association between silent brain infarctions (SBIs), microbleeds (MBs) and the prevalence of LOD. In this study we sought to evaluate the presence, accumulation and locations of SBIs and MBs, and explore the possible association between them and LOD. Methods: 65 patients of LOD diagnosed according to DSM-IV and 270 subjects of control group were enrolled and scanned by MRI to analyze the presence, numbers and locations of SBIs and MBs. Clinical and radiological characteristics were compared between LOD patients and control group. Logistic regression models were constructed to identify the independent risk factors for LOD. Results: LOD patients had higher prevalence and numbers of both SBIs and MBs. SBIs and MBs in the left hemisphere, SBIs in basal ganglia and lobar MBs were all independent risk factors for LOD. Conclusion: The presence of both SBIs and MBs were associated with a higher rate LOD. Lesions in some specific locations might be critical for the presence of LOD. PMID:24782647

Wu, Ri-Han; Feng, Chao; Xu, Yu; Hua, Ting; Liu, Xue-Yuan; Fang, Min

2014-01-01

35

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

36

Data-Brain Modeling Based on Brain Informatics Methodology  

Microsoft Academic Search

This paper presents a case study on data-brain construction based on brain informatics (BI) methodology. The data-brain is a conceptual brain data model, which represents functional relationships among multiple human brain data sources, with respect to all major aspects and capabilities of human information processing system for systematic investigation and understanding of human intelligence. On one hand, developing such a

Jianhui Chen; Ning Zhong

2008-01-01

37

The time course of ischemic damage and cerebral perfusion in a rat model of space-occupying cerebral infarction.  

PubMed

We aimed to establish a rat model of space-occupying hemispheric infarction to evaluate potential treatment strategies. For adequate timing of therapy in future experiments, we studied the development of tissue damage, edema formation, and perfusion over time with different MRI techniques. Permanent middle cerebral artery (MCA) occlusion was performed in 32 Fisher-344 rats. Forty-six MRI experiments including diffusion weighted (DW), T2-weighted (T2W), flow-sensitive alternating inversion recovery (FAIR) perfusion-weighted, and T1-weighted (T1W) imaging before and after gadolinium were performed at 1, 3, 8, 16, 24, and 48 h of ischemia. MCA occlusion consistently led to infarction of the complete MCA territory. Mortality was 75%. Lesion volumes as derived from apparent diffusion coefficient (ADC) and T2 maps increased to maximum values of 400+/-48 mm3 at 24 h and 420+/-54 mm3 at 48 h of ischemia, respectively. Midline shift peaked at 24 h. The area with diffusion-perfusion deficit decreased to a minimum at 24 h after onset of ischemia and perfusion of the contralateral hemisphere dropped at the same time point. Leakage of gadolinium through the blood-brain barrier in the entire infarct occurred within 3 h of ischemia. Permanent intraluminal MCA occlusion in Fisher-344 rats is an adequate model for space-occupying cerebral infarction. Rats may benefit from intervention aimed at reducing tissue shift and intracranial pressure (ICP), and at improving cerebral blood flow, if initiated before 24 h after MCA occlusion. The value of treatment modalities depending on an intact blood-brain barrier should be questioned. PMID:15196969

Hofmeijer, J; Veldhuis, W B; Schepers, J; Nicolay, K; Kappelle, L J; Bär, P R; van der Worp, H B

2004-07-01

38

Migraine Headache in Middle-Age and Late-Life Brain Infarcts: The Age Gene/Environment Susceptibility - Reykjavik Study  

PubMed Central

Context Migraine is considered to be an episodic condition with no long-term consequences. However, recent studies suggest that migraine attacks may be associated with pathologic changes in the brain, particularly in the cerebellum. Objective To determine whether, compared to those not reporting symptoms, individuals reporting migraine symptoms in mid-life, particularly aura, are at increased risk of late-life infarct-like lesions (hereafter referred to as infarcts). Design A population based cohort of men and women (b 1907-35) followed since 1967, answered questions about migraine symptoms in mid-life (mean age 51, range 33–65), more than 26 years prior to a late-life exam when brain MRI was acquired. Those reporting headaches once or more per month were asked about migraine symptoms, including nausea, unilateral location, photophobia, visual disturbance, and numbness. We classified headache sufferers as having migraine without aura (MO), migraine with aura (MA), or non-migraine headache. A comprehensive cardiovascular risk assessment was performed at both examinations. Setting Population-based study in Reykjavik, Iceland Participants Men and women (n=4689, 57% women). Main Outcome Measure Presence of infarcts – total and specifically located in the cortical, sub-cortical, and cerebellar regions. Results After adjusting for age, sex, and follow-up time, compared to those not reporting headaches once or more per month (n=3243), those with mid-life MA (n=361) had an increased risk of late-life infarcts (adjusted OR, 1.4; 95% confidence interval [CI], 1.1–1.8) that specifically reflected an association with cerebellar lesions in women (Women: 23.0% vs. 14.5%, adjusted OR 1.9; 95% CI 1.4–2.6 vs. Men 19.3% vs. 21.3%, adjusted OR, 1.0; 95% CI 0.6–1.8, p<0.04 for interaction by sex). There was no increased risk associated with mid-life MO or non-migraine headache or for other brain regions. Conclusions Migraine with aura in mid-life was associated with late-life prevalence of cerebellar infarcts on MRI. This association was statistically significant only for women. This is consistent with the hypothesis that MA in mid-life is associated with late-life vascular disease that appears to be specific for the cerebellum and in women. PMID:19549973

Scher, Ann I; Gudmundsson, Larus S; Sigurdsson, Sigurdur; Ghambaryan, Anna; Aspelund, Thor; Eiriksdottir, Gudny; van Buchem, Mark A.; Gudnason, Vilmundur; Launer, Lenore J.

2011-01-01

39

Neuroprotective effects of focal brain cooling on photochemically-induced cerebral infarction in rats: analysis from a neurophysiological perspective.  

PubMed

Although systemic hypothermia provides favorable outcomes in stroke patients, it has only been adopted in a limited number of patients because of fatal complications. To resolve these issues, focal brain cooling (FBC) has recently drawn attention as a less-invasive treatment for brain injuries. Therefore, we investigated whether FBC has a favorable effect on focal cerebral ischemia (FCI). Male-adult-Wistar rats were used. Under general anesthesia, a small burr hole was made and FCI was induced in the primary sensorimotor area (SI-MI) using photothrombosis. An additional craniotomy was made over the SI-MI and FBC was performed at a temperature of 15°C for 5h. Electrocorticograms (ECoG) were recorded on the border cortex of the ischemic focus. Thereafter, rats were sacrificed and the infarct area was measured. In another experiment, rats were allowed to recover for 5 days after cooling and neurobehavioral function was evaluated. FBC suppressed all ECoG frequency bands during and after cooling (p<0.05), except for the delta frequency band in the precooling versus rewarming periods. The injured areas in the cooling and non-cooling groups were 0.99±0.30 and 1.71±0.54 mm(2), respectively (p<0.03). The grip strength at 2 days after surgery was preserved in the cooling group (p<0.05). We report the novel finding that epileptiform discharges were suppressed in the ischemic border, the infarct area was reduced and neurobehaviour was preserved by FBC. These results indicate that FBC is neuroprotective in the ischemic brain and has demonstrated therapeutic potential for cerebral infarction. PMID:23268352

He, Yeting; Fujii, Masami; Inoue, Takao; Nomura, Sadahiro; Maruta, Yuichi; Oka, Fumiaki; Shirao, Satoshi; Owada, Yuji; Kida, Hiroyuki; Kunitsugu, Ichiro; Yamakawa, Toshitaka; Tokiwa, Tatsuji; Yamakawa, Takeshi; Suzuki, Michiyasu

2013-02-25

40

AITA : Brain Modelling John A. Bullinaria, 2003  

E-print Network

? Development ­ Learning and Maturation Adult Performance Measures Brain Damage / Neuropsychological Deficits 2AITA : Brain Modelling © John A. Bullinaria, 2003 1. Brain Modelling ­ What Needs Modelling Systems #12;w3s3-2 Brain Modelling ­ What Needs Modelling? It makes sense to use all available information

Bullinaria, John

41

The effect of acute medication with cilostazol, an anti-platelet drug, on the outcome of small vessel brain infarction.  

PubMed

Our objective was to investigate the effect of cilostazol in acute therapy for small vessel stroke patients. The neurologic deficits in some patients of small vessel brain infarction will progress even if a patient takes immediate medical treatments including aspirin or other antiplatelet drugs. In Japan, cilostazol, presenting not only the antiplatelet effect but also the arteriole dilation, is used for treatment of ischemic stroke. In this study, acute stroke patients with small vessel occlusion were treated with cilostazol instead of aspirin in the conventional medication after 2010. Therefore, patients between April 2007 and March 2009 were classified into the conventional group (group-con, n=220), and patients between April 2010 and March 2012 were classified into the cilostazol group (group-cilo, n=230). Enrolled patients were classified into lacunar infarction (LI) and branch atheromatous disease. Progressing stroke was defined as the increase of National Institutes of Health Stroke Scale score of 2 or more within 48 hours. The clinical outcome was assessed by the modified Rankin Scale (mRS) score at 1 month. As the result, the significant reduction in progressing stroke was dominant in the LI of brainstem (P=.01). The length of hospital stay was significantly shorter in the group-cilo compared with the group-con (18.6 and 21.2 days, P=.03). Moreover, mRS score at 1 month was significantly lower in the group-cilo than the group-con (1.9 and 2.3, P=.03). In conclusion, cilostazol reduced the risk of early neurologic deterioration of patients with small vessel brain infarction. It is eagerly desired to conduct a large randomized control trial. PMID:24513481

Nakase, Taizen; Sasaki, Masahiro; Suzuki, Akifumi

2014-07-01

42

Antiphospholipid Antibodies, Brain Infarcts, and Cognitive and Motor Decline in Aging (ABICMA): Design of a Community-based, Longitudinal, Clinical-pathological Study  

PubMed Central

The overall goal of the Antiphospholipid antibodies, Brain Infarcts, and Cognitive and Motor decline in Aging study (ABICMA) is to test the hypothesis that antiphospholipid antibodies (aPL) are associated with an increased risk of pathologically-proven brain infarcts and related to cognitive and motor decline in aging. Putative biologic mechanisms underlying the association of aPL with infarcts and the relation of aPL with clinical outcomes of cognitive and motor impairment, including vascular and other processes, will be examined. The design of this longitudinal, clinical-pathologic study involves quantifying four aPL assays, and relating these to brain infarcts, and to cognitive and motor decline. Vascular mechanisms assessed using ante-mortem magnetic resonance neuroimaging and postmortem neuropathology, as well as non-vascular mechanisms of inflammation and blood-brain barrier permeability alterations will be examined as plausible mediators of the relation of aPL to cognitive and motor impairment. We will take advantage of ante-mortem biologic specimens (longitudinally-collected sera and plasma from which aPL, annexins, C-reactive protein, and matrix metalloproteinases will be quantified), and clinical, neuroimaging, and postmortem neuropathologic data from about 800 older, community-dwelling women and men who have agreed to brain autopsy at time of death, participating in one of two ongoing studies of aging: the Religious Orders Study and the Memory and Aging Project. PMID:23095514

Arvanitakis, Zoe; Brey, Robin L.; Rand, Jacob H.; Schneider, Julie A.; Leurgans, Sue E.; Yu, Lei; Buchman, Aron S.; Arfanakis, Konstantinos; Fleischman, Debra A.; Boyle, Patricia A.; Bennett, David A.; Levine, Steven R.

2013-01-01

43

Traumatic dissection of the internal carotid artery: simultaneous infarct of optic nerve and brain  

PubMed Central

Key Clinical Message Traumatic intracranial internal carotid artery dissection is a rare but significant cause of stroke in patients in their forties, leading to high morbidity and mortality. Simultaneous ischemic stroke and optic nerve infarction can occur. Clinical suspicion of dissection is determining in the acute management. PMID:25356244

Correa, Edgar; Martinez, Braulio

2014-01-01

44

Tachycardia in Post-Infarction Hearts: Insights from 3D Image-Based Ventricular Models  

PubMed Central

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

45

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

46

Embolic brain infarction related to posttraumatic occlusion of vertebral artery resulting from cervical spine injury: a case report  

PubMed Central

Introduction The frequency of vertebrobasilar ischemia in patients with cervical spine trauma had been regarded as low in many published papers. However, some case reports have described cervical spine injury associated with blunt vertebral artery injury. Many aspects of the management of vertebral artery injuries still remain controversial, including the screening criteria, the diagnostic modality, and the optimal treatment for various lesions. The case of a patient who had a brain infarction due to recanalization of his occluded vertebral artery following open reduction of cervical spinal dislocation is presented here. Case presentation A 41-year-old Asian man presented with C4 to C5 distractive flexion injury manifesting with quadriplegia and anesthesia below his C3 cord level (including phrenic nerve paralysis), and bowel and bladder dysfunction. Magnetic resonance angiography and computed tomography angiography showed left extracranial vertebral artery occlusion and patent contralateral vertebral artery. He was observed without antiplatelet and/or anticoagulation therapy, and underwent surgery (open reduction and internal fusion of C4 to C5, and tracheostomy) 8 hours after the injury. After surgery, supraspinal symptoms such as left horizontal nystagmus and left homonymous hemianopsia led to cranial computed tomography and magnetic resonance imaging, which showed left-side cerebellar infarction in his posterior inferior cerebellar artery territory and right-side posterior cerebral artery infarction. Magnetic resonance angiography and computed tomography angiography demonstrated patent bilateral vertebral artery (but hypoplastic right vertebral artery) and occluded right posterior cerebral artery. His injured vertebral artery was treated conservatively, which did not cause any other ischemic complications. Conclusions The management of asymptomatic vertebral artery injury is controversial with several treatment options available, including observation alone, antiplatelet therapy, anticoagulation therapy, or invasive intervention. Although there are some reports in which management with observation alone is described as safe, we should pay serious attention to the vertebral artery injury caused by cervical spine trauma. PMID:25316102

2014-01-01

47

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

PubMed

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; Kim, Jiha

2014-08-01

48

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

49

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

50

Relationship of Left Atrial Global Peak Systolic Strain with Left Ventricular Diastolic Dysfunction and Brain Natriuretic Peptide Level in Patients Presenting with Non-ST Elevation Myocardial Infarction  

PubMed Central

Background In patients presenting with non-ST elevation myocardial infarction, we investigated the relationship of left atrial deformational parameters evaluated by 2-dimensional speckle tracking imaging (2D-STI) with conventional echocardiographic diastolic dysfunction parameters and brain natriuretic peptide level. Material/Methods We enrolled 74 non-ST segment elevation myocardial infarction patients who were treated with percutaneous coronary intervention and 58 healthy control subjects. Non-ST segment elevation myocardial infarction patients had echocardiographic examination 48 h after the percutaneous coronary intervention procedure and venous blood samples were drawn simultaneously. In addition to conventional echocardiographic parameters, left atrial strain curves were obtained for each patient. Average peak left atrial strain values during left ventricular systole were measured. Results BNP values were higher in non-ST segment elevation myocardial infarction patients compared to controls. Mean left atrium peak systolic global longitudinal strain in Group 2 (the control group) was higher than in the non-ST segment elevation myocardial infarction group. Left atrium peak systolic global longitudinal strain was significantly correlated with left ventricular ejection fraction. There was a significant inverse correlation between left atrium peak systolic global longitudinal strain and brain natriuretic peptide level, left atrium volume maximum, and left atrium volume minimum. Conclusions Our study shows that Left atrium peak systolic global longitudinal strain values decreased consistently with deteriorating systolic and diastolic function in non-ST segment elevation myocardial infarction patients treated with percutaneous coronary intervention. Left atrium peak systolic global longitudinal strain measurements may be helpful as a complimentary method to evaluate diastolic function in this patient population. PMID:25338184

De?irmenci, Hüsnü; Bak?rc?, Eftal Murat; Demirta?, Levent; Duman, Hakan; Hamur, Hikmet; Ceyhun, Gökhan; Topal, Ergün

2014-01-01

51

Relationship of Left Atrial Global Peak Systolic Strain with Left Ventricular Diastolic Dysfunction and Brain Natriuretic Peptide Level in Patients Presenting with Non-ST Elevation Myocardial Infarction.  

PubMed

Background In patients presenting with non-ST elevation myocardial infarction, we investigated the relationship of left atrial deformational parameters evaluated by 2-dimensional speckle tracking imaging (2D-STI) with conventional echocardiographic diastolic dysfunction parameters and brain natriuretic peptide level. Material and Methods We enrolled 74 non-ST segment elevation myocardial infarction patients who were treated with percutaneous coronary intervention and 58 healthy control subjects. Non-ST segment elevation myocardial infarction patients had echocardiographic examination 48 h after the percutaneous coronary intervention procedure and venous blood samples were drawn simultaneously. In addition to conventional echocardiographic parameters, left atrial strain curves were obtained for each patient. Average peak left atrial strain values during left ventricular systole were measured. Results BNP values were higher in non-ST segment elevation myocardial infarction patients compared to controls. Mean left atrium peak systolic global longitudinal strain in Group 2 (the control group) was higher than in the non-ST segment elevation myocardial infarction group. Left atrium peak systolic global longitudinal strain was significantly correlated with left ventricular ejection fraction. There was a significant inverse correlation between left atrium peak systolic global longitudinal strain and brain natriuretic peptide level, left atrium volume maximum, and left atrium volume minimum. Conclusions Our study shows that Left atrium peak systolic global longitudinal strain values decreased consistently with deteriorating systolic and diastolic function in non-ST segment elevation myocardial infarction patients treated with percutaneous coronary intervention. Left atrium peak systolic global longitudinal strain measurements may be helpful as a complimentary method to evaluate diastolic function in this patient population. PMID:25338184

De?irmenci, Hüsnü; Bak?rc?, Eftal Murat; Demirta?, Levent; Duman, Hakan; Hamur, Hikmet; Ceyhun, Gökhan; Topal, Ergün

2014-01-01

52

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

53

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

54

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

55

Thromboembolic Events Predispose the Brain to Widespread Cerebral Infarction After Delayed Transient Global Ischemia in Rats  

Microsoft Academic Search

Background and Purpose—Transient distal platelet accumulation after common carotid artery thrombosis (CCAT) leads to hemodynamic, metabolic, and molecular events that may influence the response of the postthrombotic brain to secondary insults. We investigated how a thromboembolic insult would affect histopathological outcome when combined with an ischemic insult induced 24 hours later. Methods—Three groups of rats underwent either (1) CCAT 110

W. Dalton Dietrich; Gary Danton; Aviva C. Hopkins; Ricardo Prado

56

Hierarchical Models in the Brain  

PubMed Central

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

2008-01-01

57

Sulfonylurea Receptor 1 Expression in Human Cerebral Infarcts  

PubMed Central

Abstract 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

2013-01-01

58

Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats.  

PubMed

The effects of brain-derived peptides (BDP; Cerebrolysin) upon the amount of brain injury due to focal brain ischemia were assessed. Male Thomae rats were divided randomly into a sham-operated group (n = 5), an ischemic control (untreated) group (n = 7) and an ischemic BDP-treated group (n = 6) and subjected to reversible middle cerebral artery occlusion (MCAO) for 2h followed by 90min of reperfusion. Local cortical blood flow (LCBF) was monitored by Laser-Doppler flowmetry to assess the MCAO and to measure the blood flow in regions peripheral to the infarction. Infarcted areas of the hippocampus and subcortical structures were quantified in hematoxylin and eosin (H&E) stainings. Functional disturbances of the neurons were detected by immunohistochemical staining of the microtubule associated protein MAP2. Moreover, brain edema was estimated morphometrically. LCBF was estimated from the periphery of infarcted areas and was reduced to 55 to 65% of baseline values (p < 0.05). Reperfusion led to LCBF being increased again to baseline values. No differences in LCBF between the control and the BDP-treated animals were found. In the hippocampus, BDP-treated animals showed a significant reduction of loss of MAP2 immunoreactivity in the subiculum and CA1 region by 59% and 64%, respectively, in comparison to control animals (p < 0.05). The amount of irreversibly damaged neurons in these regions was decreased in tendency. However, the inner blade of the dentate gyrus in BDP-treated animals showed a significant reduction of neuronal injury by 98% (p < 0.05). Likewise, BDP treatment reduced the size of the areas showing a loss of MAP2 immunoreactivity in the thalamic and hypothalamic structures by 51% and in the mesencephalon by 81% (p < 0.05). The size of the infarcted areas in these regions (H&E) was reduced in tendency. In the caudate putamen, no protective effect of BDP-treatment could be proven. Cerebral infarction was accompanied by an increase in the volume of the ischemic hemisphere by 10 +/- 1% in the control and 8 +/- 1% in the BDP-treated animals. These findings indicate a beneficial effect for BDP treatment in ameliorating the early effects of focal brain ischemia. PMID:9700666

Schwab, M; Antonow-Schlorke, I; Zwiener, U; Bauer, R

1998-01-01

59

Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke  

Microsoft Academic Search

Background  Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical\\u000a scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more\\u000a than one year to evaluate the effect of edaravone which might reduce ischemic damage.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We sequentially enrolled acute

Taizen Nakase; Shotaroh Yoshioka; Akifumi Suzuki

2011-01-01

60

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

61

Novel drug development opportunity for relaxin in acute myocardial infarction: evidences from a swine model  

Microsoft Academic Search

The hormone relaxin has been shown to cause coronary vasodilation and to prevent ischemia\\/reperfusion-induced cardiac injury in rodents. This study provides evidence that relaxin, used as an adjunctive drug to coronary reperfusion, reduces the functional, biochemical, and histopathological signs of myocardial injury in an in vivo swine model of heart ischemia\\/reperfusion, currently used to test cardiotropic drugs for myocardial infarction.

Avio-Maria Perna; Emanuela Masini; Silvia Nistri; Vittorio Briganti; Laura Chiappini; Pierluigi Stefano; Mario Bigazzi; Cesco Pieroni; Tatiana Bani Sacchi; Daniele Bani

2005-01-01

62

Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion  

PubMed Central

Brain temperature is elevated in acute ischemic stroke, especially in the ischemic penumbra (IP). We attempted to investigate the dynamic evolution of brain temperature in different ischemic regions in a monkey model of middle cerebral artery occlusion. The brain temperature of different ischemic regions was measured with proton magnetic resonance spectroscopy (1H MRS), and the evolution processes of brain temperature were compared among different ischemic regions. We found that the normal (baseline) brain temperature of the monkey brain was 37.16°C. In the artery occlusion stage, the mean brain temperature of ischemic tissue was 1.16°C higher than the baseline; however, this increase was region dependent, with 1.72°C in the IP, 1.08°C in the infarct core, and 0.62°C in the oligemic region. After recanalization, the brain temperature of the infarct core showed a pattern of an initial decrease accompanied by a subsequent increase. However, the brain temperature of the IP and oligemic region showed a monotonously and slowly decreased pattern. Our study suggests that in vivo measurement of brain temperature could help to identify whether ischemic tissue survives. PMID:23091367

Sun, Zhihua; Zhang, Jing; Chen, Yingmin; Zhang, Yunting; Zhang, Xuejun; Guo, Hong; Yu, Chunshui

2012-01-01

63

High dose intracoronary N-acetylcysteine in a porcine model of ST-elevation myocardial infarction.  

PubMed

We sought to evaluate the safety and efficacy of N-acetylcysteine (NAC) on ischemia and reperfusion in a pig model focusing on cardio-renal protection. High doses of NAC may provide protection from contrast induced nephropathy (CIN). NAC has also been demonstrated to reduce myocardial infarction size and improve left ventricular function after ischemia in both humans and animals studies. In this study we tested the safety and cardiorenal protective efficacy of intracoronary NAC delivered in the radiographic contrast agent in a pig model that simulates the catheter based reperfusion therapy of ST elevation myocardial infarctions. 27 pigs underwent 45 min of ischemia after surgical ligation of distal left descending coronary artery. With coronary reperfusion the animals received at total of 200 mL of the contrast agent Iopamidol with and without NAC to mimic radiographic contrast use during invasive reperfusion therapy. At 24 h the following endpoints were compared: LV function (MRI, echocardiography), myocardial injury (infarct size, area-at-risk, troponin, creatinine kinase) and CIN (creatinine, BUN and renal histology). The effects of NAC on platelet reactivity were also evaluated. Intracoronary administration of NAC administered in the contrast agent is safe. NAC reduces platelet reactivity and there was a trend towards a better cardiac function at 24 h. There was no significant difference in the size of the myocardial infarction. In this model of ischemia-reperfusion high dose NAC did not protect from CIN. High dose intracoronary NAC administered with the radiographic contrast is safe but does not provide significant cardio-renal protection. PMID:23423816

Meyer, Markus; Bell, Stephen P; Chen, Zengyi; Nyotowidjojo, Iwan; Lachapelle, Richard R; Christian, Timothy F; Gibson, Pamela C; Keating, Friederike F; Dauerman, Harold L; LeWinter, Martin M

2013-11-01

64

Neural differentiation of transplanted neural stem cells in a rat model of striatal lacunar infarction: light and electron microscopic observations  

PubMed Central

The increased risk and prevalence of lacunar stroke and Parkinson's disease (PD) makes the search for better experimental models an important requirement for translational research. In this study we assess ischemic damage of the nigrostriatal pathway in a model of lacunar stroke evoked by damaging the perforating arteries in the territory of the substantia nigra (SN) of the rat after stereotaxic administration of endothelin-1 (ET-1), a potent vasoconstrictor peptide. We hypothesized that transplantation of neural stem cells (NSCs) with the capacity of differentiating into diverse cell types such as neurons and glia, but with limited proliferation potential, would constitute an alternative and/or adjuvant therapy for lacunar stroke. These cells showed neuritogenic activity in vitro and a high potential for neural differentiation. Light and electron microscopy immunocytochemistry was used to characterize GFP-positive neurons derived from the transplants. 48 h after ET-1 injection, we characterized an area of selective degeneration of dopaminergic neurons within the nigrostriatal pathway characterized with tissue necrosis and glial scar formation, with subsequent behavioral signs of Parkinsonism. Light microscopy showed that grafted cells within the striatal infarction zone differentiated with a high yield into mature glial cells (GFAP-positive) and neuron types present in the normal striatum. Electron microscopy revealed that NSCs-derived neurons integrated into the host circuitry establishing synaptic contacts, mostly of the asymmetric type. Astrocytes were closely associated with normal small-sized blood vessels in the area of infarct, suggesting a possible role in the regulation of the blood brain barrier and angiogenesis. Our results encourage the use of NSCs as a cell-replacement therapy for the treatment of human vascular Parkinsonism. PMID:22876219

Muneton-Gomez, Vilma C.; Doncel-Perez, Ernesto; Fernandez, Ana P.; Serrano, Julia; Pozo-Rodrigalvarez, Andrea; Vellosillo-Huerta, Lara; Taylor, Julian S.; Cardona-Gomez, Gloria P.; Nieto-Sampedro, Manuel; Martinez-Murillo, Ricardo

2012-01-01

65

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

66

A mathematical model of brain glucose homeostasis  

PubMed Central

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, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB) adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis. PMID:19943948

2009-01-01

67

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

68

Cerebral infarction in childhood bacterial meningitis  

Microsoft Academic Search

Forty-nine children with complicated bacterial meningitis were studied. Thirteen had abnormalities on computed tomography compatible with the diagnosis of brain infarction; one had a brain biopsy with the histological appearance of infarction. Factors exist in childhood bacterial meningitis which are associated with the development of brain infraction.

R D Snyder; J Stovring; A H Cushing; L E Davis; T L Hardy

1981-01-01

69

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

70

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

PubMed

Vertebral artery injury can be a complication of cervical spine injury. Although most cases are asymptomatic, the rare case progresses to severe neurological impairment and fatal outcomes. We experienced a case of bilateral cerebellar and brain stem infarction with fatal outcome resulting from vertebral artery injury associated with cervical spine trauma. A 69-year-old male was admitted to our hospital because of tetraplegia after falling down the stairs and hitting his head on the floor. Marked bony damage of the cervical spine was not apparent on radiographs and CT scans, so the injury was initially considered to be a cervical cord injury without bony damage. However, an intensity change in the intervertebral disc at C5/C6, and a ventral epidural hematoma were observed on MRI. A CT angiogram of the neck showed the right vertebral artery was completely occluded at the C4 level of the spine. Forty-eight hours after injury, the patient lapsed into drowsy consciousness. The cranial CT scan showed a massive low-density area in the bilateral cerebellar hemispheres and brain stem. Anticoagulation was initiated after a diagnosis of the right vertebral artery injury, but the patient developed bilateral cerebellar and brain stem infarction. The patient's brain herniation progressed and the patient died 52 h after injury. We considered that not only anticoagulation but also treatment for thrombosis would have been needed to prevent cranial embolism. We fully realize that early and appropriate treatment are essential to improve the treatment results, and constructing a medical system with a team of orthopedists, radiologists, and neurosurgeons is also very important. PMID:24061492

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

2014-01-01

71

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.

72

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

73

Wistar rats from different suppliers have a different response in an acute myocardial infarction model.  

PubMed

The Wistar rat is a commonly used strain for experimental animal models. Recently it was shown that results vary between studies using Wistar rats of different suppliers. Therefore we studied whether Wistar rats obtained from Harlan Laboratories (Ha, n=24) and Charles River (CR, n=22) had a different outcome in an acute myocardial infarction (AMI) model. AMI was induced in both Ha and CR Wistar rats by one operator. This resulted in a significantly higher survival rate for Ha (79.2±10.2%) compared with CR rats (54.2±10.2%, p<0.05). Furthermore, CR rats had lost significantly more weight after 7 days (-5.9±3.1%) compared with Ha rats (-0.8±1.7%; p<0.001), indicating a worse health status of the CR rats. Paradoxically, the induced infarct was smaller in CR rats (7.3±3.6% of the heart) compared with Ha rats (12.1±4.7%, p<0.05). This indicates that CR rats were less sensitive for the cardiomyocyte damage subsequent to AMI induction, but remarkably showed more clinical side effects indicating that Wistar rats from two suppliers had a different response within the same AMI model. PMID:24445251

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

2014-04-01

74

Brain proteomics identifies potential simvastatin targets in acute phase of stroke in a rat embolic model.  

PubMed

Finding an efficient neuroprotectant is of urgent need in the field of stroke research. The goal of this study was to test the effect of acute simvastatin administration after stroke in a rat embolic model and to explore its mechanism of action through brain proteomics. To that end, male Wistar rats were subjected to a Middle Cerebral Arteria Occlusion and simvastatin (20 mg/kg s.c) (n = 11) or vehicle (n = 9) were administered 15 min after. To evaluate the neuroprotective mechanisms of simvastatin, brain homogenates after 48 h were analyzed by two-dimensional fluorescence Difference in Gel Electrophoresis (DIGE) technology. We confirmed that simvastatin reduced the infarct volume and improved neurological impairment at 48 h after the stroke in this model. Considering our proteomics analysis, 66 spots, which revealed significant differences between groups, were analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry allowing the identification of 27 proteins. From these results, we suggest that simvastatin protective effect can be partly explained by the attenuation of the oxidative and stress response at blood-brain barrier level after cerebral ischemia. Interestingly, analyzing one of the proteins (HSP75) in plasma from stroke patients who had received simvastatin during the acute phase, we confirmed the results found in the pre-clinical model. Our aim was to study statins benefits when administered during the acute phase of stroke and to explore its mechanisms of action through brain proteomics assay. Using an embolic model, simvastatin-treated rats showed significant infarct volume reduction and neurological improvement compared to vehicle-treated group. Analyzing their homogenated brains by two-dimensional fluorescence Difference in Gel Electrophoresis (DIGE) technology, we concluded that the protective effect of simvastatin can be attributable to oxidative stress response attenuation and blood-brain barrier protection after cerebral ischemia. PMID:24661059

Campos-Martorell, Mireia; Salvador, Nelida; Monge, Marta; Canals, Francesc; García-Bonilla, Lidia; Hernández-Guillamon, Mar; Ayuso, María Irene; Chacón, Pilar; Rosell, Anna; Alcazar, Alberto; Montaner, Joan

2014-07-01

75

A rat model of photothrombotic capsular infarct with a marked motor deficit: a behavioral, histologic, and microPET study.  

PubMed

We present a new method for inducing a circumscribed subcortical capsular infarct (SCI), which imposes a persistent motor impairment in rats. Photothrombotic destruction of the internal capsule (IC) was conducted in Sprague Dawley rats (male; n=38). The motor performance of all animals was assessed using forelimb placing, forelimb use asymmetry, and the single pellet reaching test. On the basis of the degree of motor recovery, rats were subdivided into either the poor recovery group (PRG) or the moderate recovery group (MRG). Imaging assessment of the impact of SCI on brain metabolism was performed using 2-deoxy-2-[(18)F]-fluoro-D-glucose ([(18)F]-FDG) microPET (positron emission tomography). Photothrombotic lesioning using low light energy selectively disrupted circumscribed capsular fibers. The MRG showed recovery of motor performance after 1 week, but the PRG showed a persistent motor impairment for >3 weeks. Damage to the posterior limb of the IC (PLIC) is more effective for producing a severe motor deficit. Analysis of PET data revealed decreased regional glucose metabolism in the ipsilesional motor and bilateral sensory cortex and increased metabolism in the contralesional motor cortex and bilateral hippocampus during the early recovery period after SCI. Behavioral, histologic, and functional imaging findings support the usefulness of this novel SCI rat model for investigating motor recovery. PMID:24473479

Kim, Hyung-Sun; Kim, Donghyeon; Kim, Ra Gyung; Kim, Jin-Myung; Chung, Euiheon; Neto, Pedro R; Lee, Min-Cheol; Kim, Hyoung-Ihl

2014-04-01

76

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

77

Assessment of myocardial blood perfusion improved by CD151 in a pig myocardial infarction model  

PubMed Central

Aim: To appraise the efficacy of CD151-induced myocardial therapeutic angiogenesis in a pig myocardial infarction model. Methods: CD151 and anti-CD151 were constructed into the recombinant adeno-associated virus (rAAV) vector. All 26 pigs were subjected to coronary artery ligation or no surgery. Eight weeks after coronary artery ligation, the expression of CD151 was measured by Western blot and immunostaining. Capillary density was evaluated using immunostaining for von Willebrand factor (vWF). 13N-labeled NH3 positron emission computed tomography ([13N]NH3 PET) was measured to assess regional myocardial perfusion and the defect area. Results: CD151 gene delivery could increase the expression of CD151 at protein level. Over-expression of CD151 increased the density of total capillaries in the ischemic myocardium, significantly improved the blood perfusion and reduced the defect area percentage. Conclusion: This study demonstrated that the rAAV-mediated CD151 gene delivery promoted efficient neovascularization and increased the blood perfusion after myocardial infarction in pigs. PMID:19079294

Zuo, Hou-juan; Liu, Zheng-xiang; Liu, Xiao-chun; Yang, Jun; Liu, Tao; Wen, Sha; Wang, Dao-wen; Zhang, Xin

2009-01-01

78

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

79

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.

80

Characterizing preclinical models of ischemic heart failure: differences between LAD and LCx infarctions.  

PubMed

Large animal studies are an important step toward clinical translation of novel therapeutic approaches. We aimed to establish an ischemic heart failure (HF) model with a larger myocardial infarction (MI) relative to previous studies, and characterize the functional and structural features of this model. An MI was induced by occluding the proximal left anterior descending artery (LAD; n = 15) or the proximal left circumflex artery (LCx; n = 6) in Yorkshire pigs. Three pigs with sham procedures were also included. All pigs underwent hemodynamic and echocardiographic assessments before MI, at 1 mo, and 3 mo after MI. Analyses of left ventricular (LV) myocardial mechanics by means of strains and torsion were performed using speckle-tracking echocardiography and compared between the groups. The proximal LAD MI approach induced larger infarct sizes (14.2 ± 3.2% vs. 10.6 ± 1.9%, P = 0.03), depressed systolic function (LV ejection fraction; 39.8 ± 7.5% vs. 54.1 ± 4.6%, P < 0.001), and more LV remodeling (end-systolic volume index; 82 ± 25 ml/m(2) vs. 51 ± 18 ml/m(2), P = 0.02, LAD vs. LCx, respectively) compared with the LCx MI approach without compromising the survival rate. At the papillary muscle level, echocardiographic strain analysis revealed no differences in radial and circumferential strain between LAD and LCx MIs. However, in contrast with the LCx MI, the LAD MI resulted in significantly decreased longitudinal strain. The proximal LAD MI model induces more LV remodeling and depressed LV function relative to the LCx MI model. Location of MI significantly impacts the severity of HF, thus careful consideration is required when choosing an MI model for preclinical HF studies. PMID:25217654

Ishikawa, Kiyotake; Aguero, Jaume; Tilemann, Lisa; Ladage, Dennis; Hammoudi, Nadjib; Kawase, Yoshiaki; Santos-Gallego, Carlos G; Fish, Kenneth; Levine, Robert A; Hajjar, Roger J

2014-11-15

81

Association between Tumor Necrosis Factor-Alpha (–308G?A and –238G?A) Polymorphisms and Homocysteine Levels in Patients with Ischemic Strokes and Silent Brain Infarctions  

Microsoft Academic Search

Background and Purpose: The aims of this study were to evaluate the role of tumor necrosis factor-? (TNF-?) polymorphisms in patients susceptible to ischemic stroke and silent brain infarction (SBI), and to determine the relationship between TNF-? polymorphisms and plasma total homocysteine (tHcy) levels. Methods: We studied 237 patients with ischemic stroke, 257 patients with SBIs, and 216 control subjects.

Ok Joon Kim; Jae Ho Lee; Jeong Kwon Choi; Seung Hun Oh; Seung Ho Hong; Doyeun Oh; Nam Keun Kim

2010-01-01

82

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

83

Monitoring of cell therapy and assessment of cardiac function using magnetic resonance imaging in a mouse model of myocardial infarction  

Microsoft Academic Search

We have developed a mouse severe combined immunodeficient (SCID) model of myocardial infarction based on permanent coronary artery occlusion that allows long-term functional analysis of engrafted human embryonic stem cell-derived cardiomyocytes, genetically marked with green fluorescent protein (GFP), in the mouse heart. We describe methods for delivery of dissociated cardiomyocytes to the left ventricle that minimize scar formation and visualization

Linda W van Laake; Robert Passier; Jantine Monshouwer-Kloots; Marcel G Nederhoff; Dorien Ward-van Oostwaard; Loren J Field; Cees J van Echteld; Pieter A Doevendans; Christine L Mummery

2007-01-01

84

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

85

Multimodal, multidimensional models of mouse brain.  

PubMed

Naturally occurring mutants and genetically manipulated strains of mice are widely used to model a variety of human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison and to facilitate the integration of anatomic, genetic, and physiologic observations from multiple subjects and experiments. We have developed digital atlases of the C57BL/6J mouse brain (adult and neonate) as comprehensive frameworks for storing and accessing the myriad types of information about the mouse brain. Along with raw and annotated images, these contain database management systems and a set of tools for comparing information from different techniques and different animals. Each atlas establishes a canonical representation of the mouse brain and provides the tools for the manipulation and analysis of new data. We describe both these atlases and discuss how they may be put to use in organizing and analyzing data from mouse models of epilepsy. PMID:17767578

Mackenzie-Graham, Allan J; Lee, Erh-Fang; Dinov, Ivo D; Yuan, Heng; Jacobs, Russell E; Toga, Arthur W

2007-01-01

86

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; Castano, Sara; Munoz-Barrutia, Arrate; Prosper, Felipe; Ortiz-de-Solorzano, Carlos

2012-01-01

87

The Detection of Surfactant Proteins A, B, C and D in the Human Brain and Their Regulation in Cerebral Infarction, Autoimmune Conditions and Infections of the CNS  

PubMed Central

Surfactant proteins (SP) have been studied intensively in the respiratory system. Surfactant protein A and surfactant protein D are proteins belonging to the family of collectins each playing a major role in the innate immune system. The ability of surfactant protein A and surfactant protein D to bind various pathogens and facilitate their elimination has been described in a vast number of studies. Surfactant proteins are very important in modulating the host's inflammatory response and participate in the clearance of apoptotic cells. Surfactant protein B and surfactant protein C are proteins responsible for lowering the surface tension in the lungs. The aim of this study was an investigation of expression of surfactant proteins in the central nervous system to assess their specific distribution patterns. The second aim was to quantify surfactant proteins in cerebrospinal fluid of healthy subjects compared to patients suffering from different neuropathologies. The expression of mRNA for the surfactant proteins was analyzed with RT-PCR done with samples from different parts of the human brain. The production of the surfactant proteins in the brain was verified using immunohistochemistry and Western blot. The concentrations of the surfactant proteins in cerebrospinal fluid from healthy subjects and patients suffering from neuropathologic conditions were quantified using ELISA. Our results revealed that surfactant proteins are present in the central nervous system and that the concentrations of one or more surfactant proteins in healthy subjects differed significantly from those of patients affected by central autoimmune processes, CNS infections or cerebral infarction. Based on the localization of the surfactant proteins in the brain, their different levels in normal versus pathologic samples of cerebrospinal fluid and their well-known functions in the lungs, it appears that the surfactant proteins may play roles in host defense of the brain, facilitation of cerebrospinal fluid secretion and maintenance of the latter's rheological properties. PMID:24098648

Schob, Stefan; Schicht, Martin; Sel, Saadettin; Stiller, Dankwart; Kekule, Alexander; Paulsen, Friedrich; Maronde, Erik; Brauer, Lars

2013-01-01

88

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.  

PubMed

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells. PMID:16229956

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

2005-01-01

89

Modeling brain dynamics using computational neurogenetic approach  

Microsoft Academic Search

The paper introduces a novel computational approach to brain dynamics modeling that integrates dynamic gene–protein regulatory\\u000a networks with a neural network model. Interaction of genes and proteins in neurons affects the dynamics of the whole neural\\u000a network. Through tuning the gene–protein interaction network and the initial gene\\/protein expression values, different states\\u000a of the neural network dynamics can be achieved. A

Lubica Benuskova; Nikola Kasabov

2008-01-01

90

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

91

Doppler Ultrasound Driven Biomechanical Model of the Brain for  

E-print Network

- rosurgery faces an important issue for large skull openings where brain soft-tissues can exhibit large into account by the surgeon. Deformation of brain tissues occurs in the course of surgery because of physicalDoppler Ultrasound Driven Biomechanical Model of the Brain for Intraoperative Brain

Paris-Sud XI, Université de

92

Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: the population-based MRI CAMERA study.  

PubMed

Previous studies have suggested that migraine is a risk factor for brain lesions, but methodological issues hampered drawing definite conclusions. Therefore, we initiated the magnetic resonance imaging (MRI) ‘CAMERA’ (Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis) study. We summarize our previously published results. A total of 295 migraineurs and 140 controls were randomly selected from a previously diagnosed population-based sample (n = 6039), who underwent an interview, physical examination and a brain MRI scan. Migraineurs, notably those with aura, had higher prevalence of subclinical infarcts in the posterior circulation [odds ratio (OR) 13.7; 95% confidence interval (CI) 1.7, 112]. Female migraineurs were at independent increased risk of white matter lesions (WMLs; OR 2.1; 95% CI 1.0, 4.1), and migraineurs had a higher prevalence of brainstem hyperintense lesions (4.4% vs. 0.7%, P = 0.04). We observed a higher lifetime prevalence of (frequent) syncope and orthostatic insufficiency in migraineurs; future research needs to clarify whether autonomic nervous system dysfunction could explain (part of) the increased risk of WMLs in female migraineurs. Finally, in migraineurs aged < 50 years, compared with controls, we found evidence of increased iron concentrations in putamen (P = 0.02), globus pallidus (P = 0.03) and red nucleus (P = 0.03). Higher risks in those with higher attack frequency or longer disease duration were found consistent with a causal relationship between migraine and lesions. This summary of our population-based data illustrates that migraine is associated with a significantly increased risk of brain lesions. Longitudinal studies are needed to assess whether these lesions are progressive and have relevant (long-term) functional correlates. PMID:19515125

Kruit, M C; van Buchem, M A; Launer, L J; Terwindt, G M; Ferrari, M D

2010-02-01

93

Filtrate of Phellinus linteus Broth Culture Reduces Infarct Size Significantly in a Rat Model of Permanent Focal Cerebral Ischemia.  

PubMed

Phellinus linteus, a natural growing mushroom, has been known to exhibit anti-tumor, anti-inflammatory, anti-allergic and anti-oxidant effects. Aiming to exploit the neuroprotective effects of P. linteus, we evaluated its effects on infarct volume reduction in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion. Filtrate of P. linteus broth culture (various doses), fractionated filtrate (based on molecular weight) or control medium was administered intraperitoneally to rats before or after ischemia induction. Rats were killed at 24?h after the stroke surgery. Cortical and caudoputaminal infarct volumes were determined separately using an image analysis program following staining with 2,3,5-triphenyltetrazolium chloride. Significant cortical infarct volume reductions were found in the pre-treatment groups (30 and 60?minutes before onset of cerebral ischemia) compared with the control group, showing dose dependence. Posttreatment (30?minutes after ischemic onset) also significantly reduced cortical infarct volume. Furthermore, the higher molecular weight (?12?000) fraction of the culture filtrate was more effective compared with the lower molecular weight fraction. The present findings suggest that P. linteus may be a new promising approach for the treatment of focal cerebral ischemia, with the additional benefit of a wide therapeutic time window since significant infarct volume reduction is obtained by administration even after the ischemic event. Our finding that the higher molecular weight fraction of the P. linteus culture filtrate demonstrated more prominent effect may provide a clue to identify the neuroprotective substances and mechanisms. PMID:19155273

Suzuki, Sakiko; Kawamata, Takakazu; Okada, Yoshikazu; Kobayashi, Tomonori; Nakamura, Tomoyuki; Hori, Tomokatsu

2011-01-01

94

The time course of ischemic damage and cerebral perfusion in a rat model of space-occupying cerebral infarction  

Microsoft Academic Search

We aimed to establish a rat model of space-occupying hemispheric infarction to evaluate potential treatment strategies. For adequate timing of therapy in future experiments, we studied the development of tissue damage, edema formation, and perfusion over time with different MRI techniques. Permanent middle cerebral artery (MCA) occlusion was performed in 32 Fisher-344 rats. Forty-six MRI experiments including diffusion weighted (DW),

J Hofmeijer; W. B Veldhuis; J Schepers; K Nicolaij; L. J Kappelle; P. R Bär; H. B van der Worp

2004-01-01

95

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

96

Acipimox-enhanced ¹?F-fluorodeoxyglucose positron emission tomography for characterizing and predicting early remodeling in the rat infarct model.  

PubMed

The rat myocardial infarction (MI) model is widely used to study left ventricular (LV) remodeling. In this study, acipimox-enhanced (18)F-Fluorodeoxyglucose (FDG) gated-positron emission tomography (PET) was assessed for characterizing and predicting early remodeling in the rat infarct model. Nineteen Wistar rats had surgical occlusion of the left anterior descending coronary artery and 7 were sham-operated. PET was scheduled 48 h and 2 weeks later for quantifying MI area and LV function. Segments with <50% of FDG uptake had histological evidence of MI (74 ± 9% decrease in parietal thickness, fibrosis development). At 48 h, MI area was large (>35% of LV) in 6 rats, moderate (15-35% of LV) in 8 rats, limited (<15% of LV) in 5 rats and absent in the 7 sham rats. LV remodeling, assessed through the 2 weeks increase in end-diastolic volume, increased between rats with limited, moderate and large MI (+72 ± 25, +109 ± 56, +190 ± 69 ?l, respectively, P = 0.007). This 3-groups classification allowed predicting 44% of the 2 weeks increase in end-diastolic volume, and additional 34% were predicted by heart rate at 48 h. The acipimox-enhanced FDG gated-PET technique provides efficient characterization and prediction of early remodeling in the rat infarct model. PMID:22116590

Bousquenaud, Mélanie; Maskali, Fatiha; Poussier, Sylvain; Marie, Pierre-Yves; Boutley, Henri; Karcher, Gilles; Wagner, Daniel R; Devaux, Yvan

2012-08-01

97

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

Choe, Yoonsuck

98

Pruning Hidden Markov Models with Optimal Brain Surgeon  

E-print Network

1 Pruning Hidden Markov Models with Optimal Brain Surgeon Brian Mak and Kin-Wah Chan Abstract as Optimal Brain Surgeon (OBS) that has been applied to pruning neural networks in the past. In this paper Markov model, optimal brain surgeon, quadratic programming. Corresponding Author: Dr. Brian Kan-Wing Mak

Mak, Brian Kan-Wing

99

Computational Modeling of High-Level Cognition and Brain Function  

E-print Network

Computational Modeling of High-Level Cognition and Brain Function Marcel Adam Just,* Patricia A. Carpenter, and Sashank Varma Center for Cognitive Brain Imaging, Carnegie Mellon University, Pittsburgh key properties of cortical function into the design of the modeling system. Hum. Brain Mapping 8

100

Convergent models of handedness and brain lateralization  

PubMed Central

The pervasive nature of handedness across human history and cultures is a salient consequence of brain lateralization. This paper presents evidence that provides a structure for understanding the motor control processes that give rise to handedness. According to the Dynamic Dominance Model, the left hemisphere (in right handers) is proficient for processes that predict the effects of body and environmental dynamics, while the right hemisphere is proficient at impedance control processes that can minimize potential errors when faced with unexpected mechanical conditions, and can achieve accurate steady-state positions. This model can be viewed as a motor component for the paradigm of brain lateralization that has been proposed by Rogers et al. (MacNeilage et al., 2009) that is based upon evidence from a wide range of behaviors across many vertebrate species. Rogers proposed a left-hemisphere specialization for well-established patterns of behavior performed in familiar environmental conditions, and a right hemisphere specialization for responding to unforeseen environmental events. The dynamic dominance hypothesis provides a framework for understanding the biology of motor lateralization that is consistent with Roger's paradigm of brain lateralization. PMID:25339923

Sainburg, Robert L.

2014-01-01

101

Comparison of cyclic RGD peptides for ?v?3 integrin detection in a rat model of myocardial infarction  

PubMed Central

Background Expression of ?v?3 integrin is increased after myocardial infarction as part of the repair process. Increased expression of ?v?3 has been shown by molecular imaging with 18F-galacto-RGD in a rat model. The 68Ga-labelled RGD compounds 68Ga-NODAGA-RGD and 68Ga-TRAP(RGD)3 have high specificity and affinity, and may therefore serve as alternatives of 18F-galacto-RGD for integrin imaging. Methods Left coronary artery ligation was performed in rats. After 1 week, rats were imaged with [13N]NH3, followed by 18F-galacto-RGD, 68Ga-NODAGA-RGD or 68Ga-TRAP(RGD)3 using a dedicated animal PET/CT device. Rats were killed, and the activity in tissues was measured by gamma counting. The heart was sectioned for autoradiography and histology. Immunohistochemistry was performed on consecutive sections using CD31 for the endothelial cells and CD61 for ?3 expression (as part of the ?v?3 receptor). Results In vivo imaging showed focal RGD uptake in the hypoperfused area of infarcted myocardium as defined with [13N]NH3 scan. In autoradiography images, augmented uptake of all RGD tracers was observed within the infarct area as verified by the HE staining. The tracer uptake ratios (infarct vs. remote) were 4.7 ± 0.8 for 18F-galacto-RGD, 5.2 ± 0.8 for 68Ga-NODAGA-RGD, and 4.1 ± 0.7 for 68Ga-TRAP(RGD)3. The 68Ga-NODAGA-RGD ratio was higher compared to 68Ga-TRAP(RGD)3 (p = 0.04), but neither of the 68Ga tracers differed from 18F-galacto-RGD (p > 0.05). The area of augmented 68Ga-RGD uptake was associated with ?3 integrin expression (CD61). Conclusion 68Ga-NODAGA-RGD and 68Ga-TRAP(RGD)3 uptake was equally increased in the infarct area at 1 week post infarction as 18F-galacto-RGD. These results show the potential of 68Ga-labelled RGD peptides to monitor integrin expression as a part of myocardial repair and angiogenesis after ischaemic injury in vivo. PMID:23663426

2013-01-01

102

Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction  

PubMed Central

Objective: This study was performed to evaluate whether implantation of mesenchymal stem cell (MSC) would reduce left ventricular remodelling from the molecular mechanisms compared with angiotensin-converting enzyme inhibitors (ACEIs) perindopril into ischemic myocardium after acute myocardial infarction. Methods: Forty rats were divided into four groups: control, MSC, ACEI, MSC+ACEI groups. Bone marrow stem cell derived rat was injected immediately into a zone made ischemic by coronary artery ligation in MSC group and MSC+ACEI group. Phosphate-buffered saline (PBS) was injected into control group. Perindopril was administered p.o. to ACEI group and MSC+ACEI group. Six weeks after implantation, the rats were killed and heart sample was collected. Fibrillar collagen was observed by meliorative Masson’s trichome stain. Western Blotting was employed to evaluate the protein expression of matrix metalloproteinase (MMP)-2, matrix metalloproteinase (MMP)-9 in infarction zone. The transcriptional level of MMP2, MMP9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in infarction area was detected by reverse transcriptase PCR (RT-PCR) analysis. Results: The fibrillar collagen area, the protein expression of MMP2, MMP9 and the transcriptional level of MMP2, MMP9 mRNA in infarction zone reduced in MSC group, ACEI group, and MSC+ACEI group. No significant difference was detected in the expression of TIMP1 mRNA among the 4 groups. Conclusion: Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism. PMID:16845718

Wang, Jian-an; Luo, Rong-hua; Zhang, Xing; Xie, Xiao-jie; Hu, Xin-yang; He, Ai-na; Chen, Jie; Li, Jia-hui

2006-01-01

103

Effects of Age and Cortical Infarction on EEG Dynamic Changes Associated with Spike Wave Discharges in F344 Rats  

PubMed Central

Rodent models of absence seizures are used to investigate the network properties and regulatory mechanisms of the seizure's generalized spike and wave discharge (SWD). As rats age, SWDs occur more frequently, suggesting aging-related changes in the regulation of the corticothalamic mechanisms generating the SWD. We hypothesized that brain resetting mechanisms - how the brain “resets” itself to a more normal functional state following a transient period of abnormal function, e.g., a SWD - are impaired in aged animals and that brain infarction would further affect these resetting mechanisms. The main objective of this study was to determine the effects of aging, infarction, and their potential interaction on the resetting of EEG dynamics assessed by quantitative EEG (qEEG) measures of linear (signal energy measured by amplitude variation; signal frequency measured by mean zero-crossings) and nonlinear (signal complexity measured by the pattern match regularity statistic and the short-term maximum Lyapunov exponent) brain EEG dynamics in 4- and 20-month-old F344 rats with and without brain infarction. The main findings of the study were: 1) dynamic resetting of both linear and nonlinear EEG characteristics occurred following SWDs; 2) animal age significantly affected the degree of dynamic resetting in all four qEEG measures: SWDs in older rats exhibited a lower degree of dynamic resetting; 3) infarction significantly affected the degree of dynamic resetting only in terms of EEG signal complexity: SWDs in infarcted rats exhibited a lower degree of dynamic resetting; and 4) in all four qEEG measures, there was no significant interaction effect between age and infarction on dynamic resetting. We conclude that recovery of the brain to its interictal state following SWDs was better in young adult animals compared with aged animals, and to a lesser degree, in age-matched controls compared with infarction-injured animal groups, suggesting possible effects of brain resetting mechanisms and/or the disruption of the epileptogenic network that triggers SWDs. PMID:21820433

Kelly, Kevin M.; Shiau, Deng-Shan; Jukkola, Peter I.; Miller, Eric R.; Mercadante, Amanda; Quigley, Matthew M.; Nair, Sandeep P.; Sackellares, J. Chris

2011-01-01

104

A biochemical model for neurite outgrowth during brain development  

E-print Network

A biochemical model for neurite outgrowth during brain development J. FRANCON, A. MARECK Ana Maria biological event occurring during brain development at the states of neuronal differentiation is that a given Général Lec%rc, 94270 Bicêtre, France. Summary. Maximal amounts of tubulin in rat brain are observed

Paris-Sud XI, Université de

105

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

106

A New Coronary Retroinfusion Technique in theRat Infarct Model: Transjugular Cardiac Vein Catheterization  

PubMed Central

Cell delivery via the retrograde coronary route boasts less vessel embolism, myocardial injury, and arrhythmogenicity when compared with those via antegrade coronary administration or myocardial injection. However, conventional insertion into the coronary sinus and consequent bleeding complication prevent its application in small animals. To overcome the complication of bleeding, we described a modified coronary retroinfusion technique via the jugular vein route in rats with myocardial infarction (MI). A flexible wire with a bent end was inserted into the left internal jugular vein and advanced slowly along the left superior vena cava. Under direct vision, the wire was run into the left cardiac vein by rotating the wire and changing the position of its tip. A fine tube was then advanced along the wire to the left cardiac vein. This modified technique showed less lethal hemorrhage than the conventional technique. Retroinfusion via transjugular catheter enabled efficient fluid or cell dissemination to the majority areas of the free wall of the left ventricle, covering the infarcted anterior wall. In conclusion, transjugular cardiac vein catheterization may make retrocoronary infusion a more safe and practical route for delivering cell, drug, and gene therapy into the infarcted myocardium of rats. PMID:23903054

Huang, Zheyong; Shen, Yunli; Zhu, Hongmin; Xu, Jianfeng; Song, Yanan; Hu, Xinying; Shuning, Zhang; Yang, Xiangdong; Sun, Aijun; Qian, Juying; Ge, Junbo

2013-01-01

107

Infarct density distribution by MRI in the porcine model of acute and chronic myocardial infarction as a potential method transferable to the clinic.  

PubMed

To study the feasibility of a myocardial infarct (MI) quantification method [signal intensity-based percent infarct mapping (SI-PIM)] that is able to evaluate not only the size, but also the density distribution of the MI. In 14 male swine, MI was generated by 90 min of closed-chest balloon occlusion followed by reperfusion. Seven (n = 7) or 56 (n = 7) days after reperfusion, Gd-DTPA-bolus and continuous-infusion enhanced late gadolinium enhancement (LGE) MRI, and R1-mapping were carried out and post mortem triphenyl-tetrazolium-chloride (TTC) staining was performed. MI was quantified using binary [2 or 5 standard deviation (SD)], SI-PIM and R1-PIM methods. Infarct fraction (IF), and infarct-involved voxel fraction (IIVF) were determined by each MRI method. Bias of each method was compared to the TTC technique. The accuracy of MI quantification did not depend on the method of contrast administration or the age of the MI. IFs obtained by either of the two PIM methods were statistically not different from the IFs derived from the TTC measurements at either MI age. IFs obtained from the binary 2SD method overestimated IF obtained from TTC. IIVF among the three different PIM methods did not vary, but with the binary methods the IIVF gradually decreased with increasing the threshold limit. The advantage of SI-PIM over the conventional binary method is the ability to represent not only IF but also the density distribution of the MI. Since the SI-PIM methods are based on a single LGE acquisition, the bolus-data-based SI-PIM method can effortlessly be incorporated into the clinical image post-processing procedure. PMID:24718787

Varga-Szemes, Akos; Simor, Tamas; Lenkey, Zsofia; van der Geest, Rob J; Kirschner, Robert; Toth, Levente; Brott, Brigitta C; Elgavish, Ada; Elgavish, Gabriel A

2014-06-01

108

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-driven behavior. The precise mapping of incoming sensory stimuli onto motor representations relies on a ``router processing on hold, and a slow serial performance at the router stage, resulting in a performance bottleneck

Paris-Sud XI, Université de

109

Enoxaparin, a low molecular weight heparin decreases infarct size and improves sensorimotor function in a rat model of focal cerebral ischemia.  

PubMed

Possible neuroprotective effects of the low molecular weight heparin (LMWH) enoxaparin sodium (Lovenox) were evaluated in a rat model of focal ischemia. Male Sprague-Dawley rats were subjected to 90 min of occlusion of the right middle cerebral artery using the intraluminal suture method. Enoxaparin at doses of 0, 10 or 15 mg/kg was administered to groups of rats 1, 8, 24 and 32 h after artery occlusion. Motor impairment was evaluated by performance on the traverse beam and accelerating rotarod tests. Animals were sacrificed 48 h after occlusion and brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride for determination of infarct volume. Forty percent of the rats receiving 15 mg/kg enoxaparin died as a result of intracranial hemorrhage. Untreated rats exhibited large lesions involving the caudate putamen and much of the cortex. In enoxaparin - treated rats the damage was mainly confined to the caudate putamen. The sensorimotor behavior of the 10 mg/kg enoxaparin group was significantly better than that of untreated animals. Motor performance of the survivors in the 15 mg/kg group was poor due to hypoactivity and weakness resulting from excessive bleeding. These results suggest that LMWH may have a neuroprotective function. PMID:10876084

Quartermain, D; Li, Y; Jonas, S

2000-07-14

110

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.

111

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

112

Intramyocardial Transplantation and Tracking of Human Mesenchymal Stem Cells in a Novel Intra-Uterine Pre-Immune Fetal Sheep Myocardial Infarction Model: A Proof of Concept Study  

PubMed Central

Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70–75 days) were included. Ten animals either received an intra-uterine induction of MI only (n?=?4) or MI+intra-myocardial injection (IMI;n?=?6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n?=?3) or the bone-marrow (BMMSCs;n?=?3). Three animals received an intra-peritoneal injection (IPI;n?=?3; ATMSCs;n?=?2/BMMSCs;n?=?1). All procedures were performed successfully and follow-up was 7–9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×105–5×105 human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific ?-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow-Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy. PMID:23533575

Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M.; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E.; Schwartlander, Ruth; Vogel, Viola; Vogt, Peter; Grunenfelder, Jurg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P.

2013-01-01

113

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

114

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

115

A revised dosimetric model of the adult head and brain  

SciTech Connect

During the last decade, new radiopharmaceutical have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head. Brain and head models developed in the past have been only simplistic representations of this anatomic region. For example, the brain within the phantom of MIRD Pamphlet No. 5 Revised is modeled simply as a single ellipsoid of tissue With no differentiation of its internal structures. To address this need, the MIRD Committee established a Task Group in 1992 to construct a more detailed brain model to include the cerebral cortex, the white matter, the cerebellum, the thalamus, the caudate nucleus, the lentiform nucleus, the cerebral spinal fluid, the lateral ventricles, and the third ventricle. This brain model has been included within a slightly modified version of the head model developed by Poston et al. in 1984. This model has been incorporated into the radiation transport code EGS4 so as to calculate photon and electron absorbed fractions in the energy range 10 keV to 4 MeV for each of thirteen sources in the brain. Furthermore, explicit positron transport have been considered, separating the contribution by the positron itself and its associated annihilations photons. No differences are found between the electron and positron absorbed fractions; however, for initial energies of positrons greater than {approximately}0.5 MeV, significant differences are found between absorbed fractions from explicit transport of annihilation photons and those from an assumed uniform distribution of 0.511-MeV photons. Subsequently, S values were calculated for a variety of beta-particle and positron emitters brain imaging agents. Moreover, pediatric head and brain dosimetric models are currently being developed based on this adult head model.

Bouchet, L.G.; Bolch, W.E. [Univ. of Florida, Gainesville, FL (United States); Weber, D.A. [Univ. of California, Davis, CA (United States)] [and others

1996-06-01

116

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

117

Evolution of the brain tumour spheroid model: transcending current model limitations  

Microsoft Academic Search

Summary ¶Tumour recurrence and the high mortality and morbidity associated with malignant brain tumours may be attributed to the failure of current therapeutic modalities (surgery, radiation and chemotherapy) to control the invasion of malignant brain tumour cells into healthy brain tissue. Several in vitro and in vivo models have been developed and used to study brain tumour invasion and cell

A. Corcoran; L. I. F. De Ridder; D. Del Duca; O. J. P. Kalala; T. Lah; G. J. Pilkington; R. F. Del Maestro

2003-01-01

118

Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model  

PubMed Central

Background Ectonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS) when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO) in a large animal model. Methods A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg). The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8) or saline (0.9 mg/ml, n = 8), twenty minutes after balloon inflation. Area at risk (AAR) was evaluated by ex vivo SPECT. IS and MO were evaluated by ex vivo MRI. Results No differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 ± 4.2% vs 69.4 ± 5.0%, p = NS) or MO (10.7 ± 4.8% vs 11.4 ± 4.8%, p = NS), but apyrase prolonged the post-ischemic reactive hyperemia. Conclusion Apyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction. PMID:20047685

2010-01-01

119

Cell tracking and therapy evaluation of bone marrow monocytes and stromal cells using SPECT and CMR in a canine model of myocardial infarction  

PubMed Central

Background The clinical application of stem cell therapy for myocardial infarction will require the development of methods to monitor treatment and pre-clinical assessment in a large animal model, to determine its effectiveness and the optimum cell population, route of delivery, timing, and flow milieu. Objectives To establish a model for a) in vivo tracking to monitor cell engraftment after autologous transplantation and b) concurrent measurement of infarct evolution and remodeling. Methods We evaluated 22 dogs (8 sham controls, 7 treated with autologous bone marrow monocytes, and 7 with stromal cells) using both imaging of 111Indium-tropolone labeled cells and late gadolinium enhancement CMR for up to12 weeks after a 3 hour coronary occlusion. Hearts were also examined using immunohistochemistry for capillary density and presence of PKH26 labeled cells. Results In vivo Indium imaging demonstrated an effective biological clearance half-life from the injection site of ~5 days. CMR demonstrated a pattern of progressive infarct shrinkage over 12 weeks, ranging from 67–88% of baseline values with monocytes producing a significant treatment effect. Relative infarct shrinkage was similar through to 6 weeks in all groups, following which the treatment effect was manifest. There was a trend towards an increase in capillary density with cell treatment. Conclusion This multi-modality approach will allow determination of the success and persistence of engraftment, and a correlation of this with infarct size shrinkage, regional function, and left ventricular remodeling. There were overall no major treatment effects with this particular model of transplantation immediately post-infarct. PMID:19397809

Wisenberg, Gerald; Lekx, Katie; Zabel, Pam; Kong, Huafu; Mann, Rupinder; Zeman, Peter R; Datta, Sudip; Culshaw, Caroline N; Merrifield, Peter; Bureau, Yves; Wells, Glenn; Sykes, Jane; Prato, Frank S

2009-01-01

120

An improved dosimetric model of the head and brain  

E-print Network

range 10 keV to 4 MeV. All twenty-three regions included in the revised head and brain model were taken as target regions. S-values were also calculated for several radionuclides used in brain imaging, and also deposited in the thyroid, the skull...

Bouchet, Lionel Gerard

2012-06-07

121

Representation of internal models of action in the autistic brain  

E-print Network

Representation of internal models of action in the autistic brain Courtney C Haswell1, Jun Izawa1, Lauren R Dowell2, Stewart H Mostofsky2,3 & Reza Shadmehr1 Children with autism spectrum disorder (ASD as children learned to control a novel tool and found that the autistic brain built a stronger than normal

Shadmehr, Reza

122

A Neurocomputational Model of an Imitation Deficit Following Brain Lesion  

Microsoft Academic Search

This paper investigates the neural mechanisms of visuo-motor imitation in humans through convergent evidence from neuroscience. In particular, we consider a deficit in imitation following callosal brain le- sion, based on the rational that looking at how imitation is impaired can unveil its underlying neural principles. We ground the functional archi- tecture and information flow of our model in brain

Biljana Petreska; Aude G. Billard

2006-01-01

123

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

124

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

125

Thalamic infarction following a Russell's viper bite.  

PubMed

We report a case of a Russell's viper (Daboia russelii) bite involving a 55-year-old male who developed a bilateral thalamic infarction. Although the coagulopathy was controlled within twenty-four hours, the patient became restless and disoriented. Due to the initial prolonged clotting time, we suspected an intracranial bleed. T2 magnetic resonance imaging (MRI) of the brain showed bilateral infarcts of the thalamus. Cerebral infarction secondary to snake envenomation has been reported before, but to our knowledge bilateral involvement of the thalamus has not been reported. PMID:23431827

Ittyachen, Abraham M; Jose, Mohan B

2012-09-01

126

Transcranial magnetic stimulation and brain atrophy: a computer-based human brain model study  

Microsoft Academic Search

This paper is aimed at exploring the effect of cortical brain atrophy on the currents induced by transcranial magnetic stimulation\\u000a (TMS). We compared the currents induced by various TMS conditions on several different MRI derived finite element head models\\u000a of brain atrophy, incorporating both decreasing cortical volume and widened sulci. The current densities induced in the cortex\\u000a were dependent upon

Tim Wagner; Uri Eden; Felipe Fregni; Antoni Valero-Cabre; Ciro Ramos-Estebanez; Valerie Pronio-Stelluto; Alan Grodzinsky; Markus Zahn; Alvaro Pascual-Leone

2008-01-01

127

Nonparametric hierarchical Bayesian model for functional brain parcellation  

E-print Network

We develop a method for unsupervised analysis of functional brain images that learns group-level patterns of functional response. Our algorithm is based on a generative model that comprises two main layers. At the lower ...

Lashkari, Danial

128

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

129

Brain tumor modeling: glioma growth and interaction with chemotherapy  

NASA Astrophysics Data System (ADS)

In last decade increasingly mathematical models of tumor growths have been studied, particularly on solid tumors which growth mainly caused by cellular proliferation. In this paper we propose a modified model to simulate the growth of gliomas in different stages. Glioma growth is modeled by a reaction-advection-diffusion. We begin with a model of untreated gliomas and continue with models of polyclonal glioma following chemotherapy. From relatively simple assumptions involving homogeneous brain tissue bounded by a few gross anatomical landmarks (ventricles and skull) the models have been expanded to include heterogeneous brain tissue with different motilities of glioma cells in grey and white matter. Tumor growth is characterized by a dangerous change in the control mechanisms, which normally maintain a balance between the rate of proliferation and the rate of apoptosis (controlled cell death). Result shows that this model closes to clinical finding and can simulate brain tumor behavior properly.

Banaem, Hossein Y.; Ahmadian, Alireza; Saberi, Hooshangh; Daneshmehr, Alireza; Khodadad, Davood

2011-10-01

130

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

131

Fuzzy object models for newborn brain MR image segmentation  

NASA Astrophysics Data System (ADS)

Newborn brain MR image segmentation is a challenging problem because of variety of size, shape and MR signal although it is the fundamental study for quantitative radiology in brain MR images. Because of the large difference between the adult brain and the newborn brain, it is difficult to directly apply the conventional methods for the newborn brain. Inspired by the original fuzzy object model introduced by Udupa et al. at SPIE Medical Imaging 2011, called fuzzy shape object model (FSOM) here, this paper introduces fuzzy intensity object model (FIOM), and proposes a new image segmentation method which combines the FSOM and FIOM into fuzzy connected (FC) image segmentation. The fuzzy object models are built from training datasets in which the cerebral parenchyma is delineated by experts. After registering FSOM with the evaluating image, the proposed method roughly recognizes the cerebral parenchyma region based on a prior knowledge of location, shape, and the MR signal given by the registered FSOM and FIOM. Then, FC image segmentation delineates the cerebral parenchyma using the fuzzy object models. The proposed method has been evaluated using 9 newborn brain MR images using the leave-one-out strategy. The revised age was between -1 and 2 months. Quantitative evaluation using false positive volume fraction (FPVF) and false negative volume fraction (FNVF) has been conducted. Using the evaluation data, a FPVF of 0.75% and FNVF of 3.75% were achieved. More data collection and testing are underway.

Kobashi, Syoji; Udupa, Jayaram K.

2013-03-01

132

Optimizing Experimental Design for Comparing Models of Brain Function  

Microsoft Academic Search

This article presents the first attempt to formalize the optimization of experimental design with the aim of comparing models of brain function based on neuroimaging data. We demonstrate our approach in the context of Dynamic Causal Modelling (DCM), which relates experimental manipulations to observed network dynamics (via hidden neuronal states) and provides an inference framework for selecting among candidate models.

Jean Daunizeau; Kerstin Preuschoff; Karl Friston; Klaas Stephan

2011-01-01

133

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

134

A revised dosimetric model of the adult head and brain  

SciTech Connect

During the last decade, several new radiopharmaceuticals have been introduced for brain imaging. The marked differences of these tracers in tissue specificicity within the brain and their increasing use for diagnostic studies support the need for a more antihropomorphic model of the human brain and head. Brain and head models developed in the past have comprised only simplistic representations of this anatomic region. A new brain model has been developed which includes eight subregions: the caudate nucleus, the cerebellium, the cerebral cortex, the lateral ventricles, the lentiform nucleus, the thalamus, the third ventricle and the white matter. This brain model has been included within a slightly modified version of the head model developed by Poston et al. in 1984. The head model, which includes both the thyroid and eyes, was modified in this work to include the cerebrospinal fluid within the cranial and spinal regions. Absorbed fractions of energy for photon and electron sources located in thirteen source regions within the new head model were calculated using the EGS4 Monte Carlo radiation transport code for radiations in the energy range 10 keV to 4 MeV. S-values were calculated for five radionuclides used in brain imaging ({sup 11}C, {sup 15}O, {sup 18}F, {sup 99m}Tc and {sup 123}I) and for three radionuclides showing selective uptake in the thyroid ({sup 99m}Tc, {sup 123}I, and {sup 131}I). S-values were calculated using 100 discrete energy points in the beta-emission spectrum of the different radionuclides. 17 refs., 14 figs., 3 tabs.

Bouchet, L.G.; Bolch, W.E.; Weber, D.A.; Atkins, H.L.; Poston, J.W. [Texas A& M Univ., College Station, TX (United States)]|[Univ. of California, Davis, CA (United States)]|[State Univ. of New York, Stony Brook, NY (United States)

1996-07-01

135

Comparison of electrical conductivities of various brain phantom gels: Developing a 'Brain Gel Model'  

PubMed Central

The use of conducting gels to mimic brain and other tissues is of increasing interest in the development of new medical devices. Currently, there are few such models that can be utilized at physiologic temperatures. In this work, the conductivities of agar, agarose and gelatin gels were manipulated by varying NaCl concentration from 0–1 mg/ml. The AC conductivity was measured at room and physiological temperatures (37°C) in the 100–500 Hz frequency range. Conductivity (?) was nearly independent of frequency but increased linearly with NaCl concentration and was higher at physiological temperatures in these gels. A formula for predicting conductivity as a function of NaCl concentration was derived for each gel type. The overall goal is to develop a ‘brain gel model’, for studying low frequency electrical properties of the brain and other tissues at physiological temperatures. PMID:23139442

Kandadai, Madhuvanthi A.; Raymond, Jason L.; Shaw, George J.

2012-01-01

136

Computational modeling of brain tumors: discrete, continuum or hybrid?  

Microsoft Academic Search

\\u000a In spite of all efforts, patients diagnosed with highly malignant brain tumors (gliomas), continue to face a grim prognosis.\\u000a Achieving significant therapeutic advances will also require a more detailed quantitative understanding of the dynamic interactions\\u000a among tumor cells, and between these cells and their biological microenvironment. Data-driven computational brain tumor models\\u000a have the potential to provide experimental tumor biologists with

Zhihui Wang; Thomas S. Deisboeck

2009-01-01

137

Computational modeling of brain tumors: discrete, continuum or hybrid?  

Microsoft Academic Search

In spite of all efforts, patients diagnosed with highly malignant brain tumors (gliomas), continue to face a grim prognosis.\\u000a Achieving significant therapeutic advances will also require a more detailed quantitative understanding of the dynamic interactions\\u000a among tumor cells, and between these cells and their biological microenvironment. Data-driven computational brain tumor models\\u000a have the potential to provide experimental tumor biologists with

Zhihui Wang; Thomas S. Deisboeck

2008-01-01

138

Brain covariance selection: better individual functional connectivity models using population prior  

E-print Network

Brain covariance selection: better individual functional connectivity models using population prior bertrand.thirion@inria.fr Abstract Spontaneous brain activity, as observed in functional neuroimaging, has been shown to display reproducible structure that expresses brain architecture and car- ries markers

Paris-Sud XI, Université de

139

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.

140

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

141

Traumatic Brain Injury Pathophysiology\\/Models  

Microsoft Academic Search

\\u000a Traumatic brain injury (TBI) represents a major burden on health care worldwide. In the US, TBI accounts for 435,000 emergency\\u000a department visits, 37,000 hospital admissions, and approximately 2,500 deaths each year. Of the patients affected, 48% are\\u000a impaired by chronic physical, cognitive, and psychosocial deficits. While aggressive early rehabilitation improves function\\u000a (Cowen et al. Arch Phys Med Rehabil 76:797–803, 1995;

Peter A. Walker; Nathan D. Allison

142

Exenatide Reduces Infarct Size and Improves Cardiac Function in a Porcine Model of Ischemia and Reperfusion Injury  

Microsoft Academic Search

Objectives This study sought to examine whether exenatide is capable of reducing myocardial infarct size. Background Exenatide is a glucagon-like peptide (GLP)-1 analogue with insulinotropic and insulinomimetic properties. Because insulin and GLP-1 have been described as reducing apoptosis, exenatide might confer cardioprotection after acute myocardial infarction (MI). Methods Pigs were randomized to exenatide or phosphate-buffered saline (PBS) treatment after 75

Leo Timmers; José P. S. Henriques; Dominique P. V. de Kleijn; J. Hans DeVries; Hans Kemperman; Paul Steendijk; Cees W. J. Verlaan; Marjolein Kerver; Jan J. Piek; Pieter A. Doevendans; Gerard Pasterkamp; Imo E. Hoefer

2009-01-01

143

Electrocardiograms Corresponding to the Development of Myocardial Infarction in Anesthetized WHHLMI Rabbits (Oryctolagus cuniculus), an Animal Model for Familial Hypercholesterolemia  

PubMed Central

The aim of this study was to determine whether features indicative of myocardial ischemia occur in the electrocardiograms (ECG) in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for human familial hypercholesterolemia. ECG were recorded in 110 anesthetized WHHLMI rabbits (age, 10 to 39 mo) by using unipolar and bipolar limb leads with or without chest leads. We noted the following electrocardiographic changes: T wave inversion (37.4%), ST segment depression (31.8%), deep Q wave (16.3%), reduced R wave amplitude (7.3%), ST segment elevation (2.7%), and high T wave (1.8%). These ECG changes resembled those in human patients with coronary heart disease. Histopathologic examination revealed that the left ventricular wall showed acute myocardial lesions, including loss of cross-striations, vacuolar degeneration, coagulation necrosis of cardiac myocytes, and edema between myofibrils, in addition to chronic myocardial lesions such as myocardial fibrosis. The coronary arteries that caused these ECG changes were severely stenosed due to atherosclerotic lesions. Ischemic ECG changes corresponded to the locations of the myocardial lesions. Normal ECG waveforms were similar between WHHLMI rabbits and humans, in contrast to the large differences between rabbits and mice or rats. In conclusion, ischemic ECG changes in WHHLMI rabbits reflect the location of myocardial lesions, making this model useful for studying coronary heart disease. PMID:23114045

Kobayashi, Tsutomu; Ito, Takashi; Yamada, Satoshi; Kuniyoshi, Nobue; Shiomi, Masashi

2012-01-01

144

Selfreparing Neural Networks: A Model for Recovery from Brain Damage  

Microsoft Academic Search

We introduce selfrepairing neural networks as a model for recovery from brain damage. Small lesions are repaired through reinstatement of the redundancy in the network's connections. With mild lesions, this process can model autonomous recovery. Moderate lesions require patterned input. In this paper, we discuss implementations in three types of network of increasing biological plausibility. We also mention some results

Jaap M. J. Murre; Robert Griffioen; I. H. Robertson

2003-01-01

145

Model-Based Brain and Tumor Segmentation Nathan Moon, 2  

E-print Network

1 Model-Based Brain and Tumor Segmentation 1 Nathan Moon, 2 Elizabeth Bullitt, 4 Koen van Leemput Gasthuisberg, B-3000 Leuven, Belgium email: gerig@cs.unc.edu Abstract-- Combining image segmentation based, however, prevents segmentation of structures that are not part of the model. In practical applications, we

Gerig, Guido

146

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

147

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

148

Classical Wave Model of Quantum-Like Processing in Brain  

NASA Astrophysics Data System (ADS)

We discuss the conjecture on quantum-like (QL) processing of information in the brain. It is not based on the physical quantum brain (e.g., Penrose) - quantum physical carriers of information. In our approach the brain created the QL representation (QLR) of information in Hilbert space. It uses quantum information rules in decision making. The existence of such QLR was (at least preliminary) confirmed by experimental data from cognitive psychology. The violation of the law of total probability in these experiments is an important sign of nonclassicality of data. In so called "constructive wave function approach" such data can be represented by complex amplitudes. We presented 1,2 the QL model of decision making. In this paper we speculate on a possible physical realization of QLR in the brain: a classical wave model producing QLR . It is based on variety of time scales in the brain. Each pair of scales (fine - the background fluctuations of electromagnetic field and rough - the cognitive image scale) induces the QL representation. The background field plays the crucial role in creation of "superstrong QL correlations" in the brain.

Khrennikov, A.

2011-01-01

149

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

150

Functional CT Perfusion Imaging in Predicting the Extent of Cerebral Infarction from a 3Hour Middle Cerebral Arterial Occlusion in a Primate Stroke Model  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Our purpose was to determine whether cerebral perfusion functional CT (fCT), performed after endovascular middle cerebral artery (MCA) occlusion, can be used to predict final cerebral infarction extent in a primate model. METHODS: fCT with bolus tracking was performed before and 30 and 150 minutes after 3-hour digital subtraction angiography (DSA)- guided endovascular MCA occlusion in five

Leena M. Hamberg; George J. Hunter; Kenneth I. Maynard; Chris Owen; Pearse P. Morris; Christopher M. Putman; Christopher Ogilvy; R. Gilberto Gonzalez

151

Modeling Brain Resonance Phenomena Using a Neural Mass Model  

Microsoft Academic Search

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

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

2011-01-01

152

A revised dosimetric model of the head and brain  

SciTech Connect

The use of PET and SPECT radiopharmaceuticals in brain imaging has greatly expanded over the past several years. Many of these agents localize within particular subregions of the brain, thus allowing for detailed physiologic and metabolic imaging. Dosimetric models to support these advances in nuclear medicine have been lacking. For example, the brain within the phantom of MIRD Pamphlet No. 5 Revised is modeled simply as a single ellipsoid of tissue with no differentiation of its internal structures. To address this need, the MIRD Committee established a Task Group in 1992 to construct a revised dosimetric model of the brain to include the following subregions: the cerebral cortex, the white matter, the cerebellum, the thalamus, the caudate nucleus, the lentiform nucleus (putamen and globus pallidus), the cerebral spinal fluid (within the subarachnoid space of the brain), the lateral ventricles, and the third ventricle. Estimates of both electron and photon absorbed fractions (AF) were subsequently calculated using the EGS4 radiation transport code. For most of the internal brain structures, electron AFs are shown to fall fellow unity for all regions within the energy range of {approximately}200 keV to 4 MeV. For example, AFs for the caudate nucleus as both a source and target region and estimated as 0.98, 0.84, 0.39 for 200-keV, 1-MeV, and 4-MeV electron sources, respectively. Corresponding AFs within the white matter as a source and target region are estimated as 1.0, 0.95, and 0.79 for these same electron energies. Revised S values were subsequently calculated for a variety of beta-particle and positron emitters used in brain imaging.

Bolch, W.E.; Poston, J.W. Sr. [Texas A& M Univ., College Station, TX (United States)

1995-05-01

153

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

154

Accumulation of Iron in a Model of Myocardial Infarction and Its Cell Toxicity in Cardiomyocytes  

PubMed Central

Introduction: Despite advancements in medicine leading to a marked decline in mortality due to acute myocardial infarction (MI), mortality due to post-MI heart failure (HF) remains high. Left ventricular (LV) remodeling is important in the pathogenesis of HF following MI. Previous reports investigating iron overload in anemia and chronic liver cirrhosis suggest that excess iron exhibits cell toxicity in multiple organ systems. During acute MI, ischemia/reperfusion (I/R) injury caused by temporary coronary ischemia results in massive necrosis followed by fibrosis. Previous reports studying tissue injury demonstrated that iron accumulation suppresses wound healing and exacerbates tissue injury in other organs. However, the role of iron in scar formation and LV remodeling is not well characterized. Methods: To address this, we investigated iron, transferrin, and fibrosis in heart tissue sections after I/R injury, and potential cytotoxic effects of iron in the form of FeCl3 on HL-1 and H9C2 cardiomyocytes. Mice underwent surgical I/R injury using left anterior descending coronary ligation to induce 30-minute transient ischemia. The hearts were harvested 1 week later and prepared for histological assays. Results: Masson's trichrome staining revealed fibrosis from the anterior to posterior wall in the mid-myocardium. Perl's iron staining revealed non-transferrin bound iron localized in scar tissue at anterior and posterior aspects of the heart. Immunohistochemistry found ferritin localization to areas of fibrosis, specifically in the extracellular fluid of mid-myocardium and intracellular fluid of fibroblasts and surrounding cardiomyocytes. While iron was undetectable in iron stains of sham operated mice, more than 50 cells were positive with the iron stain in I/R group. Image J (NIH) showed increased anti-ferritin staining in the I/R group compared to sham controls (more than a four-fold increase). To further investigate this, HL-1 and H9C2 cardiomyocytes were cultured with doses of 1 µM to 1 mM FeCl3 for 24 hours, and cell death was analyzed with Live/Dead Cell Viability Assay (Invitrogen). Treatment greater than 100 µM decreased cell viability, and significant cell death (n=6, P<.05) was observed in cardiomyocytes exposed to 50 µM FeCl3 or more, and that excess iron leads to cell death. Conclusions: These results suggest that iron accumulation may play a role in cardiac cell death and fibrosis in ventricular myofiber remodeling after I/R injury. Taken together, excess iron in MI may induce cell death, leading to LV remodeling following I/R injury. Understanding the role of iron accumulation in the heart could develop new therapeutic strategies for treating multiple heart diseases including HF.

Higa, Jason K; Matsui, Takashi

2014-01-01

155

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

156

Immunological considerations of modern animal models of malignant primary brain tumors  

E-print Network

engineered mouse models of brain cancer and the promise ofschwannoma. Cancer 2005, Barth RF: Rat brain tumor models inbrain tumor model and its response to therapy with 1,3-bis(2-chloroethyl)-1-nitro- sourea. Cancer

2009-01-01

157

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

158

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; Avila Rodriguez, Marco Fidel; Cespedes Rubio, Angel

2013-01-01

159

Modeling the blood-brain barrier using stem cell sources  

PubMed Central

The blood–brain barrier (BBB) is a selective endothelial interface that controls trafficking between the bloodstream and brain interstitial space. During development, the BBB arises as a result of complex multicellular interactions between immature endothelial cells and neural progenitors, neurons, radial glia, and pericytes. As the brain develops, astrocytes and pericytes further contribute to BBB induction and maintenance of the BBB phenotype. Because BBB development, maintenance, and disease states are difficult and time-consuming to study in vivo, researchers often utilize in vitro models for simplified analyses and higher throughput. The in vitro format also provides a platform for screening brain-penetrating therapeutics. However, BBB models derived from adult tissue, especially human sources, have been hampered by limited cell availability and model fidelity. Furthermore, BBB endothelium is very difficult if not impossible to isolate from embryonic animal or human brain, restricting capabilities to model BBB development in vitro. In an effort to address some of these shortcomings, advances in stem cell research have recently been leveraged for improving our understanding of BBB development and function. Stem cells, which are defined by their capacity to expand by self-renewal, can be coaxed to form various somatic cell types and could in principle be very attractive for BBB modeling applications. In this review, we will describe how neural progenitor cells (NPCs), the in vitro precursors to neurons, astrocytes, and oligodendrocytes, can be used to study BBB induction. Next, we will detail how these same NPCs can be differentiated to more mature populations of neurons and astrocytes and profile their use in co-culture modeling of the adult BBB. Finally, we will describe our recent efforts in differentiating human pluripotent stem cells (hPSCs) to endothelial cells with robust BBB characteristics and detail how these cells could ultimately be used to study BBB development and maintenance, to model neurological disease, and to screen neuropharmaceuticals. PMID:23305164

2013-01-01

160

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

161

A mathematical model of blood, cerebrospinal fluid and brain dynamics.  

PubMed

Using first principles of fluid and solid mechanics a comprehensive model of human intracranial dynamics is proposed. Blood, cerebrospinal fluid (CSF) and brain parenchyma as well as the spinal canal are included. The compartmental model predicts intracranial pressure gradients, blood and CSF flows and displacements in normal and pathological conditions like communicating hydrocephalus. The system of differential equations of first principles conservation balances is discretized and solved numerically. Fluid-solid interactions of the brain parenchyma with cerebral blood and CSF are calculated. The model provides the transitions from normal dynamics to the diseased state during the onset of communicating hydrocephalus. Predicted results were compared with physiological data from Cine phase-contrast magnetic resonance imaging to verify the dynamic model. Bolus injections into the CSF are simulated in the model and found to agree with clinical measurements. PMID:19219605

Linninger, Andreas A; Xenos, Michalis; Sweetman, Brian; Ponkshe, Sukruti; Guo, Xiaodong; Penn, Richard

2009-12-01

162

Exercise Reduces Infarct Volume and Facilitates Neurobehavioral Recovery: Results From a Systematic Review and Meta-analysis of Exercise in Experimental Models of Focal Ischemia.  

PubMed

Background. Regular exercise reduces the risk of a first-ever stroke and is associated with smaller infarcts. Although evidence has suggested that therapeutic exercise following stroke is beneficial, we do not yet know whether exercise reduces stroke severity and improves functional recovery. The mechanisms underlying any benefit remain unclear. Objective. To conduct a systematic review and meta-analysis of studies testing exercise in animal models of ischemic stroke where outcomes were measured as infarct volume, neurobehavioral score, neurogenesis, or a combination of these. We also sought evidence of publication bias. Methods. We searched 3 online databases for publications reporting the use of exercise in focal cerebral ischemia. We used DerSimonian and Laird normalized random-effects meta-analysis and meta-regression to determine the impact of study quality and design on the efficacy of exercise. Results. Overall, exercise reduced infarct volume by 25.2% (95% confidence interval [CI] = 19.0%-31.3%; 65 experiments and 986 animals) and improved neurobehavioral score by 38.2% (95% CI = 29.1%-47.3%; 42 experiments; n = 771). For both outcomes, larger effects were seen when exercise preceded ischemia rather than came after it. For neurobehavioral scores, we found evidence of publication bias. Reported study quality was moderate (median score 5/10). Both model-specific (eg, type of ischemia) and exercise-specific characteristics influenced reported outcome. Conclusion. Exercise, either before or after ischemia, reduced infarct volume and improved neurobehavioral score. However, overall estimates of efficacy were higher in studies at risk of bias, and for neurobehavioral outcomes, there was evidence of a substantial publication bias. PMID:24553105

Egan, Kieren J; Janssen, Heidi; Sena, Emily S; Longley, Lesa; Speare, Sally; Howells, David W; Spratt, Neil J; Macleod, Malcolm R; Mead, Gillian E; Bernhardt, Julie

2014-10-01

163

Kindling and status epilepticus models of epilepsy: rewiring the brain  

Microsoft Academic Search

This review focuses on the remodeling of brain circuitry associated with epilepsy, particularly in excitatory glutamate and inhibitory GABA systems, including alterations in synaptic efficacy, growth of new connections, and loss of existing connections. From recent studies on the kindling and status epilepticus models, which have been used most extensively to investigate temporal lobe epilepsy, it is now clear that

Kiyoshi Morimoto; Margaret Fahnestock; Ronald J Racine

2004-01-01

164

Directions for Mind, Brain, and Education: Methods, Models, and Morality  

ERIC Educational Resources Information Center

In this article we frame a set of important issues in the emerging field of Mind, Brain, and Education in terms of three broad headings: methods, models, and morality. Under the heading of methods we suggest that the need for synthesis across scientific and practical disciplines entails the pursuit of usable knowledge via a catalytic symbiosis…

Stein, Zachary; Fischer, Kurt W.

2011-01-01

165

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

166

FK419, a nonpeptide platelet glycoprotein IIb\\/IIIa antagonist, ameliorates brain infarction associated with thrombotic focal cerebral ischemia in monkeys: comparison with tissue plasminogen activator  

Microsoft Academic Search

The binding of platelet glycoprotein (GP) IIb\\/IIIa to fibrinogen is the final common pathway in platelet aggregation, a process known to play a key role in the pathogenesis of ischemic brain damage. We compared the effects of FK419, a novel nonpeptide GPIIb\\/IIIa antagonist, with recombinant tissue plasminogen activator (rt-PA) on middle cerebral artery (MCA) patency and ischemic brain damage in

Masashi Maeda; Akira Moriguchi; Kayoko Mihara; Toshiaki Aoki; Hiroyuki Takamatsu; Nobuya Matsuoka; Seitaro Mutoh; Toshio Goto

2005-01-01

167

Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model.  

PubMed

Treatment of myocardial infarction (MI) with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal MI models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of MI using a fully grown non-immune-compromised rat model. Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were randomized to receive intramyocardial injections of adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, or phosphate-buffered saline 1 week following induction of MI. After 4 weeks, left ventricular ejection fraction (LVEF) was improved in the adipose-derived stem cell group, and scar wall thickness was greater compared with the saline group. Adipose-derived as well as bone marrow-derived mesenchymal stem cells prevented left ventricular end diastolic dilation. Neither of the cell groups displayed increased angiogenesis in the myocardium compared with the saline group. Adipose-derived stem cells from a human ischemic patient preserved cardiac function following MI, whereas this could not be demonstrated for bone marrow-derived mesenchymal stem cells, with only adipose-derived stem cells leading to an improvement in LVEF. Neither of the stem cell types induced myocardial angiogenesis, raising the question whether donor age and health have an effect on the efficacy of stem cells used in the treatment of MI. PMID:23211469

Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Holst-Hansen, Claus; Kastrup, Jens; Baandrup, Ulrik; Zachar, Vladimir; Fink, Trine; Simonsen, Ulf

2014-02-01

168

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

169

The effects of the endothelin ETA receptor antagonist, FR 139317, on infarct size in a rabbit model of acute myocardial ischaemia and reperfusion.  

PubMed Central

1. The effects were investigated of the ETA receptor antagonist, FR 139317, on endothelin-1 (ET-1)-induced coronary vasoconstriction in the isolated perfused heart of the rabbit. In addition, this study examined whether FR 139317 reduced infarct size in a rabbit model of coronary artery occlusion and reperfusion. 2. In the rabbit isolated perfused heart, ET-1 (1-100 pmol) elicited a dose-dependent increase in coronary perfusion pressure (CPP). For example, 30 pmol ET-1 caused CPP to rise by 22 +/- 8 mmHg and 100 pmol ET-1 by 47 +/- 10 mmHg (n = 8). Infusion of FR 139317 (1 microM) significantly attenuated the increase in CPP caused by ET-1 (30 pmol: 3 +/- 1 mmHg, 100 pmol: 8 +/- 2 mmHg; n = 8). 3. In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 45 or 60 min of coronary artery occlusion followed by 2 h of reperfusion was 47 +/- 6% (n = 6) and 55 +/- 7% (n = 5), respectively. A continuous infusion of FR 139317 (0.2 mg kg-1 min-1 preceded by a loading dose of 1.0 mg kg-1, i.v.; n = 5-6) had no effect on the extent of the myocardial infarct size (45 min: 47 +/- 6%; 60 min: 49 +/- 7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8032665

McMurdo, L.; Thiemermann, C.; Vane, J. R.

1994-01-01

170

A mathematical model of blood, cerebrospinal fluid and brain dynamics  

Microsoft Academic Search

Using first principles of fluid and solid mechanics a comprehensive model of human intracranial dynamics is proposed. Blood,\\u000a cerebrospinal fluid (CSF) and brain parenchyma as well as the spinal canal are included. The compartmental model predicts\\u000a intracranial pressure gradients, blood and CSF flows and displacements in normal and pathological conditions like communicating\\u000a hydrocephalus. The system of differential equations of first

Andreas A. Linninger; Michalis Xenos; Brian Sweetman; Sukruti Ponkshe; Xiaodong Guo; Richard Penn

2009-01-01

171

Task-Specific Functional Brain Geometry from Model Maps  

Microsoft Academic Search

In this paper we propose model maps to derive and repre- sent the intrinsic functional geometry of a brain from functional magnetic resonance imaging (fMRI) data for a specific task. Model maps repre- sent 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

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

2008-01-01

172

The Effect of Tobacco Control Measures during a Period of Rising Cardiovascular Disease Risk in India: A Mathematical Model of Myocardial Infarction and Stroke  

PubMed Central

Background We simulated tobacco control and pharmacological strategies for preventing cardiovascular deaths in India, the country that is expected to experience more cardiovascular deaths than any other over the next decade. Methods and Findings A microsimulation model was developed to quantify the differential effects of various tobacco control measures and pharmacological therapies on myocardial infarction and stroke deaths stratified by age, gender, and urban/rural status for 2013 to 2022. The model incorporated population-representative data from India on multiple risk factors that affect myocardial infarction and stroke mortality, including hypertension, hyperlipidemia, diabetes, coronary heart disease, and cerebrovascular disease. We also included data from India on cigarette smoking, bidi smoking, chewing tobacco, and secondhand smoke. According to the model's results, smoke-free legislation and tobacco taxation would likely be the most effective strategy among a menu of tobacco control strategies (including, as well, brief cessation advice by health care providers, mass media campaigns, and an advertising ban) for reducing myocardial infarction and stroke deaths over the next decade, while cessation advice would be expected to be the least effective strategy at the population level. In combination, these tobacco control interventions could avert 25% of myocardial infarctions and strokes (95% CI: 17%–34%) if the effects of the interventions are additive. These effects are substantially larger than would be achieved through aspirin, antihypertensive, and statin therapy under most scenarios, because of limited treatment access and adherence; nevertheless, the impacts of tobacco control policies and pharmacological interventions appear to be markedly synergistic, averting up to one-third of deaths from myocardial infarction and stroke among 20- to 79-y-olds over the next 10 y. Pharmacological therapies could also be considerably more potent with further health system improvements. Conclusions Smoke-free laws and substantially increased tobacco taxation appear to be markedly potent population measures to avert future cardiovascular deaths in India. Despite the rise in co-morbid cardiovascular disease risk factors like hyperlipidemia and hypertension in low- and middle-income countries, tobacco control is likely to remain a highly effective strategy to reduce cardiovascular deaths. Please see later in the article for the Editors' Summary PMID:23874160

Basu, Sanjay; Glantz, Stanton; Bitton, Asaf; Millett, Christopher

2013-01-01

173

Resuscitation speed affects brain injury in a large animal model of traumatic brain injury and shock  

PubMed Central

Background Optimal fluid resuscitation strategy following combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remain controversial and the effect of resuscitation infusion speed on outcome is not well known. We have previously reported that bolus infusion of fresh frozen plasma (FFP) protects the brain compared with bolus infusion of 0.9% normal saline (NS). We now hypothesize reducing resuscitation infusion speed through a stepwise infusion speed increment protocol using either FFP or NS would provide neuroprotection compared with a high speed resuscitation protocol. Methods 23 Yorkshire swine underwent a protocol of computer controlled TBI and 40% hemorrhage. Animals were left in shock (mean arterial pressure of 35 mmHg) for two hours prior to resuscitation with bolus FFP (n?=?5, 50 ml/min) or stepwise infusion speed increment FFP (n?=?6), bolus NS (n?=?5, 165 ml/min) or stepwise infusion speed increment NS (n?=?7). Hemodynamic variables over a 6-hour observation phase were recorded. Following euthanasia, brains were harvested and lesion size as well as brain swelling was measured. Results Bolus FFP resuscitation resulted in greater brain swelling (22.36?±?1.03% vs. 15.58?±?2.52%, p?=?0.04), but similar lesion size compared with stepwise resuscitation. This was associated with a lower cardiac output (CO: 4.81?±?1.50 l/min vs. 5.45?±?1.14 l/min, p?=?0.03). In the NS groups, bolus infusion resulted in both increased brain swelling (37.24?±?1.63% vs. 26.74?±?1.33%, p?=?0.05) as well as lesion size (3285.44?±?130.81 mm3 vs. 2509.41?±?297.44 mm3, p?=?0.04). This was also associated with decreased cardiac output (NS: 4.37?±?0.12 l/min vs. 6.35?±?0.10 l/min, p?model of combined TBI and HS, stepwise resuscitation protected the brain compared with bolus resuscitation. PMID:25116886

2014-01-01

174

Toward modeling of regional myocardial ischemia and infarction: generation of realistic coronary arterial tree for the heart model of the XCAT phantom  

NASA Astrophysics Data System (ADS)

A realistic 3D coronary arterial tree (CAT) has been developed for the heart model of the computer generated 3D XCAT phantom. The CAT allows generation of a realistic model of the location, size and shape of the associated regional ischemia or infarction for a given coronary arterial stenosis or occlusion. This in turn can be used in medical imaging applications. An iterative rule-based generation method that systematically utilized anatomic, morphometric and physiologic knowledge was used to construct a detailed realistic 3D model of the CAT in the XCAT phantom. The anatomic details of the myocardial surfaces and large coronary arterial vessel segments were first extracted from cardiac CT images of a normal patient with right coronary dominance. Morphometric information derived from porcine data from the literature, after being adjusted by scaling laws, provided statistically nominal diameters, lengths, and connectivity probabilities of the generated coronary arterial segments in modeling the CAT of an average human. The largest six orders of the CAT were generated based on the physiologic constraints defined in the coronary generation algorithms. When combined with the heart model of the XCAT phantom, the realistic CAT provides a unique simulation tool for the generation of realistic regional myocardial ischemia and infraction. Together with the existing heart model, the new CAT provides an important improvement over the current 3D XCAT phantom in providing a more realistic model of the normal heart and the potential to simulate myocardial diseases in evaluation of medical imaging instrumentation, image reconstruction, and data processing methods.

Fung, George S. K.; Segars, W. Paul; Veress, Alexander I.; Gullberg, Grant T.; Tsui, Benjamin M. W.

2009-02-01

175

The immunosuppressant FTY720 prolongs survival in a mouse model of diet-induced coronary atherosclerosis and myocardial infarction.  

PubMed

FTY720, an analogue of sphingosine-1-phosphate, is cardioprotective during acute injury. Whether long-term FTY720 affords cardioprotection is unknown. Here, we report the effects of oral FTY720 on ischemia/reperfusion injury and in hypomorphic apoE mice deficient in SR-BI receptor expression (ApoeR61(h/h)/SRB1(-/- mice), a model of diet-induced coronary atherosclerosis and heart failure. We added FTY720 (0.3 mg·kg(-1)·d(-1)) to the drinking water of C57BL/6J mice. After ex vivo cardiac ischemia/reperfusion injury, these mice had significantly improved left ventricular (LV) developed pressure and reduced infarct size compared with controls. Subsequently, ApoeR61(h/h)/SRB1(-/-) mice fed a high-fat diet for 4 weeks were treated or not with oral FTY720 (0.05 mg·kg(-1)·d(-1)). This sharply reduced mortality (P < 0.02) and resulted in better LV function and less LV remodeling compared with controls without reducing hypercholesterolemia and atherosclerosis. Oral FTY720 reduced the number of blood lymphocytes and increased the percentage of CD4+Foxp3+ regulatory T cells (Tregs) in the circulation, spleen, and lymph nodes. FTY720-treated mice exhibited increased TGF-? and reduced IFN-? expression in the heart. Also, CD4 expression was increased and strongly correlated with molecules involved in natural Treg activity, such as TGF-? and GITR. Our data suggest that long-term FTY720 treatment enhances LV function and increases longevity in mice with heart failure. These benefits resulted not from atheroprotection but from systemic immunosuppression and a moderate reduction of inflammation in the heart. PMID:24508946

Wang, Guanying; Kim, Roy Y; Imhof, Isabella; Honbo, Norman; Luk, Fu S; Li, Kang; Kumar, Nikit; Zhu, Bo-Qing; Eberlé, Delphine; Ching, Daniel; Karliner, Joel S; Raffai, Robert L

2014-02-01

176

Brain covariance selection: better individual functional connectivity models using population prior  

E-print Network

Brain covariance selection: better individual functional connectivity models using population prior.thirion@inria.fr Abstract Spontaneous brain activity, as observed in functional neuroimaging, has been shown to display reproducible structure that expresses brain architecture and car- ries markers of brain pathologies

177

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

178

Survivin-Dependent Angiogenesis in Ischemic Brain  

PubMed Central

Approaches to regulating angiogenesis in the brain, which may diminish parenchymal damage after stroke, are lacking. Survivin, the inhibitor of apoptosis protein, is up-regulated in vitro in vascular endothelial cells by angiogenic factors, including vascular endothelial cell growth factor (VEGF). To evaluate the in vivo role of survivin in the brain in response to hypoxia/ischemia, we used a mouse model of stroke and show that 2 days after permanent middle cerebral artery occlusion, survivin is uniquely expressed by microvessels that form in the peri-infarct and infarct regions. The extent of vascularization of the infarct is dependent on expression of survivin, since vessel density is significantly reduced in mice with heterozygous deficiency of the survivin gene (survivin+/? mice), even though infarct sizes were not different. Hypoxia alone induces survivin expression in the brain, by cultured endothelial cells and by embryonic stem cells, but this response is at least partially independent of VEGF, hypoxia inducible factor 1?, or placental growth factor. Delineating the spatiotemporal pattern of expression of survivin after stroke, and the molecular mechanisms by which this is regulated, may provide novel approaches to therapeutically optimize angiogenesis in a variety of ischemic disorders. PMID:12937134

Conway, Edward M.; Zwerts, Femke; Van Eygen, Veerle; DeVriese, Astrid; Nagai, Nobuo; Luo, Wei; Collen, Desire

2003-01-01

179

Modeling Behavioral and Brain Imaging Phenomena in Transcription Typing with Queuing Networks and Reinforcement Learning Algorithms  

E-print Network

, and then describes how the model simulated the two brain imaging phenomena and three behavioral phenomena in learning). In this paper we focus on modeling the learning aspect of the behavioral phenomena and brain imaging phenomenaModeling Behavioral and Brain Imaging Phenomena in Transcription Typing with Queuing Networks

Wu, Changxu (Sean)

180

N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a global utilization of strategies to open occluded arteries (GUSTO)IV substudy circulation  

Microsoft Academic Search

Background—Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients. Methods and

Stefan K. James; Bertil Lindahl; Agneta Siegbahn

2003-01-01

181

Metabolically active rat brain slices as a model to study the regulation of protein phosphorylation in mammalian brain.  

PubMed

The reversible protein phosphorylation is the most important cellular regulation of the biological functions of many proteins. Disregulation of protein phosphorylation is involved in pathogeneses of several human diseases. The abnormal hyperphosphorylation of microtubule-associated protein tau and its aggregation into neurofibrillary tangles in selective neurons is one of the major brain pathologies of Alzheimer's disease and several other related neurodegenerative diseases. Here we present metabolically competent rat brain slices as a model to study the regulation of protein phosphorylation in brain. Employing this model we have been able to study the abnormal hyperphosphorylation of tau and other microtubule-associated proteins. We have evaluated the activity and intactness of the rat brain slices both biochemically and morphologically. Selective inhibition of protein phosphatase 2A in these rat brain slices by the treatment with okadaic acid induced hyperphosphorylation of tau at many abnormal sites seen in Alzheimer's disease brain and the accumulation of hyperphosphorylated tau in pyramidal neurons of the cortex and hippocampus. The regulation of the phosphorylation of high-molecular-weight microtubule-associated protein, MAP1b, was also studied with this model. This model enables studies on the regulation of protein phosphorylation not only biochemically, but also histochemically and immunocytochemically. Furthermore, unlike cultured cells, the neurons in the brain slices reside in the physiological environment of the brain consisting of natural extracellular matrix, neuronal connectivity, and neuronal-glial interactions. PMID:11223412

Gong, C X; Lidsky, T; Wegiel, J; Grundke-Iqbal, I; Iqbal, K

2001-02-01

182

In vivo models of primary brain tumors: pitfalls and perspectives  

PubMed Central

Animal modeling for primary brain tumors has undergone constant development over the last 60 years, and significant improvements have been made recently with the establishment of highly invasive glioblastoma models. In this review we discuss the advantages and pitfalls of model development, focusing on chemically induced models, various xenogeneic grafts of human cell lines, including stem cell–like cell lines and biopsy spheroids. We then discuss the development of numerous genetically engineered models available to study mechanisms of tumor initiation and progression. At present it is clear that none of the current animal models fully reflects human gliomas. Yet, the various model systems have provided important insight into specific mechanisms of tumor development. In particular, it is anticipated that a combined comprehensive knowledge of the various models currently available will provide important new knowledge on target identification and the validation and development of new therapeutic strategies. PMID:22679124

Huszthy, Peter C.; Daphu, Inderjit; Niclou, Simone P.; Stieber, Daniel; Nigro, Janice M.; Sakariassen, Per ?.; Miletic, Hrvoje; Thorsen, Frits; Bjerkvig, Rolf

2012-01-01

183

A Novel Mouse Model of Penetrating Brain Injury  

PubMed Central

Penetrating traumatic brain injury (pTBI) has been difficult to model in small laboratory animals, such as rats or mice. Previously, we have established a non-fatal, rat model for pTBI using a modified air-rifle that accelerates a pellet, which hits a small probe that then penetrates the experimental animal’s brain. Knockout and transgenic strains of mice offer attractive tools to study biological reactions induced by TBI. Hence, in the present study, we adapted and modified our model to be used with mice. The technical characterization of the impact device included depth and speed of impact, as well as dimensions of the temporary cavity formed in a brain surrogate material after impact. Biologically, we have focused on three distinct levels of severity (mild, moderate, and severe), and characterized the acute phase response to injury in terms of tissue destruction, neural degeneration, and gliosis. Functional outcome was assessed by measuring bodyweight and motor performance on rotarod. The results showed that this model is capable of reproducing major morphological and neurological changes of pTBI; as such, we recommend its utilization in research studies aiming to unravel the biological events underlying injury and regeneration after pTBI. PMID:25374559

Cernak, Ibolja; Wing, Ian D.; Davidsson, Johan; Plantman, Stefan

2014-01-01

184

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

PubMed

The influence of noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) on the extent of ischemic cortical stroke was investigated in experiments on white mongrel male rats with ischemia induced by a combination of the middle cerebral artery occlusion with ipsilateral common carotid artery ligation. Animals were treated with noopept (0.5 mg/kg, i.p.) according to the following schedule: 15 min and 2, 24, and 48 h after the occlusion. Test rats were decapitated 72 h after occlusion, brains were extracted and frozen, and thin brain slices were stained with 2,3,5-triphenyltetrazolium chloride. The slices were scanned and processed using Auc 1 computer program, which estimates the percentage of damaged area relative to that of the whole ipsilateral hemisphere. The conditions of coagulation the distal segment of middle cerebral artery were selected, which caused necrosis localized in the fronto-parietal and dorso-lateral regions of the brain cortex without any damage of subcortical structures. The extent of the brain damage in control group (treated by saline) was 18.6%, while that in the group treated with noopept was 12.2%, thus demonstrating a decrease in the infarction area by 34.5% (p < 05). The data on noopept efficacy on the model of the extensive ischemic injury of brain cortex show that this drug has good prospects for use in the neuroprotective treatment of stroke. PMID:16995431

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

2006-01-01

185

The bistable brain: a neuronal model with symbiotic interactions  

E-print Network

In general, the behavior of large and complex aggregates of elementary components can not be understood nor extrapolated from the properties of a few components. The brain is a good example of this type of networked systems where some patterns of behavior are observed independently of the topology and of the number of coupled units. Following this insight, we have studied the dynamics of different aggregates of logistic maps according to a particular {\\it symbiotic} coupling scheme that imitates the neuronal excitation coupling. All these aggregates show some common dynamical properties, concretely a bistable behavior that is reported here with a certain detail. Thus, the qualitative relationship with neural systems is suggested through a naive model of many of such networked logistic maps whose behavior mimics the waking-sleeping bistability displayed by brain systems. Due to its relevance, some regions of multistability are determined and sketched for all these logistic models.

Ricardo Lopez-Ruiz; Daniele Fournier-Prunaret

2012-08-01

186

JAMA Patient Page: Myocardial Infarction  

MedlinePLUS

... of 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 ...

187

A hierarchical coherent-gene-group model for brain development.  

PubMed

We have described a strategy to analyze the data available on brain genes expression, using the concept of coherent-gene groups controlled by transcription factors (TFs). A hierarchical model of gene-expression patterns during brain development was established that identified the genes assumed to behave as functionally coding. Analysis of the concerned signaling pathways and processes showed distinct temporal gene-expression patterns in relation with neurogenesis/synaptogenesis. We identified the hierarchical tree of TF networks that determined the patterns of genes expressed during brain development. Some 'master TFs' at the top level of the hierarchy regulated the expression of gene groups. Enhanced/decreased activity of a few master TFs may explain paradoxes raised by the genetic determination of autism-spectrum disorders and schizophrenia. Our analysis showed gene-TF networks, common or related, to these disorders that exhibited two maxima of expression, one in the prenatal and the other at early postnatal period of development, consistent with the view that these disorders originate in the prenatal period, develop in the postnatal period, and reach the ultimate neural and behavioral phenotype with different sets of genes regulating each of these periods. We proposed a strategy for drug design based upon the temporal patterns of expression of the concerned TFs. Ligands targeting specific TFs can be designed to specifically affect the pathological evolution of the mutated gene(s) in genetically predisposed patients when administered at relevant stages of brain development. PMID:23173912

Tsigelny, I F; Kouznetsova, V L; Baitaluk, M; Changeux, J-P

2013-03-01

188

Signal transmission competing with noise in model excitable brains  

NASA Astrophysics Data System (ADS)

This is a short review of recent studies in our group on how weak signals may efficiently propagate in a system with noise-induced excitation-inhibition competition which adapts to the activity at short-time scales and thus induces excitable conditions. Our numerical results on simple mathematical models should hold for many complex networks in nature, including some brain cortical areas. In particular, they serve us here to interpret available psycho-technical data.

Marro, J.; Mejias, J. F.; Pinamonti, G.; Torres, J. J.

2013-01-01

189

Towards dynamical system models of language-related brain potentials  

PubMed Central

Event-related brain potentials (ERP) are important neural correlates of cognitive processes. In the domain of language processing, the N400 and P600 reflect lexical-semantic integration and syntactic processing problems, respectively. We suggest an interpretation of these markers in terms of dynamical system theory and present two nonlinear dynamical models for syntactic computations where different processing strategies correspond to functionally different regions in the system’s phase space. PMID:19003488

Gerth, Sabrina; Vasishth, Shravan

2008-01-01

190

Creating Physical 3D Stereolithograph Models of Brain and Skull  

Microsoft Academic Search

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

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

2007-01-01

191

An infant mouse model of brain damage in pneumococcal meningitis  

Microsoft Academic Search

Bacterial meningitis due to Streptococcus pneumoniae is associated with an significant mortality rate and persisting neurologic sequelae including sensory-motor deficits, seizures,\\u000a and impairments of learning and memory. The histomorphological correlate of these sequelae is a pattern of brain damage characterized\\u000a by necrotic tissue damage in the cerebral cortex and apoptosis of neurons in the hippocampal dentate gyrus. Different animal\\u000a models

Denis Grandgirard; Oliver Steiner; Martin G. Täuber; Stephen L. Leib

2007-01-01

192

Amelioration of ischemic brain damage by peritoneal dialysis  

PubMed Central

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patients. PMID:23999426

Godino, Maria del Carmen; Romera, Victor G.; Sanchez-Tomero, Jose Antonio; Pacheco, Jesus; Canals, Santiago; Lerma, Juan; Vivancos, Jose; Moro, Maria Angeles; Torres, Magdalena; Lizasoain, Ignacio; Sanchez-Prieto, Jose

2013-01-01

193

MSC-based VEGF gene therapy in rat myocardial infarction model using facial amphipathic bile acid-conjugated polyethyleneimine.  

PubMed

Mesenchymal stem cells (MSCs) have attracted much attention in regenerative medicine owing to their apparent usefulness as multi-potent replacement cells. The potential of MSC therapy can be further improved by transforming MSCs with therapeutic genes that maximize the efficacy of gene therapy and their own therapeutic ability. Since most conventional transfection methodologies have shown marginal success in delivering exogenous genes into primary cultured cells, efficient gene transfer into primary MSCs is a prerequisite for the development of MSC-based gene therapy strategies to achieve repair and regeneration of damaged tissues. Herein, facially amphipathic bile acid-modified polyethyleneimine (BA-PEI) conjugates were synthesized and used to transfer hypoxia-inducible vascular endothelial growth factor gene (pHI-VEGF) in MSCs for the treatment of rat myocardial infarction. Under the optimized transfection conditions, the BA-PEI conjugates significantly increased the VEGF protein expression levels in rat MSCs, compared with traditional transfection methods such as Lipofectamine™ and branched-PEI (25 kDa). Furthermore, the prepared pHI-VEGF-engineered MSCs (VEGF-MSCs) resulted in improved cell viability, particularly during severe hypoxic exposure in vitro. The transplantation of MSCs genetically modified to overexpress VEGF by BA-PEI enhanced the capillary formation in the infarction region and eventually attenuated left ventricular remodeling after myocardial infarction in rats. This study demonstrates the applicability of the BA-PEI conjugates for the efficient transfection of therapeutic genes into MSCs and the feasibility of using the genetically engineered MSCs in regenerative medicine for myocardial infarction. PMID:24280192

Moon, Hyung-Ho; Joo, Min Kyung; Mok, Hyejung; Lee, Minhyung; Hwang, Ki-Chul; Kim, Sung Wan; Jeong, Ji Hoon; Choi, Donghoon; Kim, Sun Hwa

2014-02-01

194

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 60min 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

195

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

196

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

197

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

198

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

199

SyM-BBB: A Microfluidic Blood Brain Barrier Model  

PubMed Central

Current techniques for mimicking the Blood-Brain Barrier (BBB) largely use incubation chambers (Transwell) separated with a filter and matrix coating to represent and to study barrier permeability. These devices have several critical shortcomings; (a) they do not reproduce critical microenvironmental parameters, primarily anatomical size or hemodynamic shear stress, (b) they often do not provide real-time visualization capability, and (c) they require a large amount of consumables. To overcome these limitations, we have developed a microfluidics based Synthetic Microvasculature model of the Blood-Brain Barrier (SyM-BBB). The SyM-BBB platform is comprised of a plastic, disposable and optically clear microfluidic chip with a microcirculation sized two-compartment chamber. The chamber is designed in such a way as to permit the realization of side-by-side apical and basolateral compartments, thereby simplifying fabrication and facilitating integration with standard instrumentation. The individually addressable apical side is seeded with endothelial cells and the basolateral side can support neuronal cells or conditioned media. In the present study, an immortalized Rat Brain Endothelial cell line (RBE4) was cultured in SyM-BBB with a perfusate of Astrocyte Conditioned Media (ACM). Biochemical analysis showed upregulation of tight junction molecules while permeation studies showed an intact BBB. Finally, transporter assay was successfully demonstrated in SyM-BBB indicating a functional model. PMID:23344641

Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Nichols, Joseph B.; Mills, Ivy R.; Sidoryk-Wegrzynowicz, Marta; Aschner, Michael; Pant, Kapil

2013-01-01

200

Science Sampler: Modeling the effects of drugs on the brain  

NSDL National Science Digital Library

The following activity teaches students about the neurobiological consequences of drug use on their brains and behavior. Students make clay models that allow them to visualize how drugs affect neural communication. If you're concerned that this activity may be too advanced, studies have shown that even third-grade students with some knowledge of the circulatory and nervous systems are able to comprehend the effects of drugs on the body and behavior (Sigelman et al., 2003). This activity aligns with the AAAS science benchmarks on human organisms, cells, model making, and personal health.

Brier, Georgia; Dahlberg, Linda

2007-11-01

201

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

2012-06-07

202

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

203

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

204

Improved myocardial perfusion and cardiac function by controlled-release basic fibroblast growth factor using fibrin glue in a canine infarct model*  

PubMed Central

Objective: Angiogenic therapy is emerging as a potential strategy for the treatment of ischemic heart disease but is limited by a relatively short half-life of growth factors. Fibrin glue (FG) provides a reservoir for controlled-release of growth factors. The aim of this study was to evaluate the effects of basic fibroblast growth factor (bFGF) incorporating FG on angiogenesis and cardiac performance in a canine infarct model. Methods: Acute myocardial infarction was induced by ligation of the left anterior descending coronary artery (LAD). Group I (n=6) underwent ligation of LAD alone. In Group II, transmural channels were created in the infarct area (n=6). In Group III, non-transmural channels were created to locate FG cylinders containing bFGF (n=6). Eight weeks after operation, myocardial perfusion was assessed by single photon emission computed tomography, cardiac function by echocardiography, and vascular development by immunohistochemical staining. Results: Total vascular density and the number of large vessels (internal diameter ?50 ?m) were dramatically higher in Group III than in Groups I and II at eight weeks. Only the controlled-release group exhibited an improvement in regional myocardial perfusion associated with lower defect score. Animals in Group III presented improved cardiac regional systolic and diastolic functions as well as global systolic function in comparison with the other two groups. Conclusions: Enhanced and sustained angiogenic response can be achieved by controlled-release bFGF incorporating FG within transmyocardial laser channels, thus enabling improvement in myocardial perfusion and cardiac function. PMID:21121066

Nie, Shao-ping; Wang, Xiao; Qiao, Shi-bin; Zeng, Qiu-tang; Jiang, Ju-quan; Liu, Xiao-qing; Zhu, Xiang-ming; Cao, Guo-xiang; Ma, Chang-sheng

2010-01-01

205

Regional Mechanics Determine Collagen Fiber Structure in Healing Myocardial Infarcts  

PubMed Central

Following myocardial infarction, the mechanical properties of the healing infarct are an important determinant of heart function and the risk of progression to heart failure. In particular, mechanical anisotropy (having different mechanical properties in different directions) in the healing infarct can preserve pump function of the heart. Based on reports of different collagen structures and mechanical properties in various animal models, we hypothesized that differences in infarct size, shape, and/or location produce different patterns of mechanical stretch that guide evolving collagen fiber structure. We tested the effects of infarct shape and location using a combined experimental and computational approach. We studied mechanics and collagen fiber structure in cryoinfarcts in 53 Sprague-Dawley rats and found that regardless of shape or orientation, cryoinfarcts near the equator of the left ventricle stretched primarily in the circumferential direction and developed circumferentially aligned collagen, while infarcts at the apex stretched similarly in the circumferential and longitudinal direction and developed randomly oriented collagen. In a computational model of infarct healing, an effect of mechanical stretch on fibroblast and collagen alignment was required to reproduce the experimental results. We conclude that mechanical environment determines collagen fiber structure in healing myocardial infarcts. Our results suggest that emerging post-infarction therapies that alter regional mechanics will also alter infarct collagen structure, offering both potential risks and novel therapeutic opportunities. PMID:22418281

Fomovsky, Gregory M.; Rouillard, Andrew D.; Holmes, Jeffrey W.

2012-01-01

206

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

207

Cyclosporin safety in a simplified rat brain tumor implantation model.  

PubMed

Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker) cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate). This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08 ± 6.7 mm(3) on the 7(th) day and 67.25 ± 19.8 mm(3) on 9(th) day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated. PMID:22218474

Felix, Francisco H C; Fontenele, Juvenia B; Teles, Milena G; Bezerra Neto, João E; Santiago, Márcia H A M; Picanço Filho, Roberto L; Menezes, Dalgimar B de; Viana, Glauce S B; Moraes, Manoel O de

2012-01-01

208

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

209

Global case management: using the case management model for the care of patients with acute myocardial infarction in a military hospital in Turkey.  

PubMed

This study was planned in an experimental manner to use the "case management model" for the care of patients with acute myocardial infarction (MI), and to determine the effect of this method on the quality of care, patient and nurse satisfaction, and the patient's inpatient duration at the hospital. Data for the study were obtained using the Patient Information Form, Acute MI Care Protocol (Clinical Pathway), Care Monitoring Scale and Scoring Form, Acute MI Nursing Care Plan, Patient Education Booklet, and a Patient and Nurse Satisfaction Evaluation Survey. Evaluation results showed that the patient group where the case management model was used had increased quality of care, decreased inpatient stay, and increased satisfaction of the patient and the nurse. Therefore, it was suggested that the case management model be used in healthcare institutions in Turkey, care protocols for various diagnoses be developed, and nurses should be trained as case managers to increase the quality of care at healthcare institutions. PMID:16926693

Tosun, Nuran; Akbayrak, Nalan

2006-01-01

210

Dissipation and memory capacity in the quantum brain model  

E-print Network

The quantum model of the brain proposed by Ricciardi and Umezawa is extended to dissipative dynamics in order to study the problem of memory capacity. It is shown that infinitely many vacua are accessible to memory printing in a way that in sequential information recording the storage of a new information does not destroy the previously stored ones, thus allowing a huge memory capacity. The mechanism of information printing is shown to induce breakdown of time-reversal symmetry. Thermal properties of the memory states as well as their relation with squeezed coherent states are finally discussed.

Giuseppe Vitiello

1995-02-06

211

Dissipation and memory capacity in the quantum brain model  

E-print Network

The quantum model of the brain proposed by Ricciardi and Umezawa is extended to dissipative dynamics in order to study the problem of memory capacity. It is shown that infinitely many vacua are accessible to memory printing in a way that in sequential information recording the storage of a new information does not destroy the previously stored ones, thus allowing a huge memory capacity. The mechanism of information printing is shown to induce breakdown of time-reversal symmetry. Thermal properties of the memory states as well as their relation with squeezed coherent states are finally discussed.

Vitiello, G

1995-01-01

212

Comparison of the Cardiac MicroPET Images Obtained Using [(18)F]FPTP and [(13)N]NH3 in Rat Myocardial Infarction Models.  

PubMed

The short half-life of current positron emission tomography (PET) cardiac tracers limits their widespread clinical use. We previously developed a (18)F-labeled phosphonium cation, [(18)F]FPTP, that demonstrated sharply defined myocardial defects in a corresponding infarcted myocardium. The aim of this study was to compare the image properties of PET scans obtained using [(18)F]FPTP with those obtained using [(13)N]NH3 in rat myocardial infarction models. Perfusion abnormality was analyzed in 17 segments of polar map images. The myocardium-to-liver and myocardium-to-lung ratios of [(18)F]FPTP were 10.48 and 2.65 times higher, respectively, than those of [(13)N]NH3 in images acquired 30 min after tracer injection. The myocardial defect size measured by [(18)F]FPTP correlated more closely with the hypoperfused area measured by quantitative 2,3,5-triphenyltetrazolium chloride staining (r = 0.89, P < 0.01) than did [(13)N]NH3 (r = 0.84, P < 0.01). [(18)F]FPTP might be useful as a replacement for the myocardial agent [(13)N]NH3 in cardiac PET/CT applications. PMID:25313324

Kim, Dong-Yeon; Kim, Hyeon Sik; Jang, Hwa Youn; Kim, Ju Han; Bom, Hee-Seung; Min, Jung-Joon

2014-10-01

213

Experimental models of brain ischemia: a review of techniques, magnetic resonance imaging, and investigational cell-based therapies.  

PubMed

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

2014-01-01

214

POSTER PRESENTATION Open Access Multistability in large scale models of brain  

E-print Network

, , ) = 1 2 (1 + tanh ( (xi - ))) (3) where W is the N = 66 nodes human connectome [3], x is the nodePOSTER 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

Paris-Sud XI, Université de

215

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

216

The Impact of Trimetazidine Treatment on Left Ventricular Functions and Plasma Brain Natriuretic Peptide Levels in Patients with Non-ST Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention  

PubMed Central

Background and Objectives The aim of this study was to investigate the impact of treatment with oral trimetazidine (TMZ) applied before and after percutaneous coronary interventions (PCI) on short-term left ventricular functions and plasma brain natriuretic peptide (BNP) levels in patients with non-ST segment elevation myocardial infarction (NSTEMI) undergoing PCI. Subjects and Methods The study included 45 patients who were undergoing PCI with the diagnosis of NSTEMI. The patients were randomized into two groups. The first group (n=22) of the patients hospitalized with the diagnosis of NSTEMI was given conventional therapy plus 60 mg TMZ just prior to PCI. Treatment with TMZ was continued for one month after the procedure. TMZ treatment was not given to the second group (n=23). Echocardiography images were recorded and plasma BNP levels were measured just prior to the PCI and on the 1st and 30th days after PCI. Results The myocardial performance index (MPI) was greater in the second group (p=0.02). In the comparison of BNP levels, they significantly decreased in both of the groups during the 30-day follow-up period (29.0±8 and 50.6±33, p<0.01 respectively). However, decreasing of BNP levels was higher in the group administered with TMZ. The decrease of left ventriclular end-diastolic volume was observed in all groups at 30 days after intervention, but was higher in the group administered with TMZ (p=0.01). Conclusion Trimetazidine treatment commencing prior to PCI and continued after PCI in patients with NSTEMI provides improvements in MPI, left ventricular end diastolic volume and a decrease in BNP levels. PMID:23964292

Karakelleo?lu, ?ule; Gündo?du, Fuat; Ta?, Muhammed Hakan; Kaya, Ahmet; Duman, Hakan; De?irmenci, Hüsnü; Hamur, Hikmet; ?im?ek, Ziya

2013-01-01

217

Kindling and status epilepticus models of epilepsy: rewiring the brain.  

PubMed

This review focuses on the remodeling of brain circuitry associated with epilepsy, particularly in excitatory glutamate and inhibitory GABA systems, including alterations in synaptic efficacy, growth of new connections, and loss of existing connections. From recent studies on the kindling and status epilepticus models, which have been used most extensively to investigate temporal lobe epilepsy, it is now clear that the brain reorganizes itself in response to excess neural activation, such as seizure activity. The contributing factors to this reorganization include activation of glutamate receptors, second messengers, immediate early genes, transcription factors, neurotrophic factors, axon guidance molecules, protein synthesis, neurogenesis, and synaptogenesis. Some of the resulting changes may, in turn, contribute to the permanent alterations in seizure susceptibility. There is increasing evidence that neurogenesis and synaptogenesis can appear not only in the mossy fiber pathway in the hippocampus but also in other limbic structures. Neuronal loss, induced by prolonged seizure activity, may also contribute to circuit restructuring, particularly in the status epilepticus model. However, it is unlikely that any one structure, plastic system, neurotrophin, or downstream effector pathway is uniquely critical for epileptogenesis. The sensitivity of neural systems to the modulation of inhibition makes a disinhibition hypothesis compelling for both the triggering stage of the epileptic response and the long-term changes that promote the epileptic state. Loss of selective types of interneurons, alteration of GABA receptor configuration, and/or decrease in dendritic inhibition could contribute to the development of spontaneous seizures. PMID:15193778

Morimoto, Kiyoshi; Fahnestock, Margaret; Racine, Ronald J

2004-05-01

218

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

219

In vitro models of the blood-brain barrier.  

PubMed

The blood-brain barrier (BBB) proper is composed of endothelial cells (ECs) of the cerebral microvasculature, which are interconnected by tight junctions (TJs) that in turn form a physical barrier restricting paracellular flux. Tight control of vascular permeability is essential for the homeostasis and functionality of the central nervous system (CNS). In vitro BBB models have been in use for decades and have been of great benefit in the process of investigating and understanding the cellular and molecular mechanisms underlying BBB establishment. BBB integrity changes can be addressed in vitro by determining cell monolayer permeability (Pe) to different solutes and measuring trans-endothelial electrical resistance (TEER).This chapter describes procedures that can be utilized for both freshly isolated mouse brain microvascular ECs (MBMECs) and murine or human brain EC lines (bEnd5 or hCMEC/D3), cultivated either as a single monolayer or in cocultivation with primary mouse astrocytes (ACs). It starts with detailed information on how to perform transwell cell culture, including coating of inserts and seeding of the ECs and ACs. Moreover, it encompasses instructions for electrical assessment of the in vitro BBB using the more recent cellZscope(®) device, which was traditionally performed with chopstick electrodes of voltohmmeter type (EVOM). From continuous impedance measurements, the cellZscope(®) device provides TEER (paracellular resistance) and cell membrane capacitance (Ccl-transcellular resistance), two independent measures of monolayer integrity. Additionally, this chapter provides guidance through subsequent experiments such as permeability analysis (Pe, flux), expression analysis (qRT-PCR and Western blotting), and localization analysis of BBB junction proteins (immunocytochemistry) using the same inserts subjected earlier to impedance analysis.As numerous diseases are associated with BBB breakdown, researchers aim to continuously improve and refine in vitro BBB models to mimic in vivo conditions as closely as possible. This chapter summarizes protocols with the intention to provide a collection of BBB in vitro assays that generate reproducible results not only with primary brain ECs but also with EC lines to open up the field for a broader spectrum of researchers who intend to investigate the BBB in vitro particularly aiming at therapeutic aspects. PMID:24510883

Czupalla, Cathrin J; Liebner, Stefan; Devraj, Kavi

2014-01-01

220

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

E-print Network

entry into the systemic circulation, substances must interact with the blood-brain barrier (BBB) en route to brain tissue targets. Many substances with CNS activity, including drugs of abuse, cross the BBB by simple passive diffusion (Oldendorf 1974...; Levin 1980; Cornford et al. 1982). Accordingly, the BBB plays an important role in regulating access of drugs of abuse to the brain. Recent evidence suggests that some drugs of abuse may alter BBB permeability characteristics. The permeability...

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

1992-01-01

221

Fast, sequence adaptive parcellation of brain MR using parametric models.  

PubMed

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

2013-01-01

222

Impairments in verb morphology after brain injury: A connectionist model  

PubMed Central

The formation of the past tense of verbs in English has been the focus of the debate concerning connectionist vs. symbolic accounts of language. Brain-injured patients differ with respect to whether they are more impaired in generating irregular past tenses (take–took) or past tenses for nonce verbs (wug–wugged). Such dissociations have been taken as evidence for distinct “rule” and “associative” memory systems in morphology and against the connectionist approach in which a single system is used for all forms. We describe a simulation model in which these impairments arise from damage to phonological or semantic information, which have different effects on generalization and irregular forms, respectively. The results provide an account of the bases of impairments in verb morphology and show that these impairments can be explained within connectionist models that do not use rules or a separate mechanism for exceptions. PMID:10377460

Joanisse, Marc F.; Seidenberg, Mark S.

1999-01-01

223

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

224

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

E-print Network

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), dynamic modeling, therapeutic modeling. I. INTRODUCTION Elevated ICP associated with TBI is a major

225

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

226

Cerebral Infarction due to a Spontaneous Tumor Embolus from Lung Cancer  

Microsoft Academic Search

A cerebral infarction of the left occipital lobe developed in a 6 5-year-old man with squamous cell carcinoma of the right lung. Neurological examinations and brain CT showed findings typical of ordinary infarction. Postmortem examination revealed a tumor embolus within the posterior cerebral artery. Such spontaneous tumor emboli large enough to obstruct a larger-sized artery are rare.

Kazuyoshi Imaizumi; Takanao Murate; Joji Ohno; Kaoru Shimokata

1995-01-01

227

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

228

Neuropathological basis of age-associated brain atrophy  

PubMed Central

OBJECTIVE To examine the association between brain atrophy during life and neuropathology in an elderly population. DESIGN Cohort study of community dwelling elderly PARTICPANTS Seventy-one healthy elderly were selected from participants of the Oregon Brain Aging Study for having an autopsy, >1 MRI scan and the last MRI scan within 36 months of death. MAIN OUTCOME MEASURES The associations between brain volume trajectories (ventricular, total brain and hippocampal) and time interaction terms for neurofibrillary tangles (NFTs), neuritic plaques (NPs), gross infarcts, microinfarcts, amyloid angiopathy, Lewy bodies, APOE ?4 presence, and clinical diagnosis (no cognitive impairment, mild cognitive impairment (MCI) and dementia, as time varying covariates) were examined in mixed effects models, adjusting for duration of follow up and age at death. RESULTS Ventricular volume trajectory was significantly associated with age, presence of infarcts, NFT and NP scores, the ?4 allele and dementia diagnosis. Total brain volume trajectory was significantly associated with age, and MCI diagnosis. Hippocampal volume trajectory was significantly associated with amyloid angiopathy. CONCLUSION Ventricular volume trajectory is more sensitive than total brain and hippocampal volume trajectories as a marker of accruing Alzheimer disease and vascular pathology in elderly individuals. The association between brain volume trajectories and cognitive impairment (MCI and dementia) remained after controlling for the degree of neuropathology and other covariates. This suggests that there may be other factors, not measured in this study that may be contributing to brain atrophy in those with cognitive impairment. PMID:23552688

Erten-Lyons, D.; Dodge, H. H.; Woltjer, R.; Silbert, L.C.; Howieson, D.B.; Kramer, P.; Kaye, J. A.

2013-01-01

229

Informing pedagogy through the brain-targeted teaching model.  

PubMed

Improving teaching to foster creative thinking and problem-solving for students of all ages will require two essential changes in current educational practice. First, to allow more time for deeper engagement with material, it is critical to reduce the vast number of topics often required in many courses. Second, and perhaps more challenging, is the alignment of pedagogy with recent research on cognition and learning. With a growing focus on the use of research to inform teaching practices, educators need a pedagogical framework that helps them interpret and apply research findings. This article describes the Brain-Targeted Teaching Model, a scheme that relates six distinct aspects of instruction to research from the neuro- and cognitive sciences. PMID:23653775

Hardiman, Mariale

2012-01-01

230

Informing Pedagogy Through the Brain-Targeted Teaching Model  

PubMed Central

Improving teaching to foster creative thinking and problem-solving for students of all ages will require two essential changes in current educational practice. First, to allow more time for deeper engagement with material, it is critical to reduce the vast number of topics often required in many courses. Second, and perhaps more challenging, is the alignment of pedagogy with recent research on cognition and learning. With a growing focus on the use of research to inform teaching practices, educators need a pedagogical framework that helps them interpret and apply research findings. This article describes the Brain-Targeted Teaching Model, a scheme that relates six distinct aspects of instruction to research from the neuro- and cognitive sciences. PMID:23653775

Hardiman, Mariale

2012-01-01

231

Aircraft noise, air pollution, and mortality from myocardial infarction  

Microsoft Academic Search

OBJECTIVE: Myocardial infarction has been associated with both transportation noise and air pollution. We examined residential exposure to aircraft noise and mortality from myocardial infarction, taking air pollution into account. METHODS: We analyzed the Swiss National Cohort, which includes geocoded information on residence. Exposure to aircraft noise and air pollution was determined based on geospatial noise and air-pollution (PM10) models

A. Huss; A. Spoerri; M. Egger; M. Roosli

2010-01-01

232

Decompressive craniectomy after unsuccessful intravenous thrombolysis of malignant cerebral infarction  

PubMed Central

Background: Intravenous recombinant tissue plasminogen activator (rt-PA) is an approved treatment for acute ischemic stroke within 4.5 h of symptoms onset. Decompressive craniectomy (DC) has been shown as an effective therapeutic modality in malignant middle cerebral artery (MCA) infarction. As rt-PA could result in hemorrhagic complication during or after any surgery DC may be associated with severe bleeding after intravenous thrombolysis. Case Description: A 57-year-old woman was presented 90 min after the sudden onset of left hemiplegia. Despite intravenous thrombolytic therapy, she lost consciousness within 48 h and brain CT scan showed a right malignant MCA infarction associated with a small bleeding. DC was performed without any complication. The patient improved dramatically. Conclusion: DC could be done safety for malignant MCA infarction after unsuccessful intravenous thrombolytic therapy even the later was complicated with intra-infarction hemorrhage.

Baharvahdat, Humain; Etemadrezaie, Hamid; Zabyhian, Samira; Valipour, Zahra; Ganjeifar, Babak; Mousavi Mirzaye, Seyed Mohammad; Sasannejad, Payam; Ghandehari, Kavian

2014-01-01

233

Myocardial infarction and weather.  

PubMed

The association of meterological factors with acute myocardial infarction was studied within a one-year period in Helsinki. Seasonal variation was found with the lowest incidence in summer and the highest in late autumn. Environmental temperature was not significantly correlated with the incidence of myocardial infarction but the case fatality rate was higher on coldest days. Atmospheric pressure turned out to be the meteorological variable with the highest correlation with the occurrence of myocardial infarction. Rapid decrease in atmospheric pressure was also associated with increased incidence of acute myocardial infarction. Relative humidity had little independent effect. The weather types with highest and lowest risk of heart attack were determined by the combined use of factor and cluster analysis. The most unfavourable turned out to be a relatively cold and moist weather with low atmospheric pressure, common in Helsinki during early winter and late autumn. The incidence of infarction did not increase on typical cold and dry winter days. The most favourable weather was warm, dry and stable summer weather. The difference in incidences between most and least favourable weather types was three-fold. PMID:616207

Sarna, S; Romo, M; Siltanen, P

1977-08-01

234

A Performance Model of Selection Techniques for P300-Based Brain-Computer Interfaces  

E-print Network

A Performance Model of Selection Techniques for P300-Based Brain-Computer Interfaces Jean [2], and to move a wheelchair [6]. Studies on the design and evaluation of P300-based interac- tive propose a model to predict the performance of selection techniques using Brain-Computer Interfaces based

Casiez, Géry

235

Every cloud has a silver lining: Weather forecasting models could predict brain tumor  

E-print Network

Every cloud has a silver lining: Weather forecasting models could predict brain tumor growth Ever prediction ? a modern state estimation algorithm known as a Local Ensemble Transform Kalman Filter: An Application of Data "Every cloud has a silver lining: Weather forecasting models could predict brain tumor

Kuang, Yang

236

Learning the Cell-Graphs: Macroscopic Modeling of Brain Tumors Cigdem Gunduz  

E-print Network

Learning the Cell-Graphs: Macroscopic Modeling of Brain Tumors C¸igdem G¨und¨uz B¨ulent Yener S. Humayun Gultekin December 8, 2003 Abstract Diffuse gliomas are brain tumors that invade the surrounding of the invasion. The graph theoretical model is used by a machine learning algorithm. The learning algorithm uses

Bystroff, Chris

237

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

238

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

239

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

240

A Spectral Graphical Model Approach for Learning Brain Connectivity Network of Children's Narrative Comprehension  

PubMed Central

Abstract Narrative comprehension is a fundamental cognitive skill that involves the coordination of different functional brain regions. We develop a spectral graphical model with model averaging to study the connectivity networks underlying these brain regions using fMRI data collected from a story comprehension task. Based on the spectral density matrices in the frequency domain, this model captures the temporal dependency of the entire fMRI time series between brain regions. A Bayesian model averaging procedure is then applied to select the best directional links that constitute the brain network. Using this model, brain networks of three distinct age groups are constructed to assess the dynamic change of network connectivity with respect to age. PMID:22432453

Meng, Xiangxiang; Karunanayaka, Prasanna; Holland, Scott K.

2011-01-01

241

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

242

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.

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

2012-01-01

243

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

244

Multimodal nanoprobes evaluating physiological pore size of brain vasculatures in ischemic stroke models.  

PubMed

Ischemic stroke accounts for 80% strokes and originates from a reduction of cerebral blood flow (CBF) after vascular occlusion. For treatment, the first action is to restore CBF by thrombolytic agent recombinant tissue-type plasminogen activator (rt-PA). Although rt-PA benefits clinical outcome, its application is limited by short therapeutic time window and risk of brain hemorrhage. Different to thrombolytic agents, neuroprotectants reduce neurological injuries by blocking ischemic cascade events such as excitotoxicity and oxidative stress. Nano-neuroprotectants demonstrate higher therapeutic effect than small molecular analogues due to their prolonged circulation lifetime and disrupted blood-brain barrier (BBB) in ischemic region. Even enhanced BBB permeability in ischemic territories is verified, the pore size of ischemic vasculatures determining how large and how efficient the therapeutics can pass is barely studied. In this work, nanoprobes (NPs) with different diameters are developed. In vivo multimodal imaging indicates that NP uptakes in ischemic region depended on their diameters and the pore size upper limit of ischemic vasculatures is determined as 10-11 nm. Additionally, penumbra defined as salvageable ischemic tissues performed a higher BBB permeability than infarct core. This work provides a guideline for developing nano-neuroprotectants by taking advantage of the locally enhanced BBB permeability in ischemic brain tissues. PMID:24898608

Zheng, Shuyan; Bai, Ying-Ying; Changyi, Yinzhi; Gao, Xihui; Zhang, Wenqing; Wang, Yuancheng; Zhou, Lu; Ju, Shenghong; Li, Cong

2014-11-01

245

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

246

Endocannabinoids and traumatic brain injury  

PubMed Central

Traumatic brain injury (TBI) represents the leading cause of death in young individuals. It triggers the accumulation of harmful mediators, leading to secondary damage, yet protective mechanisms are also set in motion. The endocannabinoid (eCB) system consists of ligands, such as anandamide and 2-arachidonoyl-glycerol (2-AG), receptors (e.g. CB1, CB2), transporters and enzymes, which are responsible for the ‘on-demand’ synthesis and degradation of these lipid mediators. There is a large body of evidence showing that eCB are markedly increased in response to pathogenic events. This fact, as well as numerous studies on experimental models of brain toxicity, neuroinflammation and trauma supports the notion that the eCB are part of the brain's compensatory or repair mechanisms. These are mediated via CB receptors signalling pathways that are linked to neuronal survival and repair. The levels of 2-AG, the most highly abundant eCB, are significantly elevated after TBI and when administered to TBI mice, 2-AG decreases brain oedema, inflammation and infarct volume and improves clinical recovery. The role of CB1 in mediating these effects was demonstrated using selective antagonists or CB1 knockout mice. CB2 were shown in other models of brain insults to reduce white blood cell rolling and adhesion, to reduce infarct size and to improve motor function. This review is focused on the role the eCB system plays as a self-neuroprotective mechanism and its potential as a basis for the development of novel therapeutic modality for the treatment of CNS pathologies with special emphasis on TBI. LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21418185

Shohami, Esther; Cohen-Yeshurun, Ayelet; Magid, Lital; Algali, Merav; Mechoulam, Raphael

2011-01-01

247

Alterations of brain circuits in Down syndrome murine models.  

PubMed

Trisomy 21, also referred to Down syndrome (DS), is the most common genetic cause of mental retardation, affecting 1 each 800-1000 newborn children all over the world. DS is a complex disease, determined by an extra copy of human chromosome 21 that causes an imbalanced gene dose effect. The syntenies that exist between mouse chromosomes 10, 16, and 17 and human chromosome 21 offer the opportunity for a genotype-phenotype correlation and several mouse models of DS have been developed to improve our knowledge about cognitive disabilities and brain alterations. We present here the different murine models available up to now and we discuss the neural alterations that have been described in these strains. The largest amount of studies involved the so called Ts65Dn mouse showing early alterations of nitrergic, noradrenergic and cholinergic systems at the level of the basal forebrain. Neurogenesis and spine formations are decreased in the hippocampus, as well as the whole size of the cerebellum and the number of granule cells. PMID:21946025

Gotti, Stefano; Caricati, Egidio; Panzica, GianCarlo

2011-12-01

248

Probabilistic multiobject deformable model for MR/SPECT brain image registration and segmentation  

NASA Astrophysics Data System (ADS)

A probabilistic deformable model for the representation of brain structures is described. The statistically learned deformable model represents the relative location of head (skull and scalp) and brain surfaces in MR/SPECT images pairs and accommodates the significant variability of these anatomical structures across different individuals. To provide a training set, a representative collection of 3D MRI volumes of different patients have first been registered to a reference image. The head and brain surfaces of each volume are parameterized by the amplitudes of the vibration modes of a deformable spherical mesh. For a given MR image in the training set, a vector containing the largest vibration modes describing the head and the brain is created. This random vector is statistically constrained by retaining the most significant variations modes of its Karhunen-Loeve expansion on the training population. By these means, both head and brain surfaces are deformed according to the anatomical variability observed in the training set. Two applications of the probabilistic deformable model are presented: the deformable model-based registration of 3D multimodal (MR/SPECT) brain images and the segmentation of the brain from MRI using the probabilistic constraints embedded in the deformable model. The multi-object deformable model may be considered as a first step towards the development of a general purpose probabilistic anatomical atlas of the brain.

Nikou, Christophoros; Heitz, Fabrice; Armspach, Jean-Paul

1999-05-01

249

Evolution of Cortical Activation During Recovery From Corticospinal Tract Infarction  

Microsoft Academic Search

Background and Purpose—Recovery from hemiparesis due to corticospinal tract infarction is well documented, but the mechanism of recovery is unknown. Functional MRI (fMRI) provides a means of identifying focal brain activity related to movement of a paretic hand. Although prior studies have suggested that supplementary motor regions in the ipsilesional and contralesional hemisphere play a role in recovery, little is

Randolph S. Marshall; Gerard M. Perera; Ronald M. Lazar; John W. Krakauer; Robert C. Constantine; Robert L. DeLaPaz

250

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

251

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

PubMed

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. PMID:25230100

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

2014-10-21

252

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

253

Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse  

Microsoft Academic Search

CX3CR1 (fractalkine receptor) is important for sustaining normal microglial activity in the brain. Lack of CX3CR1 reportedly results in neurotoxic microglial phenotype in disease models. The objective of this study was to test the hypothesis that the absence of CX3CR1 worsens the outcome in cerebral ischemia. We observed significantly smaller (56%) infarcts and blood-brain barrier damage in CX3CR1-deficient (CX3CR1\\/) animals

Szilamer Ferenczi; J ozsef Halasz; Zsuzsanna Kornyei

254

Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse  

Microsoft Academic Search

CX3CR1 (fractalkine receptor) is important for sustaining normal microglial activity in the brain. Lack of CX3CR1 reportedly results in neurotoxic microglial phenotype in disease models. The objective of this study was to test the hypothesis that the absence of CX3CR1 worsens the outcome in cerebral ischemia. We observed significantly smaller (56%) infarcts and blood–brain barrier damage in CX3CR1-deficient (CX3CR1?\\/?) animals

Ádám Dénes; Szilamér Ferenczi; József Halász; Zsuzsanna Környei; Krisztina J Kovács

2008-01-01

255

Anisotropic Reinforcement of Acute Anteroapical Infarcts Improves Pump Function  

PubMed Central

Background We hypothesize that a therapy that improves LV pump function early after infarction should decrease the need for compensation through sympathetic activation and dilation, thereby reducing the risk of developing heart failure. The mechanical properties of healing myocardial infarcts are an important determinant of left ventricular (LV) function, yet improving function by altering infarct properties has proven unexpectedly difficult. Using a computational model, we recently predicted that stiffening a large anterior infarct anisotropically (in only one direction) would improve LV function, while isotropic stiffening, the focus of previous studies and therapies, would not. The goal of this study was to test the novel strategy of anisotropic infarct reinforcement. Methods and Results We tested the effects of anisotropic infarct reinforcement in 10 open-chest dogs with large anteroapical infarcts that depressed LV pump function. We measured regional mechanics, LV volumes, and cardiac output at a range of preloads at Baseline, 45 minutes after coronary ligation (Ischemia), and 30 minutes later, following surgical reinforcement in the longitudinal direction (Anisotropic). Ischemia shifted the end-systolic pressure-volume relationship (ESPVR) and cardiac output curves rightward, decreasing cardiac output at matched end-diastolic pressure (EDP) by 44%. Anisotropic reinforcement significantly improved systolic function without impairing diastolic function, recovering half the deficit in overall LV function. Conclusions We conclude that anisotropic reinforcement is a promising new approach to improving LV function following a large myocardial infarction. PMID:22665716

Fomovsky, Gregory M.; Clark, Samantha A.; Parker, Katherine M.; Ailawadi, Gorav; Holmes, Jeffrey W.

2012-01-01

256

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

257

[A method of building the finite-element model with the contour line of human brain].  

PubMed

The contour line of human brain was simulated by the curve-fitting methods and then the inner area was discretized by advancing-front methods which was improved at last. The curve-fitting result was similar to the CT picture of the human brain and the discrete result of inner area could be completed quickly by improved advanced-front methods. A finite element model with the contour line of human brain was built primarily which will contribute to the next algorithm study of electrical impedance tomography in human brain. PMID:16156245

Shuai, Wanjun; Dong, Xiuzhen; Fu, Feng; You, Fusheng; Liu, Ruigang; Shi, Xuetao

2005-08-01

258

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

259

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

Microsoft Academic Search

The human brain efficiently solves certain operations such as object recognition and categorization through a massively parallel network of dedicated processors. However, human cognition also relies on the ability to perform an arbitrarily large set of tasks by flexibly recombining different processors into a novel chain. This flexibility comes at the cost of a severe slowing down and a seriality

Ariel Zylberberg; Diego Fernández Slezak; Pieter R. Roelfsema; Stanislas Dehaene; Mariano Sigman

2010-01-01

260

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

E-print Network

the attended character. Due to the low SNR and variability of EEG signals, P300-based BCI typing systems needINCORPORATION 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

261

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

262

Interpretable Semantic Vectors from a Joint Model of Brain-and Text-Based Meaning  

E-print Network

[afyshe,partha.talukdar,tom.mitchell]@cs.cmu.edu brian.murphy@qub.ac.uk Abstract Vector space models (VSMs) that can incorporate a measure of semantics not previously used to create VSMs: brain activation data and weaknesses of corpus and brain activation data to give a more complete representa- tion of semantics

263

The effect of transcranial magnetic stimulation of rat brain on behavioral models of depression  

Microsoft Academic Search

Magnetic stimulation of the brain in unanesthetized humans and animals can painlessly induce motor movements and has recently been reported to have antidepressant properties. In behavioral models of depression and electroconvulsive therapy including enhancement of apormorphine-induced stereotypy, reduction of immobility in the Porsolt swim test increases in seizure threshold for subsequent stimulation, magnetic stimulation of rat brain had effects similar

Amos Fleischmann; Katrina Prolov; Jacob Abarbanel; R. H. Belmaker

1995-01-01

264

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

265

Different effects of tirofiban and aspirin plus clopidogrel on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion  

PubMed Central

Objective To compare the effects of an aspirin–clopidogrel combination with those of the specific glycoprotein IIb/IIIa inhibitor tirofiban on myocardial no?reflow, nitric oxide concentration and activity of nitric oxide synthase (NOS) isoforms in a mini?swine model of acute myocardial infarction and reperfusion. Methods Area of no?reflow was determined by both myocardial contrast echocardiography and pathological means in 40 mini?swine randomly assigned to five study groups: eight controls, eight pretreated with aspirin–clopidogrel combination for three days, eight given an intravenous infusion of tirofiban, eight treated with ischaemic preconditioning and eight sham operated. The acute myocardial infarction and reperfusion model was created with 3?h occlusion of the left anterior descending coronary artery followed by 1?h reperfusion. Results Compared with the control group, tirofiban significantly decreased the area of no?reflow assessed echocardiographically and pathologically, from 78.5% to 22.8% and 82.3% to 23.2%, respectively (both p??0.05) except for decreasing inducible NOS activity from 0.76 to 0.39?U/mg protein (p?

Yang, Y-J; Zhao, J-L; You, S-J; Wu, Y-J; Jing, Z-C; Yang, W-X; Meng, L; Wang, Y-W; Gao, R-L

2006-01-01

266

Derivation and Validation of a Risk Standardization Model for Benchmarking Hospital Performance for Health-Related Quality of Life Outcomes after Acute Myocardial Infarction  

PubMed Central

Background Before outcomes-based measures of quality can be used to compare and improve care, they must be risk-standardized to account for variations in patient characteristics. Despite the importance of health-related quality of life (HRQL) outcomes among patients with acute myocardial infarction (AMI), no risk-standardized models have been developed. Methods and Results We assessed disease-specific HRQL using the Seattle Angina Questionnaire at baseline and 1 year later in 2693 unselected AMI patients from 24 hospitals enrolled in the TRIUMPH registry. Using 57 candidate sociodemographic, economic, and clinical variables present on admission, we developed a parsimonious, hierarchical linear regression model to predict HRQL. Eleven variables were independently associated with poor HRQL after AMI, including younger age, prior CABG, depressive symptoms, and financial difficulties (R2=20%). The model demonstrated excellent internal calibration and reasonable calibration in an independent sample of 1890 AMI patients in a separate registry, although the model slightly over-predicted HRQL scores in the higher deciles. Among the 24 TRIUMPH hospitals, 1-year unadjusted HRQL scores ranged from 67–89. After risk-standardization, HRQL scores variability narrowed substantially (range=79–83), and the group of hospital performance (bottom 20%/middle 60%/top 20%) changed in 14 of the 24 hospitals (58% reclassification with risk-standardization). Conclusions In this predictive model for HRQL after AMI, we identified risk factors, including economic and psychological characteristics, associated with HRQL outcomes. Adjusting for these factors substantially altered the rankings of hospitals as compared with unadjusted comparisons. Using this model to compare risk-standardized HRQL outcomes across hospitals may identify processes of care that maximize this important patient-centered outcome. PMID:24163068

Arnold, Suzanne V.; Masoudi, Frederick A.; Rumsfeld, John S.; Li, Yan; Jones, Philip G.; Spertus, John A.

2014-01-01

267

Intravenous HOE-642 reduces brain edema and Na uptake in the rat permanent middle cerebral artery occlusion model of stroke: evidence for participation of the blood-brain barrier Na/H exchanger  

PubMed Central

Cerebral edema forms in the early hours of ischemic stroke by processes involving increased transport of Na and Cl from blood into brain across an intact blood–brain barrier (BBB). Our previous studies provided evidence that the BBB Na–K–Cl cotransporter is stimulated by the ischemic factors hypoxia, aglycemia, and arginine vasopressin (AVP), and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema and infarct in rats subjected to permanent middle cerebral artery occlusion (pMCAO). More recently, we showed that BBB Na/H exchanger activity is also stimulated by hypoxia, aglycemia, and AVP. The present study was conducted to further investigate the possibility that a BBB Na/H exchanger also participates in edema formation during ischemic stroke. Sprague-Dawley rats were subjected to pMCAO and then brain edema and Na content assessed by magnetic resonance imaging diffusion-weighed imaging and magnetic resonance spectroscopy Na spectroscopy, respectively, for up to 210?minutes. We found that intravenous administration of the specific Na/H exchange inhibitor HOE-642 significantly decreased brain Na uptake and reduced cerebral edema, brain swelling, and infarct volume. These findings support the hypothesis that edema formation and brain Na uptake during the early hours of cerebral ischemia involve BBB Na/H exchanger activity as well as Na–K–Cl cotransporter activity. PMID:23149557

O'Donnell, Martha E; Chen, Yi-Je; Lam, Tina I; Taylor, Kelleen C; Walton, Jeffrey H; Anderson, Steven E

2013-01-01

268

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

269

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.

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

2014-01-01

270

Three-dimensional mechanisms of increased vulnerability to electric shocks in myocardial infarction: altered virtual electrode polarizations and conduction delay in the peri-infarct zone.  

PubMed

Defibrillation efficacy is decreased in infarcted hearts, but the mechanisms by which infarcted hearts are more vulnerable to electric shocks than healthy hearts remain poorly understood. The goal of this study was to provide insight into the 3D mechanisms for the increased vulnerability to electric shocks in infarcted hearts. We hypothesized that changes in virtual electrode polarizations (VEPs) and propagation delay through the peri-infarct zone (PZ) were responsible. We developed a micro anatomically detailed rabbit ventricular model with chronic myocardial infarction from magnetic resonance imaging and enriched the model with data from optical mapping experiments. We further developed a control model without the infarct. The simulation protocol involved apical pacing followed by biphasic shocks. Simulation results from both models were compared.The upper limit of vulnerability(ULV) was 8 V cm(-1) in the infarction model and 4 V cm(-1) in the control model. VEPs were less pronounced in the infarction model, providing a larger excitable area for postshock propagation but smaller transmembrane potential gradients to initiate new wavefronts. Initial post-shock transmural activation occurred at a later time in the infarction model, and the PZ served to delay propagation in subsequent beats. The presence of the PZ was found to be responsible for the increased vulnerability. PMID:22586222

Rantner, Lukas J; Arevalo, Hermenegild J; Constantino, Jason L; Efimov, Igor R; Plank, Gernot; Trayanova, Natalia A

2012-09-15

271

Three-dimensional mechanisms of increased vulnerability to electric shocks in myocardial infarction: Altered virtual electrode polarizations and conduction delay in the peri-infarct zone  

PubMed Central

Defibrillation efficacy is decreased in infarcted hearts, but the mechanisms by which infarcted hearts are more vulnerable to electric shocks than healthy hearts remain poorly understood. The goal of this study was to provide insight into the 3D mechanisms for the increased vulnerability to electric shocks in infarcted hearts. We hypothesized that changes in virtual electrode polarizations (VEPs) and propagation delay through the peri-infarct zone (PZ) were responsible. We developed a microanatomically detailed rabbit ventricular model with chronic myocardial infarction from magnetic resonance imaging and enriched the model with data from optical mapping experiments. We further developed a control model without the infarct. The simulation protocol involved apical pacing followed by biphasic shocks. Simulation results from both models were compared. The upper limit of vulnerability (ULV) was 8 V cm?1 in the infarction model and 4 V cm?1 in the control model. VEPs were less pronounced in the infarction model, providing a larger excitable area for postshock propagation but smaller transmembrane potential gradients to initiate new wavefronts. Initial post-shock transmural activation occurred at a later time in the infarction model, and the PZ served to delay propagation in subsequent beats. The presence of the PZ was found to be responsible for the increased vulnerability. PMID:22586222

Rantner, Lukas J; Arevalo, Hermenegild J; Constantino, Jason L; Efimov, Igor R; Plank, Gernot; Trayanova, Natalia A

2012-01-01

272

Robot Surgery based on the Physical Properties of the Brain - Physical Brain Model for Planning and Navigation of a Surgical Robot  

Microsoft Academic Search

This paper proposes the planning and navigation of a surgical robot to perform safe and effective operations using finite element analysis results based on physical models of the brain. The physical brain models were proposed based on the results of physical property tests. Finite element analyses of virtual tension tests were carried out under the same conditions as the actual

Aiko Yoshizawa; Jun Okamoto; Hiroshi Yamkawa; Masakatsu G. Fujie

2005-01-01

273

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

274

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

275

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

276

Brain volumetry: an active contour model-based segmentation followed by SVM-based classification.  

PubMed

In this paper a novel automatic approach to identify brain structures in magnetic resonance imaging (MRI) is presented for volumetric measurements. The method is based on the idea of active contour models and support vector machine (SVM) classifiers. The main contributions of the presented method are effective modifications on brain images for active contour model and extracting simple and beneficial features for the SVM classifier. The segmentation process starts with a new generation of active contour models, i.e., vector field convolution (VFC) on modified brain images. VFC results are brain images with the least non-brain regions which are passed on to the SVM classification. The SVM features are selected according to the structure of brain tissues, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). SVM classifiers are trained for each brain tissue based on the set of extracted features. Although selected features are very simple, they are both sufficient and tissue separately effective. Our method validation is done using the gold standard brain MRI data set. Comparison of the results with the existing algorithms is a good indication of our approach's success. PMID:21679935

Tanoori, Betsabeh; Azimifar, Zohreh; Shakibafar, Alireza; Katebi, Sarajodin

2011-08-01

277

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

278

Dietary habit profile in European communities with different risk of myocardial infarction: the impact of migration as a model of gene-environment interaction. The IMMIDIET Study.  

PubMed

The risk of myocardial infarction (MI) is lower in southern than in northern European countries. The lower rate of MI in the Mediterranean regions of Europe suggested a potential role of the traditional Mediterranean diet in the prevention of MI. Unfortunately, in the last 20 years, a tendency to adopt Westernised food habits even in southern regions of Europe is reflected by an increase in the prevalence of obesity. Therefore the impact of diet on MI risk profile among European populations needs to be reconsidered. Genetic risk factors have also been implicated in the development of MI. Genes, indeed, continuously interact with environmental factors in determining the pathogenesis of MI. The aims of the IMMIDIET study are to evaluate: 1. The present dietary habits and the risk profile of three European communities at different risk of MI; 2. The impact of migration on risk factors for MI. Dietary habits and genetic polymorphisms will be evaluated in an Italian, Belgian and British population sample. The historical Italian migration to Belgium and the integration through mixed marriage will be considered as a model of gene-environment interaction. As an index of MI risk profile, factors that are most likely under the combined influence of both dietary and genetic determinants will be investigated. PMID:11894745

Iacoviello, L; Arnout, J; Buntinx, F; Cappuccio, F P; Dagnelie, P C; de Lorgeril, M; Dirckx, C; Donati, M B; Krogh, V; Siani, A

2001-08-01

279

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

280

Abstract--Local mean-field models (MFMs) describe regional brain activities by some connected differential  

E-print Network

Abstract-- Local mean-field models (MFMs) describe regional brain activities by some connected. This method was used to investigate the role of slow modulatory variable in our EMFM when a typical anesthetic

Paris-Sud XI, Université de

281

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

282

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

283

STRIATOCAPSULAR INFARCTION; A SINGLE INSTITUTIONAL EXPERIENCE  

PubMed Central

Objective: Striatocapsular infarction is an uncommon form of deep hemispheric strokes. We analyzed the clinical presentation of this stroke to determine its core features and neurological outcome. Material and methods: This prospective, observational, short-term longitudinal study was carried out from November 1, 2009 to October 30, 2011 in the department of neurology, Sulaimaniya general teaching hospital, Iraq and involved 13 consecutive Kurdish patients who were diagnosed with striatocapsular infarction radiologically; all patients underwent routine blood tests, resting 12-lead ECG, transthoracic echocardiography, and urgent non-contrast CT brain scanning at the time of admission. All patients were reassessed clinically after 3 months. Results: Nine patients (69%) were females and 7 patients (53%) were older than 50 years of age. Infarction of the right lenticular nucleus was more common than the left one. Severe flaccid hemiplegia dominated the clinical presentation. Speech and language dysfunction were found in 4 patients (30%) while inattention and neglect were detected in 8 patients (61%). At 3 months, 4 patients were bed-ridden and 4 were wheel-chair bound; dystonia and involuntary movements did not occur. Only the patient with bilateral infarction demonstrated Parkinsonism. Conclusion: Striatocapsular infraction in Iraqi Kurdish patients was more common in females and at the right lenticular nucleus. Hypertension, smoking, and hypercholesterolemia were the commonest risk factors. Dense hemiplegia was the commonest presentation; the functional outcome was poor in the majority. After 3 months of the ischemic event, involuntary movements and dystonia were not seen, and Parkinsonism was found in one patient only. PMID:23322963

Shukir Muhammed Amin, Osama; Aziz Abdullah, Araz; Xaznadar, Amanj; Shaikhani, Mohammad

2012-01-01

284

Incidence, risk factors, and outcomes of fecal incontinence after acute brain injury: Findings from the traumatic brain injury model systems national database  

Microsoft Academic Search

Foxx-Orenstein A, Kolakowsky-Hayner S, Marwitz JH, Cifu DX, Dunbar A, Englander J, Francisco G. Incidence, risk factors, and outcomes of fecal incontinence after acute brain injury: findings from the Traumatic Brain Injury Model Systems national database. Arch Phys Med Rehabil 2003;84:231-7. Objective: To investigate the incidence, risk factors, and outcome in patients with fecal incontinence after acute brain injury. Design:

Amy Foxx-Orenstein; Stephanie Kolakowsky-Hayner; Jennifer H. Marwitz; David X. Cifu; Ann Dunbar; Jeffrey Englander; Gerard Francisco

2003-01-01

285

Cardiac macrophages and apoptosis after myocardial infarction: effects of central MR blockade.  

PubMed

After myocardial infarction (post-MI), inflammation and apoptosis contribute to progressive cardiac remodeling and dysfunction. Cardiac mineralocorticoid receptor (MR) and ?-adrenergic signaling promote apoptosis and inflammation. Post-MI, MR activation in the brain contributes to sympathetic hyperactivity and an increase in cardiac aldosterone. In the present study, we assessed the time course of macrophage infiltration and apoptosis in the heart as detected by both terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and active caspase-3 immunostaining in both myocytes and nonmyocytes, as well as the effects of central MR blockade by intracerebroventricular infusion of eplerenone at 5 ?g/day on peak changes in macrophage infiltration and apoptosis post-MI. Macrophage numbers were markedly increased in the infarct and peri-infarct zones and to a minor extent in the noninfarct part of the left ventricle at 10 days post-MI and decreased over the 3-mo study period. Apoptosis of both myocytes and nonmyocytes was clearly apparent in the infarct and peri-infarct areas at 10 days post-MI. For TUNEL, the increases persisted at 4 and 12 wk, but the number of active caspase-3-positive cells markedly decreased. Central MR blockade significantly decreased CD80-positive proinflammatory M1 macrophages and increased CD163-positive anti-inflammatory M2 macrophages in the infarct. Central MR blockade also reduced apoptosis of myocytes by 40-50% in the peri-infarct and to a lesser extent of nonmyocytes in the peri-infarct and infarct zones. These findings indicate that MR activation in the brain enhances apoptosis both in myocytes and nonmyocytes in the peri-infarct and infarct area post-MI and contributes to the inflammatory response. PMID:25100076

Rafatian, Naimeh; Westcott, Katherine V; White, Roselyn A; Leenen, Frans H H

2014-10-01

286

Comparing translational population-PBPK modelling of brain microdialysis with bottom-up prediction of brain-to-plasma distribution in rat and human.  

PubMed

The prediction of brain extracellular fluid (ECF) concentrations in human is a potentially valuable asset during drug development as it can provide the pharmacokinetic input for pharmacokinetic-pharmacodynamic models. This study aimed to compare two translational modelling approaches that can be applied at the preclinical stage of development in order to simulate human brain ECF concentrations. A population-PBPK model of the central nervous system was developed based on brain microdialysis data, and the model parameters were translated to their corresponding human values to simulate ECF and brain tissue concentration profiles. In parallel, the PBPK modelling software Simcyp was used to simulate human brain tissue concentrations, via the bottom-up prediction of brain tissue distribution using two different sets of mechanistic tissue composition-based equations. The population-PBPK and bottom-up approaches gave similar predictions of total brain concentrations in both rat and human, while only the population-PBPK model was capable of accurately simulating the rat ECF concentrations. The choice of PBPK model must therefore depend on the purpose of the modelling exercise, the in vitro and in vivo data available and knowledge of the mechanisms governing the membrane permeability and distribution of the drug. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25044007

Ball, Kathryn; Bouzom, François; Scherrmann, Jean-Michel; Walther, Bernard; Declèves, Xavier

2014-11-01

287

Inflammatory Consequences in a Rodent Model of Mild Traumatic Brain Injury  

PubMed Central

Abstract Mild traumatic brain injury (mTBI), particularly mild “blast type” injuries resulting from improvised exploding devices and many sport-caused injuries to the brain, result in long-term impairment of cognition and behavior. Our central hypothesis is that there are inflammatory consequences to mTBI that persist over time and, in part, are responsible for resultant pathogenesis and clinical outcomes. We used an adaptation (1 atmosphere pressure) of a well-characterized moderate-to-severe brain lateral fluid percussion (LFP) brain injury rat model. Our mild LFP injury resulted in acute increases in interleukin-1?/? and tumor necrosis factor alpha levels, macrophage/microglial and astrocytic activation, evidence of heightened cellular stress, and blood–brain barrier (BBB) dysfunction that were evident as early as 3-6?h postinjury. Both glial activation and BBB dysfunction persisted for 18 days postinjury. PMID:23360201

Rea, Harriet C.; Johnson, Kathia M.; Parsley, Margaret A.; Unabia, Geda C.; Xu, GuoJing; Infante, Smitha K.; DeWitt, Douglas S.; Hulsebosch, Claire E.

2013-01-01

288

Modelling the Healthy Premature Infant Brain Brian G. Booth1  

E-print Network

University 2 Division of Neurology, BC Children's Hospital 1. The Background 8% of infants in Canada are born to white matter brain injuries at, or near, time of birth [2]. Diffusion MRI can be used to assess white. This research is undertaken in collaboration with BC Children's Hospital and is partially funded by NSERC. 4

Hamarneh, Ghassan

289

Modeling the Evolution of Decision Rules in the Human Brain  

E-print Network

Plexus, in press.) #12;Selfishness vs. Cooperation Eisler and Levine (Brain and Mind, 2002): Cortical-and-befriend) Orbital prefrontal cortex is main area for deciding between these patterns based on context. NATURE AND NURTURE! #12;Possible fight-or-flight network BRAINSTEM LIMBIC SYSTEM Perception from cortex of fearful

Andras, Peter

290

Ultrastructural features of a brain injury model in cat  

Microsoft Academic Search

We present qualitative and quantitative ultrastructural observations on the changes induced in neuroglia and blood vessels of gray matter of cat brain by an experimental acceleration-deceleration injury which, when used alone, causes negligible morbidity and mortality, but, when combined with systemic hypoxia, leads to coma and delayed death in approximately 50% of experimental subjects. An increase in the proportion of

K. D. Barron; M. P. Dentinger; H. K. Kimelberg; L. R. Nelson; R. S. Bourke; S. Keegan; R. Mankes; E. J. Cragoe

1988-01-01

291

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

292

Symptomatic bilateral isolated perforator infarction following aneurysmal subarachnoid hemorrhage  

PubMed Central

Vasospasm following aneurysmal subarachnoid hemorrhage (SAH) occurs in the extraparenchymal vessels in the subarachnoid space at the base of the brain. Ischemia/ Infarction affecting primarily the perforator vessels in isolation, following aneurysmal SAH is uncommon. A 28-year-old man with a ruptured middle cerebral artery aneurysm underwent clipping of the aneurysm. He developed delayed bilateral deep seated infarcts involving both internal capsular regions, the thalamus and basal ganglia without any major vessel infarct. The patient was managed with triple H (hypertensive hypervolemic hemodilutional) therapy and calcium channel antagonists but did not show any improvement and remained in poor neurological status. Perforator vasospasm occurring secondary to aneurysmal SAH, though documented in experimental animal studies, has rarely been reported in humans in a clinical setting. The present case provides evidence, albeit indirect, of isolated perforator vasospasm, which possibly should be the target of future therapeutic strategies. PMID:23546349

Salunke, Pravin; Gupta, Sunil K

2013-01-01

293

Establishing a model of middle cerebral artery occlusion in rabbits using endovascular interventional techniques  

PubMed Central

This study aimed to establish a minimally invasive and easily controllable focal cerebral ischemia model in rabbits using interventional techniques for use in the study of thrombolytic treatment, and to evaluate the feasibility and reproducibility of the technique. Under the guidance of digital subtraction angiography (DSA), focal cerebral infarction was produced by blocking the middle cerebral artery with arterial emboli to establish a rabbit brain artery occlusion model. DSA and diffusion magnetic resonance imaging (MRI) were used to observe the cerebral vascular obstruction infarction, while modified Bederson scoring was used to evaluate the neurological impairment. The animals were sacrificed 24 h after surgery and brain tissues were stained with 2,3,5-triphenyltetrazolium chloride (TTC) to evaluate the occlusion of the middle cerebral artery and pathological changes. The rabbit brain artery occlusion models were successfully established and the animals survived following embolization. Cerebral infarctions were observed in the brains of all animal models. The focal cerebral infarction rabbit model established by vascular interventional techniques is simple, minimally invasive and reliable, and may be used for early diagnosis of cerebral infarction and clinical thrombolysis studies. PMID:24137295

FENG, LEI; LIU, JUN; CHEN, JIAN; PAN, LI; FENG, GUANG

2013-01-01

294

Protective role for type 4 metabotropic glutamate receptors against ischemic brain damage  

Microsoft Academic Search

We examined the influence of type 4 metabotropic glutamate (mGlu4) receptors on ischemic brain damage using the permanent middle cerebral artery occlusion (MCAO) model in mice and the endothelin-1 (Et-1) model of transient focal ischemia in rats. Mice lacking mGlu4 receptors showed a 25% to 30% increase in infarct volume after MCAO as compared with wild-type littermates. In normal mice,

Slavianka G Moyanova; Federica Mastroiacovo; Lidia V Kortenska; Rumiana G Mitreva; Erminia Fardone; Ines Santolini; Mónica Sobrado; Giuseppe Battaglia; Valeria Bruno; Ferdinando Nicoletti; Richard T Ngomba

2011-01-01

295

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

296

A performance model of selection techniques for p300-based brain-computer interfaces  

Microsoft Academic Search

In this paper, we propose a model to predict the performance of selection techniques using Brain-Computer Interfaces based on P300 signals. This model is based on Markov the- ory and can compute both the time required to select a target and the number of visual flashes needed. We illustrate how to use this model with three different interaction techniques to

Jean-baptiste Sauvan; Anatole Lécuyer; Fabien Lotte; Géry Casiez

2009-01-01

297

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

298

Segmental testicular infarction.  

PubMed

Segmental testicular infarction is described in 11-years-old-child presented with acute left hemiscrotal pain and swelling. Clinical examination suggested left testicular tenderness with no evidence of intratesticular mass and the rest of the scrotal contents were normal. Color doppler study suggested a well circumscribed avascular lesion in the upper pole of left testis and provided a clue to diagnosis. Partial orchidectomy resulted in a satisfactory recovery and provided histopathological confirmation of diagnosis. Authors review their experience with this rare entity and the pertinent literature. PMID:15684456

Sharma, Shyam B; Gupta, Vipul

2005-01-01

299

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

PubMed Central

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

2014-01-01

300

Formation and life-time of memory domains in the dissipative quantum model of brain  

E-print Network

We show that in the dissipative quantum model of brain the time-dependence ofthe frequencies of the electrical dipole wave quanta leads to the dynamicalorganization of the memories in space (i.e. to their localization in more orless diffused regions of the brain) and in time (i.e. to their longer orshorter life-time). The life-time and the localization in domains of the memorystates also depend on internal parameters and on the number of links that thebrain establishes with the external world. These results agree with thephysiological observations of the dynamic formation of neural circuitry whichgrows as brain develops and relates to external world.

Alfinito, E

2000-01-01

301

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

302

Biomarkers in acute myocardial infarction  

Microsoft Academic Search

Myocardial infarction causes significant mortality and morbidity. Timely diagnosis allows clinicians to risk stratify their patients and select appropriate treatment. Biomarkers have been used to assist with timely diagnosis, while an increasing number of novel markers have been identified to predict outcome following an acute myocardial infarction or acute coronary syndrome. This may facilitate tailoring of appropriate therapy to high-risk

Daniel Chan; Leong L Ng

2010-01-01

303

Reverse brain drain in South Korea: State-led model  

Microsoft Academic Search

Korea’s reverse brain drain (RBD) has been an organized government effort, rather than a spontaneous social phenomenon, in\\u000a that various policies and the political support of President Park, Chung-Hee were instrumental in laying the ground work for\\u000a its success. Particular features of Korea’s RBD policies are the creation of a conducive domestic environment (i.e., government-sponsored\\u000a strategic R & D institution-building,

Bang-Song L. Yoon

1992-01-01

304

Topics in Magnetic Resonance. Imaging (1999), 10, 16-36 Modeling Mind and Brain Modeling the Mind: High-Field fMRI-Activation During Cognition  

E-print Network

Topics in Magnetic Resonance. Imaging (1999), 10, 16-36 Modeling Mind and Brain Modeling the Mind function in the brain, but also cognitive function. This latter meaning of "function" is the first medical and scientific opportunity to perform radiology not only on the brain, but also of the mind. In this article, we

305

EEG model and location in brain when enjoying music.  

PubMed

The aim of this study was to confirm the character of EEG and the location in brain when a person was enjoying different rhythm music. It made the subjects excited when they enjoyed different rhythm music, the EEG signals are collected with Phoenix Digital EEG with 128 channels, and compared with the ones before the subjects enjoying the music. Obvious differences have been found between them. And the character of EEG has a little differences when the subjects enjoyed different rhythm music. The character of EEG is 30 Hz when the subjects enjoyed Skating Waltz, the height of wave crest is about 200; the character of EEG is 32 Hz when the subjects enjoyed Radetzy-March, the height of wave crest is about 300-500; the character of EEG is 28 Hz and 38 Hz when the subjects enjoyed Disco music, the height of wave crest is about 200. Then using the software of ASA 3 Course designed by ANT company of Germany, the location in brain was confirmed when a person had excited. The region of the location in brain when a person was excited was focused in the area of the middle abdomen in the pons' side. PMID:17282795

Lu, Huisheng; Wang, Mingshi; Yu, Hongqiang

2005-01-01

306

ORMOSIL nanoparticles as a non-viral gene delivery vector for modeling polyglutamine induced brain pathology  

Microsoft Academic Search

Studies have shown the presence of expanded polyQ containing proteins in brain cells related to Huntington disease (HD) and other poly-glutamine disorders. We report the use of organically modified silica (ORMOSIL) nanoparticles as an efficient non-viral gene carrier in an effort to model brain pathology associated with those disorders induced by expanded polyQ peptides. In experiment 1, plasmids expressing Hemaglutinin-tagged

I. Klejbor; E. K. Stachowiak; D. J. Bharali; I. Roy; I. Spodnik; J. Morys; E. J. Bergey; P. N. Prasad; M. K. Stachowiak

2007-01-01

307

Three-dimensional Gaussian model to define brain metastasis limits on 11C-methionine PET  

Microsoft Academic Search

PurposeSince 11C-methionine (MET) heavily accumulates in brain tumors, PET with MET (MET—PET) is proposed for the image-guided planning of their targeted therapy. Determination of bulk tumor limits is therefore a crucial component of MET—PET image analysis. We aimed at validating a Gaussian model of tumor delineation on MET—PET. We choose MET—PET and MRI data obtained in brain metastases to adjust

Bich-Ngoc-Thanh Tang; Gaetan Van Simaeys; Daniel Devriendt; Niloufar Sadeghi; Olivier Dewitte; Nicolas Massager; Philippe David; Marc Levivier; Serge Goldman

2008-01-01

308

Different effects of K Ca and K ATP agonists on brain tumor permeability between syngeneic and allogeneic rat models  

Microsoft Academic Search

The blood–brain tumor barrier (BTB) significantly limits delivery of effective concentrations of chemotherapeutic drugs to brain tumors. Previous studies suggest that BTB permeability may be modulated via alteration in the activity of potassium channels. In this study, we studied the relationship of BTB permeability increase mediated by potassium channel agonists to channel expression in two rat brain tumor models. Intravenous

Keith L. Black; Dali Yin; Bindu M. Konda; Xiao Wang; Jinwei Hu; MinHee K. Ko; Jennifer-Ann Bayan; Manuel R. Sacapano; Andres J. Espinoza; John M. Ong; Dwain Irvin; Yan Shu

2008-01-01

309

Manifold modeling for brain population analysis Samuel Gerber *, Tolga Tasdizen, P. Thomas Fletcher, Sarang Joshi, Ross Whitaker, and the Alzheimers  

E-print Network

Manifold modeling for brain population analysis Samuel Gerber *, Tolga Tasdizen, P. Thomas Fletcher Brain MRI Manifold learning Computer aided clinical diagnosis a b s t r a c t This paper describes a method for building efficient representations of large sets of brain images. Our hypothesis

Utah, University of

310

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

311

Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke  

PubMed Central

Background and Purpose Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. Methods C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. Results LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. Conclusions Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke. PMID:22438957

Yang, Di; Li, Suk-Yee; Yeung, Chung-Man; Chang, Raymond Chuen-Chung; So, Kwok-Fai; Wong, David; Lo, Amy C. Y.

2012-01-01

312

Modeling dynamic functional information flows on large-scale brain networks.  

PubMed

Growing evidence from the functional neuroimaging field suggests that human brain functions are realized via dynamic functional interactions on large-scale structural networks. Even in resting state, functional brain networks exhibit remarkable temporal dynamics. However, it has been rarely explored to computationally model such dynamic functional information flows on large-scale brain networks. In this paper, we present a novel computational framework to explore this problem using multimodal resting state fMRI (R-fMRI) and diffusion tensor imaging (DTI) data. Basically, recent literature reports including our own studies have demonstrated that the resting state brain networks dynamically undergo a set of distinct brain states. Within each quasi-stable state, functional information flows from one set of structural brain nodes to other sets of nodes, which is analogous to the message package routing on the Internet from the source node to the destination. Therefore, based on the large-scale structural brain networks constructed from DTI data, we employ a dynamic programming strategy to infer functional information transition routines on structural networks, based on which hub routers that most frequently participate in these routines are identified. It is interesting that a majority of those hub routers are located within the default mode network (DMN), revealing a possible mechanism of the critical functional hub roles played by the DMN in resting state. Also, application of this framework on a post trauma stress disorder (PTSD) dataset demonstrated interesting difference in hub router distributions between PTSD patients and healthy controls. PMID:24579202

Lv, Peili; Guo, Lei; Hu, Xintao; Li, Xiang; Jin, Changfeng; Han, Junwei; Li, Lingjiang; Liu, Tianming

2013-01-01

313

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

314

Intravenous Administration of Human Umbilical Cord Blood-Derived AC133+ Endothelial Progenitor Cells in Rat Stroke Model Reduces Infarct Volume: Magnetic Resonance Imaging and Histological Findings  

PubMed Central

Abstract Endothelial progenitor cells (EPCs) hold enormous therapeutic potential for ischemic vascular diseases. Previous studies have indicated that stem/progenitor cells derived from human umbilical cord blood (hUCB) improve functional recovery in stroke models. Here, we examined the effect of hUCB AC133+ EPCs on stroke development and resolution in a middle cerebral artery occlusion (MCAo) rat model. Since the success of cell therapies strongly depends on the ability to monitor in vivo the migration of transplanted cells, we also assessed the capacity of magnetic resonance imaging (MRI) to track in vivo the magnetically labeled cells that were administered. Animals were subjected to transient MCAo and 24 hours later injected intravenously with 107 hUCB AC133+ EPCs. MRI performed at days 1, 7, and 14 after the insult showed accumulation of transplanted cells in stroke-affected hemispheres and revealed that stroke volume decreased at a significantly higher rate in cell-treated animals. Immunohistochemistry analysis of brain tissues localized the administered cells in the stroke-affected hemispheres only and indicated that these cells may have significantly affected the magnitude of endogenous proliferation, angiogenesis, and neurogenesis. We conclude that transplanted cells selectively migrated to the ischemic brain parenchyma, where they exerted a therapeutic effect on the extent of tissue damage, regeneration, and time course of stroke resolution. PMID:23934909

Iskander, Asm; Knight, Robert A.; Zhang, Zheng Gang; Ewing, James R.; Shankar, Adarsh; Varma, Nadimpalli Ravi S.; Bagher-Ebadian, Hassan; Ali, Meser M.; Arbab, Ali S.

2013-01-01

315

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

316

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; Scalabri, 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-Ponce, Valerie; Guy, Jacky; Filosa, Stefania; Hayek, Joussef; D'Esposito, Maurizio

2014-01-01

317

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

318

Failure to Demonstrate Peri-Infarct Depolarizations by Repetitive MR Diffusion Imaging in Acute Human Stroke  

Microsoft Academic Search

Background and Purpose—Peri-infarct depolarizations (PIDs) have been demonstrated with diffusion-weighted MRI (DWI) in experimental stroke and are regarded as an important mechanism of ischemic injury. We tested the hypothesis that PIDs are of relevance for the early enlargement of human brain infarcts. Methods—Ten stroke patients were investigated by repetitive imaging of the apparent diffusion coefficient (ADC) in the acute phase

Tobias Back; Jochen G. Hirsch; Kristina Szabo; Achim Gass

319

Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy.  

PubMed

Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. [3H] gamma-aminobutyric acid, [14C] butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of [3H] gamma-aminobutyric acid and [113mIn] transferrin were calculated using [14C] butanol as the highly extracted reference compound. The [113mIn] transferrin data were also used to "correct" the brain uptake index of [3H] gamma-aminobutyric acid for intravascular retention of [3H] gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid [3H] gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy. These findings indicate that transfer of gamma-aminobutyric acid from plasma to brain extracellular fluid is increased in the model of hepatic encephalopathy studied; hence, they provide support for the hypothesis that plasma-derived gamma-aminobutyric acid may contribute to the neural inhibition of hepatic encephalopathy due to fulminant hepatic failure. PMID:2298374

Bassett, M L; Mullen, K D; Scholz, B; Fenstermacher, J D; Jones, E A

1990-03-01

320

Vascular risk factors and longitudinal changes on brain MRI  

PubMed Central

Objective: To evaluate associations between vascular risk factors and changes in burden of infarcts, ventricular size (VS), sulcal widening (SW), and white matter hyperintensities (WMH) in an initially middle-aged, biracial cohort from the Atherosclerosis Risk in Communities (ARIC) study. Methods: Initial brain magnetic resonance (MR) scans and evaluations for vascular risk factors were performed in 1,812 ARIC participants in 1994–1995. In 2004–2006, 1,130 ARIC participants underwent repeat MR scans. MR scans were rated using a validated 9-point scale for VS, SW, and WMH. Infarcts were recorded. Multiple logistic regression analysis was used to assess associations between vascular risk factors and change between MR scans of one or more grades in VS, SW, WMH, or appearance of new infarcts, controlling for age, sex, and race. Results: At baseline, the 1,112 participants with usable scans (385 black women, 200 black men, 304 white women, 223 white men) had a mean age of 61.7 ± 4.3 years. In adjusted models, diabetes at baseline was associated with incident infarcts (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.29–2.95) and worsening SW (OR 2.10, 95% CI 1.36–3.24). Hypertension at baseline was associated with incident infarcts (OR 1.73, 95% CI 1.23–2.42). In subjects with the highest tertile of fasting blood sugar and systolic blood pressure at baseline, the risk of incident infarcts was 3.68 times higher (95% CI 1.89–7.19) than those in the lowest tertile for both. Conclusion: Both atrophic and ischemic imaging changes were driven by altered glycemic and blood pressure control beginning in midlife. Neurology® 2011;76:1879–1885 PMID:21543737

Penman, A.D.; Catellier, D.J.; Coker, L.H.; Shibata, D.K.; Sharrett, A.R.; Mosley, T.H.

2011-01-01

321

The brain's router: a cortical network model of serial processing in the primate brain.  

PubMed

The human brain efficiently solves certain operations such as object recognition and categorization through a massively parallel network of dedicated processors. However, human cognition also relies on the ability to perform an arbitrarily large set of tasks by flexibly recombining different processors into a novel chain. This flexibility comes at the cost of a severe slowing down and a seriality of operations (100-500 ms per step). A limit on parallel processing is demonstrated in experimental setups such as the psychological refractory period (PRP) and the attentional blink (AB) in which the processing of an element either significantly delays (PRP) or impedes conscious access (AB) of a second, rapidly presented element. Here we present a spiking-neuron implementation of a cognitive architecture where a large number of local parallel processors assemble together to produce goal-driven behavior. The precise mapping of incoming sensory stimuli onto motor representations relies on a "router" network capable of flexibly interconnecting processors and rapidly changing its configuration from one task to another. Simulations show that, when presented with dual-task stimuli, the network exhibits parallel processing at peripheral sensory levels, a memory buffer capable of keeping the result of sensory processing on hold, and a slow serial performance at the router stage, resulting in a performance bottleneck. The network captures the detailed dynamics of human behavior during dual-task-performance, including both mean RTs and RT distributions, and establishes concrete predictions on neuronal dynamics during dual-task experiments in humans and non-human primates. PMID:20442869

Zylberberg, Ariel; Fernández Slezak, Diego; Roelfsema, Pieter R; Dehaene, Stanislas; Sigman, Mariano

2010-04-01

322

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

PubMed Central

The human brain efficiently solves certain operations such as object recognition and categorization through a massively parallel network of dedicated processors. However, human cognition also relies on the ability to perform an arbitrarily large set of tasks by flexibly recombining different processors into a novel chain. This flexibility comes at the cost of a severe slowing down and a seriality of operations (100–500 ms per step). A limit on parallel processing is demonstrated in experimental setups such as the psychological refractory period (PRP) and the attentional blink (AB) in which the processing of an element either significantly delays (PRP) or impedes conscious access (AB) of a second, rapidly presented element. Here we present a spiking-neuron implementation of a cognitive architecture where a large number of local parallel processors assemble together to produce goal-driven behavior. The precise mapping of incoming sensory stimuli onto motor representations relies on a “router” network capable of flexibly interconnecting processors and rapidly changing its configuration from one task to another. Simulations show that, when presented with dual-task stimuli, the network exhibits parallel processing at peripheral sensory levels, a memory buffer capable of keeping the result of sensory processing on hold, and a slow serial performance at the router stage, resulting in a performance bottleneck. The network captures the detailed dynamics of human behavior during dual-task-performance, including both mean RTs and RT distributions, and establishes concrete predictions on neuronal dynamics during dual-task experiments in humans and non-human primates. PMID:20442869

Zylberberg, Ariel; Fernandez Slezak, Diego; Roelfsema, Pieter R.; Dehaene, Stanislas; Sigman, Mariano

2010-01-01

323

Microvascular Resistance Predicts Myocardial Salvage and Infarct Characteristics in ST-Elevation Myocardial Infarction  

PubMed Central

Background The pathophysiology of myocardial injury and repair in patients with ST?elevation myocardial infarction is incompletely understood. We investigated the relationships among culprit artery microvascular resistance, myocardial salvage, and ventricular function. Methods and Results The index of microvascular resistance (IMR) was measured by means of a pressure? and temperature?sensitive coronary guidewire in 108 patients with ST?elevation myocardial infarction (83% male) at the end of primary percutaneous coronary intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were performed early (2 days; n=108) and late (3 months; n=96) after myocardial infarction. T2?weighted? and late gadolinium–enhanced cardiac magnetic resonance delineated the ischemic area at risk and infarct size, respectively. Myocardial salvage was calculated by subtracting infarct size from area at risk. Univariable and multivariable models were constructed to determine the impact of IMR on cardiac magnetic resonance–derived surrogate outcomes. The median (interquartile range) IMR was 28 (17–42) mm Hg/s. The median (interquartile range) area at risk was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%). IMR was a significant multivariable predictor of early myocardial salvage, with a multiplicative effect of 0.87 (95% confidence interval 0.82 to 0.92) per 20% increase in IMR; P<0.001. In patients with anterior myocardial infarction, IMR was a multivariable predictor of early and late myocardial salvage, with multiplicative effects of 0.82 (95% confidence interval 0.75 to 0.90; P<0.001) and 0.92 (95% confidence interval 0.88 to 0.96; P<0.001), respectively. IMR also predicted the presence and extent of microvascular obstruction and myocardial hemorrhage. Conclusion Microvascular resistance measured during primary percutaneous coronary intervention significantly predicts myocardial salvage, infarct characteristics, and left ventricular ejection fraction in patients with ST?elevation myocardial infarction. (J Am Heart Assoc. 2012;1:e002246 doi: 10.1161/JAHA.112.002246) PMID:23130166

Payne, Alexander R.; Berry, Colin; Doolin, Orla; McEntegart, Margaret; Petrie, Mark C.; Lindsay, M. Mitchell; Hood, Stuart; Carrick, David; Tzemos, Niko; Weale, Peter; McComb, Christie; Foster, John; Ford, Ian; Oldroyd, Keith G.

2012-01-01

324

Multifunctional Liposomes Reduce Brain ?-Amyloid Burden and Ameliorate Memory Impairment in Alzheimer's Disease Mouse Models  

PubMed Central

Alzheimer's disease is characterized by the accumulation and deposition of plaques of ?-amyloid (A?) peptide in the brain. Given its pivotal role, new therapies targeting A? are in demand. We rationally designed liposomes targeting the brain and promoting the disaggregation of A? assemblies and evaluated their efficiency in reducing the A? burden in Alzheimer's disease mouse models. Liposomes were bifunctionalized with a peptide derived from the apolipoprotein-E receptor-binding domain for blood–brain barrier targeting and with phosphatidic acid for A? binding. Bifunctionalized liposomes display the unique ability to hinder the formation of, and disaggregate, A? assemblies in vitro (EM experiments). Administration of bifunctionalized liposomes to APP/presenilin 1 transgenic mice (aged 10 months) for 3 weeks (three injections per week) decreased total brain-insoluble A?1–42 (?33%), assessed by ELISA, and the number and total area of plaques (?34%) detected histologically. Also, brain A? oligomers were reduced (?70.5%), as assessed by SDS-PAGE. Plaque reduction was confirmed in APP23 transgenic mice (aged 15 months) either histologically or by PET imaging with [11C]Pittsburgh compound B (PIB). The reduction of brain A? was associated with its increase in liver (+18%) and spleen (+20%). Notably, the novel-object recognition test showed that the treatment ameliorated mouse impaired memory. Finally, liposomes reached the brain in an intact form, as determined by confocal microscopy experiments with fluorescently labeled liposomes. These data suggest that bifunctionalized liposomes destabilize brain A? aggregates and promote peptide removal across the blood–brain barrier and its peripheral clearance. This all-in-one multitask therapeutic device can be considered as a candidate for the treatment of Alzheimer's disease. PMID:25319699

Balducci, Claudia; Mancini, Simona; Minniti, Stefania; La Vitola, Pietro; Zotti, Margherita; Sancini, Giulio; Mauri, Mario; Cagnotto, Alfredo; Colombo, Laura; Fiordaliso, Fabio; Grigoli, Emanuele; Salmona, Mario; Snellman, Anniina; Haaparanta-Solin, Merja; Forloni, Gianluigi; Re, Francesca

2014-01-01

325

Multifunctional Liposomes Reduce Brain ?-Amyloid Burden and Ameliorate Memory Impairment in Alzheimer's Disease Mouse Models.  

PubMed

Alzheimer's disease is characterized by the accumulation and deposition of plaques of ?-amyloid (A?) peptide in the brain. Given its pivotal role, new therapies targeting A? are in demand. We rationally designed liposomes targeting the brain and promoting the disaggregation of A? assemblies and evaluated their efficiency in reducing the A? burden in Alzheimer's disease mouse models. Liposomes were bifunctionalized with a peptide derived from the apolipoprotein-E receptor-binding domain for blood-brain barrier targeting and with phosphatidic acid for A? binding. Bifunctionalized liposomes display the unique ability to hinder the formation of, and disaggregate, A? assemblies in vitro (EM experiments). Administration of bifunctionalized liposomes to APP/presenilin 1 transgenic mice (aged 10 months) for 3 weeks (three injections per week) decreased total brain-insoluble A?1-42 (-33%), assessed by ELISA, and the number and total area of plaques (-34%) detected histologically. Also, brain A? oligomers were reduced (-70.5%), as assessed by SDS-PAGE. Plaque reduction was confirmed in APP23 transgenic mice (aged 15 months) either histologically or by PET imaging with [(11)C]Pittsburgh compound B (PIB). The reduction of brain A? was associated with its increase in liver (+18%) and spleen (+20%). Notably, the novel-object recognition test showed that the treatment ameliorated mouse impaired memory. Finally, liposomes reached the brain in an intact form, as determined by confocal microscopy experiments with fluorescently labeled liposomes. These data suggest that bifunctionalized liposomes destabilize brain A? aggregates and promote peptide removal across the blood-brain barrier and its peripheral clearance. This all-in-one multitask therapeutic device can be considered as a candidate for the treatment of Alzheimer's disease. PMID:25319699

Balducci, Claudia; Mancini, Simona; Minniti, Stefania; La Vitola, Pietro; Zotti, Margherita; Sancini, Giulio; Mauri, Mario; Cagnotto, Alfredo; Colombo, Laura; Fiordaliso, Fabio; Grigoli, Emanuele; Salmona, Mario; Snellman, Anniina; Haaparanta-Solin, Merja; Forloni, Gianluigi; Masserini, Massimo; Re, Francesca

2014-10-15

326

Multi-infarct dementia  

MedlinePLUS

... disorders of the brain One such disorder is Alzheimer disease. Symptoms of Alzheimer disease can be similar to those ... Personality changes and loss of social skills As dementia worsens, symptoms are more obvious and the ability to take ...

327

Development of a Conceptual Model to Predict Physical Activity Participation in Adults with Brain Injuries  

ERIC Educational Resources Information Center

The purpose was to examine psychosocial factors that influence the physical activity behaviors of adults with brain injuries. Two differing models, based on Harter's model of self-worth, were proposed to examine the relationship between perceived competence, social support, physical self-worth, affect, and motivation. Adults numbering 384 with…

Driver, Simon

2008-01-01

328

A multilevel model for movement rehabilitation in Traumatic Brain Injury (TBI) using Virtual Environments  

Microsoft Academic Search

This paper presents a conceptual model for movement rehabilitation of traumatic brain injury (TBI) using virtual environments. This hybrid model integrates principles from ecological systems theory with recent advances in cognitive neuroscience, and supports a multilevel approach to both assessment and treatment. Performance outcomes at any stage of recovery are determined by the interplay of task, individual, and environmental\\/contextual factors.

Peter H. Wilson; Patrick Thomas; David Shum; Jonathan Duckworth; Mark Gugliemetti; H. Rudolph; N. Mumford; R. Eldridge

2006-01-01

329

Xenopus Embryos as a Model to Study the Genetic Mechanisms of Brain Development  

Microsoft Academic Search

The review considers the advantages of Xenopus embryos as an experimental model to study the molecular-genetic mechanisms of embryo development. The results are described that were obtained with this model in studies on the early brain development within the framework of the Russian program Human Genome.

A. G. Zaraisky

2004-01-01

330

A unifying explanation of primary generalized seizures through nonlinear brain modeling and bifurcation analysis  

E-print Network

A unifying explanation of primary generalized seizures through nonlinear brain modeling predictions with regards to seizure phenomena. We show that mapping the structure of the nonlinear bifurcation-clonic and absence seizures are predicted and interrelated by the global bifurcation diagram of the model's dynamics

331

Automated Model-Based Tissue Classification of MR Images of the Brain  

Microsoft Academic Search

We describe a fully automated method for model- based tissue classification of magnetic resonance (MR) images of the brain. The method interleaves classification with estimation of the model parameters, improving the classification at each iteration. The algorithm is able to segment single- and multi- spectral MR images, corrects for MR signal inhomogeneities, and incorporates contextual information by means of Markov

Koen Van Leemput; Frederik Maes; Dirk Vandermeulen; Paul Suetens

1999-01-01

332

Predictive models for pressure-driven fluid infusions into brain parenchyma  

PubMed Central

Direct infusions into brain parenchyma of biological therapeutics for serious brain diseases have been, and are being, considered. However, individual brains, as well as distinct cytoarchitectural regions within brains, vary in their response to fluid flow and pressure. Further, the tissue responds dynamically to these stimuli, requiring a nonlinear treatment of equations that would describe fluid flow and drug transport in brain. We here report in detail on an individual–specific model and a comparison of its prediction with simulations for living porcine brains. Two critical features we introduced into our model — absent from previous ones, but requirements for any useful simulation — are the infusion-induced interstitial expansion and the backflow. These are significant determinants of the flow. Another feature of our treatment is the use of cross–property relations to obtain individual–specific parameters that are coefficients in the equations. The quantitative results are at least encouraging, showing a high fraction of overlap between the computed and measured volumes of distribution of a tracer molecule, and are potentially clinically useful. Several improvements are called for; principally a treatment of the interstitial expansion more fundamentally based on poroelasticity, and a better delineation of the diffusion tensor of a particle confined to the interstitial spaces. PMID:21891847

Raghavan, Raghu; Brady, Martin

2011-01-01

333

Optimal Gaussian Mixture Models of Tissue Intensities in Brain MRI of Patients with Multiple-Sclerosis  

NASA Astrophysics Data System (ADS)

Brain tissue segmentation is important in studying markers in human brain Magnetic Resonance Images (MRI) of patients with diseases such as Multiple Sclerosis (MS). Parametric segmentation approaches typically assume unimodal Gaussian distributions on MRI intensities of individual tissue classes, even in applications on multi-spectral images. However, this assumption has not been rigorously verified especially in the context of MS. In this work, we evaluate the local MRI intensities of both healthy and diseased brain tissues of 21 multi-spectral MRIs (63 volumes in total) of MS patients for adherence to this assumption. We show that the tissue intensities are not uniform across the brain and vary across (anatomical) regions of the brain. Consequently, we show that Gaussian mixtures can better model the multi-spectral intensities. We utilize an Expectation Maximization (EM) based approach to learn the models along with a symmetric Jeffreys divergence criterion to study differences in intensity distributions. The effects of these findings are also empirically verified on automatic segmentation of brains with MS.

Xiao, Yiming; Shah, Mohak; Francis, Simon; Arnold, Douglas L.; Arbel, Tal; Collins, D. Louis

334

Formation and life-time of memory domains in the dissipative quantum model of brain  

E-print Network

We show that in the dissipative quantum model of brain the time-dependence of the frequencies of the electrical dipole wave quanta leads to the dynamical organization of the memories in space (i.e. to their localization in more or less diffused regions of the brain) and in time (i.e. to their longer or shorter life-time). The life-time and the localization in domains of the memory states also depend on internal parameters and on the number of links that the brain establishes with the external world. These results agree with the physiological observations of the dynamic formation of neural circuitry which grows as brain develops and relates to external world.

E. Alfinito; G. Vitiello

2000-02-03

335

Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic-ischemic injury in developing brains.  

PubMed

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is up-regulated in oligodendrocytes (OLs) in mouse models for genetic neurological disorders including globoid cell leukodystrophy (twitcher) and GM1 and GM2 gangliosidoses and in the brain of patients with multiple sclerosis. Since L-PGDS-deficient twitcher mice undergo extensive neuronal death, we concluded that L-PGDS functions protectively against neuronal degeneration. In this study, we investigated whether L-PGDS is also up-regulated in acute and massive brain injury resulting from neonatal hypoxic-ischemic encephalopathy (HIE). Analysis of brains from human neonates who had died from HIE disclosed that the surviving neurons in the infarcted lesions expressed L-PGDS. Mouse models for neonatal HIE were made on postnatal day (PND) 7. Global infarction in the ipsilateral hemisphere was evident at 24h after reoxygenation in this model. Intense L-PGDS immunoreactivity was already observed at 10 min after reoxygenation in apparently normal neurons in the cortex, and thereafter, in neurons adjacent to the infarcted area. Quantitative RT-PCR revealed that the L-PGDS mRNA level of the infarcted hemisphere was 33-fold higher than that of the sham-operated mouse brains at 1h after reoxygenation and that it decreased to the normal level by 24h thereafter. Furthermore, in both human and mouse brains, many of L-PGDS-positive cells were also immunoreactive for p53; and some of these expressed cleaved caspase-3. The expression of L-PGDS in degenerating neurons implies that L-PGDS functions as an early stress protein to protect against neuronal death in the HIE brain. PMID:17499437

Taniguchi, Hidetoshi; Mohri, Ikuko; Okabe-Arahori, Hitomi; Kanekiyo, Takahisa; Kagitani-Shimono, Kuriko; Wada, Kazuko; Urade, Yoshihiro; Nakayama, Masahiro; Ozono, Keiichi; Taniike, Masako

2007-06-01

336

A model of personality change after traumatic brain injury and the development of the Brain Injury Personality Scales  

PubMed Central

Objective The aims of this study were to develop models of personality change after traumatic brain injury (TBI) based on information provided by the TBI survivor and a significant other (SO), and to compare the models generated from the two different sources of information. Methods Individuals with and without TBI and an SO were interviewed separately about their current personality. The SOs were also interviewed about the personality of the TBI survivor before the injury. A subset of TBI survivors and their SOs were interviewed twice to assess test–retest reliability. Items which were not associated with personality change after TBI, which could not be measured reliably or which did not contribute to the model, were excluded. Results Of the 123 original items, 29 items from the interview with the survivor and 31 items from the interview with the SO were retained to form the Brain Injury Personality Scales. Separate factor analyses of ratings from each interview (survivor and SO) resulted in seven first order factors. The second order factor analyses for each interview resulted in four factors. Concordance between the information obtained from the two interviews was low. Conclusions The information obtained from the interviews with the TBI survivors and the SOs produced two models with a similar structure: three superordinate factors of personality items (affective regulation, behavioural regulation and engagement) and one superordinate factor of items relevant to mental state (restlessness and range of thought). Despite the similarity in structure, the content of the information obtained from the two interviews was different. PMID:17259352

Obonsawin, M C; Jefferis, S; Lowe, R; Crawford, J R; Fernandes, J; Holland, L; Woldt, K; Worthington, E; Bowie, G

2007-01-01

337

A finite element model of region-specific response for mild diffuse brain injury.  

PubMed

It is well known that rotational loading is responsible for a spectrum of diffuse brain injuries spanning from concussion to diffuse axonal trauma. Many experimental studies have been performed to understand the pathological and biomechanical factors associated with diffuse brain injuries. Finite element models have also been developed to correlate experimental findings with intrinsic variables such as strain. However, a paucity of studies exist examining the combined role of the strain-time parameter. Consequently, using the principles of finite element analysis, the present study introduced the concept of sustained maximum principal strain (SMPS) criterion and explored its potential applicability to diffuse brain injury. An algorithm was developed to determine if the principal strain in a finite element of the brain exceeded a specified magnitude over a specific time interval. The anatomical and geometrical details of the rat for the two-dimensional model were obtained from published data. Using material properties from literature and iterative techniques, the model was validated under three distinct rotational loading conditions indicative of non-injury, concussion, and diffuse axonal trauma. Validation results produced a set of material properties to define the model and were deemed appropriate to examine the role of sustained strain as an indicator of the mechanics of mild diffuse brain injury at the local level. Using a separate set of histological data obtained from graded mild diffuse brain injury experimental studies in rats, different formulations of SMPS criterion were evaluated. For the hippocampus and parietal cortex regions, 4-4 SMPS criterion was found to most closely match with the pattern of histological results. This was further verified by correlating the fractional areas to the time of unconsciousness for each animal group. Although not fully conclusive, these results are valuable in the understanding of diffuse brain injury pathologies following rotational loading. PMID:20058555

Fijalkowski, Ronald J; Yoganandan, Narayan; Zhang, Jiangyue; Pintar, Frank A

2009-11-01

338

Masquerades of myocardial infarction.  

PubMed Central

I summarize these observations in Figure 1. It represents every person in a hypothetical population who has myocardial infarction. A large but unknown number, some believe almost half, never get help. Mobile coronary care units are reducing this group, but so far only a little. When the diagnosis is not understood the disease is not recognized. Then come discovery and popularization. Hereafter masquerades hide some cases and the diagnosis is missed. Somewhere fairly early the diagnostic fad leads to false positive diagnosis. As new techniques are discovered, perfected and mastered, false positive errors and masquerades leading to oversights diminish but still exist. All the skill and technical virtuosity in the world will not be applied if we do not think of the disease. When we think of it, even obscure cases may be resolved easily. PMID:960416

Bean, W. B.

1976-01-01

339

Managing Malignant Cerebral Infarction  

PubMed Central

Opinion statement Managing patients with malignant cerebral infarction remains one of the foremost challenges in medicine. These patients are at high risk for progressive neurologic deterioration and death due to malignant cerebral edema, and they are best cared for in the intensive care unit of a comprehensive stroke center. Careful initial assessment of neurologic function and of findings on MRI, coupled with frequent reassessment of clinical and radiologic findings using CT or MRI are mandatory to promote the prompt initiation of treatments that will ensure the best outcome in these patients. Significant deterioration in either neurologic function or radiologic findings or both demand timely treatment using the best medical management, which may include osmotherapy (mannitol or hypertonic saline), endotracheal intubation, and mechanical ventilation. Under appropriate circumstances, decompressive craniectomy may be warranted to improve outcome or to prevent death. PMID:21190097

Sahuquillo, Juan; Sheth, Kevin N.; Kahle, Kristopher T.; Walcott, Brian P.

2011-01-01

340

Myocardial infarction after taking eletriptan.  

PubMed

We report the case of a 53-year-old male patient with a medical history significant for paroxysmal atrial fibrillation, migraines with visual aura and non-obstructive coronary artery disease, who sustained a non-ST-elevation myocardial infarction a few hours after taking eletriptan as abortive therapy for migraine headaches. We believe this case implies a causal association between eletriptan and myocardial infarction, considering the timing of both drug intake and symptom onset. To the best of our knowledge this is the first reported myocardial infarction attributable to eletriptan overdose in a patient without obstructive coronary artery disease. PMID:25155004

Dias, Andre; Franco, Emiliana; Hebert, Kathy; Mercedes, Ana

2014-01-01

341

Pruning Hidden Markov Models With Optimal Brain Surgeon  

Microsoft Academic Search

A method of pruning hidden Markov models (HMMs) is presented. The main purpose is to find a good HMM topology for a given task with improved generaliza- tion capability. As a side effect, the resulting model will also save memory and computation costs. The first goal falls into the active research area of model selection. From the model-theoretic research community,

Brian Kan-wing Mak; Kin-wah Chan

2005-01-01

342

Insights into cytoprotection from ground squirrel hibernation, a natural model of tolerance to profound brain oligaemia  

PubMed Central

Progression of acute ischaemic brain damage is complex and multifactorial. Also, evidence suggests that participating molecules and signal transduction pathways can function differently in different cellular contexts. Hibernation torpor, a model of natural tolerance to profoundly reduced blood flow and oxygen delivery to brain, along with models of induced ischaemic tolerance can guide efforts to identify cytoprotective mechanisms that are multifactorial and that target multiple mechanisms in multiple cellular contexts. Post-translational modification of proteins by conjugation with the SUMO (small ubiquitin-related modifier) is massively increased in hibernation and may be such a mechanism. PMID:17073805

Lee, Y.-J.; Hallenbeck, J.M.

2007-01-01

343

A mechanical model predicts morphological abnormalities in the developing human brain  

NASA Astrophysics Data System (ADS)

The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

2014-07-01

344

Do antioxidant vitamins reduce infarct size following acute myocardial ischemia\\/reperfusion?  

Microsoft Academic Search

There is controversy concerning the ability of antioxidant vitamins to reduce myocardial infarct size. We sought to determine whether a brief prophylactic treatment of vitamin C or vitamin C plus Trolox (a water-soluble form of vitamin E) could reduce myocardial infarct size in an experimental model. We used an anesthetized open-chest rabbit model in which a branch of the circumflex

Stephen D. Bellows; Sharon L. Hale; Boris Zalman Simkhovich; Gregory Louis Kay; Robert Alan Kloner

1995-01-01

345

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

PubMed Central

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 conducted for an autoregressive model with 5 latent variables (brain regions), each defined by 3 indicators (successive activity time bins). A series of simulations were then run by generating data from an existing pool of 51 typical readers (aged 7.5-12.5 years). Sample sizes ranged between 20 and 1,000 participants and for each sample size 1,000 replications were run. Results were evaluated using chi-square Type I errors, model convergence, mean RMSEA (root mean square error of approximation) values, confidence intervals of the RMSEA, structural path stability, and D-Fit index values. Results suggested that 70 to 80 participants were adequate to model relationships reflecting close to not so close fit as per MacCallum et al.'s recommendations. Sample sizes of 50 participants were associated with satisfactory fit. It is concluded that structural equation modeling is a viable methodology to model complex regional interdependencies in brain activation in pediatric populations.

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

2014-01-01

346

Does nitric oxide contribute to iron-dependent brain injury after experimental cerebral ischaemia?  

Microsoft Academic Search

Experimental and clinical data suggest that iron has a key role in cerebral ischaemia. We measure infarct volume and analyse\\u000a the nitric oxide responses to brain injury in rat stroke model after increased oral iron intake. Permanent middle cerebral\\u000a artery occlusion (MCAO) was performed in a group of 20 male Wistar rats, 10 of which were fed with a control

A. Gámez; T. Carbonell; R. Rama

2003-01-01

347

Impacts of noise on a field theoretical model of the human brain  

NASA Astrophysics Data System (ADS)

Salient properties of the spatio-temporal patterns in MEG recordings of human brain activity, such as macroscopic coherence of a limited number of modes and the occurrence of phase transitions, have been successfully described with the help of field theoretical models for the dendritic currents in the cortex. So far, however, these models have ignored the effects of noise which play an important role in the emergence of such properties. The present article provides a formal treatment of the effects of stochastic fluctuations in the vicinity of the phase transitions that were observed by Kelso in his so-called Julliard experiment [Fuchs et al., Phase transition in the human brain: spatial mode dynamics, Int. J. Bifurcation and Chaos 2 (1992) 917-939; H. Haken, Principles of Brain Functioning, Springer, Berlin, 1996; J.A.S. Kelso, Dynamic Patterns - The Self-organization of Brain and Behavior, MIT Press, Cambridge, 1995]. To describe and examine these effects, the field theoretical model proposed by Jirsa and Haken [A field theory of electromagnetic brain activity, Phys. Rev. Lett. 77 (1996) 960-963; A derivation of a macroscopic field theory of the brain from the quasi-microscopic neural dynamics, Physica D 99 (1997) 503-526] was extended by incorporating Gaussian white noise. The extended model describes the stochastic properties of the most dominant spatio-temporal components, including stochastic variations of the amplitudes of the extracted spatial modes. Furthermore, the model captures critical phenomena such as critical slowing down and critical fluctuations, which are derived analytically. These theoretical results are generalized by means of numerical simulations of amplitude and phase dynamics.

Frank, T. D.; Daffertshofer, A.; Beek, P. J.; Haken, H.

1999-03-01

348

Brain growth trajectories in mouse strains with central and peripheral serotonin differences: relevance to autism models.  

PubMed

The genetic heterogeneity of autism spectrum disorders (ASDs) suggests that their underlying neurobiology involves dysfunction at the neural network level. Understanding these neural networks will require a major collaborative effort and will depend on validated and widely accepted animal models. Many mouse models have been proposed in autism research, but the assessment of their validity often has been limited to measuring social interactions. However, two other well-replicated findings have been reported in ASDs: transient brain overgrowth in early postnatal life and elevated 5-HT (serotonin) levels in blood platelets (platelet hyperserotonemia). We examined two inbred mouse strains (C57BL/6 and BALB/c) with respect to these phenomena. The BALB/c strain is less social and exhibits some other autistic-like behaviors. In addition, it has a lower 5-HT synthesis rate in the central nervous system due to a single-nucleotide polymorphism in the tryptophan hydroxylase 2 (Tph2) gene. The postnatal growth of brain mass was analyzed with mixed-effects models that included litter effects. The volume of the hippocampal complex and the thickness of the somatosensory cortex were measured in 3D-brain reconstructions from serial sections. The postnatal whole-blood 5-HT levels were assessed with high-performance liquid chromatography. With respect to the BALB/c strain, the C57BL/6 strain showed transient brain overgrowth and persistent blood hyperserotonemia. The hippocampal volume was permanently enlarged in the C57BL/6 strain, with no change in the adult brain mass. These results indicate that, in mice, autistic-like shifts in the brain and periphery may be associated with less autistic-like behaviors. Importantly, they suggest that consistency among behavioral, anatomical, and physiological measures may expedite the validation of new and previously proposed mouse models of autism, and that the construct validity of models should be demonstrated when these measures are inconsistent. PMID:22450231

Flood, Z C; Engel, D L J; Simon, C C; Negherbon, K R; Murphy, L J; Tamavimok, W; Anderson, G M; Janušonis, S

2012-05-17

349

An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction: The importance of model validation  

Microsoft Academic Search

BACKGROUND: To examine interactions among the angiotensin converting enzyme (ACE) insertion\\/deletion, plasminogen activator inhibitor-1 (PAI-1) 4G\\/5G, and tissue plasminogen activator (t-PA) insertion\\/deletion gene polymorphisms on risk of myocardial infarction using data from 343 matched case-control pairs from the Physicians Health Study. We examined the data using both conditional logistic regression and the multifactor dimensionality reduction (MDR) method. One advantage of

Christopher S. Coffey; Patricia R. Hebert; Marylyn D. Ritchie; Harlan M. Krumholz; J. Michael Gaziano; Paul M. Ridker; Nancy J. Brown; Douglas E. Vaughan; Jason H. Moore

2004-01-01

350

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-related research, which can potentially improve MI patient management in the future upon clinical translation of the optimized PET tracers. PMID:24380040

Orbay, Hakan; Zhang, Yin; Valdovinos, Hector F; Song, Guoqing; Hernandez, Reinier; Theuer, Charles P; Hacker, Timothy A; Nickles, Robert J; Cai, Weibo

2014-01-01

351

Neuroprotective treatment of cerebral infarction: an experimental study.  

PubMed

We investigated the effect of the amniotic-derived peptide Plaferon-LB on cerebral tissue damage during photochemical insults in rats. Plaferon-LB (US patent number: 20070123467 A1) was extracted from the amniochorionic membrane of a human placenta and showed a relatively strong antihypoxic effect compared to other interferon. Thrombotic infarction was induced by photochemical illumination after intravenous injection of Rose Bengal. The infarct volume, cerebral tissue oxygen tension, cerebral blood flow, and capillary damage were measured in the following groups: untreated control rats, Plaferon-LB-alone rats, insult-alone rats, and insult in Plaferon-LB pretreated rats. The technique of electron paramagnetic resonance (EPR) spectroscopy was used to study free-radical metabolites in the blood and brain tissue ex vivo. Plaferon-LB alone had no effect on systemic blood pressure, cerebral blood flow, and reactive metabolites in the brains of intact animals. In the insult-alone group, a focal hemorrhage was observed in the ischemic area. The cerebral blood flow and tissue oxygen pressure declined to zero within an hour and remained at this level throughout the insult. The treatment with Plaferon-LB 0.5 hr before illumination resulted in a significant reduction of the median infarct size in the insult-alone group. The total length and percentage ratio of thrombotic vessels were significantly diminished in the infarct area. The intensity of Fe2+, Mn2+ -, Mo5+ -xanthinoxidase-containing complexes, and nitric oxide EPR signals was decreased, and the electron transport in the mitochondria was normalized. The results indicate a significant beneficial effect of Plaferon-LB on cerebral infarct, which is likely due to its antioxidative properties. PMID:23126386

Sanikidze, Tamar V; Beridze, Maia; Mitagvaria, Nodar; Bakhtadze, Sophia; Khan, Nadeem

2013-02-01

352

Microvascular lesions in the brain and retina: The AGES-Reykjavik Study  

PubMed Central

Objective To investigate whether the severity and location of cerebral white matter hyperintensities (WMHs) and brain infarcts are correlated with the signs of retinal microvascular abnormalities in the elderly. Methods The study included 4176 men and women (mean age, 76 years) who participated in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study. Digital retinal images of both dilated eyes were taken and evaluated for the presence of retinal focal arteriolar signs (focal arteriolar narrowing and arteriovenous nicking) and retinopathy lesions (retinal blot hemorrhages and microaneurysms). Brain MRI scans were acquired and evaluated for the presence and distribution of cerebral infarcts and WMHs. Logistic and multinomial logistic models were constructed to estimate the association of retinal microvascular signs to brain lesions. Results Controlling for demographic and major cardiovascular risk factors, retinal focal arteriolar signs, but not retinopathy lesions, were significantly associated with an increasing load of subcortical and periventricular WMHs. The strongest association was found between retinal arteriolar signs and a heavier WMH load, specifically in subcortical frontal lobe and periventricular frontal and parietal caps. There was a tendency towards bilateral retinal focal arteriolar narrowing being more strongly associated with the heavier load of subcortical WMHs. Arteriovenous nicking was significantly associated with subcortical infarcts. Interpretation In older adults, retinal focal arteriolar signs, but not retinopathy lesions, are correlated with the load of diffuse WMHs, particularly those located in the subcortical frontal lobe and the periventricular frontal and parietal caps of the brain. PMID:19475677

Qiu, Chengxuan; Cotch, Mary Frances; Sigurdsson, Sigurdur; Klein, Ronald; Jonasson, Fridbert; Klein, Barbara E. K.; Garcia, Melissa; Jonsson, Palmi V.; Harris, Tamara B.; Eiriksdottir, Gudny; Kjartansson, Olafur; van Buchem, Mark A.; Gudnason, Vilmundur; Launer, Lenore J.

2009-01-01

353

Neurobiology of the basal platyhelminth Macrostomum lignano : map and digital 3D model of the juvenile brain neuropile  

Microsoft Academic Search

We have analyzed brain structure in Macrostomum lignano, a representative of the basal platyhelminth taxon Macrostomida. Using confocal microscopy and digital 3D modeling software\\u000a on specimens labeled with general markers for neurons (tyrTub), muscles (phalloidin), and nuclei (Sytox), an atlas and digital\\u000a model of the juvenile Macrostomum brain was generated. The brain forms a ganglion with a central neuropile surrounded

Joshua Morris; Albert Cardona; Maria Del Mar De Miguel-Bonet; Volker Hartenstein

2007-01-01

354

Brain damage in a new hemorrhagic shock model in the rat using long-term recovery  

SciTech Connect

A new shock model in the rat using hemorrhagic hypotension for production of brain damage is described. Hemorrhagic shock was induced by lowering arterial blood pressure with bleeding. The MABP was maintained at approximately 25 mm Hg, accompanied by isoelectric EEG, and then shed blood was retransfused. At 1 week of recovery, morphological and 45Ca autoradiographic changes were examined. No brain damage was observed in rats after 1 min of isoelectric EEG. Mild neuronal damage in the hippocampal CA1 subfield was seen in some animals after 2 min of isoelectric EEG. Severe and consistent neuronal loss in the hippocampal CA1 subfield was recognized after 3 min of isoelectric EEG. Additional damage was also seen in the dentate hilus and the thalamus in some animals. This model can be used to study the pathophysiology of postshock brain damage and to assess new therapies following shock.

Yamauchi, Y.; Kato, H.; Kogure, K. (Tohoku Univ. School of Medicine, Sendai (Japan))

1990-03-01

355

Inductive modeling using causal studies in neuroeconomics: brains on drugs  

Microsoft Academic Search

This paper introduces a new approach to economic analysis. We show how to move from deductive to inductive modeling and thereby reunite economics with approaches used in the natural sciences. This paper presents the empathy-generosity-punishment model as an example of research based on observation, experimentation, and the elimination of alternatives. Inductive modeling in neuroeconomics allows the identification of the physiologic

Moana Vercoe; Paul J. Zak

2010-01-01

356

Mental modeling and mind-brain-reality relationship  

Microsoft Academic Search

In reality modeling rely on the knowledge that we have, whether they are real or imaginary, naive or sophisticated, our mental models are often constructed on fragmentary information, based on a partial understanding of what is happening and naive psychology. Most research on mental modeling focused on the study of cognitive processes that occur in the human mind in specific

2011-01-01

357

Model analyses of visual biofeedback training for EEG-based brain-computer interface  

Microsoft Academic Search

The primary goal of this study was to construct a simulation model of a biofeedback brain-computer interface (BCI) system to analyze the effect of biofeedback training on BCI users. A mathematical model of a man-machine visual-biofeedback\\u000a BCI system was constructed to simulate a subject using a BCI system to control cursor movements. The model consisted of a\\u000a visual tracking system,

Chih-Wei Chen; Ming-Shaung Ju; Yun-Nien Sun; Chou-Ching K. Lin

2009-01-01

358

A paradigm for epileptic seizure prediction using a coupled oscillator model of the brain  

Microsoft Academic Search

This paper presents a novel theoretical paradigm for epileptic seizure prediction based on a coupled oscillator model of brain dynamics. This model is used to investigate prediction methods capable of tracking the synchronization changes that may lead to a seizure. Previous results indicate that state-space reconstruction of a coupled oscillator model from an EEG-like signal is ill-posed, therefore, monitoring system

Elma O'Sullivan-Greene; Iven Mareels; Dean Freestone; Levin Kulhmann; Anthony Burkitt

2009-01-01

359

Deformable templates guided discriminative models for robust 3D brain MRI segmentation.  

PubMed

Automatically segmenting anatomical structures from 3D brain MRI images is an important task in neuroimaging. One major challenge is to design and learn effective image models accounting for the large variability in anatomy and data acquisition protocols. A deformable template is a type of generative model that attempts to explicitly match an input image with a template (atlas), and thus, they are robust against global intensity changes. On the other hand, discriminative models combine local image features to capture complex image patterns. In this paper, we propose a robust brain image segmentation algorithm that fuses together deformable templates and informative features. It takes advantage of the adaptation capability of the generative model and the classification power of the discriminative models. The proposed algorithm achieves both robustness and efficiency, and can be used to segment brain MRI images with large anatomical variations. We perform an extensive experimental study on four datasets of T1-weighted brain MRI data from different sources (1,082 MRI scans in total) and observe consistent improvement over the state-of-the-art systems. PMID:23836390

Liu, Cheng-Yi; Iglesias, Juan Eugenio; Tu, Zhuowen

2013-10-01

360

Computational modeling of high-level cognition and brain function.  

PubMed

This article describes a computational modeling architecture, 4CAPS, which is consistent with key properties of cortical function and makes good contact with functional neuroimaging results. Like earlier cognitive models such as SOAR, ACT-R, 3CAPS, and EPIC, the proposed cognitive model is implemented in a computer simulation that predicts observable variables such as human response times and error patterns. In addition, the proposed 4CAPS model accounts for the functional decomposition of the cognitive system and predicts fMRI activation levels and their localization within specific cortical regions, by incorporating key properties of cortical function into the design of the modeling system. PMID:10524604

Just, M A; Carpenter, P A; Varma, S

1999-01-01

361

Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics  

PubMed Central

Endothelial cells with tight junctions along with the basement membrane and astrocyte end feet surround cerebral blood vessels to form the blood-brain barrier1. The barrier selectively excludes molecules from crossing between the blood and the brain based upon their size and charge. This function can impede the delivery of therapeutics for neurological disorders. A number of chemotherapeutic drugs, for example, will not effectively cross the blood-brain barrier to reach tumor cells2. Thus, improving the delivery of drugs across the blood-brain barrier is an area of interest. The most prevalent methods for enhancing the delivery of drugs to the brain are direct cerebral infusion and blood-brain barrier disruption3. Direct intracerebral infusion guarantees that therapies reach the brain; however, this method has a limited ability to disperse the drug4. Blood-brain barrier disruption (BBBD) allows drugs to flow directly from the circulatory systeminto the brain and thus more effectively reach dispersed tumor cells. Three methods of barrier disruption include osmotic barrier disruption, pharmacological barrier disruption, and focused ultrasound with microbubbles. Osmotic disruption, pioneered by Neuwelt, uses a hypertonic solution of 25% mannitol that dehydrates the cells of the blood-brain barrier causing them to shrink and disrupt their tight junctions. Barrier disruption can also be accomplished pharmacologically with vasoactive compounds such as histamine5 and bradykinin6. This method, however, is selective primarily for the brain-tumor barrier7. Additionally, RMP-7, an analog of the peptide bradykinin, was found to be inferior when compared head-to-head with osmotic BBBD with 25% mannitol8. Another method, focused ultrasound (FUS) in conjunction with microbubble ultrasound contrast agents, has also been shown to reversibly open the blood-brain barrier9. In comparison to FUS, though, 25% mannitol has a longer history of safety in human patients that makes it a proven tool for translational research10-12. In order to accomplish BBBD, mannitol must be delivered at a high rate directly into the brain's arterial circulation. In humans, an endovascular catheter is guided to the brain where rapid, direct flow can be accomplished. This protocol models human BBBD as closely as possible. Following a cut-down to the bifurcation of the common carotid artery, a catheter is inserted retrograde into the ECA and used to deliver mannitol directly into the internal carotid artery (ICA) circulation. Propofol and N2O anesthesia are used for their ability to maximize the effectiveness of barrier disruption13. If executed properly, this procedure has the ability to safely, effectively, and reversibly open the blood-brain barrier and improve the delivery of drugs that do not ordinarily reach the brain 8,13,14. PMID:23222697

Martin, Jacob A.; Maris, Alexander S.; Ehtesham, Moneeb; Singer, Robert J.

2012-01-01

362

Electric Field Encephalography as a Tool for Functional Brain Research: A Modeling Study  

PubMed Central

We introduce the notion of Electric Field Encephalography (EFEG) based on measuring electric fields of the brain and demonstrate, using computer modeling, that given the appropriate electric field sensors this technique may have significant advantages over the current EEG technique. Unlike EEG, EFEG can be used to measure brain activity in a contactless and reference-free manner at significant distances from the head surface. Principal component analysis using simulated cortical sources demonstrated that electric field sensors positioned 3 cm away from the scalp and characterized by the same signal-to-noise ratio as EEG sensors provided the same number of uncorrelated signals as scalp EEG. When positioned on the scalp, EFEG sensors provided 2–3 times more uncorrelated signals. This significant increase in the number of uncorrelated signals can be used for more accurate assessment of brain states for non-invasive brain-computer interfaces and neurofeedback applications. It also may lead to major improvements in source localization precision. Source localization simulations for the spherical and Boundary Element Method (BEM) head models demonstrated that the localization errors are reduced two-fold when using electric fields instead of electric potentials. We have identified several techniques that could be adapted for the measurement of the electric field vector required for EFEG and anticipate that this study will stimulate new experimental approaches to utilize this new tool for functional brain research. PMID:23844066

Petrov, Yury; Sridhar, Srinivas

2013-01-01

363

Model-based variational smoothing and segmentation for diffusion tensor imaging in the brain.  

PubMed

This article applies a unified approach to variational smoothing and segmentation to brain diffusion tensor image data along user-selected attributes derived from the tensor, with the aim of extracting detailed brain structure information. The application of this framework simultaneously segments and denoises to produce edges and smoothed regions within the white matter of the brain that are relatively homogeneous with respect to the diffusion tensor attributes of choice. This approach enables the visualization of a smoothed, scale invariant representation of the tensor data field in a variety of diverse forms. In addition to known attributes such as fractional anisotropy, these representations include selected directional tensor components and additionally associated continuous valued edge fields that might be used for further segmentation. A comparison is presented of the results of three different data model selections with respect to their ability to resolve white matter structure. The resulting images are integrated to provide better perspective of the model properties (edges, smoothed image, and so forth) and their relationship to the underlying brain anatomy. The improvement in brain image quality is illustrated both qualitatively and quantitatively, and the robust performance of the algorithm in the presence of added noise is shown. Smoothing occurs without loss of edge features because of the simultaneous segmentation aspect of the variational approach, and the output enables better delineation of tensors representative of local and long-range association, projection, and commissural fiber systems. PMID:16943628

Desai, Mukund; Kennedy, David N; Mangoubi, Rami; Shah, Jayant; Karl, Clem; Worth, Andrew; Makris, Nikos; Pien, Homer

2006-01-01

364

Generative models of rich clubs in Hebbian neuronal networks and large-scale human brain networks.  

PubMed

Rich clubs arise when nodes that are 'rich' in connections also form an elite, densely connected 'club'. In brain networks, rich clubs incur high physical connection costs but also appear to be especially valuable to brain function. However, little is known about the selection pressures that drive their formation. Here, we take two complementary approaches to this question: firstly we show, using generative modelling, that the emergence of rich clubs in large-scale human brain networks can be driven by an economic trade-off between connection costs and a second, competing topological term. Secondly we show, using simulated neural networks, that Hebbian learning rules also drive the emergence of rich clubs at the microscopic level, and that the prominence of these features increases with learning time. These results suggest that Hebbian learning may provide a neuronal mechanism for the selection of complex features such as rich clubs. The neural networks that we investigate are explicitly Hebbian, and we argue that the topological term in our model of large-scale brain connectivity may represent an analogous connection rule. This putative link between learning and rich clubs is also consistent with predictions that integrative aspects of brain network organization are especially important for adaptive behaviour. PMID:25180309

Vértes, Petra E; Alexander-Bloch, Aaron; Bullmore, Edward T

2014-10-01

365

Transcranial magnetic stimulation of mouse brain using high-resolution anatomical models  

NASA Astrophysics Data System (ADS)

Transcranial magnetic stimulation (TMS) offers the possibility of non-invasive treatment of brain disorders in humans. Studies on animals can allow rapid progress of the research including exploring a variety of different treatment conditions. Numerical calculations using animal models are needed to help design suitable TMS coils for use in animal experiments, in particular, to estimate the electric field induced in animal brains. In this paper, we have implemented a high-resolution anatomical MRI-derived mouse model consisting of 50 tissue types to accurately calculate induced electric field in the mouse brain. Magnetic field measurements have been performed on the surface of the coil and compared with the calculations in order to validate the calculated magnetic and induced electric fields in the brain. Results show how the induced electric field is distributed in a mouse brain and allow investigation of how this could be improved for TMS studies using mice. The findings have important implications in further preclinical development of TMS for treatment of human diseases.

Crowther, L. J.; Hadimani, R. L.; Kanthasamy, A. G.; Jiles, D. C.

2014-05-01

366

Beta-amyloid deposition in brain is enhanced in mouse models of arterial hypertension.  

PubMed

There are conflicting evidence regarding the association of hypertension with Alzheimer's disease (AD), and so far it is still unexplored whether increased blood pressure levels can be mechanistically related to the pathophysiology of AD. Since the deposition of beta-amyloid (A beta) in brain represents the first pathogenetic event in the onset of AD, in this study we investigated the role of hypertension in the brain deposition of A beta. We analyzed two independent mouse models of hypertension. In both models we observed an increased permeability of blood-brain barrier in cortex and hippocampus. More interestingly, in the same areas hypertensive mice showed a marked positivity to anti-A beta antibodies and the presence of A beta-like fragments. Finally, we analyzed mice after passive immunotherapy with anti-A beta IgG. We observed that this latter approach determined a markedly reduced A beta immunopositivity in both cortex and hippocampus. Our study demonstrates that chronic hypertension determines an impairment of the blood-brain barrier permeability with deposition of A beta in brain tissue and that passive immunotherapy prevents this latter phenomenon. PMID:17673335

Gentile, Maria Teresa; Poulet, Roberta; Di Pardo, Alba; Cifelli, Giuseppe; Maffei, Angelo; Vecchione, Carmine; Passarelli, Francesca; Landolfi, Alessandro; Carullo, Pierluigi; Lembo, Giuseppe

2009-02-01

367

Permeability analysis of neuroactive drugs through a dynamic microfluidic in vitro blood-brain barrier model.  

PubMed

This paper presents the permeability analysis of neuroactive drugs and correlation with in vivo brain/plasma ratios in a dynamic microfluidic blood-brain barrier (BBB) model. Permeability of seven neuroactive drugs (Ethosuximide, Gabapentin, Sertraline, Sunitinib, Traxoprodil, Varenicline, PF-304014) and trans-endothelial electrical resistance (TEER) were quantified in both dynamic (microfluidic) and static (transwell) BBB models, either with brain endothelial cells (bEnd.3) in monoculture, or in co-culture with glial cells (C6). Dynamic cultures were exposed to 15 dyn/cm(2) shear stress to mimic the in vivo environment. Dynamic models resulted in significantly higher average TEER (respective 5.9-fold and 8.9-fold increase for co-culture and monoculture models) and lower drug permeabilities (average respective decrease of 0.050 and 0.052 log(cm/s) for co-culture and monoculture) than static models; and co-culture models demonstrated higher average TEER (respective 90 and 25% increase for static and dynamic models) and lower drug permeability (average respective decrease of 0.063 and 0.061 log(cm/s) for static and dynamic models) than monoculture models. Correlation of the resultant logP e values [ranging from -4.06 to -3.63 log(cm/s)] with in vivo brain/plasma ratios (ranging from 0.42 to 26.8) showed highly linear correlation (R (2) > 0.85) for all model conditions, indicating the feasibility of the dynamic microfluidic BBB model for prediction of BBB clearance of pharmaceuticals. PMID:25118670

Booth, R; Kim, H

2014-12-01

368

PACAP38 Differentially Effects Genes and CRMP2 Protein Expression in Ischemic Core and Penumbra Regions of Permanent Middle Cerebral Artery Occlusion Model Mice Brain  

PubMed Central

Pituitary adenylate-cyclase activating polypeptide (PACAP) has neuroprotective and axonal guidance functions, but the mechanisms behind such actions remain unclear. Previously we examined effects of PACAP (PACAP38, 1 pmol) injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO) along with control saline (0.9% NaCl) injection. Transcriptomic and proteomic approaches using ischemic (ipsilateral) brain hemisphere revealed differentially regulated genes and proteins by PACAP38 at 6 and 24 h post-treatment. However, as the ischemic hemisphere consisted of infarct core, penumbra, and non-ischemic regions, specificity of expression and localization of these identified molecular factors remained incomplete. This led us to devise a new experimental strategy wherein, ischemic core and penumbra were carefully sampled and compared to the corresponding contralateral (healthy) core and penumbra regions at 6 and 24 h post PACAP38 or saline injections. Both reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to examine targeted gene expressions and the collapsin response mediator protein 2 (CRMP2) protein profiles, respectively. Clear differences in expression of genes and CRMP2 protein abundance and degradation product/short isoform was observed between ischemic core and penumbra and also compared to the contralateral healthy tissues after PACAP38 or saline treatment. Results indicate the importance of region-specific analyses to further identify, localize and functionally analyse target molecular factors for clarifying the neuroprotective function of PACAP38. PMID:25257527

Hori, Motohide; Nakamachi, Tomoya; Shibato, Junko; Rakwal, Randeep; Tsuchida, Masachi; Shioda, Seiji; Numazawa, Satoshi

2014-01-01

369

Analysis of biotinylated generation 4 poly(amidoamine) (PAMAM) dendrimer distribution in the rat brain and toxicity in a cellular model of the blood-brain barrier.  

PubMed

Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through the blood-brain barrier (BBB) via carrier-mediated endocytosis. The purpose of this research was to: (1) measure toxicity using lactate dehydrogenase (LDH) assays of generation (G)4 biotinylated and non-biotinylated poly(amidoamine) (PAMAM) dendrimers in a co-culture model of the BBB, (2) determine distribution of dendrimers in the rat brain, kidney, and liver following systemic administration of dendrimers, and (3) conduct atomic force microscopy (AFM) on rat brain sections following systemic administration of dendrimers. LDH measurements showed that biotinylated dendrimers were toxic to cell co-culture after 48 h of treatment. Distribution studies showed evidence of biotinylated and non-biotinylated PAMAM dendrimers in brain. AFM studies showed evidence of dendrimers only in brain tissue of treated rats. These results indicate that biotinylation does not decrease toxicity associated with PAMAM dendrimers and that biotinylated PAMAM dendrimers distribute in the brain. Furthermore, this article provides evidence of nanoparticles in brain tissue following systemic administration of nanoparticles supported by both fluorescence microscopy and AFM. PMID:24048286

Hemmer, Ruth; Hall, Andrew; Spaulding, Robert; Rossow, Brett; Hester, Michael; Caroway, Megan; Haskamp, Anthony; Wall, Steven; Bullen, Heather A; Morris, Celeste; Haik, Kristi L

2013-01-01

370

Efficient Multilevel Brain Tumor Segmentation With Integrated Bayesian Model Classification  

Microsoft Academic Search

We present a new method for automatic segmentation of heterogeneous image data that takes a step toward bridging the gap between bottom-up affinity-based segmentation methods and top-down generative model based approaches. The main contribution of the paper is a Bayesian formulation for incorporating soft model assignments into the calculation of affinities, which are conventionally model free. We integrate the resulting

Jason J. Corso; Eitan Sharon; Shishir Dube; Suzie El-saden; Usha Sinha; Alan L. Yuille

2008-01-01

371

Optimal control of drug delivery to brain tumors for a PDE driven model using the Galerkin finite element method  

E-print Network

Optimal control of drug delivery to brain tumors for a PDE driven model using the Galerkin finite is used to examine the optimal drug delivery to brain tumors. The PDE driven mathematical model and the drug concentration. An optimal control problem is formulated keeping in mind the primary goals

Hanson, Floyd B.

372

Strain Variability, Injury Distribution, and Seizure Onset in a Mouse Model of Stroke in the Immature Brain  

Microsoft Academic Search

Neonatal stroke is an important cause of neurologic morbidity and cerebral palsy. Recently, we have determined that in postnatal day 12 CD1 mice unilateral carotid ligation alone results in seizures and brain injury. We have shown that, in this model, seizure scores correlate with brain injury scores. We have applied this model to another strain of mice to assess strain-related

Anne M. Comi; Michael V. Johnston; Mary Ann Wilson

2005-01-01

373

Dynamic brain structural changes after left hemisphere subcortical stroke.  

PubMed

This study aimed to quantify dynamic structural changes in the brain after subcortical stroke and identify brain areas that contribute to motor recovery of affected limbs. High-resolution structural MRI and neurological examinations were conducted at five consecutive time points during the year following stroke in 10 patients with left hemisphere subcortical infarctions involving motor pathways. Gray matter volume (GMV) was calculated using an optimized voxel-based morphometry technique, and dynamic changes in GMV were evaluated using a mixed-effects model. After stroke, GMV was decreased bilaterally in brain areas that directly or indirectly connected with lesions, which suggests the presence of regional damage in these "healthy" brain tissues in stroke patients. Moreover, the GMVs of these brain areas were not correlated with the Motricity Index (MI) scores when controlling for time intervals after stroke, which indicates that these structural changes may reflect an independent process (such as axonal degeneration) but cannot affect the improvement of motor function. In contrast, the GMV was increased in several brain areas associated with motor and cognitive functions after stroke. When controlling for time intervals after stroke, only the GMVs in the cognitive-related brain areas (hippocampus and precuneus) were positively correlated with MI scores, which suggests that the structural reorganization in cognitive-related brain areas may facilitate the recovery of motor function. However, considering the small sample size of this study, further studies are needed to clarify the exact relationships between structural changes and recovery of motor function in stroke patients. PMID:22431281

Fan, Fengmei; Zhu, Chaozhe; Chen, Hai; Qin, Wen; Ji, Xunming; Wang, Liang; Zhang, Yujin; Zhu, Litao; Yu, Chunshui

2013-08-01

374

Detection of dynamic brain networks modulated by acupuncture using a graph theory model  

E-print Network

Detection of dynamic brain networks modulated by acupuncture using a graph theory model Lijun Bai acupuncture manipulation have already demonstrated significant modulatory effects on wide limbic of acupuncture, however, knowledge on the organization of such large-scale cortical networks behind the active

Tian, Jie

375

P300 based brain-computer interface using Hidden Markov Models  

Microsoft Academic Search

This paper reports on preliminary work on the use of hidden Markov models (HMMs) approach for tasks classification in P300-based brain-computer interface (BCI) system. Every HMM is trained on a set of electroencephalogram (EEG) records issued from different sessions corresponding to the same task. The HMMs that has been built take into account the variability of EEGs during different sessions.

Salah Helmy; Tarik Al-ani; Yskandar Hamam; Essam El-madbouly

2008-01-01

376

A Generative Model for Brain Tumor Segmentation in Multi-Modal Images  

E-print Network

A Generative Model for Brain Tumor Segmentation in Multi-Modal Images Bjoern H. Menze1,2 , Koen Van automated method for channel-specific tumor segmentation in such multi- dimensional images. Generative the same shape and extend of pathology in all modalities, the standard multi-channel segmentation may i

Golland, Polina

377

A new rat brain tumor model: Glioma disseminated via the cerebral spinal fluid pathways  

Microsoft Academic Search

A rat brain tumor model has been developed with the clinical and pathological features of dissemination via the cerebral spinal fluid (CSF) pathways. A precise number of 9L gliosarcoma cells (5 × 102 to 5 × 105) is stereotactically injected into the CSF of the lateral ventricle. The interval until the onset of neurological symptoms and then death is reproducible

Arleta B. Rewers; Edward S. Redgate; Melvin Deutsch; Edwin R. Fisher; Sallie S. Boggs

1990-01-01

378

Point process modeling on decoding and encoding for Brain Machine Interfaces  

Microsoft Academic Search

Point process modeling has the potential to capture the specificity of neural firing where the information is contained in the spike time occurrence. We aim at building an adaptive signal processing framework for brain machine interfaces working directly in the spike domain. However, the signal processing tools for continuous stochastic processes faces challenge when implemented directly on point processes. Under

Yiwen Wang; Jose C. Principe

2009-01-01

379

Researchers Find that Tumor Stem Cells are Good Models for Brain Tumor Research  

Cancer.gov

Researchers have found that tumor stem cell lines derived directly from human glioblastoma brain tumors are a better model to study the biology and physiology of glioblastomas than are cancer cell lines that have been commonly used in cancer research laboratories.

380

The dissipative quantum model of brain: how does memory localize in correlated neuronal domains  

Microsoft Academic Search

The mechanism of memory localization in extended domains is described in the\\u000aframework of the parametric dissipative quantum model of brain. The size of the\\u000adomains and the capability in memorizing depend on the number of links the\\u000asystem is able to establish with the external world.

Eleonora Alfinito; Giuseppe Vitiello

2000-01-01

381

The dissipative quantum model of brain: how do memory localize in correlated neuronal domains  

E-print Network

The mechanism of memory localization in extended domains is described in the framework of the parametric dissipative quantum model of brain. The size of the domains and the capability in memorizing depend on the number of links the system is able to establish with the external world.

E. Alfinito; G. Vitiello

2000-06-14

382

The dissipative quantum model of brain how do memory localize in correlated neuronal domains  

E-print Network

The mechanism of memory localization in extended domains is described in the framework of the parametric dissipative quantum model of brain. The size of the domains and the capability in memorizing depend on the number of links the system is able to establish with the external world.

Alfinito, E

2000-01-01

383

Differential effects of trisomy on brain shape and volume in related aneuploid mouse models  

Microsoft Academic Search

Down syndrome (DS) results from inheritance of three copies of human chromosome 21 (Hsa21). Individuals with DS have a significantly smaller brain size overall and a disproportionately small cerebellum. The small cerebellum is seen in Ts65Dn mice, which have segmental trisomy for orthologs of about half the genes on Hsa21 and provide a genetic model for DS. While small cerebellar

Kristina Aldridge; Roger H. Reeves; Lisa E. Olson; Joan T. Richtsmeier

2007-01-01

384

Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer's disease  

Microsoft Academic Search

Elevated brain iron content, which has been observed in late-stage human Alzheimer's disease, is a potential target for early diagnosis. However, the time course for iron accumulation is currently unclear. Using the PSAPP mouse model of amyloid plaque formation, we conducted a time course study of metal ion content and distribution [iron (Fe), copper (Cu), and zinc (Zn)] in the

A. C. Leskovjan; L. Miller; A. Kretlow; A. Lanzirotti; R. Barrea; S. Vogt

2010-01-01

385

Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer's disease  

Microsoft Academic Search

Elevated brain iron content, which has been observed in late-stage human Alzheimer's disease, is a potential target for early diagnosis. However, the time course for iron accumulation is currently unclear. Using the PSAPP mouse model of amyloid plaque formation, we conducted a time course study of metal ion content and distribution [iron (Fe), copper (Cu), and zinc (Zn)] in the

Andreana C. Leskovjan; Ariane Kretlow; Antonio Lanzirotti; Raul Barrea; Stefan Vogt; Lisa M. Miller

2011-01-01

386

Effects of pituitary adenylate cyclase activating polypeptide in a rat model of traumatic brain injury  

Microsoft Academic Search

Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely distributed neuropeptide that has numerous different actions. Recent studies have shown that PACAP exerts neuroprotective effects not only in vitro but also in vivo, in animal models of global and focal cerebral ischemia, Parkinson's disease and axonal injuries. Traumatic brain injury has an increasing mortality and morbidity and it evokes diffuse

Orsolya Farkas; Andrea Tamás; Andrea Zsombok; Dóra Regl?di; József Pál; Andras Büki; István Lengvári; John T. Povlishock; Tamás Dóczi

2004-01-01

387

Information Flow in Ising Models on Brain Sebastiano Stramaglia1,2,3  

E-print Network

is characterized by the maximal amount of information flow in the system, and that this does not hap- pen when signatures of the law of diminishing marginal returns, some nodes showing disparity between incoming by anticorrelated components). Keywords: Ising model, criticality, brain, Transfer entropy, Granger causality. 1

Cortes, Jesus

388

Spheroid Preparation from Hanging Drops: Characterization of a Model of Brain Tumor Invasion  

Microsoft Academic Search

Background: The use of three-dimensional in vitro models of brain tumor invasion has provided a system for reconstructing some of the cellular microenvironments present in the tumor mass. While spheroids of murine and human astrocytoma cells can be prepared using spinning cultures, spheroid preparation using many cell lines is not amenable to this method. We have developed a reproducible system

Danny Del Duca; Tamra Werbowetski; Rolando F. Del Maestro

2004-01-01

389

Mortality following rehabilitation in the Traumatic Brain Injury Model Systems of Care  

Microsoft Academic Search

Abstract. While many outcomes after traumatic brain injury (TBI) have been systematically investigated, the most basic of all outcomes – survival – has been neglected. The purpose of this study was to investigate mortality in a cohort of 2,178 individuals with TBI completing inpatient rehabilitation in one of 15 National Institute on Disability and Rehabilitation Research-funded TBI Model Systems of

Cynthia Harrison-felix; Gale Whiteneck; Michael Devivo; Flora M. Hammond; Amitabh Jha

390

Multivariate nonlinear mixed model to analyze longitudinal image data: MRI study of early brain development  

Microsoft Academic Search

With great potential in studying neuro-development, neuro-degeneration, and the aging process, longitudinal image data is gaining increasing interest and attention in the neuroimaging community. In this paper, we present a parametric nonlinear model to statistically study multivariate longitudinal data with asymptotic properties. We demonstrate our preliminary results in a combined study of two longitudinal neuroimaging data sets of early brain

Shun Xu; Martin Styner; John Gilmore; Joseph Piven; Guido Gerig

2008-01-01

391

Model Based Variational Smoothing and Segmentation For Diffusion Tensor Imaging in the Brain  

E-print Network

02144. %MGH-HST Center for Biomarkers in Imaging, Department of Radiology, Massachusetts generalModel Based Variational Smoothing and Segmentation For Diffusion Tensor Imaging in the Brain Mukund. ` Center for Morphometric Analysis and MGH/MIT Athinoula A. Martinos Center for Biomedical Imaging

Shah, Jayant M.

392

Positive effects of noise on cognitve performance: Explaining the Moderate Brain Arousal model  

Microsoft Academic Search

Distractors and environmental noise has long been regarded as detrimental for cognitive processing. In particular children with Attention Deficit Hyperactivity Disorder (ADHD) are extremely sensitive to distraction from task irrelevant stimuli. However, recently it has been shown that exposure to auditory white noise facilitated cognitive performance in ADHD children whereas control children performed worse. The Moderate Brain Arousal (MBA) model

Göran Söderlund; Sverker Sikström

2008-01-01

393

Brain-learning-model-based DSP teaching environment for communication systems  

Microsoft Academic Search

The description of a virtual, remote, and distributed laboratory for teaching communication systems is presented; it is based on physiological and psychological models of how the brain carries out the capture and retention of knowledge, thus facilitating the process of learning, reducing the time of assimilation, and achieving a longer retention of the assimilated material. The system includes: an application

Jaime-Alberto Parra-Plaza; Ferney-Orlando Amaya

2004-01-01

394

A motion correction system for brain tomography based on biologically motivated models  

Microsoft Academic Search

A motion correction system for brain tomography is presented, which employs two calibrated video cameras and three vision models (CIECAM'97, RETINA, and BMV). The system is evaluated on the pictures monitoring a subjects head while simulating PET scanning (n=12) and on the face images of subjects with different skin colours (n=31). The results on 2D images with known moving parameters

Sergey Anishenko; Vladislav Osinov; Dmitry Shaposhnikov; Lubov Podladchikova; Richard Comley; Konstantin Sukholentsev; Xiaohong W. Gao

2008-01-01

395

Brains Rule!: A Model Program for Developing Professional Stewardship among Neuroscientists  

ERIC Educational Resources Information Center

Brains Rule! Neuroscience Expositions, funded through a National Institute on Drug Abuse Science Education Drug Abuse Partnership Award, has developed a successful model for informal neuroscience education. Each Exposition is a "reverse science fair" in which neuroscientists present short neuroscience teaching modules to students. This study…

Zardetto-Smith, Andrea M.; Mu, Keli; Carruth, Laura L.; Frantz, Kyle J.

2006-01-01

396

Macroscopic Models of Local Field Potentials and the Apparent 1/f Noise in Brain Activity  

E-print Network

Macroscopic Models of Local Field Potentials and the Apparent 1/f Noise in Brain Activity Claude Be Scientifique, Gif-sur-Yvette, France ABSTRACT The power spectrum of local field potentials (LFPs) has been reported to scale as the inverse of the frequency, but the origin of this 1/f noise is at present unclear

Destexhe, Alain

397

Ruminant organotypic brain-slice cultures as a model for the investigation of CNS listeriosis  

PubMed Central

Central nervous system (CNS) infections in ruminant livestock, such as listeriosis, are of major concern for veterinary and public health. To date, no host-specific in vitro models for ruminant CNS infections are available. Here, we established and evaluated the suitability of organotypic brain-slices of ruminant origin as in vitro model to study mechanisms of Listeria monocytogenes CNS infection. Ruminants are frequently affected by fatal listeric rhombencephalitis that closely resembles the same condition occurring in humans. Better insight into host–pathogen interactions in ruminants is therefore of interest, not only from a veterinary but also from a public health perspective. Brains were obtained at the slaughterhouse, and hippocampal and cerebellar brain-slices were cultured up to 49 days. Viability as well as the composition of cell populations was assessed weekly. Viable neurons, astrocytes, microglia and oligodendrocytes were observed up to 49 days in vitro. Slice cultures were infected with L. monocytogenes, and infection kinetics were monitored. Infected brain cells were identified by double immunofluorescence, and results were compared to natural cases of listeric rhombencephalitis. Similar to the natural infection, infected brain-slices showed focal replication of L. monocytogenes and bacteria were predominantly observed in microglia, but also in astrocytes, and associated with axons. These results demonstrate that organotypic brain-slice cultures of bovine origin survive for extended periods and can be infected easily with L. monocytogenes. Therefore, they are a suitable model to study aspects of host–pathogen interaction in listeric encephalitis and potentially in other neuroinfectious diseases. PMID:22804762

Guldimann, Claudia; Lejeune, Beatrice; Hofer, Sandra; Leib, Stephen L; Frey, Joachim; Zurbriggen, Andreas; Seuberlich, Torsten; Oevermann, Anna

2012-01-01

398

Using normalization 3D model for automatic clinical brain quantative analysis and evaluation  

NASA Astrophysics Data System (ADS)

Functional medical imaging, such as PET or SPECT, is capable of revealing physiological functions of the brain, and has been broadly used in diagnosing brain disorders by clinically quantitative analysis for many years. In routine procedures, physicians manually select desired ROIs from structural MR images and then obtain physiological information from correspondent functional PET or SPECT images. The accuracy of quantitative analysis thus relies on that of the subjectively selected ROIs. Therefore, standardizing the analysis procedure is fundamental and important in improving the analysis outcome. In this paper, we propose and evaluate a normalization procedure with a standard 3D-brain model to achieve precise quantitative analysis. In the normalization process, the mutual information registration technique was applied for realigning functional medical images to standard structural medical images. Then, the standard 3D-brain model that shows well-defined brain regions was used, replacing the manual ROIs in the objective clinical analysis. To validate the performance, twenty cases of I-123 IBZM SPECT images were used in practical clinical evaluation. The results show that the quantitative analysis outcomes obtained from this automated method are in agreement with the clinical diagnosis evaluation score with less than 3% error in average. To sum up, the method takes advantage of obtaining precise VOIs, information automatically by well-defined standard 3-D brain model, sparing manually drawn ROIs slice by slice from structural medical images in traditional procedure. That is, the method not only can provide precise analysis results, but also improve the process rate for mass medical images in clinical.

Lin, Hong-Dun; Yao, Wei-Jen; Hwang, Wen-Ju; Chung, Being-Tau; Lin, Kang-Ping

2003-05-01

399

Experimental Models of Anxiety for Drug Discovery and Brain Research  

E-print Network

. Kalueff Abstract Animal models have been vital to recent advances in experimental neuroscience, including will be addressed accordingly. Key words: Anxiety, experimental animal models, anxiolytic drugs, anxiogenic drugs confounding experimental data. 2. Materials 2.1. Animals 1. Various inbred, selectively bred (for specific

Kalueff, Allan V.

400

Neuropeptides and the social brain: potential rodent models of autism  

Microsoft Academic Search

Conducting basic scientific research on a complex psychiatric disorder, such as autism, is a challenging prospect. It is difficult to dissociate the fundamental neurological and psychological processes that are disturbed in autism and, therefore, it is a challenge to discover accurate and reliable animal models of the disease. Because of their role in animal models of social processing and social

Miranda M. Lim; Isadora F. Bielsky; Larry J. Young

2005-01-01

401

Hemicraniectomy after middle cerebral artery infarction with life-threatening Edema trial (HAMLET). Protocol for a randomised controlled trial of decompressive surgery in space-occupying hemispheric infarction  

Microsoft Academic Search

BACKGROUND: Patients with a hemispheric infarct and massive space-occupying brain oedema have a poor prognosis. Despite maximal conservative treatment, the case fatality rate may be as high as 80%, and most survivors are left severely disabled. Non-randomised studies suggest that decompressive surgery reduces mortality substantially and improves functional outcome of survivors. This study is designed to compare the efficacy of

Jeannette Hofmeijer; G Johan Amelink; Ale Algra; Jan van Gijn; Malcolm R Macleod; L Jaap Kappelle; H Bart van der Worp

2006-01-01

402

Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model  

NASA Astrophysics Data System (ADS)

We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8+