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1

Neovasculature and blood-brain barrier in ischemic brain infarct  

Microsoft Academic Search

The cellular events occurring in ischemic brain infarcts of 1 day to 8 weeks duration were investigated. The material consisted of 17 human postmortem brains with anemic infarcts caused by occlusive vascular diseases. Using antiserum against human plasma albumin as a marker for the breakdown of blood-brain barrier and ammoniacal silver nitrate stain to demonstrate the vasculature, the onset and

H. Mei Liu

1988-01-01

2

Silent Brain Infarcts in Patients With Manifest Vascular Disease  

Microsoft Academic Search

Background and Purpose—Silent infarcts are frequently found on MRIs of brains of healthy elderly persons (aged 60 years). The purpose of this study was to investigate the prevalence and determinants of silent infarcts in a population of patients with clinically manifest vascular disease. Methods—To detect silent infarcts, MR images were made in 308 participants of the Second Manifestations of ARTerial

Janneke L. P. Giele; Theo D. Witkamp; Willem P. T. M. Mali

2010-01-01

3

Limitations of tetrazolium salts in delineating infarcted brain  

Microsoft Academic Search

Tetrazolium salts, histochemical indicators of mitochondrial respiratory enzymes, have been used by some pathologists to detect infarcts in myocardium. We explored the utility of this technique in detecting experimental brain infarcts and report our findings. Infarcts were produced in cats, gerbils, and rats by unilateral temporal and permanent cerebral vessel occlusion. After various time periods the animals were killed, and

T. M. Liszczak; E. T. Hedley-Whyte; J. F. Adams; D. H. Han; V. S. Kolluri; F. X. Vacanti; R. C. Heros; N. T. Zervas

1984-01-01

4

Lower prevalence of silent brain infarcts in the physically active  

PubMed Central

Objective: To examine the independent association between physical activity and subclinical cerebrovascular disease as measured by silent brain infarcts (SBI) and white matter hyperintensity volume (WMHV). Methods: The Northern Manhattan Study (NOMAS) is a population-based prospective cohort examining risk factors for incident vascular disease, and a subsample underwent brain MRI. Our primary outcomes were SBI and WMHV. Baseline measures of leisure-time physical activity were collected in person. Physical activity was categorized by quartiles of the metabolic equivalent (MET) score. We used logistic regression models to examine the associations between physical activity and SBI, and linear regression to examine the association with WMHV. Results: There were 1,238 clinically stroke-free participants (mean age 70 ± 9 years) of whom 60% were women, 65% were Hispanic, and 43% reported no physical activity. A total of 197 (16%) participants had SBI. In fully adjusted models, compared to those who did not engage in physical activity, those in the upper quartile of MET scores were almost half as likely to have SBI (adjusted odds ratio 0.6, 95% confidence interval 0.4–0.9). Physical activity was not associated with WMHV. Conclusions: Increased levels of physical activity were associated with a lower risk of SBI but not WMHV. Engaging in moderate to heavy physical activities may be an important component of prevention strategies aimed at reducing subclinical brain infarcts.

Moon, Y.P.; Paik, M.C.; Yoshita, M.; DeCarli, C.; Sacco, R.L.; Elkind, M.S.V.; Wright, C.B.

2011-01-01

5

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.

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

2012-01-01

6

Platelets, alcohol consumption, and onset of brain infarction.  

PubMed Central

OBJECTIVES: Previous investigations have suggested that recurrent rebound thrombocytosis after alcohol misuse may be a factor in the pathogenesis of thromboembolic disease. Alcohol consumption, platelet count, and platelet function were examined among patients of working age with brain infarction. METHODS: Platelet count and risk factors for stroke were studied in 426 stroke patients and 157 control patients in hospital. The measures were platelet count obtained within four days after the stroke onset, in vitro adenosine diphosphate induced platelet aggregation, associated thromboxane B2 formation, and urinary excretion of 11-dehydrothromboxane B2. RESULTS: After adjustment for sex, age, cardiac disease, diabetes, and alcohol intake, hypertension (OR 3.4, 95% confidence interval (95% CI) 2.0-6.0) and current smoking (OR 2.1, 95% CI 1.4-3.3) were associated with an increased risk for brain infarction. Platelet count shortly after the onset of disease was higher in the stroke patients than in the controls (OR 1.05/10(10)/1 platelets; 95% CI 1.02-1.09). The patients with brain infarction who were heavy alcohol drinkers (n = 144) showed both thrombocytosis (OR 2.30, 95% CI 0.82-6.44) and thrombocytopenia (OR 3.20, 95% CI 1.19 to 8.59) more often at the onset of the stroke than the other patients with brain infarction. The thromboxane variables showed inconsistent associations with the onset of stroke. There was no consistent platelet abnormality among alcohol misusers at the onset of ischaemic brain infarction. CONCLUSIONS: Alcohol induced thrombocytopenia and rebound thrombocytosis were both often seen at the onset of brain infarction in patients who were heavy alcohol drinkers. Therefore, other mechanisms which could contribute to the high frequency of recurrences of ischaemic stroke among heavy drinkers should be investigated.

Numminen, H; Hillbom, M; Juvela, S

1996-01-01

7

SPECT study of low intensity He-Ne laser intravascular irradiation therapy for brain infarction  

NASA Astrophysics Data System (ADS)

We used single photon emission computed tomography (SPECT) in brain perfusion imaging to study the changes of regional cerebral blood flow (rCBF) and cerebral function in brain infarction patients treated with intravascular laser irradiation of blood (ILIB). 17 of 35 patients with brain infarction were admitted to be treated by ILIB on the base of standard drug therapy, and SPECT brain perfusion imaging was performed before and after ILIB therapy with self-comparison. The results were analyzed in quantity with brain blood flow function change rate (BFCR%) model. Effect of ILIB during the therapy process in the other 18 patients were also observed. In the 18 patients, SPECT indicated an improvement of rCBF (both in focus and in total brain) and cerebral function after a 30 min-ILIB therapy. And the 17 patients showed an enhancement of total brain rCBF and cerebral function after ILIB therapy in comparison with that before, especially for the focus side of the brain. The enhancement for focus itself was extremely obvious with a higher significant difference (P<0.0001). The mirror regions had no significant change (P>0.05). BFCR% of foci was prominently higher than that of mirror regions (P<0.0001). In conclusion, the ILIB therapy can improve rCBF and cerebral function and activate brain cells of patients with brain infarction. The results denote new evidence of ILIB therapy for those patients with cerebral ischemia.

Xiao, Xue-Chang; Dong, Jia-Zheng; Chu, Xiao-Fan; Jia, Shao-Wei; Liu, Timon C.; Jiao, Jian-Ling; Zheng, Xi-Yuan; Zhou, Ci-Xiong

2003-12-01

8

Lacunar infarcts: no black holes in the brain are benign.  

PubMed

Lacunar infarcts--small subcortical infarcts that result from occlusion of a single penetrating artery--account for about one quarter of all ischaemic strokes. However, there are many diagnostic pitfalls, and causes other than penetrating small vessel disease in up to one third of cases. Recent studies have shown that the prognosis after lacunar infarcts is not benign; the risk of recurrent stroke is no lower than for other ischaemic stroke subtypes, and there is an increased risk for cognitive decline, dementia and death in the long term. Furthermore, silent small vessel disease in the brain at the time of an index stroke has significant prognostic implications. In the acute phase, response to intravenous thrombolysis appears to be similar to other subtypes of ischaemic strokes. Antiplatelet drugs, careful blood pressure control, statins and modification of lifestyle risk factors are key elements in secondary prevention after lacunar infarcts. PMID:18644908

Norrving, Bo

2008-08-01

9

Myeloperoxidase polymorphisms in brain infarction. Association with infarct size and functional outcome  

Microsoft Academic Search

Myeloperoxidase (MPO) has been shown to contribute to several diseases and more particularly to atherosclerosis through excessive ROS production via the MPO\\/H2O2\\/Cl? oxidation system. The aim of this study was to determine whether there is an association between MPO polymorphisms and brain infarction (BI), one of the main consequences of atherosclerosis. We investigated MPO G-463A and G-129A polymorphisms in 450

Aline Hoy; Brigitte Leininger-Muller; Odette Poirier; Gérard Siest; Marion Gautier; Alexis Elbaz; Pierre Amarenco; Sophie Visvikis

2003-01-01

10

Plasma brain natriuretic peptide concentrations predict survival after acute myocardial infarction  

Microsoft Academic Search

Objectives. This study sought to examine whether plasma brain natriuretic peptide levels can predict prognosis after myocardial infarction.Background. It has been suggested that concentrations of plasma brain natriuretic peptide reflect left ventricular function. Although the prognosis after myocardial infarctions depends on residual left ventricular function, it is not known whether plasma levels of brain natriuretic peptide after the onset of

Naoshi Arakawa; Motoyuki Nakamura; Hidehiko Aoki; Katsuhiko Hiramori

1996-01-01

11

Polymorphism of angiotensinogen gene M235T in myocardial infarction and brain infarction: a meta-analysis.  

PubMed

The angiotensinogen (AGT) gene M235T polymorphism has been reported to be associated with myocardial infarction (MI) and brain infarction (BI), but the results remain inconclusive. This meta-analysis was designed to clarify these controversies. Electronic databases were systematically searched before February 2013. A total of 38 studies with 17304 subjects met our inclusion criteria. In East Asian group, significant association was found between AGT M235T polymorphism and risk of MI (for dominant model: OR=1.79; 95% CI=1.04-3.06; for recessive model OR=2.01; 95% CI=1.21-3.36; for additive model OR=1.79; 95% CI=1.14-2.86) as well as BI (for dominant model: OR=1.66; 95% CI=1.22-2.27; for recessive model OR=1.78, 95% CI=1.29-2.46; for additive model: OR=1.64, 95% CI=1.34-2.00), while the M235T polymorphism did not impact the risk of MI in total population and other ethnicity. In the subgroup analyses by gender and age, there was lack of evidence for the association. This meta-analysis suggested an association between the M235T polymorphism and MI as well as BI in East Asian population. Further studies with larger numbers of worldwide participants are needed to understand the genetic basis of MI and BI. PMID:23933419

Liang, Xinyue; Qiu, Jie; Liu, Xiangju; Li, Xiao; Zhao, Shaohua; Wang, Jing; Ma, Yabing; Gao, Haiqing

2013-08-08

12

Brain infarction following 5-fluorouracil and cisplatin therapy.  

PubMed

Five patients with oropharyngeal cancer treated with 5-fluorouracil and cisplatin had ischemic stroke within 2 to 5 days after the drug infusion. This occurred during the second course of chemotherapy in three patients, and during the third course in two patients. There may be a relation between treatment and brain infarction because 1) there was no other cause identified despite extensive tests, including postmortem examination in one patient; 2) there was a short delay between treatment infusion and stroke; and 3) there was a similar pattern of ischemic stroke after the second or third course of chemotherapy. PMID:9748055

El Amrani, M; Heinzlef, O; Debroucker, T; Roullet, E; Bousser, M G; Amarenco, P

1998-09-01

13

Lacunar infarcts: no black holes in the brain are benign  

Microsoft Academic Search

Lacunar infarcts—small subcortical infarcts that result from occlusion of a single penetrating artery—account for about one quarter of all ischaemic strokes. However, there are many diagnostic pitfalls, and causes other than penetrating small vessel disease in up to one third of cases. Recent studies have shown that the prognosis after lacunar infarcts is not benign; the risk of recurrent stroke

B Norrving

2008-01-01

14

Brain natriuretic peptide release in acute myocardial infarction.  

PubMed

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

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

2012-08-01

15

Appearance of nuclear-sorted caspase-12 fragments in cerebral cortical and hippocampal neurons in rats damaged by autologous blood clot embolic brain infarctions.  

PubMed

Following endoplasmic reticulum (ER) stress, cerebral infarctions have been reported to involve an apoptotic process, including the activation of the caspase cascade. To confirm whether fragmented caspase-12, which is activated by cleavage and is detectable during ER stress, is also involved in embolic cerebral infarctions in rats, we adopted an autologous blood clot model for the analysis of cerebral infarctions. We performed experiments in rats with brain infarctions, which are closely related to embolic cerebral infarctions. We utilized a homologous blood clot, i.e., natural materials, to form the infarct area. Our findings reveal that caspase-12 is fragmented when infarct areas form in cerebral cortical neurons. Interestingly, we observed that these fragments translocated to the nuclei of not only cerebral cortical neurons but hippocampal neurons. We further found that glucose-regulated protein 78 (GRP78), a marker of ER stress, is up-regulated in both cerebral cortical and hippocampal neurons during cerebral infarction. This result suggests that the fragmentation of caspase-12 and the subsequent nuclear translocation of these fragments are involved in the brain infarction process in rats. PMID:21476018

Shimoke, Koji; Matsuki, Yoshinori; Fukunaga, Kenji; Matsumura, Yoshinobu; Fujita, Eriko; Sugihara, Kensuke; Nobuhara, Masamichi; Maruoka, Hiroki; Ikeuchi, Toshihiko; Kudo, Motoshige

2011-04-08

16

Myocardial Infarct Size Measurement in the Mouse Chronic Infarction Model: Comparison of Area- and Length-Based Approaches  

PubMed Central

Efficacy of potential treatments for myocardial infarction (MI) is commonly assessed by histological measurement of infarct size in rodent models. In experiments involving an acute MI setting, measurement of the infarcted area in tissue sections of the left ventricle (LV) is a standard approach to determine infarct size. This approach has also been used in the chronic infarct setting to measure infarct area several weeks post-MI. We tested the hypothesis that due to wall thinning that is known to occur in the chronic setting, the area measurement approach would be less appropriate. We compared infarct measurements in tissue sections based on (1) infarct area, (2) epicardial and endocardial infarct arc lengths, and (3) midline infarct arc length. Infarct size from all three measurement approaches correlated significantly with LV ejection fraction (LVEF) and wall motion abnormality. However, the infarct size values derived from area measurement were significantly smaller than those from the other measurements, and the range of values obtained was compressed 0.4-fold. The midline method was able to detect the expected size differences between infarcts of variable severity resulting from proximal vs. distal ligation of the coronary artery. Segmental infarct size was correlated with segmental wall motion abnormality. We conclude that both area- and length-based measurements can determine relative infarct size over a wide range of severity but the area-based measurements are substantially more compressed due to wall thinning, and that the estimation of infarct midlines is a simple, reliable approach to infarct size assessment.

Takagawa, Junya; Zhang, Yan; Wong, Maelene L.; Sievers, Richard E.; Kapasi, Neel K.; Wang, Yan; Yeghiazarians, Yerem; Lee, Randall J.; Grossman, William; Springer, Matthew L.

2009-01-01

17

Effect of transcranial magnetic stimulation on the expression of c-Fos and brain-derived neurotrophic factor of the cerebral cortex in rats with cerebral infarct  

Microsoft Academic Search

Summary  The effect of transcranial magnetic stimulation (TMS) on the neurological functional recovery and expression of c-Fos and\\u000a brain-derived neurotrophic factor (BDNF) of the cerebral cortex in rats with cerebral infarction was investigated. Cerebral\\u000a infarction models were established by using left middle cerebral artery occlusion (MCAO) and were randomly divided into a\\u000a model group (n=40) and a TMS group (n=40). TMS

Xiaoqiao Zhang; Yuanwu Mei; Chuanyu Liu; Shanchun Yu

2007-01-01

18

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

PubMed Central

The neonatal hypoxia-ischemia rat model referred to as the Rice–Vannucci model is extensively used to study perinatal hypoxia-ischemia and child brain injury. One of the major weaknesses of this model is its inconsistency of brain infarction among animals. We hypothesize that the inconsistency of infarction is caused by prolonged operation time and therefore isoflurane exposure. Neonatal hypoxia-ischemia was induced in postnatal days 7 and 10 rat pups by unilateral right common carotid ligation followed by 2.5 h of hypoxia (8% oxygen). The incision-to-ligation (ITL) was defined as the amount of time from initial incision (4 min after 2% isoflurane exposure) to completion of carotid ligation (at which point isoflurane exposure was also terminated). In the first part of the study, the ITL of each group was designated to be 5, 13, and 21 min. In the second part of the study, the ITL is designated to 4 min; however, continued isoflurane was used to make 5, 13, and 21 min isoflurane exposure for each group. Percentages of brain infarction were assessed at 48 h following surgery. Motor deficits were accessed by Rotarod test. Marked brain infarction was observed in the 5-min ITL group and a decrease of brain infarction observed in the 13-and 21-min groups (P<0.05). In the second part of the study, marked brain infarction was observed in the 5-min isoflurane exposure group, and a decrease of brain infarction was observed in each of the 13- and 21-min isoflurane exposure groups (P<0.05). Similar tendencies were observed in Rotarod tests than 5-min ITL and 5-min isoflurane groups showed more marked deficits (P<0.05). This study demonstrated that brain infarction inconsistency of the neonatal hypoxia-ischemia rat pup model is related to the operation time. The observed time-dependent decrease of brain infarction is correlated to the isoflurane exposure time. Shorter operation and isoflurane exposure improves this model consistency of brain infarction and motor deficits.

Chen, Hank; Burris, Michael; Fajilan, Adrain; Spagnoli, Fred; Tang, Jiping

2011-01-01

19

Bilateral suppression of the sympathetic nervous system in hemispheric brain infarction  

Microsoft Academic Search

To assess sympathetic system function after hemispheric brain infarction rostral to the hypothalamus we investigated 24 patients\\u000a with infarction in the territory of the middle cerebral artery. Anisocoria and basal lacrimal gland secretion were determined.\\u000a The ninhydrin test was performed and the sympathetic skin response recorded in both hands and feet. The functions assessed\\u000a by these tests were found to

Susanne Schwalen; Andre Altermann; Johannes Jörg; Kerstin Berg; Bernhard Maximilian Cramer

1996-01-01

20

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

PubMed Central

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

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

2013-01-01

21

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.

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

22

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

PubMed

Evidence of the impact of air temperature and pressure on cardiovascular morbidity is still quite limited and controversial, and even less is known about the potential influence of geomagnetic activity. The objective of this study was to assess impacts of air temperature, barometric pressure and geomagnetic activity on hospitalizations with myocardial infarctions and brain strokes. We studied 2,833 myocardial infarctions and 1,096 brain strokes registered in two Moscow hospitals between 1992 and 2005. Daily event rates were linked with meteorological and geomagnetic conditions, using generalized linear model with controls for day of the week, seasonal and long-term trends. The number of myocardial infarctions decreased with temperature, displayed a U-shaped relationship with pressure and variations in pressure, and increased with geomagnetic activity. The number of strokes increased with temperature, daily temperature range and geomagnetic activity. Detrimental effects on strokes of low pressure and falling pressure were observed. Relative risks of infarctions and strokes during geomagnetic storms were 1.29 (95 % CI 1.19-1.40) and 1.25 (1.10-1.42), respectively. The number of strokes doubled during cold spells. The influence of barometric pressure on hospitalizations was relatively greater than the influence of geomagnetic activity, and the influence of temperature was greater than the influence of pressure. Brain strokes were more sensitive to inclement weather than myocardial infarctions. This paper provides quantitative estimates of the expected increases in hospital admissions on the worst days and can help to develop preventive health plans for cardiovascular diseases. PMID:23700198

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

2013-05-23

23

White Matter Lesions and Lacunar Infarcts Are Independently and Differently Associated with Brain Atrophy: The SMART-MR Study  

Microsoft Academic Search

Objective: To investigate the independent association of white matter lesions (WML) and lacunar infarcts (LI) with measures of global brain atrophy on MRI. Methods: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 840 patients (mean age 58 ± 10 years, 80% male) without cortical, large subcortical or infratentorial infarcts. Brain

Auke P. A. Appelman; Koen L. Vincken; Yolanda van der Graaf; Anne L. M. Vlek; Theo D. Witkamp; Willem P. T. M. Mali; Mirjam I. Geerlings

2010-01-01

24

DEVELOPMENT OF A RAT MODEL OF PHOTOTHROMBOTIC ISCHEMIA AND INFARCTION WITHIN THE CAUDOPUTAMEN  

PubMed Central

Background and Purpose Basal ganglia infarction is typically caused by the occlusion of deep arteries and the formation of relatively small lesions called lacunes. In the present study, a rat model of lacunar infarction was induced by photothrombotic occlusion of the small vessels within the caudate-putamen and subsequently characterized. Methods Male Sprague-Dawley rats (n=143) were anesthetized, and Rose Bengal dye (20mg/kg) was intravenously injected. The left caudoputamen was exposed to cold white light for 5–10 min via a stereotaxically-implanted polymethylmethacrylate optic fiber (0.5–0.75 mm diameter). Neurological and morphological changes were assessed at various times during the following 6 weeks. Local cerebral blood flow was measured 90 min after photothrombosis by [14C]-N-isopropyl-p-iodoamphetamine quantitative autoradiography. The time course of blood-brain barrier (BBB) opening and ischemic brain edema as well as the effects of aspirin and tissue plasminogen activator (tPA) treatment were also determined. Results A virtually round infarct with thrombosed parenchymal vessels surrounded by a layer of selective neuronal death was formed within the caudoputamen; it turned into a cystic cavity (lacune) over 6 weeks. A central zone of markedly reduced blood flow and surrounding oligemic zone were observed 90 min after light exposure. Lesion size was proportional to light exposure, and the severity and duration of neurological deficits paralleled infarct size. Early BBB opening with edema peaked at day one. After tPA treatment, infarction volume and neurological deficits were reduced. Conclusions This study describes a new rat model of lacunar infarction by photothrombotic occlusion of the microvessels within the caudoputamen. With this model, infarct size correlates with the severity and duration of the neuropathology and can be varied by altering light exposure.

Kuroiwa, Toshihiko; Xi, Guohua; Hua, Ya; Nagaraja, Tavarekere N.; Fenstermacher, Joseph D.; Keep, Richard F

2009-01-01

25

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

Microsoft Academic Search

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

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

2010-01-01

26

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…

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

2006-01-01

27

Masticatory Force and Function in Patients with Hemispheric Brain Infarction and Hemiplegia  

Microsoft Academic Search

Recent functional animal studies have reported that the motor control of masticatory muscle function is bilaterally guided by both hemispheres, which may fundamentally differ from the cortical control of limb muscle function. In this study, we investigated whether unilateral cortical brain infarction induces different impairments in masticatory and upper limb motor performance. Evidence of the importance of both hemispheres in

P. Kemppainen; A. Waltimo; H. Palomäki; O. Salonen; M. Könönen; M. Kaste

1999-01-01

28

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

29

Early diagnosis of rats with acute myocardial infarction by measurement of brain natriuretic peptide.  

PubMed

The aim of this study was to detect early changes (within 1-4 h) in the brain natriuretic peptide (BNP) levels of rats with acute myocardial infarction (AMI). A total of 35 Wistar rats were established as models of AMI and 30 sham-operated rats were used as the control group. The myocardia of the two groups were observed using a transmission electron microscope (TEM) prior to and following surgery. A double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used to detect the serum BNP and cardiac troponin I (cTnI) concentrations before and 1-4 h after surgery. Following the successful establishment of the AMI models, serum BNP concentrations were significantly increased within 1-4 h compared with the values prior to surgery and with those of the control group (all P<0.01). The serum BNP concentration reached its highest level 2 h after AMI (532.25±15.16 ng/l). No significant changes were observed in the cTnI serum levels of the AMI group within 1-4 h compared with the values before AMI and those in the control group (all P>0.05). In the 1-4 h following the establishment of the AMI model, significant positive correlations were identified between the serum BNP concentrations and the size of the AMI and the most marked correlation occurred 2 h after AMI (r=0.72, P<0.05). No significant differences were noted in the serum concentrations of BNP and cTnI in the control group prior to and following the sham surgery (all P>0.05). BNP may be used as a blood marker for the early diagnosis of AMI, particularly 1-4 h after the onset of AMI, and to predict the size of the infarct area. PMID:23596490

Li, Jian; Yin, Fang-Fang; Hou, Ying-Long

2013-02-18

30

Changes of circadian blood pressure patterns and cardiovascular parameters indicate lateralization of sympathetic activation following hemispheric brain infarction  

Microsoft Academic Search

The effects of left- and right-sided hemispheric brain infarction on variability in circadian blood pressure and cardiovascular measures were investigated in 35 patients to test for asymmetry of the sympathetic consequences of stroke. No significant differences regarding age, size of infarction or extent and frequency of damage to the insular cortex could be detected between the two groups. Patients with

Dirk Sander; Jürgen Klingelhöfer

1995-01-01

31

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

32

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

PubMed

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

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

1994-01-01

33

Mobile Aortic Plaques Are a Cause of Multiple Brain Infarcts Seen on Diffusion-Weighted Imaging  

Microsoft Academic Search

Background and Purpose—Multiple brain infarcts are often seen on diffusion-weighted images in cardioembolic stroke patients. Recently, mobile aortic plaques (MAPs) have been proposed as embolic sources. However, the clinical characteristics of patients with MAPs are unclear. Methods—We prospectively studied patients with acute ischemic stroke who underwent transesophageal echocardiogra- phy. The patients were classified into 3 groups based on transesophageal echocardiography

Yuji Ueno; Kazumi Kimura; Yasuyuki Iguchi; Kensaku Shibazaki; Takeshi Inoue; Nobutaka Hattori; Takao Urabe

2010-01-01

34

Cognitive Models of the Brain  

Microsoft Academic Search

The human brain is the most complicated organ in the universe and a new frontier yet to be explored in an interdisciplinary approach. Investigation of the brain is a unique problem that requires recursive mental power to explore the brain using the brain. This paper attempts to develop functional and cognitive models of the brain by using cognitive informatics and

Yingxu Wang; Ying Wang

2002-01-01

35

Panax notoginseng Attenuates the Infarct Volume in Rat Ischemic Brain and the Inflammatory Response of Microglia.  

PubMed

The roots of Panax notoginseng (PN) are commonly used as a therapeutic agent to stop hemorrhage and as a tonic to promote health in traditional Korean medicine. Stroke triggers an inflammatory response that not only plays a central role in the pathogenesis of cerebral ischemia, but also induces secondary damage. This study was designed to investigate the neuroprotective effects of the methanol extract of PN on the infarct volume induced by middle cerebral artery occlusion (MCAO) (90-min occlusion and 24-h reperfusion) in rat brains. The PN extract (50 mg/kg, i.p.) was administered 2 h after the onset of MCAO. The PN-treated groups had a reduction in infarct volume by 23.82 +/- 8.9%. In the PN extract-treated groups, the microglial density was significantly decreased in the peri-infarct region; the underlying mechanism was inhibition of inflammatory mediators, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, via blocking of the NF-kappaB pathway. Furthermore, in vitro studies showed that the PN extract significantly reduced the production of iNOS-derived NO and COX-2-derived prostaglandin E(2) through the regulation of gene transcription levels in primary microglia and BV-2 cells. These results suggest that anti-inflammatory and microglial activation inhibitory effects of the PN extract may contribute to its neuroprotective effects in brain ischemia. PMID:19305121

Son, Hye Young; Han, Hyung Soo; Jung, Hyo Won; Park, Yong-Ki

2009-03-01

36

Surgical Porcine Myocardial Infarction Model through Permanent Coronary Occlusion  

PubMed Central

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

Munz, Maria R; Faria, Miguel A; Monteiro, Joana R; Aguas, Artur P; Amorim, Mario J

2011-01-01

37

Neuroglobin Over Expressing Mice: Expression Pattern and Effect on Brain Ischemic Infarct Size  

PubMed Central

Background Stroke is a major cause of death and severe disability, but effective treatments are limited. Neuroglobin, a neuronal heme-globin, has been advocated as a novel pharmacological target in combating stroke and neurodegenerative disorders based on cytoprotective properties. Using thoroughly validated antibodies and oligos, we give a detailed brain anatomical characterization of transgenic mice over expressing Neuroglobin. Moreover, using permanent middle artery occlusion the effect of elevated levels of Neuroglobin on ischemic damage was studied. Lastly, the impact of mouse strain genetic background on ischemic damage was investigated. Principal Findings A four to five fold increase in Neuroglobin mRNA and protein expression was seen in the brain of transgenic mice. A ?-actin promoter was used to drive Neuroglobin over expression, but immunohistochemistry and in situ hybridization showed over expression to be confined to primarily the cortex, hippocampus, cerebellum, and only in neurons. The level and expression pattern of endogenous Neuroglobin was unaffected by insertion of the over expressing Ngb transgene. Neuroglobin over expression resulted in a significant reduction in infarct volume 24 hours after ischemia. Immunohistochemistry showed no selective sparing of Neuroglobin expressing cells in the ischemic core or penumbra. A significant difference in infarct volume was found between mice of the same strain, but from different colonies. Significance In contrast to some previous reports, Neuroglobin over expression is not global but confined to a few well-defined brain regions, and only in neurons. This study confirms previous reports showing a correlation between reduced infarct volume and elevated Neuroglobin levels, but underlines the need to study the likely contribution from compensatory mechanisms to the phenotype following a genetic perturbation. We also stress, that care should be taken when comparing results where different mouse strains and colonies have been used due to large genetic background contribution to the observed phenotype.

Raida, Zindy; Hundahl, Christian Ansgar; Nyengaard, Jens R.; Hay-Schmidt, Anders

2013-01-01

38

Modeling Myocardial Infarction in Mice: Methodology, Monitoring, Pathomorphology  

PubMed Central

Myocardial infarction is one of the most serious and widespread diseases in the world. In this work, a minimally invasive method for simulating myocardial infarction in mice is described in the Russian Federation for the very first time; the procedure is carried out by ligation of the coronary heart artery or by controlled electrocoagulation. As a part of the methodology, a series of anesthetic, microsurgical and revival protocols are designed, owing to which a decrease in the postoperational mortality from the initial 94.6 to 13.6% is achieved. ECG confirms the development of large-focal or surface myocardial infarction. Postmortal histological examination confirms the presence of necrosis foci in the heart muscles of 87.5% of animals. Altogether, the medical data allow us to conclude that an adequate mouse model for myocardial infarction was generated. A further study is focused on the standardization of the experimental procedure and the use of genetically modified mouse strains, with the purpose of finding the most efficient therapeutic approaches for this disease.

Ovsepyan, A.A.; Panchenkov, D.N.; Prokhortchouk, E.B.; Telegin, G.B.; Zhigalova, N.A.; Golubev, E.P.; Sviridova, T.E.; Matskeplishvili, S.T.; Skryabin, K.G.; Buziashvili, U.I.

2011-01-01

39

A New Non-Human Primate Model of Photochemically Induced Cerebral Infarction  

PubMed Central

Background and Purpose Rat models of photochemically induced cerebral infarction have been readily studied, but to date there are no reports of transcranial photochemically induced infarctions in the marmoset. In this report, we used this non-human primate as a model of cerebral thrombosis and observed the recovery process. Methods Five common marmosets were used. Cerebral ischemia was produced via intravascular thrombosis induced by an intravenous injection of Rose Bengal and irradiation with green light. After inducing cerebral infarction, we observed the behavior of marmosets via a continuous video recording. We evaluated maximum speed, mean speed, and distance traveled in 1 min. In addition, we evaluated scores for feeding behavior, upper limb grip, and lower limb grip. We confirmed the infarct area after cerebral infarction using 2,3,5-triphenyltetrazolium chloride staining in a separate marmoset. Results We found functional decreases 2 days after creating the cerebral infarction in all measurements. Total distance traveled, average speed, upper limb score, and feeding behavior score did not recover to pre-infarction levels within 28 days. Maximum speed in 1 min and lower limb score recovered 28 days after infarction as compared to pre-infarction levels. We confirmed the infarct area of 11.4 mm×6.8 mm as stained with 2,3,5-triphenyltetrazolium chloride. Conclusion We were able to create a primate photothrombosis-induced cerebral infarction model using marmosets and observe functional recovery. We suggest that this is a useful model for basic research of cerebral infarction.

Ohwatashi, Akihiko; Kamikawa, Yurie; Yoshida, Akira; Kawahira, Kazumi

2013-01-01

40

[Association between Bam HI RFLP p53 gene polymorphism and brain infarction volume in patients with atherothrombotic ischemic stroke].  

PubMed

A significant association between Bam HI RFLP p53 gene polymorphism and brain infarction volume in patients with atherothrombotic ischemic stroke (AIS) from Moscow population was found. Biallelic Bam HI polymorphism in exon 5 of p53 gene was studied in 96 AIS patients, 100 their healthy siblings, 41 patients with chronic ischemic disease and 42 their healthy siblings. Magnetic resonance tomography with morphometric program "Osiris" (the Hospital of the University, Geneva) for infarction volume measuring was used on day 1 and 7 after stroke onset. The patients with (-/-) p53 Bam HI genotype had the smaller brain infarction sizes (< 40 cm3), comparing to those with (-/+) (chi 2 = 19.7; p < 0.001) and (+/+) (chi 2 = 12.3; p < 0.001) genotypes. According to Bayes statistics, development of smaller infarction size in AIS may be predicted with over than 65% probability in the patients with (-/-) p53 Bam HI genotype. A significant association between p53 Bam HI polymorphism and infarction volume in patients with carotid atherothrombotic stroke confirms an important role of apoptosis in ischemic brain lesions formation that demands temporary antiapoptotic influence on patients with stroke. PMID:12830514

Skvortsova, V I; Limborskaia, S A; Slominski?, P A; Gubski?, L V; Kol'tsova, E A; Shetova, I M; Shamalov, N A; Tupitsina, T I; Platonova, I A

2003-01-01

41

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

NASA Astrophysics Data System (ADS)

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

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

2012-11-01

42

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

Microsoft Academic Search

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

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

1988-01-01

43

Cosmic rays as indicator of space weather influence on frequency of infarct myocardial, brain strokes, car and train accidents  

NASA Astrophysics Data System (ADS)

By Dorman et al. (1999) was shown that CR Forbush-decreases can be considered as indicators of space phenomenon influence on the infarct myocardial, brain stroke, and car accident frequency. The obtained results are bigger than statistical errors in 4-7 times. In Dorman et al. (1999) we used daily averaged data on frequency of infarcts myocardial, brain strokes, and car accidents, obtained from ambulance organizations of Moscow for the period January 1979 December 1981 and of Leningrad (now St. Petersburg) for the period January 1987 December 1989. In the present researchwe will use monthly averaged data of infarct myocardial, brain stroke, and car accident frequencies as well as monthly data of train accident frequencies of two types (1-stcaused by the man factor, and the 2-nd ~@~S caused by the technological factorss) on the Siberian railways for the period 1 January 1986 ~@~S 30 November 1993. These daata allow us to estimate the possible connection of space weather changing (controlled by CR intensity and solar activity long-term variations) with frequency of people deceases (as infarcts myocardial and brain strokes), and car accidents as well as with frequency of train accidents caused by the man factor.

Dorman, L. I.; Iucci, N.; Ptitsyna, N. G.; Villoresi, G.

2001-08-01

44

Relationship between diffusion-weighted MR images, cerebral blood flow, and energy state in experimental brain infarction  

Microsoft Academic Search

The regional evolution of brain infarction was studied in Wistar rats submitted to remotely controlled thread occlusion of the middle cerebral artery. Occlusion was performed in the magnet of an NMR tomography system to allow continuous recording of diffusion-weighted images. After 30 min (n = 6) or 2 h (n = 9), cerebral blood flow was measured by [14C] iodoantipyrine

Kanehisa Kohno; Mathias Hoehn-Berlage; Günter Mies; Tobias Back; Konstantin-Alexander Hossmann

1995-01-01

45

Value of brain natriuretic peptide after acute myocardial infarction Akut miyokard infarktüsü sonras› beyin natriüretik peptid'in deeri  

Microsoft Academic Search

Objective: Brain natriuretic peptide (BNP) is secreted predominantly from the ventricles in response to increased wall stress, which is known to be one of the major forces driving left ventricular (LV) remodeling. In this prospective study, we evaluated value of BNP levels in acute myocardial infarction (MI) patients for the prediction of heart failure during one year of follow-up. Methods:

Ela Kavlak; Cennet Erbafl; Sezer Karc

46

Repeated application of an electric field increases BDNF in the brain, enhances spatial learning, and induces infarct tolerance.  

PubMed

Development of a safe method to increase brain-derived neurotrophic factor (BDNF) in the brain is expected to have utility in enhancing learning and memory, in protecting the brain, and in suppressing appetite. We investigated the effects of whole-body exposure to high voltage electric potential (HELP), which generates an electric field and current density in the body, on BDNF levels in the brain, spatial learning, or resistance to cerebral infarction development after focal ischemia. Adult mice (C57BL/6J) were exposed to 3.5 kV, or 5.8 kV for 5 h a day, making indirect contact with the ground via room air, over 1, 3, 6 or 12 consecutive weeks. After treatment, BDNF levels, performances in the Morris water maze task (MWM), or development of infarct lesion after focal ischemia was analyzed. Treatment with 3.5 kV for 1, 3, 6 or 12 weeks, or with 5.8 kV for 1, 3 or 12 weeks increased BDNF levels in the cortex (P<0.05, one-way ANOVA). Every HELP treatment differentially improved escape latency in the MWM, compared with the corresponding untreated controls (P<0.05, one-way ANOVA). Treatment with 3.5 kV for 6 or 12 weeks, but not with 5.8 kV protected the brain suppressing cerebral infarction development (P<0.05). The HELP treatment with 3.5 kV for 6 or 12 weeks improves spatial learning, gently suppressing body weight gain, and protects the brain against cerebral infarction. PMID:18439988

Yanamoto, Hiroji; Miyamoto, Susumu; Nakajo, Yukako; Nakano, Yoshikazu; Hori, Takuya; Naritomi, Hiroaki; Kikuchi, Haruhiko

2008-03-20

47

Prognostic value of N-terminal pro-brain natriuretic peptide in elderly people with acute myocardial infarction: prospective observational study  

Microsoft Academic Search

Objective To examine the influence of age on the predictive value of N-terminal pro-brain natriuretic (NT-proBNP) peptide assay in acute myocardial infarction.Design Prospective observational study.Setting All intensive care units in one French region.Participants 3291 consecutive patients admitted for an acute myocardial infarction, from the RICO survey (a French regional survey for acute myocardial infarction).Main outcome measure Cardiovascular death at 1

L Lorgis; M Zeller; G Dentan; P Sicard; P Buffet; I L’Huillier; J C Beer; M Vincent-Martin; H Makki; P Gambert; Y Cottin

2009-01-01

48

Purinergic Receptor Stimulation Reduces Cytotoxic Edema and Brain Infarcts in Mouse Induced by Photothrombosis by Energizing Glial Mitochondria  

PubMed Central

Treatments to improve the neurological outcome of edema and cerebral ischemic stroke are severely limited. Here, we present the first in vivo single cell images of cortical mouse astrocytes documenting the impact of single vessel photothrombosis on cytotoxic edema and cerebral infarcts. The volume of astrocytes expressing green fluorescent protein (GFP) increased by over 600% within 3 hours of ischemia. The subsequent growth of cerebral infarcts was easily followed as the loss of GFP fluorescence as astrocytes lysed. Cytotoxic edema and the magnitude of ischemic lesions were significantly reduced by treatment with the purinergic ligand 2-methylthioladenosine 5? diphosphate (2-MeSADP), an agonist with high specificity for the purinergic receptor type 1 isoform (P2Y1R). At 24 hours, cytotoxic edema in astrocytes was still apparent at the penumbra and preceded the cell lysis that defined the infarct. Delayed 2MeSADP treatment, 24 hours after the initial thrombosis, also significantly reduced cytotoxic edema and the continued growth of the brain infarction. Pharmacological and genetic evidence are presented indicating that 2MeSADP protection is mediated by enhanced astrocyte mitochondrial metabolism via increased inositol trisphosphate (IP3)-dependent Ca2+ release. We suggest that mitochondria play a critical role in astrocyte energy metabolism in the penumbra of ischemic lesions, where low ATP levels are widely accepted to be responsible for cytotoxic edema. Enhancement of this energy source could have similar protective benefits for a wide range of brain injuries.

Zheng, Wei; Watts, Lora Talley; Holstein, Deborah M.; Prajapati, Suresh I.; Keller, Charles; Grass, Eileen H.; Walter, Christi A.; Lechleiter, James D.

2010-01-01

49

Optic nerve infarction and post-ischemic inflammation in the rodent model of anterior ischemic optic neuropathy (rAION)  

PubMed Central

Nonarteritic anterior ischemic optic neuropathy (NAION) results from isolated anterior optic nerve (ON)-axonal ischemia near the retina–optic nerve junction. We utilized a rodent model of NAION (rAION) to study the in vivo inflammatory response after pure axonal ischemic infarct. ON ischemia was generated using laser-coupled rose Bengal dye photoactivation, and the infarct localized using tetrazolium red and histology. ON inflammation was evaluated following infarct using extrinsic macrophage (ED1) and microglial (isolated Iba1) cell markers. In naive ONs, some ED1(+)/Iba1(+) cells, representing extrinsic macrophages, were present in intraretinal ON region, but not in the retroscleral (isolated ON) region. Numerous ED1(?)/Iba1(+) cells, likely representing intrinsic microglia, were present throughout the entire ON. One day post-stroke, slight increases in both ED1(+) and Iba1(+) cells were apparent in the eye region immediately surrounding the anterior ON. Three days post-stroke, there was marked infiltration and aggregates of ED1(+)/Iba1(+) cells, with axon structural disruption in the region of the ischemic infarct. ED1(+) and Iba1(+) cells were present in the portion of the ON surrounding the infarct, possibly representing a penumbral region similar to that seen in ischemic brain infarcts. Although ED1(+) cells decreased by 7–14 days post-stroke, large numbers of Iba1(+) cells persisted in the anterior ON. Similar to other CNS ischemic strokes, pure axonal ischemia results in the early recruitment of extrinsic macrophages to the ischemic region. Manipulation of the inflammatory response may be an important variable that could potentially improve visual outcome.

Zhang, Cheng; Guo, Yan; Miller, Neil R.; Bernstein, Steven L.

2009-01-01

50

Optic nerve infarction and post-ischemic inflammation in the rodent model of anterior ischemic optic neuropathy (rAION).  

PubMed

Nonarteritic anterior ischemic optic neuropathy (NAION) results from isolated anterior optic nerve (ON)-axonal ischemia near the retina-optic nerve junction. We utilized a rodent model of NAION (rAION) to study the in vivo inflammatory response after pure axonal ischemic infarct. ON ischemia was generated using laser-coupled rose Bengal dye photoactivation, and the infarct localized using tetrazolium red and histology. ON inflammation was evaluated following infarct using extrinsic macrophage (ED1) and microglial (isolated Iba1) cell markers. In naive ONs, some ED1(+)/Iba1(+) cells, representing extrinsic macrophages, were present in intraretinal ON region, but not in the retroscleral (isolated ON) region. Numerous ED1(-)/Iba1(+) cells, likely representing intrinsic microglia, were present throughout the entire ON. One day post-stroke, slight increases in both ED1(+) and Iba1(+) cells were apparent in the eye region immediately surrounding the anterior ON. Three days post-stroke, there was marked infiltration and aggregates of ED1(+)/Iba1(+) cells, with axon structural disruption in the region of the ischemic infarct. ED1(+) and Iba1(+) cells were present in the portion of the ON surrounding the infarct, possibly representing a penumbral region similar to that seen in ischemic brain infarcts. Although ED1(+) cells decreased by 7-14 days post-stroke, large numbers of Iba1(+) cells persisted in the anterior ON. Similar to other CNS ischemic strokes, pure axonal ischemia results in the early recruitment of extrinsic macrophages to the ischemic region. Manipulation of the inflammatory response may be an important variable that could potentially improve visual outcome. PMID:19401181

Zhang, Cheng; Guo, Yan; Miller, Neil R; Bernstein, Steven L

2009-01-15

51

Association Between the Glu298Asp Polymorphism in the Endothelial Constitutive Nitric Oxide Synthase Gene and Brain Infarction  

Microsoft Academic Search

Background and Purpose—Nitric oxide (NO) synthesized by endothelial constitutive NO synthase (ecNOS) plays a key role in vascular regulation and atherosclerosis. Little is known concerning the role of the ecNOS gene ( NOS3) as a risk factor for brain infarction (BI). Our aim was to investigate the relation between the Glu298Asp polymorphism in exon 7o fNOS3 with BI and its

Alexis Elbaz; Odette Poirier; Thierry Moulin; Francois Chedru; Francois Cambien; Pierre Amarenco

52

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

53

Sca-1-positive cardiac stem cell migration in a cardiac infarction model.  

PubMed

Adult myocardium has the capacity for repair and regeneration, which is derived from cardiac stem cells (CSCs). In this study, we assessed the migration and changes in numbers of Sca-1-positive CSCs after myocardial infarction (MI) in vivo and in vitro. In this study, we showed that in a rat MI model the CSCs emerged around the vessels near the peri-infarct zone and in the epicardium of the infarcted area. Four weeks after infarction, no differences in the expression of connexin 43 (Cx43) were observed in the peri-infarct and infarct zones. In vitro, we mimicked tissue ischemia and hypoxia by using a culture environment of 5 % O? and a wound healing assay to monitor the migration of CSCs. In conclusion, under hypoxic conditions, the CSCs, conveyed by blood vessels, migrated from the niche to the infarct zone for repairing the damaged myocytes. The number of endogenous migrating CSCs was proportionate to the repair time after infarction, rather than the degree of infarction. Four weeks after MI, the expression of Cx43 was not altered in migratory CSCs, namely no enhanced gap-junctional communication with cardiomyocytes was seen in the CSCs. Further studies are necessary to delineate the molecular mechanisms that drive the migration of CSCs after MI. PMID:23400327

Liu, Jingjin; Wang, Yongshun; Du, Wenjuan; Yu, Bo

2013-06-01

54

Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats  

PubMed Central

Background The therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) was investigated. Methods Adult male Sprague-Dawley (SD) rats (n = 30) were divided into IS plus intra-venous 1 mL saline (at 0, 12 and 24 h after IS induction) (control group) and IS plus intra-venous ADMSCs (2.0 × 106) (treated interval as controls) (treatment group) after occlusion of distal left internal carotid artery. The rats were sacrificed and brain tissues were harvested on day 21 after the procedure. Results The results showed that BIA was larger in control group than in treatment group (p < 0.001). The sensorimotor functional test (Corner test) identified a higher frequency of turning movement to left in control group than in treatment group (p < 0.05). mRNA expressions of Bax, caspase 3, interleukin (IL)-18, toll-like receptor-4 and plasminogen activator inhibitor-1 were higher, whereas Bcl-2 and IL-8/Gro were lower in control group than in treatment group (all p < 0.05). Western blot demonstrated a lower CXCR4 and stromal-cell derived factor-1 (SDF-1) in control group than in treatment group (all p < 0.01). Immunohistofluorescent staining showed lower expressions of CXCR4, SDF-1, von Willebran factor and doublecortin, whereas the number of apoptotic nuclei on TUNEL assay was higher in control group than in treatment group (all p < 0.001). Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01). Conclusions ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.

2010-01-01

55

Reperfusion of cerebral artery thrombosis by the GPIb-VWF blockade with the Nanobody ALX-0081 reduces brain infarct size in guinea pigs.  

PubMed

Thrombolytic therapy is the cornerstone of treatment of acute atherothrombotic ischemic stroke but is associated with brain hemorrhage; antiplatelet therapy has limited efficacy and is still associated with intracranial bleeding. Therefore, new antithrombotic approaches with a better efficacy/safety ratio are required. We have assessed the effect of ALX-0081, a Nanobody against the A1 domain of von Willebrand factor (VWF) that blocks VWF binding to GPIb, of the thrombolytic agent recombinant tissue plasminogen activator (rtPA), and of the GPIIb/IIIa antagonist tirofiban, in a middle cerebral artery (MCA) thrombosis model in guinea pigs. Drugs were administered before, immediately after, or 15 or 60 minutes after the total occlusion of the MCA. ALX-0081 prevented MCA thrombosis and induced reperfusion when given immediately after and 15 minutes after complete occlusion and reduced brain damage without inducing hemorrhage, whereas tirofiban prevented thrombosis but did not induce reperfusion and induced striking brain hemorrhage. rtPA also induced reperfusion when given 60 minutes after occlusion but provoked brain hemorrhage. Skin bleeding time was not modified or was moderately prolonged by ALX-0081, whereas tirofiban and rtPA prolonged it. The inhibition of the GPIb-VWF axis in guinea pigs prevents cerebral artery thrombosis and induces early reperfusion without provoking intracerebral bleeding thus reducing brain infarct area. PMID:23589671

Momi, Stefania; Tantucci, Michela; Van Roy, Maarten; Ulrichts, Hans; Ricci, Giovanni; Gresele, Paolo

2013-04-15

56

Ginkgo biloba leaf extract (EGb761) combined with neuroprotective agents reduces the infarct volumes of gerbil ischemic brain.  

PubMed

Ginkgo biloba exerts many pharmacological actions. It possesses antioxidant properties, the ability of neurotransmitter/receptor modulation and antiplatelet activation factor. This research is designed to investigate the neuroprotective effects of long-term treatment with EGb761 (a standard form of the extract of Ginkgo biloba leaf) in combination with MgSO(4), FK506, or MK-801 on the infarct volume of male gerbils' brain induced by unilateral middle cerebral artery occlusion (MCAO). Thirty-five gerbils fed a standard diet were intragastrically given water or EGb761 (100 mg/kg/day) for one week. Five randomized groups were established: control (n = 7), EGb761 (n = 8), EGb761 + MgSO(4) (n = 7), EGb761 + FK506 (n = 7), and EGb761 + MK-801 (n = 6). The three drug-combination groups were injected with MgSO(4) (90 mg/kg), FK506 (0.5 mg/kg), or MK-801 (1 mg/kg), respectively 30 min before MCAO. Gerbils were anesthetized and craniectomized to expose the right middle cerebral artery (MCA). The right MCA was constricted with an 8-0 suture to produce a permanent ligation for 24 hours. Postmortem infarct volumes were determined by quantitative image analysis of 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain sections. Results showed that the total infarct volumes of the four treated groups either EGb761 alone or in combination with drugs were lower than the control group by 36.1% (EGb761 alone), 40.3% (EGb761 + MgSO(4)), 35.3% (EGb761 + FK506), and 56.4% (EGb761 + MK-801), respectively (p < 0.01). The main affected areas of the brain in the four treated groups were significantly focused between 4 and 6 mm from the frontal pole, when compared to the control group (p < 0.01). All animals in the five groups had infarctions in both cortex and subcortex. These results indicate that long-term pre-treatment of EGb761 administered either alone or in combination with drugs significantly effective neuroprotection on infarct volume in gerbil ischemic brains. PMID:17080546

Chung, Shu-Ying; Cheng, Fu-Chou; Lee, Ming-Shih; Lin, Jing-Ying; Lin, Ming-Cheng; Wang, Ming-Fu

2006-01-01

57

A Plasma Model of Brain Dynamics  

Microsoft Academic Search

A plasma model of the brain is proposed to explain the long range correlations observed in the nervous system of the living brain and to understand such mental functions of the brain as the remembering (as well as forgetting) and the recalling of information received from the external world. In this model a waking but inattentive state of the brain

Noboru Hokkyo

1972-01-01

58

Tooth loss is associated with brain white matter change and silent infarction among adults without dementia and stroke.  

PubMed

Periodontal disease is a predictor of stroke and cognitive impairment. The association between the number of lost teeth (an indicator of periodontal disease) and silent infarcts and cerebral white matter changes on brain CT was investigated in community-dwelling adults without dementia or stroke. Dental examination and CT were performed in 438 stroke- and dementia-free subjects older than 50 yr (mean age, 63 ± 7.9 yr), who were recruited for an early health check-up program as part of the Prevention of Stroke and Dementia (PRESENT) project between 2009 and 2010. In unadjusted analyses, the odds ratio (OR) for silent cerebral infarcts and cerebral white matter changes for subjects with 6-10 and > 10 lost teeth was 2.3 (95% CI, 1.38-4.39; P = 0.006) and 4.2 (95% CI, 1.57-5.64; P < 0.001), respectively, as compared to subjects with 0-5 lost teeth. After adjustment for age, education, hypertension, diabetes mellitus, hyperlipidemia, and smoking, the ORs were 1.7 (95% CI, 1.08-3.69; P = 0.12) and 3.9 (95% CI, 1.27-5.02; P < 0.001), respectively. These findings suggest that severe tooth loss may be a predictor of silent cerebral infarcts and cerebral white matter changes in community-dwelling, stroke- and dementia-free adults. PMID:23772160

Minn, Yang-Ki; Suk, Seung-Han; Park, Hyunyoung; Cheong, Jin-Sung; Yang, Hyunduk; Lee, Sungik; Do, Seung-Yeon; Kang, Ji-Sook

2013-06-03

59

Tooth Loss Is Associated with Brain White Matter Change and Silent Infarction among Adults without Dementia and Stroke  

PubMed Central

Periodontal disease is a predictor of stroke and cognitive impairment. The association between the number of lost teeth (an indicator of periodontal disease) and silent infarcts and cerebral white matter changes on brain CT was investigated in community-dwelling adults without dementia or stroke. Dental examination and CT were performed in 438 stroke- and dementia-free subjects older than 50 yr (mean age, 63 ± 7.9 yr), who were recruited for an early health check-up program as part of the Prevention of Stroke and Dementia (PRESENT) project between 2009 and 2010. In unadjusted analyses, the odds ratio (OR) for silent cerebral infarcts and cerebral white matter changes for subjects with 6-10 and > 10 lost teeth was 2.3 (95% CI, 1.38-4.39; P = 0.006) and 4.2 (95% CI, 1.57-5.64; P < 0.001), respectively, as compared to subjects with 0-5 lost teeth. After adjustment for age, education, hypertension, diabetes mellitus, hyperlipidemia, and smoking, the ORs were 1.7 (95% CI, 1.08-3.69; P = 0.12) and 3.9 (95% CI, 1.27-5.02; P < 0.001), respectively. These findings suggest that severe tooth loss may be a predictor of silent cerebral infarcts and cerebral white matter changes in community-dwelling, stroke- and dementia-free adults.

Minn, Yang-Ki; Park, Hyunyoung; Cheong, Jin-Sung; Yang, Hyunduk; Lee, Sungik; Do, Seung-Yeon; Kang, Ji-Sook

2013-01-01

60

Development of an Animal Model for Spontaneous Myocardial Infarction (WHHLMI Rabbit)  

Microsoft Academic Search

Objective—Coronary heart disease is the most common cause of death in developed countries. However, there are no suitable animal models that mimic spontaneous myocardial infarction in humans. In this study, we attempted to obtain a rabbit strain with spontaneous myocardial infarction by selective breeding of coronary atherosclerosis-prone Watanabe heritable hyperlipidemic (WHHL) rabbits, designated as WHHLMI rabbits. Methods and Results—WHHLMI rabbits

Masashi Shiomi; Takashi Ito; Satoshi Yamada; Seinosuke Kawashima; Jianglin Fan

2010-01-01

61

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

2013-07-02

62

Laser-targeted photosensitizer-induced lung injury: noninvasive rat model of pulmonary infarction.  

PubMed

Pulmonary infarction is a life-threatening lung injury that requires rapid and accurate diagnosis for proper treatment. Targetable and reproducible small-animal models that would allow experimental development and preclinical evaluation of diagnostic methods for detecting pulmonary infarction are critically missing. The authors report here a novel procedure to selectively induce pulmonary infarction by photodestructive laser-light irradiation in a targeted location within a specific lung compartment after administration of a photosensitizer. Histopathological analysis of the illuminated lung tissue revealed massive hemorrhage and vascular occlusion after acute injury localized to the site of irradiation. Collapse of alveolar structure, neutrophil influx, and necrosis were subsequently observed. Computed tomography (CT) scans showed evidence of abnormal density and airspace consolidation in the irradiated area of the lung, but not elsewhere in the lung compartment. Perfusion imaging using 99mTc-labeled macroaggregated albumin by single-photon emission computed tomography revealed diminished scintigraphic signal in the opaque area of infarcted lung tissue. The histological changes, CT findings, and perfusion characteristics of pulmonary infarction are mimicked using laser-irradiated, photosensitizer-mediated photodestruction to selectively induce chronic lung injury in a localized area. This small-animal model can be easily and readily used for targeted induction of pulmonary infarction in a designated area of lung compartment and offers the potential for use in evaluating novel diagnostic and therapeutic methods. PMID:22122508

Chrastina, Adrian; Schnitzer, Jan E

2011-11-28

63

The effect of hydrogel injection on cardiac function and myocardial mechanics in a computational post-infarction model.  

PubMed

An emerging therapy to limit adverse heart remodelling following myocardial infarction (MI) is the injection of polymers into the infarcted left ventricle (LV). In the few numerical studies carried out in this field, the definition and distribution of the hydrogel in the infarcted myocardium were simplified. In this computational study, a more realistic biomaterial distribution was simulated after which the effect on cardiac function and mechanics was studied. A validated finite element heart model was used in which an antero-apical infarct was defined. Four infarct models were created representing different temporal phases in the progression of a MI. Hydrogel layers were simulated in the infarcted myocardium in each model. Biomechanical and functional improvement of the LV was found after hydrogel inclusion in the ischaemic models representing the early phases of MI. In contrast, only functional but no mechanical restitution was shown in the scar model due to hydrogel presence. PMID:22439799

Kortsmit, Jeroen; Davies, Neil H; Miller, Renee; Macadangdang, Jesse R; Zilla, Peter; Franz, Thomas

2012-03-22

64

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

PubMed Central

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

Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

2012-01-01

65

Neurobehavioural deficits correlate with the cerebral infarction volume of stroke animals: a comparative study on ischaemia-reperfusion and photothrombosis models.  

PubMed

The study investigated the correlation between infarction areas and behavioural deficits in middle cerebral artery occlusion (MCAO) and photothrombosis stroke models. In the MCAO model, a 0.38 mm-diameter silicone-coated thread was introduced through the left external carotid artery and advanced 18 mm via the internal carotid artery to the origin of middle cerebral artery of male Sprague-Dawley rats weighing 300-350 g. The thread was removed for reperfusion after occlusion for 0.5, 1 or 2h. In the photothrombosis model, after a midline incision on the scalp, a focused light (10,000 lux, 6 mm-diameter) was delivered 1mm anterior to the bregma and 3mm left of the midline for 5, 10 or 20 min. During the first 2 min of irradiation, Rose Bengal dye (30 mg/kg) was injected intravenously. Twenty four hours post-surgery, the animals were subjected to neurological scoring and behavioural performances, and were sacrificed for macroscopic and microscopic examinations of brain injury. Total infarction volumes in the MCAO model rats increased in an occlusion time-dependent manner, while the infarction volumes in photothrombosis model rats plateaued relatively quickly with no time-dependent increase. The MCAO model displayed neurological scores and behavioural deficits that correlated well with infarction volumes, while relatively poor correlation between infarction volume and neurobehavioural abnormalities was evident in the photothrombosis model. The results indicate the suitability of the MCAO model for studies on preventive or therapeutic compounds related to functional recovery, although the photothrombosis model might be useful to generate focused lesions leading to the location-related behavioural changes. PMID:22134000

Choi, Byong-il; Park, Dongsun; Lee, Sun Hee; Bae, Dae-Kwon; Yang, Goeun; Yang, Yun-Hui; Kim, Tae Kyun; Choi, Ehn-Kyoung; Lee, Hwa-Jeong; Choi, Kyung-Chul; Nahm, Sang-Seop; Kim, Yun-Bae

2011-11-12

66

Comparing diffusion-weighted and T2-weighted MR imaging for the quantification of infarct size in a neonatal rat hypoxic–ischemic model at 24 h post-injury  

Microsoft Academic Search

PurposeIn a neonatal rat model of hypoxic–ischemic (HI) brain injury, using T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), we aim to determine the best MRI method of lesion quantification that reflects infarct size.

Yanxin Wang; Pik-To Cheung; Gary X. Shen; Inderjeet Bhatia; Ed Xue Wu; Deqiang Qiu; Pek-Lan Khong

2007-01-01

67

Atypical megadolichoectasia manifesting as brain infarction rapidly followed by fatal subarachnoid hemorrhage.  

PubMed

A 71-year-old female, without medical or family history for cerebrovascular disease, presented with basilar and bilateral carotid dolichoectasia manifesting as dysarthria and hemisensory disturbance, which resolved spontaneously within a day. She suffered brainstem infarction 28 months later, manifesting as drowsiness, dysarthria, and right hemiparesis. Her consciousness level progressively deteriorated to stupor within 4 days. Computed tomography taken on the 5th day confirmed cerebellar infarct in the perfusion area of the superior cerebellar artery but did not show subarachnoid hemorrhage. She died of acute respiratory failure on the 7th day. Autopsy demonstrated a tear in the lateral wall of the broad-based aneurysm on the ectatic basilar artery and diffuse subarachnoid hemorrhage. Vertebrobasilar ectasia is a dynamic vasculopathy that may rapidly progress in the affected basilar artery following an indolent clinical course. The prognosis for patients with vertebrobasilar ectasia may depend mainly on the pathological changes in the basilar artery. PMID:19226335

Tsutsumi, Satoshi; Yasumoto, Yukimasa; Ito, Masanori

2010-10-01

68

Closed-chest experimental porcine model of acute myocardial infarction–reperfusion  

Microsoft Academic Search

IntroductionProgress in cardiovascular regenerative medicine research requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to assess the validity of a porcine endovascular model of myocardial infarction and reperfusion.

Armando Pérez de Prado; Carlos Cuellas-Ramón; Marta Regueiro-Purriños; J. Manuel Gonzalo-Orden; Claudia Pérez-Martínez; José R. Altónaga; M. José García-Iglesias; M. Asunción Orden-Recio; Juan F. García-Marín; Felipe Fernández-Vázquez

2009-01-01

69

Peri-infarct flow transients predict outcome in rat focal brain ischemia.  

PubMed

Spreading depolarizations are accompanied by transient changes in cerebral blood flow (CBF). In a post hoc analysis of previously studied control rats we analyzed CBF time courses after middle cerebral artery occlusion in the rat in order to test whether intra-ischemic flow, reperfusion, and different parameters of peri-infarct flow transients (PIFTs) (amplitude, number) can predict outcome. Sprague-Dawley rats anesthetized with either halothane (n=23) or isoflurane (n=32) underwent 90-min filament occlusion of the middle cerebral artery followed by 72 h of reperfusion. The infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Relative CBF changes were monitored by laser Doppler flowmetry at 4-5 mm lateral, and 1-2mm posterior to Bregma. An additional filament occlusion study (n=12) was performed to validate that PIFTs were coupled to direct current shifts of spreading depolarization. The PIFT-direct current shift study revealed that every PIFT was associated with a negative direct current shift typical of spreading depolarization. Post-hoc analysis showed that the number of PIFTs, especially with the combination of intra-ischemic level of flow, can predict the development of cortical infarcts. These findings show that PIFTs can serve as an early biomarker in predicting outcome in preclinical animal studies. PMID:22986160

Lückl, J; Dreier, J P; Szabados, T; Wiesenthal, D; Bari, F; Greenberg, J H

2012-09-15

70

Measures of brain morphology and infarction in the framingham heart study: establishing what is normal  

Microsoft Academic Search

Numerous anatomical and brain imaging studies find substantial differences in brain structure between men and women across the span of human aging. The ability to extend the results of many of these studies to the general population is limited, however, due to the generally small sample size and restrictive health criteria of these studies. Moreover, little attention has been paid

Charles DeCarli; Joseph Massaro; Danielle Harvey; John Hald; Mats Tullberg; Rhoda Au; Alexa Beiser; Ralph D’Agostino; Philip A. Wolf

2005-01-01

71

Experimental Model of Small Deep Infarcts Involving the Hypothalamus in Rats Changes in Body Temperature and Postural Reflex  

Microsoft Academic Search

Background and Purpose—Intraluminal middle cerebral artery (MCA) occlusion in rats has been reported to cause hyperthermia assumed to be caused by hypothalamic damage. To clarify the effects of hypothalamic ischemia on body temperature and to obtain a model simulating lacunar infarction, we attempted to produce small infarcts in deep structures (including the hypothalamus). Methods—A surgical suture was advanced to occlude

Zhen He; Takemori Yamawaki; Shaohua Yang; Arthur L. Day; James W. Simpkins; Hiroaki Naritomi

72

Modeling of the Brain for Injury Prevention  

Microsoft Academic Search

\\u000a From an ethical point of view, it is extremely difficult to propose a well-controlled human subject study aimed at understanding\\u000a brain injury mechanisms and establishing the associated tolerance values. For this reason, many numerical models of the human\\u000a and animal head or brain have been developed over the past several decades in an attempt to obtain in-depth insights into\\u000a brain

King H. Yang; Haojie Mao; Christina Wagner; Feng Zhu; Clifford C. Chou; Albert I. King

73

On the influence of space storms on the frequency of infarct-myocardial, brain strokes, and hard car accidents; possible using of CR for their forecasting  

NASA Astrophysics Data System (ADS)

We consider the influence of space storms as strong interplanetary shock waves causing great cosmic ray Forbush-decreases and big geomagnetic storms on the people health at the ground level We used data of more than 7 millions ambulance cases in Moscow and St Petersburg included information on daily numbers of the hard traffic accidents infarctions and brain strokes We found that during space storms the average daily numbers of hard traffic accidents with using ambulances as well as infarctions and brain strokes confirmed by medical personal increase by 17 4 pm 3 1 10 5 pm 1 2 and 7 0 pm 1 7 respectively We show that the forecasting of these dangerous apace phenomena can be done partly by using cosmic ray data on pre-increase and pre-decrease effects as well as on the change of 3-D cosmic ray anisotropy

Dorman, L. I.; Iucci, N.; Ptitsyna, N. G.; Villoresi, G.

74

Cerebral blood flow and metabolism in patients with silent brain infarction: occult misery perfusion in the cerebral cortex  

PubMed Central

OBJECTIVES—Silent brain infarction (SBI) is of growing interest as a possible risk factor for symptomatic stroke. Although morphological characteristics of SBI have been well defined, their characteristic patterns of cerebral blood flow (CBF) and metabolism are in dispute. The purpose of this study was to elucidate CBF and metabolism in patients with SBI in relation to symptomatic stroke.?METHODS—The patients underwent PET and were separated into three groups; control group (C group), with no lesions on CT (n=9, mean age 57), SBI group, with no neurological signs or history of stroke, but with ischaemic lesions on CT (n=9, mean age 63), and brain infarction group (BI group), with neurological deficits and compatible CT lesions in the area supplied by perforating arteries (n=19, mean age 56). Regional CBF, oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO2), and cerebral blood volume (CBV) were measured by PET.?RESULTS—Mean values for CBF to the cerebral cortex and deep grey matter were lower in the SBI group (31.6 (SD 5.8) and 34.3 (SD 6.9) ml/100 g/min, respectively) and in the BI group (30.8 (SD 5.2), 33.9 (SD 5.9), respectively) than in the C group (36.0 (SD 6.6) and 43.5 (SD 9.5), respectively). Although mean CMRO2 of deep grey matter (2.36 (SD 0.52) ml/100 g/min) was significantly decreased in the SBI group compared with the C group (2.76 (SD 0.480), p<0.01), CMRO2 of the cortical area was as well preserved in the SBI patients (2.36 (SD 0.39)) as in the controls (2.48 (SD 0.32)) with a compensatory increase of mean OEF (0.45 (SD 0.06) and 0.41 (SD 0.05), respectively).?CONCLUSIONS—Patients with SBI showed decreased CBF and CMRO2 in deep grey matter. On the other hand, decreased CBF with milder increased OEF, resulting in preserved CMRO2 in the cerebral cortex indicates the presence of occult misery perfusion, suggesting that patients with SBI have reduced cerebral perfusional reserves.??

Nakane, H.; Ibayashi, S.; Fujii, K.; Sadoshima, S.; Irie, K.; Kitazono, T.; Fujishima, M.

1998-01-01

75

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

76

Hyperglycaemia and infarct size in animal models of middle cerebral artery occlusion: systematic review and meta-analysis  

PubMed Central

Poststroke hyperglycaemia (PSH) is common, has an unclear pathophysiology, and is associated with poor outcomes. Animal studies report conflicting findings. We systematically reviewed the effects of hyperglycaemia on infarct volume in middle cerebral artery occlusion (MCAO) models, generating weighted mean differences between groups using random effects models summarised as effect size (normalised to control group infarct volume as 100%) and 95% confidence interval. Of 72 relevant papers, 23 reported infarct volume. Studies involved 664 animals and 35 distinct comparisons. Hyperglycaemia was induced by either streptozotocin (STZ, 17 comparisons, n=303) or dextrose (18 comparisons, n=356). Hyperglycaemic animals had infarcts that were 94% larger, but STZ was associated with significantly greater increase in infarct volumes than dextrose infusion (140% larger versus 48% larger). In seven studies, insulin did not significantly reduce infarct size and results were heterogeneous. Although hyperglycaemia exacerbates infarct volume in MCAO models, studies are heterogeneous, and do not address the common clinical problem of PSH because they have used either the STZ model of type I diabetes or extremely high glucose loads. Insulin had a nonsignificant and significantly heterogeneous effect. Further studies with relevant models may inform clinical trial design.

MacDougall, Niall J J; Muir, Keith W

2011-01-01

77

Long-term effects of hepatocyte growth factor gene therapy in rat myocardial infarct model.  

PubMed

We investigated the long-term effects of human hepatocyte growth factor (HGF) gene therapy in a rat myocardial infarct model. Treatment adenovirus coexpressing the HGF therapeutic gene and the human sodium/iodide symporter (NIS) reporter gene or control adenovirus expressing the NIS gene alone were injected directly into the infarct border zone immediately after permanent coronary ligation in rats (n=6 each). A uniform disease state was confirmed in the acute phase in terms of impaired left ventricular (LV) function by cine magnetic resonance imaging (MRI), large infarct extent by (99m)Tc-tetrofosmin single-photon emission computed tomography (SPECT) and successful gene transfer and expression by (99m)TcO(4)(-) SPECT. After a 10-week follow-up, repeated cine MRI demonstrated no significant difference in the LV ejection fraction between the time points or groups, but a significantly increased end-diastolic volume from the acute to the chronic phase without a significant difference between the groups. Capillary density was significantly higher in the treatment group, whereas arteriole density remained unchanged. Two-photon excitation fluorescence microscopy revealed extremely thin capillaries (2-5??m), and their irregular networks increased in the infarct border zone of the treated myocardium. Our results indicated that single HGF gene therapy alone induced an immature and irregular microvasculature. PMID:21918549

Jin, Y-N; Inubushi, M; Masamoto, K; Odaka, K; Aoki, I; Tsuji, A B; Sagara, M; Koizumi, M; Saga, T

2011-09-15

78

Higher coated-platelet levels are associated with stroke recurrence following nonlacunar brain infarction.  

PubMed

Coated-platelets are procoagulant platelets observed upon dual-agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in patients with nonlacunar (large-vessel) ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage as compared with controls. The purpose of this study was to investigate a possible relationship between coated-platelet levels and stroke recurrence in patients with nonlacunar ischemic stroke. We assayed coated-platelet levels in 190 consecutive patients with nonlacunar stroke who were followed for up to 12 months; 20 subjects experienced recurrent stroke. Subjects were categorized into tertiles of coated-platelet levels. The distributions of time-to-recurrent stroke were estimated for each tertile using cumulative incidence curves and compared statistically using a log-rank test. The cumulative incidence of recurrent stroke at 12 months differed among the coated-platelet tertiles: 2% for the first tertile (lowest coated-platelet levels), 18% for the second tertile, and 17% for the third tertile (overall log-rank test, P=0.019). These data suggest that higher levels of coated-platelets, measured shortly after a nonlacunar stroke, are associated with an increased incidence of stroke recurrence. This observation offers an additional tool for identifying patients at highest risk for stroke recurrence following a nonlacunar (large-vessel) infarct. PMID:23149559

Prodan, Calin I; Stoner, Julie A; Cowan, Linda D; Dale, George L

2012-11-14

79

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

Microsoft Academic Search

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

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

2010-01-01

80

Simple models of human brain functional networks  

PubMed Central

Human brain functional networks are embedded in anatomical space and have topological properties—small-worldness, modularity, fat-tailed degree distributions—that are comparable to many other complex networks. Although a sophisticated set of measures is available to describe the topology of brain networks, the selection pressures that drive their formation remain largely unknown. Here we consider generative models for the probability of a functional connection (an edge) between two cortical regions (nodes) separated by some Euclidean distance in anatomical space. In particular, we propose a model in which the embedded topology of brain networks emerges from two competing factors: a distance penalty based on the cost of maintaining long-range connections; and a topological term that favors links between regions sharing similar input. We show that, together, these two biologically plausible factors are sufficient to capture an impressive range of topological properties of functional brain networks. Model parameters estimated in one set of functional MRI (fMRI) data on normal volunteers provided a good fit to networks estimated in a second independent sample of fMRI data. Furthermore, slightly detuned model parameters also generated a reasonable simulation of the abnormal properties of brain functional networks in people with schizophrenia. We therefore anticipate that many aspects of brain network organization, in health and disease, may be parsimoniously explained by an economical clustering rule for the probability of functional connectivity between different brain areas.

Vertes, Petra E.; Alexander-Bloch, Aaron F.; Gogtay, Nitin; Giedd, Jay N.; Rapoport, Judith L.; Bullmore, Edward T.

2012-01-01

81

Vigorous response in plasma N-terminal pro-brain natriuretic peptide (NT-BNP) to acute myocardial infarction.  

PubMed

Acute myocardial infarction (MI) results in activation of neurohormonal systems and increased plasma concentrations of myocardial enzymes and structural proteins. We hypothesized that plasma levels of N-terminal pro-brain natriuretic peptide (NT-BNP) would respond more vigorously after MI than those of other natriuretic peptides. We also sought to compare this response with that of the established myocardial injury markers troponin T (TnT), myoglobin and creatine kinase MB (CK-MB). We obtained multiple blood samples for measurement of atrial natriuretic peptide (ANP), N-terminal pro-ANP, brain natriuretic peptide (BNP) and NT-BNP along with CK-MB, TnT and myoglobin in 24 patients presenting to the Coronary Care Unit within 6 h of onset of MI. Multiple samples were obtained in the first 24 h, then at 72 h, 1 week, 6 weeks and 12 weeks. NT-BNP increased rapidly to peak at 24 h and exhibited greater ( P <0.001) absolute increments from baseline compared with BNP and ANP, whereas NT-ANP did not change from baseline. Proportional increments in NT-BNP were also greater than those for the other natriuretic peptides ( P <0.05). Natriuretic peptide levels reached their peak around 24 h, later than peak TnT, CK-MB and myoglobin (peak between 1-10 h), and NT-BNP and ANP remained elevated on average for 12 weeks. Our present results, with detailed sampling of a cohort of acute MI patients, demonstrate greater absolute and proportional increments in NT-BNP than ANP or BNP with sustained elevation of these peptides at 12 weeks. PMID:12974669

Gill, Denzil; Seidler, Timothy; Troughton, Richard W; Yandle, Timothy G; Frampton, Christopher M; Richards, Mark; Lainchbury, John G; Nicholls, Gary

2004-02-01

82

Depression after myocardial infarction: TNF-?-induced alterations of the blood-brain barrier and its putative therapeutic implications.  

PubMed

Patients experiencing an acute myocardial infarction (AMI) have a three times higher chance to develop depression. Vice versa, depressive symptoms increase the risk of cardiovascular events. The co-existence of both conditions is associated with substantially worse prognosis. Although the underlying mechanism of the interaction is largely unknown, inflammation is thought to be of pivotal importance. AMI-induced peripheral cytokines release may cause cerebral endothelial leakage and hence induces a neuroinflammatory reaction. The neuroinflammation may persist even long after the initial peripheral inflammation has subsided. Among those selected brain regions that are prone to blood-brain barrier dysfunction, the paraventricular nucleus of the hypothalamus (PVN), a major center for cardiovascular autonomic regulation, is indicated to play a mediating role. Optimal cardiovascular therapy improves cardiovascular prognosis without major effects on depression. By the same token, antidepressant therapy in cardiovascular disease is associated with modest improvement in depressive symptoms, however without improvement in cardiac outcome. The failure of current antidepressants and the growing number of patients suffering from both conditions legitimize the search for better antidepressive therapies, from patients as well as society perspectives. Though we appreciate the mutual character of the interaction between depression and AMI, the present review focuses on the side of AMI induced depression and discusses the role of inflammation, represented by the proinflammatory cytokine TNF-?, as potential underlying mechanism. It is conceivable that inhibition of the inflammatory response post-AMI, through targeted anti-inflammatory pharmacotherapeutical agents may prevent the development of depressive symptoms and ultimately may improve cardiovascular outcomes. PMID:23415700

Liu, Hui; Luiten, Paul G M; Eisel, Uli L M; Dejongste, Mike J L; Schoemaker, Regien G

2013-02-13

83

Effects of Edaravone, a Free Radical Scavenger, on Photochemically Induced Cerebral Infarction in a Rat Hemiplegic Model  

PubMed Central

Edaravone is a free radical scavenger that protects the adjacent cortex during cerebral infarction. We created a hemiparetic model of cerebral thrombosis from a photochemically induced infarction with the photosensitive dye, rose bengal, in rats. We examined the effects of edaravone on recovery in the model. A total of 36 adult Wistar rats were used. The right sensorimotor area was irradiated with green light with a wavelength of 533?nm (10?mm diameter), and the rose bengal was injected intravenously to create an infarction. The edaravone group was injected intraperitoneally with edaravone (3?mg/kg), and the control group was injected with saline. The recovery process of the hemiplegia was evaluated with the 7-step scale of Fenny. The infarcted areas were measured after fixation. The recovery of the paralysis in the edaravone-treated group was significantly earlier than that in the untreated group. Seven days later, both groups were mostly recovered and had scores of 7, and the infarction region was significantly smaller in the edaravone-treated group. Edaravone reduced the infarction area and promoted the functional recovery of hemiparesis from cerebral thrombosis in a rat model. These findings suggest that edaravone treatment would be effective in clinical patients recovering from cerebral infarction.

Harada, Katsuhiro; Ohwatashi, Akihiko; Kamikawa, Yurie

2013-01-01

84

Automated variable selection methods for logistic regression produced unstable models for predicting acute myocardial infarction mortality  

Microsoft Academic Search

Abstract Objectives: Automated variable selection methods,are frequently used to determine,the independent,predictors of an outcome. The objective of this study was to determine the reproducibility of logistic regression models,developed,using automated,variable selection methods. Study Design and Setting: An initial set of 29 candidate variables were considered for predicting mortality after acute myocardial infarction (AMI). We drew 1,000 bootstrap samples from a dataset

Peter C. Austin; Jack V. Tu

85

An Improved Transplantation Strategy for Mouse Mesenchymal Stem Cells in an Acute Myocardial Infarction Model  

Microsoft Academic Search

To develop an effective therapeutic strategy for cardiac regeneration using bone marrow mesenchymal stem cells (BM-MSCs), the primary mouse BM-MSCs (1st BM-MSCs) and 5th passage BM-MSCs from ?-galactosidase transgenic mice were respectively intramyocardially transplanted into the acute myocardial infarction (AMI) model of wild type mice. At the 6th week, animals\\/tissues from the 1st BM-MSCs group, the 5th passage BM-MSCs group,

Jianliang Jin; Yingming Zhao; Xiao Tan; Chun Guo; Zhijian Yang; Dengshun Miao

2011-01-01

86

A Soluble Fn14-Fc Decoy Receptor Reduces Infarct Volume in a Murine Model of Cerebral Ischemia  

PubMed Central

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily. TWEAK acts on responsive cells via binding to a small cell surface receptor named Fn14. Recent studies have demonstrated that TWEAK can stimulate numerous cellular responses including cell proliferation, migration, and proinflammatory molecule production, but the role of this cytokine in cardiovascular disease and stroke has not been established. The present study investigated whether TWEAK or Fn14 expression was regulated in a murine model of cerebral ischemia and whether TWEAK played a role in ischemia-mediated cell death. We found that TWEAK and Fn14 were expressed by primary mouse cerebral cortex-derived astrocytes and neurons cultured in vitro. Also, both the TWEAK and Fn14 proteins were present at elevated levels in the ischemic penumbra region after middle cerebral artery occlusion. Finally, we report that intracerebroventricular injection of a soluble Fn14-Fc decoy receptor immediately after middle cerebral artery occlusion significantly reduced infarct volume and the extent of microglial cell activation and apoptotic cell death in the ischemic penumbra. We conclude that the cytokine TWEAK may play an important role in ischemia-induced brain injury and that inhibition of TWEAK expression or function in the brain may represent a novel neuroprotective strategy to treat ischemic stroke.

Yepes, Manuel; Brown, Sharron A.N.; Moore, Elizabeth G.; Smith, Elizabeth P.; Lawrence, Daniel A.; Winkles, Jeffrey A.

2005-01-01

87

The protective effects of T cell deficiency against brain injury are ischemic model-dependent in rats.  

PubMed

Previous studies have reported that T cell deficiency reduced infarct sizes after transient middle cerebral artery (MCA) suture occlusion in mice. However, how reperfusion and different models affect the detrimental effects of T cells have not been studied. We investigated the effects of T cell deficiency in nude rats using two stroke models and compared their infarct sizes with those in WT rats. In the distal MCA occlusion (MCAo) model, the distal MCA was permanently occluded and the bilateral common carotid arteries (CCAs) were transiently occluded for 60 min. In the suture MCAo model, the MCA was transiently occluded for 100 min by the insertion of a monofilament suture. Our results showed that T cell deficiency resulted in about a 50% reduction in infarct size in the suture MCAo model, whereas it had no effect in the distal MCAo model, suggesting the protective effects of T cell deficiency are dependent on the ischemic model used. We further found more total T cells, CD4 T cells and CD8 T cells in the ischemic brains of WT rats in the suture MCAo model than in the distal MCAo model. In addition, we detected more CD68-expressing macrophages in the ischemic brains of WT rats than in nude rats in the suture MCAo but not the distal MCAo model. Lymphocyte reconstitution in nude rats resulted in larger infarct sizes in the suture MCAo, but not in the distal MCAo stroke model. The results of regional CBF measurement indicated a total reperfusion in the MCAo model but only a partial reperfusion in the distal MCAo model. In conclusion, the protective effects of T cell deficiency on brain injury are dependent on the ischemic model used; likely associated with different degrees of reperfusion. PMID:23228347

Xiong, Xiaoxing; Gu, Lijuan; Zhang, Hongfei; Xu, Baohui; Zhu, Shengmei; Zhao, Heng

2012-12-08

88

Sulfonylurea receptor 1 expression in human cerebral infarcts.  

PubMed

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

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

2013-09-01

89

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.

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

2013-01-01

90

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.

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

91

Manifold modeling for brain population analysis.  

PubMed

This paper describes a method for building efficient representations of large sets of brain images. Our hypothesis is that the space spanned by a set of brain images can be captured, to a close approximation, by a low-dimensional, nonlinear manifold. This paper presents a method to learn such a low-dimensional manifold from a given data set. The manifold model is generative-brain images can be constructed from a relatively small set of parameters, and new brain images can be projected onto the manifold. This allows to quantify the geometric accuracy of the manifold approximation in terms of projection distance. The manifold coordinates induce a Euclidean coordinate system on the population data that can be used to perform statistical analysis of the population. We evaluate the proposed method on the OASIS and ADNI brain databases of head MR images in two ways. First, the geometric fit of the method is qualitatively and quantitatively evaluated. Second, the ability of the brain manifold model to explain clinical measures is analyzed by linear regression in the manifold coordinate space. The regression models show that the manifold model is a statistically significant descriptor of clinical parameters. PMID:20579930

Gerber, Samuel; Tasdizen, Tolga; Thomas Fletcher, P; Joshi, Sarang; Whitaker, Ross

2010-06-04

92

Modeling of functional brain imaging data  

NASA Astrophysics Data System (ADS)

The richness and complexity of data sets obtained from functional neuroimaging studies of human cognitive behavior, using techniques such as positron emission tomography and functional magnetic resonance imaging, have until recently not been exploited by computational neural modeling methods. In this article, following a brief introduction to functional neuroimaging methodology, two neural modeling approaches for use with functional brain imaging data are described. One, which uses structural equation modeling, examines the effective functional connections between various brain regions during specific cognitive tasks. The second employs large-scale neural modeling to relate functional neuroimaging signals in multiple, interconnected brain regions to the underlying neurobiological time-varying activities in each region. These two modeling procedures are illustrated using a visual processing paradigm.

Horwitz, Barry

1999-03-01

93

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

94

Modeling the hemodynamic response to brain activation  

Microsoft Academic Search

Neural activity in the brain is accompanied by changes in cerebral blood flow (CBF) and blood oxygenation that are detectable with functional magnetic resonance imaging (fMRI) techniques. In this paper, recent mathematical models of this hemodynamic response are reviewed and integrated. Models are described for: (1) the blood oxygenation level dependent (BOLD) signal as a function of changes in cerebral

Richard B. Buxton; Kâmil Uluda?; David J. Dubowitz; Thomas T. Liu

2004-01-01

95

Enriched environment preconditioning induced brain ischemic tolerance without reducing infarct volume and edema: the possible role of enrichment-related physical activity increase.  

PubMed

External stimuli, including environmental enrichment (EE) and physical activity, have been shown to significantly facilitate recovery from brain injury. However, whether EE can be used as a preconditioning method to induce cerebral ischemic tolerance has never been investigated. Furthermore, whether, and to what extent, such environmental stimuli regulate physical activity to promote neuroprotection is largely unclear. To examine the neuroprotective effects of pre-ischemic EE (PIEE) and to investigate the relationship between these effects and EE-induced physical activity, we tested neurobehavioral and morphological recovery of rats following transient focal cerebral ischemia. Our study showed that PIEE improved the recovery of motor function, spatial learning and memory without reduction in brain edema or infarct volume. We also found that PIEE robustly increased the level of physical activity of rats that positively correlated with the extent of neurobehavioral recovery. Our results suggest that PIEE may induce brain ischemic tolerance through, at least partially, increasing physical activity. PMID:23501217

Xie, Hongyu; Wu, Yi; Jia, Jie; Liu, Gang; Zhang, Feng; Zhang, Qi; Yu, Kewei; Hu, Yongshan; Bai, Yulong; Hu, Ruiping

2013-03-15

96

Intravenous infusion of mesenchymal stem cells enhances regional perfusion and improves ventricular function in a porcine model of myocardial infarction  

Microsoft Academic Search

Transplantation of stem cells may improve regional perfusion and post-infarct ventricular function, but the optimal dose and\\u000a efficacy of cell delivery via the intravenous route has not been determined. This study tested the hypothesis that intravenous\\u000a infusion of bone marrow-derived mesenchymal stem cells (MSCs) enhances regional perfusion and improves ventricular function\\u000a after myocardial infarction. In a closed-chest pig model, the

Michael E. Halkos; Zhi-Qing Zhao; Faraz Kerendi; Ning-Ping Wang; Rong Jiang; L. Susan Schmarkey; Bradley J. Martin; Arshed A. Quyyumi; Walter L. Few; Hajime Kin; Robert A. Guyton; Jakob Vinten-Johansen

2008-01-01

97

Heliox and oxygen reduce infarct volume in a rat model of focal ischemia.  

PubMed

Normobaric hyperoxia treatment has recently been demonstrated to be remarkably beneficial in acute focal ischemia. The present study compared hyperoxia treatment with a novel heliox treatment. Adult male rats breathed 30% oxygen and 70% nitrogen (control group), 100% oxygen (hyperoxia group), or 30% oxygen and 70% helium (heliox group) during a middle cerebral artery occlusion for 2 h and a 1-hour reperfusion (n=6 in each group). Neurological deficits were scored at 3 and 24 h post focal ischemia. Neither the physiological parameters (body temperature, blood pressure, heart rate, O(2) saturation, and laser Doppler cerebral blood) nor the 3-hour post ischemia neurological scores differed between groups. However, the neurological scores showed a statistically significant improvement at 24 h post ischemia in the heliox group (p<0.05). The infarct volume (mean+SD) as measured by 2,3,5-triphenyltetrazolium staining included 36+/-17% of the involved hemisphere in the control group, 16+/-14% in the hyperoxia group, and 4+/-2% in the heliox group (p<0.01). In conclusion, whereas hyperoxia reduced the infarct volume, heliox further reduced the infarct volume and improved 24-hour neurological deficits in a rat model of focal ischemia. This suggests that a greater benefit may accrue from heliox therapy. PMID:17467695

Pan, Yi; Zhang, Haibo; VanDeripe, Donald R; Cruz-Flores, Salvador; Panneton, W Michael

2007-03-30

98

Multimodal, Multidimensional Models of Mouse Brain  

PubMed Central

Summary 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.

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

2011-01-01

99

Compact continuum brain model for human electroencephalogram  

NASA Astrophysics Data System (ADS)

A low-dimensional, compact brain model has recently been developed based on physiologically based mean-field continuum formulation of electric activity of the brain. The essential feature of the new compact model is a second order time-delayed differential equation that has physiologically plausible terms, such as rapid corticocortical feedback and delayed feedback via extracortical pathways. Due to its compact form, the model facilitates insight into complex brain dynamics via standard linear and nonlinear techniques. The model successfully reproduces many features of previous models and experiments. For example, experimentally observed typical rhythms of electroencephalogram (EEG) signals are reproduced in a physiologically plausible parameter region. In the nonlinear regime, onsets of seizures, which often develop into limit cycles, are illustrated by modulating model parameters. It is also shown that a hysteresis can occur when the system has multiple attractors. As a further illustration of this approach, power spectra of the model are fitted to those of sleep EEGs of two subjects (one with apnea, the other with narcolepsy). The model parameters obtained from the fittings show good matches with previous literature. Our results suggest that the compact model can provide a theoretical basis for analyzing complex EEG signals.

Kim, J. W.; Shin, H.-B.; Robinson, P. A.

2007-12-01

100

Inadvertent occlusion of the anterior choroidal artery explains infarct variability in the middle cerebral artery thread occlusion stroke model.  

PubMed

Intraluminal occlusion of the middle cerebral artery (MCAo) in rodents is perhaps the most widely used model of stroke, however variability of infarct volume and the ramifications of this on sample sizes remains a problem, particularly for preclinical testing of potential therapeutics. Our data and that of others, has shown a dichotomous distribution of infarct volumes for which there had previously been no clear explanation. When studying perfusion computed tomography cerebral blood volume (CBV) maps obtained during intraluminal MCAo in rats, we observed inadvertent occlusion of the anterior choroidal artery (AChAo) in a subset of animals. We hypothesized that the combined occlusion of the MCA and AChA may be a predictor of larger infarct volume following stroke. Thus, we aimed to determine the correlation between AChAo and final infarct volume in rats with either temporary or permanent MCA occlusion (1 h, 2 h, or permanent MCAo). Outbred Wistar rats (n?=?28) were imaged prior to and immediately following temporary or permanent middle cerebral artery occlusion. Presence of AChAo on CBV maps was shown to be a strong independent predictor of 24 h infarct volume (??=?0.732, p <0.001). This provides an explanation for the previously observed dichotomous distribution of infarct volumes. Interestingly, cortical infarct volumes were also larger in rats with AChAo, although the artery does not supply cortex. This suggests an important role for perfusion of the MCA territory beyond the proximal occlusion through AChA-MCA anastomotic collateral vessels in animals with a patent AChAo. Identification of combined MCAo and AChAo will allow other investigators to tailor their stroke model to reduce variability in infarct volumes, improve statistical power and reduce sample sizes in preclinical stroke research. PMID:24069448

McLeod, Damian D; Beard, Daniel J; Parsons, Mark W; Levi, Christopher R; Calford, Mike B; Spratt, Neil J

2013-09-17

101

Inadvertent Occlusion of the Anterior Choroidal Artery Explains Infarct Variability in the Middle Cerebral Artery Thread Occlusion Stroke Model  

PubMed Central

Intraluminal occlusion of the middle cerebral artery (MCAo) in rodents is perhaps the most widely used model of stroke, however variability of infarct volume and the ramifications of this on sample sizes remains a problem, particularly for preclinical testing of potential therapeutics. Our data and that of others, has shown a dichotomous distribution of infarct volumes for which there had previously been no clear explanation. When studying perfusion computed tomography cerebral blood volume (CBV) maps obtained during intraluminal MCAo in rats, we observed inadvertent occlusion of the anterior choroidal artery (AChAo) in a subset of animals. We hypothesized that the combined occlusion of the MCA and AChA may be a predictor of larger infarct volume following stroke. Thus, we aimed to determine the correlation between AChAo and final infarct volume in rats with either temporary or permanent MCA occlusion (1 h, 2 h, or permanent MCAo). Outbred Wistar rats (n?=?28) were imaged prior to and immediately following temporary or permanent middle cerebral artery occlusion. Presence of AChAo on CBV maps was shown to be a strong independent predictor of 24 h infarct volume (??=?0.732, p <0.001). This provides an explanation for the previously observed dichotomous distribution of infarct volumes. Interestingly, cortical infarct volumes were also larger in rats with AChAo, although the artery does not supply cortex. This suggests an important role for perfusion of the MCA territory beyond the proximal occlusion through AChA-MCA anastomotic collateral vessels in animals with a patent AChAo. Identification of combined MCAo and AChAo will allow other investigators to tailor their stroke model to reduce variability in infarct volumes, improve statistical power and reduce sample sizes in preclinical stroke research.

McLeod, Damian D.; Beard, Daniel J.; Parsons, Mark W.; Levi, Christopher R.; Calford, Mike B.; Spratt, Neil J.

2013-01-01

102

The Effect of Combined Therapy of Exercise and Nootropic Agent on Cognitive Function in Focal Cerebral Infarction Rat Model  

PubMed Central

Objective To investigate the effect of combined therapy of exercise and nootropic agent on cognitive function in a focal cerebral infarction rat model. Method Forty 10-week old male Sprague-Dawley rats were subjected to photothrombotic cerebral infarction of the left parietal lobe. All rats were randomly divided into 4 groups: group A was photothrombotic cerebral infarction rats without any treatment (n=10); group B was photothrombotic cerebral infarction rats with swimming exercise (n=10); group C was photothrombotic cerebral infarction rats with oral administration of acetyl-L-carnitine (n=10); group D was photothrombotic cerebral infarction rats with swimming exercise and oral administration of acetyl-L-carnitine (n=10). Cognitive function was evaluated using the Morris water maze test on the 1st day, and the 1st, 2nd, and 4th week after the induction of cerebral infarction. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in the hippocampus were measured. The neuronal cells of the hippocampus were histopathologically evaluated. Results The escape latency was shorter in groups B, C, and D than in group A. However, the differences were not statistically significant at the 1st, 2nd and 4th week. The activity of SOD was the highest in group D. The level of MDA was the lowest in group D. We observed more normal neuronal cells in groups B, C, and D. Conclusion The combined therapy of exercise and nootropic agent was helpful in ameliorating oxidative stress in the focal cerebral infarction rat model. However, the effect did not translate into improvement of cognitive function.

Song, Min-Keun; Seon, Hyo-Jeong; Kim, In-Gyu; Han, Jae-Young; Choi, In-Sung

2012-01-01

103

Brain-skull boundary conditions in a computational deformation model  

Microsoft Academic Search

Brain shift poses a significant challenge to accurate image-guided neurosurgery. To this end, finite element (FE) brain models have been developed to estimate brain motion during these procedures. The significance of the brain-skull boundary conditions (BCs) for accurate predictions in these models has been explored in dynamic impact and inertial rotation injury computational simulations where the results have shown that

Songbai Ji; Fenghong Liu; David Roberts; Alex Hartov; Keith Paulsen

2007-01-01

104

Virtual Electrophysiologic Study in a Three-dimensional Cardiac MRI Model of Porcine Myocardial Infarction  

PubMed Central

Objective This study sought to test the hypothesis that “virtual” electrophysiologic studies (EPS) on an anatomic platform generated by 3D MRI reconstruction of the left ventricle (LV) can reproduce the reentrant circuits of induced ventricular tachycardia (VT) in a porcine model of myocardial infarction (MI). Background Delayed-enhancement MRI has been used to characterize MI and “gray zones”, which are thought to reflect heterogeneous regions of viable and non-viable myocytes. Methods MI by coronary artery occlusion was induced in eight pigs. After a recovery period, 3D cardiac MRIs were obtained from each pig in-vivo. Normal areas, gray zones, and infarct cores were classified based on voxel intensity. In the computer model, gray zones were assigned slower conduction and longer action potential durations than those for normal myocardium. Virtual EPS was performed and was compared to results of actual in vivo programmed stimulation and non-contact mapping. Results The LV volumes ranged from 97.8 to 166.2 cm3 with 4.9 to 17.5% of voxels classified as infarct zones. Six of the seven pigs that developed VT during actual EPS were also inducible with virtual EPS. Four of the six pigs that had simulated VT had reentrant circuits that approximated the circuits seen with non-contact mapping, while the remaining two had similar circuits but propagating in opposite directions. Conclusions This initial study demonstrates the feasibility of applying a mathematical model to MRI reconstructions of the LV to predict VT circuits. Virtual EPS may be helpful to plan catheter ablation strategies or to identify patients who are at risk for future episodes of VT.

Ng, Jason; Jacobson, Jason T; Ng, Justin K; Gordon, David; Lee, Daniel C; Carr, James C.; Goldberger, Jeffrey J

2012-01-01

105

Brain drain, remittances, and fertility model  

Microsoft Academic Search

How do high and low skilled migration affect fertility and human capital in migrants’ origin countries? This question is analyzed within an overlapping generations model where parents choose the number of high and low skilled children they would like to have. Individuals migrate with a certain probability and remit to their parents. It is shown that a brain drain induces

Luca Marchiori; Patrice Pieretti; Benteng Zou

2008-01-01

106

Traumatic brain injury: from model to man  

Microsoft Academic Search

Brain injury is the leading cause of death in trauma patients and produces a large amount of disability. Unfortunately, it is particularly prevalent in young adults, with all the suffering and socio-economic loss this implies. It has a complex neurobiology that has been elucidated largely in animal models, but it has been more difficult to apply the knowledge gained to

R. G. M. Jackson; K. M. Sales; D. P. McLaughlin; J. A. Stamford

2002-01-01

107

A Layered Reference Model of the Brain  

Microsoft Academic Search

Abstract– A variety of life functions and cognitive processes have been identified in cognitive informatics, psychology, cognitive science, and neurophilosophy. This paper attempts to develop a Layered Reference Model of the ,Brain ,(LRMB) that ,formally and rigorously explains ,the functional mechanisms and cognitive processes of the ,natural intelligence. A comprehensive and coherent set of mental processes and their relationships is

Yingxu Wang; Shushma Patel; Dilip Patel; Ying Wang

2003-01-01

108

Injectable hydrogel properties influence infarct expansion and extent of postinfarction left ventricular remodeling in an ovine model  

PubMed Central

A recent trend has emerged that involves myocardial injection of biomaterials, containing cells or acellular, following myocardial infarction (MI) to influence the remodeling response through both biological and mechanical effects. Despite the number of different materials injected in these approaches, there has been little investigation into the importance of material properties on therapeutic outcomes. This work focuses on the investigation of injectable hyaluronic acid (MeHA) hydrogels that have tunable mechanics and gelation behavior. Specifically, two MeHA formulations that exhibit similar degradation and tissue distribution upon injection but have differential moduli (~8 versus ~43 kPa) were injected into a clinically relevant ovine MI model to evaluate the associated salutary effect of intramyocardial hydrogel injection on the remodeling response based on hydrogel mechanics. Treatment with both hydrogels significantly increased the wall thickness in the apex and basilar infarct regions compared with the control infarct. However, only the higher-modulus (MeHA High) treatment group had a statistically smaller infarct area compared with the control infarct group. Moreover, reductions in normalized end-diastolic and end-systolic volumes were observed for the MeHA High group. This group also tended to have better functional outcomes (cardiac output and ejection fraction) than the low-modulus (MeHA Low) and control infarct groups. This study provides fundamental information that can be used in the rational design of therapeutic materials for treatment of MI.

Ifkovits, Jamie L.; Tous, Elena; Minakawa, Masahito; Morita, Masato; Robb, J. Daniel; Koomalsingh, Kevin J.; Gorman, Joseph H.; Gorman, Robert C.; Burdick, Jason A.

2010-01-01

109

Studies of isolated global brain ischaemia: I. A new large animal model of global brain ischaemia and its baseline perfusion studies  

PubMed Central

OBJECTIVES Neurological injury after global brain ischaemia (i.e. sudden death) remains problematic, despite improving cardiac survival. Unfortunately, sudden death models introduce unwanted variables for studying the brain because of multiple organ injury. To circumvent this, a new minimally invasive large animal model of isolated global brain ischaemia, together with baseline perfusion studies is described. METHODS The model employs neck and small (3–4 inches) supra-sternal incisions to block inflow from carotid and vertebral arteries for 30 min of normothermic ischaemia. Neurological changes after 24 h in six pigs was compared with six Sham pigs assessing neurological deficit score (NDS, 0 = normal, 500 = brain death), brain oedema and cerebral infarction by 2,3,5-triphenyltetrazolium chloride (TTC) stain. Six other pigs had baseline perfusion characteristics in this new model evaluated at carotid flows of 750, 550 and 450 cc/min, with cerebral perfusion pressure, cerebral oximeter saturation [IN Vivo Optical Spectroscopy (INVOS)] and transcranial O2 uptake measurements. RESULTS The model never altered cardiac or pulmonary function, and six Sham pigs had normal (NDS = 0) neurological recovery without brain injury. Conversely, 24 h analysis showed that 30 min of global normothermic brain ischaemia caused multiple post-reperfusion seizures (P < 0.001 versus Sham), raised NDS (231 ± 16; P < 0.001 versus Sham) in four of six survivors and caused marked post-brain oedema (P < 0.001 versus Sham) and extensive cerebral infarctions (TTC stain; P < 0.001 versus Sham). Baseline perfusion showed 750 cc/min flow rate produced normal INVOS levels and O2 consumption at mean 90–100 mmHg carotid pressure. Carotid pressure and INVOS fell at mid- and low-flow rates. Although INVOS did not change, 450 cc/min flow lowered global O2 consumption, which further decreased after transient ischaemia (30 s) and 5 min of reperfusion. CONCLUSIONS This new isolated global brain model consistently caused anatomic, biochemical and functional neurological damage in pigs after 30 min of ischaemia. Flows of 750 cc/min maintained normal mean systemic arterial (90–100 mmHg) pressure, INVOS levels and O2 consumption. Cerebral pressure and INVOS fell in mid- and low-flow studies. A disparity existed between INVOS oxygen saturation and global O2 consumption at lower flow rates of 450 cc/min following transient ischaemia, indicating that surface oxygen saturation measurement does not reflect global brain O2 consumption.

Allen, Bradley S.; Ko, Yoshihiro; Buckberg, Gerald D.; Sakhai, Sean; Tan, Zhong

2012-01-01

110

Investigation of T2-weighted signal intensity of infarcted myocardium and its correlation with delayed enhancement magnetic resonance imaging in a porcine model with reperfused acute myocardial infarction  

Microsoft Academic Search

To assess the signal pattern in T2-weighted images (T2WI) and determine its relation to persistent microvascular obstruction\\u000a (PMO) and intramyocardial hemorrhage in a porcine model with reperfused acute myocardial infarction. Left anterior descending\\u000a artery was occluded (90 or 180 min) and reperfused (90 min). T2WI and delayed-enhanced magnetic resonance images (DE-MRI)\\u000a were acquired. The T2WI signal pattern, T2WI contrast ratio, PMO, and

Seong Hoon Choi; Joon-Won Kang; Sang-Tae Kim; Byung Han Lee; Eun Ju Chun; Karl H. Schuleri; Sang Il Choi; Tae-Hwan Lim

2009-01-01

111

HIF-1alpha inhibition ameliorates neonatal brain injury in a rat pup hypoxic-ischemic model.  

PubMed

Hypoxia-inducible factor-1alpha (HIF-1alpha) has been considered as a regulator of both prosurvival and prodeath pathways in the nervous system. The present study was designed to elucidate the role of HIF-1alpha in neonatal hypoxic-ischemic (HI) brain injury. Rice-Vannucci model of neonatal hypoxic-ischemic brain injury was used in seven-day-old rats, by subjecting unilateral carotid artery ligation followed by 2 h of hypoxia (8% O2 at 37 degrees C). HIF-1alpha activity was inhibited by 2-methoxyestradiol (2ME2) and enhanced by dimethyloxalylglycine (DMOG). Results showed that 2ME2 exhibited dose-dependent neuroprotection by decreasing infarct volume and reducing brain edema at 48 h post HI. The neuroprotection was lost when 2ME2 was administered 3 h post HI. HIF-1alpha upregulation by DMOG increased the permeability of the BBB and brain edema compared with HI group. 2ME2 attenuated the increase in HIF-1alpha and VEGF 24 h after HI. 2ME2 also had a long-term effect of protecting against the loss of brain tissue. The study showed that the early inhibition of HIF-1alpha acutely after injury provided neuroprotection after neonatal hypoxia-ischemia which was associated with preservation of BBB integrity, attenuation of brain edema, and neuronal death. PMID:18602008

Chen, Wanqiu; Jadhav, Vikram; Tang, Jiping; Zhang, John H

2008-06-14

112

Characterization of an original model of myocardial infarction provoked by coronary artery thrombosis induced by ferric chloride in pig  

Microsoft Academic Search

BackgroundGreat advances have been made in the prevention of thrombotic disorders by developments of new pharmacological and surgical treatments. Animal models of arterial thrombosis have largely contributed to the discovery and to the validation of original treatments. The purpose of the present work was to develop and validate an original model of acute myocardial infarction provoked in pig by thrombosis

Jean-Michel Dogné; Stéphanie Rolin; Michel Pétein; Vincent Tchana-Sato; Alexandre Ghuysen; Bernard Lambermont; Julien Hanson; David Magis; Patrick Segers; Bernard Pirotte; Bernard Masereel; Pierre Drion; Vincent D'Orio; Philippe Kolh

2005-01-01

113

Modeling brain dynamics using computational neurogenetic approach.  

PubMed

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

Benuskova, Lubica; Kasabov, Nikola

2008-09-16

114

Dynamic geometry, brain function modeling, and consciousness.  

PubMed

Pellionisz and Llinás proposed, years ago, a geometric interpretation towards understanding brain function. This interpretation assumes that the relation between the brain and the external world is determined by the ability of the central nervous system (CNS) to construct an internal model of the external world using an interactive geometrical relationship between sensory and motor expression. This approach opened new vistas not only in brain research but also in understanding the foundations of geometry itself. The approach named tensor network theory is sufficiently rich to allow specific computational modeling and addressed the issue of prediction, based on Taylor series expansion properties of the system, at the neuronal level, as a basic property of brain function. It was actually proposed that the evolutionary realm is the backbone for the development of an internal functional space that, while being purely representational, can interact successfully with the totally different world of the so-called "external reality". Now if the internal space or functional space is endowed with stochastic metric tensor properties, then there will be a dynamic correspondence between events in the external world and their specification in the internal space. We shall call this dynamic geometry since the minimal time resolution of the brain (10-15 ms), associated with 40 Hz oscillations of neurons and their network dynamics, is considered to be responsible for recognizing external events and generating the concept of simultaneity. The stochastic metric tensor in dynamic geometry can be written as five-dimensional space-time where the fifth dimension is a probability space as well as a metric space. This extra dimension is considered an imbedded degree of freedom. It is worth noticing that the above-mentioned 40 Hz oscillation is present both in awake and dream states where the central difference is the inability of phase resetting in the latter. This framework of dynamic geometry makes it possible to distinguish one individual from another. In this paper we shall investigate the role of dynamic geometry in brain function modeling and the neuronal basis of consciousness. PMID:18166391

Roy, Sisir; Llinás, Rodolfo

2008-01-01

115

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

PubMed Central

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

2011-01-01

116

Admittance-based pressure-volume loop measurements in a porcine model of chronic myocardial infarction.  

PubMed

The aim of this study was to validate admittance-based pressure-volume (PV) loop measurements for the assessment of cardiac function in a porcine model of chronic myocardial infarction. The traditional PV loop measurement technique requires hypertonic saline injections for parallel conductance correction prior to signal conversion into volume. Furthermore, it assumes a linear relationship between conductance and volume. More recently, an admittance-based technique has been developed, which continuously measures parallel conductance and uses a non-linear equation for volume calculation. This technique has not yet been evaluated in a large-animal model of myocardial ischaemia. Eleven pigs underwent invasive PV measurements with the admittance system (AS) and the traditional conductance system followed by three-dimensional echocardiography (3DE). After baseline measurements, pigs were subjected to 90 min left anterior descending coronary artery occlusion, followed by the same measurements at 8 weeks follow-up. In the healthy heart, the AS showed good agreement with 3DE for left ventricular volumes and a reasonable correlation for ejection fraction (r = 0.756, P = 0.007). At follow-up, an increase in end-systolic volume was observed with 3DE (+15.4 ± 14.4 ml, P = 0.005) and the AS (+34.6 ± 36.1 ml, P = 0.010). The ejection fraction measured with 3DE (-13.2 ± 5.2%, P < 0.001) and the AS (-20.3 ± 11.2%, P < 0.001) significantly decreased. We conclude that the AS can be used for quantitative monitoring of changes in cardiac function induced by myocardial infarction and provides comparable results to 3DE, rendering it a useful tool for functional testing in large-animal cardiac models. PMID:23955306

van Hout, G P J; de Jong, R; Vrijenhoek, J E P; Timmers, L; Duckers, H J; Hoefer, I E

2013-08-16

117

The preventive effect of garlicin on a porcine model of myocardial infarction reperfusion no-reflow.  

PubMed

OBJECTIVE: To evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). METHODS: Twenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA). RESULTS: Left ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group <0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01). CONCLUSTIONS: Garlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA. PMID:22539198

Li, Jia-Hui; Yang, Peng; Li, Ai-Li; Wang, Yong; Shi, Zai-Xiang; Ke, Yuan-Nan; Li, Xian-Lun

2012-04-26

118

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

119

Transepicardial autologous bone marrow-derived mononuclear cell therapy in a porcine model of chronically infarcted myocardium  

Microsoft Academic Search

ObjectiveCell therapy is becoming a viable strategy to improve revascularization and myocardial function after myocardial injury. We evaluated the effect of bone marrow-derived mononuclear cell (BMMNC) transplantation on collateral vessel development and myocardial function in a porcine model of chronically infarcted heart.

Ron Waksman; Jana Fournadjiev; Richard Baffour; Rajbabu Pakala; David Hellinga; Laurent Leborgne; Hamid Yazdi; Edouard Cheneau; Roswitha Wolfram; Rufus Seabron; Kenneth Horton; Frank Kolodgie; Renu Virmani; Elias Rivera

2004-01-01

120

Influence of Embryonic Cardiomyocyte Transplantation on the Progression of Heart Failure in a Rat Model of Extensive Myocardial Infarction  

Microsoft Academic Search

S. Etzion, A. Battler, I. M. Barbash, E. Cagnano, P. Zarin, Y. Granot, L. H. Kedes, R. A. Kloner and J. Leor. Influence of Embryonic Cardiomyocyte Transplantation on the Progression of Heart Failure in a Rat Model of Extensive Myocardial Infarction. Journal of Molecular and Cellular Cardiology (2001) 33, 0000–0000. Cell transplantation has been proposed as a future therapy for

Sharon Etzion; Alexander Battler; Israel M. Barbash; Emanuela Cagnano; Parvin Zarin; Yosef Granot; Laurence H. Kedes; Robert A. Kloner; Jonathan Leor

2001-01-01

121

Rehmannia Glutinosa Extract Activates Endothelial Progenitor Cells in a Rat Model of Myocardial Infarction through a SDF-1 ?/CXCR4 Cascade  

PubMed Central

Objectives Endothelial progenitor cells (EPCs) can be used to repair tissues after myocardial infarction (MI) but EPC activators have adverse reactions. Rehmannia glutinosa is a herb used in traditional Chinese medicine, which can promote bone-marrow proliferation and protect the ischemic myocardium. We investigated the effects of Rehmannia glutinosa extract (RGE) on EPCs in a rat model of MI. Methods A total of 120 male Wistar rats were randomized to 2 groups (n?=?60 each) for treatment: high-dose RGE (1.5 g·kg?1·day?1 orally) for 8 weeks, then left anterior descending coronary artery ligation, mock surgery or no treatment, then RGE orally for 4 weeks; or normal saline (NS) as the above protocol. The infarct region of the left ventricle was assessed by serial sectioning and morphology. EPCs were evaluated by number and function. Protein and mRNA levels of CD133, vascular endothelial growth factor receptor 2 (VEGFR2), chemokine C-X-C motif receptor 4 (CXCR4), stromal cell–derived factor-1? (SDF-1?) were measured by immunohistochemistry, Western blot and quantitative PCR analysis. Results RGE significantly improved left ventricular function, decreased the ischemic area and the apoptotic index in the infarct myocardium, also decreased the concentration of serum cardiac troponin T and brain natriuretic peptide at the chronic stage after MI (from week 2 to week 4). RGE increased EPC number, proliferation, migration and tube-formation capacity. It was able to up-regulate the expression of angiogenesis-associated ligand/receptor, including CD133, VEGFR2 and SDF-1?/CXCR4. In vitro, the effect of RGE on SDF-1?/CXCR4 cascade was reversed by the CXCR4 specific antagonist AMD3100. Conclusion RGE may enhance the mobilization, migration and therapeutic angiogenesis of EPCs after MI by activating the SDF-1?/CXCR4 cascade.

Wang, Ying-Bin; Liu, Yun-Fang; Lu, Xiao-Ting; Yan, Fang-Fang; Wang, Bo; Bai, Wen-Wu; Zhao, Yu-Xia

2013-01-01

122

Zebrafish as an alternative model for hypoxic-ischemic brain damage  

PubMed Central

Acute cerebral ischemia is one of the leading causes of mortality and chronic disability. Animal models provide an essential tool for understanding the complex cellular and molecular pathophysiology of hypoxic-ischemia and for testing novel neuroprotective drugs in the pre-clinical setting. In this study we tested zebrafish as a novel model for hypoxic-ischemic brain damage. We built an air-proof chamber where water inside had a low oxygen concentration (0.6-0.8 mg/L) proximate to complete hypoxia. Each zebrafish was placed individually in the hypoxia chamber and was subjected to hypoxia treatment until it became motionless, lying on its side on the bottom of the chamber (time to hypoxia = 679.52 ± 90 seconds, mean ± SD, n =23), followed by transferring into a recovery beaker. Overall, 60.87% of subjects did not recover from hypoxia while 39% survived. The size and distribution of brain injury were determined by triphenyltetrazolium chloride (TTC) staining. Bilateral, moderate to complete TTC decoloration or demarcation of the infarct after 10 minutes of hypoxic treatment was clearly visible in the optic tectum of the optic lobe. The size of the infarct expanded to the deep structure of the optic lobe with longer hypoxic treatments. The zebrafish that survived hypoxia experienced initial twitching followed by unbalanced erratic movements until they regained coordinated, balanced swimming ability. These data indicate that zebrafish are susceptible to hypoxic attack and suggest that the model we present in this study can be used as an alternative model to evaluate hypoxia-induced brain damage.

Yu, Xinge; Li, Yang V

2011-01-01

123

Use of Serum Markers to Measure Acute Myocardial Infarct Size: Lessons of a Nonlinear Dynamical Model  

Microsoft Academic Search

During acute myocardial infarction, dying cells in the myocardium release a number of chemicals that appear in the blood stream. By sampling the blood and assaying for these markers at intervals after infarction, we obtain a measure of the amount of myocardium lost, and the area under the marker concentration curve with time has been used to estimate the size

Robin T. Vollmer

1997-01-01

124

Animal models of traumatic brain injury.  

PubMed

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

Xiong, Ye; Mahmood, Asim; Chopp, Michael

2013-02-01

125

Prophylactic amiodarone and lidocaine improve survival in an ovine model of large size myocardial infarction.  

PubMed

BACKGROUND: Large animal models serve as a critical link in the translation of basic science to clinical practice. However, large animal models of myocardial infarction (MI), especially large size MI, have been associated with high mortality because of arrhythmia. The prophylactic effect of amiodarone and lidocaine were retrospectively reviewed in our ovine MI model. MATERIALS AND METHODS: A total of 114 Dorset hybrid sheep with 25%-30% MI were included in the present study. The sheep were prophylactically treated with amiodarone plus lidocaine before ligation of the four to six coronary artery branches supplying the apex of the heart (arrhythmia prevention [AP] group, n = 45) and with epinephrine (shock prevention [SP] group, n = 49), respectively. The sheep without prophylactic treatment (no prevention [NP] group, n = 20) were used as the control group. The incidence of arrhythmia requiring treatment, mortality due to arrhythmia, hemodynamics, and arterial blood gas values during surgery were analyzed in these three groups. RESULTS: No significant difference was found in infarct size among the three groups. The incidence of arrhythmia requiring treatment was significantly decreased in the AP group compared with that in the NP or SP groups (4.4% for AP versus 35% for NP and 45% for SP groups; P < 0.05). The mortality due to lethal arrhythmia was 2.2% in the AP group, significantly lower than that in the NP group (15%) or SP group (18.4%). Other than the heart rate, no significant differences were found in the hemodynamic data between the AP and NP groups. Metabolic acidosis was not observed in any group, as indicated by the pH and lactate values. CONCLUSIONS: Prophylactic amiodarone plus lidocaine decreased the mortality due to lethal arrhythmia after acute MI in our sheep model without significant negative effects on the hemodynamics. However, epinephrine improved the hemodynamics but also increased the mortality due to lethal arrhythmia. Thus, prophylactic amiodarone plus lidocaine is recommended to improve the stability in a large MI animal model. PMID:23773712

Li, Tieluo; Wei, Xufeng; Watkins, A Claire; Sanchez, Pablo G; Wu, Zhongjun J; Griffith, Bartley P

2013-06-01

126

Experimental models of repetitive brain injuries.  

PubMed

Repetitive traumatic brain injury (TBI) occurs in a significant portion of trauma patients, especially in specific populations, such as child abuse victims or athletes involved in contact sports (e.g. boxing, football, hockey, and soccer). A continually emerging hypothesis is that repeated mild injuries may cause cumulative damage to the brain, resulting in long-term cognitive dysfunction. The growing attention to this hypothesis is reflected in several recent experimental studies of repeated mild TBI in vivo. These reports generally demonstrate cellular and cognitive dysfunction after repetitive injury using rodent TBI models. In some cases, data suggests that the effects of a second mild TBI may be synergistic, rather than additive. In addition, some studies have found increases in cellular markers associated with Alzheimer's disease after repeated mild injuries, which demonstrates a direct experimental link between repetitive TBI and neurodegenerative disease. To complement the findings from humans and in vivo experimentation, my laboratory group has investigated the effects of repeated trauma in cultured brain cells using a model of stretch-induced mechanical injury in vitro. In these studies, hippocampal cells exhibited cumulative damage when mild stretch injuries were repeated at either 1-h or 24-h intervals. Interestingly, the extent of damage to the cells was dependent on the time between repeated injuries. Also, a very low level of stretch, which produced no cell damage on its own, induced cell damage when it was repeated several times at a short interval (every 2 min). Although direct comparisons to the clinical situation are difficult, these types of repetitive, low-level, mechanical stresses may be similar to the insults received by certain athletes, such as boxers, or hockey and soccer players. This type of in vitro model could provide a reliable system in which to study the mechanisms underlying cellular dysfunction following repeated injuries. As this area of TBI research continues to evolve, it will be imperative that models of repetitive injury replicate injuries in humans as closely as possible. For example, it will be important to model appropriately concussive episodes versus even lower level injuries (such as those that might occur during boxing matches). Suitable inter-injury intervals will also be important parameters to incorporate into models. Additionally, it will be crucial to design and utilize proper controls, which can be more challenging than experimental approaches to single mild TBI. It will also be essential to combine, and compare, data derived from in vitro experiments with those conducted with animals in vivo. These issues, as well as a summary of findings from repeated TBI research, are discussed in this review. PMID:17618983

Weber, John T

2007-01-01

127

A risk model derived from the National Registry of Myocardial Infarction 2 database for predicting mortality after coronary artery bypass grafting during acute myocardial infarction  

Microsoft Academic Search

The mortality risk associated with coronary artery bypass grafting (CABG) after acute myocardial infarction (AMI) remains controversial. Although elective CABG is quite safe, the effects of recent myocardial infarction, gender, and other clinical factors on perioperative mortality rates are not completely understood. The objective of this study was to determine in-hospital mortality rates for patients with AMI receiving CABG and

Jonathan G Zaroff; Dante G diTommaso; Hal V Barron

2002-01-01

128

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

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; Kekulé, Alexander; Paulsen, Friedrich; Maronde, Erik; Bräuer, Lars

2013-09-30

129

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.

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

2013-01-01

130

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction  

PubMed Central

Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action.

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-01-01

131

Functional assessment of adipose stem cells for xenotransplantation using myocardial infarction immunocompetent models: comparison with bone marrow stem cells.  

PubMed

Recently, preclinical studies have shown that allogeneic adipose-derived stem cells (ASCs), like bone marrow-derived mesenchymal stem cell (BMSCs) have significant clinical benefits in treating cardiovascular diseases, such as ischemic/infarcted heart. In this study, we tested whether ASCs are also immune tolerant, such that they can be used as universal donor cells for myocardial regenerative therapy. The study also focuses on investigating the potential therapeutic effects of human ASCs (hASCs) for myocardial infarction in xenotransplant model, and compares its effects with that of hBMSCs. The in vitro study confirms the superior proliferation potential and viability of hASCs under normoxic and stressed hypoxic conditions compared with hBMSCs. hASCs also show higher potential in adopting cardiomyocyte phenotype. The major findings of the in vivo study are that (1) both hASCs and hBMSCs implanted into immunocompetent rat hearts with acute myocardial infarction survived the extreme environment of xenogeneic mismatch for 6 weeks; (2) both hASCs and hBMSCs showed significant improvement in myocardial pro/anti-inflammatory cytokine levels with no detectable inflammatory reaction, despite the lack of any immunosuppressive therapy; and (3) hASCs contributed to the remarkable improvement in cardiac function and reduced infarction which was significantly better than that of hBMSC and untreated control groups. Thus, our findings suggest the feasibility of using ASCs, instead of BMSCs, as universal donor cells for xenogeneic or allogeneic cell therapy. PMID:22205499

Paul, Arghya; Srivastava, Sapna; Chen, Guangyong; Shum-Tim, Dominique; Prakash, Satya

2013-11-01

132

An Improved Transplantation Strategy for Mouse Mesenchymal Stem Cells in an Acute Myocardial Infarction Model  

PubMed Central

To develop an effective therapeutic strategy for cardiac regeneration using bone marrow mesenchymal stem cells (BM-MSCs), the primary mouse BM-MSCs (1st BM-MSCs) and 5th passage BM-MSCs from ?-galactosidase transgenic mice were respectively intramyocardially transplanted into the acute myocardial infarction (AMI) model of wild type mice. At the 6th week, animals/tissues from the 1st BM-MSCs group, the 5th passage BM-MSCs group, control group were examined. Our results revealed that, compared to the 5th passage BM-MSCs, the 1st BM-MSCs had better therapeutic effects in the mouse MI model. The 1st BM-MSCs maintained greater differentiation potentials towards cardiomocytes or vascular endothelial cells in vitro. This is indicated by higher expressions of cardiomyocyte and vascular endothelial cell mature markers in vitro. Furthermore, we identified that 24 proteins were down-regulated and 3 proteins were up-regulated in the 5th BM-MSCs in comparison to the 1st BM-MSCs, using mass spectrometry following two-dimensional electrophoresis. Our data suggest that transplantation of the 1st BM-MSCs may be an effective therapeutic strategy for cardiac tissue regeneration following AMI, and altered protein expression profiles between the 1st BM-MSCs and 5th passage BM-MSCs may account for the difference in their maintenance of stemness and their therapeutic effects following AMI.

Jin, Jianliang; Zhao, Yingming; Tan, Xiao; Guo, Chun; Yang, Zhijian; Miao, Dengshun

2011-01-01

133

Endothelin-1-induced reduction of myocardial infarct size by activation of ATP-sensitive potassium channels in a rabbit model of myocardial ischaemia and reperfusion.  

PubMed Central

1. This study examined whether endothelin-1 (ET-1) reduces infarct size in a rabbit model of acute coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effect of ET-1 was due to the activation of ATP-sensitive potassium (KATP) channels by using two selective antagonists, glibenclamide and sodium 5-hydroxydecanoate (5-HD). 2. In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2 h of reperfusion was 55 +/- 4% (n = 11). ET-1 (0.3 nmol kg-1), administered as a bolus injection into the left ventricle, had no effect on infarct size (62 +/- 2%, n = 4). A lower dose of ET-1 (0.03 nmol kg-1) resulted in a significant reduction in infarct size (infarct size 43 +/- 3%; P < 0.05, n = 16). The higher dose (0.3 nmol kg-1), but not the lower dose of ET-1 caused a significant rise in blood pressure, pressure rate index and hence, myocardial oxygen consumption. 3. The reduction in infarct size afforded by ET-1 (0.03 nmol kg-1) was abolished by pretreatment of rabbits with the KATP channel inhibitors, glibenclamide (0.3 mg kg-1) and 5-HD (5 mg kg-1), (infarct size 59 +/- 3 and 63 +/- 4% respectively; n = 4-9). 4. We propose that ET-1 reduces infarct size by opening KATP channels.

Hide, E. J.; Piper, J.; Thiemermann, C.

1995-01-01

134

Modeling brain resonance phenomena using a neural mass model.  

PubMed

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

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

2011-12-22

135

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

PubMed Central

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.

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

2011-01-01

136

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

2011-04-06

137

Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model  

PubMed Central

Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.

2010-01-01

138

Virtual reality in brain intervention: models and applications.  

PubMed

Human body models are key components of VR surgical simulators. We overview here our efforts and share experience in constructing cerebral models and using them in VR-based applications for brain intervention. We have constructed four groups of brain atlases: anatomical, functional, vascular, and physically-based. The atlas-assisted VR systems discussed here are applied to stereotactic and functional neurosurgery, interventional neuroradiology, and brain stereotaxy. We also briefly feature our concept of future surgery. PMID:17281151

Nowinski, Wieslaw

2005-01-01

139

Transmural Peak Systolic Strain and Strain Rate Predict Transmural Myocardial Blood Flow in a Pig Myocardial Infarction Model  

Microsoft Academic Search

Objective: To test the hypothesis that the transmural variation of the longitudinal myocardial peak systolic strain (Sp) and strain rate (SRp) can predict the transmural distribution of myocardial blood flow (MBF) in a pig model of acute myocardial infarction. Methods: The longitudinal Sp and SRp were measured by echocardiography in both subendocardium (Sp-endo, SRp-endo) and subepicardium (Sp-epi, SRp-epi) in the

Huixia Lu; Guihua Yao; Huili Lin; Xinsheng Xu; Changjiang Li; Xiaolu Li; Huiwen Sun; Lihang Qi; Chengmei Zhang; Fenglei Zhang; Mengxiong Tang; Mei Zhang; Yun Zhang

2009-01-01

140

The effects of simvastatin on angiogenesis: studied by an original model of atherosclerosis and acute myocardial infarction in rabbit  

Microsoft Academic Search

Statins have shown pleiotropic effects, many of them independent of their impact on lipids. Angiogenesis can be beneficial\\u000a in the acute myocardial infarction to improve circulation. However, it also can be harmful due to worsening of atherosclerosis.\\u000a Here, we established a new minimal invasive rabbit model to study ischemic myocardium and atherosclerosis together to mimic\\u000a clinical scenario. We demonstrated that

Wei Shen; Hai-Ming Shi; Wei-Hu Fan; Xin-Ping Luo; Bo Jin; Yong Li

2011-01-01

141

[Influence of ademol on NO metabolism indices in rats with modeling myocardial infarction].  

PubMed

It was established in experiments on the rats in the acute period of modeling pituitrin-isadrin myocardial infarction the formation of nitrogen monoxide decreases along with its accelerated transformation into peroxynitrite. It was evidenced by more than double inhibition of NO synthase activity in the myocardium and by decreasing the amount of nitrates on the background of the increasing level of peroxynitrites' marker--nitrotyrosine by 246.6% at an average. Experimental therapy of rats by ademol which is a derivate of adamantan (1-adamantiloxy-3-morpholino-2 propanol hydrochloride) better than by corvitin normalizes the processes of synthesis of nitric oxide. At the same time ademol probably exceeded the reference drug in ability to increase NO synthase activity and amount of nitrate, and promoted a decrease of the level of nitrotyrosine in the myocardium on the average by 36.3; 50.6 and 12.7%, respectively. Corrective influence of ademol on indicators of metabolism in NO system under the conditions of acute cardiac ischemia indicates to promicing development of domestic cardioprotector on its base. PMID:23937052

Khodakivs'ky?, O A; Pavlov, S V; Bukhtiiarova, N V

142

Integrative Pathway-Centric Modeling of Ventricular Dysfunction after Myocardial Infarction  

PubMed Central

Background A significant proportion of myocardial infarction (MI) patients undergo complex, coordinated perturbations at the molecular level that may eventually drive the occurrence of ventricular dysfunction and heart failure. Despite advances in the elucidation of key processes implicated in this condition, traditional methods relying on gene expression data and the identification of individual biomarkers in isolation pose major limitations not only for improving prediction power, but also for model interpretability. Mechanisms underlying clinical responses after MI remain elusive and there is no biomarker with the capacity to accurately predict ventricular dysfunction after MI. This calls for the exploration of system-level modeling of ventricular dysfunction in post-MI patients. Within this discovery framework key perturbations and predictive patterns are characterized by the integrated biological activity levels observed in pathways, rather than in individual genes. Methodology/Principal Findings Here we report an integrative approach to identifying pathways related with ventricular dysfunction post MI with potential prognostic and therapeutic value. We found that a diversity of pathway-level perturbations can be profiled in samples of patients with ventricular dysfunction post MI, most of which represent major reductions of gene expression. Highly perturbed pathways included those implicated in antigen-dependent B-cell activation and the synthesis of leucine. By analyzing patient-specific samples encoded with information derived from highly-perturbed pathways, it is possible to visualize differential prognostic patterns and to perform computational classification of patients with areas under the receiver operating characteristic curve above 0.75. We also demonstrate how the integration of the outcomes generated by different pathway-based analysis models may improve ventricular dysfunction prediction performance. Significance This research offers an alternative, comprehensive view of key relationships and perturbations that may trigger the emergence or prevention of ventricular dysfunction post-MI.

Azuaje, Francisco; Devaux, Yvan; Wagner, Daniel R.

2010-01-01

143

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

NSDL National Science Digital Library

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

Jr., Archibald J.; Johnson, John I.; Pecore, John; Rose, Jordan D.; Carruth, Laura L.; Demetrikopoulos, Melissa K.

2006-07-01

144

Hyperglycemia Increases Infarct Size in Collaterally Perfused but not End-Arterial Vascular Territories  

Microsoft Academic Search

Summary: Hyperglycemia exacerbates neuronal injury in the setting of reversible brain ischemia, but its effect on focal thrombotic infarction has been less extensively characterized. We investigated this problem in two rat models of focal vascular occlusion. In Model I, the right middle cerebral artery (MCA) was exposed via a subtemporal craniotomy in halothane- and nitrous oxide-anesthetized Wistar rats and was

Ricardo Prado; Myron D. Ginsberg; W. Dalton Dietrich; Brant D. Watson; Raul Busto

1988-01-01

145

The Modeling and Functional Connectivity of the Brain  

NASA Astrophysics Data System (ADS)

The brain is considered to be the most complex system, a fertile ground for understanding the complexity of its functions through dynamical modeling. In this talk, we present some biophysical models that help to reveal the complexity of visual functions of the brain through functional self-organization processes. We also present some recent results on how the functional connectivity arises and changes in the brain, reflecting the underlying dynamics of nervous systems. The implications of our work to the brain function are discussed. Note from Publisher: This article contains the abstract only.

Kim, Seunghwan

2008-12-01

146

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

147

Multidetector-row computed tomographic evaluation of myocardial perfusion in reperfused chronic myocardial infarction: value of color-coded perfusion map in a porcine model  

Microsoft Academic Search

We aimed to develop color-coded CT perfusion maps (CPM) of infarcted myocardium and assess the utility of CPM in evaluating\\u000a ischemic heart disease on a cardiac multi-detector CT (MDCT) in a porcine reperfused-myocardial-infarction model. Myocardial\\u000a infarctions were induced by 30 min occlusions of the proximal left anterior descending coronary artery (LAD) in 17 healthy\\u000a adult female pigs. First-pass and 5 min-delayed cardiac

Nam Yeol Yim; Yun-Hyeon Kim; Song Choi; Hyun Ju Seon; Yeong Cheol Kim; Gwang Woo Jeong; Byeong In Min; Sang Rok Lee; Myeong Ho Jeong; Jae Kyu Kim; Jin Gyoon Park; Heoung Keun Kang

2009-01-01

148

Admission N-terminal pro-brain natriuretic peptide and its interaction with admission troponin T and ST segment resolution for early risk stratification in ST elevation myocardial infarction  

Microsoft Academic Search

Objective: To assess the long term prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission and its prognostic interaction with both admission troponin T (TnT) concentrations and resolution of ST segment elevation in fibrinolytic treated ST elevation myocardial infarction (STEMI).Design and setting: Substudy of the ASSENT (assessment of the safety and efficacy of a new thrombolytic) -2 and ASSENT-PLUS

E Bjo?rklund; T Jernberg; P Johanson; P Venge; M Dellborg; L Wallentin; B Lindahl

2006-01-01

149

Swine experimental model to evaluate stem cells implant post myocardial infarction by perfusion gated-SPET.  

PubMed

Autologous bone marrow stromal cells (BMSC) implant after swine experimental myocardial infarct (MI) was investigated by serial technetium-99m ((99m)Tc)-tetrofosmin gated single photon emission tomography (G-SPET) and compared with immuno-histochemical findings. The aim was to evaluate if intramyocardial BMSC implant produces any prolonged effect in the left ventricle (LV) perfusion and function. Eleven pigs underwent left anterior descending artery (LAD) ligature; in seven of them BMSC were injected in the border zone of the MI, while in the remaining four saline solution was injected at the same site. After LAD ligature G-SPET scans at 48h and at 5 and 10 weeks (w) after the implant were performed. Uptake defect size and LV function analysis were performed comparing 48h to 5w and 10w studies. Statistical evaluation was performed with Friedman test and unpaired Wilcoxon test. The comparison between a progressive reduction of Perfusion Image Score was observed from 48h to 5w and to 10w in the treated group (Friedman test: ?²= 13.56; P=0.01). No variation was observed in the control group (Friedman test: ?²=3; P= 0.223). Comparison of the absolute variation (?) between treated and control group resulted significant (Wilcoxon test W=10; P=0.007). Similar positive results were also observed for the relative extension of the uptake defect, wall motion and LVEF analysis. Histological data of our swine model demonstrated that autologous BMSC implanted in the damaged myocardium area had survived and differentiated into cells with typical features of myocardiocytes. Gated SPET is a reliable tool to evaluate prolonged positive effects of autologous BMSC implant in swine experimental MI model. In conclusion, autologous BMSC implanted can improve perfusion, induce cell regeneration, reduce wall motion abnormalities and prevent severe LV dysfunction in swines. PMID:22413107

Niccoli-Asabella, Artor; Ferlan, Giovanni; Crovace, Antonio; Notaristefano, Antonio; Rubini, Domenico; Altini, Corinna; Pisani, Antonio; Rubini, Giuseppe

150

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

151

ACHTUNG-Rule: a new and improved model for prognostic assessment in myocardial infarction  

PubMed Central

Background: Thrombolysis In Myocardial Infarction (TIMI), Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (PURSUIT) and Global Registry of Acute Coronary Events (GRACE) scores have been developed for risk stratification in myocardial infarction (MI). The latter is the most validated score, yet active research is ongoing for improving prognostication in MI. Aim: Derivation and validation of a new model for intrahospital, post-discharge and combined/total all-cause mortality prediction – ACHTUNG-Rule – and comparison with the GRACE algorithm. Methods: 1091 patients admitted for MI (age 68.4 ± 13.5, 63.2% males, 41.8% acute MI with ST-segment elevation (STEMI)) and followed for 19.7 ± 6.4 months were assigned to a derivation sample. 400 patients admitted at a later date at our institution (age 68.3 ± 13.4, 62.7% males, 38.8% STEMI) and followed for a period of 7.2 ± 4.0 months were assigned to a validation sample. Three versions of the ACHTUNG-Rule were developed for the prediction of intrahospital, post-discharge and combined (intrahospital plus post-discharge) all-cause mortality prediction. All models were evaluated for their predictive performance using the area under the receiver operating characteristic (ROC) curve, calibration through the Hosmer–Lemeshow test and predictive utility within each individual patient through the Brier score. Comparison through ROC curve analysis and measures of risk reclassification – net reclassification improvement index (NRI) or Integrated Discrimination Improvement (IDI) – was performed between the ACHTUNG versions for intrahospital, post-discharge and combined mortality prediction and the equivalent GRACE score versions for intrahospital (GRACE-IH), post-discharge (GRACE-6PD) and post-admission 6-month mortality (GRACE-6). Results: Assessment of calibration and overall performance of the ACHTUNG-Rule demonstrated a good fit (p value for the Hosmer–Lemeshow goodness-of-fit test of 0.258, 0.101 and 0.550 for ACHTUNG-IH, ACHTUNG-T and ACHTUNG-R, respectively) and high discriminatory power in the validation cohort for all the primary endpoints (intrahospital mortality: AUC ACHTUNG-IH 0.886 ± 0.035 vs. AUC GRACE-IH 0.906 ± 0.026; post-discharge mortality: AUC ACHTUNG-R 0.827 ± 0.036 vs. AUC GRACE-6PD 0.811 ± 0.034; combined/total mortality: AUC ACHTUNG-T 0.831 ± 0.028 vs. AUC GRACE-6 0.815 ± 0.033). Furthermore, all versions of the ACHTUNG-Rule accurately reclassified a significant number of patients in different, more appropriate, risk categories (NRI ACHTUNG-IH 17.1%, p (2-sided) = 0.0021; NRI ACHTUNG-R 22.0%, p = 0.0002; NRI ACHTUNG-T 18.6%, p = 0.0012). The prognostic performance of the ACHTUNG-Rule was similar in both derivation and validation samples. Conclusions: All versions of the ACHTUNG-Rule have shown excellent discriminative power and good calibration for predicting intrahospital, post-discharge and combined in-hospital plus post-discharge mortality. The ACHTUNG version for intrahospital mortality prediction was not inferior to its equivalent GRACE model, and ACHTUNG versions for post-discharge and combined/total mortality demonstrated apparent superiority. External validation in wider, independent, preferably multicentre, registries is warranted before its potential clinical implementation.

Providencia, Rui; Paiva, Luis; Caetano, Francisca; Almeida, Ines; Gomes, Pedro; Marques, Antonio Leitao

2012-01-01

152

Experimental models of repetitive brain injuries  

Microsoft Academic Search

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

John T. Weber

2007-01-01

153

MODELING BLAST-RELATED BRAIN INJURY  

Microsoft Academic Search

Recent military conicts in Iraq and Afghanistan have highlighted the wartime eect of traumatic brain in- jury (TBI). While it is not clear why TBI has been so prominent in these particular conicts, one reason may be that improvements in body armor have led to in- creased survivability of blasts. Closed traumatic brain injury covers a spectrum of central nervous

M. Nyein; A. J erusalem; R. Radovitzky; D. Moore; L. Noels

154

Computer model for the Zebra fish brain  

Microsoft Academic Search

We are presenting an interdisciplinary Computer Science project (with the Biology Department at Wagner College). A group of faculty and a group of undergraduate students at Wagner College have been studying the microscopic structures of the Zebra-fish brain to better understand how the human brain is affected by the things we do.

Paul Pedersen; Justin Schneider

2005-01-01

155

Biomechanical Modeling of the Brain for Computer-Assisted Neurosurgery  

Microsoft Academic Search

\\u000a During neurosurgery, the brain significantly deforms. Despite the enormous complexity of the brain (see Chap. 2) many aspects\\u000a of its response can be reasonably described in purely mechanical terms, such as displacements, strains and stresses. They\\u000a can therefore be analyzed using established methods of continuum mechanics. In this chapter, we discuss approaches to biomechanical\\u000a modeling of the brain from the

K. Miller; A. Wittek; G. Joldes

156

Signal transduction and neurosurvival in experimental models of brain injury.  

PubMed

Brain injury and neurodegenerative disease are linked by their primary pathological consequence-death of neurons. Current approaches for the treatment of neurodegeneration are limited. In this review, we discuss animal models of human brain injury and molecular biological data that have been obtained from their analysis. In particular, signal transduction pathways that are associated with neurosurvival following injury to the brain are presented and discussed. PMID:12507684

Butler, T L; Kassed, C A; Pennypacker, K R

2003-01-30

157

Peri-infarct blood-brain barrier dysfunction facilitates induction of spreading depolarization associated with epileptiform discharges.  

PubMed

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

Lapilover, E G; Lippmann, K; Salar, S; Maslarova, A; Dreier, J P; Heinemann, U; Friedman, A

2012-07-07

158

Transmural distribution of myocardial infarction: difference between the right and left ventricles in a canine model  

SciTech Connect

The evolution of myocardial infarction 24 hours after ligating both the right coronary artery and the obtuse marginal branch of the left circumflex coronary artery was examined in 33 anesthetized dogs. Postmortem coronary angiography and a tracer microsphere technique were used to determine risk areas and their collateral blood flows, respectively. The mean weight of the risk areas was 11.3 +/- 0.5 g (mean +/- SEM) in the right ventricle and 10.5 +/- 0.9 g in the left ventricle (NS). The weight of infarcted tissue was 5.7 +/- 0.7 g in the right ventricle and 5.2 +/- 0.9 g in the left ventricle (NS). In both ventricles, infarct weight was linearly related to risk area size, and the percent of risk area necrosis was inversely correlated with the extent of collateral flow at 24 hours of coronary ligation, defined as the mean myocardial blood flow inside the central risk area. Ratios of infarct to risk area between the subendocardial and subepicardial layers were 0.76 +/- 0.06 and 0.28 +/- 0.05 in the right and left ventricles, respectively (p less than 0.01, between ventricles, n = 31), which coincided well with subendocardial-to-subepicardial-flow ratios at 24 hours, ie, 0.86 +/- 0.04 in the right ventricle and 0.32 +/- 0.06 in the left ventricle (p less than 0.01). The regional distribution of myocardial infarction correlated well with flow distribution inside the risk area; the slope of these relations was similar between the subendocardium and subepicardium in the right ventricle, whereas in the left ventricle it was larger in the subendocardium than in the subepicardium. Thus, in the dog, the inherent change in the regional distribution of coronary collateral blood flow is an important modifier in the evolution of myocardial infarction, especially in the left ventricle.

Ohzono, K.; Koyanagi, S.; Urabe, Y.; Harasawa, Y.; Tomoike, H.; Nakamura, M.

1986-07-01

159

Ultrasound Bio-microscopy for Measurement of Coronary Artery Flow and Estimation of Infarct Size in a Mouse Model of Acute Myocardial Infarction.  

PubMed

Ultrasound bio-microscopy was used to measure hemodynamic changes in the left main coronary artery after myocardial infarction (MI), and its usefulness in estimating infarct size was evaluated. MI was induced by left anterior descending artery ligation. Diastolic peak velocity (Vd), mean flow velocity (Vmean) and the velocity-time integral (VTI) were measured 2 and 6 h after MI. Serum troponin I levels were assayed 2, 6 and 12 h after MI. At 2 h, Vmean and VTI significantly differed between mice that underwent low and high left anterior descending artery ligation; Vd, Vmean and VTI were correlated with infarct size (r = -0.557, -0.693 and -0.672, respectively; all p < 0.01). Infarct size was more strongly correlated with 2-h ultrasound bio-microscopy measurements than with 2-h serum troponin I level. Measurement of coronary artery blood flow by ultrasound bio-microscopy may be useful for early estimation of infarct size in mice. PMID:23993171

Su, Rui-Juan; Zhang, Jun-Meng; Li, Rong-Juan; Sun, Yan; Jiang, Bo; Ma, Ning; Li, Zhi-An; Luo, Xiang-Hong; Song, Li; Xue, Jing-Li; Wang, Zheng; Yang, Ya

2013-08-27

160

Measurement of oxygenation at the site of stem cell therapy in a murine model of myocardial infarction.  

PubMed

We have developed a noninvasive EPR (electron paramagnetic resonance) oximetry, based on a new class of oxygen-sensing nano-particulate probe (LiNc-BuO), for simultaneous monitoring of stem-cell therapy and in situ oxygenation (partial pressure of oxygen, pO2) in a mouse model of acute myocardial infarction (AMI). AMI was induced by a permanent occlusion of left-anterior-descending (LAD) coronary artery. Skeletal myoblast (SM) cells were used for therapy. The oximetry probe was implanted in the mid-ventricular region using a needle. Tissue histological studies after 3 weeks of implantation of the probe revealed significant fibrosis, which was solely due to the needle track and not due to the probe particles. The feasibility of long-term monitoring of pO2 was established in control (non-infarct) group of hearts (> 3 months; pO2 = 15.0 +/- 1.2 mmHg,). A mixture of the probe with/without SM cells (1 x 10(5)) was implanted as a single injection in the infarcted region and the myocardial tissue pO2 at the site of cell therapy was measured for 4 weeks. The pO2 was significantly higher in infarcted hearts treated with SM cells (pO2 = 3.5 +/- 0.9 mmHg) compared to untreated hearts (pO2 = 1.6 +/- 0.7 mmHg). We have demonstrated, for the first time, the feasibility of monitoring pO2 in mouse hearts after stem cell therapy. PMID:18290313

Khan, Mahmood; Kutala, Vijay Kumar; Wisel, Sheik; Chacko, Simi M; Kuppusamy, M Lakshmi; Kwiatkowski, Pawel; Kuppusamy, Periannan

2008-01-01

161

The effect of c-fos on acute myocardial infarction and the significance of metoprolol intervention in a rat model.  

PubMed

Over-expression of c-fos may play a role in some diseases. Research pertaining to the expression of c-fos in acute myocardial ?nfarction (AMI) is rare, and the detailed role of c-fos in AMI has not been reported. Therefore, the purpose of this project was to elucidate the detailed effect of c-fos on AMI rats and evaluate the effect of a metoprolol intervention. An AMI rat model was established for the purposes of this study. The expression of c-fos in AMI was evaluated via immunohistochemical analysis and in situ hybridization. Simultaneously, we investigated the effect of c-fos on AMI rats via medicinal treatment with c-fos monoclonal antibody, isoproterenol, and metoprolol. Positive c-Fos protein expression and c-fos mRNA expression in cardiomyocytes were increased at 1, 3, 7, and 10 days after ligation in AMI rats compared with a sham-operated group. Peak expression occurred at 3 days after ligation. The weight percentage fraction of infarct size was decreased in rats treated with c-fos monoclonal antibody compared with the control normal saline treatment group. The weight percentage fraction of infarction size was increased after c-fos was increased via the administration of isoproterenol. c-Fos protein expression and the infarct size in rats treated with metoprolol were also decreased compared with the control normal saline treatment group. The results showed that c-fos expression rapidly increased after coronary ligation; c-fos plays an important role in myocardial lesions and is likely to be involved in the pathogenesis of AMI as well. Metoprolol can inhibit the expression of c-fos and has a positive therapeutic effect on rats after AMI; the involvement effect of metoprolol on myocardial infarction might be correlated with its effect on the inhibition of c-fos. PMID:23054911

Zhang, Song; Zhang, Meiqi; Goldstein, Steven; Li, Yigang; Ge, Junbo; He, Ben; Ruiz, George

2013-03-01

162

Iterative Full Head Finite Element Model for Deep Brain Stimulation  

Microsoft Academic Search

In order to understand the mechanisms involved in deep brain stimulation, several finite element models have been made using reduced part of the head and simplified boundary conditions. In this study, we present a method to obtain the potential created by deep brain stimulation while including the natural boundary conditions on the head surface. The use of an iterative procedure

G. Walckiers; J.-P. Thiran; J. R. Mosig; C. Polio

2007-01-01

163

Modeling Integration and Dissociation in Brain and Cognitive Development  

Microsoft Academic Search

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

Randall C. O'Reilly

164

Bayesian approach for network modeling of brain structural features  

NASA Astrophysics Data System (ADS)

Brain connectivity patterns are useful in understanding brain function and organization. Anatomical brain connectivity is largely determined using the physical synaptic connections between neurons. In contrast statistical brain connectivity in a given brain population refers to the interaction and interdependencies of statistics of multitudes of brain features including cortical area, volume, thickness etc. Traditionally, this dependence has been studied by statistical correlations of cortical features. In this paper, we propose the use of Bayesian network modeling for inferring statistical brain connectivity patterns that relate to causal (directed) as well as non-causal (undirected) relationships between cortical surface areas. We argue that for multivariate cortical data, the Bayesian model provides for a more accurate representation by removing the effect of confounding correlations that get introduced due to canonical dependence between the data. Results are presented for a population of 466 brains, where a SEM (structural equation modeling) approach is used to generate a Bayesian network model, as well as a dependency graph for the joint distribution of cortical areas.

Joshi, Anand A.; Joshi, Shantanu H.; Leahy, Richard M.; Shattuck, David W.; Dinov, Ivo; Toga, Arthur W.

2010-03-01

165

Synergetic brain model for human-like motion patterns recognition  

Microsoft Academic Search

The ability of human brain in making decisions based on the available information stored in the memory and the information provided through cognitive process are the motivations of simulating human intelligence. This paper presents a brain model able to recognize biological behavioral patterns of human locomotion using synergetic approach. Two human-like motion patterns are studied here: slow and fast walking

I. Za'balawi; Loo Chu Kiong; Wong Eng Kiong

2010-01-01

166

Evaluation of Autophagy Using Mouse Models of Brain Injury  

PubMed Central

SUMMARY Autophagy is a homeostatic, carefully regulated, and dynamic process for intracellular recycling of bulk proteins, aging organelles, and lipids. Autophagy occurs in all tissues and cell types, including the brain and neurons. Alteration in the dynamics of autophagy has been observed in many diseases of the central nervous system. Disruption of autophagy for an extended period of time results in accumulation of unwanted proteins and neurodegeneration. However, the role of enhanced autophagy after acute brain injury remains undefined. Established mouse models of brain injury will be valuable in clarifying the role of autophagy after brain injury, and are the topic of discussion in this review.

Au, Alicia K.; Bayir, Hulya; Kochanek, Patrick M.; Clark, Robert S. B.

2009-01-01

167

Incidence, Manifestations, and Predictors of Brain Infarcts Defined by Serial Cranial Magnetic Resonance Imaging in the Elderly: The Cardiovascular Health Study  

Microsoft Academic Search

Background and Purpose—MRI-defined infarcts are common in the elderly. We sought to explore incidence, manifestations, and predictors of such infarcts. Methods—The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of 5888 people aged 65 years. Participants have had extensive baseline and follow-up evaluations; 1433 participants underwent 2 MRI scans separated by 5 years and had no infarcts on initial

W. T. Longstreth; Corinne Dulberg; Teri A. Manolio; Michael R. Lewis; Norman J. Beauchamp; Daniel O'Leary; Jeff Carr; Curt D. Furberg

2002-01-01

168

[The protective effect of mannitol and artificial blood (perfluorochemicals) on hemorrhagic infarction -- experimental study (author's transl)].  

PubMed

It has previously been thought difficult to produce hemorrhagic infarction in animals. Using the thalamic infarction model in the dog, the production of hemorrhagic infarction can be achieved consistently. In this study, the protective effect of mannitol and/or artificial blood (perfluorochemicals) on the hemorrhagic infarction was investigated. Adult mongrel dogs weighing about 10 kg each were used. Following temporal craniotomy, thalamic ischemia was produced by occluding four trunk arteries (the internal carotid, anterior cerebral, middle cerebral and posterior communicating arteries). Dogs which showed EEG changes indicative of thalamic ischemia were used in further experiments. The dogs were divided into 4 groups: (I) non-treated, (II) mannitol-treated, (III) fluorochemical-treated and (IV) mannitol and fluorochemical-treated. All dogs in each group underwent 6 hours of vascular occlusion followed by 1 hour recirculation. In order to evaluate the degree of hemorrhagic infarction, classification into 4 grades was done. Grade O: pale infarction without microscopical bleeding; Grade I: pale infarction wit microscopical bleeding; Grade II: a few sites of macroscopical petecheal bleeding; and Grade III: diffuse macroscopital petecheal bleeding. In the non-treated animals, autopsied brains showed hemorrhagic infarction in all cases. In mannitol-treated animals, some protective effect was found, especially in cases in which mannitol was administered within 60 minutes following occlusion. Hemorrhagic infarction was not suppressed in any of the fluorochemical-treated animals, but there was no hemorrhagic infarction in any of the animals treated with both mannitol and fluorochemicals. The present results are thought to indicate that these drugs administered together are effective in the treatment of hemorrhagic cerebral infarction. PMID:6798484

Kagawa, S; Koshu, K; Yoshimoto, T; Suzuki, J

1981-11-01

169

The grasshopper: a novel model for assessing vertebrate brain uptake.  

PubMed

The aim of the present study was to develop a blood-brain barrier (BBB) permeability model that is applicable in the drug discovery phase. The BBB ensures proper neural function, but it restricts many drugs from entering the brain, and this complicates the development of new drugs against central nervous system diseases. Many in vitro models have been developed to predict BBB permeability, but the permeability characteristics of the human BBB are notoriously complex and hard to predict. Consequently, one single suitable BBB permeability screening model, which is generally applicable in the early drug discovery phase, does not yet exist. A new refined ex vivo insect-based BBB screening model that uses an intact, viable whole brain under controlled in vitro-like exposure conditions is presented. This model uses intact brains from desert locusts, which are placed in a well containing the compound solubilized in an insect buffer. After a limited time, the brain is removed and the compound concentration in the brain is measured by conventional liquid chromatography-mass spectrometry. The data presented here include 25 known drugs, and the data show that the ex vivo insect model can be used to measure the brain uptake over the hemolymph-brain barrier of drugs and that the brain uptake shows linear correlation with in situ perfusion data obtained in vertebrates. Moreover, this study shows that the insect ex vivo model is able to identify P-glycoprotein (Pgp) substrates, and the model allows differentiation between low-permeability compounds and compounds that are Pgp substrates. PMID:23671124

Andersson, Olga; Hansen, Steen Honoré; Hellman, Karin; Olsen, Line Rørbæk; Andersson, Gunnar; Badolo, Lassina; Svenstrup, Niels; Nielsen, Peter Aadal

2013-05-13

170

[Cerebellar infarctions and their mechanisms].  

PubMed

Cerebellar infarcts have been neglected for a long time and are now shown well by CT and especially MRI. Some infarcts involve the full territory supplied by a cerebellar artery. They are frequently complicated by edema with brain stem compression and supratentorial hydrocephalus, requiring at times emergency surgery, and are often accompanied by other medullary, medial pontine, mesencephalic, thalamic and occipital infarcts. On the other hand, partial territory infarcts are usually confined to the cerebellum and have a benign outcome with total recovery or minimal disability. They are more common than full territory infarcts. However, clinical presentations are similar to those full territory infarcts, differing mainly by the lack of drowsiness or unconsciousness. The main symptoms are vertigo, headache, vomiting, unsteadiness of gait and dysarthria. Signs include ipsilateral limb dysmetria, ipsilateral axial lateropulsion, ataxia and dysarthria. Vertigo is more severe and rotary in posterior inferior cerebellar artery territory infarcts, whereas dysarthria and ataxia are prominent in superior cerebellar artery territory infarcts. A few brain stem signs are sometimes added. In these territorial cerebellar infarcts, cardioembolism is the most common cause. Atherosclerotic occlusion comes next, involving the intracranial part of the vertebral artery and, less frequently, the lower basilar artery, both locations inaccessible to surgery. Other causes are artery to artery embolism from a vertebral artery origin stenosis, or the aortic arch, in situ intracranial branch atherosclerotic occlusion, and vertebral artery dissection. Border zone cerebellar infarcts occur in one third of the cases. They are small cortical or deep infarcts. They have the same symptoms and signs as territorial infarcts except for more frequent postural symptoms occurring over days, weeks or months after the ischemic event. The infarcts mainly have a thromboembolic mechanism, and sometimes have a hemodynamic mechanism: 1) focal cerebellar hypoperfusion due to large artery occlusive disease in more than half the cases, 2) small or end (pial) artery disease due to hypercoagulable state (thrombocythemia, polycythemia, hypereosinophilia, disseminated intravascular coagulation), arteritis or intracranial atheroma, and 3) rarely systemic hypotension due to cardiac arrest. PMID:8091085

Amarenco, P

1993-01-01

171

Phosphonate-modified GdDTPA complexes. II. Evaluation in a rat myocardial infarct model.  

PubMed

The localization of 1-hydroxy-3-aminopropane-1,1-diphosphonate-modified GdDTPA (GdDTPA-HPDP) and 4-amino-butane-1,1-diphosphonate-modified GdDTPA (GdDTPA-BDP) in (1) normal and (2) infarcted rat hearts has been measured. The phosphonate-modified agents are preferentially retained in infarcted myocardium. The ratio of GdDTPA-HPDP accumulated in whole infarcted heart to that detected in normal heart is 15 at 2 hours after injecting a dose of 50 to 100 mumol/kg; the ratio is 2 for GdDTPA. At these doses, significant changes are detected in the tissue relaxation rates. An average relaxivity of 11.2 (mmol-sec)-1 is calculated for the agent in the infarcted whole heart. GdDTPA-BDP, in comparison, displayed prolonged blood retention. The result is a low diseased-to-normal heart ratio (approximately 2) at 2 hours, making this agent less attractive as a contrast agent. PMID:2055714

Adzamli, I K; Johnson, D; Blau, M

1991-02-01

172

Spinal Infarcts  

Microsoft Academic Search

In the last decade typical signs of spinal cord ischemia have been reported. Confirming and supporting signs of acute ischemic\\u000a myelomalacia are vertebral body infarction and the pathognomonic contrast enhancement of the cauda equina in the course of\\u000a the disease. Moreover, bone infarction strongly indicates the proximal occlusion and the level of the affected segmental artery.\\u000a Cartilaginous disc embolism, embolism

Michael Mull; Armin Thron

173

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.

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

174

Targeted Over-Expression of Glutamate Transporter 1 (GLT-1) Reduces Ischemic Brain Injury in a Rat Model of Stroke  

PubMed Central

Following the onset of an ischemic brain injury, the excitatory neurotransmitter glutamate is released. The excitotoxic effects of glutamate are a major contributor to the pathogenesis of a stroke. The aim of this study was to examine if overexpression of a glutamate transporter (GLT-1) reduces ischemic brain injury in a rat model of stroke. We generated an adeno-associated viral (AAV) vector expressing the rat GLT-1 cDNA (AAV-GLT1). Functional expression of AAV-GLT1 was confirmed by increased glutamate clearance rate in non-stroke rat brain as measured by in vivo amperometry. AAV-GLT1 was injected into future cortical region of infarction 3 weeks prior to 60 min middle cerebral artery occlusion (MCAo). Tissue damage was assessed at one and two days after MCAo using TUNEL and TTC staining, respectively. Behavioral testing was performed at 2, 8 and 14 days post-stroke. Animals receiving AAV-GLT1, compared to AAV-GFP, showed significant decreases in the duration and magnitude of extracellular glutamate, measured by microdialysis, during the 60 minute MCAo. A significant reduction in brain infarction and DNA fragmentation was observed in the region of AAV-GLT1 injection. Animals that received AAV-GLT1 showed significant improvement in behavioral recovery following stroke compared to the AAV-GFP group. We demonstrate that focal overexpression of the glutamate transporter, GLT-1, significantly reduces ischemia-induced glutamate overflow, decreases cell death and improves behavioral recovery. These data further support the role of glutamate in the pathogenesis of ischemic damage in brain and demonstrate that targeted gene delivery to decrease the ischemia-induced glutamate overflow reduces the cellular and behavioral deficits caused by stroke.

Hinzman, Jason; Wires, Emily M.; Chiocco, Matthew J.; Howard, Douglas B.; Shen, Hui; Gerhardt, Greg; Hoffer, Barry J.; Wang, Yun

2011-01-01

175

Erythropoietin as a neuroprotectant for neonatal brain injury: animal models.  

PubMed

Prematurity and perinatal hypoxia-ischemia are common problems that result in significant neurodevelopmental morbidity and high mortality worldwide. The Vannucci model of unilateral brain injury was developed to model perinatal brain injury due to hypoxia-ischemia. Because the rodent brain is altricial, i.e., it develops postnatally, investigators can model either preterm or term brain injury by varying the age at which injury is induced. This model has allowed investigators to better understand developmental changes that occur in susceptibility of the brain to injury, evolution of brain injury over time, and response to potential neuroprotective treatments. The Vannucci model combines unilateral common carotid artery ligation with a hypoxic insult. This produces injury of the cerebral cortex, basal ganglia, hippocampus, and periventricular white matter ipsilateral to the ligated artery. Varying degrees of injury can be obtained by varying the depth and duration of the hypoxic insult. This chapter details one approach to the Vannucci model and also reviews the neuroprotective effects of erythropoietin (Epo), a neuroprotective treatment that has been extensively investigated using this model and others. PMID:23456865

Traudt, Christopher M; Juul, Sandra E

2013-01-01

176

The hippocampus and the brain: a neural network model  

Microsoft Academic Search

A brain-mapped neural network that combines attentional and configural mechanisms is able to characterize the attributes of multiple classical conditioning paradigms and to describe the effects of many neurophysiological manipulations. As shown in Buhusi and Schmajuk (1996), the attentional-configural model describes neural activity in several brain regions. As also shown in Buhusi and Schmajuk (1996), the attentional-configural model has been

Nestor Schmajuk

1999-01-01

177

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

178

Cardioprotective effect of liposomal prostaglandin E1 on a porcine model of myocardial infarction reperfusion no-reflow  

Microsoft Academic Search

Objective  To evaluate whether liposomal prostaglandin E1 (lipo-PGE1) can decrease reperfusion no-reflow in a catheter-based porcine\\u000a model of acute myocardial infarction (AMI).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Twenty-two male Chinese mini-swines were randomized into three groups: six in a sham-operation group, and eight each in the\\u000a control and lipo-PGE1 groups. The distal part of the left anterior descending coronary artery (LAD) in the latter two groups

Jia-hui Li; Peng Yang; Ai-li Li; Yong Wang; Yuan-nan Ke; Xian-lun Li

2011-01-01

179

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

PubMed

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

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

2012-07-12

180

Osteopontin reduced hypoxia-ischemia neonatal brain injury by suppression of apoptosis in a rat pup model  

PubMed Central

Background and Purpose Osteopontin (OPN) is neuroprotective in ischemic brain injuries in adult experimental models, therefore, we hypothesized that OPN would provide neuroprotection and improve long term neurological function in the immature brain after hypoxic-ischemic (HI) injury. Methods HI was induced by unilateral ligation of the right carotid artery followed by hypoxia (8% O2 for 2h) in postnatal day 7 rats. OPN (0.03 µg or 0.1 µg) was injected intracerebroventricularly at 1h post HI. Temporal expression of endogenous OPN was evaluated in the normal rat brain at the age of day 0, 4, 7, 11, 14, and 21, and in the ipsilateral hemisphere following HI. The effects of OPN were evaluated using TTC staining, apoptotic cell death assay, and cleaved caspase-3 expression. Neurological function was assessed by Morris water maze test. Results Endogenous OPN expression in the brain was the highest at the age of day 0, with continuous reduction till the age of day 21 during development. After HI injury, endogenous OPN expression was increased and peaked at 48h. Exogenous OPN decreased infarct volume and improved neurological outcomes 7 weeks after HI injury. OPN-induced neuroprotection was blocked by an integrin antagonist. Conclusions OPN-induced neuroprotection was associated with cleaved-caspase-3 inhibition and antiapoptotic cell death. OPN treatment improved long-term neurological function against neonatal HI brain injury.

Chen, Wanqiu; Ma, Qingyi; Suzuki, Hidenori; Hartman, Richard; Tang, Jiping; Zhang, John H.

2011-01-01

181

Cardioprotective effect of liposomal prostaglandin E1 on a porcine model of myocardial infarction reperfusion no-reflow*  

PubMed Central

Objective: To evaluate whether liposomal prostaglandin E1 (lipo-PGE1) can decrease reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). Methods: Twenty-two male Chinese mini-swines were randomized into three groups: six in a sham-operation group, and eight each in the control and lipo-PGE1 groups. The distal part of the left anterior descending coronary artery (LAD) in the latter two groups was completely occluded for 2 h, and then reperfused for 3 h. Lipo-PGE1 (1 ?g/kg) was injected 10 min before LAD occlusion until reperfusion for 1 h in the lipo-PGE1 group. Hemodynamic data and proinflammatory cytokines were examined before AMI, 2 h after occlusion, and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining were performed to evaluate the myocardial no-reflow area (NRA). Results: Left ventricular systolic pressure and end-diastolic pressure significantly improved in the lipo-PGE1 group after reperfusion compared with the control group and also 2 h after AMI (P<0.05 for both). MCE and double staining both showed that lipo-PGE1 decreased reperfusion NRA after AMI (P<0.05, P<0.01). Lipo-PGE1 decreased serum interleukin-6 (IL-6) and tumor necrosis factor-? (TNF-?) after myocardial infarction reperfusion (P<0.05 for both). Conclusions: Lipo-PGE1 is cardioprotective in our porcine model of myocardial infarction reperfusion no-reflow, decreasing NRA and attenuating the inflammatory response.

Li, Jia-hui; Yang, Peng; Li, Ai-li; Wang, Yong; Ke, Yuan-nan; Li, Xian-lun

2011-01-01

182

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

183

Neurodynamic Models of Brain in Psychiatry  

Microsoft Academic Search

The history of brain theory is described in terms of three kinds of theory of perception. The most widely used kind sees perception as dependent on passive inflow from the environment of information that is used to make and process representations of objects and events. A second kind views perception as an active search for information that is inherent in

Walter J Freeman

2003-01-01

184

Cerebral infarction does not occur typically at night.  

PubMed Central

In a hospital-based series of 66 consecutive patients with non-progressive cerebral infarction, the time of onset and the type of infarction on computed tomography were studied retrospectively. Forty-six (78%) patients suffered cerebral infarction between 6 am and 6 pm. Only five patients (8%) had their infarct between midnight and 6 am. Only three patients had a watershed-infarct, and these occurred during the daytime. Our results do not support the belief that atherothrombotic brain infarction is largely determined by haemodynamic factors.

van der Windt, C; van Gijn, J

1988-01-01

185

Development of a Model for Whole Brain Learning of Physiology  

ERIC Educational Resources Information Center

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

Eagleton, Saramarie; Muller, Anton

2011-01-01

186

Human cadaver brain infusion model for neurosurgical training  

Microsoft Academic Search

BackgroundMicroneurosurgical technique and anatomical knowledge require extensive laboratory training before mastering these skills. There are diverse training models based on synthetic materials, anesthetized animals, cadaver animals, or human cadaver. Human cadaver models are especially beneficial because they are the closest to live surgery with the greatest disadvantage of lacking hemodynamic factors. We developed the “brain infusion model” to provide a

Jon Olabe; Javier Olabe; Vidal Sancho

2009-01-01

187

Brain Anatomical Structure Segmentation by Hybrid Discriminative\\/Generative Models  

Microsoft Academic Search

In this paper, a hybrid discriminative\\/generative model for brain anatomical structure segmentation is proposed. The learning aspect of the approach is emphasized. In the dis- criminative appearance models, various cues such as intensity and curvatures are combined to locally capture the complex appearances of different anatomical structures. A probabilistic boosting tree (PBT) framework is adopted to learn multiclass discriminative models

Zhuowen Tu; Katherine L. Narr; Piotr Dollár; Ivo D. Dinov; Paul M. Thompson; Arthur W. Toga

2008-01-01

188

A mouse model of human repetitive mild traumatic brain injury  

Microsoft Academic Search

A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight

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

189

Image guided constitutive modeling of the silicone brain phantom  

NASA Astrophysics Data System (ADS)

The goal of this work is to develop reliable constitutive models of the mechanical behavior of the in-vivo human brain tissue for applications in neurosurgery. We propose to define the mechanical properties of the brain tissue in-vivo, by taking the global MR or CT images of a brain response to ventriculostomy - the relief of the elevated intracranial pressure. 3D image analysis translates these images into displacement fields, which by using inverse analysis allow for the constitutive models of the brain tissue to be developed. We term this approach Image Guided Constitutive Modeling (IGCM). The presented paper demonstrates performance of the IGCM in the controlled environment: on the silicone brain phantoms closely simulating the in-vivo brain geometry, mechanical properties and boundary conditions. The phantom of the left hemisphere of human brain was cast using silicon gel. An inflatable rubber membrane was placed inside the phantom to model the lateral ventricle. The experiments were carried out in a specially designed setup in a CT scanner with submillimeter isotropic voxels. The non-communicative hydrocephalus and ventriculostomy were simulated by consequently inflating and deflating the internal rubber membrane. The obtained images were analyzed to derive displacement fields, meshed, and incorporated into ABAQUS. The subsequent Inverse Finite Element Analysis (based on Levenberg-Marquardt algorithm) allowed for optimization of the parameters of the Mooney-Rivlin non-linear elastic model for the phantom material. The calculated mechanical properties were consistent with those obtained from the element tests, providing justification for the future application of the IGCM to in-vivo brain tissue.

Puzrin, Alexander; Skrinjar, Oskar; Ozan, Cem; Kim, Sihyun; Mukundan, Srinivasan

2005-04-01

190

Nitrates in myocardial infarction.  

PubMed

Until two decades ago nitroglycerin was contraindicated in acute myocardial infarction (MI). Studies in the canine model demonstrated that low-dose intravenous (i.v.) infusion, carefully titrated to decrease mean blood pressure by 10% but not below 80 mmHg, during early stages of acute MI produced marked reduction of left ventricular (LV) preload, improvement in regional perfusion, and limitation of infarct size and remodeling. However, more i.v. nitroglycerin to decrease blood pressure further resulted in a paradoxical J-curve effect, with hypoperfusion and increased infarct size. Clinical studies have confirmed that low-dose i.v. nitroglycerin infusion for the first 48 hours after acute MI is safe, not only for improving performance in LV failure, but also for limiting ischemic injury, infarct size, remodeling, and infarct-related complications, including deaths in-hospital and up to 1 year. Recent studies suggest that more prolonged therapy with nitrates spanning the healing phase of acute anterior Q-wave MI can further limit LV remodeling and preserve function. Preliminary results of the recently completed ISIS-4 megatrial suggest, however, that long-term nitrate in patients with suspected MI in the 1990s does not improve survival significantly. PMID:7848898

Jugdutt, B I

1994-08-01

191

Enhancement of subsurface brain shift model accuracy: a preliminary study  

NASA Astrophysics Data System (ADS)

Biomechanical models that describe soft-tissue deformations provide a relatively inexpensive way to correct registration errors in image guided neurosurgical systems caused by non-rigid brain shifts. Quantifying the factors that cause this deformation to sufficient precision is a challenging task. To circumvent this difficulty, atlas-based method have been developed recently which allow for uncertainty yet still capture the first order effects associated with brain deformations. More specifically, the technique involves building an atlas of solutions to account for the statistical uncertainty in factors that control the direction and magnitude of brain shift. The inverse solution is driven by a sparse intraoperative surface measurement. Since this subset of data only provides surface information, it could bias the reconstruction and affect the subsurface accuracy of the model prediction. Studies in intraoperative MR have shown that the deformation in the midline, tentorium, and contralateral hemisphere is relatively small. The falx cerebri and tentorium cerebelli, two of the important dural septa, act as rigid membranes supporting the brain parenchyma and compartmentalizing the brain. Accounting for these structures in models may be an important key to improving subsurface shift accuracy. The goals of this paper are to describe a novel method developed to segment the tentorium cerebelli, develop the procedure for modeling the dural septa and study the effect of those membranes on subsurface brain shift.

Garg, Ishita; Ding, Siyi; Coffey, Aaron M.; Dumpuri, Prashanth; Thompson, Reid C.; Dawant, Benoit M.; Miga, Michael I.

2010-03-01

192

Neurocritical Care Monitoring Correlates with Neuropathology in a Swine Model of Pediatric Traumatic Brain Injury  

PubMed Central

BACKGROUND Small animal models have been used in traumatic brain injury (TBI) research to investigate the basic mechanisms and pathology of TBI. Unfortunately, successful TBI investigations in small animal models have not resulted in marked improvements in clinical outcomes of TBI patients. OBJECTIVE To develop a clinically relevant immature large animal model of pediatric neurocritical care following TBI. METHODS Eleven 4 week old piglets were randomized to either rapid axial head rotation without impact (N=6) or instrumented sham (N=5). All animals had an intracranial pressure monitor, brain tissue oxygen (PbtO2) probe, and cerebral microdialysis probe placed in the frontal lobe and data collected for 6 h following injury. RESULTS Injured animals had sustained elevations in intracranial pressure and lactate-pyruvate ratio (LPR), and decreased PbtO2 compared to sham. PbtO2 and LPR from separate frontal lobes had strong linear correlation in both sham and injured animals. Neuropathologic examination demonstrated significant axonal injury and infarct volumes in injured animals compared to sham at 6 hours post-injury. Averaged over time, PbtO2 in both injured and sham animals had a strong inverse correlation with total injury volume. Average LPR had a strong correlation with total injury volume. CONCLUSION LPR and PbtO2 can be utilized as serial non-terminal secondary markers in our injury model for neuropathology, and as evaluation metrics for novel interventions and therapeutics in the acute post-injury period. This translational model bridges a vital gap in knowledge between TBI studies in small animal models and clinical trials in the pediatric TBI population.

Friess, Stuart H.; Ralston, Jill; Eucker, Stephanie A.; Helfaer, Mark A; Smith, Colin; Margulies, Susan S.

2011-01-01

193

Modelling the short term consequences of smoking cessation in England on the hospitalisation rates for acute myocardial infarction and stroke  

PubMed Central

OBJECTIVES—To estimate the short term event and cost consequences of achieving two smoking cessation targets for England among a cohort of 35-64 year olds, in terms of the number of hospitalised acute myocardial infarctions (AMIs) and strokes avoided.?DESIGN—A spreadsheet model based on previous work and using data for England was constructed to simulate the effects of achieving the target set out in the government's tobacco white paper (target 1). We also examined the consequence of achieving the intensive smoking reduction witnessed in California (target 2).?RESULTS—Target 1 would result in 347 AMI and 214 stroke hospitalisations avoided in the year 2000, and by 2010 this would be 6386 AMI and 4964 strokes avoided. Achieving target 2 would result in 739 AMI and 455 stroke hospitalisations avoided in 2000, and 14 554 AMI and 11 304 strokes avoided by 2010. Achieving target 1 would save £524 million (£423 million discounted at a rate of 2.67% for stroke and 2.31% for AMI) and target 2 would save £1.14 billion (£921 million discounted) in terms of National Health Service costs.?CONCLUSION—In the short term (11 years), reductions in the prevalence of smoking will produce sizeable reductions in both events and hospital costs.???Keywords: smoking cessation modelling cost; acute myocardial infarction; stroke

Naidoo, B.; Stevens, W.; McPherson, K.

2000-01-01

194

Treatment of reperfused ischemia with adipose-derived stem cells in a preclinical Swine model of myocardial infarction.  

PubMed

The aim of the study was to determine the long-term effect of transplantation of adipose-derived stromal cells (ADSCs) in a preclinical model of ischemia/reperfusion (I/R). I/R was induced in 28 Goettingen minipigs by 120 min of coronary artery occlusion followed by reperfusion. Nine days later, surviving animals were allocated to receive transendocardial injection of a mean of 213.6 ± 41.78 million green fluorescent protein (GFP)-expressing ADSCs (n = 7) or culture medium as control (n = 9). Heart function, cell engraftment, and histological analysis were performed 3 months after transplantation. Transplantation of ADSCs induced a statistically significant long-lasting (3 months) improvement in cardiac function and geometry in comparison with control animals. Functional improvement was associated with an increase in angiogenesis and vasculogenesis and a positive effect on heart remodeling with a decrease in fibrosis and cardiac hypertrophy in animals treated with ADSCs. Despite the lack of cell engraftment after 3 months, ADSC transplantation induced changes in the ratio between MMP/TIMP. Our results indicate that transplantation of ADSCs, despite the lack of long-term significant cell engraftment, increases vessel density and prevents adverse remodeling in a clinically relevant model of myocardial infarction, strongly suggesting a paracrine-mediated effect. ADSCs thus constitute an attractive candidate for the treatment of myocardial infarction. PMID:22524986

Mazo, Manuel; Hernández, Salomón; Gavira, Juan José; Abizanda, Gloria; Araña, Miriam; López-Martínez, Tania; Moreno, Cristina; Merino, Juana; Martino-Rodríguez, Alba; Uixeira, Alicia; García de Jalón, José A; Pastrana, Juan; Martínez-Caro, Diego; Prósper, Felipe

2012-04-17

195

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

PubMed Central

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

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

2013-01-01

196

Intravenous infusion of mesenchymal stem cells enhances regional perfusion and improves ventricular function in a porcine model of myocardial infarction.  

PubMed

Transplantation of stem cells may improve regional perfusion and post-infarct ventricular function, but the optimal dose and efficacy of cell delivery via the intravenous route has not been determined. This study tested the hypothesis that intravenous infusion of bone marrow-derived mesenchymal stem cells (MSCs) enhances regional perfusion and improves ventricular function after myocardial infarction. In a closed-chest pig model, the LAD coronary artery was occluded for 75 min by angioplasty balloon inflation followed by 12 weeks of reperfusion. After 15 min of reperfusion, pigs randomly received 1 of 4 treatments: (1) Vehicle (Control, n = 10); (2) 1 x 10(6) MSCs/kg (1 mill, n = 7); (3) 3 x 10(6) MSCs/kg (3 mill, n = 8) and (4) 10 x 10(6) MSCs/kg (10 mill, n = 8). Angiogenesis was demonstrated by immunohistochemical staining, myocardial blood flow (steady state and vasodilator reserve) was measured using 15 microm neutron-activated microspheres, and cardiac function was determined by contrast left ventriculography (ejection fraction) and pressure-volume relationships. After 12 week of reperfusion, von Willebrand Factor-positive vessels and tissue vascular endothelial growth factor (VEGF) expression in the scar zone was significantly greater in all MSCs-treated animals relative to Control. Steady state myocardial blood flow in the scar tissue was comparable among groups. However, adenosine recruited vasodilator reserve in the scar zone induced by intracoronary adenosine was significantly higher in the MSC-treated animals compared to Control. Furthermore, preload-recruitable stroke work and systolic performance were significantly greater compared to Control. In conclusion, these data demonstrate that intravenous delivery of MSCs during early reperfusion augments vasculogenesis, enhances regional perfusion, and improves post-infarct ventricular function. The results suggest that intravenous infusion of MSCs is an effective modality for the treatment of ischemia/reperfusion induced myocardial injury. PMID:18704259

Halkos, Michael E; Zhao, Zhi-Qing; Kerendi, Faraz; Wang, Ning-Ping; Jiang, Rong; Schmarkey, L Susan; Martin, Bradley J; Quyyumi, Arshed A; Few, Walter L; Kin, Hajime; Guyton, Robert A; Vinten-Johansen, Jakob

2008-08-14

197

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

198

Development and validation of a simple model to predict severe coronary artery disease after myocardial infarction: Potential impact on cardiac catheterization use in the United States and Canada  

Microsoft Academic Search

Background Improved patient selection may optimize the efficiency of cardiac catheterization in both high- and low-rate regions. The purpose of this study was to develop and validate a clinical model for predicting high-risk coronary artery disease (CAD) after myocardial infarction (MI) and to examine the model's potential impact on the use rate of both US and Canadian catheterization practices. Methods

Wayne B. Batchelor; Daniel B. Mark; J. David Knight; Christopher B. Granger; Paul W. Armstrong; Robert M. Califf; Eric D. Peterson

2003-01-01

199

Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome  

PubMed Central

Background Cerebral ischaemia initiates an inflammatory response in the brain and periphery. We assessed the relationship between peak values of plasma interleukin-6 (IL-6) in the first week after ischaemic stroke, with measures of stroke severity and outcome. Methods Thirty-seven patients with ischaemic stroke were prospectively recruited. Plasma IL-6, and other markers of peripheral inflammation, were measured at pre-determined timepoints in the first week after stroke onset. Primary analyses were the association between peak plasma IL-6 concentration with both modified Rankin score (mRS) at 3 months and computed tomography (CT) brain infarct volume. Results Peak plasma IL-6 concentration correlated significantly (p < 0.001) with CT brain infarct volume (r = 0.75) and mRS at 3 months (r = 0.72). It correlated similarly with clinical outcome at 12 months or stroke severity. Strong associations were also noted between either peak plasma C-reactive protein (CRP) concentration or white blood cell (WBC) count, and all outcome measures. Conclusions These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke, and clinical outcome.

Smith, Craig J; Emsley, Hedley CA; Gavin, Carole M; Georgiou, Rachel F; Vail, Andy; Barberan, Elisa M; del Zoppo, Gregory J; Hallenbeck, John M; Rothwell, Nancy J; Hopkins, Stephen J; Tyrrell, Pippa J

2004-01-01

200

S-allylcysteine mediates cardioprotection in an acute myocardial infarction rat model via a hydrogen sulfide-mediated pathway.  

PubMed

S-allylcysteine (SAC) is an organosulfur-containing compound derived from garlic. Studies have shown that garlic is beneficial in the treatment of cardiovascular diseases. This study aims to elucidate if SAC is responsible for this cardioprotection using acute myocardial infarction (AMI) rat models. In addition, we hypothesized that SAC may mediate cardioprotection via a hydrogen sulfide (H(2)S)-related pathway. Rats were pretreated with saline, SAC (50 mg x kg(-1) x day(-1)), SAC + propagylglycine (PAG; 50 mg + 10 mg x kg(-1) x day(-1)) or PAG (10 mg x kg(-1) x day(-1)) for 7 days before AMI induction and killed 48 h after. Our results showed that SAC significantly lowered mortality (12.5% vs. 33.3%, P < 0.05) and reduced infarct size. SAC + PAG- and PAG-treated rats had larger infarct sizes than controls (60.9 +/- 0.01 and 62.0 +/- 0.03%, respectively, vs. 50.0 +/- 0.03%; P < 0.05). Pretreatment with SAC did not affect BP, but BP was significantly elevated in SAC + PAG and PAG-treated groups (P < 0.05). In addition, plasma H(2)S levels and left ventricular cystathionine-gamma-lyase (CSE) activities were analyzed to investigate the involvement of H(2)S. CSE is the enzyme responsible for H(2)S production in the heart. SAC increased left ventricular CSE activity in AMI rats (2.75 +/- 0.34 vs. 1.23 +/- 0.16 micromol x g protein(-1) x h(-1); P < 0.01). SAC + PAG-treated rats had significantly lower CSE activity compared with the SAC-treated group (1.22 +/- 0.27 vs. 2.75 +/- 0.34 micromol x g protein(-1) x h(-1); P < 0.05). Similarly, SAC-treated rats had higher plasma H(2)S concentration compared with controls and the SAC + PAG-treated group. Protein expression studies revealed that SAC upregulated CSE expression (1.1-fold of control; P < 0.05), whereas SAC + PAG and PAG downregulated its expression (0.88-fold of control in both groups; P < 0.005). In conclusion, our study provides novel evidence that SAC is protective in myocardial infarction via an H(2)S-related pathway. PMID:17766469

Chuah, Shin Chet; Moore, Philip K; Zhu, Yi Zhun

2007-08-31

201

Modeling the impact of lesions in the human brain.  

PubMed

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 a computational model. We simulate the dynamic effects of lesions placed in different regions of the cerebral cortex by recording changes in the pattern of endogenous ("resting-state") neural activity. We find that lesions produce specific patterns of altered functional connectivity among distant regions of cortex, often affecting both cortical hemispheres. The magnitude of these dynamic effects depends on the lesion location and is partly predicted by structural network properties of the lesion site. In the model, lesions along the cortical midline and in the vicinity of the temporo-parietal junction result in large and widely distributed changes in functional connectivity, while lesions of primary sensory or motor regions remain more localized. The model suggests that dynamic lesion effects can be predicted on the basis of specific network measures of structural brain networks and that these effects may be related to known behavioral and cognitive consequences of brain lesions. PMID:19521503

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

2009-06-12

202

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

NSDL National Science Digital Library

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

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

2008-10-01

203

Exponential Random Graph Modeling for Complex Brain Networks  

PubMed Central

Exponential random graph models (ERGMs), also known as p* models, have been utilized extensively in the social science literature to study complex networks and how their global structure depends on underlying structural components. However, the literature on their use in biological networks (especially brain networks) has remained sparse. Descriptive models based on a specific feature of the graph (clustering coefficient, degree distribution, etc.) have dominated connectivity research in neuroscience. Corresponding generative models have been developed to reproduce one of these features. However, the complexity inherent in whole-brain network data necessitates the development and use of tools that allow the systematic exploration of several features simultaneously and how they interact to form the global network architecture. ERGMs provide a statistically principled approach to the assessment of how a set of interacting local brain network features gives rise to the global structure. We illustrate the utility of ERGMs for modeling, analyzing, and simulating complex whole-brain networks with network data from normal subjects. We also provide a foundation for the selection of important local features through the implementation and assessment of three selection approaches: a traditional p-value based backward selection approach, an information criterion approach (AIC), and a graphical goodness of fit (GOF) approach. The graphical GOF approach serves as the best method given the scientific interest in being able to capture and reproduce the structure of fitted brain networks.

Simpson, Sean L.; Hayasaka, Satoru; Laurienti, Paul J.

2011-01-01

204

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

Microsoft Academic Search

Brain extraction from head magnetic resonance (MR) images is a classification problem of segmenting image volumes into brain and non-brain regions. It is a difficult task due to the convoluted brain surface and the inapparent brain\\/non-brain boundaries in images. This paper presents an automated, robust, and accurate brain extraction method which utilizes a new implicit deformable model to well represent

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

2009-01-01

205

Thermal imaging of brain tumors in a rat glioma model  

NASA Astrophysics Data System (ADS)

We have explored the capability of thermal imaging for the detection of brain tumors in a rat glioma mode. Fourteen Wistar rats were injected stereotactically with 100,000 C6 glioma cells. Approximately one and two weeks post implantation, the rats underwent bilateral craniotomy and the exposed brain surface was imaged with a short wave thermal camera. Thermal images were obtained at both low (approximately 28.7 degree(s)C) and high (approximately 38 degree(s)C) core temperatures. Temperature gradients between the tumor site and the contralateral normal brain were calculated. Overall, the tumors appeared cooler than normal brain, for both high and low core temperatures. Average temperature difference between tumor and normal brain were maximal in more advanced tumors (two weeks) and at higher core temperatures. At one week (N equals 6), the average temperature gradient between tumor and normal sites was 0.1 degree(s)C and 0.2 degree(s)C at low and high core temperatures respectively (P$GTR0.05). At two weeks (N equals 8), the average temperature gradient was 0.3 degree(s)C and 0.7 degree(s)C at low and high core temperatures respectively (P<0.05). We conclude that thermal imaging can detect temperature differences between tumor and normal brain tissue in this model, particularly in more advanced tumors. Thermal imaging may provide a novel means to identify brain tumors intraoperatively.

Papaioannou, Thanassis; Thompson, Reid C.; Kateb, Babak; Sorokoumov, Oleg; Grundfest, Warren S.; Black, Keith L.

2002-05-01

206

Modeling decisions by brains that think, feel, and vegetate  

Microsoft Academic Search

This paper summarizes three interrelated neural network models of data on emotionally influenced decision making: the first on a gambling task, the second on probability judgment, and the third on probability weighting. The networks incorporate data on executive regions of the brain and organizing principles such as adaptive resonance and fuzzy traces that have been utilized to model other cognitive

Daniel S. Levine

2011-01-01

207

Binding in models of perception and brain function  

Microsoft Academic Search

The development of the concept of feature binding as fundamental to neural dynamics has made possible recent advances in the modeling of difficult problems of perception and brain function. Major weaknesses of past neural modeling (most prominently its inability to work with natural stimuli and its ‘learning-time’ barrier) have been traced back to improper treatment of the binding issue. Signal

Christoph von der Malsburg

1995-01-01

208

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.

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

209

Creating physical 3D stereolithograph models of brain and skull.  

PubMed

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

2007-10-31

210

Injectable microsphere/hydrogel hybrid system containing heat shock protein as therapy in a murine myocardial infarction model.  

PubMed

Abstract Heat shock proteins, acting as molecular chaperones, protect heart muscle from ischemic injury and offer a potential approach to therapy. Here we describe preparation of an injectable form of heat shock protein 27, fused with a protein transduction domain (TAT-HSP27) and contained in a hybrid system of poly(d,l-lactic-co-glycolic acid) microsphere and alginate hydrogel. By varying the porous structure of the microspheres, the release of TAT-HSP27 from the hybrid system was sustained for two weeks in vitro. The hybrid system containing TAT-HSP27 was intramyocardially injected into a murine myocardial infarction model, and its therapeutic effect was evaluated in vivo. The sustained delivery of TAT-HSP27 substantially suppressed apoptosis in the infarcted site, and improved the ejection fraction, end-systolic volume and maximum pressure development in the heart. Local and sustained delivery of anti-apoptotic proteins such as HSP27 using a hybrid system may present a promising approach to the treatment of ischemic diseases. PMID:23952941

Lee, Jangwook; Cha, Min-Ji; Lim, Kwang Suk; Kim, Jang-Kyung; Lee, Sang-Kyung; Kim, Yong-Hee; Hwang, Ki-Chul; Lee, Kuen Yong

2013-08-19

211

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.

2010-01-01

212

Calcium-activated potassium channels mediated blood-brain tumor barrier opening in a rat metastatic brain tumor model  

Microsoft Academic Search

BACKGROUND: The blood-brain tumor barrier (BTB) impedes the delivery of therapeutic agents to brain tumors. While adequate delivery of drugs occurs in systemic tumors, the BTB limits delivery of anti-tumor agents into brain metastases. RESULTS: In this study, we examined the function and regulation of calcium-activated potassium (KCa) channels in a rat metastatic brain tumor model. We showed that intravenous

Jinwei Hu; Xiangpeng Yuan; MinHee K Ko; Dali Yin; Manuel R Sacapano; Xiao Wang; Bindu M Konda; Andres Espinoza; Ksenia Prosolovich; John M Ong; Dwain Irvin; Keith L Black

2007-01-01

213

Models for predicting blood-brain barrier permeation.  

PubMed

The endothelial blood-brain barrier (BBB) ensures an optimal environment for proper neural function in vertebrates; however, it also creates a major obstacle for the medical treatment of brain diseases. Despite significant progress in the development of various in vitro and in silico models for predicting BBB permeation, many challenges remain and, so far, no model is able to meet the early drug discovery demands of the industry for reliability and time and cost efficiency. Recently, it was found that the grasshopper (Locusta migratoria) brain barrier has similar functionality as the vertebrate BBB. The insect model can thus be used as a surrogate for the vertebrate BBB as it meets the demands required during the drug discovery phase. PMID:21513815

Nielsen, Peter Aadal; Andersson, Olga; Hansen, Steen Honoré; Simonsen, Klaus Bæk; Andersson, Gunnar

2011-04-12

214

Animal models of traumatic brain injury: Is there an optimal model to reproduce human brain injury in the laboratory?  

Microsoft Academic Search

Compared to other neurological diseases, the research surrounding traumatic brain injury (TBI) has a more recent history. The establishment and use of animal models of TBI remains vital to understand the pathophysiology of this highly complex disease. Such models share the ultimate goals of reproducing patterns of tissue damage observed in humans (thus rendering them clinically relevant), reproducible and highly

M. C. Morganti-Kossmann; E. Yan; N. Bye

2010-01-01

215

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

PubMed Central

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

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

2013-01-01

216

Benefits of standardizing the treatment of arrhythmias in the sheep (Ovis aries) model of chronic heart failure after myocardial infarction.  

PubMed

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

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

2013-01-01

217

Constitutive model for brain tissue under finite compression.  

PubMed

While advances in computational models of mechanical phenomena have made it possible to simulate dynamically complex problems in biomechanics, accurate material models for soft tissues, particularly brain tissue, have proven to be very challenging. Most studies in the literature on material properties of brain tissue are performed in shear loading and very few tackle the behavior of brain in compression. In this study, a viscoelastic constitutive model of bovine brain tissue under finite step-and-hold uniaxial compression with 10 s(-1) ramp rate and 20 s hold time has been developed. The assumption of quasi-linear viscoelasticity (QLV) was validated for strain levels of up to 35%. A generalized Rivlin model was used for the isochoric part of the deformation and it was shown that at least three terms (C(10), C(01) and C(11)) are needed to accurately capture the material behavior. Furthermore, for the volumetric deformation, a two parameter Ogden model was used and the extent of material incompressibility was studied. The hyperelastic material parameters were determined through extracting and fitting to two isochronous curves (0.06 s and 14 s) approximating the instantaneous and steady-state elastic responses. Viscoelastic relaxation was characterized at five decay rates (100, 10, 1, 0.1, 0 s(-1)) and the results in compression and their extrapolation to tension were compared against previous models. PMID:22281404

Laksari, Kaveh; Shafieian, Mehdi; Darvish, Kurosh

2012-01-24

218

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

219

Bihemispheric Subcortical Infarcts in the Middle Cerebral Artery Territory  

PubMed Central

Background and purpose: Previous studies have suggested embolic mechanisms for bihemispheric subcortical infarcts involving the anterior and posterior circulation. However, the mechanism of bihemispheric subcortical infarcts in middle cerebral artery (MCA) territories remains uncertain. We describe a patient with acute bihemispheric subcortical infarcts in restricted MCA territories suggesting an embolic mechanism. Case description: A 62-year-old woman with a history of hypertension and hyperlipidemia suddenly presented with left hemiplegia. Diffusion-weighted and T2-weighted magnetic resolution imaging of the brain showed multiple subcortical high intensity in the MCA territories. There were no acute infarctions in the cerebrum, brain stem, or cerebellum, including cortical lesions. The patient had no carotid, internal carotid artery, or MCA disease. Conclusion: Bihemispheric subcortical infarcts in the MCA territory are likely to have a proximal embolic source and such infarcts could be associated with multiple subcortical infarcts due to small vessel disease.

Kataoka, Hiroshi; Kumazawa, Masahiro; Izumi, Tesseki; Ueno, Satoshi

2011-01-01

220

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

PubMed Central

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

2013-01-01

221

Value of segmental myocardial strain by 2-dimensional strain echocardiography for assessment of scar area induced in a rat model of myocardial infarction  

PubMed Central

Objectives Two-dimensional strain echocardiography (2DSE) technique has enabled accurate quantification of regional myocardial function. This experimental study was aimed to investigate the value of 2DSE in detection of segmental regional myocardial dysfunction induced by fibrosis following myocardial infarction in a small animal (rat) model. Methods A rat model of myocardial infarction was established by ligation of the proximal left anterior descending coronary artery in 17 SD rats. Regional myocardial function was detected by 2DSE at baseline and 4-weeks post-infarction, including end-systolic radial strain and strain rate (SR and SrR) and end-systolic circumferential strain and strain rate (SC and SrC) of each of six segments at papillary level. According to the size of scar found by histologic Masson staining, the optimal cutoff points of parameters for detecting scar area were analyzed and the sensitivity and specificity of every parameter to detect myocardial scar were obtained using ROC. Results (1) Comparing with parameters measured at baseline, there were significant decreases in SR, SrR, SC and SrC of each segment at 4 weeks post-infarction, with the worst in the infarct area (32.90 ± 8.79 vs 11.18 ± 3.89, 6.28 ± 1.35 vs 3.18 ± 0.47, -14.46 ± 2.21 vs -6.30 ± 2.17 and 4.93 ± 0.95 vs 2.59 ± 1.16, respectively) (all P < 0.05). (2)By 4 weeks, the myocardium of infarct area (anteroseptum, anterior and anterolateral) had fibrosis (31.33 ± 9.89, 73.42 ± 13.21 and 13.99 ± 3.24%, respectively) with minimal fibrosis in inferoseptal segment (0.32 ± 0.19%), no fibrosis was found in the inferior and inferolateral segments. (3)Significant negative correlations were found between the size of segmental scar and 2DSE parameters (r-value -0.61 ~ -0.80, all P < 0.01) with the strongest correlation in SR. SR less than 10% has 84% sensitivity and 98% specificity for detecting segments of scar area greater than 30% with AUC = 0.97. Conclusions 2DSE is able to assess regional myocardial dysfunction in a rat model of myocardial infarction and has high accuracy in detecting infarct segments with scar area greater than 30%.

2012-01-01

222

Modeling the blood-brain barrier using stem cell sources.  

PubMed

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

Lippmann, Ethan S; Al-Ahmad, Abraham; Palecek, Sean P; Shusta, Eric V

2013-01-10

223

Detection of hidden objects in brain model with near-infrared phased-array optical system  

Microsoft Academic Search

Solid brain models with a brain-like background have been constructed and tested by a near IR phased array optical system. Two different kinds of detection geometry, remission and transmission, have been tested on brain models. These two kinds of geometry scan different area of the brain mode and both have a good deductibility in the detection area. A 6 mm

Qingming Luo; Britton Chance; Shuoming Zhou

1998-01-01

224

Experimental model for civilian ballistic brain injury biomechanics quantification.  

PubMed

Biomechanical quantification of projectile penetration using experimental head models can enhance the understanding of civilian ballistic brain injury and advance treatment. Two of the most commonly used handgun projectiles (25-cal, 275 m/s and 9 mm, 395 m/s) were discharged to spherical head models with gelatin and Sylgard simulants. Four ballistic pressure transducers recorded temporal pressure distributions at 308kHz, and temporal cavity dynamics were captured at 20,000 frames/second (fps) using high-speed digital video images. Pressures ranged from 644.6 to -92.8 kPa. Entry pressures in gelatin models were higher than exit pressures, whereas in Sylgard models entry pressures were lower or equivalent to exit pressures. Gelatin responded with brittle-type failure, while Sylgard demonstrated a ductile pattern through formation of micro-bubbles along projectile path. Temporary cavities in Sylgard models were 1.5-2x larger than gelatin models. Pressures in Sylgard models were more sensitive to projectile velocity and diameter increase, indicating Sylgard was more rate sensitive than gelatin. Based on failure patterns and brain tissue rate-sensitive characteristics, Sylgard was found to be an appropriate simulant. Compared with spherical projectile data, full-metal jacket (FMJ) projectiles produced different temporary cavity and pressures, demonstrating shape effects. Models using Sylgard gel and FMJ projectiles are appropriate to enhance understanding and mechanisms of ballistic brain injury. PMID:17166502

Zhang, Jiangyue; Yoganandan, Narayan; Pintar, Frank A; Guan, Yabo; Gennarelli, Thomas A

2006-12-12

225

A 3D brain deformation model experiencing comparable surgical loads  

Microsoft Academic Search

During the past 10 years, the finite element method (FEM) has been successfully employed to model the neuroanatomy under varying load conditions. Loading conditions used in previous work can be predominantly separated into two categories. The first category concerns large accelerations of the head followed by a sharp deceleration or impact. The second category considers maladies of the brain such

Michael I. Miga; Keith D. Paulsen; Francis E. Kennedy; P. Jack Hoopes; Alex Hartov; David W. Roberts

1997-01-01

226

Magnetic Resonance Imaging in Experimental Models of Brain Disorders  

Microsoft Academic Search

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

Rick M. Dijkhuizen; Klaas Nicolay

2003-01-01

227

Sparse coding and challenges for Bayesian models of the brain.  

PubMed

While the target article provides a glowing account for the excitement in the field, we stress that hierarchical predictive learning in the brain requires sparseness of the representation. We also question the relation between Bayesian cognitive processes and hierarchical generative models as discussed by the target article. PMID:23663363

Trappenberg, Thomas; Hollensen, Paul

2013-05-10

228

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

229

A model of associative memory in the brain  

Microsoft Academic Search

A model of associative memory for time varying spatial patterns is proposed and simulated on a digital computer. This is a network composed of many neuron-like elements, and shows an ability for associative memory similar to that of the brain.

Kunihiko Fukushima

1973-01-01

230

The musician's brain as a model of neuroplasticity  

Microsoft Academic Search

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

Eckart Altenmüller; Lutz Jäncke; Thomas F. Münte

2002-01-01

231

Stochastic Model of Tsc1 Lesions in Mouse Brain  

PubMed Central

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder due to mutations in either TSC1 or TSC2 that affects many organs with hamartomas and tumors. TSC-associated brain lesions include subependymal nodules, subependymal giant cell astrocytomas and tubers. Neurologic manifestations in TSC comprise a high frequency of mental retardation and developmental disorders including autism, as well as epilepsy. Here, we describe a new mouse model of TSC brain lesions in which complete loss of Tsc1 is achieved in multiple brain cell types in a stochastic pattern. Injection of an adeno-associated virus vector encoding Cre recombinase into the cerebral ventricles of mice homozygous for a Tsc1 conditional allele on the day of birth led to reduced survival, and pathologic findings of enlarged neurons, cortical heterotopias, subependymal nodules, and hydrocephalus. The severity of clinical and pathologic findings as well as survival was shown to be dependent upon the dose and serotype of Cre virus injected. Although several other models of TSC brain disease exist, this model is unique in that the pathology reflects a variety of TSC-associated lesions involving different numbers and types of cells. This model provides a valuable and unique addition for therapeutic assessment.

Zuang, Xuan; Sena-Esteves, Miguel; Bronson, Roderick; Brockmann, Jillian; Gianni, Davide; Wojtkiewicz, Gregory R.; Chen, John W.; Stemmer-Rachamimov, Anat; Kwiatkowski, David J.; Breakefield, Xandra O.

2013-01-01

232

Obesity and the brain: how convincing is the addiction model?  

Microsoft Academic Search

An increasingly influential perspective conceptualizes both obesity and overeating as a food addiction accompanied by corresponding brain changes. Because there are far-reaching implications for clinical practice and social policy if it becomes widely accepted, a critical evaluation of this model is important. We examine the current evidence for the link between addiction and obesity, identifying several fundamental shortcomings in the

Hisham Ziauddeen; I. Sadaf Farooqi; Paul C. Fletcher

2012-01-01

233

ST-IM model: a whole brain approach to implementation  

Microsoft Academic Search

Purpose – The purpose of the paper is to present a practical case study of a mid-size Indian organisation, where the whole brain thinking (WBT) approach has been successfully used to align strategy to development needs, based on a simple but powerful model, the ST-IM™; the authors also share how WBT has been useful in increasing the effectiveness of the

Prasad Deshpande; Suhas Baxi

2011-01-01

234

Blast Model of Traumatic Brain Injury in Swine.  

National Technical Information Service (NTIS)

The purpose of this study is to develop a survival model of blast- induced traumatic brain injury (BI-TBI) in swine. Two air guns were constructed, each having different lengths, air chamber volumes and barrel diameters. Air velocity was measured with a b...

S. Panter

2011-01-01

235

A Next Generation Modeling Environment PLATO: Platform for Collaborative Brain System Modeling  

Microsoft Academic Search

\\u000a To understand the details of brain function, a large scale system model that reflects anatomical and neurophysiological characteristics\\u000a needs to be implemented. Though numerous computational models of different brain areas have been proposed, these integration\\u000a for the development of a large scale model have not yet been accomplished because these models were described by different\\u000a programming languages, and mostly because

Shiro Usui; Keiichiro Inagaki; Takayuki Kannon; Yoshimi Kamiyama; Shunji Satoh; Nilton L. Kamiji; Yutaka Hirata; Akito Ishihara; Hayaru Shouno

2009-01-01

236

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

PubMed Central

This paper is aimed at exploring the effect of cortical brain atrophy on the currents induced by transcranial magnetic stimulation (TMS). We compared the currents induced by various TMS conditions on several different MRI derived finite element head models of brain atrophy, incorporating both decreasing cortical volume and widened sulci. The current densities induced in the cortex were dependent upon the degree and type of cortical atrophy and were altered in magnitude, location, and orientation when compared to healthy head models. Predictive models of the degree of current density attenuation as a function of the scalp-to-cortex distance were analyzed, concluding that those which ignore the electromagnetic field–tissue interactions lead to inaccurate conclusions. Ultimately, the precise site and population of neural elements stimulated by TMS in an atrophic brain cannot be predicted based on healthy head models which ignore the effects of the altered cortex on the stimulating currents. Clinical applications of TMS should be carefully considered in light of these findings.

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

2012-01-01

237

Spinal Cord Infarction  

MedlinePLUS

... Contact NINDS Adobe Reader Microsoft Word Viewer NINDS Spinal Cord Infarction Information Page Table of Contents (click ... is being done? Clinical Trials Organizations What is Spinal Cord Infarction? Spinal cord infarction is a stroke ...

238

Models in search of a brain  

Microsoft Academic Search

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

Bradley C. Love; Todd M. Gureckis

2007-01-01

239

Emotional neglect in childhood and cerebral infarction in older age  

PubMed Central

Objective: The purpose of the study was to test the hypothesis that a higher level of childhood adversity is associated with increased risk of cerebral infarction in old age. Methods: Older participants in a longitudinal clinical–pathologic study rated adverse childhood experiences (e.g., emotional neglect, parental intimidation and violence) on a previously established 16-item scale. During a mean of 3.5 years of follow-up, there were 257 deaths, with 206 brain autopsies (80.2). Number of chronic cerebral infarcts (gross plus microscopic; expressed as 0, 1, or >1) was determined in a uniform neuropathologic examination, which had been completed in 192 individuals at the time of these analyses. Results: Childhood adversity scores ranged from 0 to 31 (mean = 8.3, SD = 6.4). In an ordinal logistic regression model adjusted for age, sex, and education, higher adversity was associated with higher likelihood of chronic cerebral infarction. In analyses of childhood adversity subscales, only emotional neglect was associated with infarction (odds ratio [OR] = 1.097; 95% confidence interval [CI] 1.048–1.148). The likelihood of infarction was 2.8 times higher (95% CI 2.0–4.1) in those reporting a moderately high level of childhood emotional neglect (score = 6, 75th percentile) vs a moderately low level of neglect (score = 1, 25th percentile). Results were comparable in subsequent analyses that controlled for lifetime socioeconomic status, cardiovascular risk factors, and an anxiety-related trait. Conclusion: Emotional neglect in childhood may be a risk factor for cerebral infarction in old age.

Boyle, Patricia A.; Levine, Steven R.; Yu, Lei; Anagnos, Sophia E.; Buchman, Aron S.; Schneider, Julie A.; Bennett, David A.

2012-01-01

240

Unraveling the ischemic brain transcriptome in a permanent middle cerebral artery occlusion mouse model by DNA microarray analysis.  

PubMed

Brain ischemia, also termed cerebral ischemia, is a condition in which there is insufficient blood flow to the brain to meet metabolic demand, leading to tissue death (cerebral infarction) due to poor oxygen supply (cerebral hypoxia). Our group is interested in the protective effects of neuropeptides for alleviating brain ischemia, as well as the underlying mechanisms of their action. The present study was initiated to investigate molecular responses at the level of gene expression in ischemic brain tissue. To achieve this, we used a mouse permanent middle cerebral artery occlusion (PMCAO) model in combination with high-throughput DNA microarray analysis on an Agilent microarray platform. Briefly, the right (ipsilateral) and left (contralateral) hemispheres of PMCAO model mice were dissected at two time points, 6 and 24 hours post-ischemia. Total RNA from the ischemic (ipsilateral) hemisphere was subjected to DNA microarray analysis on a mouse whole genome 4x44K DNA chip using a dye-swap approach. Functional categorization using the gene ontology (GO, MGD/AMIGO) of numerous changed genes revealed expression pattern changes in the major categories of cellular process, biological regulation, regulation of biological process, metabolic process and response to stimulus. Reverse-transcriptase PCR (RT-PCR) analysis on randomly selected highly up- or downregulated genes validated, in general, the microarray data. Using two time points for this analysis, major and minor trends in gene expression and/or functions were observed in relation to early- and late-response genes and differentially regulated genes that were further classified into specific pathways or disease states. We also examined the expression of these genes in the contralateral hemisphere, which suggested the presence of bilateral effects and/or differential regulation. This study provides the first ischemia-related transcriptome analysis of the mouse brain, laying a strong foundation for studies designed to elucidate the mechanisms regulating ischemia and to explore the neuroprotective effects of agents such as target neuropeptides. PMID:22015461

Hori, Motohide; Nakamachi, Tomoya; Rakwal, Randeep; Shibato, Junko; Nakamura, Keisuke; Wada, Yoshihiro; Tsuchikawa, Daisuke; Yoshikawa, Akira; Tamaki, Keiji; Shioda, Seiji

2011-10-20

241

Experimental model for civilian ballistic brain injury biomechanics quantification  

Microsoft Academic Search

Biomechanical quantification of projectile penetration using experimental head models can enhance the understanding of civilian ballistic brain injury and advance treatment. Two of the most commonly used handgun projectiles (25-cal, 275m\\/s and 9mm, 395m\\/s) were discharged to spherical head models with gelatin and Sylgard simulants. Four ballistic pressure transducers recorded temporal pressure distributions at 308kHz, and temporal cavity dynamics were

Jiangyue Zhang; Narayan Yoganandan; Frank A. Pintar; Yabo Guan; Thomas A. Gennarelli

2007-01-01

242

Self-Organized Criticality Model for Brain Plasticity  

Microsoft Academic Search

Networks of living neurons exhibit an avalanche mode of activity,\\u000aexperimentally found in organotypic cultures. Here we present a model based on\\u000aself-organized criticality and taking into account brain plasticity, which is\\u000aable to reproduce the spectrum of electroencephalograms (EEG). The model\\u000aconsists in an electrical network with threshold firing and activity-dependent\\u000asynapse strenghts. The system exhibits an avalanche activity

Lucilla de Arcangelis; Carla Perrone-Capano; Hans J. Herrmann

2006-01-01

243

Obesity and the brain: how convincing is the addiction model?  

PubMed

An increasingly influential perspective conceptualizes both obesity and overeating as a food addiction accompanied by corresponding brain changes. Because there are far-reaching implications for clinical practice and social policy if it becomes widely accepted, a critical evaluation of this model is important. We examine the current evidence for the link between addiction and obesity, identifying several fundamental shortcomings in the model, as well as weaknesses and inconsistencies in the empirical support for it from human neuroscientific research. PMID:22414944

Ziauddeen, Hisham; Farooqi, I Sadaf; Fletcher, Paul C

2012-03-14

244

Cerebral organoids model human brain development and microcephaly.  

PubMed

The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem 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 help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in 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

2013-08-28

245

Modeling brain adaptation to focal damage.  

PubMed Central

Determining how feature maps in the cerebral cortex adapt to sudden, focal damage is important for gaining a deeper understanding of neurological illnesses such as stroke. In this paper we describe a neural model of the region of primary sensory cortex related to upper extremity proprioception, and show how the feature map there reorganizes following a simulated lesion. A perilesion zone with decreased activity appears and then gradually expands with time. These results differ from those seen with previous models of cortical lesions, and offer an alternative mechanism to the "ischemic penumbra" seen in certain types of stroke.

Goodall, S.; Reggia, J. A.; Cho, S.

1994-01-01

246

The effect of a peptide-modified thermo-reversible methylcellulose on wound healing and LV function in a chronic myocardial infarction rodent model.  

PubMed

Myocardial infarction is the main contributor to heart failure. In this study we examined whether modification of a thermo-reversible cellulose-based polymer with extracellular-matrix derived functional groups could promote wound healing and improve cardiac function in a chronic rodent model of ischemic cardiomyopathy. To beneficially influence the microenvironment of the injured myocardium, we conjugated either the RGD peptide or the HepIII peptide to the polymer. In vitro cell adhesion studies showed that the peptide-modified polymer promoted cell attachment to the polymer surface. Injection of the thermo-reversible polymer into the aneurismal infarct region of the left ventricle showed that the peptide-modified polymer exhibited significantly improved left ventricular function, increased angiogenesis, decreased infarct size, and an increase in cardiomyocytes within the infarct region at 5 weeks post-treatment (P < 0.05). The results of this study demonstrate that a peptide-modified thermo-reversible polymer has the capability to alter left ventricular (LV) geometry, increase LV function, and promote myocardial regeneration in a chronic model of ischemic cardiomyopathy. PMID:23895998

Mihardja, Shirley S; Gonzales, Jose A; Gao, Dongwei; Sievers, Richard E; Fang, Qizhi; Stillson, Carol A; Yu, Jiashing; Peng, Michelle; Lee, Randall J

2013-07-26

247

Plasma Brain Natriuretic Peptide (BNP) as an Indicator of Left Ventricular Function, Early Outcome and Mechanical Complications after Acute Myocardial Infarction  

PubMed Central

Aims: This study investigated the prognostic value of B type natriuretic peptide (BNP) in acute myocardial infarction (AMI) patients and its relation with left ventricular function and post-myocardial infarction complications. Methods: In this cross-sectional study, plasma BNP level was measured for 42 consecutive patients (mean ± SD: 61.6 ± 10.85 years old) with acute ST elevation myocardial infarction (MI) and 42 healthy, age and gender matched subjects. Result: BNP level in AMI patients were significantly higher than control group (P < 0.001). Regarding to infarct location, the highest BNP level measured in inferoposterior MI (BNP = 4436.63 ± 6188.159 pg/ml) and the lowest one indicated in standalone inferior MI (BNP = 598.83 ± 309.867 pg/ml (P = 0.071). There was significant reverse relation between BNP and EF (P = 0.006, OR = ?0.47) and a significant relationship between BNP and killip classification (P = 0.036). There was no significant relation between diastolic and right-ventricular function and BNP level (P = 0.61, P = 0.21). The highest BNP level was detected in LV septal rupture and false aneurysm (P = 0.02) and in ventricular tachycardia, but without significant relationship (P = 0.25). Conclusion: After the onset of AMI, BNP blood level can be used as an important predictor for left ventricular dysfunction, killip classification, early mechanical complications and cardiac death.

Fazlinezhad, A.; Rezaeian, M. Khadem; Yousefzadeh, H.; Ghaffarzadegan, K.; Khajedaluee, M.

2011-01-01

248

Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model  

PubMed Central

Cerebral small vessel disease (CSVD, cerebral microangiopathy) leads to dementia and stroke-like symptoms. Lacunes, white matter lesions (WML) and microbleeds are the main pathological correlates depicted in in-vivo imaging diagnostics. Early studies described segmental arterial wall disorganizations of small penetrating cerebral arteries as the most pronounced underlying histopathology of lacunes. Luminal narrowing caused by arteriolosclerosis was supposed to result in hypoperfusion with WML and infarcts. We have used the model of spontaneously hypertensive stroke-prone rats (SHRSP) for a longitudinal study to elucidate early histological changes in small cerebral vessels. We suggest that endothelial injuries lead to multiple sites with blood brain barrier (BBB) leakage which cause an ongoing damage of the vessel wall and finally resulting in vessel ruptures and microbleeds. These microbleeds together with reactive small vessel occlusions induce overt cystic infarcts of the surrounding parenchyma. Thus, multiple endothelial leakage sites seem to be the starting point of cerebral microangiopathy. The vascular system reacts with an activated coagulatory state to these early endothelial injuries and by this induces the formation of stases, accumulations of erythrocytes, which represent the earliest detectable histological peculiarity of small vessel disease in SHRSP. In this review we focus on the meaning of the BBB breakdown in CSVD and finally discuss possible consequences for clinicians.

2013-01-01

249

COG1410, a novel apolipoprotein-E mimetic, improves functional and morphological recovery in a rat model of focal brain ischemia.  

PubMed

Apolipoprotein E (apoE) is the primary apolipoprotein synthesized in the brain in response to injury with known neuroprotective effects exerted through antioxidant, antiinflammatory, antiexcitotoxic, and neurotrophic mechanisms. We have previously demonstrated that COG1410, an apoE mimetic peptide, exerts neuroprotective and antiinflammatory effects in a murine model of traumatic brain injury (TBI). As in TBI, ischemia-reperfusion injury is a component of acute stroke, which displays a pharmacogenetic association with the APOE4 gene. Using an intraluminal middle cerebral occlusion (MCAO) model in rats, we found that a single intravenous injection of COG1410 at 120 min post-MCAO significantly improved vestibulomotor function, decreased poststroke locomotor asymmetry, and decreased infarct volume of the ipsilateral hemisphere. These results support further exploration of a novel apoE-mimetic peptide, COG1410, as a therapeutic treatment for stroke. PMID:18803296

Tukhovskaya, Elena A; Yukin, Alexey Yu; Khokhlova, Oksana N; Murashev, Arkady N; Vitek, Michael P

2009-02-15

250

Dynamic Bayesian network modeling for longitudinal brain morphometry.  

PubMed

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

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

2011-09-22

251

Self-Organized Criticality Model for Brain Plasticity  

NASA Astrophysics Data System (ADS)

Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Here we present a model that is based on self-organized criticality and takes into account brain plasticity, which is able to reproduce the spectrum of electroencephalograms (EEG). The model consists of an electrical network with threshold firing and activity-dependent synapse strengths. The system exhibits an avalanche activity in a power-law distribution. The analysis of the power spectra of the electrical signal reproduces very robustly the power-law behavior with the exponent 0.8, experimentally measured in EEG spectra. The same value of the exponent is found on small-world lattices and for leaky neurons, indicating that universality holds for a wide class of brain models.

de Arcangelis, Lucilla; Perrone-Capano, Carla; Herrmann, Hans J.

2006-01-01

252

S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke.  

PubMed

Preservation of endothelial functions with low-dose nitric oxide (NO) and inhibition of excessive production of NO from inducible NO synthase (iNOS) is a potential therapeutic approach for acute stroke. Based on this hypothesis, an NO modulator, S-nitrosoglutathione (GSNO) was used, which provided neuroprotection in a rat model of focal cerebral ischemia. Administration of GSNO after the onset of ischemia reduced infarction and improved cerebral blood flow. To understand the mechanism of protection, the involvement of inflammation in ischemic brain injury was examined. Treatment with GSNO reduced the expression of tumor necrosis factor-alpha, interleukin-1beta, and iNOS; inhibited the activation of microglia/macrophage (ED1, CD11-b); and downregulated the expression of leukocyte function-associated antigen-1 and intercellular adhesion molecule-1 in the ischemic brain. The number of apoptotic cells (including neurons) and the activity of caspase-3 were also decreased after GSNO treatment. Further, the antiinflammatory effect of GSNO on expression of iNOS and activation of NF-kappaB machinery in rat primary astrocytes and in the murine microglial cell line BV2 was tested. Cytokine-mediated expression of iNOS and activation of NF-kappaB were inhibited by GSNO treatment. That GSNO protects the brain against ischemia/reperfusion injury by modulating NO systems, resulting in a reduction in inflammation and neuronal cell death was documented by the results. PMID:15647746

Khan, Mushfiquddin; Sekhon, Bipanjeet; Giri, Shailendra; Jatana, Manu; Gilg, Anne G; Ayasolla, Kamesh; Elango, Chinnasamy; Singh, Avtar K; Singh, Inderjit

2005-02-01

253

Constitutive modelling of brain tissue: experiment and theory.  

PubMed

Recent developments in computer-integrated and robot-aided surgery--in particular, the emergence of automatic surgical tools and robots--as well as advances in virtual reality techniques, call for closer examination of the mechanical properties of very soft tissues (such as brain, liver, kidney, etc.). The ultimate goal of our research into the biomechanics of these tissues is the development of corresponding, realistic mathematical models. This paper contains experimental results of in vitro, uniaxial, unconfined compression of swine brain tissue and discusses a single-phase, non-linear, viscoelastic tissue model. The experimental results obtained for three loading velocities, ranging over five orders of magnitude, are presented. The applied strain rates have been much lower than those applied in previous studies, focused on injury modelling. The stress-strain curves are concave upward for all compression rates containing no linear portion from which a meaningful elastic modulus might be determined. The tissue response stiffened as the loading speed increased, indicating a strong stress-strain rate dependence. The use of the single-phase model is recommended for applications in registration, surgical operation planning and training systems as well as a control system of an image-guided surgical robot. The material constants for the brain tissue are evaluated. Agreement between the proposed theoretical model and experiment is good for compression levels reaching 30% and for loading velocities varying over five orders of magnitude. PMID:9456379

Miller, K; Chinzei, K

254

A Simple Prognostic Classification Model for Postprocedural Complications After Percutaneous Coronary Intervention for Acute Myocardial Infarction (from the New York State Percutaneous Coronary Intervention Database)  

Microsoft Academic Search

Previous postprocedural complications risk scores have shown very good performance. However, the need for real-time risk score computation makes their implementation in an emergency situation challenging. Therefore, we developed an easy-to-use prognostic clas- sification model for postprocedural complications after early percutaneous coronary inter- vention for acute myocardial infarction. The model was developed on the New York State percutaneous coronary intervention

Abdissa Negassa; E. Scott Monrad; Vankeepuram S. Srinivas

2009-01-01

255

Restoring Blood-Brain Barrier P-Glycoprotein Reduces Brain Amyloid-? in a Mouse Model of Alzheimer's DiseaseS?  

PubMed Central

Reduced clearance of amyloid-? (A?) from brain partly underlies increased A? brain accumulation in Alzheimer's disease (AD). The mechanistic basis for this pathology is unknown, but recent evidence suggests a neurovascular component in AD etiology. We show here that the ATP-driven pump, P-glycoprotein, specifically mediates efflux transport of A? from mouse brain capillaries into the vascular space, thus identifying a critical component of the A? brain efflux mechanism. We demonstrate in a transgenic mouse model of AD [human amyloid precursor protein (hAPP)-overexpressing mice; Tg2576 strain] that brain capillary P-glycoprotein expression and transport activity are substantially reduced compared with wild-type control mice, suggesting a mechanism by which A? accumulates in the brain in AD. It is noteworthy that dosing 12-week-old, asymptomatic hAPP mice over 7 days with pregnenolone-16?-carbonitrile to activate the nuclear receptor pregnane X receptor restores P-glycoprotein expression and transport activity in brain capillaries and significantly reduces brain A? levels compared with untreated control mice. Thus, targeting intracellular signals that up-regulate blood-brain barrier P-glycoprotein in the early stages of AD has the potential to increase A? clearance from the brain and reduce A? brain accumulation. This mechanism suggests a new therapeutic strategy in AD.

Hartz, Anika M. S.; Miller, David S.

2010-01-01

256

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.

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

2012-01-01

257

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice  

PubMed Central

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2. Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4. The resulting hematomas and lacerations cause a vascular response 3,5, and the morphological and functional damage of the white matter leads to diffuse axonal injury 6-8. Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure 9. Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals 10-12, which ultimately result in long-term neurological disabilities 13,14. Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1. The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15. Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17. The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull 18. Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury 19. It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation 20. We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP.

Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P.; Thakker-Varia, Smita

2011-01-01

258

Lateral fluid percussion: model of traumatic brain injury in mice.  

PubMed

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull (18). Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury (19). It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation (20). We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP. PMID:21876530

Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P; Thakker-Varia, Smita

2011-08-22

259

Modelling blood flow and metabolism in the piglet brain during hypoxia-ischaemia: simulating brain energetics.  

PubMed

We have developed a computational model to simulate hypoxia-ischaemia (HI) in the neonatal piglet brain. It has been extended from a previous model by adding the simulation of carotid artery occlusion and including pH changes in the cytoplasm. Here, simulations from the model are compared with near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy (MRS) measurements from two piglets during HI and short-term recovery. One of these piglets showed incomplete recovery after HI, and this is modelled by considering some of the cells to be dead. This is consistent with the results from MRS and the redox state of cytochrome-c-oxidase as measured by NIRS. However, the simulations do not match the NIRS haemoglobin measurements. The model therefore predicts that further physiological changes must also be taking place if the hypothesis of dead cells is correct. PMID:23852513

Moroz, Tracy; Hapuarachchi, Tharindi; Bainbridge, Alan; Price, David; Cady, Ernest; Baer, Ether; Tachtsidis, Ilias; Broad, Kevin; Ezzati, Mojgan; Robertson, Nicola J; Thomas, David; Golay, Xavier; Cooper, Chris E

2013-01-01

260

A Category Theory Model for Learning and Memory of the Human Brain  

Microsoft Academic Search

Learning and memory, which are important functions of the human brain, are the foundations of thinking. Revealing the learning and memory mechanism of human brain is the core objective and main development way of the intelligent science. Improved human brain functional structure model, a memory prediction structural framework on the brain structure and function are proposed. And then we work

Pan Hong-jun; Yao Xiao-qiu; Qi Chang-song; Chen Hong-tao

2010-01-01

261

Increased mitochondrial DNA deletion in the brain of SAMP8, a mouse model for spontaneous oxidative stress brain  

Microsoft Academic Search

Oxidative stress is considered to be closely correlated with degenerative brain abnormalities. In this study, the plausibility of a SAMP8 strain mouse showing memory deterioration and short life span as an oxidative stress brain model was evaluated. Mitochondrial DNA deletions were detected using polymerase chain reaction (PCR) as cumulative spontaneous oxidative stress. In the 4–8-week-old SAMP8 brain, multiple mitochondrial DNA

Yasuhisa Fujibayashi; Shoko Yamamoto; Atsuo Waki; Junji Konishi; Yoshiharu Yonekura

1998-01-01

262

Violent traumatic brain injury: Occurrence, patient characteristics, and risk factors from the traumatic brain injury model systems project  

Microsoft Academic Search

Hanks RA, Wood DL, Millis S, Harrison-Felix C, Pierce CA, Rosenthal M, Bushnik T, High WM Jr, Kreutzer J. Violent traumatic brain injury: occurrence, patient characteristics, and risk factors from the Traumatic Brain Injury Model Systems project. Arch Phys Med Rehabil 2003;84:249-54. Objectives: To examine the occurrence of and characteristics associated with violent traumatic brain injury (TBI) in the Traumatic

Robin A. Hanks; Deborah L. Wood; Scott Millis; Cynthia Harrison-Felix; Christopher A. Pierce; Mitchell Rosenthal; Tamara Bushnik; Walter M. High; Jeffrey Kreutzer

2003-01-01

263

Normal brain ageing: models and mechanisms  

PubMed Central

Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria–reactive oxygen species (ROS)–intracellular Ca2+. The perturbation in the relationship between the members of this metabolic triad generate a state of decreased homeostatic reserve, in which the aged neurons could maintain adequate function during normal activity, as demonstrated by the fact that normal ageing is not associated with widespread neuronal loss, but become increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischaemia or neurodegenerative processes. This review will concentrate on some of the evidence showing altered mitochondrial function with ageing and also discuss some of the functional consequences that would result from such events, such as alterations in mitochondrial Ca2+ homeostasis, ATP production and generation of ROS.

Toescu, Emil C

2005-01-01

264

Neuronal regeneration in a zebrafish model of adult brain injury.  

PubMed

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

Kishimoto, Norihito; Shimizu, Kohei; Sawamoto, Kazunobu

2011-10-25

265

Prevention of Adverse Electrical and Mechanical Remodeling with Bi-Ventricular Pacing in a Rabbit Model of Myocardial Infarction  

PubMed Central

Background: Biventricular (BIV) pacing can improve cardiac function in heart failure (HF). Objective: To investigate the mechanisms of benefit of BIV pacing using a rabbit model of myocardial infarction (MI). Methods: New Zealand White rabbits were divided into 4 groups: sham-operated (C), MI with no pacing (MI), MI with right ventricular pacing (MI+RV), and MI with BIV pacing (MI+BIV), and underwent serial electrocardiograms and echocardiograms. At 4 weeks, hearts were excised and tissue was extracted from various areas of the left ventricle (LV). Results: Four weeks after coronary ligation, BIV pacing prevented systolic and diastolic dilation of the LV as well as the reduction in its fractional shortening, restored the QRS width and the rate-dependent QT intervals to their baseline values, and prevented the decline of the ether-a-go-go (erg) protein levels. This prevention of remodeling was not documented in the MI+RV groups. Conclusions: In this rabbit model of BIV pacing and MI, we demonstrate prevention of adverse mechanical and electrical remodeling of the heart. These changes may underlie some of the benefits seen with BIV pacing in HF patients with more severe LV dysfunction.

Saba, Samir; Mathier, Michael A.; Mehdi, Haider; Gursoy, Erdal; Liu, Tong; Choi, Bum-Rak; Salama, Guy; London, Barry

2008-01-01

266

A therapist experiential model of treatment for brain injury.  

PubMed

The Therapist Experiential Model of Treatment (TEMT) captures the commonality of clinical reactions and challenges that therapists encounter when treating patients with acquired brain injury and their support networks in outpatient multidisciplinary treatment settings. A three-tier coping paradigm depicts therapists' fluctuating demeanor, adjustment, and overall outlook. Patient, system, and internal variables facilitate or impede professional efficacy and growth. The TEMT is an effective mentalizing tool, catalyzing self-exploration of countertransference, burnout, and fractionalized working alliances. PMID:21500958

Klonoff, Pamela S

2011-03-01

267

Towards dynamical system models of language-related brain potentials  

Microsoft Academic Search

Event-related brain potentials (ERP) are important neural correlates of cognitive processes. In the domain of language processing,\\u000a the N400 and P600 reflect lexical-semantic integration and syntactic processing problems, respectively. We suggest an interpretation\\u000a of these markers in terms of dynamical system theory and present two nonlinear dynamical models for syntactic computations\\u000a where different processing strategies correspond to functionally different regions

Peter beim Graben; Sabrina Gerth; Shravan Vasishth

2008-01-01

268

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

269

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

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

2007-01-01

270

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.

Gerth, Sabrina; Vasishth, Shravan

2008-01-01

271

A mathematical model for self-limiting brain tumors  

Microsoft Academic Search

It is puzzling that certain brain tumors exhibit arrested exponential growth. We have observed in pediatric low-grade astrocytomas (LGA) at a certain volume ?100–150cm3 that the tumor ceases to grow. This observation led us to develop a macroscopic mathematical model for LGA growth kinetics that assumes the flow through the surface of the astrocytoma of a triggering agent or “promoter”

William I. Newman; Jorge A. Lazareff

2003-01-01

272

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

273

[Surgical decompression for massive cerebellar infarction].  

PubMed

The authors report 10 patients with progressive neurological deterioration due to massive cerebellar infarctions. Computerized tomography scans confirmed obstructive hydrocephalus and brain stem compression. All 10 patients (seven men, three women; mean age, 59 years) were treated by external ventricular drainage and decompressive suboccipital craniectomy. After discharge from the hospital, they were followed up (23-101 months) and their functional independence was evaluated by the Barthel Index. The condition of three patients with brain-stem infarction had deteriorated despite decompressive surgery. Two of these died during the acute stage and one because severely disabled. The remaining seven patients showed neurological improvement during the postoperative period. Four patients with preoperative Japan Coma Scale of 100 returned to their previous jobs within the follow-up period and three patients with preoperative Japan Coma Scale of 200 required some assistance in daily activities. It is suggested that decompressive surgery may be beneficial for massive cerebellar infarction. The postoperative prognosis depends mainly on the presence or absence of coexisting brain-stem infarction. It is possible that, without brain-stem infarction, patients who remained in a "dependent" state may have recovered better if they had been operated on earlier. PMID:7845519

Ogasawara, K; Koshu, K; Nagamine, Y; Fujiwara, S; Mizoi, K; Yoshimoto, T

1995-01-01

274

Fluid-percussion-induced traumatic brain injury model in rats  

PubMed Central

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

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

2013-01-01

275

Modeling glucose uptake in the brain for positron emission tomography  

SciTech Connect

A simulation study of transport and utilization of glucose in brain tissue is presented in relation to the sue of Positron Emission Tomography (PET) with healthy and diseased subjects. A physiologically-based, comprehensive compartmental model including recirculation and peripheral distribution of labeled glucose is developed, and the system of equations solved numerically for various sets of values of the rate constants: k{sub 1}, k{sub 2} and k{sub 3}. Comparison between experimental curves and curves simulated with the model suggests that a decrease in k{sub 3} may be the main reason for the impaired uptake of glucose in subjects with Alzheimer's disease. Simulated experimental data generated by the comprehensive model were fitted by nonlinear regression to a two-compartment model with a step-infusion input. The fitted rate constants k{sub 1} and k{sub 2} were shown to be 30 to 50% different from the theoretical ones, whereas their ratio remained essentially invariant. On the other hand, k{sub 3} values showed departures in the range of 5 to 20%. It is concluded that the application of the constant infusion model to PET may allow obtaining useful information with respect to the steps of brain glucose uptake in health and disease. Correct estimation of absolute values of the transport constants k{sub 1} and k{sub 2}, however, may require the use of a distributed model and short time, one pass experiments.

Massaldi, H.A.; Roman, F. (Univ. de Buenos Aires (Argentina))

1990-02-26

276

Paeonol reduced cerebral infarction involving the superoxide anion and microglia activation in ischemia-reperfusion injured rats.  

PubMed

Both Moutan cortex of Paeonia suffruticosa Andrews (MC) and the root of Paeonia lactiflora Pall (PL) are important Traditional Chinese herbs used commonly to treat inflammatory and pyretic disorders. Paeonol, a common component of MC causes anti-platelet aggregation and scavenges free radicals. Therefore, the aim of the present study is to investigate the effects of Paeonol on cerebral infarct. A total of 60 male Sprague-Dawley (SD) rats were studied. An animal model of cerebral infarct was established by occluding both common carotid arteries and the right middle cerebral artery for 90 min, followed by a 24 h period of reperfusion. The percentage of cerebral infarction area to total brain area in each piece of brain tissue, and neuro-deficit score were measured. Superoxide anion was determined by the number of lucigenin-chemiluminescence (CL) counts. ED1 (mouse anti rat CD68) and interleukin-1beta (IL-1beta) immunostaining in the cerebral infarction region were also investigated for activation of microglia. The results indicated that Paeonol 15 and 20 mg/kg pretreatment and 20 mg posttreatment reduced the cerebral infarction area; Paeonol 15 and 20 mg/kg pretreatment reduced the neuro-deficit score. In addition, Paeonol 20 mg/kg pretreatment reduced the lucigenin-CL counts at 2 h period of reperfusion. The number of ED1 and IL-1beta immunoreactive cells also reduced in the cerebral infarction region; there were no significant changes in blood sugar levels. The results show that Paeonol reduced cerebral infarct and neuro-deficit in rat, suggesting Paeonol might play a similar role in reducing cerebral infarction in humans. Paeonol suppresses and scavenges superoxide anion, and inhibit microglia activation and IL-1beta in ischemia-reperfusion injured rats. PMID:16458462

Hsieh, Ching-Liang; Cheng, Chin-Yi; Tsai, Tung-Hu; Lin, I-hsin; Liu, Chung-Hsiang; Chiang, Su-Yin; Lin, Jaung-Geng; Lao, Chih-Jui; Tang, Nou-Ying

2006-02-03

277

Usefulness of MRI to Differentiate Between Temporary and Long-Term Coronary Artery Occlusion in a Minimally Invasive Model of Experimental Myocardial Infarction  

Microsoft Academic Search

The surgical technique employed to determine an experimental ischemic damage is a major factor in the subsequent process of\\u000a myocardial scar development. We set out to establish a minimally invasive porcine model of myocardial infarction using cardiac\\u000a contrast-enhanced magnetic resonance imaging (ce-MRI) as the basic diagnostic tool. Twenty-seven domestic pigs were randomized\\u000a to either temporary or permanent occlusion of the

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

2009-01-01

278

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

279

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.

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

280

In Vivo Diagnostic Imaging Using Micro-CT: Sequential and Comparative Evaluation of Rodent Models for Hepatic/Brain Ischemia and Stroke  

PubMed Central

Background There is an increasing need for animal disease models for pathophysiological research and efficient drug screening. However, one of the technical barriers to the effective use of the models is the difficulty of non-invasive and sequential monitoring of the same animals. Micro-CT is a powerful tool for serial diagnostic imaging of animal models. However, soft tissue contrast resolution, particularly in the brain, is insufficient for detailed analysis, unlike the current applications of CT in the clinical arena. We address the soft tissue contrast resolution issue in this report. Methodology We performed contrast-enhanced CT (CECT) on mouse models of experimental cerebral infarction and hepatic ischemia. Pathological changes in each lesion were quantified for two weeks by measuring the lesion volume or the ratio of high attenuation area (%HAA), indicative of increased vascular permeability. We also compared brain images of stroke rats and ischemic mice acquired with micro-CT to those acquired with 11.7-T micro-MRI. Histopathological analysis was performed to confirm the diagnosis by CECT. Principal Findings In the models of cerebral infarction, vascular permeability was increased from three days through one week after surgical initiation, which was also confirmed by Evans blue dye leakage. Measurement of volume and %HAA of the liver lesions demonstrated differences in the recovery process between mice with distinct genetic backgrounds. Comparison of CT and MR images acquired from the same stroke rats or ischemic mice indicated that accuracy of volumetric measurement, as well as spatial and contrast resolutions of CT images, was comparable to that obtained with MRI. The imaging results were also consistent with the histological data. Conclusions This study demonstrates that the CECT scanning method is useful in rodents for both quantitative and qualitative evaluations of pathologic lesions in tissues/organs including the brain, and is also suitable for longitudinal observation of the same animals.

Hayasaka, Naoto; Nagai, Nobuo; Kawao, Naoyuki; Niwa, Atsuko; Yoshioka, Yoshichika; Mori, Yuki; Shigeta, Hiroshi; Kashiwagi, Nobuo; Miyazawa, Masaaki; Satou, Takao; Higashino, Hideaki; Matsuo, Osamu; Murakami, Takamichi

2012-01-01

281

SyM-BBB: a microfluidic Blood Brain Barrier model.  

PubMed

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

2013-03-21

282

Drosophila melanogaster as a Model Organism of Brain Diseases  

PubMed Central

Drosophila melanogaster has been utilized to model human brain diseases. In most of these invertebrate transgenic models, some aspects of human disease are reproduced. Although investigation of rodent models has been of significant impact, invertebrate models offer a wide variety of experimental tools that can potentially address some of the outstanding questions underlying neurological disease. This review considers what has been gleaned from invertebrate models of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, metabolic diseases such as Leigh disease, Niemann-Pick disease and ceroid lipofuscinoses, tumor syndromes such as neurofibromatosis and tuberous sclerosis, epilepsy as well as CNS injury. It is to be expected that genetic tools in Drosophila will reveal new pathways and interactions, which hopefully will result in molecular based therapy approaches.

Jeibmann, Astrid; Paulus, Werner

2009-01-01

283

Predicting brain injury under impact with a strain measure from analytical models  

Microsoft Academic Search

Caused by strain deformation in brain tissue, diffuse axonal injury (DAI) is one of the most devastating types of traumatic brain injury; it frequently occurs in automobile crashes. Although offering detailed anatomical structures, finite-element human head models require complete knowledge of material properties of the head and need high computational capacity. Similar to a brain injury model developed in the

H. Zou; J. P. Schmiedeler

2008-01-01

284

Biothermal Model of Patient for Brain Hypothermia Treatment  

NASA Astrophysics Data System (ADS)

A biothermal model of patient is proposed and verified for the brain hypothermia treatment, since the conventionally applied biothermal models are inappropriate for their unprecedented application. The model is constructed on the basis of the clinical practice of the pertinent therapy and characterized by the mathematical relation with variable ambient temperatures, in consideration of the clinical treatments such as the vital cardiopulmonary regulation. It has geometrically clear representation of multi-segmental core-shell structure, database of physiological and physical parameters with a systemic state equation setting the initial temperature of each compartment. Its step response gives the time constant about 3 hours in agreement with clinical knowledge. As for the essential property of the model, the dynamic temperature of its face-core compartment is realized, which corresponds to the tympanic membrane temperature measured under the practical anesthesia. From the various simulations consistent with the phenomena of clinical practice, it is concluded that the proposed model is appropriate for the theoretical analysis and clinical application to the brain hypothermia treatment.

Wakamatsu, Hidetoshi; Gaohua, Lu

285

Transient ischemic attack with infarction: A unique syndrome?  

Microsoft Academic Search

It is debated whether transient symptoms associated with infarction (TSI) are best considered a minor ischemic stroke, a subtype of transient ischemic attack (TIA), or a separate ischemic brain syndrome. We studied clinical and imaging features to establish similarities and differences among ischemic stroke, TIA without infarction, and TSI. 87 consecutive patients with TIA and 74 patients with ischemic stroke were studied.

Hakan Ay; Walter J. Koroshetz; Thomas Benner; Mark G. Vangel; Ona Wu; Lee H. Schwamm; A. Gregory Sorensen

2006-01-01

286

Optimization in Brain? - Modeling Human Behavior and Brain Activation Patterns with Queuing Network and Reinforcement Learning Algorithms  

Microsoft Academic Search

\\u000a Here we present a novel approach to model brain and behavioral phenomena of multitask performance, which integrates queuing\\u000a networks with reinforcement learning algorithms. Using the queuing network as the static platform of brain structure and reinforcement\\u000a learning as the dynamic algorithm to quantify the learning process, this model successfully accounts for several behavioral\\u000a phenomena related to the learning process of

Changxu Wu; Marc Berman; Yili Liu

287

From synthetic modeling of social interaction to dynamic theories of brain-body-environment-body-brain systems.  

PubMed

Synthetic approaches to social interaction support the development of a second-person neuroscience. Agent-based models and psychological experiments can be related in a mutually informing manner. Models have the advantage of making the nonlinear brain-body-environment-body-brain system as a whole accessible to analysis by dynamical systems theory. We highlight some general principles of how social interaction can partially constitute an individual's behavior. PMID:23883749

Froese, Tom; Iizuka, Hiroyuki; Ikegami, Takashi

2013-08-01

288

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

289

Neural models that convince: Model hierarchies and other strategies to bridge the gap between behavior and the brain  

Microsoft Academic Search

Computational modeling of the brain holds great pro mise as a bridge from brain to behavior. To fulfill this promise, however, it is not enough for models to be 'biologically plausible': models must be structurally accurate. Here, we analyze wha t this entails for so-called psychobiological models, models that address behavior as well as bra in function in some detail.

Martijn Meeter; Janneke F. M. Jehee; Jaap M. J. Murre

2007-01-01

290

Automated variable selection methods for logistic regression produced unstable models for predicting acute myocardial infarction mortality  

Microsoft Academic Search

ObjectivesAutomated variable selection methods are frequently used to determine the independent predictors of an outcome. The objective of this study was to determine the reproducibility of logistic regression models developed using automated variable selection methods.

Peter C. Austin; Jack V. Tu

2004-01-01

291

Multispectral brain tumor segmentation based on histogram model adaptation  

NASA Astrophysics Data System (ADS)

Brain tumor segmentation and quantification from MR images is a challenging task. The boundary of a tumor and its volume are important parameters that can have direct impact on surgical treatment, radiation therapy, or on quantitative measurements of tumor regression rates. Although a wide range of different methods has already been proposed, a commonly accepted approach is not yet established. Today, the gold standard at many institutions still consists of a manual tumor outlining, which is potentially subjective, and a time consuming and tedious process. We propose a new method that allows for fast multispectral segmentation of brain tumors. An efficient initialization of the segmentation is obtained using a novel probabilistic intensity model, followed by an iterative refinement of the initial segmentation. A progressive region growing that combines probability and distance information provides a new, flexible tumor segmentation. In order to derive a robust model for brain tumors that can be easily applied to a new dataset, we retain information not on the anatomical, but on the global cross-subject intensity variability. Therefore, a set of multispectral histograms from different patient datasets is registered onto a reference histogram using global affine and non-rigid registration methods. The probability model is then generated from manual expert segmentations that are transferred to the histogram feature domain. A forward and backward transformation of a manual segmentation between histogram and image domain allows for a statistical analysis of the accuracy and robustness of the selected features. Experiments are carried out on patient datasets with different tumor shapes, sizes, locations, and internal texture.

Rexilius, Jan; Hahn, Horst K.; Klein, Jan; Lentschig, Markus G.; Peitgen, Heinz-Otto

2007-03-01

292

The musician's brain as a model of neuroplasticity.  

PubMed

Studies of experience-driven neuroplasticity at the behavioural, ensemble, cellular and molecular levels have shown that the structure and significance of the eliciting stimulus can determine the neural changes that result. Studying such effects in humans is difficult, but professional musicians represent an ideal model in which to investigate plastic changes in the human brain. There are two advantages to studying plasticity in musicians: the complexity of the eliciting stimulus music and the extent of their exposure to this stimulus. Here, we focus on the functional and anatomical differences that have been detected in musicians by modern neuroimaging methods. PMID:12042882

Münte, Thomas F; Altenmüller, Eckart; Jäncke, Lutz

2002-06-01

293

Representation of internal models of action in the autistic brain.  

PubMed

Children with autism spectrum disorder (ASD) have deficits in motor control, imitation and social function. Does a dysfunction in the neural basis of representing internal models of action contribute to these problems? We measured patterns of generalization as children learned to control a novel tool and found that the autistic brain built a stronger than normal association between self-generated motor commands and proprioceptive feedback; furthermore, the greater the reliance on proprioception, the greater the child's impairments in social function and imitation. PMID:19578379

Haswell, Courtney C; Izawa, Jun; Dowell, Lauren R; Mostofsky, Stewart H; Shadmehr, Reza

2009-07-05

294

Use of dapsone as a neuroprotector in cerebral infarction  

US Patent & Trademark Office Database

The use of dapsone is the first effective treatment against the disabling consequences associated with cerebral infarction in patients. Dapsone was evaluated as a neuroprotector in the cerebral infarction model produced by the occlusion of the middle cerebral artery in rats and in patients suffering from acute cerebral infarction caused by thromboembolism. In both studies, dapsone displayed a reduction of between 70 and 90% in the adverse effects which occur as a consequence of the infarction.

Rios Castaneda; Luis Camilo (Mexico City, MX); Altagracia Martinez; Marina (Mexico City, MX); Nader Kawachi; Juan (Mexico City, MX); Kravzov Jinich; Jaime (Mexico City, MX)

2012-09-18

295

A simulation model for analysing brain structure deformations  

NASA Astrophysics Data System (ADS)

Recent developments of medical software applications—from the simulation to the planning of surgical operations—have revealed the need for modelling human tissues and organs, not only from a geometric point of view but also from a physical one, i.e. soft tissues, rigid body, viscoelasticity, etc. This has given rise to the term 'deformable objects', which refers to objects with a morphology, a physical and a mechanical behaviour of their own and that reflects their natural properties. In this paper, we propose a model, based upon physical laws, suitable for the realistic manipulation of geometric reconstructions of volumetric data taken from MR and CT scans. In particular, a physically based model of the brain is presented that is able to simulate the evolution of different nature pathological intra-cranial phenomena such as haemorrhages, neoplasm, haematoma, etc and to describe the consequences that are caused by their volume expansions and the influences they have on the anatomical and neuro-functional structures of the brain.

Di Bona, Sergio; Lutzemberger, Ludovico; Salvetti, Ovidio

2003-12-01

296

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

Microsoft Academic Search

Differences in cognitive aging rates among mammals suggest that the pace of brain aging is genetically determined. In this work, we investigate the possibility that brain aging is an extension of brain development. It is possible that a subset of developmental mechanisms are extreme cases of antagonistic pleiotropy in that they are necessary for reaching adulthood and yet later cause

João Pedro de Magalhães; Anders Sandberg

2005-01-01

297

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

SciTech Connect

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

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

2007-04-15

298

Relationship between retrograde coronary blood flow and the extent of no-reflow and infarct size in a porcine ischemia-reperfusion model.  

PubMed

Recanalization of an infarct-related artery does not predictably reflect tissue reperfusion. We examined the relationship between coronary blood flow (CBF) pattern during reperfusion and infarcted (IA) and no-reflow (NR) area in a porcine ischemia-reperfusion model. The mid-left anterior descending artery of 18 pigs was occluded for 1 h and reperfused for 2 h. CBF during reperfusion was measured with a transit-time ultrasound flowmeter, while systemic arterial and left atrial pressures were monitored. IA and NR were measured with triphenyl tetrazolium chloride and thioflavin staining, respectively. In 13 pigs, early systolic retrograde CBF developed within the first 30 min and persisted throughout reperfusion. No retrograde CBF was observed in five pigs. Mean retrograde CBF at 2 h of reperfusion predicted a larger IA (r?=?0.71; p?=?0.001). Time-to-development of retrograde CBF was inversely related to IA (r?=?-0.55; p?=?0.019) and NR (r?=?-0.62; p?=?0.006). A larger IA (OR 1.12, 95% CI 1.01-1.24, p?=?0.037) and NR (OR 1.09, 95% CI 1.01-1.18, p?=?0.037) predicted the presence of retrograde CBF. Retrograde CBF during recanalization of the infarct-related artery predicts IA and NR and might be used as an index of successful reperfusion at the tissue level. PMID:21153063

Stavrakis, Stavros; Terrovitis, John; Tsolakis, Elias; Drakos, Stavros; Dalianis, Argirios; Bonios, Michael; Koudoumas, Dimitrios; Malliaras, Konstantinos; Nanas, John

2010-12-09

299

Long-Term Left Ventricular Remodelling in Rat Model of Nonreperfused Myocardial Infarction: Sequential MR Imaging Using a 3T Clinical Scanner  

PubMed Central

Purpose. To evaluate whether 3T clinical MRI with a small-animal coil and gradient-echo (GE) sequence could be used to characterize long-term left ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI) using semi-automatic segmentation software (SASS) in a rat model. Materials and Methods. 5 healthy rats were used to validate left ventricular mass (LVM) measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned at 2 and 4 weeks after surgery to allow for functional and structural analysis of the heart. Measurements included ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the heart were quantified using wall thickness analyses. Results. LVM validation in healthy rats demonstrated high correlation between MR and postmortem values. Functional assessment at 4 weeks after MI revealed considerable reduction in EF, increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE sequence generated images in a rat heart with adequate signal-to-noise ratio (SNR) for successful semiautomatic segmentation to accurately and rapidly evaluate long-term LVR after MI.

Saleh, Muhammad G.; Sharp, Sarah-Kate; Alhamud, Alkathafi; Spottiswoode, Bruce S.; van der Kouwe, Andre J. W.; Davies, Neil H.; Franz, Thomas; Meintjes, Ernesta M.

2012-01-01

300

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)

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

1994-01-01

301

X-Ray Fused With Magnetic Resonance Imaging (XFM) to Target Endomyocardial Injections: Validation in a Swine Model of Myocardial Infarction  

PubMed Central

Background Magnetic resonance imaging (MRI) permits 3-dimensional (3D) cardiac imaging with high soft tissue contrast. X-ray fluoroscopy provides high-resolution, 2-dimensional (2D) projection imaging. We have developed real-time x-ray fused with MRI (XFM) to guide invasive procedures that combines the best features of both imaging modalities. We tested the accuracy of XFM using external fiducial markers to guide endomyocardial cell injections in infarcted swine hearts. Methods and Results Endomyocardial injections of iron-labeled mesenchymal stromal cells admixed with tissue dye were performed in previously infarcted hearts of 12 Yucatan miniswine (weight, 33 to 67 kg). Features from cardiac MRI were displayed combined with x-ray in real time to guide injections. During 130 injections, operators were provided with 3D surfaces of endocardium, epicardium, myocardial wall thickness (range, 2.6 to 17.7 mm), and infarct registered with live x-ray images to facilitate device navigation and choice of injection location. XFM-guided injections were compared with postinjection MRI and with necropsy specimens obtained 24 hours later. Visual inspection of the pattern of dye staining on 2,3,5-triphenyltetrazolium chloride–stained heart slices agreed (?=0.69) with XFM-derived injection locations mapped onto delayed hyperenhancement MRI and the susceptibility artifacts seen on the postinjection T2*-weighted gradient echo MRI. The distance between the predicted and actual injection locations in vivo was 3.2±2.6 mm (n=64), and 75% of injections were within 4.1 mm of the predicted location. Conclusions Three-dimensional to two-dimensional registration of x-ray and MR images with the use of external fiducial markers accurately targets endomyocardial injection in a swine model of myocardial infarction.

de Silva, Ranil; Gutierrez, Luis F.; Raval, Amish N.; McVeigh, Elliot R.; Ozturk, Cengizhan; Lederman, Robert J.

2006-01-01

302

Induction of angiogenesis via topical delivery of basic-fibroblast growth factor from polyvinyl alcohol-dextran blend hydrogel in an ovine model of acute myocardial infarction.  

PubMed

Hydrogels are currently used as interesting constructs for the delivery of proteins. In this study, a novel polyvinyl alcohol-dextran (PVA-Dex) blend hydrogel was used for controlled delivery of basic-fibroblast growth factor (bFGF). These biocompatible constructs were sutured to the epicardium as patches on the heart surface to provide slow release of bFGF to the infarcted site in an ovine model of myocardial infarction (MI). Eighteen sheep were randomly divided into three groups (n = 6 each), including group I (control without any patch and bFGF), group II (patch without bFGF) and group III (patch incorporating 100 µg bFGF). They were subjected to coronary artery ligation after lateral thoracotomy, and then in groups II and III the patches were implanted 20-30 min after MI. Cardiac function was assessed by both echocardiography and magnetic resonance imaging (MRI) 2 months after implantation. Then the animals were sacrificed and the hearts subjected to histopathological examination, immunohistochemistry and electron microscopy. Heart lysates were subject to protein expression analysis through western blotting. The results showed that sustained release of bFGF using PVA-Dex blend hydrogel strongly stimulated angiogenesis and increased wall thickness index in the infarcted myocardium. The patch also significantly attenuated the increase in left ventricular end-systolic diameter, but it did not improve cardiac function within 2 months of myocardial infarction. In conclusion, PVA-Dex gel incorporating bFGF can be used as a sustained release construct for therapeutic angiogenesis in ischaemic heart disease. PMID:22674791

Fathi, Ezzatollah; Nassiri, Seyed Mahdi; Atyabi, Nahid; Ahmadi, Seyed Hossein; Imani, Mohammad; Farahzadi, Raheleh; Rabbani, Shahram; Akhlaghpour, Shahram; Sahebjam, Mohammad; Taheri, Mohammad

2012-06-04

303

Myocardial Infarction Research Unit.  

National Technical Information Service (NTIS)

The interdisciplinary program has been concerned with basic mechanisms involved in acute myocardial infarction in the experimental setting, and with the natural history and therapy of acute myocardial infarction in man. The laboratory program has devised ...

J. Ross

1975-01-01

304

Myocardial Infarction Research Unit.  

National Technical Information Service (NTIS)

Clinical and laboratory investigations are conducted to provide a better understanding and more effective treatment of myocardial infarction. Patients with acute myocardial infarction are carefully characterized by clinical, hemodynamic, electrophysiologi...

C. E. Rackley

1975-01-01

305

Myocardial Infarction Research Unit.  

National Technical Information Service (NTIS)

Five hundred patients have undergone hemodynamic evaluation in the Myocardial Infarction Research Unit. Over 200 of these studies have been carried out within the first 24 hours of infarction. The relation of hemodynamic parameters to patient survival has...

B. Pitt

1975-01-01

306

Effect of VEGF Receptor Antagonist (VGA1155) on Brain Edema in the Rat Cold Injury Model  

Microsoft Academic Search

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and a strong vascular permeability factor. Blockade of VEGF may have a potential to treat brain edema after brain injury. In the rat cold injury model, the VEGF receptor antagonist VGA1155 significantly reduced the brain water content and the maximum effect was obtained when given at 30 minutes after

JUNJI KOYAMA; SHIGERU MIYAKE; TAKASHI SASAYAMA; TAKESHI KONDOH; EIJI KOHMURA

2007-01-01

307

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

308

A mouse model of human repetitive mild traumatic brain injury.  

PubMed

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

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

2011-09-12

309

Macrophage Roles Following Myocardial Infarction  

PubMed Central

Following myocardial infarction (MI), circulating blood monocytes respond to chemotactic factors, migrate into the infarcted myocardium, and differentiate into macrophages. At the injury site, macrophages remove necrotic cardiac myocytes and apoptotic neutrophils; secrete cytokines, chemokines, and growth factors; and modulate phases of the angiogenic response. As such, the macrophage is a primary responder cell type that is involved in the regulation of post-MI wound healing at multiple levels. This review summarizes what is currently known about macrophage functions post-MI and borrows literature from other injury and inflammatory models to speculate on additional roles. Basic science and clinical avenues that remain to be explored are also discussed.

Lambert, Jessica M.; Lopez, Elizabeth F.; Lindsey, Merry L.

2010-01-01

310

The Low Molecular Weight Heparin Enoxaparin Reduces Infarct Size in a Rat Model of Temporary Focal Ischemia1  

Microsoft Academic Search

Low molecular weight heparins (LMWHs) have significantly reduced infarct size in animal studies but they have not been effective in clinical trials, probably because they were administered after ischemic injury had become irreversible. The present study was designed to explore the temporal characteristics of the LMWH enoxaparin with the objective of determining the duration of the treatment window in a

David Quartermain; Yong Sheng Li; Saran Jonas

2003-01-01

311

Transdifferentiating potential of the human peripheral blood mononuclear cell transplanted into myocardial infarction model of nude mouse  

Microsoft Academic Search

Adult human peripheral blood cells have been shown to differentiate into mature cells of nonhematopoietic tissues. We investigated whether these cells could also transdifferentiate into human cardiomyocytes,endothelial cells, and smooth muscle cells in vivo. Myocardial infarction was created in nude mice by ligating the left anterior descending coronary artery,after which adult peripheral blood cells were injected into the tail vein.

Zhang Zhi; Zhuge Ying; Zhu Yan-qi; Dai Qiu-yan; Sun Bao-gui

2005-01-01

312

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.

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

313

Amelioration of ischemic brain damage by peritoneal dialysis.  

PubMed

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, María Del Carmen; Romera, Victor G; Sánchez-Tomero, José Antonio; Pacheco, Jesus; Canals, Santiago; Lerma, Juan; Vivancos, José; Moro, María Angeles; Torres, Magdalena; Lizasoain, Ignacio; Sánchez-Prieto, José

2013-09-03

314

Model creation and deformation for the automatic segmentation of the brain in MR images  

Microsoft Academic Search

In this paper a method for the automatic segmentation of the brain in magnetic resonance images is presented and validated. The proposed method involves two steps: 1) the creation of an initial model, and 2) the deformation of this model to fit the exact contours of the brain in the images. A new method to create the initial model has

Georges B. Aboutanos; Jyrki Nikanne; Nancy Watkins; B. M. Dawan

1999-01-01

315

Multiple Monophasic Shocks Improve Electrotherapy of Ventricular Tachycardia in a Rabbit Model of Chronic Infarction  

PubMed Central

Background Previously, we showed that the cardioversion threshold (CVT) for ventricular tachycardia (VT) is phase-dependent, when a monophasic shock (1MP) is used. I Objective In this study, we aimed to extend these findings to a biphasic shock (1BP), and to compare efficacy of phase-independent multiple monophasic (5MP) and biphasic shocks (5BP). Methods Panoramic optical mapping with Blebbistatin (5 µM) was performed in post-MI rabbit hearts (n = 8). Flecainide (1.64 ± 0.68 µM) was administered to promote sustained arrhythmias. 5MP and 5BP were applied within one VT cycle length (CL). Results were compared to 1BP and antitachycardia pacing (ATP). Results We observed monomorphic VT with CL = 149.6 ± 18.0 ms. Similar to 1MP, CVTs of 1BP were found to be phase-dependent and the max vs. min CVT was 8.6 ± 1.7 vs. 3.7 ± 1.9 V/cm, respectively (p = 0.0013). Efficacy of 5MP was higher than 1BP and 5BP. CVT was 3.2 ± 1.4 vs. 5.3 ± 1.9 V/cm, for 5MP vs. 5BP, respectively (p = 0.00027). 5MP vs. averaged 1BP CVT was 3.6 ± 2.1 vs. 6.8 ± 1.5 V/cm, respectively (p = 0.00024). ATP was found completely ineffective in this model. Conclusions Maintenance of shock-induced virtual electrode polarization (VEP) by multiple monophasic shocks over a VT cycle is responsible for unpinning of reentry leading to self-termination. Elimination of VEP by shock polarity reversal during multiple biphasic shocks proved ineffective. A significant reduction in CVT may be achieved by applying multiple monophasic shocks within one VT CL or one single shock at the proper coupling interval.

Li, Wenwen; Ripplinger, Crystal M.; Lou, Qing; Efimov, Igor R.

2010-01-01

316

Pharmacokinetic Modeling of Non-Linear Brain Distribution of Fluvoxamine in the Rat  

PubMed Central

Introduction A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine. Materials and methods Rats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1, 3.7 or 7.3 mg.kg?1 of fluvoxamine. Analysis With increasing dose a disproportional increase in brain concentrations was observed. The kinetics of brain distribution was estimated by simultaneous analysis of plasma, free brain ECF and total brain tissue concentrations. The PK model consists of three compartments for fluvoxamine concentrations in plasma in combination with a catenary two compartment model for distribution into the brain. In this catenary model, the mass exchange between a shallow perfusion-limited and a deep brain compartment is described by a passive diffusion term and a saturable active efflux term. Results The model resulted in precise estimates of the parameters describing passive influx into (kin) of 0.16 min?1 and efflux from the shallow brain compartment (kout) of 0.019 min?1 and the fluvoxamine concentration at which 50% of the maximum active efflux (C50) is reached of 710 ng.ml?1. The proposed brain distribution model constitutes a basis for precise characterization of the PK–PD correlation of fluvoxamine by taking into account the non-linearity in brain distribution.

Geldof, Marian; Freijer, Jan; van Beijsterveldt, Ludy

2007-01-01

317

Inhibitory Control in Children with Frontal Infarcts Related to Sickle Cell Disease  

Microsoft Academic Search

Evidence from past studies indicates that children with traumatic brain injury experience difficulties with inhibitory control. Less is known about inhibitory control in children with frontal brain injury related to cerebral infarction. We compared the inhibitory performance of children with frontal infarcts related to sickle cell disease with that of a control group of children with sickle cell disease but

Shawn E. Christ; Asif Moinuddin; Robert C. McKinstry; Michael DeBaun; Desirée A. White

2007-01-01

318

Importance of Behavioral Manipulations and Measures in Rat Models of Brain Damage and Brain Repair  

Microsoft Academic Search

Abstract The relevance of careful behavioral measures and manipu- lations in animal research on neural plasticity and brain damage,has become,increasingly clear. Recent research in adult rats indicates that an understanding of neural restruc- turing after brain damage,requires an understanding of how it is influenced by postinjury behavioral experiences. Other research indicates that optimizing,pharmacological,and other treatments for brain damage,may,require their com-

Theresa A. Jones; Scott D. Bury; Deanna L. Adkins-muir; Linslee M. Luke; Rachel P. Allred; Jon T. Sakata

319

Modeling of a Segmented Electrode for Desynchronizing Deep Brain Stimulation  

PubMed Central

Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders like Parkinson’s disease. The electrodes, implanted in the target area within the human brain, generate an electric field which activates nerve fibers and cell bodies in the vicinity. Even though the different target nuclei display considerable differences in their anatomical structure, only few types of electrodes are currently commercially available. It is desirable to adjust the electric field and in particular the volume of tissue activated around the electrode with respect to the corresponding target nucleus in a such way that side effects can be reduced. Furthermore, a more selective and partial activation of the target structure is desirable for an optimal application of novel stimulation strategies, e.g., coordinated reset neuromodulation. Hence we designed a DBS electrode with a segmented design allowing a more selective activation of the target structure. We created a finite element model (FEM) of the electrode and analyzed the volume of tissue activated for this electrode design. The segmented electrode activated an area in a targeted manner, of which the dimension and position relative to the electrode could be controlled by adjusting the stimulation parameters for each electrode contact. According to our computational analysis, this directed stimulation might be superior with respect to the occurrence of side effects and it enables the application of coordinated reset neuromodulation under optimal conditions.

Buhlmann, J.; Hofmann, L.; Tass, P. A.; Hauptmann, C.

2011-01-01

320

A Model for Diffusion in White Matter in the Brain  

PubMed Central

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

Sen, Pabitra N.; Basser, Peter J.

2005-01-01

321

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

NASA Astrophysics Data System (ADS)

The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. While early results suggested a small decrease in o-Ps pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.

Quarles, C. A.; Ballmann, Charles; Yang, S. H.

2009-04-01

322

Brain–Machine Interfaces Based on Computational Model  

Microsoft Academic Search

\\u000a The research about brain computer interface or brain machine interface has been widely developed in this decade. Implant methods\\u000a are already used for eye or ear as retinal implant or cochlear implant, these devices stimulate peripheral nerve. In this\\u000a case, the stimulus site is peripheral and the information from each sensor is input signal of the brain. Brain Machine Interface

Yasuharu Koike; Hiroyuki Kambara; Natsue Yoshimura; Duk Shin

323

Quantitative comparison of thermal dose models in normal canine brain  

PubMed Central

Purpose: Minimally invasive thermal ablative therapies as alternatives to conventional surgical management of solid tumors and other pathologies is increasing owing to the potential benefits of performing these procedures in an outpatient setting with reduced complications and comorbidity. Magnetic resonance temperature imaging (MRTI) measurement allows existing thermal dose models to use the spatiotemporal temperature history to estimate the thermal damage to tissue. However, the various thermal dose models presented in the literature employ different parameters and thresholds, affecting the reliability of thermal dosimetry. In this study, the authors quantitatively compared three thermal dose models (Arrhenius rate process, CEM43, and threshold temperature) using the dice similarity coefficient (DSC). Methods: The DSC was used to compare the spatial overlap between the region of thermal damage as predicted by the models for in vivo normal canine brain during thermal therapy to the region of thermal damage as revealed by contrast-enhanced T1-weighted images acquired immediately after therapy (<20 min). The outer edge of the hyperintense rim of the ablation region was used as the surrogate marker for the limits of thermal coagulation. The DSC was also used to investigate the impact of varying the thresholds on each models’ ability to predict the zone of thermal necrosis. Results: At previously reported thresholds, the authors found that all three models showed good agreement (defined as DSC>0.7) with post-treatment imaging. All three models examined across the range of commonly applied thresholds consistently showed highly accurate spatial overlap, low variability, and little dependence on temperature uncertainty. DSC values corresponding to cited thresholds were not significantly different from peak DSC values. Conclusions: Thus, the authors conclude that the all three thermal dose models can be used as a reliable surrogate for postcontrast tissue damage verification imaging in rapid ablation procedures and can also be used to enhance the capability of MRTI to control thermal therapy in real time.

Yung, Joshua P.; Shetty, Anil; Elliott, Andrew; Weinberg, Jeffrey S.; McNichols, Roger J.; Gowda, Ashok; Hazle, John D.; Stafford, R. Jason

2010-01-01

324

[Cerebral infarction].  

PubMed

Diabetes mellitus is the second major risk factor for ischemic stroke. Recent increase in atherothrombotic stroke appears to be related with recent increasing of diabetes. Diabetes is, however, a risk factor not only for atherothrombotic stroke but also for lacunar stroke because there is no difference in prevalence of diabetes between atherothrombotic and lacunar strokes. Diabetes can be a risk factor for cardioembolic stroke as well because the major cause of cardioembolic stroke is atrial fibrillation, and diabetes is a risk factor for stroke in patients with atrial fibrillation. Acute ischemic stroke should be classified into above three subtypes according to the brain and artery imaging as well as cardiac sources of embolism. In hyper-acute patients within 3 hours of onset and without early ischemic signs on CT or ischemic lesions less than one third of the hemisphere on magnetic resonance diffusion-weighted imaging, thrombolytic therapy with alteplase is indicated. In acute stroke patients later than 3 hours of onset, argatroban, heparin, and ozagrel are indicated for atherothrombotic, cardioembolic, and lacunar stroke, respectively. For stroke prevention, total management is required by simultaneous treatments for all risk factors existed. In secondary prevention for stroke, in addition to the more strict control of risk factors antithrombotic therapy is required, that is, antiplatelet therapy is indicated for non-cardioembolic stroke, and anticoagulant therapy is indicated for cardioembolic stroke. PMID:17087294

Uchiyama, Shinichiro

2006-11-01

325

Mapping Metabolic Brain Activity in Three Models of Hepatic Encephalopathy  

PubMed Central

Cirrhosis is a common disease in Western countries. Liver failure, hyperammonemia, and portal hypertension are the main factors that contribute to human cirrhosis that frequently leads to a neuropsychiatric disorder known as hepatic encephalopathy (HE). In this study, we examined the differential contribution of these leading factors to the oxidative metabolism of diverse brain limbic system regions frequently involved in memory process by histochemical labelling of cytochrome oxidase (COx). We have analyzed cortical structures such as the infralimbic and prelimbic cotices, subcortical structures such as hippocampus and ventral striatum, at thalamic level like the anterodorsal, anteroventral, and mediodorsal thalamus, and, finally, the hypothalamus, where the mammillary nuclei (medial and lateral) were measured. The severest alteration is found in the model that mimics intoxication by ammonia, followed by the thioacetamide-treated group and the portal hypertension group. No changes were found at the mammillary bodies for any of the experimental groups.

Mendez, Marta; Fidalgo, Camino; Aller, Maria Angeles; Arias, Jaime; Arias, Jorge L.

2013-01-01

326

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

2012-05-03

327

The study of pre-processing method of brain vessel segmentation based on parameterized statistical model  

Microsoft Academic Search

For the 3D brain MRI parameterized statistical model segmentation method, the pre-processing method of brain image is brought forward for the model. First the DWM(directional weighted median) filter and Gaussian template are used to de-noise the brain MRI image. Then the Laplacian operator is used to sharpen the image, and the Robert operator is used to realize the edge detection,

Wang Xing-ce; Xu Feng; Leng Chang; Zhou Ming-quan; Wu Zhong-ke; Liu Xin-yu

2010-01-01

328

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

ERIC Educational Resources Information Center

|The brain is a truly fascinating structure! It controls the body and allows everyone to think, learn, speak, move, feel, remember, and experience emotions. Although the brain is a single organ, it is very complex and has several regions, each having a specific function. These functionally diverse regions work together to allow for coordination of…

Demetrikopoulos, Melissa K.; Pecore, John; Rose, Jordan D.; Fobbs, Archibald J., Jr.; Johnson, John I.; Carruth, Laura L.

2006-01-01

329

Transcending Right Brain/Left Brain Boundaries: The Teacher as Model.  

ERIC Educational Resources Information Center

|One of the deepest and most debilitating schisms in the university classroom, as in life, is that between the left and right sides of the brain, reason and emotion, the head and the heart. More and more college English teachers have become aware of the value of addressing the whole brain, the whole person. Teachers set up goals and communicate…

Bump, Jerome

330

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

ERIC Educational Resources Information Center

The brain is a truly fascinating structure! It controls the body and allows everyone to think, learn, speak, move, feel, remember, and experience emotions. Although the brain is a single organ, it is very complex and has several regions, each having a specific function. These functionally diverse regions work together to allow for coordination of…

Demetrikopoulos, Melissa K.; Pecore, John; Rose, Jordan D.; Fobbs, Archibald J., Jr.; Johnson, John I.; Carruth, Laura L.

2006-01-01

331

Enhanced Generation of Reactive Oxygen Species in the Limb Skeletal Muscles From a Murine Infarct Model of Heart Failure  

Microsoft Academic Search

Background—The generation of reactive oxygen species (ROS) is enhanced in the failing myocardium. We hypothesized that ROS were also increased in the limb skeletal muscles in heart failure. Methods and Results—Myocardial infarction (MI) was created in mice by ligating the left coronary artery. After 4 weeks, the left ventricle was dilated and contractility was diminished by echocardiography. Left ventricular end-diastolic

Hiroyuki Tsutsui; Tomomi Ide; Shunji Hayashidani; Nobuhiro Suematsu; Tetsuya Shiomi; Jing Wen; Kei-ichiro Nakamura; Kazuhiro Ichikawa; Hideo Utsumi; Akira Takeshita

332

Modelling of the human brain with detailed anatomy for numerical simulation of surgical interventions  

NASA Astrophysics Data System (ADS)

During the design and simulation process of MEMS medical devices used in neurosurgery, there is a need to build a brain model with detailed anatomy and physical properties incorporated as a platform to conduct numerical analysis. This paper presents a study on constructing a brain model for simulation of medical device interventions during neurosurgery. A brain atlas was utilized to develop a detailed model consisting of multiple structures. Two types of atlas model were generated employing different mesh types and biomechanical properties suited for various applications. The developed model was able to capture the detailed anatomy of the brain and reflect the application-dependant biomechanical behaviour based on material modelling of brain tissue under surgical intervention.

Gao, Chunping; Eng Hock Tay, Francis; Nowinski, Wieslaw L.

2006-04-01

333

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.

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

2013-01-01

334

Perinatal Hypoxic-Ischemic Brain Damage: Evolution of an Animal Model  

Microsoft Academic Search

Early research in the Vannucci laboratory prior to 1981 focused largely on brain energy metabolism in the developing rat. At that time, there was no experimental model to study the effects of perinatal hypoxia-ischemia in the rodent, despite the tremendous need to investigate the pathophysiology of perinatal asphyxial brain damage in infants. Accordingly, we developed such a model in the

Robert C. Vannucci; Susan J. Vannucci

2005-01-01

335

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.

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

336

Age Dependent Susceptibility to Infarct Growth in Women  

PubMed Central

Background It is not known if there is a relationship between gender and tissue outcome in human ischemic stroke. We sought to identify whether the proportion of initially ischemic to eventually infarcted tissue was different between men and women with ischemic stroke. Methods We studied 141 consecutive patients with acute ischemic stroke who had a baseline MRI obtained within 12 hours of symptom onset, a follow-up imaging on day 4 or later, and DWI/MTT mismatch on initial MRI. Lesion growth was calculated as percentage of mismatch tissue that underwent infarction on follow-up (Percentage Mismatch Lost or PML). Multivariable analyses explored the effect of gender and other predictors of tissue outcome on PML. Results There was no difference in median PML between men (19%) and women (11%) (p=0.720). There was, however, an interaction between gender and age; median PML was 7% (0–12%) in women and 18% (1–35%) in men younger than the population median (71 years, p=0.061). The PML was not different between men and women ?71 years old (25% in both groups). The linear regression model revealed gender (p=0.027) and the interaction between age and gender (p=0.023) as independent predictors of PML. Conclusion There is an age-by-gender interaction in tissue outcome after ischemic stroke; brain infarcts in women younger than 70 years grow approximately 50% less than infarcts in their male counterparts. These findings extend the well-known concept that there is a differential age-by-gender effect on stroke incidence, mortality, and functional outcome to the tissue level.

Gokcay, Figen; Arsava, Ethem Murat; Baykaner, Tuna; Vangel, Mark; Garg, Priya; Wu, Ona; Singhal, Aneesh B.; Furie, Karen L.; Sorensen, A. Gregory; Ay, Hakan

2011-01-01

337

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

PubMed Central

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

2012-01-01

338

Transient hypothermia reduces focal ischemic brain injury in the rat.  

PubMed

The effect of transient hypothermia on focal cerebral ischemia was evaluated using a rat model of permanent middle cerebral artery (MCA) occlusion. MCA occlusion was performed on 10 rats at a temporalis muscle temperature of 24 degrees C (hypothermic group) and on 10 rats at 36 degrees C (normothermic group). Rats in the hypothermic group were maintained at 24 degrees C for 1 hour after MCA occlusion and then allowed to rewarm to 36 degrees C over the next 2 hours. Animals in both groups were killed 24 hours after MCA occlusion. Cerebral infarcts were visualized by staining of coronal brain sections with 2,3,5-triphenyltetrazolium chloride. Normothermic rats displayed an average infarct volume of 233.1 +/- 13.2 mm3 (standard error of the mean), whereas hypothermic rats had an average infarct volume of 166.2 +/- 22.8 mm3 (P less than 0.01). Expressed as a percentage of the volume of the right hemisphere, the normothermic group had an infarct volume of 22.1 +/- 1.5% and the hypothermic group an infarct volume of 16.0 +/- 2.2% (P less than 0.05). These results demonstrate that transient hypothermia to a temporalis muscle temperature of 24 degrees C significantly reduces subsequent infarct size in an experimental model of permanent arterial occlusion. PMID:1922703

Onesti, S T; Baker, C J; Sun, P P; Solomon, R A

1991-09-01

339

Brain Tumor Susceptibility: the Role of Genetic Factors and Uses of Mouse Models to Unravel Risk  

PubMed Central

Brain tumors are relatively rare but deadly cancers, and present challenges in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain, with surgery, radiation and chemotherapy options carrying potentially lasting morbidity for patients and incomplete cure of the tumor. The development of methods to prevent or detect brain tumors at an early stage is extremely important to reduce damage to the brain from the tumor and the therapy. Developing effective prevention or early detection methods requires a deep understanding of the risk factors for brain tumors. This review explores the difficulties in assessing risk factors in rare diseases such as brain tumors, and discusses how mouse models of cancer can aid in a better understanding of genetic risk factors for brain tumors.

Reilly, Karlyne M.

2009-01-01

340

Transient ischemic attack with infarction: a unique syndrome?  

PubMed

It is debated whether transient symptoms associated with infarction (TSI) are best considered a minor ischemic stroke, a subtype of transient ischemic attack (TIA), or a separate ischemic brain syndrome. We studied clinical and imaging features to establish similarities and differences among ischemic stroke, TIA without infarction, and TSI. Eighty-seven consecutive patients with TIA and 74 patients with ischemic stroke were studied. All underwent diffusion-weighted imaging on admission. Symptom duration and infarct volume were determined in each group. Thirty-six patients (41.3%) with TIA had acute infarct(s). Although TIA-related infarcts were smaller than those associated with ischemic stroke (mean, 0.7 vs 27.3 ml; p < 0.001), there was no lesion size threshold that distinguished ischemic stroke from TSI. In contrast, the symptom duration probability density curve was not broad, but instead peaked early with only a few patients having symptoms for longer than 200 minutes. The probability density function for symptom duration was similar between TIA with or without infarction. The in-hospital recurrent ischemic stroke and TIA rate was 19.4% in patients with TSI and 1.3% in those with ischemic stroke. TIA with infarction appears to have unique features separate from TIA without infarction and ischemic stroke. We propose identifying TSI as a separate clinical syndrome with distinct prognostic features. PMID:15852402

Ay, Hakan; Koroshetz, Walter J; Benner, Thomas; Vangel, Mark G; Wu, Ona; Schwamm, Lee H; Sorensen, A Gregory

2005-05-01

341

A Drosophila model of closed head traumatic brain injury.  

PubMed

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

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

2013-10-14

342

Using computational models to relate structural and functional brain connectivity  

PubMed Central

Modern imaging methods allow a non-invasive assessment of both structural and functional brain connectivity. This has lead to the identification of disease-related alterations affecting functional connectivity. The mechanism of how such alterations in functional connectivity arise in a structured network of interacting neural populations is as yet poorly understood. Here we use a modeling approach to explore the way in which this can arise and to highlight the important role that local population dynamics can have in shaping emergent spatial functional connectivity patterns. The local dynamics for a neural population is taken to be of the Wilson–Cowan type, whilst the structural connectivity patterns used, describing long-range anatomical connections, cover both realistic scenarios (from the CoComac database) and idealized ones that allow for more detailed theoretical study. We have calculated graph–theoretic measures of functional network topology from numerical simulations of model networks. The effect of the form of local dynamics on the observed network state is quantified by examining the correlation between structural and functional connectivity. We document a profound and systematic dependence of the simulated functional connectivity patterns on the parameters controlling the dynamics. Importantly, we show that a weakly coupled oscillator theory explaining these correlations and their variation across parameter space can be developed. This theoretical development provides a novel way to characterize the mechanisms for the breakdown of functional connectivity in diseases through changes in local dynamics.

Hlinka, Jaroslav; Coombes, Stephen

2012-01-01

343

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

NASA Astrophysics Data System (ADS)

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

Liley, David T. J.; Frascoli, Federico

344

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 ...

345

Insular dwarfism in hippos and a model for brain size reduction in Homo floresiensis.  

PubMed

Body size reduction in mammals is usually associated with only moderate brain size reduction, because the brain and sensory organs complete their growth before the rest of the body during ontogeny. On this basis, 'phyletic dwarfs' are predicted to have a greater relative brain size than 'phyletic giants'. However, this trend has been questioned in the special case of dwarfism of mammals on islands. Here we show that the endocranial capacities of extinct dwarf species of hippopotamus from Madagascar are up to 30% smaller than those of a mainland African ancestor scaled to equivalent body mass. These results show that brain size reduction is much greater than predicted from an intraspecific 'late ontogenetic' model of dwarfism in which brain size scales to body size with an exponent of 0.35. The nature of the proportional change or grade shift observed here indicates that selective pressures on brain size are potentially independent of those on body size. This study demonstrates empirically that it is mechanistically possible for dwarf mammals on islands to evolve significantly smaller brains than would be predicted from a model of dwarfing based on the intraspecific scaling of the mainland ancestor. Our findings challenge current understanding of brain-body allometric relationships in mammals and suggest that the process of dwarfism could in principle explain small brain size, a factor relevant to the interpretation of the small-brained hominin found on the Island of Flores, Indonesia. PMID:19424156

Weston, Eleanor M; Lister, Adrian M

2009-05-01

346

Quantitative genetic modeling of variation in human brain morphology  

Microsoft Academic Search

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

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

2001-01-01

347

Information-based modeling of event-related brain dynamics  

Microsoft Academic Search

We discuss the theory and practice of applying independent component analysis (ICA) to electroencephalographic (EEG) data. ICA blindly decomposes multi-channel EEG data into maximally independent component processes (ICs) that typically express either particularly brain generated EEG activities or some type of non-brain artifacts (line or other environmental noise, eye blinks and other eye movements, or scalp or heart muscle activity).

Julie Onton; Scott Makeig

2006-01-01

348

A Model for Diffusion in White Matter in the Brain  

Microsoft Academic Search

Diffusion of molecules in brain and other tissues is important in a wide range of biological processes and measurements ranging from the delivery of drugs to diffusion-weighted magnetic resonance imaging. Diffusion tensor imaging is a powerful noninvasive method to characterize neuronal tissue in the human brain in vivo. As a first step toward understanding the relationship between the measured macroscopic

Pabitra N. Sen; Peter J. Bassery

2005-01-01

349

MRI Assessment of the Blood-Brain Barrier in a Hamster Model of Scrapie  

Microsoft Academic Search

Magnetic resonance (MR) imaging in combination with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhancement was used to investigate the integrity of the blood-brain barrier in a hamster model of scrapie (263K) during the clinical phase of the disease. The post Gd-DTPA images of the infected hamster brain showed marked enhancement, which was not present in control animals. These results suggest that blood-brain barrier

Yuen-Li Chung; Alun Williams; John S. Beech; Steve C. R. Williams; Jimmy D. Bell; Jane I. Cox; James Hope

1995-01-01

350

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

PubMed

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

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

2012-11-27

351

Biokinetics of radiolabeled Iodophenylpentadecanoic acid (I-123-IPPA) and thallium-201 in a rabbit model of chronic myocardial infarction measured using a series of thermoluminescent dosimeters  

NASA Astrophysics Data System (ADS)

The biokinetics of Iodophenylpentadecanoic acid (123I-IPPA) during a chronic period of myocardial infarction were determined and compared to 201Tl. IPPA was assessed as a perfusion and metabolic tracer in the scintigraphic diagnosis of coronary artery disease. The myocardial clearance kinetics were measured by placing a series of thermoluminescent dosimeters (TLDs) on normal and infarcted tissue to measure the local myocardial activity content over time. The arterial blood pool activity was fit to a bi-exponential function for 201Tl and a tri-exponential function for 123I-IPPA to estimate the left ventricle contribution to TLD response. At equilibrium, the blood pool contribution was estimated experimentally to be less than 5% of the total TLD response. The method was unable to resolve the initial uptake of the imaging agent due in part to the 2 minute TLD response integration time and in part to the 30 second lag time for the first TLD placement. A noticeable disparity was observed between the tracer concentrations of IPPA in normal and ischemic tissue of approximately 2:1. The fitting parameters (representing the biokinetic eigenvalue rate constants) were related to the fundamental rate constants of a recycling biokinetic model. The myocardial IPPA content within normal tissue was elevated after approximately 130 minutes post injection. This phenomenon was observed in all but one (950215) of the IPPA TLD kinetics curves.

Medich, David Christopher

1997-09-01

352

Recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) attenuates infarct size and myeloperoxidase activity in a canine model of ischemia-reperfusion.  

PubMed

The role of P-selectin in the process of reperfusion injury was evaluated using a recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) in a canine coronary artery balloon occlusion model. rPSGL-Ig (1 mg/kg) or saline was given as an intravenous bolus 15 min before balloon deflation. Balloon occlusion time was 90 min followed by either 120 min or 7 days reperfusion. Infarct size was significantly reduced in the treatment group when expressed either as percentage of the area at risk or as absolute infarct size. Histological analysis showed that extensive myocardial injury and neutrophil infiltration were reduced by rPSGL-Ig. Myeloperoxidase activity (MPO) was significantly reduced in the risk area in the rPSGL-Ig group. Left ventricular ejection fraction was significantly less impaired during the first 24 h after reperfusion in the rPSGL-Ig group, although there was no difference by 7-day follow-up. Thus, administration of rPSGL-Ig decreases myocardial injury and inflammatory response for at least 7 days after reperfusion of ischemic myocardium. PMID:12152656

Wang, Kai; Zhou, Xiaorong; Zhou, Zhongmin; Tarakji, Khaldoun; Qin, Jian Xin; Sitges, Marta; Shiota, Takahiro; Forudi, Farhad; Schaub, Robert G; Kumar, Anjali; Penn, Marc S; Topol, Eric J; Lincoff, A Michael

2002-07-01

353

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

Microsoft Academic Search

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

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

354

Bone marrow mesenchymal stem cell transplantation in acute brain trauma. Improvement of brain glucose metabolism in a rat model.  

PubMed

Aim:This study was performed to evaluate the effects of intravenously transplanted rat bone-marrow derived mesenchymal stem cells (rBMSCs) in an acute brain trauma model using serial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in rat models. Animals, methods: Trauma models were made using a controlled cortical impact injury device. The stem cell treatment group was treated with intravenous injections of BMSCs, and models without stem cell therapy comprised the control group. Serial 18F-FDG PET images were obtained 1, 7, 14, 21, and 28 days after trauma. The difference in 18F-FDG uptake between day 1 and each time point after trauma was analyzed with SPM2 (uncorrected p < 0.005). Results:The stem cell treatment group demonstrated significantly higher 18F-FDG uptake in the right parietal region at 14 days after trauma than at 1 day after trauma. An increase in glucose metabolism in the right parietal cortex appeared on days 21 and 28 after trauma in the group without stem cell treatment. The 18F-FDG uptake in the brain was improved over a broader area, including the right parietal and right primary somatosensory cortex, on days 21 and 28 after trauma in the stem cell treatment group compared with the group without stem cell treatment. Conclusion: BMSC therapy in trauma models led to improved glucose metabolism. This result might support the therapeutic effect of stem cells in brain trauma. PMID:23677328

Park, B-N; Yoon, J-K; An, Y-S

2013-05-15

355

Deformable registration of brain tumor images via a statistical model of tumor-induced deformation  

Microsoft Academic Search

An approach to the deformable registration of three-dimensional brain tumor images to a normal brain atlas is presented. The approach involves the integration of three components: a biomechanical model of tumor mass-effect, a statistical approach to estimate the model’s parameters, and a deformable image registration method. Statistical properties of the sought deformation map from the atlas to the image of

Ashraf Mohamed; Evangelia I. Zacharaki; Dinggang Shen; Christos Davatzikos

2006-01-01

356

Computational Models of Language Toward Brain-Style Computing  

Microsoft Academic Search

\\u000a The human brain consists of a neural system as hardware and a language system as software. It is, therefore, possible to take\\u000a two approaches to create the human brain. While the hardware-centered approach is based on computational neuroscience, it\\u000a is possible to base the software-centered approach on linguistics.\\u000a \\u000a \\u000a Brain-style computing is considered as one of the main research areas in

Michio Sugeno

2006-01-01

357

Studying the neurovascular unit: an improved blood–brain barrier model  

Microsoft Academic Search

The blood–brain barrier (BBB) closely interacts with the neuronal parenchyma in vivo. To replicate this interdependence in vitro, we established a murine coculture model composed of brain endothelial cell (BEC) monolayers with cortical organotypic slice cultures. The morphology of cell types, expression of tight junctions, formation of reactive oxygen species, caspase-3 activity in BECs, and alterations of electrical resistance under

Christoph M Zehendner; Heiko J Luhmann; Christoph RW Kuhlmann; CRW Kuhlmann

2009-01-01

358

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

ERIC Educational Resources Information Center

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

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

2010-01-01

359

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

Microsoft Academic Search

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

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

2010-01-01

360

Diffusion tensor-based fast marching for modeling human brain connectivity network  

Microsoft Academic Search

Diffusion tensor imaging (DTI) is an effective modality in studying the connectivity of the brain. To eliminate possible biases caused by fiber extraction approaches due to low spatial resolution of DTI and the number of fibers obtained, the fast marching (FM) algorithm based on the whole diffusion tensor information is proposed to model and study the brain connectivity network. Our

Hai Li; Zhong Xue; Kemi Cui; Stephen T. C. Wong

2011-01-01

361

Blood flow and oxygen delivery to human brain during functional activity: Theoretical modeling and experimental data  

Microsoft Academic Search

Coupling of cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in physiologically activated brain states remains the subject of debates. Recently it was suggested that CBF is tightly coupled to oxidative metabolism in a nonlinear fashion. As part of this hypothesis, mathematical models of oxygen delivery to the brain have been described in which disproportionately large increases

Mark A. Mintun; Brian N. Lundstrom; Abraham Z. Snyder; Andrei G. Vlassenko; Gordon L. Shulman; Marcus E. Raichle

2001-01-01

362

Usefulness of MRI to Differentiate Between Temporary and Long-Term Coronary Artery Occlusion in a Minimally Invasive Model of Experimental Myocardial Infarction  

SciTech Connect

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

Abegunewardene, Nico, E-mail: nico@uni-mainz.de; Vosseler, Markus; Gori, Tommaso [Johannes Gutenberg-University Mainz, Second Medical Clinic (Germany); Hoffmann, Nico [Johannes Gutenberg-University Mainz, Section of Medical Physics (Germany); Schmidt, Kai-Helge; Becker, Dietmar [Johannes Gutenberg-University Mainz, Second Medical Clinic (Germany); Kreitner, Karl-Friedrich [Johannes Gutenberg-University Mainz, Clinic for Radiology (Germany); Petersen, Steffen E. [John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR) (United Kingdom); Schreiber, Laura M. [Johannes Gutenberg-University Mainz, Section of Medical Physics (Germany); Horstick, Georg; Muenzel, Thomas [Johannes Gutenberg-University Mainz, Second Medical Clinic (Germany)

2009-09-15

363

Thalamic infarcts and hemorrhages.  

PubMed

The anatomy and supply of thalamic arteries are briefly described here. Thalamic infarcts and small-size hemorrhages are classified according to their sites: (1) posterolateral, (2) anterolateral, (3) medial, and (4) dorsal. (1) Posterolateral hemorrhages or lateral thalamic infarcts are usually characterized by severe motor impairment and sensory loss. Transient reduced consciousness, vertical-gaze abnormalities, and small fixed pupils may be evidenced. (2) Patients with anterolateral hemorrhages or tuberothalamic artery infarcts present frontal-type neuropsychological symptoms associated with mild hemiparesis and hemihypesthesia. (3) Medially located hemorrhages or paramedian artery infarcts have decreased levels of consciousness, vertical- and horizontal-gaze abnormalities, amnesia, and abulia. (4) Dorsal hemorrhages or posterior choroidal artery infarcts present with minimal transient hemiparesis and hemihypesthesia; apraxia, aphasia, and amnesia have also been described. PMID:22377880

Amici, Serena

2012-02-14

364

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

NASA Astrophysics Data System (ADS)

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

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

2013-04-01

365

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

PubMed Central

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

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

2013-01-01

366

Cerebral infarction in patient with minimal change nephrotic syndrome  

PubMed Central

We report a case of 68-year-old Caucasian man who presented with cerebral infarcts secondary to arterial thrombosis associated with nephrotic syndrome. His initial presentation included edema of legs, left hemiparesis, and right-sided cerebellar signs. Investigations with computed tomography and magnetic resonance imaging of brain showed multiple cerebral infarcts in middle cerebral and posterior cerebral artery territory. Blood and urine investigations also showed impaired renal function, hypercholesterolemia, hypoalbuminaemia, and nephrotic range proteinuria. Renal biopsy showed minimal change disease. Cerebral infarcts were treated with antiplatelet agents and nephrotic syndrome was treated with high dose steroids. Patient responded well to the treatment and is all well till date.

Babu, A.; Boddana, P.; Robson, S.; Ludeman, L.

2013-01-01

367

How well can in vitro brain microcapillary endothelial cell models predict rodent in vivo blood-brain barrier permeability?  

PubMed

The object of the study was to improve the blood-brain barrier (BBB) permeability in vitro-invivo correlations (IVIVC) between in vitro brain microcapillary endothelial cell (BMEC) models and the well-tested rodent in situ brain perfusion technique. Porcine, bovine, rat, mouse, and human in vitro BMEC apparent permeability values, P(e), (14 studies from several laboratories: 229 P(e), 60 compounds) were analyzed by a novel biophysical model encoded in a weighted nonlinear regression procedure to determine the aqueous boundary layer (ABL) thickness and the paracellular parameters: porosity-pathlength (dual-pore model), pore radius, and water channel electrostatic potential. The refined parameters were then used to transform the P(e) values into the transendothelial permeability (P(c)) values. Porcine BMEC mono-culture models showed tight junctions comparable to those reported in several Caco-2 studies. Bovine cultures were somewhat leakier. In the human primary cultured cell and the hCMEC/D3 cell line data, IVIVC based on P(e) values has r(2) = 0.14. With transformed permeability values, r(2) = 0.58. Comparable improvements were found in the other species data. By using the in vitro transendothelial P(c) values in place of the apparent P(e) values, IVIVC can be dramatically improved. PMID:21514381

Avdeef, Alex

2011-04-14

368

Brain to Computer Communication: Ethical Perspectives on Interaction Models  

Microsoft Academic Search

Brain Computer Interfaces (BCIs) enable one to control peripheral ICT and robotic devices by processing brain activity on-line.\\u000a The potential usefulness of BCI systems, initially demonstrated in rehabilitation medicine, is now being explored in education,\\u000a entertainment, intensive workflow monitoring, security, and training. Ethical issues arising in connection with these investigations\\u000a are triaged taking into account technological imminence and pervasiveness of

Guglielmo Tamburrini

2009-01-01

369

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.

Karakelleoglu, Sule; Gundogdu, Fuat; Tas, Muhammed Hakan; Kaya, Ahmet; Duman, Hakan; Degirmenci, Husnu; Hamur, Hikmet; Simsek, Ziya

2013-01-01

370

Modelling non-invasive brain stimulation in cognitive neuroscience.  

PubMed

Non-invasive brain stimulation (NIBS) is a method for the study of cognitive function that is quickly gaining popularity. It bypasses the correlative approaches of other imaging techniques, making it possible to establish a causal relationship between cognitive processes and the functioning of specific brain areas. Like lesion studies, NIBS can provide information about where a particular process occurs. However, NIBS offers the opportunity to study brain mechanisms beyond process localisation, providing information about when activity in a given brain region is involved in a cognitive process, and even how it is involved. When using NIBS to explore cognitive processes, it is important to understand not only how NIBS functions but also the functioning of the neural structures themselves. We know that NIBS techniques have the potential to transiently influence behaviour by altering neuronal activity, which may have facilitatory or inhibitory behavioural effects, and these alterations can be used to understand how the brain works. Given that NIBS necessarily involves the relatively indiscriminate activation of large numbers of neurons, its impact on a neural system can be easily understood as modulation of neural activity that changes the relation between noise and signal. In this review, we describe the mutual interactions between NIBS and brain activity and provide an updated and precise perspective on the theoretical frameworks of NIBS and their impact on cognitive neuroscience. By transitioning our discussion from one aspect (NIBS) to the other (cognition), we aim to provide insights to guide future research. PMID:23827785

Miniussi, Carlo; Harris, Justin A; Ruzzoli, Manuela

2013-07-01

371

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

372

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

373

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

NASA Astrophysics Data System (ADS)

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

Yang, Sh.; Ballmann, C.; Quarles, C. A.

2009-03-01

374

Intravenous nitroglycerin unloading in acute myocardial infarction.  

PubMed

Low-dose intravenous nitroglycerin infusion can be safely administered during acute myocardial infarction to unload the left ventricle and salvage ischemic myocardium and left ventricular geometry and function. In an experimental conscious dog model, low-dose infusion titrated to decrease mean blood pressure by 10% over the first 6 hours after coronary artery ligation resulted in 51% decrease in infarct size, 54% decrease in preload, and more than 50% increase in collateral blood flow. The same benefits were seen when methoxamine was given to counteract that 10% decrease in blood pressure. Similar short-term nitroglycerin infusion also limited remodeling in the dog model. More important, no myocardial salvage was seen with excessive nitroglycerin-induced hypotension to levels less than 80 mm Hg. Clinically, prolonged low-dose nitroglycerin infusion was evaluated in a prospective, randomized, single-blinded, placebo-controlled study of 310 patients with acute infarction: 154 received nitroglycerin and 156 received placebo. Nitroglycerin was titrated to reduce mean blood pressure by 10% in normotensive patients and up to 30% in hypertensive (blood pressure greater than 140/90 mm Hg) patients, but not to less than 80 mm Hg. Nitroglycerin produced several benefits compared with placebo: (1) smaller creatine kinase infarct size; (2) less regional left ventricular dysfunction, better global ejection fraction, and less infarct expansion and thinning; (3) better clinical functional status and hemodynamics; (4) fewer inhospital complications such as acute left ventricular failure and dilation due to marked infarct expansion, left ventricular thrombus, cardiogenic shock, and infarct extension; and (5) fewer deaths up to 1 year in patients with anterior Q-wave infarction. PMID:1836097

Jugdutt, B I

1991-11-18

375

AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction.  

PubMed

We have demonstrated that scar formation after myocardial infarction (MI) is associated with an endogenous pool of CD44(pos)CD45(neg) 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 the 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 30days. AICAR-dependent AMPK signaling led to mobilization of an endogenous CD44(pos)CD45(neg) 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; Mejia Osuna, Patricia; Entman, Mark L

2013-07-19

376

Brain Tumor Stem Cells as Therapeutic Targets in Models of Glioma  

PubMed Central

At this time, brain tumor stem cells remain a controversial hypothesis while malignant brain tumors continue to present a dire prognosis of severe morbidity and mortality. Yet, brain tumor stem cells may represent an essential cellular target for glioma therapy as they are postulated to be the tumorigenic cells responsible for recurrence. Targeting oncogenic pathways that are essential to the survival and growth of brain tumor stem cells represents a promising area for developing therapeutics. However, due to the multiple oncogenic pathways involved in glioma, it is necessary to determine which pathways are the essential targets for therapy. Furthermore, research still needs to comprehend the morphogenic processes of cell populations involved in tumor formation. Here, we review research and discuss perspectives on models of glioma in order to delineate the current issues in defining brain tumor stem cells as therapeutic targets in models of glioma.

Laks, Dan Richard; Visnyei, Koppany

2010-01-01

377

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.

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

2013-01-01

378

Computational representation of a realistic head and brain volume conductor model: electroencephalography simulation and visualization study.  

PubMed

Computational head and brain volume conductor modeling is a practical and non-invasive method to investigate neuroelectrical activity in the brain. Anatomical structures included in a model affect the flow of volume currents and the resulting scalp surface potentials. The influence of different tissues within the head on scalp surface potentials was investigated by constructing five highly detailed, realistic head models from segmented and processed Visible Human Man digital images. The models were: (1) model with 20 different tissues, that is, skin, dense connective tissue (fat), aponeurosis (muscle), outer, middle and inner tables of the scalp, dura matter, arachnoid layer (including cerebrospinal fluid), pia matter, six cortical layers, eye tissue, muscle around the eye, optic nerve, temporal muscle, white matter and internal air, (2) model with three main inhomogeneities, that is, scalp, skull, brain, (3) model with homogeneous scalp and remaining inhomogeneities, (4) model with homogeneous skull and remaining inhomogeneities, and (5) model with homogeneous brain matter and remaining inhomogeneities. Scalp potentials because of three different dipolar sources in the parietal-occipital lobe were computed for all five models. Results of a forward solution revealed that tissues included in the model and the dipole source location directly affect the simulated scalp surface potentials. The major finding indicates that significant change in the scalp surface potentials is observed when the brain's distinctions are removed. The other modifications, for example, layers of the scalp and skull are important too, but they have less effect on the overall results. PMID:23109383

Kybartaite, Asta

2012-05-17

379

Multi-Modal Approach for Investigating Brain and Behavior Changes in an Animal Model of Traumatic Brain Injury  

PubMed Central

Abstract Use of novel approaches in imaging modalities is needed for enhancing diagnostic and therapeutic outcomes of persons with a traumatic brain injury (TBI). This study explored the feasibility of using functional magnetic resonance imaging (fMRI) in conjunction with behavioral measures to target dynamic changes in specific neural circuitries in an animal model of TBI. Wistar rats were randomly assigned to one of two groups (traumatic brain injury/sham operation). TBI rats were subjected to the closed head injury (CHI) model. Any observable motor deficits and cognitive deficits associated with the injury were measured using beam walk and Morris water maze tests, respectively. fMRI was performed to assess the underlying post-traumatic cerebral anatomy and function in acute (24 hours after the injury) and chronic (7 and 21 days after the injury) phases. Beam walk test results detected no significant differences in motor deficits between groups. The Morris water maze test indicated that cognitive deficits persisted for the first week after injury and, to a large extent, resolved thereafter. Resting state functional connectivity (rsFC) analysis detected initially diminished connectivity between cortical areas involved in cognition for the TBI group; however, the connectivity patterns normalized at 1 week and remained so at the 3 weeks post-injury time point. Taken together, we have demonstrated an objective in vivo marker for mapping functional brain changes correlated with injury-associated cognitive behavior deficits and offer an animal model for testing potential therapeutic interventions options.

Heffernan, Meghan E.; Huang, Wei; Sicard, Kenneth M.; Bratane, Bernt T.; Sikoglu, Elif M.; Zhang, Nanyin; Fisher, Marc

2013-01-01

380

PET studies of brain energy metabolism in a model of subcortical dementia: Progressive Supranuclear Palsy.  

National Technical Information Service (NTIS)

In 41 patients with clinically determined Progressive Supranuclear Palsy, a model of degenerative subcortical dementia, alterations in regional brain energy metabolism with respect to control subjects have investigated using positron computed tomography a...

J. Blin J. C. Baron H. Cambon B. Dubois B. Pillon

1988-01-01

381

Tobacco and myocardial infarction: is snuff less dangerous than cigarettes?  

PubMed Central

OBJECTIVE--To estimate the risk of myocardial infarction in snuff users, cigarette smokers, and non-tobacco users in northern Sweden, where using snuff is traditional. DESIGN--Case-control study. SETTING--Northern Sweden. SUBJECTS--All 35-64 year old men who had had a first myocardial infarction and a population based sample of 35-64 year old men who had not had an infarction in the same geographical area. MAIN OUTCOME MEASURE--Tobacco consumption (regular snuff dipping, regular cigarette smoking, non-tobacco use) and risk of acute myocardial infarction. RESULTS--59 of 585 (10%) patients who had a first myocardial infarction and 87 of 589 (15%) randomly selected men without myocardial infarction were non-smokers who used snuff daily. The age adjusted odds ratio for myocardial infarction was 0.89 (95% confidence interval 0.62 to 1.29) for exposure to snuff and 1.87 (1.40 to 2.48) for cigarette smoking compared with non-tobacco users, showing an increased risk in smokers but not in snuff dippers. Regular cigarette smokers had a significantly higher risk of myocardial infarction than regular snuff dippers (age adjusted odds ratio 2.09; 1.39 to 3.15). Smoking, but not snuff dipping, predicted myocardial infarction in a multiple logistic regression model that included age and level of education. CONCLUSIONS--In middle aged men snuff dipping is associated with a lower risk of myocardial infarction than cigarette smoking.

Huhtasaari, F.; Asplund, K.; Lundberg, V.; Stegmayr, B.; Wester, P. O.

1992-01-01

382

Experimental myocardial infarction  

PubMed Central

The hemodynamic effects of tachycardia induced by atrial pacing were investigated in left ventricular failure of acute and healing experimental myocardial infarction in 20 intact, conscious dogs. Myocardial infarction was produced by gradual inflation of a balloon cuff device implanted around the left anterior descending coronary artery 10-15 days prior to the study. 1 hr after acute myocardial infarction, atrial pacing at a rate of 180 beats/min decreased left ventricular end-diastolic pressure from 19 to 8 mm Hg and left atrial pressure from 17 to 12 mm Hg, without change in cardiac output. In the healing phase of myocardial infarction 1 wk later, atrial pacing decreased left ventricular end-diastolic pressure from 17 to 9 mm Hg and increased the cardiac output by 37%. This was accompanied by evidence of peripheral vasodilation. In two dogs with healing anterior wall myocardial infarction, left ventricular failure was enhanced by partial occlusion of the circumflex coronary artery. Both the dogs developed pulmonary edema. Pacing improved left ventricular performance and relieved pulmonary edema in both animals. In six animals propranolol was given after acute infarction, and left ventricular function deteriorated further. However the pacing-induced augmentation of cardiac function was unaltered and, hence, is not mediated by sympathetics. The results show that the spontaneous heart rate in left ventricular failure of experimental canine myocardial infarction may be less than optimal and that maximal cardiac function may be achieved at higher heart rates. Images

Kumar, Raj; Joison, Julio; Gilmour, David P.; Molokhia, Farouk A.; Pegg, C. A. S.; Hood, William B.

1971-01-01

383

Neurobehavioral abnormalities in a brain-specific NADPH-cytochrome P450 reductase knockout mouse model  

PubMed Central

The aim of the present study was to test a new hypothesis that brain cytochrome P450 reductase (CPR) and CPR-dependent enzymes play important roles in behavioral performance. A mouse model with brain neuron-specific deletion of the Cpr gene (brain-Cpr-null) was recently generated. Brain-Cpr-null mice and wild-type (WT) littermates were compared in a variety of behavioral assays. Notable differences were found in the exploratory behavior assay: for both males and females, activity in the center of the chamber was significantly higher for brain-Cpr-null than for WT mice on days 2 and 3 of the assay, although no significant difference was found between the two groups in anxiety-like behavior in the elevated zero maze. Furthermore, in the fear-conditioning assay, brain-Cpr-null mice exhibited significantly less activity suppression than did WT controls. This deficit in activity suppression was not accompanied by any difference between WT and brain-Cpr-null mice in nociceptive responses to foot shocks. Abnormal activity suppression was also observed in both male and female brain-Cpr-null mice during the contextual memory test. However, in the Morris water maze assay, the brain-Cpr-null and WT mice were indistinguishable, indicating normal spatial memory in the mutant mice. These data collectively indicate a novel role of the Cpr gene in fear conditioning and memory.

Fang, Cheng; Bolivar, Valerie J.; Gu, Jun; Yang, Weizhu; Zeitlin, Scott O.; Ding, Xinxin

2012-01-01

384

Brain extraction from cerebral MRI volume using a hybrid level set based active contour neighborhood model.  

PubMed

BACKGROUND: The extraction of brain tissue from cerebral MRI volume is an important pre-procedure for neuroimage analyses. The authors have developed an accurate and robust brain extraction method using a hybrid level set based active contour neighborhood model. METHODS: The method uses a nonlinear speed function in the hybrid level set model to eliminate boundary leakage. When using the new hybrid level set model an active contour neighborhood model is applied iteratively in the neighborhood of brain boundary. A slice by slice contour initial method is proposed to obtain the neighborhood of the brain boundary. The method was applied to the internet brain MRI data provided by the Internet Brain Segmentation Repository (IBSR). RESULTS: In testing, a mean Dice similarity coefficient of 0.95+/-0.02 and a mean Hausdorff distance of 12.4+/-4.5 were obtained when performing our method across the IBSR data set (18 x1.5 mm scans). The results obtained using our method were very similar to those produced using manual segmentation and achieved the smallest mean Hausdorff distance on the IBSR data. CONCLUSIONS: An automatic method of brain extraction from cerebral MRI volume was achieved and produced competitively accurate results. PMID:23587217

Jiang, Shaofeng; Zhang, Weirui; Wang, Yu; Chen, Zhen

2013-04-12

385

Brain extraction from cerebral MRI volume using a hybrid level set based active contour neighborhood model  

PubMed Central

Background The extraction of brain tissue from cerebral MRI volume is an important pre-procedure for neuroimage analyses. The authors have developed an accurate and robust brain extraction method using a hybrid level set based active contour neighborhood model. Methods The method uses a nonlinear speed function in the hybrid level set model to eliminate boundary leakage. When using the new hybrid level set model an active contour neighborhood model is applied iteratively in the neighborhood of brain boundary. A slice by slice contour initial method is proposed to obtain the neighborhood of the brain boundary. The method was applied to the internet brain MRI data provided by the Internet Brain Segmentation Repository (IBSR). Results In testing, a mean Dice similarity coefficient of 0.95±0.02 and a mean Hausdorff distance of 12.4±4.5 were obtained when performing our method across the IBSR data set (18 × 1.5 mm scans). The results obtained using our method were very similar to those produced using manual segmentation and achieved the smallest mean Hausdorff distance on the IBSR data. Conclusions An automatic method of brain extraction from cerebral MRI volume was achieved and produced competitively accurate results.

2013-01-01

386

Viscoelastic Modeling of Brain Tissue: A Fractional Calculus-Based Approach  

Microsoft Academic Search

In recent years, the mechanical study of the brain has become a major topic in the field of biomechanics. A global biomechanical\\u000a model of the brain could find applications in neurosurgery and haptic device design. It would also be useful for car makers,\\u000a who could then evaluate the possible trauma due to impact. Such a model requires the design of

Vincent Libertiaux; Frédéric Pascon

387

Cerebral Hypoxia—Ischemia in Neonatal Rats or Mice: A Model of Perinatal Brain Injury  

Microsoft Academic Search

The most widespread animal model of perinatal brain injury is the neonatal rodent cerebral hypoxia—ischemia (HI) model. Ischemic\\u000a brain injury is produced through unilateral common carotid artery ligation followed by moderate hypoxia. Carotid ligation\\u000a alone does not induce any injury, nor does hypoxia alone, but the combination produces multifocal ischemic injury in the cortex,\\u000a hippocampus, striatum, and thalamus in the

Changlian Zhu; Xiaoyang Wang; Klas Blomgren

388

Towards Real-Time Distributed Signal Modeling for Brain-Machine Interfaces  

Microsoft Academic Search

New architectures for Brain-Machine Interface communication and control use mixture models for expanding rehabilitation capabilities of disabled patients. Here we present and test a dynamic data-driven (BMI) Brain-Machine Interface architecture that relies on multiple pairs of forward-inverse models to predict, control, and learn the trajectories of a robotic arm in a real-time closed- loop system. A method of window-RLS was

Jack Digiovanna; Loris Marchal; Prapaporn Rattanatamrong; Ming Zhao; Shalom Darmanjian; Babak Mahmoudi; Justin C. Sanchez; José C. Príncipe; Linda Hermer-vazquez; Renato J. O. Figueiredo; José A. B. Fortes

2007-01-01

389

Finite Element Modeling of Brain Tumor Mass-Effect from 3D Medical Images  

Microsoft Academic Search

\\u000a Motivated by the need for methods to aid the deformable registration of brain tumor images, we present a three-dimensional\\u000a (3D) mechanical model for simulating large non-linear deformations induced by tumors to the surrounding encephalic tissues.\\u000a The model is initialized with 3D radiological images and is implemented using the finite element (FE) method. To simulate\\u000a the widely varying behavior of brain

Ashraf Mohamed; Christos Davatzikos

2005-01-01

390

ATL 313, A Selective A2A Adenosine Receptor Agonist, Reduces Myocardial Infarct Size in a Rat Ischemia/Reperfusion Model  

PubMed Central

Objective: The cardioprotective effects of activation of the A2A adenosine receptor (A2AAR) on ischemia/reperfusion injury in the heart remain controversial. We investigated whether ATL 313, a new selective A2AAR agonist, could reduce myocardial infarct size in a rat ischemia/reperfusion model. Methods: Sprague-Dawley rats were subjected to a 40 minute occlusion of the left coronary artery followed by 3 hours reperfusion. Hemodynamics were monitored during the procedure. The rats were divided into 3 groups: Group 1 received continuous intravenous infusion of saline given 10 min prior to ischemia and throughout reperfusion (n=8); Group 2 received continuous intravenous infusion of 10 ng/kg/min of ATL 313 given 10 min prior to ischemia, and throughout reperfusion (n=8); and group 3 received an intravenous bolus of ATL 313 (900 ng/Kg body weight) given 10 min prior to ischemia, and continuous intravenous infusion of 10 ng/kg/min of ATL 313 started at 20 min after ischemia and throughout reperfusion (n=8). After euthanasia of the rats, the hearts were harvested for the assessment of risk zone and zone of necrosis of the left ventricle. Results: The percentage of risk zone in the left ventricle was similar among group 1 (47 ± 3.7 %), group 2 (41.5 ± 4.2 %) and group 3 (42.4 ± 3.8 %). However, the infarct size, expressed as a percentage of the risk zone, was significantly decreased in group 3 (30.6 ± 5 %, P=0.01) compared with group 1 (53.8 ± 6.2 %) and group 2 (52.1 ± 4.8 %). In group 3, the bolus injection of ATL 313 caused a reduction in blood pressure during the procedure, and decreased heart rate and LV ±dp/dt before coronary artery occlusion; but increased LV +dp/dt at the end of reperfusion compared to the other 2 groups. Conclusion: A2AAR agonist ATL313 significantly reduced infarct size and improved LV contractility at the end of reperfusion assessed by LV dp/dt at a dose of 900 ng/Kg. The mechanisms for the observed cardioprotection effect of ATL313 remain to be determined.

Dai, Wangde; Hale, Sharon L; Nayak, Rohith; Kloner, Robert A

2009-01-01

391

Quantum-like model of processing of information in the brain based on classical electromagnetic field.  

PubMed

We propose a model of quantum-like (QL) processing of mental information. This model is based on quantum information theory. However, in contrast to models of "quantum physical brain" reducing mental activity (at least at the highest level) to quantum physical phenomena in the brain, our model matches well with the basic neuronal paradigm of the cognitive science. QL information processing is based (surprisingly) on classical electromagnetic signals induced by joint activity of neurons. This novel approach to quantum information is based on representation of quantum mechanics as a version of classical signal theory which was recently elaborated by the author. The brain uses the QL representation (QLR) for working with abstract concepts; concrete images are described by classical information theory. Two processes, classical and QL, are performed parallely. Moreover, information is actively transmitted from one representation to another. A QL concept given in our model by a density operator can generate a variety of concrete images given by temporal realizations of the corresponding (Gaussian) random signal. This signal has the covariance operator coinciding with the density operator encoding the abstract concept under consideration. The presence of various temporal scales in the brain plays the crucial role in creation of QLR in the brain. Moreover, in our model electromagnetic noise produced by neurons is a source of superstrong QL correlations between processes in different spatial domains in the brain; the binding problem is solved on the QL level, but with the aid of the classical background fluctuations. PMID:21683119

Khrennikov, Andrei

2011-06-12