Sample records for brain infarction model

  1. Correcting for Brain Swelling's Effects on Infarct Volume Calculation After Middle Cerebral Artery Occlusion in Rats.

    PubMed

    McBride, Devin W; Klebe, Damon; Tang, Jiping; Zhang, John H

    2015-08-01

    Evaluating infarct volume is the primary outcome for experimental ischemic stroke studies and is a major factor in determining translation of a drug into clinical trials. Numerous algorithms are available for evaluating this critical value, but a major limitation of current algorithms is that brain swelling is not appropriately considered. The model by Lin et al. is widely used, but overestimates swelling within the infarction, yielding infarct volumes which do not reflect the true infarct size. Herein, a new infarct volume algorithm is developed to minimize the effects of both peri-infarct and infarct core swelling on infarct volume measurement. 2,3,5-Triphenyl-2H-tetrazolium chloride-stained brain tissue of adult rats subjected to middle cerebral artery occlusion was used for infarct volume analysis. When both peri-infarct swelling and infarction core swelling are removed from infarct volume calculations, such as accomplished by our algorithm, larger infarct volumes are estimated than those of Lin et al.'s algorithm. Furthermore, the infarct volume difference between the two algorithms is the greatest for small infarcts (<10 % of brain volume) when peri-infarct swelling is the greatest. Finally, using data from four published studies, our algorithm is compared to Lin et al.'s algorithm. Our algorithm offers a more reliable estimation of the infarct volume after ischemic brain injury, and thus may provide the foundation for comparing infarct volumes between experimental studies and standardizing infarct volume quantification to aid in the selection of the best candidates for clinical trials. PMID:25933988

  2. Aphasia Owing to Subcortical Brain Infarcts in Childhood

    Microsoft Academic Search

    Ariel Gout; Nathalie Seibel; Constance Rouvière; Béatrice Husson; Brigitte Hermans; Nicole Laporte; Hazim Kadhim; Cécile Grandin; Pierre Landrieu; Guillaume Sébire

    2005-01-01

    The aim of this study was to further define the clinical features of subcortical aphasia in children with deep brain infarcts and to define the sequelae associated with childhood strokes. We retrospectively studied nine children with left subcortical brain infarcts who presented with acquired language disorder and underwent language investigations based on standardized tests. Stroke in these patients involved the

  3. Platelets, alcohol consumption, and onset of brain infarction.

    PubMed Central

    Numminen, H; Hillbom, M; Juvela, S

    1996-01-01

    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. PMID:8890776

  4. Aphasia owing to subcortical brain infarcts in childhood.

    PubMed

    Gout, Ariel; Seibel, Nathalie; Rouvière, Constance; Husson, Béatrice; Hermans, Brigitte; Laporte, Nicole; Kadhim, Hazim; Grin, Cécile; Landrieu, Pierre; Sébire, Guillaume

    2005-12-01

    The aim of this study was to further define the clinical features of subcortical aphasia in children with deep brain infarcts and to define the sequelae associated with childhood strokes. We retrospectively studied nine children with left subcortical brain infarcts who presented with acquired language disorder and underwent language investigations based on standardized tests. Stroke in these patients involved the left internal capsule, lenticular or thalamic nuclei, or a combination of these. Early aphasic manifestations following the deep cerebral infarcts affected language expression. These included mutism, nonfluent speech, word finding difficulties, and phonemic and semantic paraphasia. Speech comprehension was generally more preserved. All patients subsequently improved, although variably; sequelae such as dysfluency, word finding difficulties, and written language learning impairment could be detected through standardized tests in six of them (all younger than 6 years at the time of the infarct). Two of the three remaining patients (both older than 6 years at the time of the infarct) had a full recovery. Our study confirms the concept of childhood subcortical aphasia, depicts the linguistic profile in these patients, and sustains the indication of systematic formal language assessment during the follow-up of all children with subcortical infarct involving the dominant hemisphere. PMID:16417851

  5. Enhanced expression of aquaporin 4 in human brain with infarction

    Microsoft Academic Search

    Kazuko Aoki; Toshiki Uchihara; Kuniaki Tsuchiya; Ayako Nakamura; Kenji Ikeda; Yoshihiro Wakayama

    2003-01-01

    A series of human brains with cerebral infarction obtained at autopsy were investigated to clarify the possible contribution of aquaporin 4 (AQP4) to the development of brain edema. Cellular localization of AQP4 and its relation to ischemic foci were examined with double-labeling immunohistochemistry. AQP4 immunoreactivity (IR) was more intense at the periphery of ischemic foci than at their center. Double-labeling

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

    E-print Network

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

    –28) there were 108 infarct "non-expansion” voxels and 113 infarct "expansion” voxels (of which 80 were “complete expansion” and 33 “partial expansion” voxels). Brain choline concentration increased for each change in expansion category from "non-expansion", via...

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

    PubMed Central

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

    2013-01-01

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

  8. Co-elevation of brain natriuretic peptide and proprotein-processing endoprotease furin after myocardial infarction in rats

    Microsoft Academic Search

    Yoshie Sawada; Masahiro Inoue; Tsugiyasu Kanda; Tetsuo Sakamaki; Shigeyasu Tanaka; Naoto Minamino; Ryozo Nagai; Toshiyuki Takeuchi

    1997-01-01

    We investigated the expression of the yeast Kex2 family endoproteases furin and PACE4, and brain natriuretic peptide (BNP) in the atrium and ventricle after infarction as well as the conversion of the BNP precursor ?BNP to BNP-45. In a rat heart failure model, plasma BNP rose in two phases – first at day 3, and again at day 14. BNP

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

    Microsoft Academic Search

    B Norrving

    2008-01-01

    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

  10. Serial changes in plasma brain natriuretic peptide concentration at the infarct and non-infarct sites in patients with left ventricular remodelling after myocardial infarction

    PubMed Central

    Hirayama, A; Kusuoka, H; Yamamoto, H; Sakata, Y; Asakura, M; Higuchi, Y; Mizuno, H; Kashiwase, K; Ueda, Y; Okuyama, Y; Hori, M; Kodama, K

    2005-01-01

    Objectives: To clarify the role of infarct and non-infarct sites on left ventricular (LV) remodelling after myocardial infarction by measuring brain natriuretic peptide (BNP) from each site. Methods and results: BNP from the aorta and the anterior interventricular vein (AIV) was measured in 45 patients with first anterior myocardial infarction at one, six, and 18 months. The LV was significantly dilated (> 10 ml/m2 of end diastolic volume from one to 18 months) in 20 patients (remodelling (R) group) but not in 25 others (non-remodelling (NR) group). Patient characteristics and LV functions did not differ significantly at one month but plasma BNP concentration was higher in group R than in group NR (336 (288) v 116 (106) pg/ml, p < 0.01), predicting the degree of LV dilatation. The difference in BNP concentration between the aortic root and AIV (?BNP), reflecting BNP secreted from the infarct site, did not differ at one month. In both groups BNP and ?BNP significantly decreased from one to six months (p < 0.05) and decreased from six months to 18 months, but the change was not significant. BNP and ?BNP were significantly higher in group R than in group NR after six months, when LV dilatation was not evident in both groups. Conclusion: Enhanced BNP secretion at one month in the non-infarct and infarct ventricular sites predicts subsequent LV dilatation (that is, remodelling). The slower process of LV remodelling decreased BNP secretion at both sites. Thus, BNP concentration should be useful for monitoring ventricular remodelling after infarction. PMID:15774610

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  12. Retinal microvascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study.

    PubMed

    Cheung, Ning; Mosley, Thomas; Islam, Amirul; Kawasaki, Ryo; Sharrett, A Richey; Klein, Ronald; Coker, Laura H; Knopman, David S; Shibata, Dean K; Catellier, Diane; Wong, Tien Y

    2010-07-01

    Silent brain infarct and white matter lesions are common radiological findings associated with the risk of clinical stroke and dementia; however, our understanding of their underlying pathophysiology and risk factors remains limited. This study aimed to determine whether assessment of retinal microvascular abnormalities could provide prognostic information regarding the risk of brain infarct and white matter lesions on magnetic resonance imaging. This study is based on a subset of 810 middle-aged persons without clinical stroke or baseline magnetic resonance imaging infarct enrolled in the Atherosclerosis Risk in Communities Brain Magnetic Resonance Imaging Study, a prospective, population-based study. Participants had a baseline magnetic resonance imaging brain examination and retinal photography in 1993-1995, and returned for a repeat magnetic resonance imaging examination in 2004-2006. Magnetic resonance images were graded for presence of any cerebral infarct, infarct with lacunar characteristics and white matter lesions according to standardized protocols. Retinal photographs were graded for presence of retinopathy lesions and retinal arteriolar abnormalities following a standardized protocol. Over a median follow-up of 10.5 years, 164 (20.2%) participants developed cerebral infarct, 131 (16.2%) developed lacunar infarct, 182 (24.2%) developed new white matter lesions and 49 (6.1%) had evidence of white matter lesion progression. After adjusting for age, gender, race, cardiovascular risk factors and carotid intima-media thickness, retinopathy was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval 1.42-5.60) and lacunar infarct (odds ratio 3.19; 95% confidence interval: 1.56-6.50). Retinal arteriovenous nicking was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval: 1.66-4.76), lacunar infarct (odds ratio 2.48; 95% confidence interval: 1.39-4.40) and white matter lesion incidence (odds ratio 2.12; 95% confidence interval: 1.18-3.81) and progression (odds ratio 2.22; 95% confidence interval: 1.00-5.88). In conclusion, retinal microvascular abnormalities are associated with emergence of subclinical magnetic resonance imaging brain infarcts and white matter lesions, independent of shared risk factors. Retinal vascular imaging may offer a non-invasive tool to investigate the pathogenesis and natural history of cerebral small-vessel disease. PMID:20519327

  13. Aggressive Decompressive Surgery in Patients with Massive Hemispheric Embolic Cerebral Infarction Associated with Severe Brain Swelling

    Microsoft Academic Search

    K. Mori; A. Aoki; T. Yamamoto; N. Horinaka; M. Maeda

    2001-01-01

    Summary  ?Massive hemispheric cerebral infarction, also known as malignant infarction, is characterized by rapid clinical deterioration\\u000a due to brain swelling and downward transtentorial herniation, and is associated with a mortality of 80%. Early patient selection\\u000a and establishment of the optimum therapeutic modality are important to improve the outcome. Early clinical, computed tomography\\u000a (CT), and angiographic characteristics were analysed to identify patients

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

    Microsoft Academic Search

    Steve Leu; Yu-Chun Lin; Chun-Man Yuen; Chia-Hung Yen; Ying-Hsien Kao; Cheuk-Kwan Sun; Hon-Kan Yip

    2010-01-01

    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

  15. Concealment of neonatal cerebral infarction on MRI by normal brain water

    Microsoft Academic Search

    J. B. Moore; C. P. Parker; R. J. Smith; B. D. Goethe

    1987-01-01

    Magnetic resonance imaging (MRI) is highly sensitive in detecting cerebral infarction in adults, both in the acute and chronic\\u000a stages. Cytotoxic and vasogenic edema produce an increase in the water content of acutely ischemic brain, resulting in good\\u000a tissue contrast from adjacent normal brain on spin density, T1 and T2 weighted MR images. Gliosis and other chronic brain changes are

  16. Brain sigma-1 receptor stimulation improves mental disorder and cardiac function in mice with myocardial infarction.

    PubMed

    Ito, Koji; Hirooka, Yoshitaka; Sunagawa, Kenji

    2013-08-01

    Mental disorder after myocardial infarction (MI) is reported by many epidemiological studies and is associated with a poor prognosis. The reduction of brain sigma-1 receptor (S1R) plays an important role in the pathogenesis of mental disorder, and we recently demonstrated that the reduction of brain S1R causes sympathoexcitation. However, the role of brain S1R in the association between MI and mental disorder, such as depression or cognitive impairment, remains unclear. To investigate this, we performed left coronary artery ligation on mice to produce an MI model (MI-mice). Compared with sham-operated controls (Sham-mice), MI-mice showed augmented sympathetic activity, decreased cardiac function, and lower S1R expression in both the hypothalamus and hippocampus. Furthermore, MI-mice displayed decreased Y-maze spontaneous alternation (a maker of spatial working memory), decreased circadian variation in locomotor activity, and increased immobility time in the tail suspension test (markers of depression-like behavior). Intracerebroventricular infusion of the S1R agonist PRE084 in MI-mice improved both mental disorder and cardiac function with lowered sympathetic activity and the recovery of the S1R expression in both the hypothalamus and hippocampus. These results indicate that brain S1R is decreased in MI-mice and that this plays an important role in the coexistence of increased heart failure via sympathoexcitation and mental disorders, such as depression or cognitive impairment. PMID:23615161

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

    NASA Astrophysics Data System (ADS)

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

    2005-03-01

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

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

    Microsoft Academic Search

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

    2001-01-01

    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

  19. Infarction of 'non-core-non-penumbral' tissue after stroke: multivariate modelling of clinical impact.

    PubMed

    Alawneh, Josef A; Jones, Peter Simon; Mikkelsen, Irene Klærke; Cho, Tae-Hee; Siemonsen, Susanne; Mouridsen, Kim; Ribe, Lars; Morris, Rhiannon S; Hjort, Niels; Antoun, Nagui; Gillard, Jonathan H; Fiehler, Jens; Nighoghossian, Norbert; Warburton, Elizabeth A; Ostergaard, Leif; Baron, Jean-Claude

    2011-06-01

    There is considerable intersubject variability in early neurological course after anterior circulation stroke, yet the pathophysiology underlying this variability is not fully understood. Here, we hypothesize that, although not predicted by current pathophysiological models, infarction of 'non-core-non-penumbral' (i.e. clinically silent) brain tissue may nevertheless occur, and negatively influence clinical course over and above the established positive impact of penumbral salvage. In order to test this hypothesis, non-core-non-penumbral tissue was identified in two independent prospectively recruited cohorts, using computed tomography perfusion, and magnetic resonance perfusion- and diffusion-weighted imaging, respectively. Follow-up structural magnetic resonance imaging was obtained about 1 month later in all patients to map the final infarct. The volumes of both the acutely silent but eventually infarcted tissue, and the eventually non-infarcted penumbra, were determined by performing voxel-wise analysis of the acute and follow-up image sets, using previously validated perfusion thresholds. Early neurological course was expressed as change in National Institutes of Health Stroke Scale scores between the acute and 1-month assessments, relative to the acute score. The relationship between the acutely silent but eventually infarcted tissue volume and early neurological course was tested using a multivariate regression model that included the volume of non-infarcted penumbra. Thirty-four and 58 patients were recruited in the computed tomography perfusion and magnetic resonance perfusion cohorts, respectively (mean onset-to-imaging time: 136 and 156 min; 27 and 42 patients received intravenous thrombolysis, respectively). Infarction of acutely silent tissue was identified in most patients in both cohorts. Although its volume (median 0.2 and 2 ml, respectively) was much smaller than that of salvaged penumbra (59.3 and 93 ml, respectively), it was substantial in ?10% of patients. As expected, salvaged penumbra strongly positively influenced early neurological course. Even after correcting for the latter effect in the multivariate model, infarction of acutely silent tissue independently negatively influenced early neurological course in both cohorts (P=0.018 and 0.031, respectively). This is the first systematic study to document infarction of acutely silent tissue after anterior circulation stroke, and to show that it affects a sizeable fraction of patients and has the predicted negative impact on clinical course. These findings were replicated in two independent cohorts, regardless of the perfusion imaging modality used. Preventing infarction of the tissue not initially at risk should have direct clinical benefit. PMID:21616971

  20. Huoxue Rongluo Tablet reduces matrix metalloproteinase-9 expression in infarcted brain tissue

    PubMed Central

    Zhou, Desheng; Li, Mei; Hu, Hua; Chen, Yao; Yang, Yang; Zhong, Jie; Liu, Lijuan

    2013-01-01

    Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3:2:6:2:3:3:3:3. Huoxue Rongluo Tablet is a well-established and common pre-scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat-ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression. PMID:25206642

  1. Huoxue Rongluo Tablet reduces matrix metalloproteinase-9 expression in infarcted brain tissue.

    PubMed

    Zhou, Desheng; Li, Mei; Hu, Hua; Chen, Yao; Yang, Yang; Zhong, Jie; Liu, Lijuan

    2013-12-01

    Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3:2:6:2:3:3:3:3. Huoxue Rongluo Tablet is a well-established and common pre-scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat-ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression. PMID:25206642

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

    Microsoft Academic Search

    Slaven Pikija; Vladimir Trkulja; Nedeljko Sokol

    2006-01-01

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

  3. Genome-wide association studies of mri-defined brain infarcts: Meta-analysis from the charge consortium

    Microsoft Academic Search

    S. Debette; J. C. Bis; M. Fornage; H. A. Schmid; M. A. Ikram; S. Sigurdsson; G. Heiss; M. V. Struchalin; A. V. Smith; Lugt van der A; C. DeCarli; T. Lumley; D. S. Knopman; C. Enzinger; G. Eiriksdottir; P. J. Koudstaal; A. L. DeStefano; B. M. Psaty; C. Dufouil; D. J. Catellier; F. Fazekas; T. Aspelund; Y. S. Aulchenko; A. Beiser; J. I. Rotter; C. Tzourio; D. K. Shibata; M. Tscherner; T. B. Harris; F. Rivadeneira Ramirez; L. D. Atwood; K. Rice; R. F. Gottesman; Buchem van M. A; A. G. Uitterlinden; M. Kelly-Hayes; M. Cushman; Y. Zhu; E. Boerwinkle; V. Gudnason; A. Hofman; J. R. Romero; M. M. B. Breteler; R. Schmidt; L. J. Launer; W. T. Longstreth

    2010-01-01

    Background and Purpose-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

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

    PubMed Central

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

    2013-01-01

    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. PMID:24098534

  5. Prevalence and associated factors of silent brain infarcts in a Mediterranean cohort of hypertensives.

    PubMed

    Delgado, Pilar; Riba-Llena, Iolanda; Tovar, José L; Jarca, Carmen I; Mundet, Xavier; López-Rueda, Antonio; Orfila, Francesc; Llussà, Judit; Manresa, Josep M; Alvarez-Sabín, José; Nafría, Cristina; Fernández, José L; Maisterra, Olga; Montaner, Joan

    2014-09-01

    Silent brain infarcts (SBIs) are detected by neuroimaging in approximately 20% of elderly patients in population-based studies. Limited evidence is available for hypertensives at low cardiovascular risk countries. Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study (ISSYS) is aimed to assess the prevalence and risk factors of SBIs in a hypertensive Mediterranean population. This is a cohort study in randomly selected hypertensives, aged 50 to 70 years old, and free of clinical stroke and dementia. On baseline, all participants underwent a brain magnetic resonance imaging to assess prevalence and location of silent infarcts, and data on vascular risk factors, comorbidities, and the presence of subclinical cardiorenal damage (left ventricular hypertrophy and microalbuminuria) were collected. Multivariate analyses were performed to determine SBIs associated factors. A total of 976 patients (49.4% men, mean age 64 years) were enrolled, and 163 SBIs were detected in 99 participants (prevalence 10.1%; 95% CI, 8.4%-12.2%), most of them (64.4%) located in the basal ganglia and subcortical white matter. After adjustment, besides age and sex, microalbuminuria and increasing total cardiovascular risk (assessed by the Framingham-calibrated for Spanish population risk function) were independently associated with SBIs. Male sex increased the odds of having SBIs in 2.5 as compared with females. Our results highlight the importance of considering both global risk assessment and sex differences in hypertension and may be useful to design future preventive interventions of stroke and dementia. PMID:24958500

  6. MRI and PET in mouse models of myocardial infarction.

    PubMed

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

    2013-01-01

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

  7. Reduced brain edema and infarct volume in aquaporin-4 deficient mice after transient focal cerebral ischemia.

    PubMed

    Yao, Xiaoming; Derugin, Nikita; Manley, Geoffrey T; Verkman, A S

    2015-01-01

    Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet lining the blood-brain barrier. AQP4 deletion in mice is associated with improved outcomes in global cerebral ischemia produced by transient carotid artery occlusion, and focal cerebral ischemia produced by permanent middle cerebral artery occlusion (MCAO). Here, we investigated the consequences of 1-h transient MCAO produced by intraluminal suture blockade followed by 23 h of reperfusion. In nine AQP4(+/+) and nine AQP4(-/-) mice, infarct volume was significantly reduced by an average of 39 ± 4% at 24h in AQP4(-/-) mice, cerebral hemispheric edema was reduced by 23 ± 3%, and Evans Blue extravasation was reduced by 31 ± 2% (mean ± SEM). Diffusion-weighted magnetic resonance imaging showed greatest reduction in apparent diffusion coefficient around the occlusion site after reperfusion, with remarkably lesser reduction in AQP4(-/-) mice. The reduced infarct volume in AQP4(-/-) mice following transient MCAO supports the potential utility of therapeutic AQP4 inhibition in stroke. PMID:25449874

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

    PubMed Central

    2014-01-01

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

  9. Spatiotemporal brain imaging and modeling

    E-print Network

    Lin, Fa-Hsuan, 1972-

    2004-01-01

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

  10. Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats.

    PubMed

    Chang, Yi; Hsieh, Cheng-Ying; Peng, Zi-Aa; Yen, Ting-Lin; Hsiao, George; Chou, Duen-Suey; Chen, Chien-Ming; Sheu, Joen-Rong

    2009-01-01

    Puerarin, a major isoflavonoid derived from the Chinese medical herb Radix puerariae (kudzu root), has been reported to be useful in the treatment of various cardiovascular diseases. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of puerarin on inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. Treatment of puerarin (25 and 50 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia in rats. Administration of puerarin at 50 mg/kg, showed marked reduction in infarct size compared with that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor-1alpha (HIF-1alpha), inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions as well as the mRNA expression of tumor necrosis factor-alpha (TNF-alpha) in ischemic regions. These expressions were markedly inhibited by the treatment of puerarin (50 mg/kg). In addition, puerarin (10-50 microM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by formyl-Met-Leu-Phe. On the other hand, puerarin (20-500 microM) did not significantly inhibit the thiobarbituric acid-reactive substance reaction in rat brain homogenates. An electron spin resonance (ESR) method was conducted on the scavenging activity of puerarin on the free radicals formed. Puerarin (200 and 500 microM) did not reduce the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate that puerarin is a potent neuroprotective agent on MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1alpha and TNF-alpha activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and neutrophil activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, puerarin treatment may represent a novel approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders. PMID:19272172

  11. Myocardial infarction and intramyocardial injection models in swine

    PubMed Central

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

    2014-01-01

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

  12. [Experimental model of venous hemorrhagic infarction by cerebral sinus occlusion].

    PubMed

    Fujita, K; Kojima, N; Matsumoto, S

    1984-08-01

    A new experimental model of the hemorrhagic infarction was devised to study the pathophysiology of the hemorrhagic infarction of the venous origin. To make a model of the hemorrhagic infarction by sinus occlusion, mixture of alpha-cyanoacrylate monomer and pantopaque was injected through a catheter introduced into the superior sagittal sinus in 15 dogs, using embolization technique. These dogs were divided into three groups according to the volume of the mixture injected into the sinus. In control groups (3 dogs), no mixture was injected. For partial sinus occlusion (5 dogs), 0.5-1.0 ml of mixture was injected into the sinus and 1.0-1.5 ml of mixture, for complete sinus occlusion (7 dogs). Changes of intracranial pressure (ICP), superior sagittal sinus pressure (SSSP), tissue pressure (TP) rCBF and histological changes were evaluated before and after sinus occlusion. The following results were obtained. (1) In control groups, ICP, SSSP and TP were 9 +/- 2.2 mmHg, 4 +/- 2.5 mmHg and 4-5 mmHg respectively, but in partial and complete sinus occlusion, SSSP and TP were higher than ICP. ICP, SSSP & TP were 32 +/- 5.4 mmHg, 35 +/- 6.5 mmHg and 37-42 mg, in partial sinus occlusion and 62 +/- 5.9 mmHg, 65 +/- 6.0 mmHg, 65-72 mmHg in complete sinus occlusion. (2) R-CBF in partial sinus occlusion showed no change even after sinus occlusion, but in complete sinus occlusion, decreased to 20% of that of the control group due to marked venous congestion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6504262

  13. Brain perivascular macrophages and the sympathetic response to inflammation in rats after myocardial infarction.

    PubMed

    Yu, Yang; Zhang, Zhi-Hua; Wei, Shun-Guang; Serrats, Jordi; Weiss, Robert M; Felder, Robert B

    2010-03-01

    Inflammation is associated with increased sympathetic drive in cardiovascular diseases. Blood-borne proinflammatory cytokines, markers of inflammation, induce cyclooxygenase 2 (COX-2) activity in perivascular macrophages of the blood-brain barrier. COX-2 generates prostaglandin E(2), which may enter the brain and increase sympathetic nerve activity. We examined the contribution of this mechanism to augmented sympathetic drive in rats after myocardial infarction (MI). Approximately 24 hours after acute MI, rats received an intracerebroventricular injection (1 microL/min over 40 minutes) of clodronate liposomes (MI+CLOD) to eliminate brain perivascular macrophages, liposomes alone, or artificial cerebrospinal fluid. A week later, COX-2 immunoreactivity in perivascular macrophages and COX-2 mRNA and protein had increased in hypothalamic paraventricular nucleus of MI rats treated with artificial cerebrospinal fluid or liposomes alone compared with sham-operated rats. In MI+CLOD rats, neither perivascular macrophages nor COX-2 immunoreactivity was seen in the paraventricular nucleus, and COX-2 mRNA and protein levels were similar to those in sham-operated rats. Prostaglandin E(2) in cerebrospinal fluid, paraventricular nucleus neuronal excitation, and plasma norepinephrine were less in MI+CLOD rats than in MI rats treated with artificial cerebrospinal fluid or liposomes alone but more than in sham-operated rats. Intracerebroventricular CLOD had no effect on interleukin 1beta and tumor necrosis factor-alpha mRNA and protein in the paraventricular nucleus or plasma interleukin-1beta and tumor necrosis factor-alpha, which were increased in MI compared with sham-operated rats. In normal rats, pretreatment with intracerebroventricular CLOD reduced (P<0.05) the renal sympathetic, blood pressure, and heart rate responses to intracarotid artery injection of tumor necrosis factor-alpha (0.5 microg/kg); intracerebroventricular liposomes had no effect. The results suggest that proinflammatory cytokines stimulate sympathetic excitation after MI by inducing COX-2 activity and prostaglandin E(2) production in perivascular macrophages of the blood-brain barrier. PMID:20142564

  14. Systematic Characterization of Myocardial Inflammation, Repair, and Remodeling in a Mouse Model of Reperfused Myocardial Infarction

    PubMed Central

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

    2013-01-01

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

  15. Biphasic and monophasic pattern of brain natriuretic peptide release in acute myocardial infarction.

    PubMed

    Dili?, Mirza; Nalbanti?, Azra Durak; Arslanagi?, Amila; Huski?, Jasminko; Brdjanovi?, Snezana; Kuli?, Mehmed; Hodzi?, Enisa; Sokolovi?, Sekib; Zvizdi?, Faris; Dzubur, Alen

    2011-03-01

    This study evaluated brain natriuretic peptide (BNP) release in acute myocardial infarction (AMI), absolute values as well as pattern of its release. There are two different patterns of BNP release in AMI; monophasic pattern--concentration in the first measurement is higher than in the second one, and biphasic pattern--concentration in the first measurement is lower than in the second one. We observed significance of biphasic and monophasic pattern of BNP release related to diagnostic and prognostic value. We included in this prospective observational study total of 75 AMI patients, 52 males and 23 females, average age of 62.3 +/- 10.9 years with range of 42 to 79 years. BNP was measured and pattern of its release was evaluated. In AMI group BNP levels were significantly higher than in controls (462.88 pg/mL vs. 35.36 pg/mL, p < 0.001). We found statistically significant real negative correlation (p < 0.05) between BNP concentration and left ventricle ejection fraction (LVEF) with high correlation coefficient (r = -0.684). BNP concentrations were significantly higher among patients in Killip class II and III compared to Killip class I; Killip class I BNP = 226.18 pg/mL vs. Killip class II 622.51 pg/mL vs. Killip class III 1530.28 pg/mL, p < 0.001. BNP concentrations were significantly higher in patients with; (i) myocardial infarction vs. controls; (BNP 835.80 pg/mL vs. 243.03 pg/mL); (ii) in pts with positive major adverse cardiac events (MACE) vs. negative MACE (BNP 779.08 pg/mL vs. 242.28 pg/mL, p < 0.001); (iii) in pts with positive compared to negative left ventricle (LV) remodelling (BNP 840.77 pg/mL vs. 341.41 pg/mL, p < 0.001). Group with biphasic pattern of BNP release had significantly higher BNP concentration compared to monophasic pattern group. In biphasic pattern group we found significant presence of lower LVEF, Killip class II and III, LV remodelling and MACE. We found that BNP is strong marker of adverse cardiac events in patients presenting with a myocardial infarction. In our AMI group we found significant elevation of BNP and it is suspected that second peak secretion is not only due to systolic dysfunction and subsequent remodeling of LV but also due to impact of ischaemia. Patients with biphasic pattern probably have worse prognosis due to severe coronary heart disease. Besides its diagnostic role as a simple blood marker of systolic function, BNP is also important prognostic marker who helps making clinical decision about early invasive vs. conservative management. PMID:21667539

  16. Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects

    Microsoft Academic Search

    Jay G. Shake; Peter J. Gruber; William A. Baumgartner; Guylaine Senechal; Jennifer Meyers; J. Mark Redmond; Mark F. Pittenger; Bradley J. Martin

    2002-01-01

    Background. A novel therapeutic option for the treatment of acute myocardial infarction involves the use of mesenchymal stem cells (MSCs). The purpose of this study was to investigate whether implantation of autologous MSCs results in sustained engraftment, myogenic differentiation, and improved cardiac function in a swine myocardial infarct model.Methods. MSCs were isolated and expanded from bone marrow aspirates of 14

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

    PubMed Central

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

    2015-01-01

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

  18. Harm Avoidance and Cerebral Infarction

    PubMed Central

    Wilson, Robert S.; Boyle, Patricia A.; Levine, Steven R.; Yu, Lei; Hoganson, George M.; Buchman, Aron S.; Schneider, Julie A.; Bennett, David A.

    2014-01-01

    Objective Harm avoidance, a trait indicative of behavioral inhibition, is associated with disability and dementia in old age, but the basis of these associations is uncertain. We test the hypothesis that higher level of harm avoidance is associated with increased likelihood of cerebral infarction. Methods Older persons without dementia completed a standard measure of harm avoidance. During a mean of 3.5 years of follow-up, 257 (of 1,082) individuals died of whom 206 (80%) underwent brain autopsy. Number of chronic cerebral infarcts (microscopic plus gross; expressed as 0,1, or >1) was assessed on neuropathologic examination, completed in 192 individuals at the time of analyses. Results On postmortem examination, chronic cerebral infarcts were found in 89 (42 with 1, 47 with >1). Higher harm avoidance was associated with higher likelihood of infarcts (odds ratio = 1.083, 95% confidence interval 1.040–1.128). A moderately high level of the trait (score=17, 75th percentile) was associated with a 2.4-fold increase in the likelihood of infarction compared to a moderately low level of the trait (score = 6, 25th percentile). These associations persisted in models that controlled for other cardiovascular risk factors. Conclusion Higher level of the harm avoidance trait may be a risk factor for cerebral infarction. PMID:24364391

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

    PubMed Central

    Correa, Edgar; Martinez, Braulio

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    Microsoft Academic Search

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

    2005-01-01

    I.v. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared

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

    PubMed Central

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

    2013-01-01

    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

  3. A case of embolic stroke imitating atherothrombotic brain infarction before massive hemorrhage from an infectious aneurysm caused by Streptococci.

    PubMed

    Kanai, Ryuichi; Shinoda, Jun; Irie, Seiichiro; Inoue, Koji; Sato, Teiko; Tsutsumi, Yutaka

    2012-11-01

    Early detection followed by treatment with antibiotics in conjunction with direct or endovascular surgery is integral in the management of patients with intracranial infectious aneurysms. These aneurysms often manifest as massive intracranial hemorrhages, which severely deteriorate the outcome. It is very important to detect infectious aneurysms before they rupture. Although usually associated with infective endocarditis, these aneurysms can occur in a variety of clinical settings. We present a case of ?-Streptococcus-provoked infectious aneurysm in a patient without infective endocarditis, initially presenting as atherothrombotic-like brain infarction, before massive intracranial hemorrhage. The present case alerts clinicians to keep in mind possible development of infectious aneurysms, even in patients who appear to be suffering from atherothrombotic stoke, especially in patients presenting with signs of infection. PMID:22133741

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

    Microsoft Academic Search

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

    2005-01-01

    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

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

    PubMed Central

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

    2014-01-01

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

  6. Regional left ventricular myocardial contractility and stress in a finite element model of posterobasal myocardial infarction.

    PubMed

    Wenk, Jonathan F; Sun, Kay; Zhang, Zhihong; Soleimani, Mehrdad; Ge, Liang; Saloner, David; Wallace, Arthur W; Ratcliffe, Mark B; Guccione, Julius M

    2011-04-01

    Recently, a noninvasive method for determining regional myocardial contractility, using an animal-specific finite element (FE) model-based optimization, was developed to study a sheep with anteroapical infarction (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001). Using the methodology developed in the previous study (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001), which incorporates tagged magnetic resonance images, three-dimensional myocardial strains, left ventricular (LV) volumes, and LV cardiac catheterization pressures, the regional myocardial contractility and stress distribution of a sheep with posterobasal infarction were investigated. Active material parameters in the noninfarcted border zone (BZ) myocardium adjacent to the infarct (T(max_B)), in the myocardium remote from the infarct (T(max_R)), and in the infarct (T(max_I)) were estimated by minimizing the errors between FE model-predicted and experimentally measured systolic strains and LV volumes using the previously developed optimization scheme. The optimized T(max_B) was found to be significantly depressed relative to T(max_R), while T(max_I) was found to be zero. The myofiber stress in the BZ was found to be elevated, relative to the remote region. This could cause further damage to the contracting myocytes, leading to heart failure. PMID:21428685

  7. Regional assessment of LV wall in infarcted heart using tagged MRI and cardiac modelling

    NASA Astrophysics Data System (ADS)

    Jahanzad, Zeinab; Miin Liew, Yih; Bilgen, Mehmet; McLaughlin, Robert A.; Onn Leong, Chen; Chee, Kok Han; Aziz, Yang Faridah Abdul; Ung, Ngie Min; Lai, Khin Wee; Ng, Siew-Cheok; Lim, Einly

    2015-05-01

    A segmental two-parameter empirical deformable model is proposed for evaluating regional motion abnormality of the left ventricle. Short-axis tagged MRI scans were acquired from 10 healthy subjects and 10 postinfarct patients. Two motion parameters, contraction and rotation, were quantified for each cardiac segment by fitting the proposed model using a non-rigid registration algorithm. The accuracy in motion estimation was compared to a global model approach. Motion parameters extracted from patients were correlated to infarct transmurality assessed with delayed-contrast-enhanced MRI. The proposed segmental model allows markedly improved accuracy in regional motion analysis as compared to the global model for both subject groups (1.22–1.40?mm versus 2.31–2.55?mm error). By end-systole, all healthy segments experienced radial displacement by ~25–35% of the epicardial radius, whereas the 3 short-axis planes rotated differently (basal: 3.3° mid:???1° and apical:???4.6°) to create a twisting motion. While systolic contraction showed clear correspondence to infarct transmurality, rotation was nonspecific to either infarct location or transmurality but could indicate the presence of functional abnormality. Regional contraction and rotation derived using this model could potentially aid in the assessment of severity of regional dysfunction of infarcted myocardium.

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

    Microsoft Academic Search

    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

    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

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

    E-print Network

    California at Davis, University of

    2005-01-01

    differences in brain structure between men and women across the span of human aging. The ability to extend 2200 male and female participants of the Framingham Heart Study who ranged in age from 34 to 97 years generally not significant after correcting for gender related differences in head size. Age explained

  10. MIQuant – Semi-Automation of Infarct Size Assessment in Models of Cardiac Ischemic Injury

    PubMed Central

    Esteves, Tiago; de Pina, Maria de Fátima; Guedes, Joana G.; Freire, Ana; Quelhas, Pedro; Pinto-do-Ó, Perpétua

    2011-01-01

    Background The cardiac regenerative potential of newly developed therapies is traditionally evaluated in rodent models of surgically induced myocardial ischemia. A generally accepted key parameter for determining the success of the applied therapy is the infarct size. Although regarded as a gold standard method for infarct size estimation in heart ischemia, histological planimetry is time-consuming and highly variable amongst studies. The purpose of this work is to contribute towards the standardization and simplification of infarct size assessment by providing free access to a novel semi-automated software tool. The acronym MIQuant was attributed to this application. Methodology/Principal Findings Mice were subject to permanent coronary artery ligation and the size of chronic infarcts was estimated by area and midline-length methods using manual planimetry and with MIQuant. Repeatability and reproducibility of MIQuant scores were verified. The validation showed high correlation (rmidline length?=?0.981; rarea?=?0.970 ) and agreement (Bland-Altman analysis), free from bias for midline length and negligible bias of 1.21% to 3.72% for area quantification. Further analysis demonstrated that MIQuant reduced by 4.5-fold the time spent on the analysis and, importantly, MIQuant effectiveness is independent of user proficiency. The results indicate that MIQuant can be regarded as a better alternative to manual measurement. Conclusions We conclude that MIQuant is a reliable and an easy-to-use software for infarct size quantification. The widespread use of MIQuant will contribute towards the standardization of infarct size assessment across studies and, therefore, to the systematization of the evaluation of cardiac regenerative potential of emerging therapies. PMID:21980376

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

    PubMed Central

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

    2012-01-01

    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. PMID:22438975

  12. AITA : Brain Modelling John A. Bullinaria, 2003

    E-print Network

    Bullinaria, John

    ? Development ­ Learning and Maturation Adult Performance Measures Brain Damage / Neuropsychological Deficits 2. Validating the Models ­ Experimental Testing 3. Modelling Simple Cognitive Tasks ­ A Case Study Models are modelling. Brain Damage / Neuropsychological Deficits : Often performance deficits, e.g. due to brain damage

  13. Renin inhibition improves the survival of mesenchymal stromal cells in a mouse model of myocardial infarction.

    PubMed

    Franchi, Federico; Ezenekwe, Adachukwu; Wellkamp, Lukas; Peterson, Karen M; Lerman, Amir; Rodriguez-Porcel, Martin

    2014-08-01

    The aim of this study was to determine if renin inhibition is able to improve the survival of transplanted stem cells in a mouse model of myocardial infarction. Myocardial infarction was induced in FVB/NJ inbred mice (n?=?23). Bone marrow-derived mouse mesenchymal stromal cells (mMSCs, 3?×?10(5)) expressing the reporter gene firefly luciferase were delivered intramyocardially (n?=?12) and monitored non-invasively by bioluminescence imaging. A group of these mice (n?=?6) received aliskiren (15 mg/kg/day) via an osmotic pump implanted subcutaneously. The survival of mMSCs was significantly increased in those animals that received aliskiren leading to a significant improvement in systolic function after myocardial infarction. Histological analysis revealed a significant reduction in inflammation and collagen deposition in those mice that received aliskiren compared to controls. Renin inhibition of the ischemic myocardium is able to modulate the microenvironment improving the survival and efficacy of transplanted mMSCs in a mouse model of myocardial infarction. PMID:25030734

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

    MacDougall, Niall J J; Muir, Keith W

    2011-01-01

    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. PMID:21157471

  17. Intramyocardial Injection of Allogenic Bone Marrow-Derived Mesenchymal Stem Cells Without Immunosuppression Preserves Cardiac Function in a Porcine Model of Myocardial Infarction

    Microsoft Academic Search

    Raj R. Makkar; Matthew J. Price; Michael Lill; Malka Frantzen; Kaname Takizawa; Thomas Kleisli; Jie Zheng; Saibal Kar; Robert McClelan; Takeshi Miyamota; Justin Bick-Forrester; Michael C. Fishbein; Prediman K. Shah; James S. Forrester; Behrooz Sharifi; Peng-Sheng Chen; Mohammed Qayyum

    2005-01-01

    Background: We investigated the efficacy of directly injected allogenic bone marrow-derived mesenchymal stem cells in improving left ventricular function in a porcine model of myocardial infarction.Methods: Left ventricular infarction was created in 16 adult Yorkshire pigs by coil embolization and thrombotic occlusion distal to the second diagonal artery. One month after myocardial infarction was induced, the animals were randomized to

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

    Microsoft Academic Search

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

    2009-01-01

    Aim:To appraise the efficacy of CD151-induced myocardial therapeutic angiogenesis in a pig myocardial infarction model.Methods:CD151 and anti-CD151 were constructed into the recombinant adeno-associated virus (rAAV) vector. All 26 pigs were subjected to coronary artery ligation or no surgery. Eight weeks after coronary artery ligation, the expression of CD151 was measured by Western blot and immunostaining. Capillary density was evaluated using

  19. Computational Modeling of the Effects of Myocardial Infarction on Left Ventricular Hemodynamics

    NASA Astrophysics Data System (ADS)

    Vedula, Vijay; Seo, Jung Hee; Mittal, Rajat; Fortini, Stefania; Querzoli, Giorgio

    2012-11-01

    Most in-vivo and modeling studies on myocardial infarction and ischemia have been directed towards understanding the left ventricular wall mechanics including stress-strain behavior, end systolic pressure-volume correlations, ejection fraction and stroke work. Fewer studies have focused on the alterations in the intraventricular blood flow behavior due to local infarctions. Changes in the motion of the endocardium can cause local circulation and stagnation regions; these increase the blood cell residence time in the left ventricle and may eventually be implicated in thrombus formation. In the present study, we investigate the effects of myocardial infarction on the ventricular hemodynamics in simple models of the left ventricle using an immersed-boundary flow solver. Apart from the Eulerian flow features such as vorticity and velocity flow fields, pressure distribution, shear stress, viscous dissipation and pump work, we also examine the Lagrangian dynamics of the flow to gain insights into the effect of flow dynamics on thrombus formation. The study is preceded by a comprehensive validation study which is based on an in-vitro experimental model of the left ventricle and this study is also described. This research is supported by the U.S. National Science Foundation through (NSF) CDI-Type II grant IOS-1124804. Computational resources for some of the simulations were also provided in part through the NSF grant NSF-OCI-108849.

  20. Enhanced infarct stabilization and neovascularization mediated by VEGF-loaded PEGylated fibrinogen hydrogel in a rodent myocardial infarction model.

    PubMed

    Rufaihah, Abdul Jalil; Vaibavi, Srirangam Ramanujam; Plotkin, Marian; Shen, Jiayi; Nithya, Venkateswaran; Wang, Jing; Seliktar, Dror; Kofidis, Theodoros

    2013-11-01

    Most tissue engineering therapies require biomaterials that are able to induce an angiogenic response to support tissue regeneration. In addition angiogenic growth factor signaling plays an essential role in controlling the process of angiogenesis and matrices have the potential of regulating the concentration of growth factors within the cellular microenvironment. Here we demonstrated myocardial protection and improved post-infarct vascularization of the infarcted hearts using a biosynthetic injectable hydrogel consisting of polyethylene glycol and fibrinogen (PEG-fibrinogen) loaded with vascular endothelial growth factor-A (VEGF-A). Our data revealed PEG-fibrinogen hydrogel was able to store and release VEGF-A in a sustained and controlled fashion. Upon injection after coronary artery ligation, the VEGF-loaded hydrogel significantly improved arteriogenesis and cardiac performance at 4 weeks post-infarction. The results support the future application of PEG-fibrinogen for regulating growth factor signaling in cellular microenvironment and may demonstrates a new strategy for cardiovascular repair with potential for future clinical applications. PMID:23891519

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

    NASA Astrophysics Data System (ADS)

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

    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.

  2. Hierarchical models in the brain.

    PubMed

    Friston, Karl

    2008-11-01

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

  3. Hierarchical Models in the Brain

    PubMed Central

    Friston, Karl

    2008-01-01

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

  4. Cognitive informatics models of the brain

    Microsoft Academic Search

    Yingxu Wang; Ying Wang

    2006-01-01

    The human brain is the most complicated organ in the universe and a new frontier yet to be explored by an interdisciplinary approach. This paper attempts to develop logical and cognitive models of the brain by using cognitive informatics and formal methodologies. This paper adopts a memory-based approach to explore the brain and to demonstrate that memory is the foundation

  5. The isolated working heart model in infarcted rat hearts

    Microsoft Academic Search

    G Itter; W Jung; B A Schoelkens; W Linz

    2005-01-01

    Summary Congestive heart failure (CHF) is one of the most common causes of death in western countries. The aim of this study was to establish and validate the working heart model in rat hearts with CHF. In the rat model the animals show parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure.

  6. Current models of the marmoset brain.

    PubMed

    Hashikawa, Tsutomu; Nakatomi, Reiko; Iriki, Atsushi

    2015-04-01

    Since the availability of the common marmoset monkey as a primate model in neuroscience research has recently increased, much effort has been made to develop a reliable guide of the brain structures of this species. In this article, we review the development of the marmoset brain atlas and discuss a newly developed brain model, which was reconstructed from histological sections under volume-rendering technology. This kind of brain model allows virtual sections to be constructed on any axis, with nomenclatural annotations to structures in situ. This model is also applicable for the identification of structures revealed in magnetic resonance imaging studies. The brain model is accessible at the following web address: http://brainatlas.brain.riken.jp/marmoset/modules/xoonips/listitem.php?index_id=66. PMID:25817023

  7. Effect of Donepezil on Wernicke Aphasia After Bilateral Middle Cerebral Artery Infarction: Subtraction Analysis of Brain F-18 Fluorodeoxyglucose Positron Emission Tomographic Images.

    PubMed

    Yoon, Seo Yeon; Kim, Je-Kyung; An, Young-Sil; Kim, Yong Wook

    2015-01-01

    Aphasia is one of the most common neurologic deficits occurring after stroke. Although the speech-language therapy is a mainstream option for poststroke aphasia, pharmacotherapy is recently being tried to modulate different neurotransmitter systems. However, the efficacy of those treatments is still controversial. We present a case of a 53-year-old female patient with Wernicke aphasia, after the old infarction in the territory of left middle cerebral artery for 8 years and the recent infarction in the right middle cerebral artery for 4 months. On the initial evaluation, the Aphasia Quotient in Korean version of the Western Aphasia Battery was 25.6 of 100. Baseline brain F-18 fluorodeoxyglucose positron emission tomographic images demonstrated a decreased cerebral metabolism in the left temporoparietal area and right temporal lobe. Donepezil hydrochloride, a reversible acetylcholinesterase inhibitor, was orally administered 5 mg/d for 6 weeks after the initial evaluation and was increased to 10 mg/d for the following 6 weeks. After the donepezil treatment, the patient showed improvement in language function, scoring 51.0 of 100 on Aphasia Quotient. A subtraction analysis of the brain F-18 fluorodeoxyglucose positron emission tomographic images after donepezil medication demonstrated increased uptake in both middle temporal gyri, extended to the occipital area and the left cerebellum. Thus, we suggest that donepezil can be an effective therapeutic choice for the treatment of Wernicke aphasia. PMID:26166237

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

    PubMed Central

    Pokreisz, Peter; Schnitzer, Jan E.

    2013-01-01

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

  9. A novel model for prenatal brain damage

    Microsoft Academic Search

    Joseph L Nuñez; Jesse J Alt; Margaret M McCarthy

    2003-01-01

    Premature infants are at especially high risk for asphyxia, seizures, and other conditions that cause hypoxia–ischemia. These events result in abnormal brain pathology and behavioral deficits that persist throughout adolescence and into adulthood. Current rodent models of human infant hypoxic–ischemic brain damage have focused on exogenous glutamate receptor agonist exposure in the postnatal day 7 rat. While this model is

  10. Anti-edema action of thyroid hormone in MCAO model of ischemic brain stroke: Possible association with AQP4 modulation.

    PubMed

    Sadana, Prabodh; Coughlin, Lucy; Burke, Jamie; Woods, Robert; Mdzinarishvili, Alexander

    2015-07-15

    The use of neuroprotective strategies to mitigate the fatal consequences of ischemic brain stroke is a focus of robust research activity. We have previously demonstrated that thyroid hormone (T3; 3,3',5-triiodo-l-thyronine) possesses neuroprotective and anti-edema activity in pre-stroke treatment regimens when administered as a solution or as a nanoparticle formulation. In this study we have extended our evaluation of thyroid hormone use in animal models of brain stroke. We have used both transient middle cerebral artery occlusion (t-MCAO) and permanent (p-MCAO) models of ischemic brain stroke. A significant reduction of tissue infarction and a concurrent decrease in edema were observed in the t-MCAO model of brain stroke. However, no benefit of T3 was observed in p-MCAO stroke setting. Significant improvement of neurological outcomes was observed upon T3 treatment in t-MCAO mice. Further, we tested T2 (3,5-diiodo-l-thyronine) a natural deiodination metabolite of T3 in MCAO model of brain stroke. T2 potently decreased infarct size as well as edema formation. Additionally, we report here that T3 suppresses the expression of aquaporin-4 (AQP4) water channels which could be a likely mechanism of its anti-edema activity. Our studies provide evidence to stimulate clinical development of thyroid hormones for use in ischemic brain stroke. PMID:25963308

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

    Microsoft Academic Search

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

    1996-01-01

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

  12. Antiangiogenic Therapy in Brain Tumor Models

    Microsoft Academic Search

    H. J. J. A. Bernsen; A. J. van der Kogel

    1999-01-01

    The prognosis of patients with malignant brain tumors remains poor despite new developments in neurosurgery, chemotherapy and radiotherapy. Malignant gliomas are highly vascularized, and there is ample evidence that their growth is angiogenesis-dependent. Therefore, new therapeutic approaches often include the inhibition of angiogenesis. In this review, experimental studies of antiangiogenic agents in brain tumor models are summarized. The results of

  13. Effect of continuous care model on lifestyle of patients with myocardial infarction

    PubMed Central

    Molazem, Zahra; Rezaei, Soheila; Mohebbi, Zinat; Ostovan, Mohammad-Ali; Keshavarzi, Sareh

    2013-01-01

    BACKGROUND Myocardial infarction (MI) is a life threatening disease that influences the physical, psychological and social dimensions of the individual. Improper lifestyle is one of the causes of this disease. The use of nursing models could be one of the important and fundamental steps in changing the risk factors associated with MI. This study was carried out to evaluate the effect of continuous care model on the lifestyle of patients with MI. METHODS This randomized clinical trial was carried out on 70 patients with MI in coronary care units of hospitals affiliated to Shiraz University of Medical Sciences. Enrolled patients were randomly assigned to intervention or control groups using a randomization list (random permutated blocks with length 4). The continuous care model was used for 35 patients in the intervention group for a period of 3 months and in the control group, the usual cares were applied for 35 patients. Data were collected through lifestyle questionnaire before the intervention and 3 months after. The data were analyzed using chi-square, independent t-test and paired t-test. RESULTS Patients in the intervention group showed significant improvements in lifestyle (125.6 ± 15.4 vs. 180.1 ± 19.9). Moreover, the lifestyle score of intervention group was significantly better than that of the control group (117.9 ± 22.0 vs. 180.1 ± 19.9; P < 0.001) after three months. CONCLUSION Applying a continuous care model had positive effects on the lifestyle of patients with Myocardial Infarction. In order to reduce the risk factors and improve the lifestyle of patients with MI, nurses could use this model to create an effective change. PMID:23766775

  14. Effect of isoflurane post-treatment on tPA-exaggerated brain injury in a rat ischemic stroke model

    PubMed Central

    Kim, Eun Jung; Kim, So Yeon; Lee, Jae Hoon; Kim, Jeong Min; Kim, Jin-Soo; Byun, Jung Ik

    2015-01-01

    Background Intravenous tissue-type plasminogen activator (tPA) is recognized as the standard treatment for ischemic stroke. However, its narrow therapeutic window and association with an increased risk of intracranial hemorrhage have required caution when used. In this context, several approaches are required to deal with the shortcomings of such a double-edged drug. Anesthetics are known to protect against ischemic reperfusion injury, and their protective role in ischemic post-conditioning is crucial for reducing ischemia-related injury. The aim of this study was to assess the effect of isoflurane post-treatment on intracranial hemorrhage and cerebral infarction after tPA treatment for transient cerebral ischemia. Methods Cerebral ischemia was modeled in male Sprague-Dawley rats (n = 32) by occluding the right middle cerebral artery for 1 h, followed by intravenous tPA administration. Rats were randomly divided into control and isoflurane post-treatment group, and isoflurane post-treatment group was post-treated by administering 1.5% isoflurane for 1 h from the start of reperfusion. Twenty-four h after reperfusion, neurobehavioral changes were assessed. The extent of cerebral infarction and intracranial hemorrhage were also assessed by quantification of infarction volume and cerebral hemoglobin concentration from brain tissue, respectively. Results Neurobehavioral testing showed better functional outcomes in the isoflurane post-treatment group than the control group. The extent of cerebral infarction and intracranial hemorrhage were both reduced in isoflurane post-treatment group compared to control group. Conclusions Isoflurane post-treatment may mitigate infarction volume and intracranial hemorrhage in tPA-exaggerated brain injury. Our findings provide an encouraging novel approach for enhancing clinical outcomes in tPA-exaggerated brain injury.

  15. 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

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

    2013-01-01

    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

  16. G-CSF does not improve systolic function in a rat model of acute myocardial infarction

    Microsoft Academic Search

    João Pedro S. Werneck-de-Castro; Ricardo Henrique Costa-e-Sousa; Patricia Fidelis de Oliveira; Vanessa Pinho-Ribeiro; Débora B. Mello; Ramon Peçanha; Elisabete Mattos; Emerson L. Olivares; Anna Carolina V. Maia; José Geraldo Mill; Regina Coeli dos Santos Goldenberg; Antônio Carlos Campos-de-Carvalho

    2006-01-01

    \\u000a Abstract\\u000a \\u000a \\u000a Objective\\u000a   Granulocyte colony-stimulating factor (G-CSF) has been reported to improve cardiac performance by increasing the number of\\u000a bone marrow stem cell in the peripheral circulation. The aim of this study was to investigate the impact of G-CSF administration\\u000a on cardiac function in a rat model of acute myocardial infarction.\\u000a \\u000a \\u000a \\u000a \\u000a Methods\\u000a   Recombinant human G-CSF (Filgrastim, 100 ?g\\/kg, sc) twice a day

  17. A Novel and Efficient Model of Coronary Artery Ligation and Myocardial Infarction in the Mouse

    PubMed Central

    Gao, Erhe; Lei, Yong Hong; Shang, Xiying; Huang, Z. Maggie; Zuo, Lin; Boucher, Matthieu; Fan, Qian; Chuprun, J. Kurt; Ma, Xin L.; Koch, Walter J.

    2010-01-01

    Rationale Coronary artery ligation to induce myocardial infarction (MI) in mice is typically performed by an invasive and time consuming approach that requires ventilation and chest opening (classical method), often resulting in extensive tissue damage and high mortality. We developed a novel and rapid surgical method to induce MI that does not require ventilation. Objective The purpose of this study was to develop and comprehensively describe this method and directly compare it to the classical method. Methods and Results Male C57/B6 mice were grouped into four groups: new method MI (MI-N) or sham (S-N), classical method MI (MI-C) or sham (S-C). In new method, heart was manually exposed without intubation through a small incision and MI was induced. In classical method, MI was induced through a ventilated thoracotomy. Similar groups were used in an ischemia/reperfusion injury model. This novel MI procedure is rapid with an average procedure time of 1.22±0.05 min while the classical method requires 23.2±0.6 min per procedure. Surgical mortality was 3% in MI-N and 15.9% in MI-C. The rate of arrhythmia was significantly lower in MI-N. The post-surgical levels of TNF? and myeloperoxidase (MPO) were lower in new method indicating less inflammation. Overall 28 day post-MI survival rate was 68% with MI-N and 48% with MI-C. Importantly, there was no difference in infarct size or post-MI cardiac function between methods. Conclusion This new rapid method of MI in mice represents a more efficient and less damaging model of myocardial ischemic injury compared to the classical method. PMID:20966393

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

    PubMed Central

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

    2013-01-01

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

  19. Ligands for opioid and ?-receptors improve cardiac electrical stability in rat models of post-infarction cardiosclerosis and stress

    Microsoft Academic Search

    Yu. B. Lishmanov; L. N. Maslov; N. V. Naryzhnaya; S. W. Tam

    1999-01-01

    The effects of the extremely selective ?-opioid receptor agonist, [D-Arg2,Lys4]-dermorphin-(1–4)-amide (DALDA), the ?-opioid receptor agonist morphine, the ?? agonist D-Ala2, Leu5, Arg6-enkephalin (dalargin), the ?-opioid receptor agonist spiradoline and the ?1-receptor antagonist DuP 734 on ventricular fibrillation threshold (VFT) was investigated in an experimental post-infarction cardiosclerosis model and an immobilization stress-induced model in rats. Both models produced a significant decrease

  20. Usefulness of plasma brain natriuretic peptide concentration for predicting subsequent left ventricular remodeling after coronary angioplasty in patients with acute myocardial infarction.

    PubMed

    Hirayama, Atsushi; Kusuoka, Hideo; Yamamoto, Hiroyoshi; Sakata, Yasushi; Asakura, Masanori; Higuchi, Yoshiharu; Mizuno, Hiroya; Kashiwase, Kazunori; Ueda, Yasunori; Okuyama, Yuji; Hori, Masatsugu; Kodama, Kazuhisa

    2006-08-15

    To determine the relation between plasma brain natriuretic peptide (BNP) and remodeling in terms of infarct-related artery (IRA) patency, 106 patients with a first anterior wall acute myocardial infarction with a patent IRA at 1 month were studied. The IRA reoccluded at 6 months in 17 patients (reoccluded IRA) and was patent in 89 patients (patent IRA). The 2 groups did not differ with respect to clinical characteristics, hemodynamic variables, and left ventricular function at 1 month, except for left ventricular end-diastolic and systolic volumes, which were significantly greater in the reoccluded IRA group. Plasma BNP concentration in the reoccluded IRA group (336 +/- 288 pg/ml) was significantly higher than that in the patent IRA group (116 +/- 106 pg/ml) at 1 month. BNP concentration decreased significantly at 6 months in the 2 groups (reoccluded IRA vs patent IRA 152 +/- 162 vs 44 +/- 58 pg/ml, p <0.05). The increase in left ventricular volume from 1 to 6 months was significantly correlated with plasma BNP concentration at 1 month in the patent IRA group (r = 0.314, p < 0.01) and the reoccluded group (r = 0.634, p < 0.01). Linear regression analysis showed that the correlation between the 2 parameters in the 2 groups was similar. Based on stepwise multivariate linear regression analysis, only plasma BNP concentration was significantly correlated with the increase in left ventricular volume from 1 to 6 months in the 2 groups. In conclusion, these results suggest that plasma BNP concentration predicts left ventricular dilation independently of IRA patency. PMID:16893696

  1. I.V. INFUSION OF BRAIN-DERIVED NEUROTROPHIC FACTOR GENE-MODIFIED HUMAN MESENCHYMAL STEM CELLS PROTECTS AGAINST INJURY IN A CEREBRAL ISCHEMIA MODEL IN ADULT RAT

    PubMed Central

    NOMURA, T.; HONMOU, O.; HARADA, K.; HOUKIN, K.; HAMADA, H.; KOCSIS, J. D.

    2008-01-01

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

  2. Ligands for opioid and sigma-receptors improve cardiac electrical stability in rat models of post-infarction cardiosclerosis and stress.

    PubMed

    Lishmanov YuB; Maslov, L N; Naryzhnaya, N V; Tam, S W

    1999-01-01

    The effects of the extremely selective mu-opioid receptor agonist, [D-Arg2,Lys4]-dermorphin-(1-4)-amide (DALDA), the mu-opioid receptor agonist morphine, the mu/delta agonist D-Ala2, Leu5, Arg6-enkephalin (dalargin), the kappa-opioid receptor agonist spiradoline, and the sigma1-receptor antagonist DuP 734 on ventricular fibrillation threshold (VFT) was investigated in an experimental post-infarction cardiosclerosis model and an immobilization stress-induced model in rats. Both models produced a significant decrease in VFT. The postinfarction cardiosclerosis-induced decrease in VFT was significantly reversed by intravenous administration of dalargin (0.1 mg/kg), DALDA (0.1 mg/kg), or morphine HCl (1.5 mg/kg). Pretreatment with naloxone (0.2 mg/kg) completely eliminated the increase in cardiac electrical stability produced by DALDA. Both spiradoline (8 mg/kg, i.p.) and DuP 734 (1 mg/kg, i.p.) produced a significant increase in VFT in rats with post-infarction cardiosclerosis. This effect of spiradoline was blocked by nor-binaltorphimine. The immobilization stress-induced decrease in VFT was significantly reversed by administration of either DALDA, spiradoline or DuP 734. In conclusion, activation of either mu- or kappa1-opioid receptors or blockade of sigma1-receptors reversed the decrease in VFT in both cardiac compromised models. Since DALDA and dalargin essentially do not cross blood brain barriers, their effects on VFT may be mediated through peripheral mu-opioid receptors. PMID:10403501

  3. Coupled Hemodynamic-Biochemical Modeling of Thrombus Formation in Infarcted Left Ventricles

    NASA Astrophysics Data System (ADS)

    Seo, Jung Hee; Vedula, Vijay; George, Richard; Mittal, Rajat

    2013-11-01

    Patients with heart failure (HF) and left ventricular (LV) systolic dysfunction have higher rates of thromboembolic events including embolic stroke and peripheral arterial thrombi. A common cause of arterial emboli in HF patients is myocardial infarction (MI) and subsequent left ventricular thrombus (LVT) formation. Stagnation of blood and endocardial injury are hypothesized to promote the development of LVT. The identification of high risk patients and the pharmacologic prevention of LVT formation are the keys to preventing embolic events. Stratification of patients at risk for LVT formation is currently limited, and primarily based on global assessment of ventricular function and image based assessment of ventricular wall motion. In this study, we explore a method to predict LVT risk using a multi-physics computational model. The blood flow in the left ventricle is simulated by solving the incompressible Navier-Stokes equation using an immersed boundary method and this is coupled to a convection-diffusion-reaction equation based model of platelet activation and coagulation. The results are then correlated with the other hemodynamic metrics such as wall shear stress and residence time to develop quantitative metrics for the LVT risk prediction. Patients with heart failure (HF) and left ventricular (LV) systolic dysfunction have higher rates of thromboembolic events including embolic stroke and peripheral arterial thrombi. A common cause of arterial emboli in HF patients is myocardial infarction (MI) and subsequent left ventricular thrombus (LVT) formation. Stagnation of blood and endocardial injury are hypothesized to promote the development of LVT. The identification of high risk patients and the pharmacologic prevention of LVT formation are the keys to preventing embolic events. Stratification of patients at risk for LVT formation is currently limited, and primarily based on global assessment of ventricular function and image based assessment of ventricular wall motion. In this study, we explore a method to predict LVT risk using a multi-physics computational model. The blood flow in the left ventricle is simulated by solving the incompressible Navier-Stokes equation using an immersed boundary method and this is coupled to a convection-diffusion-reaction equation based model of platelet activation and coagulation. The results are then correlated with the other hemodynamic metrics such as wall shear stress and residence time to develop quantitative metrics for the LVT risk prediction. Supported by NSF CDI-Type II grant IOS-1124804, Computational resource by XSEDE NSF grant TG-CTS100002.

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

    PubMed

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

    2014-12-01

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

  5. A model for lupus brain disease

    PubMed Central

    Diamond, Betty; Volpe, Bruce T.

    2015-01-01

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

  6. Endothelium and myocyte cellular insulin receptor alterations in a rat model of myocardial infarction.

    PubMed

    Jaroudi, Wael A; Jurjus, Abdo R; El-Sabban, Marwan E; Kamal, Maud T; Bitar, Khalil M; Bikhazi, Anwar B

    2003-03-01

    Ischemic heart disease is considered to be one of the leading causes of death in adults. While extensive research on mechanisms contributing to the pathogenesis of myocardial infarction (MI) has been underway, it is not known whether insulin receptor characteristics and postreceptor signaling have been fully addressed as yet. Present work attempts to investigate whether the remodeling process effectively induces alteration(s) in insulin-binding characteristics at the coronary endothelium and cardiomyocytes using a rat heart model of MI. MI was induced by ligation of the left anterior descending coronary artery of adult male Sprague-Dawley rats. Two animal groups were used in the study: (i) sham-operated CHAPS-untreated and CHAPS-treated, and (ii) MI CHAPS-untreated and MI CHAPS-treated. A physical model describing 1:1 stoichiometry of reversible insulin binding to its receptors present on the endothelium and at cardiomyocytes after CHAPS treatment was considered for data analysis. Quantitation of the collected effluents after heart perfusion, the inlet at the aortic and outlet at the coronary sinus sites, were curve fitted using a first-order Bessel function, which determines the binding constants (k(n)), the reversible constant (k(-n)), the dissociation constant (k(d) = k(-n)/k(n)), and the residency time constant (tau = 1/k(-n)). In addition, hearts were excised, separated into right and left ventricles, and individually weighed, and areas of infarcted regions were measured. Results of the MI group showed significant increases in relative heart mass, left ventricle mass, and right ventricle mass normalized to total body mass. MI induced severe ischemia and irreversible myocardial injury as assessed by planimetry and histologic studies. The data showed differences in insulin receptor affinities at the endothelial and cardiac myocytes in the sham and in the MI-operated rats. The observed reduction in the binding affinity of insulin at the myocyte postinfarction may explain the pathogenic role of insulin in ischemic heart disease and, hence, resistance. Therefore, insulin administration during and post MI might be cardioprotective. PMID:12733825

  7. Multimodal, Multidimensional Models of Mouse Brain

    PubMed Central

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

    2011-01-01

    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. PMID:17767578

  8. Assessment of distribution and evolution of Mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance

    PubMed Central

    2012-01-01

    Background We sought to investigate the relationship between infarct and dyssynchrony post- myocardial infarct (MI), in a porcine model. Mechanical dyssynchrony post-MI is associated with left ventricular (LV) remodeling and increased mortality. Methods Cine, gadolinium-contrast, and tagged cardiovascular magnetic resonance (CMR) were performed pre-MI, 9 ± 2 days (early post-MI), and 33 ± 10 days (late post-MI) post-MI in 6 pigs to characterize cardiac morphology, location and extent of MI, and regional mechanics. LV mechanics were assessed by circumferential strain (eC). Electro-anatomic mapping (EAM) was performed within 24 hrs of CMR and prior to sacrifice. Results Mean infarct size was 21 ± 4% of LV volume with evidence of post-MI remodeling. Global eC significantly decreased post MI (-27 ± 1.6% vs. -18 ± 2.5% (early) and -17 ± 2.7% (late), p < 0.0001) with no significant change in peri-MI and MI segments between early and late time-points. Time to peak strain (TTP) was significantly longer in MI, compared to normal and peri-MI segments, both early (440 ± 40 ms vs. 329 ± 40 ms and 332 ± 36 ms, respectively; p = 0.0002) and late post-MI (442 ± 63 ms vs. 321 ± 40 ms and 355 ± 61 ms, respectively; p = 0.012). The standard deviation of TTP in 16 segments (SD16) significantly increased post-MI: 28 ± 7 ms to 50 ± 10 ms (early, p = 0.012) to 54 ± 19 ms (late, p = 0.004), with no change between early and late post-MI time-points (p = 0.56). TTP was not related to reduction of segmental contractility. EAM revealed late electrical activation and greatly diminished conduction velocity in the infarct (5.7 ± 2.4 cm/s), when compared to peri-infarct (18.7 ± 10.3 cm/s) and remote myocardium (39 ± 20.5 cm/s). Conclusions Mechanical dyssynchrony occurs early after MI and is the result of delayed electrical and mechanical activation in the infarct. PMID:22226320

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

    PubMed Central

    2013-01-01

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

  10. Effects of heme oxygenase-1 upregulation on blood pressure and cardiac function in an animal model of hypertensive myocardial infarction.

    PubMed

    Chen, Tian-Meng; Li, Jian; Liu, Lin; Fan, Li; Li, Xiao-Ying; Wang, Yu-Tang; Abraham, Nader G; Cao, Jian

    2013-01-01

    In this study, we evaluate the effect of HO-1 upregulation on blood pressure and cardiac function in the new model of infarct spontaneous hypertensive rats (ISHR). Male spontaneous hypertensive rats (SHR) at 13 weeks (n = 40) and age-matched male Wistar (WT) rats (n = 20) were divided into six groups: WT (sham + normal saline (NS)), WT (sham + Co(III) Protoporphyrin IX Chloride (CoPP)), SHR (myocardial infarction (MI) + NS), SHR (MI + CoPP), SHR (MI + CoPP + Tin Mesoporphyrin IX Dichloride (SnMP)), SHR (sham + NS); CoPP 4.5 mg/kg, SnMP 15 mg/kg, for six weeks, one/week, i.p., n = 10/group. At the sixth week, echocardiography (UCG) and hemodynamics were performed. Then, blood samples and heart tissue were collected. Copp treatment in the SHR (MI + CoPP) group lowered blood pressure, decreased infarcted area, restored cardiac function (left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), +dp/dt(max), (-dp/dt(max))/left ventricular systolic pressure (LVSP)), inhibited cardiac hypertrophy and ventricular enlargement (downregulating left ventricular end-systolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and heart weight/body weight (HW/BW)), lowered serum CRP, IL-6 and Glu levels and increased serum TB, NO and PGI2 levels. Western blot and immunohistochemistry showed that HO-1 expression was elevated in the SHR (MI + CoPP) group, while co-administration with SnMP suppressed the benefit functions mentioned above. In conclusion, HO-1 upregulation can lower blood pressure and improve post-infarct cardiac function in the ISHR model. These functions may be involved in the inhibition of inflammation and the ventricular remodeling process and in the amelioration of glucose metabolism and endothelial dysfunction. PMID:23358254

  11. Generative models, brain function and neuroimaging.

    PubMed

    Friston, K J; Price, C J

    2001-07-01

    The representational capacity and inherent function of any neuron, neuronal population or cortical area in the brain is dynamic and context-sensitive. Functional integration, or interactions among brain systems, that employ driving (bottom up) and backward (top-down) connections, mediate this adaptive and contextual specialisation. A critical consequence is that neuronal responses, in any given cortical area, can represent different things at different times. This can have fundamental implications for the design of brain imaging experiments and the interpretation of their results. Our arguments are developed under generative models of brain function, where higher-level systems provide a prediction of the inputs to lower-level regions. Conflict between the two is resolved by changes in the higher-level representations, which are driven by the ensuing error in lower regions, until the mismatch is "cancelled". From this perspective the specialisation of any region is determined both by bottom-up driving inputs and by top-down predictions. Specialisation is therefore not an intrinsic property of any region but depends on both forward and backward connections with other areas. Because the latter have access to the context in which the inputs are generated they are in a position to modulate the selectivity or specialisation of lower areas. The implications for classical models (e.g., classical receptive fields in electrophysiology, classical specialisation in neuroimaging and connectionism in cognitive models) are severe and suggest these models may provide incomplete accounts of real brain architectures. Here we focus on the implications for cognitive neuroscience in the context of neuroimaging. PMID:11501732

  12. Relationship between Retrograde Coronary Blood Flow and the Extent of No-Reflow and Infarct Size in a Porcine Ischemia–Reperfusion Model

    Microsoft Academic Search

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

    2011-01-01

    Recanalization of an infarct-related artery does not predictably reflect tissue reperfusion. We examined the relationship\\u000a between coronary blood flow (CBF) pattern during reperfusion and infarcted (IA) and no-reflow (NR) area in a porcine ischemia–reperfusion\\u000a model. The mid-left anterior descending artery of 18 pigs was occluded for 1 h and reperfused for 2 h. CBF during reperfusion\\u000a was measured with a transit-time ultrasound

  13. Imaging of VEGF Receptor in a Rat Myocardial Infarction Model Using PET

    PubMed Central

    Rodriguez-Porcel, Martin; Cai, Weibo; Gheysens, Olivier; Willmann, Jürgen K.; Chen, Kai; Wang, Hui; Chen, Ian Y.; He, Lina; Wu, Joseph C.; Li, Zi-bo; Mohamedali, Khalid A.; Kim, Sehoon; Rosenblum, Michael G.; Chen, Xiaoyuan; Gambhir, Sanjiv Sam

    2010-01-01

    Myocardial infarction (MI) leads to left ventricular (LV) remodeling, which leads to the activation of growth factors such as vascular endothelial growth factor (VEGF). However, the kinetics of a growth factor's receptor expression, such as VEGF, in the living subject has not yet been described. We have developed a PET tracer (64Cu-DOTA-VEGF121 [DOTA is 1,4,7,10-tetraazadodecane-N,N?,N?,N??-tetraacetic acid]) to image VEGF receptor (VEGFR) expression after MI in the living subject. Methods In Sprague–Dawley rats, MI was induced by ligation of the left coronary artery and confirmed by ultrasound (n = 8). To image and study the kinetics of VEGFRs, 64Cu-DOTA-VEGF121 PET scans were performed before MI induction (baseline) and on days 3, 10, 17, and 24 after MI. Sham-operated animals served as controls (n = 3). Results Myocardial origin of the 64Cu-DOTA-VEGF121 signal was confirmed by CT coregistration and autoradiography. VEGFR specificity of the 64Cu-DOTA-VEGF121 probe was confirmed by in vivo use of a 64Cu-DOTA-VEGFmutant. Baseline myocardial uptake of 64Cu-DOTA-VEGF121 was minimal (0.30 ± 0.07 %ID/g [percentage injected dose per gram of tissue]); it increased significantly after MI (day 3, 0.97 ± 0.05 %ID/g; P < 0.05 vs. baseline) and remained elevated for 2 wk (up to day 17 after MI), after which time it returned to baseline levels. Conclusion We demonstrate the feasibility of imaging VEGFRs in the myocardium. In summary, we imaged and described the kinetics of 64Cu-DOTA-VEGF121 uptake in a rat model of MI. Studies such as the one presented here will likely play a major role when studying pathophysiology and assessing therapies in different animal models of disease and, potentially, in patients. PMID:18375924

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

    PubMed

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

    2014-06-01

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

  15. Statistical quantification of brain shape deformation with homologous brain shape modeling

    Microsoft Academic Search

    KOSUKE YAMAGUCHI; S. Kobashi; K. Kuramoto; Y. T. Kitamura; S. Imawaki; Y. Hata

    2010-01-01

    Brain shape is deformed regionally by kinds of cerebral diseases and the degree of progress. Therefore quantitative evaluation of the deformation using MR images is effective for diagnosis of cerebral diseases. We proposed a homologous brain shape modeling deformation for quantitative evaluation of the brain shape using sulcal-distribution index (SDI) in MR images. So in this paper, we propose the

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

    PubMed Central

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

    2015-01-01

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

  17. The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model

    Microsoft Academic Search

    Sang Yup Lim; Yong Sook Kim; Youngkeun Ahn; Myung Ho Jeong; Moon Hwa Hong; Soo Yeon Joo; Kwang Il Nam; Jeong Gwan Cho; Peter M. Kang; Jong Chun Park

    Objective: This study was designed to examine whether mesenchymal stem cells (MSCs) transduced with Akt enhance cardiac repair after transplantation into the ischemic porcine heart. Methods: MSCs isolated from porcine bone marrow and transduced with myr-Akt were transplanted into porcine hearts after experimental myocardial infarction (MI) using intracoronary injection (Group I, vehicle; Group II, MSCs; Group III, Akt-MSCs). Myocardial single

  18. The structure of emotions during acute myocardial infarction: A model of coping

    Microsoft Academic Search

    Angelo A. Alonzo; Nancy R. Reynolds

    1998-01-01

    The present state of medical care for heart attacks, or acute myocardial infarction (AMI), clearly indicates that rapidly and expeditiously seeking definitive medical care will reduce morbidity and prevent mortality. Despite the clearly established advantages of rapid AMI treatment, the time from the onset of acute symptoms of AMI to definitive medical care is often prolonged and individuals with a

  19. Performance Bounds for Dynamic Causal Modeling of Brain Connectivity

    E-print Network

    Swindlehurst, A. Lee

    that represents the simplest brain circuit that would produce the same event-related potentials (ERP's) measuredPerformance Bounds for Dynamic Causal Modeling of Brain Connectivity Shun Chi Wu and A. Lee and causal interactions between different regions of the brain. The goal of these models is to accurately

  20. Dynamic geometry, brain function modeling, and consciousness.

    PubMed

    Roy, Sisir; Llinás, Rodolfo

    2008-01-01

    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

  1. Modeling brain dynamics using computational neurogenetic approach

    PubMed Central

    Kasabov, Nikola

    2008-01-01

    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

  2. Modeling brain dynamics using computational neurogenetic approach.

    PubMed

    Benuskova, Lubica; Kasabov, Nikola

    2008-12-01

    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

  3. Spinal Cord Infarction

    MedlinePLUS

    ... Awards Enhancing Diversity Find People About NINDS NINDS Spinal Cord Infarction Information Page Table of Contents (click to ... is being done? Clinical Trials Organizations What is Spinal Cord Infarction? Spinal cord infarction is a stroke either ...

  4. INFARCT DENSITY DISTRIBUTION BY MRI IN THE PORCINE MODEL OF ACUTE AND CHRONIC MYOCARDIAL INFARCTION AS A POTENTIAL METHOD TRANSFERABLE TO THE CLINIC

    PubMed Central

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

    2014-01-01

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

  5. Doppler Ultrasound Driven Biomechanical Model of the Brain for

    E-print Network

    Paris-Sud XI, Université de

    Doppler Ultrasound Driven Biomechanical Model of the Brain for Intraoperative Brain features. This low-cost system relies on loca- lized 2D Doppler ultrasound imaging of the brain which makes, Doppler ultrasound. hal-00706803,version1-11Jun2012 Author manuscript, published in "Soft Tissue

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

    PubMed Central

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

    2009-01-01

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

  7. Clinical features of acute corpus callosum infarction patients

    PubMed Central

    Yang, Li-Li; Huang, Yi-Ning; Cui, Zhi-Tang

    2014-01-01

    The clinical manifestation of acute corpus callosum (CC) infarction is lack of specificity and complex, so it is easily missed diagnosis and misdiagnosis in the early stage. The present study aims to describe the clinical features of the acute CC infarction. In this study, 25 patients with corpus callosum infarction confirmed by the brain MRI/DWI and the risk factors were summarized. Patients were classified into genu infarction (3 cases), body infarction (4cases), body and genu infarction (4 cases), body and splenium infarction (1 case), splenium infarction (13 cases) according to lesion location. Clinical manifestation and prognosis were analyzed among groups. The results indicated that CC infarction in patients with high-risk group accounted for 72%, moderate-risk group accounted for 20%, low-risk group (8%). The main risk factors are carotid intimal thickening or plaque formation, hypertension, hyperlipidemia, cerebral artery stenosis, and so on. The CC infarction often merged with other parts infarction, and splenium infarction had the highest incidence, the clinical symptoms in the body infarction which can appear typical signs and symptoms, but in other parts infarction which always merged many nerve defect symptoms. The body infarction prognosis is poor; the rest parts of infarction are more favorable prognosis. In conclusion, CC infarction has the highest incidence in the stroke of high-risk group; neck color Doppler and TCD examination can be found as early as possible to explore the pathogenic factors. Prognosis is usually much better by treatment according to the location and risk factors. PMID:25197390

  8. Analysis of different routes of administration of heterologous 5-azacytidine-treated mesenchymal stem cells in a porcine model of myocardial infarction.

    PubMed

    Moscoso, I; Barallobre, J; de Ilarduya, O M; Añón, P; Fraga, M; Calviño, R; Aldama, G; Doménech, N

    2009-01-01

    Stem cell therapy constitutes an exciting, powerful therapy to repair the heart. Nevertheless, there are numerous doubts about the best route of stem cell administration to achieve implantation into the injured myocardium. Development of a preclinical, large animal model may be useful to obtain a better approach to clinical situations. The aim of this work was to study the effectiveness of various routes of heterologous bone marrow mesenchymal stem cell (MSCs) administration in a porcine model of myocardial infarction. MSC treated with 5-azacytidine were stained with a fluorescent compound (DiO) before their administration to previously infarcted pigs via 3 routes: intracoronary (IC), intramyocardial (IM), or endocardial (EC; n = 5 each group). Healthy, noninfarcted animals were used as a control group. At 30 days after delivery, hearts were divided into 12 parts: infarcted zone (1-6), right-left atria, interatrial and interventricular septa, and right-left ventricles. In each zone we looked for and quantified, injected fluorescence-stained cells. In the animals in which presence of DiO-stained cells was detected, cells were located preferentially in the infarcted zone and not in the atria, ventricles, or septa. Comparing various administration routes, the mean number of engrafted cells within the infarct zone was significantly greater after IC infusion than either IM or EC injection. Fluorescent cells were not observed in healthy zones of the myocardium or in healthy animals. PMID:19715895

  9. On a Quantum Model of Brain Activities

    NASA Astrophysics Data System (ADS)

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

    2010-01-01

    One of the main activities of the brain is the recognition of signals. A first attempt to explain the process of recognition in terms of quantum statistics was given in [6]. Subsequently, details of the mathematical model were presented in a (still incomplete) series of papers (cf. [7, 2, 5, 10]). In the present note we want to give a general view of the principal ideas of this approach. We will introduce the basic spaces and justify the choice of spaces and operations. Further, we bring the model face to face with basic postulates any statistical model of the recognition process should fulfill. These postulates are in accordance with the opinion widely accepted in psychology and neurology.

  10. Modeling Brain Energy Metabolism and Function: A Multiparametric Monitoring Approach

    Microsoft Academic Search

    Larisa Vatova; Sigal Meilin; Tamar Manor

    Mathematical modeling of brain function is an important tool needed for a better understanding of experimental results and clinical situations. In the present study, we are constructing and testing a mathematical model capable of simulating changes in brain energy metabolism that develop in real time under various pathophysiological conditions. The model incorporates the following pa- rameters: cerebral blood flow, partial

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

    NSDL National Science Digital Library

    Archibald J. Fobbs Jr.

    2006-07-01

    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).

  12. Rethinking segregation and integration: contributions of whole-brain modelling.

    PubMed

    Deco, Gustavo; Tononi, Giulio; Boly, Melanie; Kringelbach, Morten L

    2015-07-01

    The brain regulates information flow by balancing the segregation and integration of incoming stimuli to facilitate flexible cognition and behaviour. The topological features of brain networks - in particular, network communities and hubs - support this segregation and integration but do not provide information about how external inputs are processed dynamically (that is, over time). Experiments in which the consequences of selective inputs on brain activity are controlled and traced with great precision could provide such information. However, such strategies have thus far had limited success. By contrast, recent whole-brain computational modelling approaches have enabled us to start assessing the effect of input perturbations on brain dynamics in silico. PMID:26081790

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

    E-print Network

    Andrzejak, Artur

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

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

    E-print Network

    Paris-Sud XI, Université de

    The Brain's Router: A Cortical Network Model of Serial Processing in the Primate Brain Ariel-driven behavior. The precise mapping of incoming sensory stimuli onto motor representations relies on a ``router processing on hold, and a slow serial performance at the router stage, resulting in a performance bottleneck

  15. Diffusion Modeling in BrainSuite13 Justin P. Haldar

    E-print Network

    Leahy, Richard M.

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

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

    PubMed Central

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

    2011-01-01

    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. PMID:21273567

  17. Suramin reduces infarct volume in a model of focal brain ischemia in rats

    Microsoft Academic Search

    Alexander Kharlamov; Stephen C. Jones; Kyle D. Kim

    2002-01-01

    .   Extracellular adenosine 5'-triphosphate (ATP) provides excitatory transmission in the central nervous system. Stimulation\\u000a by ATP of ionotropic ligand-gated ion channel purinoceptors (P2X) leads to increased intracellular calcium levels, and activation of P2X receptors may be involved in the process of excitotoxic neuronal injury caused by stroke. Suramin, as an agent that is known\\u000a to block P2X receptors at a

  18. Progress on the paternal brain: theory, animal models, human brain research, and mental health implications.

    PubMed

    Swain, J E; Dayton, C J; Kim, P; Tolman, R M; Volling, B L

    2014-01-01

    With a secure foundation in basic research across mammalian species in which fathers participate in the raising of young, novel brain-imaging approaches are outlining a set of consistent brain circuits that regulate paternal thoughts and behaviors in humans. The newest experimental paradigms include increasingly realistic baby-stimuli to provoke paternal cognitions and behaviors with coordinated hormone measures to outline brain networks that regulate motivation, reflexive caring, emotion regulation, and social brain networks with differences and similarities to those found in mothers. In this article, on the father brain, we review all brain-imaging studies on PubMed to date on the human father brain and introduce the topic with a selection of theoretical models and foundational neurohormonal research on animal models in support of the human work. We discuss potentially translatable models for the identification and treatment of paternal mood and father-child relational problems, which could improve infant mental health and developmental trajectories with potentially broad public health importance. PMID:25798491

  19. On a Mathematical Model of Brain Activities

    SciTech Connect

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

    2007-12-03

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

  20. A toy model of the brain

    Microsoft Academic Search

    B. Hoeneisen; F. Pasmay

    2004-01-01

    We have designed a toy brain and have written computer code that simulates it. This toy brain is flexible, modular, has hierarchical learning and recognition, has short and long term memory, is distributed (i.e. has no central control), is asynchronous, and includes parallel and series processing. We have simulated the neurons calculating their internal voltages as a function of time.

  1. Canine spontaneous brain tumors: A large animal model for BNCT

    SciTech Connect

    Gavin, P.R.; Kraft, S.L.; Wendling, L.R.; Miller, D.L.

    1988-01-01

    Brain tumors occur spontaneously on dogs with an incidence similar to that in humans. Brain tumors of dogs have histologic, radiologic, and other diagnostic similarities to human brain tumors. Tumor kinetics and biologic behavior of these tumors in dogs are also similar to that in man. Recent studies indicate that conventional radiation therapy of brain tumors of dogs result in a survival interval appropriate to study the late radiation reactions in the surrounding normal brain and other tissues within the irradiated field. The relatively large size of the dog allows identical diagnostic and therapeutic modalities and methodology. The dog's head size enables the complex dosimetric variables to be relevant to that found in human radiation therapy. For these reasons, spontaneous brain tumors in the dog are an excellent model to study neuon capture theory (NCT). 7 refs., 1 fig., 3 tabs.

  2. Int. Rev. Neurobiology Friston KJ et al Modelling brain responses

    E-print Network

    Paris-Sud XI, Université de

    Int. Rev. Neurobiology ­ Friston KJ et al Modelling brain responses Karl J Friston, William Penny in "International Review of Neurobiology 2005;66:89-124" DOI : 10.1016/S0074-7742(05)66003-5 #12;Int. Rev. Neurobiology ­ Friston KJ et al ABSTRACT Inferences about brain function, using neuroimaging data, rest

  3. Modeling Brain Energy Metabolism and Function: A Multiparametric Monitoring Approach

    Microsoft Academic Search

    Larisa Vatov; Ziv Kizner; Eytan Ruppin; Sigal Meilin; Tamar Manor; Avraham Mayevsky

    2006-01-01

    Mathematical modeling of brain function is an important tool needed for a better understanding of experimental results and\\u000a clinical situations. In the present study, we are constructing and testing a mathematical model capable of simulating changes\\u000a in brain energy metabolism that develop in real time under various pathophysiological conditions. The model incorporates the\\u000a following parameters: cerebral blood flow, partial oxygen

  4. The Virtual Brain Integrates Computational Modeling and Multimodal Neuroimaging

    PubMed Central

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

    2013-01-01

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

  5. Localized reentry. Mechanism of induced sustained ventricular tachycardia in canine model of recent myocardial infarction.

    PubMed Central

    Garan, H; Ruskin, J N

    1984-01-01

    This study was undertaken to investigate the mechanism underlying sustained monomorphic ventricular tachycardia (VT) in late experimental canine myocardial infarction. The hypothesis that sustained and "organized" continuous electrical activity (CEA) displaying a reproducible pattern with recurrent components recorded by bipolar endocardial, intramural, or epicardial electrodes in 10 animals during electrically induced sustained monomorphic VT represented reentrant excitation in an anatomically small area of the ventricle, was evaluated in the light of the following observations: Organized CEA always preceded the first monomorphic ventricular complex (QRS) of VT as well as the discrete local electrograms from closely surrounding sites during the initiation of VT. The site of organized CEA corresponded to the site of origin of sustained VT determined by iso-chronous contour map analysis of activation sequence. Ventricular pacing at rates more rapid than that of VT failed to terminate VT despite ventricular capture unless it transformed CEA into discrete local electrograms. VT could be terminated in three animals, with a single, critically timed premature stimulus delivered at a critically located focus close to the site of CEA, which would result in local capture and interrupted CEA. In six animals, surgical ablation of the site of organized CEA effectively prevented the reinitiation of sustained VT by programmed cardiac stimulation. These data showed that organized CEA and sustained VT were closely associated phenomena and suggested that organized CEA probably represented an important component of the tachycardia circuit. Images PMID:6746899

  6. Screening for Myocardial Infarction and Ischemic Stroke

    Microsoft Academic Search

    Devin L. Brown; Lynda D. Lisabeth; Stanley J. Chetcuti; P. Michael Grossman; Thomas Alexander; J. Douglas Pappas; Mauro Moscucci; Kim A. Eagle; Nelda M. Garcia; Melinda A. Smith; Lewis B. Morgenstern

    2007-01-01

    Studies that accurately identify myocardial infarction (MI) and stroke within populations would provide valuable epidemiological information as well as data on vascular disease prevention. We performed a pilot study to assess the feasibility of adding MI surveillance to an ongoing population-based stroke surveillance study, the Brain Attack Surveillance in Corpus Christi (BASIC) Project. We also tested two screening methods for

  7. Brain Shift Modeling for Use in Neurosurgery

    Microsoft Academic Search

    Oskar M. Skrinjar; Dennis D. Spencer; James S. Duncan

    1998-01-01

    Surgical navigation systems are used intraoperatively to help the surgeon to ascertain her or his position and to guide tools\\u000a within the patient frame with respect to registered structures of interest in the preoperative images. However, these systems\\u000a are subject to inaccuracy caused by intraoperative brain movement (brain shift) since they assume that the intracranial structures\\u000a are rigid. Experiments show

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

    PubMed

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

    2013-01-01

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

  9. Action of acetylstrophanthidin on experimental myocardial infarction.

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  10. Delayed, but Marked, Expression of Apolipoprotein E Is Involved in Tissue Clearance After Cerebral Infarction

    Microsoft Academic Search

    Kazuo Kitagawa; Masayasu Matsumoto; Keisuke Kuwabara; Toshiho Ohtsuki; Masatsugu Hori

    2001-01-01

    Clearance of infarct tissue would be an important process for tissue repair after a stroke. Delayed clearance may hamper reconstitution of the blood–brain barrier and glial boundary formation. Recent growing evidence has indicated that apolipoprotein E (APOE), a major apoprotein, plays an important role in lipid transport and homeostasis in the brain. The tissue in the infarction contains abundant lipids

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

    PubMed Central

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

    2012-01-01

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

  12. Effect and mechanism of fluoxetine on electrophysiology in vivo in a rat model of postmyocardial infarction depression

    PubMed Central

    Liang, Jinjun; Yuan, Xiaoran; Shi, Shaobo; Wang, Fang; Chen, Yingying; Qu, Chuan; Chen, Jingjing; Hu, Dan; Yang, Bo

    2015-01-01

    Background Major depression is diagnosed in 18% of patients following myocardial infarction (MI), and the antidepressant fluoxetine is shown to effectively decrease depressive symptoms and improve coronary heart disease prognosis. We observed the effect of fluoxetine on cardiac electrophysiology in vivo in a rat model of post-MI depression and the potential mechanism. Methods and results Eighty adult male Sprague Dawley rats (200–250 g) were randomly assigned to five groups: normal control (control group), MI (MI group), depression (depression group), post-MI depression (model group), and post-MI depression treated with intragastric administration of 10 mg/kg fluoxetine (fluoxetine group). MI was induced by left anterior descending coronary artery ligation. Depression was developed by 4-week chronic mild stress (CMS). Behavior measurement was done before and during the experiment. Electrophysiology study in vivo and Western blot analysis were carried on after 4 weeks of CMS. After 4 weeks of CMS, depression-like behaviors were observed in the MI, depression, and model groups, and chronic fluoxetine administration could significantly improve those behaviors (P<0.05 vs model group). Fluoxetine significantly increased the ventricular fibrillation threshold compared with the model group (20.20±9.32 V vs 14.67±1.85 V, P<0.05). Expression of Kv4.2 was significantly reduced by 29%±12%, 24%±6%, and 41%±15%, respectively, in the MI group, CMS group, and model group, which could be improved by fluoxetine (30%±9%). But fluoxetine showed no improvement on the MI-induced loss of Cx43. Conclusion The susceptibility to ventricular arrhythmias was increased in depression and post-MI depression rats, and fluoxetine may reduce the incidence of ventricular arrhythmia in post-MI depression rats and thus improve the prognosis. This may be related in part to the upregulation of Kv4.2 by fluoxetine. PMID:25709400

  13. A Bayesian Model of Category-Specific Emotional Brain Responses

    PubMed Central

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

    2015-01-01

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

  14. [18F]FEBMP: Positron Emission Tomography Imaging of TSPO in a Model of Neuroinflammation in Rats, and in vitro Autoradiograms of the Human Brain

    PubMed Central

    Tiwari, Anjani K.; Ji, Bin; Yui, Joji; Fujinaga, Masayuki; Yamasaki, Tomoteru; Xie, Lin; Luo, Rui; Shimoda, Yoko; Kumata, Katsushi; Zhang, Yiding; Hatori, Akiko; Maeda, Jun; Higuchi, Makoto; Wang, Feng; Zhang, Ming-Rong

    2015-01-01

    We evaluated the efficacy of 2-[5-(4-[18F]fluoroethoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-methyl-N-phenylacetamide] ([18F]FEBMP) for positron emission tomography (PET) imaging of translocator protein (18 kDa, TSPO). Dissection was used to determine the distribution of [18F]FEBMP in mice, while small-animal PET and metabolite analysis were used for a rat model of focal cerebral ischemia. [18F]FEBMP showed high radioactivity uptake in mouse peripheral organs enriched with TSPO, and relatively high initial brain uptake (2.67 ± 0.12% ID/g). PET imaging revealed an increased accumulation of radioactivity in the infarcted striatum, with a maximum ratio of 3.20 ± 0.12, compared to non-injured striatum. Displacement with specific TSPO ligands lowered the accumulation levels in infarcts to those on the contralateral side. This suggests that the increased accumulation reflected TPSO-specific binding of [18F]FEBMP in vivo. Using a simplified reference tissue model, the binding potential on the infarcted area was 2.72 ± 0.27. Metabolite analysis in brain tissues showed that 83.2 ± 7.4% and 76.4 ± 2.1% of radioactivity was from intact [18F]FEBMP at 30 and 60 min, respectively, and that this ratio was higher than in plasma (8.6 ± 1.9% and 3.9 ± 1.1%, respectively). In vitro autoradiography on postmortem human brains showed that TSPO rs6971 polymorphism did not affect binding sites for [18F]FEBMP. These findings suggest that [18F]FEBMP is a promising new tool for visualization of neuroinflammation.

  15. ND-309, a novel compound, ameliorates cerebral infarction in rats by antioxidant action.

    PubMed

    Tian, Jingwei; Li, Guisheng; Liu, Zhifeng; Zhang, Shumin; Qu, Guiwu; Jiang, Wanglin; Fu, Fenghua

    2008-09-19

    Extract of danshen (Salvia miltiorrhiza Bunge.) has been clinically prescribed in China to treat patients with stroke. The novel compound designated ND-309, namely isopropyl-beta-(3,4-dihydroxyphenyl)-alpha-hydroxypropanoate is a new metabolite of danshen in rat brain. The present study was conducted to investigate whether ND-309 has a protective effect on brain injury after focal cerebral ischemia, and to determine the possible mechanism. Adult male SD rats were subjected to middle cerebral artery occlusion (MCAO) by bipolar electro-coagulation. Behavioral tests were used to evaluate the damage to central nervous system. The cerebral infarct volume and edema were assessed to evaluate the brain patho-physiological changes. Spectrophotometric or spectrofluorometric assay methods were used to determine the generation of reactive oxygen species (ROS), activities of superoxide dismutase (SOD) and glutathione-peroxidase (GSH-Px), contents of malondialdehyde (MDA) and adenosine triphosphate (ATP), as well as respiratory control ratio of the brain mitochondria. The results showed that treatment with ND-309 significantly decreased neurological deficit scores, reduced infarct volume and the edema compared with the model group. Meanwhile, ND-309 significantly increased the brain ATP content, improved mitochondrial energy metabolism, attenuated the elevation of MDA content, the decrease in SOD, GSH-Px activity and the generation of ROS in brain mitochondria. All of these findings indicate that ND-309 has the protective potential against cerebral ischemia injury and its protective effects may be due to the amelioration of cerebral energy metabolism and its antioxidant property. PMID:18652875

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

    E-print Network

    Paris-Sud XI, Université de

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

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

    PubMed Central

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

    2013-01-01

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

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

    Microsoft Academic Search

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

    2008-01-01

    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

  19. Segmentation of Brain MRI Image with GVF Snake Model

    Microsoft Academic Search

    Wang Guoqiang; Wang Dongxue

    2010-01-01

    Medical image segmentation is the foundation and research focus in the medical image processing field. In this paper the normalized GVF Snake model combines with traditional edge detection is proposed for the brain MRI image semiautomatic segmentation. The thinning Canny result is used to calculate the edge map gradient of the GVF snake model. Then the normalized GVF snake model

  20. What Cascade Spreading Models Can Teach Us about the Brain.

    PubMed

    Gonzalez-Castillo, Javier; Bandettini, Peter A

    2015-06-17

    The precise relationship between functional and structural connectivity in the brain is not well understood. Research in this area has, so far, mostly remained descriptive. In this issue of Neuron, Miši? et al. (2015) forge a promising new direction by modeling the propagation of information as it relates to spatially constrained network properties. From these preliminary results a glimmer of hope in uncovering deep principles of brain organization begins to emerge. PMID:26087160

  1. Epidural cooling for selective brain hypothermia in porcine model

    Microsoft Academic Search

    H. Cheng; J. Shi; L. Zhang; Q. Zhang; H. Yin; L. Wang

    2006-01-01

    Summary  Background. Hypothermia has been shown to be neuroprotective in many animal models and several human trials of brain ischemic and trauma.\\u000a However systemic hypothermia may result in fatal complications. This study was undertaken to test epidural cooling as a new\\u000a method of inducing selective brain hypothermia.\\u000a \\u000a Method. Six adult swine (mean mass, 33.8 3.6?kg) were studied. Anesthesia was maintained with

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

    PubMed

    Huang, Bing S; Leenen, Frans H H

    2009-06-01

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

  3. Animal models of traumatic brain injury: a critical evaluation.

    PubMed

    O'Connor, William T; Smyth, Aoife; Gilchrist, Michael D

    2011-05-01

    Animal models are necessary to elucidate changes occurring after brain injury and to establish new therapeutic strategies towards a stage where drug efficacy in brain injured patients (against all classes of symptoms) can be predicted. In this review, six established animal models of head trauma, namely fluid percussion, rigid indentation, inertial acceleration, impact acceleration, weight-drop and dynamic cortical deformation are evaluated. While no single animal model is entirely successful in reproducing the complete spectrum of pathological changes observed after injury, the validity of these animal models including face, construct, etiological and construct validity and how the models constitute theories about brain injury is addressed. The various types of injury including contact (direct impact) and non-contact (acceleration/deceleration) and their associated pathologies are described. The neuropathologic classifications of brain injury including primary and secondary, focal and diffuse are discussed. Animal models and their compatibility with microdialysis studies are summarised particularly regarding the role of excitatory and inhibitory amino acid neurotransmitters. This review concludes that the study of neurotransmitter interactions within and between brain regions can facilitate the development of novel compounds targeted to treat those cognitive deficits not limited to a single pharmacological class and may be useful in the investigation of new therapeutic strategies and pharmacological testing for improved treatment for traumatic head injury. PMID:21256863

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

    PubMed

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

    2015-05-01

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

  5. Dynamic causal modelling of brain-behaviour relationships.

    PubMed

    Rigoux, L; Daunizeau, J

    2015-08-15

    In this work, we expose a mathematical treatment of brain-behaviour relationships, which we coin behavioural Dynamic Causal Modelling or bDCM. This approach aims at decomposing the brain's transformation of stimuli into behavioural outcomes, in terms of the relative contribution of brain regions and their connections. In brief, bDCM places the brain at the interplay between stimulus and behaviour: behavioural outcomes arise from coordinated activity in (hidden) neural networks, whose dynamics are driven by experimental inputs. Estimating neural parameters that control network connectivity and plasticity effectively performs a neurobiologically-constrained approximation to the brain's input-outcome transform. In other words, neuroimaging data essentially serves to enforce the realism of bDCM's decomposition of input-output relationships. In addition, post-hoc artificial lesions analyses allow us to predict induced behavioural deficits and quantify the importance of network features for funnelling input-output relationships. This is important, because this enables one to bridge the gap with neuropsychological studies of brain-damaged patients. We demonstrate the face validity of the approach using Monte-Carlo simulations, and its predictive validity using empirical fMRI/behavioural data from an inhibitory control task. Lastly, we discuss promising applications of this work, including the assessment of functional degeneracy (in the healthy brain) and the prediction of functional recovery after lesions (in neurological patients). PMID:26008885

  6. RNase therapy assessed by magnetic resonance imaging reduces cerebral edema and infarction size in acute stroke.

    PubMed

    Walberer, Maureen; Tschernatsch, Marlene; Fischer, Silvia; Ritschel, Nouha; Volk, Kai; Friedrich, Carolin; Bachmann, Georg; Mueller, Clemens; Kaps, Manfred; Nedelmann, Max; Blaes, Franz; Preissner, Klaus T; Gerriets, Tibo

    2009-02-01

    Ischemic stroke causes cell necrosis with the exposure of extracellular ribonucleic acid (RNA) and other intracellular material. As shown recently, extracellular RNA impaired the blood-brain-barrier and contributed to vasogenic edema-formation. Application of ribonuclease 1 (RNase 1) diminished edema-formation and also reduced lesion volume in experimental stroke. Here we investigate whether reduction of lesion volume is due to the reduction of edema or of other neuroprotective means. Neuroprotective and edema protective effects of RNase 1 pretreatment were assessed using a temporary middle cerebral artery occlusion (MCAO) model in rats. Lesion volume was assessed on magnetic resonance imaging (MRI). T2-relaxation-time and midline-shift as well as brain water content (wet-dry-method) were measured to quantify edema formation. The impact of edema formation on infarct volume was evaluated in craniectomized animals. Exogenous RNase 1 was well tolerated and reduced edema-formation and infarct size (26.7% +/- 10.7% vs. 41.0% +/- 10.3%; p<0.01) at an optimal dose of 42 microg/kg as compared to placebo. Craniectomized animals displayed a comparable edema reduction but no reduction in infarct size. The present study introduces a hitherto unrecognized mechanism of ischemic brain damage and a novel neuroprotective approach towards acute stroke treatment. PMID:19355922

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

    NASA Astrophysics Data System (ADS)

    Wang, Zhihui; Deisboeck, Thomas S.

    In spite of all efforts, patients diagnosed with highly malignant brain tumors (gliomas), continue to face a grim prognosis. Achieving significant therapeutic advances will also require a more detailed quantitative understanding of the dynamic interactions among tumor cells, and between these cells and their biological microenvironment. Data-driven computational brain tumor models have the potential to provide experimental tumor biologists with such quantitative and cost-efficient tools to generate and test hypotheses on tumor progression, and to infer fundamental operating principles governing bidirectional signal propagation in multicellular cancer systems. This review highlights the modeling objectives of and challenges with developing such in silico brain tumor models by outlining two distinct computational approaches: discrete and continuum, each with representative examples. Future directions of this integrative computational neuro-oncology field, such as hybrid multiscale multiresolution modeling are discussed.

  8. MR image denoising method for brain surface 3D modeling

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

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

    PubMed

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

    2015-03-01

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

  10. Classical Wave Model of Quantum-Like Processing in Brain

    NASA Astrophysics Data System (ADS)

    Khrennikov, A.

    2011-01-01

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

  11. Electrocardiographic changes during exposure to residual oil fly ash (ROFA) particles in a rat model of myocardial infarction.

    PubMed

    Wellenius, Gregory A; Saldiva, Paulo H N; Batalha, Joao R F; Krishna Murthy, G G; Coull, Brent A; Verrier, Richard L; Godleski, John J

    2002-04-01

    Epidemiological studies have reported a positive association of short-term increases in ambient particulate matter (PM) with daily mortality and hospital admissions for cardiovascular disease. Although patients with cardiopulmonary disease appear to be most at risk, particulate-related cardiac effects following myocardial infarction (MI) have not been examined. To improve understanding of mechanisms, we developed and tested a model for investigating the effects of inhaled PM on arrhythmias and heart rate variability (HRV), a measure of autonomic nervous system activity, in rats with acute MI. Left-ventricular MI was induced in 31 Sprague-Dawley rats by thermocoagulation of the left coronary artery; 32 additional rats served as sham-operated controls. Diazepam-sedated rats were exposed (1 h) to residual oil fly ash (ROFA), carbon black, or room air at 12-18 h after surgery. Each exposure was immediately preceded and followed by a 1-h exposure to room air (baseline and recovery periods, respectively). Lead-II electrocardiograms were recorded. In the MI group, 41% of rats exhibited one or more premature ventricular complexes (PVCs) during the baseline period. Exposure to ROFA, but not to carbon black or room air, increased arrhythmia frequency in animals with preexisting PVCs. Furthermore, MI rats exposed to ROFA, but not to carbon black or room air, decreased HRV. There was no difference in arrhythmia frequency or HRV among sham-operated animals. These results underscore the usefulness of this model for elucidating the physiologic mechanisms of pollution-induced cardiovascular arrhythmias and contribute to defining the specific constituents of ambient particles responsible for arrhythmias. PMID:11896300

  12. Prediction of infarct volume and neurologic outcome by using automated multiparametric perfusion-weighted magnetic resonance imaging in a primate model of permanent middle cerebral artery occlusion

    PubMed Central

    Sasaki, Makoto; Kudo, Kohsuke; Honjo, Kaneyoshi; Hu, Jin-Qing; Wang, Hai-Bin; Shintaku, Katsuya

    2011-01-01

    By optimizing thresholds, we identified the perfusion-weighted magnetic resonance imaging (PWI) parameters that accurately predict final infarct volume and neurologic outcome in a primate model of permanent middle cerebral artery (MCA) occlusion. Ten cynomolgus monkeys underwent PWI and diffusion-weighted imaging (DWI) at 3 and 47?hours, respectively, after right MCA occlusion using platinum coils, and were killed at 48?hours. Volumes of the hypoperfused areas on PWI were automatically measured using different thresholds and 11 parametric maps to determine the optimum threshold (at which least difference was found between the average volumes on PWI and those determined using specimens or DWI). In the case of arrival time (AT), cerebral blood volume (CBV), time to peak (TTP), time to maximum (Tmax), and cerebral blood flow (CBF) determined using deconvolution techniques, the volume of the hypoperfused area significantly correlated with the infarct volumes and the neurologic deficit scores with small variations, whereas in the case of mean transit time and nondeconvolution CBF, relatively poor correlations with large variations were seen. At optimum threshold, AT, CBV, TTP, Tmax, and deconvolution CBF can accurately predict the final infarct volume and neurologic outcome in monkeys with permanent MCA occlusion. PMID:20588314

  13. The Protective Effect of Puerarin on Myocardial Infarction Reperfusion Injury (MIRI): A Meta-Analysis of Randomized Studies in Rat Models

    PubMed Central

    Wenjun, Huang; Jing, Wen; Tao, Li; Liang, Mao; Yan, Yang; Xiaorong, Zeng; Rui, Zhou

    2015-01-01

    Background Although puerarin is generally considered as a protective agent for cardio-cerebrovascular diseases, the exact effect on reducing myocardial infarction reperfusion injury (MIRI) is not well understood. This study aimed to pool previous randomized controlled studies based on rat models to evaluate the effects of puerarin on MIRI. Material/Methods Relevant studies were searched among PubMed, Embase, Medline, and CNKI (China National Knowledge Infrastructure). To assess the therapeutic effects of protective effects of puerarin on myocardial infarction reperfusion injury, the outcome indicators which were reported in at least 3 original studies were extracted and pooled, including size of myocardial ischemia (MIS) and myocardial infarction (MIN), creatine kinase (CK), methylene dioxyamphetamine (MDA), and superoxide dismutase (SOD). Results Administration of puerarin could effectively reduce the size of MIN after MIR (mean difference: ?29.20, 95%CI: ?44.90 to ?13.51, p=0.0003). Puerarin directly led to decreased CK (mean difference: ?6.89, 95%CI: ?9.40 to ?4.38, p=0.00001) and MDA (mean difference: ?2.41, 95%CI: ?3.14 to ?1.68, p<0.00001) and increased serum SOD (mean difference: 63.97, 95%CI: 38.19 to 89.75, p<0.00001). Conclusions Puerarin might have a protective effect in myocardial tissues during MIRI through increasing SOD and decreasing CK and MDA. However, more animal studies and randomized controlled clinical trials are required to confirm these results. PMID:26067875

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

    PubMed Central

    LI, RUI-JUN; HE, KUN-LUN; LI, XIN; WANG, LI-LI; LIU, CHUN-LEI; HE, YUN-YUN

    2015-01-01

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

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

    SciTech Connect

    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

    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.

  16. The Protective Effect of Puerarin on Myocardial Infarction Reperfusion Injury (MIRI): A Meta-Analysis of Randomized Studies in Rat Models.

    PubMed

    Wenjun, Huang; Jing, Wen; Tao, Li; Ling, Mao; Yan, Yang; Xiaorong, Zeng; Rui, Zhou

    2015-01-01

    BACKGROUND Although puerarin is generally considered as a protective agent for cardio-cerebrovascular diseases, the exact effect on reducing myocardial infarction reperfusion injury (MIRI) is not well understood. This study aimed to pool previous randomized controlled studies based on rat models to evaluate the effects of puerarin on MIRI. MATERIAL AND METHODS Relevant studies were searched among PubMed, Embase, Medline, and CNKI (China National Knowledge Infrastructure). To assess the therapeutic effects of protective effects of puerarin on myocardial infarction reperfusion injury, the outcome indicators which were reported in at least 3 original studies were extracted and pooled, including size of myocardial ischemia (MIS) and myocardial infarction (MIN), creatine kinase (CK), methylene dioxyamphetamine (MDA), and superoxide dismutase (SOD). RESULTS Administration of puerarin could effectively reduce the size of MIN after MIR (mean difference: -29.20, 95%CI: -44.90 to -13.51, p=0.0003). Puerarin directly led to decreased CK (mean difference: -6.89, 95%CI: -9.40 to -4.38, p=0.00001) and MDA (mean difference: -2.41, 95%CI: -3.14 to -1.68, p<0.00001) and increased serum SOD (mean difference: 63.97, 95%CI: 38.19 to 89.75, p<0.00001). CONCLUSIONS Puerarin might have a protective effect in myocardial tissues during MIRI through increasing SOD and decreasing CK and MDA. However, more animal studies and randomized controlled clinical trials are required to confirm these results. PMID:26067875

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

    PubMed

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

    2015-07-01

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

  18. Design of a Statistical Model of Brain Shape

    Microsoft Academic Search

    Lionel Le Briquer; James C. Gee

    1997-01-01

    . This paper describes a statistical shape model of the brainextending through the whole organ. The variability in a normal populationis described by global deformation modes. The model is based onthe analysis of homologous deformations mapping similar structures inbrain images.1 IntroductionLarge variations exist across individuals in the morphology of the brain. Clinicaldiagnosis of diseases affecting the shape require the evaluation

  19. Task-specific functional brain geometry from model maps.

    PubMed

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

    2008-01-01

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

  20. Exercise preconditioning reduces ischemia reperfusion-induced focal cerebral infarct volume through up-regulating the expression of HIF-1?.

    PubMed

    Wang, Lu; Deng, Wenqian; Yuan, Qiongjia; Yang, Huijun

    2015-03-01

    To study the effect and mechanism of exercise preconditioning on focal cerebral ischemia reperfusion induced cerebral infarction via rat model; Sixty Sprague Dawley rats were divided into three groups at random: ischemia reperfusion group (IR, n=24), sham group (sham, n=12) and exercise preconditioning group (EP, n=24). Group EP carried out moderate exercise preconditioning for 4 weeks (swimming with non-weight bearing, 60 minutes/day, 6 days/week), Rats in Group EP and IR were established cerebral ischemia reperfusion injury model by Zea Longa's thread method. The cerebral infarct volume in rat of different group was evaluated after 2%TTC staining, expression of HIF-1? in rats' brain was detected by real-time RT-PCR, immunohistochmeistry method and western blot. No cerebral infarction and significant expression of HIF-1? in Group sham. Compared with Group IR, there was smaller infarct volume and stronger HIF-1? expression in Group EP (P<0.05). Moderate exercise preconditioning reduces ischemia reperfusion induced focal cerebral infarct volume through up-regulating the expression of HIF-1?. PMID:25796156

  1. Brain Shift Correction Based on a Boundary Element Biomechanical Model with Different

    E-print Network

    Frey, Pascal

    Brain Shift Correction Based on a Boundary Element Biomechanical Model with Different Material on the simulation of the intraoperative brain be- havior based on a computational model of brain tissue deformation to inaccuracy due to intraoperative changes like brain shift or tumor resection. In order to correct

  2. Traumatic Brain Injury Pathophysiology\\/Models

    Microsoft Academic Search

    Peter A. Walker; Nathan D. Allison

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

  3. Resolving Structural Variability in Network Models and the Brain

    PubMed Central

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

    2014-01-01

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

  4. Models of brain injury and alterations in synaptic plasticity.

    PubMed

    Albensi, B C

    2001-08-15

    Animal models are crucial for understanding human pathophysiological processes and for understanding how connections are injured, lost, or even regenerated and/or repaired. When animal models are used in conjunction with theoretical computational models, an ideal combination is achieved that potentially yields insight and encourages the formation of new theories concerning connectionism, cognitive functioning, and synaptic mechanisms. Mechanisms regulating glutamate receptor activation and intracellular calcium levels are important for normal synaptic transmission. These mechanisms (and others) are also critical during and after brain injury when the potential exists for these mechanisms to function pathologically. Interestingly enough, the regulation of glutamate receptor activation and intracellular calcium levels is also involved in normal processes of neuronal and synaptic plasticity. In addition, studies have shown that neurotrophins and cytokines, which are released after brain injury, can be neuroprotective and may also be important in synaptic plasticity. Furthermore, synaptic plasticity is a phenomenon thought by many to be necessary for memory encoding. If this is the case, then research described in this review has significant scientific merit concerning plasticity and memory and clinical benefit for understanding pathophysiologic processes associated with brain injury and memory impairment. This paper reviews the application of experimental animal models of brain injury for simulating conditions of stroke, trauma, and epilepsy (and/or seizure generation) and the associated cellular mechanisms of brain injury. The paper also briefly addresses the advantage of using computational models in combination with experimental models for hypothesis building and for aiding in the interpretation of empirical data. Finally, it reviews studies concerning brain injury and synaptic plasticity. PMID:11494362

  5. Quantitative genetic analysis of brain size variation in sticklebacks: support for the mosaic model of brain evolution.

    PubMed

    Noreikiene, Kristina; Herczeg, Gábor; Gonda, Abigél; Balázs, Gergely; Husby, Arild; Merilä, Juha

    2015-07-01

    The mosaic model of brain evolution postulates that different brain regions are relatively free to evolve independently from each other. Such independent evolution is possible only if genetic correlations among the different brain regions are less than unity. We estimated heritabilities, evolvabilities and genetic correlations of relative size of the brain, and its different regions in the three-spined stickleback (Gasterosteus aculeatus). We found that heritabilities were low (average h(2) = 0.24), suggesting a large plastic component to brain architecture. However, evolvabilities of different brain parts were moderate, suggesting the presence of additive genetic variance to sustain a response to selection in the long term. Genetic correlations among different brain regions were low (average rG = 0.40) and significantly less than unity. These results, along with those from analyses of phenotypic and genetic integration, indicate a high degree of independence between different brain regions, suggesting that responses to selection are unlikely to be severely constrained by genetic and phenotypic correlations. Hence, the results give strong support for the mosaic model of brain evolution. However, the genetic correlation between brain and body size was high (rG = 0.89), suggesting a constraint for independent evolution of brain and body size in sticklebacks. PMID:26108633

  6. Temporal expression of miRNAs and mRNAs in a mouse model of myocardial infarction

    PubMed Central

    Port, J. David; Walker, Lori A.; Polk, Jeremy; Nunley, Karin; Buttrick, Peter M.

    2011-01-01

    Analysis of changes in gene expression is an important means to define molecular differences associated with the phenotypic changes observed in response to myocardial infarction (MI). Several studies in humans or animal models have reported differential miRNA expression in response to MI acutely (animal) or chronically (human). To determine the relative contribution of microRNA (miRNA) and mRNAs to acute and chronic temporal changes in response to MI, mRNA and miRNA expression profiles were performed in three time points post-MI. Changes in mRNA and miRNA expression was analyzed by arrays and confirmed by RT-PCR. Bioinformatic analysis demonstrated that several genes and miRNAs in various pathways are regulated in a temporal or phenotype-specific manner. Furthermore miRNA analyses indicated that miRNAs can target expression of several genes involved in multiple cardiomyopathy-related pathways. Our results suggest that: 1) Differentially regulated miRNAs are predicted to target expression of several genes in multiple biological processes involved in the response to MI; 2) antithetical and compensatory changes in miRNA expression are observed at later disease stages, including antithetical regulation of miR-29, which correlates with the expression of collagen genes, and upregulation of apoptosis-related miRNAs at early stages and antiapoptotic/growth promoting miRNAs at later stages; 3) temporally dependent changes in miRNA and mRNA expression post-MI are generally characterized by dramatic changes acutely postinjury and are normalized as disease progresses; 4) A combinatorial analysis of mRNA and miRNA expression may aid in determining factors involved in compensatory and decompensated responses to cardiac injury. PMID:21771878

  7. Analysis of Gene Expression During the Development of Congestive Heart Failure After Myocardial Infarction in Rat Models.

    PubMed

    Yu, Zhuo; Zhang, Hu; Yu, Mingli; Ye, Qing

    2015-07-13

    Our study aimed to investigate the gene expression at different myocardial infarction (MI) phases and to understand the development mechanisms of congestive heart failure (CHF) after MI. Dataset GSE1957 including 24 samples of rat left ventricles at 1-day post MI or sham operation and 7-day post MI or sham operation was downloaded from Gene Expression Ominibus. The data were normalized with an affyPLM package and differentially expressed genes (DEGs) were identified with a Linear Models for Microarray Data package. Heat maps of the DEGs were constructed using Cluster 3.0. GO (Gene Ontology) enrichment analysis of the DEGs was performed in Database for Annotation, Visualization, and Integrated Discovery. A protein-protein interaction (PPI) network was constructed by Biomolecular Interaction Network Database and visualized by Cytoscape, and a subnetwork was analyzed using plugin ClusterONE in Cytoscape. A total of 5 DEGs at 1-day post-MI, 5 DEGs at 7-day post-MI, and 7 DEGs between the MI and sham groups at 1-day and 7-day post-MI were identified. For the GO category analysis, DEGs at 1-day post-MI were enriched in response to cytokine stimulus. DEGs at 7-day post-MI were enriched in response to inorganic substance and chemical homeostasis. DEGs between 1-day and 7-day post-MI including CDK2 and CDC20 were significantly enriched in mitosis. CDK2, ANXA1, CDC20, and AQP2 were included in the PPI network, and CDK2 was the only DEG included in the subnetwork. In conclusion, the induction of DEGs at 7-day post-MI might participate in the response to a hormone and endogenous stimulus to regulate the development of CHF after MI. PMID:26104178

  8. Metabolism of orthotopic mouse brain tumor models.

    PubMed

    Rosol, Michael; Harutyunyan, Ira; Xu, Jingying; Melendez, Elizabeth; Smbatyan, Goar; Finlay, Jonathan L; Krieger, Mark D; Gonzalez-Gomez, Ignacio; Reynolds, C Patrick; Nelson, Marvin D; Erdreich-Epstein, Anat; Blüml, Stefan

    2009-01-01

    We used magnetic resonance spectroscopy to determine whether orthotopic mouse brain tumors grown as xenografts in immunocompromised mice either from human brain tumor cells implanted immediately after surgery or from cultured human tumor lines show metabolic profiles comparable to those of the original tumors. Using a 7 T scanner, spectra were acquired from mice with a human atypical teratoid/rhabdoid tumor (AT/RT) either implanted directly from the surgical specimen or first grown in culture, directly implanted choroid plexus carcinoma (CPC), and two medulloblastoma cell lines. The results were compared with spectra from these same tumors or tumor types in patients and with controls. Metabolic variability of tumors from a single cell line was also evaluated using the medulloblastoma lines. The main metabolic features of human tumors were qualitatively replicated in xenografts. AT/RTs in mice exhibited choline, creatine, and myo-inositol levels comparable to those observed in the patient. As in patients, choline was prominent in experimental CPC. Tumors from a single cell line were comparable. Significant correlations were found with key metabolites in humans and mice; however, differences including lower lipids in the implanted AT/RTs than in patient spectra and taurine observed in all animal spectra were also noted. The causes of these dissimilarities warrant further investigation. PMID:19728974

  9. Animal models of brain maldevelopment induced by cycad plant genotoxins.

    PubMed

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

    2013-12-01

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

  10. Late-onset thermal hypersensitivity after focal ischemic thalamic infarcts as a model for central post-stroke pain in rats.

    PubMed

    Blasi, Francesco; Herisson, Fanny; Wang, Shuxing; Mao, Jianren; Ayata, Cenk

    2015-07-01

    Central post-stroke pain (CPSP) is a neuropathic pain syndrome that often develops in a delayed manner after thalamic stroke. Here, we describe a new model of CPSP by stereotaxic thalamic injection of endothelin-1. Stroke rats (n=12), but not saline-injected controls (n=12), developed a progressive, contralateral cutaneous thermal hyperalgesia over 4 weeks, without motor deficits. Lesions were highly focal and mainly affected the ventral posterior thalamic complex. Tchis model reproduces the infarct location and delayed hypersensitivity typical of CPSP, and may be useful to investigate its pathophysiology and test therapies targeting recovery and pain after thalamic stroke. PMID:25899295

  11. [A clinical case of young, oral combined contraceptive using women, heterozygous carrier of the Factor V (Leiden) which revealed thrombosis of the left internal jugular vein and brain ischemia with cerebral infarction and ischemic stroke].

    PubMed

    Kovachev, S; Ramshev, K; Ramsheva, Z; Ivanov, A; Ganovska, A

    2013-01-01

    Thrombophilia is associated with increased risks of venous thrombosis in women taking oral contraceptive preparations. Universal thrombophilia screening in women prior to prescribing oral contraceptive preparations is not supported by current evidence. The case is presented of a 23 year-old women with a personal history of interruption and on the same day started with oral contraceptive (0.03 microg ethynil estradiol - 0.075 microg gestodene), which due on a 18 pill/day to acute headache, increasing vomiting and speaking defects. Physical/neurologic/gynecologic examinations observed a normal status. The MRI and CT revealed thrombosis of the left internal jugular vein and brain ischemia with cerebral infarction and ischemic stroke. The acute therapy of thrombotic findings was accompanied with many tests. The thrombophilia PCR-Real time - test finds heterozygous carrier of the Factor V (Leiden). This case shows the need of large prospective studies that should be undertaken to refine the risks and establish the associations of thrombophilias with venous thrombosis among contraceptive users. The key to a prompt diagnosis is to know the risk factors. The relative value of a thrombophilia screening programme before contraceptive using needs to be established. PMID:24501870

  12. A computational model of mild traumatic brain injury.

    PubMed

    Menon, Jayant P; Gupta, Vikram; Aravamudhan, Renga

    2012-01-01

    Electrical analysis of brain activity reveals the presence of synchronous oscillations over a range of frequencies. These rhythms are readily observed using electroencephalography (EEG). Clinical EEG data shows that Traumatic Brain Injury (TBI) alters these rhythms. Researchers have developed lumped parameter neural mass models (NMM) that can reproduce these various brain rhythms. This paper proposes an NMM based computational model of mild TBI that recreates the clinical EEG changes observed after injury. Specifically, the focus is on recreating changes observed after TBI in the 8-12 Hz alpha and the 4-8Hz theta frequency ranges. Mild TBI is simulated by increasing membrane reactivity and by decreasing synaptic connectivity in the NMM. These results indicate that clinically observed EEG changes with mild TBI are likely due to traumatic synaptic disruption and that with appropriate data, EEG may be used to quantify the extent of TBI in the future. PMID:23366150

  13. Incorporation of a Left Ventricle Finite Element Model Defining Infarction Into the XCAT Imaging Phantom

    Microsoft Academic Search

    Alexander I. Veress; William Paul Segars; Benjamin M. W. Tsui; Grant T. Gullberg

    2011-01-01

    The 4D extended cardiac-torso (XCAT) phantom was developed to provide a realistic and flexible model of the human anatomy and cardiac and respiratory motions for use in medical imaging research. A prior limitation to the phantom was that it did not accurately simulate altered functions of the heart that result from cardiac pathologies such as coronary artery disease (CAD). We

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

    PubMed Central

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

    2012-01-01

    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. PMID:18193208

  15. Lacunar infarction with oral contraceptives: An unusual case report

    PubMed Central

    Biswal, Sasmita

    2013-01-01

    Combined oral contraceptives are one of the risk factor for stroke in women. We report a case of an arterial ischemic stroke due to lacunar infarction in a 35-year-old previously healthy female patient induced after 3 years on Sukhi an oral contraceptive after two times artificial abortions. A brain MRI finding was suggestive of lacunar infarction. Her symptoms improved after stopping the oral contraceptive and putting her on I.V heparin therapy. PMID:24672193

  16. 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).

    PubMed

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

    2009-04-01

    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 classification model for postprocedural complications after early percutaneous coronary intervention for acute myocardial infarction. The model was developed on the New York State percutaneous coronary intervention database for 1999 to 2000 (consisting of 5,385 procedures) and was validated using the subsequent 2001 to 2002 database (consisting of 7,414 procedures). Tree-structured prognostic classification identified 4 key presenting features: cardiogenic shock, congestive heart failure, age, and diabetes. In the validation database, the model identified patient groups with postprocedural complications rates ranging from 1.0% to 22.8%, >22-fold increased risk. The performance of this model was similar to the Mayo Clinic and another recently published risk scores with a discrimination capacity of 78% (95% confidence interval, 75%, 80%). In conclusion, patients undergoing percutaneous coronary intervention for acute myocardial infarction can be readily stratified into distinct prognostic classes using the tree-structured model. PMID:19327419

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2006-01-01

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

  19. Orthotopic models of pediatric brain tumors in zebrafish.

    PubMed

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

    2015-03-26

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

  20. Models of the brain and evolution Neural Networks: Applications in

    E-print Network

    Widrow, Bernard

    cancellers. Each adaptive system utilizes a single- neuron neural network. The moz.t signiticant commercialModels of the brain and evolution Neural Networks: Applications in Industry, Business and BERNARD commercial application of neural network technology outside the financial industry was the airport baggage

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

    ERIC Educational Resources Information Center

    Stein, Zachary; Fischer, Kurt W.

    2011-01-01

    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…

  2. Statistical Models of the Brain 36-759 Spring, 2011

    E-print Network

    Kass, Rob

    and Machine Learning students. The course will involve (i) readings, (ii) student commentary and discussion ideas have been part of neurophysiology and the brain sciences since the first stochastic description contemporary theories of neural system behavior are built with statistical models. For ex- ample, integrate

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

    E-print Network

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

  4. Good-Enough Brain Model: Challenges, Algorithms and Discoveries in Multi-Subject Experiments

    E-print Network

    Good-Enough Brain Model: Challenges, Algorithms and Discoveries in Multi-Subject Experiments synthetic and real brain data. Using the real data, GEBM produces brain activity patterns as detect regularities and outliers in multi-subject brain activ- ity measurements. Categories and Subject

  5. A model for fatty acid transport into the brain.

    PubMed

    Hamilton, James A; Brunaldi, Kellen

    2007-09-01

    A key function of fatty acid (FA) transport into the brain is to supply polyunsaturated fatty acids (PUFA) that are not synthesized in brain cells but are essential signaling molecules and components of the phospholipid membrane. In addition, common dietary FAs such as palmitic acid are also rapidly taken up by the brain and esterified to phospholipids or oxidized to provide cellular energy. Most evidence shows that FA crossing the blood brain barrier (BBB) is derived mainly from FA/albumin complexes and, to a lesser extent, from circulating lipoproteins. Our model proposes that FA diffuse across the lipid bilayer of the BBB without specific transporters to reach brain cells. They cross the luminal and transluminal leaflets of the endothelial cells and the plasma membrane of neural cells by reversible flip-flop. Acyl-CoA synthetases trap FA by forming acyl-CoA, which cannot diffuse out of the cell. Selection of FA is controlled largely by enzymes in the pathways of intracellular metabolism, beginning with the acyl-CoA synthetase. PMID:17901540

  6. Omental Infarction Mimicking Cholecystitis

    PubMed Central

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

    2015-01-01

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

  7. Development of assessment technology for a rat myocardial infarct model using integrated PET\\/CT and MRI images

    Microsoft Academic Search

    Sang-Keun Woo; Gi Jeong Cheon; Kyeong Min Kim; WonHo Lee; Yong Jin Lee; Min Hwan Kim; Joo Hyun Kang; Young Hoon Ji; Chang Woon Choi; Sang Moo Lim

    2010-01-01

    The aim of this study was to improve quantitative assessment of rat myocardial infarct size using attenuation corrected PET polar map with gated CT image and MRI polarmap. The PET\\/CT images obtained with a small animal PET\\/CT scanner. Gating was realized with the help of an external trigger device. Contrast enhanced FLASH sequence MRI image was acquired with a 3-T

  8. Modeling Synchronization Loss in Large-Scale Brain Dynamics

    Microsoft Academic Search

    Antonio J. Pons Rivero; Jose Luis Cantero; Mercedes Atienza; Jordi García-ojalvo

    2008-01-01

    We implement a model of the large-scale dynamics of the brain, and analyze the effect of both short- and long-range connectivity\\u000a degradation on its coordinated activity, with the ultimate goal of comparing the structural and functional characteristics\\u000a of neurodegenerative diseases such as Alzheimer’s. A preliminary comparison between the results obtained with the model and\\u000a the activity measured in patients diagnosed

  9. Ekbom Syndrome Occurring with Multi Infarct Dementia

    PubMed Central

    Gautam, Priyanka; Kaur, Jaswinder

    2015-01-01

    Ekbom Syndrome is characterized by delusion that small living being infests skin. The clinical profile of this disorder has shown it to be associated with organic conditions. Neuroimaging studies implicate putamen as the brain structure involved in the pathophysiology. These are also known as organic delusional disorder and provide an opportunity to study biological causation of delusional disorder. We report a patient presented with a complaint of insects crawling on her body for last two years. She collected the peeled skin in a jar and claimed that these are insects. CT scan (brain) revealed multiple infarcts involving basal ganglia. She responded to Risperidone 4 mg daily. PMID:26023627

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

    PubMed

    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

    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

  11. Segmentation of Brain MR Images Using a Charged Fluid Model

    PubMed Central

    Valentino, Daniel J.; Duckwiler, Gary R.; Toga, Arthur W.

    2011-01-01

    In this paper, we developed a new deformable model, the charged fluid model (CFM), that uses the simulation of a charged fluid to segment anatomic structures in magnetic resonance (MR) images of the brain. Conceptually, the charged fluid behaves like a liquid such that it flows through and around different obstacles. The simulation evolves in two steps governed by Poisson’s equation. The first step distributes the elements of the charged fluid within the propagating interface until an electrostatic equilibrium is achieved. The second step advances the propagating front of the charged fluid such that it deforms into a new shape in response to the image gradient. This approach required no prior knowledge of anatomic structures, required the use of only one parameter, and provided subpixel precision in the region of interest. We demonstrated the performance of this new algorithm in the segmentation of anatomic structures on simulated and real brain MR images of different subjects. The CFM was compared to the level-set-based methods [Caselles et al. (1993) and Malladi et al. (1995)] in segmenting difficult objects in a variety of brain MR images. The experimental results in different types of MR images indicate that the CFM algorithm achieves good segmentation results and is of potential value in brain image processing applications. PMID:17926678

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

    PubMed Central

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

    2010-01-01

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

  13. Brain Stem Feedback in a Computational Model of Birdsong Sequencing

    PubMed Central

    Gibb, Leif; Gentner, Timothy Q.; Abarbanel, Henry D. I.

    2009-01-01

    Uncovering the roles of neural feedback in the brain is an active area of experimental research. In songbirds, the telencephalic premotor nucleus HVC receives neural feedback from both forebrain and brain stem areas. Here we present a computational model of birdsong sequencing that incorporates HVC and associated nuclei and builds on the model of sparse bursting presented in our preceding companion paper. Our model embodies the hypotheses that 1) different networks in HVC control different syllables or notes of birdsong, 2) interneurons in HVC not only participate in sparse bursting but also provide mutual inhibition between networks controlling syllables or notes, and 3) these syllable networks are sequentially excited by neural feedback via the brain stem and the afferent thalamic nucleus Uva, or a similar feedback pathway. We discuss the model's ability to unify physiological, behavioral, and lesion results and we use it to make novel predictions that can be tested experimentally. The model suggests a neural basis for sequence variations, shows that stimulation in the feedback pathway may have different effects depending on the balance of excitation and inhibition at the input to HVC from Uva, and predicts deviations from uniform expansion of syllables and gaps during HVC cooling. PMID:19553477

  14. Dynamic representations and generative models of brain function.

    PubMed

    Friston, K J; Price, C J

    2001-02-01

    The main point made in this article is that the representational capacity and inherent function of any neuron, neuronal population or cortical area is dynamic and context-sensitive. This adaptive and contextual specialisation is mediated by functional integration or interactions among brain systems with a special emphasis on backwards or top-down connections. The critical notion is that neuronal responses, in any given cortical area, can represent different things at different times. Our argument is developed under the perspective of generative models of functional brain architectures, where higher-level systems provide a prediction of the inputs to lower-level regions. Conflict between the two is resolved by changes in the higher-level representations, driven by the resulting error in lower regions, until the mismatch is 'cancelled'. In this model the specialisation of any region is determined both by bottom-up driving inputs and by top-down predictions. Specialisation is therefore not an intrinsic property of any region but depends on both forward and backward connections with other areas. Because these other areas have access to the context in which the inputs are generated they are in a position to modulate the selectivity or specialisation of lower areas. The implications for 'classical' models (e.g., classical receptive fields in electrophysiology, classical specialisation in neuroimaging and connectionism in cognitive models) are severe and suggest these models provide incomplete accounts of real brain architectures. Generative models represent a far more plausible framework for understanding selective neurophysiological responses and how representations are constructed in the brain. PMID:11287132

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

    PubMed Central

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

    2014-01-01

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

  16. Brain Lesion Segmentation through Physical Model Estimation

    E-print Network

    Prastawa, Marcel

    is highly correlated with many degenerative disor- ders, such as multiple sclerosis (MS), lupus, and stroke tensor fields that are obtained from Diffusion Tensor Imaging (DTI). The method per- forms segmentation using a good model of the underlying physical process or some empirical rules. Many methods have been

  17. Epileptic Seizures after Thromboembolic Cerebral Infarcts: A Positron Emission Tomographic Study

    Microsoft Academic Search

    J. De Reuck; D. Decoo; L. Algoed; P. Boon; G. Van Maele; I. Lemahieu; K. Strijckmans; P. Goethals

    1995-01-01

    In the present positron emission tomographic (PET) study regional blood flow and oxygen metabolism were compared in the infarcted and remote brain areas of two comparable groups of patients with a thromboembolic infarct the territory of the middle cerebral artery. One group of patients had developed postinfarction seizures. PET scan showed a more decreased regional blood flow (rCBF) and oxygen

  18. Lacunar Infarcts Are the Main Correlate With Cognitive Dysfunction in CADASIL

    Microsoft Academic Search

    Michael K. Liem; Jeroen van der Grond; Joost Haan; Rivka van den Boom; Michel D. Ferrari; Yvette M. Knaap; Martijn H. Breuning; Mark A. van Buchem; Huub A. M. Middelkoop; Saskia A. J. Lesnik Oberstein

    2010-01-01

    Background and Purpose—Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalop- athy is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke and cognitive decline. Previous studies have shown an association between white matter hyperintensities on brain MRI and cognitive dysfunction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencepha- lopathy. In the general

  19. A novel mouse model of penetrating brain injury.

    PubMed

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

    2014-01-01

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

  20. A Novel Mouse Model of Penetrating Brain Injury

    PubMed Central

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

    2014-01-01

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

  1. The bistable brain: a neuronal model with symbiotic interactions

    E-print Network

    Ricardo Lopez-Ruiz; Daniele Fournier-Prunaret

    2012-08-01

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

  2. Self-organization in a simple brain model

    SciTech Connect

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

    1994-03-10

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

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

    PubMed

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

    2014-04-18

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

  4. Brain Arteriovenous Malformation Modeling, Pathogenesis and Novel Therapeutic Targets

    PubMed Central

    Chen, Wanqiu; Choi, Eun-Jung; McDougall, Cameron M.; Su, Hua

    2014-01-01

    Patients harboring brain arteriovenous malformation (bAVM) are at life-threatening risk of rupture and intracranial hemorrhage (ICH). The pathogenesis of bAVM has not been completely understood. Current treatment options are invasive and ? 20% of patients are not offered interventional therapy because of excessive treatment risk. There are no specific medical therapies to treat bAVMs. The lack of validated animal models has been an obstacle for testing hypotheses of bAVM pathogenesis and testing new therapies. In this review, we summarize bAVM model development; and bAVM pathogenesis and potential therapeutic targets that have been identified during model development. PMID:24723256

  5. Towards dynamical system models of language-related brain potentials

    Microsoft Academic Search

    Peter beim Graben; Sabrina Gerth; Shravan Vasishth

    2008-01-01

    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

  6. Functional Representation of Human Embryo Brain Models Roman Durikovic Silvester Czanner

    E-print Network

    Durikovic, Roman

    Functional Representation of Human Embryo Brain Models Roman Durikovic Silvester Czanner Hirofumi embryo brain is organic and has many folds that are difficult to model or animate with conventional metamorphosis during the growth of some human embryo organs, partic- ularly brain and stomach. Popular methods

  7. 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)

    Medich, David Christopher

    1997-09-01

    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.

  8. Comparison of gene expression profiles in a porcine infarct model after intracoronary, transthoracic, or transendocardiac injection of heterologous bone marrow mesenchymal cells.

    PubMed

    Barallobre-Barreiro, J; de Ilárduya, O M; Moscoso, I; Calviño, R; Aldama, G; López-Peláez, E; Centeno, A; Doménech, N

    2009-01-01

    An in vivo porcine model of myocardial infarction was developed with the aim of comparing the effectiveness for cardiac repair of intracoronary, transthoracic, or transendocardial delivery strategies for bone marrow mesenchymal stem cells (BMMSC) using an analysis of expression levels of transcripts related to various cellular processes at 8 heart regions using quantitative reverse transcriptase polymerase chain reaction. We observed significant rises in cardiomyogenic markers Mef2C, Gata4 and Nkx2.5, and contractibility marker Serca2A at infarcted regions for cell-treated pigs. We also observed differences in Sdf1 expression related to the organ stress response between delivery strategies. Unexpectedly, increased expression of Col1A1 was detected in 2 cell-treated groups at various heart regions. Our results suggest improvements in both contractility and cardiomyogenic capability of damaged tissue after BMMSC injection, but also warned us about the relevance of the chosen delivery strategy and potential undesired effects like increasing fibrosis after treatment. PMID:19715897

  9. Role of CD11b+Gr-1+ myeloid cells in AGEs-induced myocardial injury in a mice model of acute myocardial infarction

    PubMed Central

    Yao, Tongqing; Lu, Wenbin; Zhu, Jian; Jin, Xian; Ma, Genshan; Wang, Yuepeng; Meng, Shu; Zhang, Yachen; Li, Yigang; Shen, Chengxing

    2015-01-01

    Aims: Polymorph neutrophils are the predominant inflammatory cells and play a crucial role on the pathogenesis of myocardial injury at the early stage of acute myocardial infarction (AMI). However, the precursors and the differentiation of neutrophils are not fully understood. Here we explored the role of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) on myocardial injury in the absence and presence of advanced glycation end-products (AGEs) in a mice model of AMI. Methods and Results: Male C57BL/6J mice were selected. Fluorescent actived cell sortor (FACS) data demonstrated significantly increased CD11b+Gr-1+ MDSCs both in peripheral blood circulation and in the ischemic myocardium at 24 hours post AMI. Quantitative-real-time PCR results also revealed significantly upregulated CD11b and Ly6G mRNA expression in the ischemic myocardium. AGEs treatment further aggravated these changes in AMI mice but not in sham mice. Moreover, AGEs treatment also significantly increased infarction size and enhanced cardiomyocyte apoptosis. The mRNA expression of pro-inflammatory cytokine IL-6 and iNOS2 was also significantly increased in AMI + AGEs group compared to AMI group. Conclusion: These data suggest enhanced infiltration of MDSCs by AGEs contributes to aggravated myocardial injury in AMI mice, which might be one of the mechanisms responsible for severer myocardial injury in AMI patients complicating diabetes.

  10. Avoiding Boltzmann Brain domination in holographic dark energy models

    E-print Network

    R. Horvat

    2015-02-23

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

  11. Avoiding Boltzmann Brain domination in holographic dark energy models

    E-print Network

    Horvat, R

    2015-01-01

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

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

    PubMed

    Froese, Tom; Iizuka, Hiroyuki; Ikegami, Takashi

    2013-08-01

    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

  13. Finite element decomposition and grid generation for brain modeling and visualization

    E-print Network

    Batte, David Allan

    1997-01-01

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

  14. The Drosophila neural lineages: a model system to study brain development and circuitry

    E-print Network

    Spindler, Shana R.; Hartenstein, Volker

    2010-01-01

    brain is a valuable model system to study neuron development and circuitbrain centers to behavior, the precise neuronal circuits andand circuit formation, in an in vivo setting. This is in contrast to the mammalian brain

  15. Infarcted Left Ventricles Have Stiffer Material Properties and Lower Stiffness Variation: Three-Dimensional Echo-Based Modeling to Quantify In Vivo Ventricle Material Properties.

    PubMed

    Fan, Longling; Yao, Jing; Yang, Chun; Tang, Dalin; Xu, Di

    2015-08-01

    Methods to quantify ventricle material properties noninvasively using in vivo data are of great important in clinical applications. An ultrasound echo-based computational modeling approach was proposed to quantify left ventricle (LV) material properties, curvature, and stress/strain conditions and find differences between normal LV and LV with infarct. Echo image data were acquired from five patients with myocardial infarction (I-Group) and five healthy volunteers as control (H-Group). Finite element models were constructed to obtain ventricle stress and strain conditions. Material stiffening and softening were used to model ventricle active contraction and relaxation. Systolic and diastolic material parameter values were obtained by adjusting the models to match echo volume data. Young's modulus (YM) value was obtained for each material stress-strain curve for easy comparison. LV wall thickness, circumferential and longitudinal curvatures (C- and L-curvature), material parameter values, and stress/strain values were recorded for analysis. Using the mean value of H-Group as the base value, at end-diastole, I-Group mean YM value for the fiber direction stress-strain curve was 54% stiffer than that of H-Group (136.24?kPa versus 88.68?kPa). At end-systole, the mean YM values from the two groups were similar (175.84?kPa versus 200.2?kPa). More interestingly, H-Group end-systole mean YM was 126% higher that its end-diastole value, while I-Group end-systole mean YM was only 29% higher that its end-diastole value. This indicated that H-Group had much greater systole-diastole material stiffness variations. At beginning-of-ejection (BE), LV ejection fraction (LVEF) showed positive correlation with C-curvature, stress, and strain, and negative correlation with LV volume, respectively. At beginning-of-filling (BF), LVEF showed positive correlation with C-curvature and strain, but negative correlation with stress and LV volume, respectively. Using averaged values of two groups at BE, I-Group stress, strain, and wall thickness were 32%, 29%, and 18% lower (thinner), respectively, compared to those of H-Group. L-curvature from I-Group was 61% higher than that from H-Group. Difference in C-curvature between the two groups was not statistically significant. Our results indicated that our modeling approach has the potential to determine in vivo ventricle material properties, which in turn could lead to methods to infer presence of infarct from LV contractibility and material stiffness variations. Quantitative differences in LV volume, curvatures, stress, strain, and wall thickness between the two groups were provided. PMID:25994130

  16. Acute Vertebrobasilar Territory Infarcts due to Heat Stroke.

    PubMed

    Jain, Rajendra Singh; Kumar, Sunil; Agarwal, Rakesh; Gupta, Pankaj Kumar

    2015-06-01

    Heat stroke is common in tropical country like India especially during the summer season. We report an unusual case of acute vertebrobasilar territory infarcts due to heat stroke. A middle-aged man developed hyperpyrexia (42.2°C) after strenuous fieldwork in a hot summer day. Next morning, he was found in altered sensorium. The brain imaging showed acute posteromedial midbrain and cerebellar infarcts. A diagnosis of acute ischemic stroke due to heat stroke was made, and the patient was put under the intensive care unit. Two weeks later, the patient became conscious, but had slurred speech and incoordination in all the 4 limbs. Six months after rehabilitation, the patient still have scanning speech and limb ataxia. Acute ischemic stroke worsened the prognosis in our patient. Acute infarct is a very rare neurologic manifestation of heat stroke. This case report emphasizes the importance of suspecting acute infarct in heat stroke patient. PMID:25891756

  17. [Outpatient coronary groups. 1st experiences with high-risk infarct patients after a year's model experiment].

    PubMed

    Buchbinder, W; Gocke, H; Ilker, H G; Stein, G

    1981-04-01

    One year's experience with patients after myocardial infarction with low physical capacity (high risk-patients) and their participation in coronary clubs. After satisfactory results have been recorded with coronary training-groups at Hamburg first results can be reported from a trial with a coronary exercising-group at the patient's community. Patients after myocardial infarction with low physical capacity (high risk-patients) have participated regularly in coronary club meetings. One year's observation with medical controls showed no hazards from special adapted exercises combined with health education. Cardiac complications did not occur. The exercise program aims on increasing coordination and flexibility; general aerobic endurance is not to be improved. Thus a better and more economical functioning of the cardiovascular system is reached; life quality is improved. Further propagation of the coronary exercising-program is recommended if the described precautions are observed. This way many coronary patients could benefit also from long-time participation in comprehensive care in coronary clubs, which were up to now excluded from coronary training groups because of high risk. PMID:7227944

  18. SyM-BBB: a microfluidic Blood Brain Barrier model.

    PubMed

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

    2013-03-21

    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

  19. Modeling the dynamical effects of anesthesia on brain circuits.

    PubMed

    Ching, Shinung; Brown, Emery N

    2014-04-01

    General anesthesia is a neurophysiological state that consists of unconsciousness, amnesia, analgesia, and immobility along with maintenance of physiological stability. General anesthesia has been used in the United States for more than 167 years. Now, using systems neuroscience paradigms how anesthetics act in the brain and central nervous system to create the states of general anesthesia is being understood. Propofol is one of the most widely used and the most widely studied anesthetics. When administered for general anesthesia or sedation, the electroencephalogram (EEG) under propofol shows highly structured, rhythmic activity that is strongly associated with changes in the patient's level of arousal. These highly structured oscillations lend themselves readily to mathematical descriptions using dynamical systems models. We review recent model descriptions of the commonly observed EEG patterns associated with propofol: paradoxical excitation, strong frontal alpha oscillations, anteriorization and burst suppression. Our analysis suggests that propofol's actions at GABAergic networks in the cortex, thalamus and brainstem induce profound brain dynamics that are one of the likely mechanisms through which this anesthetic induces altered arousal states from sedation to unconsciousness. Because these dynamical effects are readily observed in the EEG, the mathematical descriptions of how propofol's EEG signatures relate to its mechanisms of action in neural circuits provide anesthesiologists with a neurophysiologically based approach to monitoring the brain states of patients receiving anesthesia care. PMID:24457211

  20. The animat: new frontiers in whole brain modeling.

    PubMed

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

    2012-01-01

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

  1. Science Sampler: Modeling the effects of drugs on the brain

    NSDL National Science Digital Library

    Georgia Brier

    2007-11-01

    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.

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

    Microsoft Academic Search

    João Pedro de Magalhães; Anders Sandberg

    2005-01-01

    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

  3. Magnetic resonance lactate and lipid signals in rat brain after middle cerebral artery occlusion model

    PubMed Central

    Harada, Kuniaki; Honmou, Osamu; Liu, He; Bando, Michio; Houkin, Kiyohiro; Kocsis, Jeffery D.

    2008-01-01

    Proton magnetic resonance spectroscopy (1-H MRS) has revealed changes of metabolites in acute cerebral infarction. Although the drastic changes of lactate and N-acetyl-aspartate have been reported to be useful indicators of the ischemic damage in both humans and experimental animals, lipid signals are also detected by the short echo time sequence 1–5 days after ischemia. The objective of this study was to find a novel technique to isolate lactate signals from lipid signals in the ischemic brain. First, MRS was used to study the lipid and lactate components of a spherical phantom in vitro, and parameters were established to separate these components in vitro. Then, MR measurements were obtained from the brains of middle cerebral artery occlusion rats. All MR measurements were performed using a 7-T (300 MHz), 18.3-cm-bore superconducting magnet (Oxford Magnet Technologies) interfaced to a Unity INOVA Imaging System (Varian Technologies). T2-weighted images were obtained from a 1.0-mm-thick coronal section using a 3-cm field of view. It is well known that lipid has a shorter and lactate a longer T2 relaxation time. These distinct magnetic characteristics allowed us to separate the lactate signal from the lipid signal. Thus, adjustment of the echo time is essential to analyze the metabolites in acute cerebral infarction, which may be useful in both the clinic and laboratory. PMID:17196558

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

    PubMed Central

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

    2013-01-01

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

  5. Effects of different LAD-blocked sites on the development of acute myocardial infarction and malignant arrhythmia in a swine model

    PubMed Central

    Li, Xiaorong; Shao, Danbing; Wang, Gannan; Jiang, Ting; Wu, Honghao; Gu, Bing; Cao, Kejiang; Zhang, Jinsong; Qi, Lianwen

    2014-01-01

    Objective To explore the effects of various left anterior descending (LAD) artery-blocked sites on the development of acute myocardial infarction (AMI) and malignant arrhythmia in a swine model. Methods Twenty-two pigs underwent occlusion of the coronary artery with balloon angioplasty were randomly divided into three groups according to the blocked site of the balloon: middle-site-blocked LAD group, bottom-third-blocked LAD group and control group. Then, the development of AMI and malignant arrhythmia, including ventricular tachycardia and ventricular fibrillation during the process of model creation, were recorded. Changes of the hemodynamics, blood gas analysis, electrocardiography, and myocardial enzymes were analyzed in each group before and after occlusion. Results Middle-site-LAD blockage resulted in a larger infarction size and the corresponding incidence of ventricular fibrillation was significantly higher than that of the bottom-third-blocked group (P<0.05). After the occlusion, the QTc interval of the Middle-site-blocked LAD group was significantly longer than that in the other groups (P<0.01). Moreover, mean arterial blood pressure (MAP), left ventricular ejection fraction (LVEF), and partial pressure of oxygen (PaO2) were significantly lower, but partial pressure of carbon dioxide (PaCO2) increased, in the Middle-site-blocked-LAD group compared with that in the bottom-third-blocked group (P<0.01). Compared with the control group, the two LAD-blocked groups showed significantly higher levels of Mb, CK-MB, LDH, AST and cTnT (P<0.01) four hours after the artery occlusion. However, these indexes were not significantly different between the two LAD-blocked groups (P>0.05). Conclusions Location of LAD blockages in swine models may affect the development of AMI and malignant arrhythmia. PMID:25276369

  6. Increased brain edema in aqp4-null mice in an experimental model of subarachnoid hemorrhage

    Microsoft Academic Search

    M. J. Tait; S. Saadoun; B. A. Bell; A. S. Verkman; M. C. Papadopoulos

    2010-01-01

    We investigated the role of the glial water channel protein aquaporin-4 in brain edema in a mouse model of subarachnoid hemorrhage in which 30 ?l of blood was injected into the basal cisterns. Brain water content, intracranial pressure and neurological score were compared in wildtype and aquaporin-4 null mice. We also measured blood-brain barrier permeability, and the osmotic permeability of

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

    E-print Network

    Shah, Jayant M.

    Model Based Variational Smoothing and Segmentation For Diffusion Tensor Imaging in the Brain Mukund and segmentation to brain diffusion tensor image data along user-selected attributes derived from the tensor, with the aim of extracting detailed brain structure information. The application of this framework

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

    E-print Network

    Leahy, Richard M.

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

  9. CADASIL (“cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy”)

    Microsoft Academic Search

    H Chabriat; M.-G Bousser

    2004-01-01

    CADASIL is a small artery disease of the brain responsible for migraine with aura, subcortical ischemic strokes, mood disturbances and dementia. The disease is transmitted with an autosomal dominant pattern and usually starts during midadulthood. On MRI, the presence of more or less diffuse signal abnormalities within the white-matter associated with typical lacunar infarcts are suggestive of the disorder. The

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

    PubMed Central

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

    2013-01-01

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

  11. Dissipation and memory capacity in the quantum brain model

    E-print Network

    Giuseppe Vitiello

    1995-02-06

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

  12. Dissipation and memory capacity in the quantum brain model

    E-print Network

    Vitiello, G

    1995-01-01

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

  13. A spatially distributed computational model of brain cellular metabolism.

    PubMed

    Calvetti, Daniela; Cheng, Yougan; Somersalo, Erkki

    2015-07-01

    This paper develops a three-dimensional spatially distributed model of brain cellular metabolism and investigates how the locus of the synaptic activity in reference to the capillaries and diffusion affects the behavior of the model, a type of analysis which is impossible to carry out in spatially lumped models, which are shown to be consistent spatially averaged approximations of the distributed model. To avoid a geometrically detailed modeling of the complex structure of the tissue consisting of different cell types and the extracellular space, the distributed model is based on a novel multi-domain formulation of reaction-diffusion equations, accounting also for separate mitochondria. The model reduction relating the spatially distributed model and lower dimensional reduced models, including the well-mixed spatially lumped compartment model, is carefully explained. We illustrate the effects of losing the spatial resolution with a computed example which is based on a reduced one-dimensional distributed radial model, and look into how the model behaves when the locus of the synaptic activity in reference to the capillaries is changed. By averaging the fluxes and concentrations in the distributed radial model to correspond to quantities in a lumped model, and further by estimating the parameters in the lumped, we conclude that varying the locus of the synaptic activity in reference to the capillaries alters significantly the lumped model parameters. This observation seems to be consequential for parameter estimation procedures from data when the spatial resolution is insufficient to determine the locus of the activity, indicating that the model uncertainty is an inherent feature of lumped models. PMID:25863266

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

    PubMed Central

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  16. A simulation model for analysing brain structure deformations

    NASA Astrophysics Data System (ADS)

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

    2003-12-01

    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.

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

    PubMed

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

    2015-01-01

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

  18. CT patterns of splenic infarction: a clinical and experimental study

    SciTech Connect

    Balcar, I.; Seltzer, S.E.; Davis, S.; Geller, S.

    1984-06-01

    The computed tomographic (CT) appearance of splenic infarction has classically been described as peripheral, wedge-shaped, and low in density. Two investigations were designed to determine the appearance of splenic infarcts: (a) a clinical study of 12 patients and (b) a canine experimental model. In the clinical study, two previously undescribed patterns of splenic infarction were found. The classic peripheral, wedge-shaped defects were seen in four patients; multiple, heterogeneous lesions were seen in five; and massive hypodense lesions were noted in three. The experimental study of splenic infarction in dogs indicated that CT images can accurately depict the various phases of an infarct as it evolves through stages of congestion, hemorrhage, inflammation, organization, and fibrosis. In addition, a new contrast material - liposome-encapsulated diatrizoate - was used in one of the dogs and was found to produce greater and more sustained differences between normal and abnormal tissue than did conventional contrast material.

  19. Dyadic brain modelling, mirror systems and the ontogenetic ritualization of ape gesture

    PubMed Central

    Arbib, Michael; Ganesh, Varsha; Gasser, Brad

    2014-01-01

    The paper introduces dyadic brain modelling, offering both a framework for modelling the brains of interacting agents and a general framework for simulating and visualizing the interactions generated when the brains (and the two bodies) are each coded up in computational detail. It models selected neural mechanisms in ape brains supportive of social interactions, including putative mirror neuron systems inspired by macaque neurophysiology but augmented by increased access to proprioceptive state. Simulation results for a reduced version of the model show ritualized gesture emerging from interactions between a simulated child and mother ape. PMID:24778382

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

    PubMed Central

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

    2007-01-01

    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. PMID:17710515

  1. Avian Egg Latebra as Brain Tissue Water Diffusion Model

    PubMed Central

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

    2013-01-01

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

  2. In vitro models of the blood-brain barrier.

    PubMed

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

    2014-01-01

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

  3. Short-, middle- and long-term safety of superparamagnetic iron oxide-labeled allogeneic bone marrow stromal cell transplantation in rat model of lacunar infarction.

    PubMed

    Tan, Chengbo; Shichinohe, Hideo; Abumiya, Takeo; Nakayama, Naoki; Kazumata, Ken; Hokari, Masaaki; Hamauchi, Shuji; Houkin, Kiyohiro

    2015-06-01

    Recently, both basic and clinical studies demonstrated that bone marrow stromal cell (BMSC) transplantation therapy can promote functional recovery of patients with CNS disorders. A non-invasive method for cell tracking using MRI and superparamagnetic iron oxide (SPIO)-based labeling agents has been applied to elucidate the behavior of transplanted cells. However, the long-term safety of SPIO-labeled BMSCs still remains unclear. The aim of this study was to investigate the short-, middle- and long-term safety of the SPIO-labeled allogeneic BMSC transplantation. For this purpose, BMSCs were isolated from transgenic rats expressing green fluorescent protein (GFP) and were labeled with SPIO. The Na/K ATPase pump inhibitor ouabain or vehicle was stereotactically injected into the right striatum of wild-type rats to induce a lacunar lesion (n?=?22). Seven days after the insult, either BMSCs or SPIO solution were stereotactically injected into the left striatum. A 7.0-Tesla MRI was performed to serially monitor the behavior of BMSCs in the host brain. The animals were sacrificed after 7 days (n?=?7), 6 weeks (n?=?6) or 10 months (n?=?9) after the transplantation. MRI demonstrated that BMSCs migrated to the damage area through the corpus callosum. Histological analysis showed that activated microglia were present around the bolus of donor cells 7 days after the allogeneic cell transplantation, although an immunosuppressive drug was administered. The SPIO-labeled BMSCs resided and started to proliferate around the route of the cell transplantation. Within 6 weeks, large numbers of SPIO-labeled BMSCs reached the lacunar infarction area from the transplantation region through the corpus callosum. Some SPIO nanoparticles were phagocytized by microglia. After 10 months, the number of SPIO-positive cells was lower compared with the 7-day and 6-week groups. There was no tumorigenesis or severe injury observed in any of the animals. These findings suggest that BMSCs are safe after cell transplantation for the treatment of stroke. PMID:25376270

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

    PubMed Central

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

    2014-01-01

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

  5. Auditory disturbance as a prodrome of anterior inferior cerebellar artery infarction

    PubMed Central

    Lee, H; Cho, Y

    2003-01-01

    Objectives: To investigate the clinical and radiological features of patients presenting with an acute auditory syndrome as a prodromal symptom of anterior inferior cerebellar artery (AICA) infarction. Methods: 16 consecutive cases of AICA infarction diagnosed by brain magnetic resonance imaging completed a standardised audiovestibular questionnaire and underwent a neuro-otological evaluation by an experienced neuro-otologist. Results: Five patients (31%) had an acute auditory syndrome as a prodrome of AICA infarction one to 10 days before onset of other brain stem or cerebellar symptoms. Two types of acute auditory syndrome were found: recurrent transient hearing loss with or without tinnitus (n = 3), and a single episode of prolonged hearing loss with or without tinnitus (n = 2). The episodic symptoms were brief, lasting only minutes. The tinnitus preceding the infarction was identical to the tinnitus experienced at the time of infarction. At the time of infarction, all patients developed hearing loss, tinnitus, vertigo, and ipsilateral hemiataxia. The most commonly affected site was the middle cerebellar peduncle (n = 5). Four of the five patients had incomplete hearing loss and all had absence of vestibular function to caloric stimulation on the affected side. Conclusions: Acute auditory syndrome may be a warning sign of impending pontocerebellar infarction in the distribution of the AICA. The acute auditory syndrome preceding an AICA infarct may result from ischaemia of the inner ear or the vestibulocochlear nerve. PMID:14638883

  6. Language model applications to spelling with Brain-Computer Interfaces.

    PubMed

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

    2014-01-01

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

  7. Modeling brain circuitry over a wide range of scales.

    PubMed

    Fua, Pascal; Knott, Graham W

    2015-01-01

    If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM) see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important. In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation. PMID:25904852

  8. Modeling brain circuitry over a wide range of scales

    PubMed Central

    Fua, Pascal; Knott, Graham W.

    2015-01-01

    If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM) see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important. In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation. PMID:25904852

  9. [Stress and myocardial infarction].

    PubMed

    Csef, H; Hefner, J

    2005-03-31

    Most people throughout the world die from the consequences of cardiovascular disease. Stress and psychosocial burdens have, in the past, been underestimated with regard to the importance of their impact on the development and course of such diseases. In the INTERHEART study, psychosocial burdens occupy third place among the risk factors for developing acute myocardial infarction. The relevance of these factors is underscored by more recent studies, also with regard to the prognosis in already manifest CAH. The causes of mental stresses may be intrapsychic problems (e.g. depression). The roots may, however, also be found in the private sphere or at the workplace. On the basis of specific history-taking, relevant risk constellations can be identified for a comparatively low expenditure of time. Specific therapeutic approaches aimed at reducing and coping with stress may, in future, help prevent diseases of the heart and lower the risk of contracting a myocardial infarction. PMID:15832759

  10. Paradoxical Elevation of High Density Lipoprotein Cholesterol in Association with Lacunar-Type Cerebral Infarction

    PubMed Central

    Meng, Gui-Lin; Tan, Yan; Fang, Min; Yang, Hong-Yan; Liu, Xue-Yuan; Zhao, Yan-Xin

    2015-01-01

    Background The aim of this study was to evaluate the association between high-density lipoprotein cholesterol (HDLC) levels and the risk of lacunar infarction (LI) in a retrospective cohort study in China. Material/Methods We recruited 229 patients with obsolete brain infarctions single side (SOBI), 218 with obsolete brain infarctions bilateral sides (BOBI), 193 with both acute stroke and obsolete lacunar infarctions single side (AI&SOBI), 113 with both acute stroke and obsolete lacunar infarctions bilateral sides (AI&BOBI), and 203 without any infarctions (Control). Results 1) The plasma levels of HDLC in group BOBI, AI&SOBI, and AI&BOBI were higher than in the control group, and lower in group SOBI than in the control group (p<0.01). 2) The plasma levels of HDLC in group AI&SOBI were significantly higher than in group SOBI (p<0.01). 3) The plasma levels of HLDL were similar between group AI&SOBI and AI&BOBI. 4) There were significant relationships between HDLC and acute lacunar stroke, even after adjusting for these factors such as age, sex, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and history of diabetes (p=0.001). 4) Compared with the controls, the calculation of odds ratios indicated relative risk estimates of higher HDLC for acute lacunar stroke with obsolete lacunar infarction. Conclusions Elevated HDLC may be an independent predictor of recurrent stroke with obsolete lacunar infarctions single side in Chinese people, justifying clinical trials for secondary prevention of stroke by generally increasing HLDL level. According to the difference between single and bilateral side multiple silent lacunar infarcts, it is inferred that HDLC may increase the risk of atherothrombotic infarction but reduce the risk of cardioembolic infarction in the general Chinese population. PMID:26120926

  11. Sham Surgery and Inter-Individual Heterogeneity Are Major Determinants of Monocyte Subset Kinetics in a Mouse Model of Myocardial Infarction

    PubMed Central

    Hoffmann, Jedrzej; Ospelt, Manuel; Troidl, Christian; Voss, Sandra; Liebetrau, Christoph; Kim, Won-Keun; Rolf, Andreas; Wietelmann, Astrid; Braun, Thomas; Troidl, Kerstin; Sadayappan, Sakthivel; Barefield, David; Hamm, Christian; Nef, Holger; Möllmann, Helge

    2014-01-01

    Aims Mouse models of myocardial infarction (MI) are commonly used to explore the pathophysiological role of the monocytic response in myocardial injury and to develop translational strategies. However, no study thus far has examined the potential impact of inter-individual variability and sham surgical procedures on monocyte subset kinetics after experimental MI in mice. Our goal was to investigate determinants of systemic myeloid cell subset shifts in C57BL/6 mice following MI by developing a protocol for sequential extensive flow cytometry (FCM). Methods and Results Following cross-sectional multiplex FCM analysis we provide for the first time a detailed description of absolute quantities, relative subset composition, and biological variability of circulating classical, intermediate, and non-classical monocyte subsets in C57BL/6 mice. By using intra-individual longitudinal measurements after MI induction, a time course of classical and non-classical monocytosis was recorded. This approach disclosed a significant reduction of monocyte subset dispersion across all investigated time points following MI. We found that in the current invasive model of chronic MI the global pattern of systemic monocyte kinetics is mainly determined by a nonspecific inflammatory response to sham surgery and not by the extent of myocardial injury. Conclusions Application of sequential multiplexed FCM may help to reduce the impact of biological variability in C57BL/6 mice. Furthermore, the confounding influence of sham surgical procedures should always be considered when measuring monocyte subset kinetics in a murine model of MI. PMID:24893162

  12. Blockade of self-reactive IgM significantly reduces injury in a murine model of acute myocardial infarction

    PubMed Central

    Haas, Michael S.; Alicot, Elisabeth M.; Schuerpf, Franziska; Chiu, Isaac; Li, Jinan; Moore, Francis D.; Carroll, Michael C.

    2010-01-01

    Aims Coronary artery occlusion resulting in ischaemia/reperfusion (I/R) injury is a major cause of mortality in the western world. Circulating natural IgM has been shown to play a significant role in reperfusion injury, leading to the notion of a pathogenic response against self by the innate immune system. A specific self-antigen (non-muscle myosin heavy chain II) was recently identified as the major target of pathogenic natural IgM. Therefore, we hypothesized that a synthetic peptide mimetope (N2) or monoclonal antibodies directed against the self-antigen would prevent specific IgM binding to the self-antigen and reduce reperfusion injury in the heart. Methods and results We find that treatment with N2 peptide reduces infarct size by 47% and serum cardiac troponin-I levels by 69% following 1 h ischaemia and 24 h reperfusion. N2 peptide or an anti-N2 F(ab?)2 (21G6) is also effective at preventing IgM and complement deposition. Additionally, N2 peptide treatment significantly reduces monocyte and neutrophil infiltration at 24 h and collagen deposition at 5 days. Finally, we show that human IgM (hIgM) also includes specificity for the highly conserved self-antigen and that myocardial injury in antibody-deficient mice reconstituted with hIgM is blocked by treatment with N2 peptide or 21G6 F(ab?)2. Conclusion The findings in this study identify potential therapeutics [i.e. N2 peptide or 21G6 F(ab?)2] that prevent specific IgM binding to ischaemic antigens in the heart, resulting in a significant reduction in cardiac I/R injury. PMID:20462867

  13. Computational modeling of pedunculopontine nucleus deep brain stimulation

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  14. Computational modeling of pedunculopontine nucleus deep brain stimulation

    PubMed Central

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

    2013-01-01

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

  15. The dissipative quantum model of brain and laboratory observations Walter J. Freemana

    E-print Network

    Freeman, Walter J.

    The dissipative quantum model of brain and laboratory observations Walter J. Freemana and Giuseppe of the dissipative quantum model of brain in connection with the for- mation of coherent domains of synchronized numbers: I. INTRODUCTION The mesoscopic neural activity of neocortex appears consisting of the dynamical

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

    E-print Network

    Interpretable Semantic Vectors from a Joint Model of Brain- and Text- Based Meaning Alona Fyshe1) that can incorporate a measure of semantics not previously used to create VSMs: brain activation data recorded while people read words. The resulting model takes advan- tage of the complementary strengths

  17. Expanding the Versatility of Cardiac PET\\/CT: Feasibility of Delayed Contrast Enhancement CT for Infarct Detection in a Porcine Model

    Microsoft Academic Search

    Andrew Holz; Tetsuo Sasano; Jennifer Merrill; Stephan G. Nekolla; Albert C. Lardo

    2009-01-01

    It has recently been suggested that, similar to MRI, CT can be used to detect infarcts at high resolution by delayed myocardial contrast enhancement. In cardiac PET\\/CT, this ability to detect infarcts may increase the versatility and integrative potential of PET and CT study components. We sought to determine the fea- sibility of delayed CT-enhancement in the PET\\/CT environment and

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

    E-print Network

    Piatkowski, Jakub Przemyslaw

    2014-06-27

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

  19. Effects of high-intensity interval versus continuous moderate?intensity aerobic exercise on apoptosis, oxidative stress and metabolism of the infarcted myocardium in a rat model.

    PubMed

    Lu, Kai; Wang, Li; Wang, Changying; Yang, Yuan; Hu, Dayi; Ding, Rongjing

    2015-08-01

    The optimal aerobic exercise training (AET) protocol for patients following myocardial infarction (MI) has remained under debate. The present study therefore aimed to compare the effects of continuous moderate?intensity training (CMT) and high?intensity interval training (HIT) on cardiac functional recovery, and to investigate the potential associated mechanisms in a post?MI rat model. Female Sprague Dawley rats (8?10 weeks old) undergoing MI or sham surgery were subsequently submitted to CMT or HIT, or kept sedentary for eight weeks. Prior to and following AET, echocardiographic parameters and exercise capacity of the rats were measured. Western blotting was used to evaluate the levels of apoptosis and associated signaling pathway protein expression. The concentrations of biomarkers of oxidative stress were also determined by ELISA assay. Messenger (m)RNA levels and activity of the key enzymes for glycolysis and fatty acid oxidation, as well as the rate of adenosine triphosphate (ATP) synthesis, were also measured. Compared with the MI group, exercise capacity and cardiac function were significantly improved following AET, particularly following HIT. Left ventricular ejection fraction and fraction shortening were further improved in the MI?HIT group in comparison to that of the MI?CMT group. The two forms of AET almost equally attenuated apoptosis of the post?infarction myocardium. CMT and HIT also alleviated oxidative stress by decreasing the concentration of malondialdehyde and increasing the concentration of superoxide dismutase and glutathione peroxidase (GPx). In particular, HIT induced a greater increase in the concentration of GPx than that of CMT. AET, and HIT in particular, significantly increased the levels of mRNA and the maximal activity of phosphofructokinase?1 and carnitine palmitoyl transferase?1, as well as the maximal ratio of ATP synthesis. In addition, compared with the MI group, the expression of signaling proteins PI3K, Akt, p38mapk and AMPK was significantly altered in the MI?CMT and MI?HIT groups. HIT was superior to CMT in its ability to improve cardiac function and exercise capability in a post?MI rat model. HIT was also superior to CMT with regard to attenuating oxidative stress and improving glucolipid metabolism of the post?MI myocardium. PMID:25936391

  20. A Probabilistic Model of Functional Brain Connectivity Network for Discovering Novel Biomarkers

    PubMed Central

    Bian, Jiang; Xie, Mengjun; Topaloglu, Umit; Cisler, Josh M.

    2013-01-01

    Graph theoretical analyses of functional brain connectivity networks have been limited to a static view of brain activities over the entire timeseries. In this paper, we propose a new probabilistic model of the functional brain connectivity network, the strong-edge model, which incorporates the temporal fluctuation of neurodynamics. We also introduce a systematic approach to identifying biomarkers based on network characteristics that quantitatively describe the organization of the brain network. The evaluation results of the proposed strong-edge network model is quite promising. The biomarkers derived from the strong-edge model have achieved much higher prediction accuracy of 89% (ROCAUC: 0.96) in distinguishing depression subjects from healthy controls in comparison with the conventional network model (accuracy: 76%, ROC-AUC: 0.87). These novel biomarkers have the high potential of being applied clinically in diagnosing neurological and psychiatric brain diseases with noninvasive neuroimaging technologies. PMID:24303289

  1. Fractional Diffusion Based Modelling and Prediction of Human Brain Response to External Stimuli

    PubMed Central

    Kulish, Vladimir V.

    2015-01-01

    Human brain response is the result of the overall ability of the brain in analyzing different internal and external stimuli and thus making the proper decisions. During the last decades scientists have discovered more about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research, there were fewer efforts which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling and prediction of the human EEG signal, as an alert state of overall human brain activity monitoring, upon receiving external stimuli, based on fractional diffusion equations. The results of this modeling show very good agreement with the real human EEG signal and thus this model can be used for many types of applications such as prediction of seizure onset in patient with epilepsy. PMID:26089955

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  4. Tumor growth model for atlas based registration of pathological brain MR images

    NASA Astrophysics Data System (ADS)

    Moualhi, Wafa; Ezzeddine, Zagrouba

    2015-02-01

    The motivation of this work is to register a tumor brain magnetic resonance (MR) image with a normal brain atlas. A normal brain atlas is deformed in order to take account of the presence of a large space occupying tumor. The method use a priori model of tumor growth assuming that the tumor grows in a radial way from a starting point. First, an affine transformation is used in order to bring the patient image and the brain atlas in a global correspondence. Second, the seeding of a synthetic tumor into the brain atlas provides a template for the lesion. Finally, the seeded atlas is deformed combining a method derived from optical flow principles and a model for tumor growth (MTG). Results show that an automatic segmentation method of brain structures in the presence of large deformation can be provided.

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

    PubMed

    Weston, Eleanor M; Lister, Adrian M

    2009-05-01

    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

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

    PubMed Central

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

    2014-01-01

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

  7. A novel, minimally invasive, segmental myocardial infarction with a clear healed infarct borderzone in rabbits

    PubMed Central

    Ziv, Ohad; Schofield, Lorraine; Lau, Emily; Chaves, Lenny; Patel, Divyang; Jeng, Paul; Peng, Xuwen; Choi, Bum-Rak

    2012-01-01

    Ventricular arrhythmias in the setting of a healed myocardial infarction have been studied to a much lesser degree than acute and subacute infarction, due to the pericardial scarring, which results from the traditional open-chest techniques used for myocardial infarction (MI) induction. We sought to develop a segmental MI with low perioperative mortality in the rabbit that allows optimal visualization and therefore improved study of the infarction borderzone. Rabbits underwent MI using endovascular coil occlusion of the first obtuse marginal artery. Three weeks postprocedure, we evaluated our model by echocardiography and electrophysiology studies, optical mapping of isolated hearts, and histological studies. Seventeen rabbits underwent the protocol (12 MI and 5 sham) with a 92% survival to completion of the study (11 MI and 5 sham). MI rabbits demonstrated wall motion abnormalities on echocardiography while shams did not. At electrophysiological study, two MI rabbits had inducible ventricular tachycardia and one had inducible ventricular fibrillation. Isolated hearts demonstrated no pericardial scarring with a smooth, easily identifiable infarct borderzone. Optical mapping of the borderzone region showed successful mapping of peri-infarct reentry formation, with ventricular fibrillation inducible in 11 of 11 MI hearts and 1 of 5 sham hearts. We demonstrate successful high resolution mapping in the borderzone, showing delayed conduction in this region corresponding to late deflections in the QRS on ECG. We report the successful development of a minimally invasive MI via targeted coil delivery to the obtuse marginal artery with an exceptionally high rate of procedural survival and an arrhythmogenic phenotype. This model mimics human post-MI on echocardiography, gross pathology, histology, and electrophysiology. PMID:22447944

  8. The impact of erythropoietin on short-term changes in phosphorylation of brain protein kinases in a rat model of traumatic brain injury

    Microsoft Academic Search

    Samuel Valable; Gilles Francony; Pierre Bouzat; Marie-Cécile Fevre; Nouara Mahious; Valentine Bouet; Régine Farion; Emmanuel Barbier; Hana Lahrech; Chantal Remy; Edwige Petit; Christoph Segebarth; Myriam Bernaudin; Jean-François Payen

    2010-01-01

    We found that recombinant human erythropoietin (rhEPO) reduced significantly the development of brain edema in a rat model of diffuse traumatic brain injury (TBI) (impact-acceleration model). In this study, we investigated the molecular and intracellular changes potentially involved in these immediate effects. Brain tissue nitric oxide (NO) synthesis, phosphorylation level of two protein kinases (extracellular-regulated kinase (ERK)-1\\/-2 and Akt), and

  9. Curcumin inhibits apoptosis and brain edema induced by hypoxia-hypercapnia brain damage in rat models.

    PubMed

    Yu, Linsheng; Fan, Yanyan; Ye, Guanghua; Li, Junli; Feng, Xiangping; Lin, Kezhi; Dong, Miuwu; Wang, Zhenyuan

    2015-06-01

    Curcumin, extracted from South Asian spice turmeric, has been determined to have the promising ability in antioxidation and anti-inflammation. However, the effect of curcumin on treating brain damage has been not reported. In this article, the aim was to evaluate the effect of curcumin on cell apoptosis in rats exposed to hypoxia-hypercapnia and explore the therapeutic potential of curcumin in hypoxia-hypercapnia brain damage (HHBD). Sprague Dawley rats were randomly assigned into 3 groups: control group, hypoxia-hypercapnia group and curcumin group. The Fas/FasL expressions in HHBD rats treated by curcumin were measured by immunohistochemical staining and western blotting. The pathological changes of brain cells were observed by transmission electron microscope. Rats with HHBD showed significant increase of Fas/FasL expression and ultrastructural changes in brain tissue cells. Curcumin intervention effectively reversed the Fas/FasL-mediated apoptosis and HHBD-induced brain edema. Curcumin may be a potential therapeutic alternative for HHBD. PMID:25867253

  10. Hypertensive brain stem encephalopathy.

    PubMed

    Liao, Pen-Yuan; Lee, Chien-Chang; Chen, Cheng-Yu

    2015-01-01

    A 48-year-old man presented with headache and extreme hypertension. Computed tomography showed diffuse brain stem hypodensity. Magnetic resonance imaging revealed diffuse brain stem vasogenic edema. Hypertensive brain stem encephalopathy is an uncommon manifestation of hypertensive encephalopathy, which classically occurs at parietooccipital white matter. Because of its atypical location, the diagnosis can be challenging. Moreover, the coexistence of hypertension and brain stem edema could also direct clinicians toward a diagnosis of ischemic infarction, leading to a completely contradictory treatment goal. PMID:25082596

  11. Refinement of Pig Retroperfusion Technique: Global Retroperfusion with Ligation of the Azygos Connection Preserves Hemodynamic Function in an Acute Infarction Model in Pigs (Sus scrofa domestica)

    PubMed Central

    Harig, Frank; Hoyer, Evelyn; Labahn, Dirk; Schmidt, Joachim; Weyand, Michael; Ensminger, Stephan M

    2010-01-01

    In ischemic hearts, venous retroperfusion is a potential myocardial revascularization strategy. This study aimed to refine the technical and functional aspects of a pig model of acute myocardial infarction and retroperfusion with respect to the azygos connection. Global retroperfusion after ligation of the ramus interventricularis paraconalis (equivalent to the left anterior descending artery in humans) was performed in 16 Landrace pigs (Sus scrofa domestica). Coronary sinus perfusion was performed in 8 pigs (P+) but not in the other 8 (P–), and the azygos vein was ligated (L+) 4 of the 8 pigs in each of these groups but left open (L–) in the remaining animals. Hemodynamic performance (for example, cardiac output, stroke volume) was significantly better in P+L+ pigs that underwent coronary sinus perfusion with ligation of the azygos vein compared with all other animals. In addition, troponin I release was significant lower in P+L+ pigs (1.7 ± 1.3 ng/mL) than in P–L– (5.47 ± 2.1 ng/mL), P–L+ (6.63 ± 2.4 ng/mL), and P+L– (4.81 ± 2.3 ng/mL) pigs. Effective retrograde flow and thus hemodynamic stability was achieved by ligation of the azygos vein. Therefore, experiments focusing on global retroperfusion will benefit from effective inhibition of the blood flow through the azygos vein. PMID:20158947

  12. Treatment After Myocardial Infarction

    Microsoft Academic Search

    Wilbert S. Aronow; Macy Pavilion

    2007-01-01

    Persons after myocardial infarction (MI) should have their modifiable coronary artery risk factors intensively treated. Hypertension\\u000a should be treated with beta blockers and angiotensin-converting enzyme (ACE) inhibitors. The blood pressure should be reduced\\u000a to <140\\/90 mmHg and to <130\\/80 mmHg in persons with diabetes or renal insufficiency. The serum low-density lipoprotein cholesterol\\u000a should be reduced to 1c reduced to <7.0%. Aspirin or

  13. Establishing, versus Maintaining, Brain Function: A Neuro-computational Model of Cortical Reorganization after Injury to the Immature Brain

    E-print Network

    Varier, Sreedevi; Forsyth, Rob; 10.1017/S1355617711000993

    2011-01-01

    The effect of age at injury on outcome after acquired brain injury (ABI) has been the subject of much debate. Many argue that young brains are relatively tolerant of injury. A contrasting viewpoint due to Hebb argues that greater system integrity may be required for the initial establishment of a function than for preservation of an already-established function. A neuro-computational model of cortical map formation was adapted to examine effects of focal and distributed injury at various stages of development. This neural network model requires a period of training during which it self-organizes to establish cortical maps. Injuries were simulated by lesioning the model at various stages of this process and network function was monitored as "development" progressed to completion. Lesion effects are greater for larger, earlier, and distributed (multifocal) lesions. The mature system is relatively robust, particularly to focal injury. Activities in recovering systems injured at an early stage show changes that e...

  14. Spontaneous infarction of the breast

    Microsoft Academic Search

    J J Lucey

    1975-01-01

    Five cases of infarction of physiological hyperplastic breast tissue associated with pregnancy or lactation are reported. These presented clinically as lumps in the breast, two of which were painful. Similar cases in the literature are briefly reviewed. The demonstration of an underlying lobular pattern in the present cases and the distribution of the infarcts support the view that the so-called

  15. Modelling the anesthetized brain with ensembles of neuronal and astrocytic oscillators

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. Lasting Effects of Pediatric Traumatic Brain Injury

    Microsoft Academic Search

    Christopher C. Giza

    2006-01-01

    The number one cause of death and disability in children and teenagers is traumatic brain injury. Despite this fact, this clinical scourge receives limited research investigation. Given the remarkable recovery often seen after focal childhood brain injuries (infarction, hemorrhage, surgical excision), there is a common misconception that the younger brain is always more resilient. However, increasing evidence suggests that this

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

    PubMed Central

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

    2014-01-01

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

  19. A Drosophila model of closed head traumatic brain injury

    PubMed Central

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

    2013-01-01

    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

  20. Local Model of Arteriovenous Malformation of the Human Brain

    NASA Astrophysics Data System (ADS)

    Nadezhda Telegina, Ms; Aleksandr Chupakhin, Mr; Aleksandr Cherevko, Mr

    2013-02-01

    Vascular diseases of the human brain are one of the reasons of deaths and people's incapacitation not only in Russia, but also in the world. The danger of an arteriovenous malformation (AVM) is in premature rupture of pathological vessels of an AVM which may cause haemorrhage. Long-term prognosis without surgical treatment is unfavorable. The reduced impact method of AVM treatment is embolization of a malformation which often results in complete obliteration of an AVM. Pre-surgical mathematical modeling of an arteriovenous malformation can help surgeons with an optimal sequence of the operation. During investigations, the simple mathematical model of arteriovenous malformation is developed and calculated, and stationary and non-stationary processes of its embolization are considered. Various sequences of embolization of a malformation are also considered. Calculations were done with approximate steady flow on the basis of balanced equations derived from conservation laws. Depending on pressure difference, a fistula-type AVM should be embolized at first, and then small racemose AVMs are embolized. Obtained results are in good correspondence with neurosurgical AVM practice.

  1. Hemorrhagic infarction at 33 days after birth in a healthy full-term neonate

    PubMed Central

    Kubo, Yoshitaka; Ogasawara, Kuniaki; Kurose, Akira; Kashimura, Hiroshi; Koji, Takahiro; Otawara, Yasunari; Kamei, Jun; Akasaka, Manami; Sasaki, Makoto; Ogawa, Akira

    2011-01-01

    Intraparenchymal hemorrhage in the full-term neonate rarely occurs more than 2 weeks after birth, and its definitive cause remains unclear. In the present report, a case of a patient with intraparenchymal hemorrhage occurring 33 days after birth is described. Histological examination of the brain tissue obtained during hematoma evacuation through craniotomy showed hemorrhagic infarction. Patent foramen ovale may have been present and this may have led to spontaneous paradoxical cerebral embolism followed by hemorrhagic infarction. PMID:22140317

  2. A Mathematical Model to Elucidate Brain Tumor Abrogation by Immunotherapy with T11 Target Structure

    PubMed Central

    Chaudhuri, Swapna

    2015-01-01

    T11 Target structure (T11TS), a membrane glycoprotein isolated from sheep erythrocytes, reverses the immune suppressed state of brain tumor induced animals by boosting the functional status of the immune cells. This study aims at aiding in the design of more efficacious brain tumor therapies with T11 target structure. We propose a mathematical model for brain tumor (glioma) and the immune system interactions, which aims in designing efficacious brain tumor therapy. The model encompasses considerations of the interactive dynamics of glioma cells, macrophages, cytotoxic T-lymphocytes (CD8+ T-cells), TGF-?, IFN-? and the T11TS. The system undergoes sensitivity analysis, that determines which state variables are sensitive to the given parameters and the parameters are estimated from the published data. Computer simulations were used for model verification and validation, which highlight the importance of T11 target structure in brain tumor therapy. PMID:25955428

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

    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.

  4. Myocardial infarct size and area at risk assessment in mice

    PubMed Central

    Redfors, Bjorn; Shao, Yangzhen; Omerovic, Elmir

    2012-01-01

    Mouse models of myocardial ischemia and infarction are important in cardiovascular research. Reliable and reproducible assessment of the area at risk (AAR) and infarct size (IS) in mice is vital for deciphering mechanisms behind these common diseases, and for developing and evaluating treatment strategies. The present review will briefly describe and discuss the most common methods for determining the AAR and IS in mouse models of cardiovascular disease. Several methods exist for ex vivo assessment of IS. Conventional histological stains target the fibrous scar and require several days to pass from the time of infarct induction until the animal is euthanized, whereas triphenyltetrazolium-based techniques stain the viable tissue surrounding the infarct and can be performed on tissue harvested within a few hours after infarction. The AAR is usually stained by injecting a dye into the circulation. This dye subsequently distributes to perfused tissue but leaves the AAR unstained. In vivo assessment enables serial measurements of the IS and/or AAR and is sometimes preferable to ex vivo techniques. Echocardiography is usually the method of choice but magnetic resonance imaging-based techniques are also used. The aim of the present review was to provide basic researchers with an introduction to the various techniques used to assess and quantify the IS and AAR in experimental mouse models of myocardial ischemia-reperfusion and infarction. PMID:23592952

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

    Microsoft Academic Search

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

    2001-01-01

    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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

    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…

  7. Bosons and a Quantum Model of the Brain Karl-Heinz Fichtner Lars Fichtner

    E-print Network

    1 Bosons and a Quantum Model of the Brain Karl-Heinz Fichtner Lars Fichtner Magnetoencephalography caused by neural activation. The major sources of both the EEG and MEG are widely accepted the brain like MEG or EEG and others are based on quantum principles. For that reason it seems to be obvious

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

    Microsoft Academic Search

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

    1995-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

    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.

  10. 3D brain atlas reconstructor service--online repository of three-dimensional models of brain structures.

    PubMed

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

    2013-10-01

    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

  11. Investigation of Brain Trauma Biomechanics in Vehicle Traffic Accidents Using Human Body Computational Models

    Microsoft Academic Search

    Jikuang Yang

    \\u000a This chapter aimed to study the biomechanical response and injury mechanisms of brain in passenger car-to-pedestrian collision\\u000a event. The kinematics of head impact to a passenger car was reconstructed using multibody dynamics (MBD) models. The brain\\u000a injury biomechanics was investigated by using an FE model of human body head (HBM-head). The HBM-head model was developed\\u000a in accordance with human head

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

    PubMed Central

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

    2014-01-01

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

  13. Head and brain response to blast using sagittal and transverse finite element models.

    PubMed

    Singh, Dilaver; Cronin, Duane S; Haladuick, Tyler N

    2014-04-01

    Mild traumatic brain injury caused by blast exposure from Improvised Explosive Devices has become increasingly prevalent in modern conflicts. To investigate head kinematics and brain tissue response in blast scenarios, two solid hexahedral blast-head models were developed in the sagittal and transverse planes. The models were coupled to an Arbitrary Lagrangian-Eulerian model of the surrounding air to model blast-head interaction, for three blast load cases (5 kg C4 at 3, 3.5 and 4 m). The models were validated using experimental kinematic data, where predicted accelerations were in good agreement with experimental tests, and intracranial pressure traces at four locations in the brain, where the models provided good predictions for frontal, temporal and parietal, but underpredicted pressures at the occipital location. Brain tissue response was investigated for the wide range of constitutive properties available. The models predicted relatively low peak principal brain tissue strains from 0.035 to 0.087; however, strain rates ranged from 225 to 571 s-1. Importantly, these models have allowed us to quantify expected strains and strain rates experienced in brain tissue, which can be used to guide future material characterization. These computationally efficient and predictive models can be used to evaluate protection and mitigation strategies in future analysis. PMID:24293124

  14. PDT-induced apoptosis: investigations using two malignant brain tumor models

    NASA Astrophysics Data System (ADS)

    Lilge, Lothar D.; Menzies, Keir; Bisland, Stuart K.; Lin, Annie; Wilson, Brian C.

    2002-06-01

    PDT included necrosis in brain tissue and an intracranial tumor has been quantified for various photosensitizers, and it has been shown to be dependent on the sub-cellular localization of these photosensitizers. In quantifying non- necrotic biological endpoints, such as PDT induced apoptosis, the expression and translation of apoptosis inhibiting or promoting genes is of considerable importance. We studied the susceptibility of two glioblastoma cell lines to under go apoptotic cell death following photodynamic treatment with either Photofrin or delta-aminolevulinic acid (delta) ALA) in vivo. Murine 9L Gliosarcoma cells or human U87 Glioblastoma cells were implanted into the cortex of rats, and following 12 or 14 days of growth respectively, subjected to either Photofrin-mediated PDT or ALA-mediated PDT. 9L gliosarcoma cells express the phosphatase Tensin homologue (PTEN) tumor suppressor gene while in U87 cells PTEN is mutated. Differences in the Photofrin mediated PDT induced apoptosis were noted between the two different cell lines in vivo, suggesting that Photofrin mediated PDT may be dependent on apoptotic pathways. ALA induced PPIX showed higher selectivity towards 9L than Photofrin mediated PDT. These studies suggests that PDT could be used as an effective treatment for intracranial neoplasm. Endogenous photosensitizers such as ALA could be used to promote apoptosis in tumor cells due to PDT treatment and thereby minimize the extent of necrotic infarction in the surrounding normal brain.

  15. Acute confusional states with right middle cerebral artery infarctions.

    PubMed Central

    Mesulam, M M; Waxman, S G; Geschwind, N; Sabin, T D

    1976-01-01

    Three patients presenting predominantly with acute confusional states (ACS) are shown to have infarctions in the distribution of the right middle cerebral artery. It is suggested that the main deficit in ACS is in the function of selective attention. On the basis of cortical connections of homologous areas in the monkey brain, it is argued that this deficit arises from lesions in convergence areas for association cortex. Images PMID:1255216

  16. Admittance?based pressure–volume loops versus gold standard cardiac magnetic resonance imaging in a porcine model of myocardial infarction

    PubMed Central

    van Hout, Gerardus P. J.; Jansen, Sanne J.; Gho, Johannes M. I. H.; Doevendans, Pieter A.; van Solinge, Wouter W.; Pasterkamp, Gerard; Chamuleau, Steven A. J.; Hoefer, Imo E.

    2014-01-01

    Abstract A novel admittance?based pressure–volume system (AS) has recently been developed and introduced. Thus far, the new technique has been validated predominantly in small animals. In large animals it has only been compared to three?dimensional echocardiography (3DE) where the AS showed to overestimate left ventricular (LV) volumes. To fully determine the accuracy of this device, we compared the AS with gold standard cardiac magnetic resonance imaging (CMRI) in a porcine model of chronic myocardial infarction (MI). Fourteen pigs were subjected to 90 min closed chest balloon occlusion of the left anterior descending artery. After 8 weeks of follow up, pigs were consecutively subjected to LV volume measurements by the AS, CMRI, and 3DE under general anesthesia. The AS overestimated end diastolic volume (EDV; +20.9 ± 30.6 mL, P = 0.024) and end systolic volume (ESV; +17.7 ± 29.4 mL, P = 0.042) but not ejection fraction (EF; +2.46 ± 6.16%, P = NS) compared to CMRI. Good correlations of EDV (R = 0.626, P = 0.017) and EF (R = 0.704, P = 0.005) between the AS and CMRI were observed. EF measured by the AS and 3DE also correlated significantly (R = 0.624, P = 0.030). After subjection of pigs to MI, the AS very moderately overestimates LV volumes and shows accurate measurements for EF compared to CMRI. This makes the AS a useful tool to determine cardiac function and dynamic changes in large animal models of cardiac disease. PMID:24771693

  17. Biomechanical analysis of blast induced traumatic brain injury---A finite element modeling and validation study of blast effects on human brain

    Microsoft Academic Search

    Sumit Sharma

    2011-01-01

    An estimated 19.5% of all U.S. troops deployed to Iraq\\/Afghanistan have symptoms related to blast-induced Traumatic Brain Injury (bTBI). Up to now causal mechanisms of bTBI are unknown. Previously an anatomically detailed human head finite element model (WSUHIM) was successfully utilized to predict brain injuries from blunt impact. The measurements of wave propagation patterns within an in vivo brain continue

  18. Biomechanical analysis of blast induced traumatic brain injury- a finite element modeling and validation study of blast effects on human brain

    Microsoft Academic Search

    Sumit Sharma

    2011-01-01

    An estimated 19.5% of all U.S. troops deployed to Iraq\\/Afghanistan have symptoms related to blast-induced Traumatic Brain Injury (bTBI). Up to now causal mechanisms of bTBI are unknown. Previously an anatomically detailed human head finite element model (WSUHIM) was successfully utilized to predict brain injuries from blunt impact. The measurements of wave propagation patterns within an in vivo brain continue

  19. Postoperative cerebral venous infarction

    PubMed Central

    Agrawal, Deepak; Naik, Vikas

    2015-01-01

    Background: Postoperative cerebral venous infarction (POCVI) is not an uncommon complication in cranial surgeries. However, literature is sparse on the epidemiology and management of postoperative venous infarcts. Aims and Objectives: The aim was to study the incidence and clinico-radiological course of POCVI in patients in a tertiary level neurosurgical unit and compare the outcome between pediatric and adult patients following POCVI. Materials and Methods: In this prospective study carried out over an 8 month period, consecutive patients undergoing elective major cranial surgeries were monitored neurologically and with serial computed tomography (CT) of the head for POCVI in the postoperative period. All patients had at least one CT head done within 24 hours of surgery. Diagnosis of hemorrhagic POCVI was based on the presence of subcortical, multifocal hyperdensities with irregular margins and or low density areas in the perioperative fields. Nonhemorrhagic POCVI was diagnosed if CT showed a localized hypodensity poorly demarcated in the subcortical white matter with/without mass effect, along with the presence of fresh neurological deficits. Observations and Results: A total of 376 patients were enrolled in the study period. Of these, 26 (7%) developed POCVI. The male: female ratio was 1.2:1 and age ranged from 6 to 68 years with 12 (46%) being under the age of 18 years. Sixteen (61%) patients developed hemorrhagic POCVI and 10 (39%) patients developed nonhemorrhagic POCVI. The mean time to POCVI detection was 72 hours (range 24–144 hours). Seventeen (66%) patients were managed conservatively, and nine (34%) patients underwent decompressive craniectomy as an additional procedure for management of POCVI. In five patients (all with hemorrhagic POCVI), the infarction was an incidental finding. Of the 21 patients with symptomatic POCVI, 13 (61.9%) patients improved neurologically and were discharged with residual deficits. Two (9.5%) showed no neurological improvement till discharge, and 6 (28.5%) died during the hospital stay following POCVI. Conclusions: Children constitute a significant population (46% in our study) of the patients who develop POCVI with poor outcome similar to that seen in adult patients. PMID:25878733

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  1. Microglia function during brain development: New insights from animal models.

    PubMed

    Bilimoria, Parizad M; Stevens, Beth

    2015-08-18

    The role of microglia in healthy brains is just beginning to receive notice. Recent studies have revealed that these phagocytic cells control the patterning and wiring of the developing central nervous system (CNS) by regulating, amongst many other processes, programmed cell death, activity-dependent synaptic pruning and synapse maturation. Microglia also play important roles in the mature brain and have demonstrated effects on behavior. Converging evidence from human and mouse studies together raise questions as to the role of microglia in disorders of brain development such as autism and, schizophrenia. In this review, we summarize a number of major findings regarding the role of microglia in brain development and highlight some key questions and avenues for future study. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. PMID:25463024

  2. A statistical model for multiphoton calcium imaging of the brain

    E-print Network

    Malik, Wasim Q.

    Multiphoton calcium fluorescence imaging has gained prominence as a valuable tool for the study of brain cells, but the corresponding analytical regimes remain rather naive. In this paper, we develop a statistical framework ...

  3. Topodiagnostic investigations on the sympathoexcitatory brain stem pathway using a new method of three dimensional brain stem mapping

    PubMed Central

    Marx, J; Iannetti, G; Mika-Gruettner, A; Thoemke, F; Fitzek, S; Vucurevic, G; Urban, P; Stoeter, P; Cruccu, G; Hopf, H

    2004-01-01

    Objectives: To study the incompletely understood sympathoexcitatory pathway through the human brain stem, using a new method of three dimensional brain stem mapping on the basis of digitally postprocessed magnetic resonance imaging (MRI). Methods: 258 consecutive patients presenting with acute signs of brain stem ischaemia underwent biplane T2 and EPI diffusion weighted MRI, with slice orientation parallel and perpendicular to a transversal slice selection of the stereotactic anatomical atlas of Schaltenbrand and Wahren, 1977. The individual slices were digitally normalised and projected onto the appropriate slices of the anatomical atlas. For correlation analysis lesions were imported into a three dimensional model of the human brain stem. Results: 31 of the 258 patients had Horner's syndrome caused by acute brain stem ischaemia. Only four of the patients with Horner's syndrome had pontine infarctions, 12 had pontomedullary lesions, and 15 had medullary lesions. Correlation analysis showed significantly affected voxels in the dorsolateral medulla but not in the pons. A statistical comparison with infarct topology in patients with medullary lesions but without Horner's syndrome indicated that involvement of the medial and ventral part of affected voxels located in the ventrolateral medullary tegmentum was specific for Horner's syndrome. Conclusions: Based on this first in vivo topodiagnostic study, the central sympathoexcitatory pathway probably descends through the dorsal pons before converging on specific generators in the ventrolateral medullary tegmentum at a level below the IX and X nerve exits. PMID:14742599

  4. Depression after myocardial infarction.

    PubMed Central

    Kavanagh, T.; Shephard, R. J.; Tuck, J. A.

    1975-01-01

    The Minnesota Multiphasic Personality Inventory was completed by 101 patients 16 to 18 months after a proved myocardial infarction. The data suggested a bimodal distribution of patients. One class of patients had a relatively "normal" personality score apart from a tendency to hypomania. The second class had severe depression, with associated hysteria, hypochondriasis and psychasthenia. The severely depressed patients were older, with a greater tendency to hypertension and angina, and a tendency to smaller gains in aerobic power despite an equal intensity of endurance training. The distinction between "normal" and "depressed" postinfarction patients seems of some clinical importance, for the two classes of patients require opposite supportive techniques--restraint and encouragement, respectively. PMID:1148970

  5. Categories and functional units: An infinite hierarchical model for brain activations

    E-print Network

    Lashkari, Danial

    We present a model that describes the structure in the responses of different brain areas to a set of stimuli in terms of stimulus categories (clusters of stimuli) and functional units (clusters of voxels). We assume that ...

  6. A Model Based System For The Interpretation Of MR Human Brain Scans

    NASA Astrophysics Data System (ADS)

    Kapouleas, Ioannis; Kulikowski, Casimir A.

    1988-06-01

    This paper describes a prototype system for identifying and characterizing Multiple Sclerosis (MS) lesions in the brain from magnetic resonance (MR) images. The system is designed to obtain an initial segmentation of each cross-sectional image with low level vision methods, and then derive successive refinements of image subregions through a model-driven approach that correlates relevant information from T1 and T2 images and 3-D information from complementary cross-sections when necessary. The system uses a b-spline surface model of the brain that matches the characteristics of the individual's brain. The normal internal structures of the brain are then scaled proportionately before carrying out the successive refinement operations for the detection of the MS lesions. The low level vision and the solid modeling components of the system have been successfully tested on several hundred images from a number of MR patient studies. The first steps of model fitting have been implemented and show promising results.

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

    E-print Network

    Eleonora Alfinito; Giuseppe Vitiello

    1999-12-30

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

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

    E-print Network

    Alfinito, E; Alfinito, Eleonora; Vitiello, Giuseppe

    1999-01-01

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

  9. A Computational Model for Lesion Dynamics in Multiple Sclerosis of the Brain

    E-print Network

    Sen, Surajit

    A Computational Model for Lesion Dynamics in Multiple Sclerosis of the Brain Krishna Mohan, T. R of Pharmaceutical Sciences, State University of New York, Buffalo, NY 14260-1200, USA 1 Abstract Multiple sclerosis

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

    E-print Network

    Shahmirzadi, Danial

    2005-11-01

    This study mainly deals with the various aspects of modeling the learning processes within the brain limbic system and studying the various aspects of using it for different applications in control engineering. The current ...

  11. Effect of cytokine hemoadsorption on brain death–induced ventricular dysfunction in a porcine model

    PubMed Central

    Mikhova, Krasimira M.; Don, Creighton W.; Laflamme, Michael; Kellum, John A.; Mulligan, Michael S.; Verrier, Edward D.; Rabkin, David G.

    2013-01-01

    Objective In an effort to expand the cardiac donor pool, we tested the hypothesis that hemoadsorption of cytokines attenuates brain death–induced ventricular dysfunction. Methods Eighteen Yorkshire pigs (50–60 kg) were instrumented with a left ventricular conductance catheter. Cytokine expression, preload recruitable stroke work, and the diastolic relaxation constant tau were measured at baseline and at hourly intervals for 6 hours after induction of brain death by intracranial balloon inflation (brain death, n = 6) or sham operation (control, n = 6). In a third group (brain death + hemoadsorption, n = 6), 3 hours after induction of brain death, animals were placed on an extracorporeal circuit containing a cytokine-hemoadsorption device for the remaining 3 hours of the experiment. Myocardial water content was measured after the animals were killed. Results Six hours after induction of brain death, tumor necrosis factor and interleukin-6 were highest in the brain death group (106 ± 13.1 pg/mL and 301 ± 181 pg/mL, respectively), lowest in controls (68.3 ± 8.55 pg/mL and 37.8 ± 11 pg/mL, respectively), and intermediate in the brain death + hemoadsorption group (81.2 ± 35.2 pg/mL and 94.6 ± 20 pg/mL, respectively). Compared with controls, preload recruitable stroke work was significantly reduced in the brain death group 4 hours after the induction of brain death and was 50% of baseline by 5 hours. In the brain death + hemoadsorption group, preload recruitable stroke work was relatively preserved at 80% of baseline at similar time points. Tau remained unchanged in the control and brain death + hemoadsorption groups, whereas in the brain death group it was significantly elevated versus baseline 5 (139.3% ± 21.5%) and 6 (172% ± 16.1%) hours after induction of brain death. Myocardial water content was significantly greater in the brain death group than in the other 2 groups. Conclusions Hemoadsorption of cytokines using an extracorporeal circuit attenuates brain death–induced ventricular dysfunction in a porcine model. Improvement in function generally correlates with trends in cytokine expression, but this relationship requires further investigation. PMID:23127374

  12. Nitroglycerin Use in Myocardial Infarction Patients: Risks and Benefits

    PubMed Central

    Ferreira, Julio C.B.; Mochly-Rosen, Daria

    2012-01-01

    Acute myocardial infarction and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin remains a first-line treatment for angina pectoris and acute myocardial infarction. Nitroglycerin achieves its benefit by giving rise to nitric oxide, which causes vasodilation and increases blood flow to the myocardium. However, continuous delivery of nitroglycerin results in tolerance, limiting the use of this drug. Nitroglycerin tolerance is due, at least in part, to inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme that converts nitroglycerin to the vasodilator, nitric oxide. We have recently found that, in addition to nitroglycerin’s effect on the vasculature, sustained treatment with nitroglycerin negatively affects cardiomyocyte viability following ischemia, thus resulting in increased infarct size in a myocardial infarction model in animals. Co-administration of Alda-1, an activator of ALDH2, with nitroglycerin improves metabolism of reactive aldehyde adducts and prevents the nitroglycerin-induced increase in cardiac dysfunction following myocardial infarction. In this review, we describe the molecular mechanisms associated with the benefits and risks of nitroglycerin administration in myocardial infarction. (167 of 200). PMID:22040938

  13. Biophysically Accurate Brain Modeling and Simulation using Hybrid MPI/OpenMP Parallel Processing 

    E-print Network

    Hu, Jingzhen

    2012-07-16

    i BIOPHYSICALLY ACCURATE BRAIN MODELING AND SIMULATION USING HYBRID MPI/OPENMP PARALLEL PROCESSING A Thesis by JINGZHEN HU Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment... Copyright 2012 Jingzhen Hu iii BIOPHYSICALLY ACCURATE BRAIN MODELING AND SIMULATION USING HYBRID MPI/OPENMP PARALLEL PROCESSING A Thesis by JINGZHEN HU Submitted to the Office of Graduate Studies of Texas A&M University in partial...

  14. Crataegus special extract WS® 1442 improves cardiac function and reduces infarct size in a rat model of prolonged coronary ischemia and reperfusion

    Microsoft Academic Search

    Maris Veveris; Egon Koch; Shyam S Chatterjee

    2004-01-01

    In Germany, hydroalcoholic extracts from hawthorn (Crataegus spp.) leaves with flowers are approved drugs for the treatment of mild forms of heart insufficiency. Besides cardiotonic effects these herbal remedies have been shown to possess cardioprotective properties. We now evaluated if treatment of rats with the Crataegus special extract WS® 1442 also improves cardiac function and prevents myocardial infarction during prolonged

  15. Development of an in vitro blood–brain barrier model—cytotoxicity of mercury and aluminum

    Microsoft Academic Search

    Tarja Toimela; Hanna Mäenpää; Marika Mannerström; Hanna Tähti

    2004-01-01

    In this study, in vitro blood–brain barrier (BBB) models composed of two different cell types were compared. The aim of our study was to find an alternative human cell line that could be used in BBB models. Inorganic and organic mercury and aluminum were studied as model chemicals in the testing of the system. BBB models were composed of endothelial

  16. Quantum-like model of processing of information in the brain based on classical electromagnetic field.

    PubMed

    Khrennikov, Andrei

    2011-09-01

    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

  17. Mechanisms of brain injury related to mathematical modelling and epidemiological data.

    PubMed

    Willinger, R; Ryan, G A; McLean, A J; Kopp, C M

    1994-12-01

    Measurements of the frequency response of head impact points on the exterior and the interior of a car were used to characterize the dynamic behavior of the object that was struck. These points were then arranged in a hierarchy of increasing stiffness. Thirty-two cases in which the distribution of injury to the brain had been recorded were grouped according to the stiffness of the object struck and by the location of the impact on the head. The distribution of the brain lesions were determined for each class of stiffness and location of impact. Three probable mechanisms of brain injury were distinguished: relative motion between the brain and the skull, local bone deformation, and intracerebral stresses. Each mechanism was related to a range of stiffness and natural frequency of the structure impacted. These theories of brain injury mechanisms are consistent with observed epidemiological data and with conclusions drawn from mathematical modelling. PMID:7857491

  18. Conjugation of functionalized SPIONs with transferrin for targeting and imaging brain glial tumors in rat model.

    PubMed

    Jiang, Weili; Xie, Hui; Ghoorah, Devina; Shang, Yalei; Shi, Haojun; Liu, Fang; Yang, Xiangliang; Xu, Haibo

    2012-01-01

    Currently, effective and specific diagnostic imaging of brain glioma is a major challenge. Nanomedicine plays an essential role by delivering the contrast agent in a targeted manner to specific tumor cells, leading to improvement in accurate diagnosis by good visualization and specific demonstration of tumor cells. This study investigated the preparation and characterization of a targeted MR contrast agent, transferrin-conjugated superparamagnetic iron oxide nanoparticles (Tf-SPIONs), for brain glioma detection. MR imaging showed the obvious contrast change of brain glioma before and after administration of Tf-SPIONs in C6 glioma rat model in vivo on T2 weighted imaging. Significant contrast enhancement of brain glioma could still be clearly seen even 48 h post injection, due to the retention of Tf-SPIONs in cytoplasm of tumor cells which was proved by Prussian blue staining. Thus, these results suggest that Tf-SPIONs could be a potential targeting MR contrast agent for the brain glioma. PMID:22615995

  19. Inflammatory Consequences in a Rodent Model of Mild Traumatic Brain Injury

    PubMed Central

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

    2013-01-01

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

  20. Prenatal Brain Damage in Preeclamptic Animal Model Induced by Gestational Nitric Oxide Synthase Inhibition

    PubMed Central

    Pellicer, Begoña; Herraiz, Sonia; Leal, Antonio; Simón, Carlos; Pellicer, Antonio

    2011-01-01

    Cerebral palsy is a major neonatal handicap with unknown aetiology. There is evidence that prenatal brain injury is the leading cause of CP. Severe placental pathology accounts for a high percentage of cases. Several factors predispose to prenatal brain damage but when and how they act is unclear. The aim of this paper was to determine if hypoxia during pregnancy leads to damage in fetal brain and to evaluate the localization of this injury. An animal model of chronic hypoxia produced by chronic administration of a nitric oxide synthase inhibitor (L-NAME) was used to evaluate apoptotic activity in fetal brains and to localize the most sensitive areas. L-NAME reproduces a preeclamptic-like condition with increased blood pressure, proteinuria, growth restriction and intrauterine mortality. Apoptotic activity was increased in L-NAME brains and the most sensitive areas were the subventricular and pallidum zone. These results may explain the clinical features of CP. Further studies are needed. PMID:21490794

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

    Microsoft Academic Search

    A. Gámez; T. Carbonell; R. Rama

    2003-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  3. Amnesia due to Fornix Infarction

    Microsoft Academic Search

    Shyam S. Moudgil; Mouhannad Azzouz; Abdulkader Al-Azzaz; Marc Haut; Ludwig Gutmann

    2010-01-01

    Background and Purpose—The fornix connects various structures involved in memory. We report a patient with anterograde amnesia after an acute ischemic infarct in the anterior fornix. Case Description—A 71-year-old female with acute-onset amnesia had neuroimaging studies showing ischemic infarction of both columns and the body of the fornix and the genu of the corpus callosum. Neuropsychological evaluation revealed anterograde amnesia

  4. Patient-specific model of brain deformation: application to medical image registration.

    PubMed

    Wittek, Adam; Miller, Karol; Kikinis, Ron; Warfield, Simon K

    2007-01-01

    This contribution presents finite element computation of the deformation field within the brain during craniotomy-induced brain shift. The results were used to illustrate the capabilities of non-linear (i.e. accounting for both geometric and material non-linearities) finite element analysis in non-rigid registration of pre- and intra-operative magnetic resonance images of the brain. We used patient-specific hexahedron-dominant finite element mesh, together with realistic material properties for the brain tissue and appropriate contact conditions at boundaries. The model was loaded by the enforced motion of nodes (i.e. through prescribed motion of a boundary) at the brain surface in the craniotomy area. We suggest using explicit time-integration scheme for discretised equations of motion, as the computational times are much shorter and accuracy, for practical purposes, the same as in the case of implicit integration schemes. Application of the computed deformation field to register (i.e. align) the pre-operative images with the intra-operative ones indicated that the model very accurately predicts the displacements of the tumour and the lateral ventricles even for limited information about the brain surface deformation. The prediction accuracy improves when information about deformation of not only exposed (during craniotomy) but also unexposed parts of the brain surface is used when prescribing loading. However, it appears that the accuracy achieved using information only about the deformation of the exposed surface, that can be determined without intra-operative imaging, is acceptable. The presented results show that non-linear biomechanical models can complement medical image processing techniques when conducting non-rigid registration. Important advantage of such models over the previously used linear ones is that they do not require unrealistic assumptions that brain deformations are infinitesimally small and brain stress-strain relationship is linear. PMID:16678834

  5. Intraoperative Pontine Infarction: A Hidden Challenge

    PubMed Central

    Marcanthony, Nicholas; Farag, Ehab

    2012-01-01

    Apneusis, or apneustic respirations, is characterized by an abnormal breathing pattern involving gasping and the inability to fully expire. A loss of gag reflex and other cranial nerve deficits are also often accompanied with these respiratory changes. In neurological intensive care units (NICUs), these respiratory and airway changes are not uncommon and have been well documented (Lee et al. 1976). These clinical changes are often associated with pontine trauma as it is the core pneumotaxic center in the brain stem. We describe the airway management of a patient with an acute, occult pontine infarct status post craniectomy and cervical laminectomy for decompression of known Chiari malformation in the postanesthesia care unit (PACU). PMID:22606411

  6. MRI as a tool to study brain structure from mouse models for mental retardation

    NASA Astrophysics Data System (ADS)

    Verhoye, Marleen; Sijbers, Jan; Kooy, R. F.; Reyniers, E.; Fransen, E.; Oostra, B. A.; Willems, Peter; Van der Linden, Anne-Marie

    1998-07-01

    Nowadays, transgenic mice are a common tool to study brain abnormalities in neurological disorders. These studies usually rely on neuropathological examinations, which have a number of drawbacks, including the risk of artefacts introduced by fixation and dehydration procedures. Here we present 3D Fast Spin Echo Magnetic Resonance Imaging (MRI) in combination with 2D and 3D segmentation techniques as a powerful tool to study brain anatomy. We set up MRI of the brain in mouse models for the fragile X syndrome (FMR1 knockout) and Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus (CRASH) syndrome (L1CAM knockout). Our major goal was to determine qualitative and quantitative differences in specific brain structures. MRI of the brain of fragile X and CRASH patients has revealed alterations in the size of specific brain structures, including the cerebellar vermis and the ventricular system. In the present MRI study of the brain from fragile X knockout mice, we have measured the size of the brain, cerebellum and 4th ventricle, which were reported as abnormal in human fragile X patients, but found no evidence for altered brain regions in the mouse model. In CRASH syndrome, the most specific brain abnormalities are vermis hypoplasia and abnormalities of the ventricular system with some degree of hydrocephalus. With the MRI study of L1CAM knockout mice we found vermis hypoplasia, abnormalities of the ventricular system including dilatation of the lateral and the 4th ventricles. These subtle abnormalities were not detected upon standard neuropathological examination. Here we proved that this sensitive MRI technique allows to measure small differences which can not always be detected by means of pathology.

  7. Revisiting Hydrocephalus as a Model to Study Brain Resilience

    PubMed Central

    de Oliveira, Matheus Fernandes; Pinto, Fernando Campos Gomes; Nishikuni, Koshiro; Botelho, Ricardo Vieira; Lima, Alessandra Moura; Rotta, José Marcus

    2011-01-01

    Hydrocephalus is an entity which embraces a variety of diseases whose final result is the enlarged size of cerebral ventricular system, partially or completely. The physiopathology of hydrocephalus lies in the dynamics of circulation of cerebrospinal fluid (CSF). The consequent CSF stasis in hydrocephalus interferes with cerebral and ventricular system development. Children and adults who sustain congenital or acquired brain injury typically experience a diffuse insult that impacts many areas of the brain. Development and recovery after such injuries reflects both restoration and reorganization of cognitive functions. Classic examples were already reported in literature. This suggests the presence of biological mechanisms associated with resilient adaptation of brain networks. We will settle a link between the notable modifications to neurophysiology secondary to hydrocephalus and the ability of neuronal tissue to reassume and reorganize its functions. PMID:22232589

  8. Model-driven therapeutic treatment of neurological disorders: reshaping brain rhythms with neuromodulation

    PubMed Central

    Modolo, Julien; Legros, Alexandre; Thomas, Alex W.; Beuter, Anne

    2011-01-01

    Electric stimulation has been investigated for several decades to treat, with various degrees of success, a broad spectrum of neurological disorders. Historically, the development of these methods has been largely empirical but has led to a remarkably efficient, yet invasive treatment: deep brain stimulation (DBS). However, the efficiency of DBS is limited by our lack of understanding of the underlying physiological mechanisms and by the complex relationship existing between brain processing and behaviour. Biophysical modelling of brain activity, describing multi-scale spatio-temporal patterns of neuronal activity using a mathematical model and taking into account the physical properties of brain tissue, represents one way to fill this gap. In this review, we illustrate how biophysical modelling is beginning to emerge as a driving force orienting the development of innovative brain stimulation methods that may move DBS forward. We present examples of modelling works that have provided fruitful insights in regards to DBS underlying mechanisms, and others that also suggest potential improvements for this neurosurgical procedure. The reviewed literature emphasizes that biophysical modelling is a valuable tool to assist a rational development of electrical and/or magnetic brain stimulation methods tailored to both the disease and the patient's characteristics. PMID:22419974

  9. Effects of buyang huanwu decoction on ventricular remodeling and differential protein profile in a rat model of myocardial infarction.

    PubMed

    Zhou, Ying Chun; Liu, Bin; Li, Ying Jia; Jing, Lin Lin; Wen, Ge; Tang, Jing; Xu, Xin; Lv, Zhi Ping; Sun, Xue Gang

    2012-01-01

    Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from "Correction on Errors in Medical Classics" in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18?g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF. PMID:23049607

  10. Effects of Buyang Huanwu Decoction on Ventricular Remodeling and Differential Protein Profile in a Rat Model of Myocardial Infarction

    PubMed Central

    Zhou, Ying Chun; Liu, Bin; Li, Ying Jia; Jing, Lin Lin; Wen, Ge; Tang, Jing; Xu, Xin; Lv, Zhi Ping; Sun, Xue Gang

    2012-01-01

    Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from “Correction on Errors in Medical Classics” in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18?g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF. PMID:23049607

  11. Long-term reorganization of structural brain networks in a rabbit model of intrauterine growth restriction.

    PubMed

    Batalle, Dafnis; Muñoz-Moreno, Emma; Arbat-Plana, Ariadna; Illa, Miriam; Figueras, Francesc; Eixarch, Elisenda; Gratacos, Eduard

    2014-10-15

    Characterization of brain changes produced by intrauterine growth restriction (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This condition affects 5-10% of all pregnancies and is associated with a wide range of neurodevelopmental disorders. Better understanding of the brain reorganization produced by IUGR opens a window of opportunity to find potential imaging biomarkers in order to identify the infants with a high risk of having neurodevelopmental problems and apply therapies to improve their outcomes. Structural brain networks obtained from diffusion magnetic resonance imaging (MRI) is a promising tool to study brain reorganization and to be used as a biomarker of neurodevelopmental alterations. In the present study this technique is applied to a rabbit animal model of IUGR, which presents some advantages including a controlled environment and the possibility to obtain high quality MRI with long acquisition times. Using a Q-Ball diffusion model, and a previously published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14 control rabbits at 70 days of age (equivalent to pre-adolescence human age) were obtained. The analysis of graph theory features showed a decreased network infrastructure (degree and binary global efficiency) associated with IUGR condition and a set of generalized fractional anisotropy (GFA) weighted measures associated with abnormal neurobehavior. Interestingly, when assessing the brain network organization independently of network infrastructure by means of normalized networks, IUGR showed increased global and local efficiencies. We hypothesize that this effect could reflect a compensatory response to reduced infrastructure in IUGR. These results present new evidence on the long-term persistence of the brain reorganization produced by IUGR that could underlie behavioral and developmental alterations previously described. The described changes in network organization have the potential to be used as biomarkers to monitor brain changes produced by experimental therapies in IUGR animal model. PMID:24943271

  12. A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain.

    PubMed

    Konstas, Angelos-Aristeidis; Neimark, Matthew A; Laine, Andrew F; Pile-Spellman, John

    2007-04-01

    A three-dimensional mathematical model was developed to examine the transient and steady-state temperature distribution in the human brain during selective brain cooling (SBC) by unilateral intracarotid freezing-cold saline infusion. To determine the combined effect of hemodilution and hypothermia from the cold saline infusion, data from studies investigating the effect of these two parameters on cerebral blood flow (CBF) were pooled, and an analytic expression describing the combined effect of the two factors was derived. The Pennes bioheat equation used the thermal properties of the different cranial layers and the effect of cold saline infusion on CBF to propagate the evolution of brain temperature. A healthy brain and a brain with stroke (ischemic core and penumbra) were modeled. CBF and metabolic rate data were reduced to simulate the core and penumbra. Simulations using different saline flow rates were performed. The results suggested that a flow rate of 30 ml/min is sufficient to induce moderate hypothermia within 10 min in the ipsilateral hemisphere. The brain with stroke cooled to lower temperatures than the healthy brain, mainly because the stroke limited the total intracarotid blood flow. Gray matter cooled twice as fast as white matter. The continuously falling hematocrit was the main time-limiting factor, restricting the SBC to a maximum of 3 h. The study demonstrated that SBC by intracarotid saline infusion is feasible in humans and may be the fastest method of hypothermia induction. PMID:17170208

  13. Modeling epileptic brain states using EEG spectral analysis and topographic mapping.

    PubMed

    Direito, Bruno; Teixeira, César; Ribeiro, Bernardete; Castelo-Branco, Miguel; Sales, Francisco; Dourado, António

    2012-09-30

    Changes in the spatio-temporal behavior of the brain electrical activity are believed to be associated to epileptic brain states. We propose a novel methodology to identify the different states of the epileptic brain, based on the topographic mapping of the time varying relative power of delta, theta, alpha, beta and gamma frequency sub-bands, estimated from EEG. Using normalized-cuts segmentation algorithm, points of interest are identified in the topographic mappings and their trajectories over time are used for finding out relations with epileptogenic propagations in the brain. These trajectories are used to train a Hidden Markov Model (HMM), which models the different epileptic brain states and the transition among them. Applied to 10 patients suffering from focal seizures, with a total of 30 seizures over 497.3h of data, the methodology shows good results (an average point-by-point accuracy of 89.31%) for the identification of the four brain states--interictal, preictal, ictal and postictal. The results suggest that the spatio-temporal dynamics captured by the proposed methodology are related to the epileptic brain states and transitions involved in focal seizures. PMID:22850556

  14. Collagen-based brain microvasculature model in vitro using three-dimensional printed template.

    PubMed

    Kim, Jeong Ah; Kim, Hong Nam; Im, Sun-Kyoung; Chung, Seok; Kang, Ji Yoon; Choi, Nakwon

    2015-03-01

    We present an engineered three-dimensional (3D) in vitro brain microvasculature system embedded within the bulk of a collagen matrix. To create a hydrogel template for the functional brain microvascular structure, we fabricated an array of microchannels made of collagen I using microneedles and a 3D printed frame. By culturing mouse brain endothelial cells (bEnd.3) on the luminal surface of cylindrical collagen microchannels, we reconstructed an array of brain microvasculature in vitro with circular cross-sections. We characterized the barrier function of our brain microvasculature by measuring transendothelial permeability of 40?kDa fluorescein isothiocyanate-dextran (Stoke's radius of ?4.5?nm), based on an analytical model. The transendothelial permeability decreased significantly over 3 weeks of culture. We also present the disruption of the barrier function with a hyperosmotic mannitol as well as a subsequent recovery over 4 days. Our brain microvasculature model in vitro, consisting of system-in-hydrogel combined with the widely emerging 3D printing technique, can serve as a useful tool not only for fundamental studies associated with blood-brain barrier in physiological and pathological settings but also for pharmaceutical applications. PMID:25945141

  15. Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model.

    PubMed

    Andersson, Olga; Badisco, Liesbeth; Hansen, Ane Håkansson; Hansen, Steen Honoré; Hellman, Karin; Nielsen, Peter Aadal; Olsen, Line Rørbæk; Verdonck, Rik; Abbott, N Joan; Vanden Broeck, Jozef; Andersson, Gunnar

    2014-08-01

    In earlier studies insects were proposed as suitable models for vertebrate blood-brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain barrier of the desert locust (Schistocerca gregaria). In an in vivo study on the locust, we found an increased uptake of the two well-known Pgp substrates, rhodamine 123 and loperamide after co-administration with the Pgp inhibitors cyclosporine A or verapamil. Furthermore, ex vivo studies on isolated locust brains demonstrated differences in permeation of high and low permeability compounds. The vertebrate Pgp inhibitor verapamil did not affect the uptake of passively diffusing compounds but significantly increased the brain uptake of Pgp substrates in the ex vivo model. In addition, studies at 2°C and 30°C showed differences in brain uptake between Pgp-effluxed and passively diffusing compounds. The transcriptome data show a high degree of sequence identity of the locust Pgp transporter protein sequences to the human Pgp sequence (37%), as well as the presence of conserved domains. As in vertebrates, the locust brain-barrier function is morphologically confined to one specific cell layer and by using a whole-brain ex vivo drug exposure technique our locust model may retain the major cues that maintain and modulate the physiological function of the brain barrier. We show that the locust model has the potential to act as a robust and convenient model for assessing BBB permeability in early drug discovery. PMID:25505597

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

    E-print Network

    Alfinito, E

    2000-01-01

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

  17. Preliminary Development and Validation of an Atlas-Based Finite Element Brain Model.

    PubMed

    Miller, Logan E; Urban, Jillian E; Lillie, Elizabeth M; Stitzel, Joel D

    2015-01-01

    Traumatic brain injury (TBI) is a leading cause of disability and injury-related death, accounting for nearly one third of all injury-related deaths. To prevent and understand these types of injuries, finite element models can be employed. In this study, an anatomically accurate finite element model was developed from the International Consortium for Brain Mapping (ICBM) using a voxel-based mesh generation approach. The aim of this study was to compare relative brain displacement of the atlas-based brain model (ABM) to cadaveric data. In these experiments, neutral density targets (NDTs) were implanted in the brain and their relative motion with respect to the skull was recorded. The same boundary conditions were applied to ABM and the relative displacements of the nodes nearest to the physical location of each NDT were computed. Initial simulation and validation show good agreement with experimental data. The data obtained in this study and further development of this model will help us understand the biomechanics of head injury as well as provide a tool to predict and prevent brain injury. PMID:25996725

  18. Systemic investigation of a brain-centered model of the human energy metabolism.

    PubMed

    Göbel, Britta; Langemann, Dirk

    2011-03-01

    The regulation of the human energy metabolism is crucial to ensure the functionality of the entire organism. Deregulations may lead to severe pathologies such as diabetes mellitus and obesity. The decisive role of the brain as active controller and heavy consumer in the complex whole-body energy metabolism is the object of recent research. Latest studies suggest the priority of the brain energy supply in the competition between brain and body periphery for the available energy resources. In this paper, a systemic investigation of the human energy metabolism is presented which consists of a compartment model including periphery, blood, and brain as well as signaling paths via insulin, appetite, and ingestion. The presented dynamical system particularly contains the competition for energy between brain and body periphery. Characteristically, the hormone insulin is regarded as central feedback signal of the brain. The model realistically reproduces the qualitative behavior of the energy metabolism. Short-time observations demonstrate the physiological periodic food intake generating the typical oscillating blood glucose variations. Integration over the daily cycle yields a long-term model which shows a stable behavior in accordance with the homeostatic regulation of the energy metabolism on a long-time scale. Two types of abstract constitutive equations describing the interaction between compartments and signals are taken into consideration. These are nonlinear and linear representatives from the class of feasible relations. The robustness of the model against the choice of the representative relation is linked to evolutionary stability of existing organisms. PMID:20734159

  19. Brain Korea 21 Phase II: A New Evaluation Model. Monograph

    ERIC Educational Resources Information Center

    Seong, Somi; Popper, Steven W.; Goldman, Charles A.; Evans, David K.

    2008-01-01

    In the late 1990s, the Korea Ministry of Education and Human Resources, in response to concern over the relatively low standing of the nation's universities and researchers, launched the Brain Korea 21 program BK21). BK21 seeks to make Korean research universities globally competitive and to produce more high-quality researchers in Korea. It…

  20. Representation of internal models of action in the autistic brain

    E-print Network

    Shadmehr, Reza

    the reliance on proprioception, the greater the child's impairments in social function and imitation. Theory as children learned to control a novel tool and found that the autistic brain built a stronger than normal.7 years) and 13 typically developing children (age, 10.4 ± 1.8 years) to play a game in which they held

  1. Can Cognitive Models Explain Brain Activation During Word and Pseudoword Reading? A Meta-Analysis of 36 Neuroimaging Studies

    E-print Network

    Royal Holloway, University of London

    Can Cognitive Models Explain Brain Activation During Word and Pseudoword Reading? A Meta-Analysis of 36 Neuroimaging Studies J. S. H. Taylor Medical Research Council Cognition and Brain Sciences Unit of London Matthew H. Davis Medical Research Council Cognition and Brain Sciences Unit, Cambridge, England

  2. Bottom up modeling of the connectome: Linking structure and function in the resting brain and their changes in aging

    E-print Network

    Deco, Gustavo

    aspects and understand how dynamics and structure interact to form functional brain net- works in task connectivity patterns, and given support to the view that the brain works at a critical point at the edgeReview Bottom up modeling of the connectome: Linking structure and function in the resting brain

  3. Phosphodiesterase type 5 inhibitor Tadalafil increases Rituximab treatment efficacy in a mouse brain lymphoma model.

    PubMed

    Wang, Rong; Chen, Wenli; Zhang, Qiang; Liu, Yong; Qiao, Xiaoyun; Meng, Kui; Mao, Ying

    2015-03-01

    The treatment efficacy of Rituximab on lymphoma as an immunotherapeutic approach is confirmed, but this treatment has limited penetration through the brain micro vessels. Such limitation significantly attenuates the efficacy of systemic administration of this antibody on brain lymphomas. We aimed to confirm that Tadalafil, a long-acting phosphodiesterase type 5 inhibitor, could increase microvascular permeability and Rituximab treatment efficacy in brain lymphomas. We established a mouse brain lymphoma model by planting human-derived lymphoma cell line Raji into brain parenchyma of mice using stereotaxic techniques. After 16 days, 7.0 T magnetic resonance imaging was performed to confirm the presence of the mass. The mice were observed under near-infrared fluorescence after intravenous injection of fluorescence-labeled Rituximab. Evans Blue was used as probe to detect the microvascular permeability of brain lymphomas after Tadalafil administration. Starting from 4 days after implantation, the mice were administered different treatments. Survival analysis of brain lymphoma-loaded mice was performed. Evans Blue detection showed that Tadalafil administration could increase brain vascular permeability in the tumor-bearing group compared with control mice. Rituximab treatment prolonged the survival time of mice compared with the untreated control group (mean 25.75 vs. 20.8 days, p < 0.05). Tadalafil with Rituximab treatment resulted in the longest survival time (29 days, p < 0.05). Rituximab may be a promising therapeutic agent for the treatment of brain lymphoma. Tadalafil can enhance Rituximab treatment efficacy by improving the microvascular permeability in mice brain lymphoma. PMID:25524816

  4. Multivariate Nonlinear Mixed Model to Analyze Longitudinal Image Data: MRI Study of Early Brain Development

    E-print Network

    Utah, University of

    Multivariate Nonlinear Mixed Model to Analyze Longitudinal Image Data: MRI Study of Early Brain. In this paper, we present a parametric nonlinear model to statistically study multi- variate longitudinal data to any longitudinal data with nonlinear growth patterns that can not easily be modeled by linear methods

  5. MULTIVARIATE MODELING OF LONGITUDINAL MRI IN EARLY BRAIN DEVELOPMENT WITH CONFIDENCE MEASURES

    E-print Network

    Prastawa, Marcel

    MULTIVARIATE MODELING OF LONGITUDINAL MRI IN EARLY BRAIN DEVELOPMENT WITH CONFIDENCE MEASURES Neda and DTI (Dif- fusion Tensor Imaging) using multivariate nonlinear mixed effect modeling of temporal of longitudinal data yields a better average trajec- tory as the population model is based on individual temporal

  6. The Brain-Targeted Teaching Model for 21st-Century Schools

    ERIC Educational Resources Information Center

    Hardiman, Mariale

    2012-01-01

    "The Brain-Targeted Teaching Model for 21st-Century Schools" serves as a bridge between research and practice by providing a cohesive, proven, and usable model of effective instruction. Compatible with other professional development programs, this model shows how to apply relevant research from educational and cognitive neuroscience to classroom…

  7. Audiovestibular loss in anterior inferior cerebellar artery territory infarction: a window to early detection?

    PubMed

    Lee, Hyung

    2012-02-15

    Acute audiovestibular loss is a common neurotological condition that is characterized by sudden onset of severe prolonged (lasting days) vertigo and hearing loss and is diagnosed by the presence of canal paresis to caloric stimulation and sensorineural hearing loss on pure tone audiogram. Before 2000, papers on anterior inferior cerebellar artery (AICA) territory infarction focused mostly on associated brainstem and cerebellar findings, without a detailed description of neurotological findings. Since 2000, several reports have demonstrated that acute audiovestibular loss is an important sign for the diagnosis of AICA territory infarction. To date, at least eight subgroups of AICA infarction have been identified according to the pattern of neurotological presentations, among which the most common pattern of audiovestibular dysfunction is the combined loss of auditory and vestibular functions. Because audiovestibular loss may occur in isolation before ponto-cerebellar infarction involving AICA distribution, audiovestibular loss may serve as a window to prevent the progression of acute audiovestibular loss into more widespread areas of infarction in posterior circulation (mainly in the AICA territory). Clinician should keep in mind that acute audiovestibular loss may herald impending AICA territory infarction, especially when patients had basilar artery occlusive disease presumably close to the origin of the AICA on brain MRA, even if other central signs are absent and MRI does not demonstrate acute infarction. PMID:21996273

  8. Glutathione Suppresses Cerebral Infarct Volume and Cell Death after Ischemic Injury: Involvement of FOXO3 Inactivation and Bcl2 Expression

    PubMed Central

    Park, Joohyun; Oh, Yumi

    2015-01-01

    Ischemic stroke interrupts the flow of blood to the brain and subsequently results in cerebral infarction and neuronal cell death, leading to severe pathophysiology. Glutathione (GSH) is an antioxidant with cellular protective functions, including reactive oxygen species (ROS) scavenging in the brain. In addition, GSH is involved in various cellular survival pathways in response to oxidative stress. In the present study, we examined whether GSH reduces cerebral infarct size after middle cerebral artery occlusion in vivo and the signaling mechanisms involved in the promotion of cell survival after GSH treatment under ischemia/reperfusion conditions in vitro. To determine whether GSH reduces the extent of cerebral infarction, cell death after ischemia, and reperfusion injury, we measured infarct size in ischemic brain tissue and the expression of claudin-5 associated with brain infarct formation. We also examined activation of the PI3K/Akt pathway, inactivation of FOXO3, and expression of Bcl2 to assess the role of GSH in promoting cell survival in response to ischemic injury. Based on our results, we suggest that GSH might improve the pathogenesis of ischemic stroke by attenuating cerebral infarction and cell death. PMID:25722793

  9. Pathophysiological changes after traumatic brain injury: comparison of two experimental animal models by means of MRI

    Microsoft Academic Search

    G. Schneider; P. Fries; D. Wagner-Jochem; D. Thome; H. Laurer; B. Kramann; A. Mautes; T. Hagen

    2002-01-01

    In an experimental study MRI was used to compare the pathophysiological changes of brain tissue after lateral fluid percussion\\u000a injury (FPI) versus cold injury (CI) as models of traumatic brain injury (TBI). Two groups of Sprague-Dawley rats (n = 23) were subjected to mild FPI, respectively, CI localized over the right parietal cortex. MRI was performed at different\\u000a time points

  10. The Drosophila neural lineages: a model system to study brain development and circuitry

    Microsoft Academic Search

    Shana R. Spindler; Volker Hartenstein

    2010-01-01

    In Drosophila, neurons of the central nervous system are grouped into units called lineages. Each lineage contains cells derived from a\\u000a single neuroblast. Due to its clonal nature, the Drosophila brain is a valuable model system to study neuron development and circuit formation. To better understand the mechanisms underlying\\u000a brain development, genetic manipulation tools can be utilized within lineages to

  11. Analysis of spatio-temporal brain imaging patterns by Hidden Markov Models and serial MRI images.

    PubMed

    Wang, Ying; Resnick, Susan M; Davatzikos, Christos

    2014-09-01

    Brain changes due to development and maturation, normal aging, or degenerative disease are continuous, gradual, and variable across individuals. To quantify the individual progression of brain changes, we propose a spatio-temporal methodology based on Hidden Markov Models (HMM), and apply it on four-dimensional structural brain magnetic resonance imaging series of older individuals. First, regional brain features are extracted in order to reduce image dimensionality. This process is guided by the objective of the study or the specific imaging patterns whose progression is of interest, for example, the evaluation of Alzheimer-like patterns of brain change in normal individuals. These regional features are used in conjunction with HMMs, which aim to measure the dynamic association between brain structure changes and progressive stages of disease over time. A bagging framework is used to obtain models with good generalization capability, since in practice the number of serial scans is limited. An application of the proposed methodology was to detect individuals with the risk of developing MCI, and therefore it was tested on modeling the progression of brain atrophy patterns in older adults. With HMM models, the state-transition paths corresponding to longitudinal brain changes were constructed from two completely independent datasets, the Alzheimer Disease Neuroimaging Initiative and the Baltimore Longitudinal Study of Aging. The statistical analysis of HMM-state paths among the normal, progressive MCI, and MCI groups indicates that, HMM-state index 1 is likely to be a predictor of the conversion from cognitively normal to MCI, potentially many years before clinical symptoms become measurable. PMID:24706564

  12. MALDI Mass Spectrometric Imaging of Lipids in Rat Brain Injury Models

    Microsoft Academic Search

    Joseph A. Hankin; Santiago E. Farias; Robert M. Barkley; Kim Heidenreich; Lauren C. Frey; Kei Hamazaki; Hee-Yong Kim; Robert C. Murphy

    2011-01-01

    Matrix-assisted laser desorption ionization\\/ionization imaging mass spectrometry (MALDI IMS) with a time-of-flight analyzer\\u000a was used to characterize the distribution of lipid molecular species in the brain of rats in two injury models. Ischemia\\/reperfusion\\u000a injury of the rat brain after bilateral occlusion of the carotid artery altered appearance of the phospholipids present in\\u000a the hippocampal region, specifically the CA1 region. These

  13. Quantum-like model of processing of information in the brain based on classical electromagnetic field

    E-print Network

    Khrennikov, Andrei

    2010-01-01

    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 var...

  14. Segmentation of Brain MR Images through a Hidden Markov Random Field Model and the Expectation Maximization Algorithm

    Microsoft Academic Search

    Yongyue Zhang; Michael Brady; Stephen M. Smith

    2001-01-01

    The finite mixture (FM) model is the most commonly used model for statistical segmentation of brain magnetic reso- nance (MR) images because of its simple mathematical form and the piecewise constant nature of ideal brain MR images. However, being a histogram-based model, the FM has an intrinsic limita- tion—no spatial information is taken into account. This causes the FM model

  15. A Hydrogel Construct and Fibrin-based Glue Approach to Deliver Therapeutics in a Murine Myocardial Infarction Model.

    PubMed

    Melhem, Molly; Jensen, Tor; Reinkensmeyer, Larissa; Knapp, Luke; Flewellyn, Jordan; Schook, Lawrence

    2015-01-01

    The murine MI model is widely recognized in the field of cardiovascular disease, and has consistently been used as a first step to test the efficacy of treatments in vivo(1). The traditional, established protocol has been further fine-tuned to minimize the damage to the animal. Notably, the pectoral muscle layers are teased away rather than simply cut, and the thoracotomy is approached intercostally as opposed to breaking the ribs in a sternotomy, preserving the integrity of the ribcage. With these changes, the overall stress on the animal is decreased. Stem cell therapies aimed to alleviate the damage caused by MIs have shown promise over the years for their pro-angiogenic and anti-apoptotic benefits. Current approaches of delivering cells to the heart surface typically involve the injection of the cells either near the damaged site, within a coronary artery, or into the peripheral blood stream(2-4). While the cells have proven to home to the damaged myocardium, functionality is limited by their poor engraftment at the site of injury, resulting in diffusion into the blood stream(5). This manuscript highlights a procedure that overcomes this obstacle with the use of a cell-encapsulated hydrogel patch. The patch is fabricated prior to the surgical procedure and is placed on the injured myocardium immediately following the occlusion of the left coronary artery. To adhere the patch in place, biocompatible external fibrin glue is placed directly on top of the patch, allowing for it to dry to both the patch and the heart surface. This approach provides a novel adhesion method for the application of a delicate cell-encapsulating therapeutic construct. PMID:26132813

  16. Interferon-Beta Blocks Infiltration of Inflammatory Cells and Reduces Infarct Volume After Ischemic Stroke in the Rat

    Microsoft Academic Search

    Wouter B. Veldhuis; Joris W. Derksen; Sarah Floris; Peter H. van der Meide; Helga E. de Vries; Janneke Schepers; Ine M. P. Vos; Christien D. Dijkstra; L. Jaap Kappelle; Klaas Nicolay; Peter R Bär

    2003-01-01

    The inflammatory response that exacerbates cerebral injury after ischemia is an attractive therapeutic target: it progresses over days and strongly contributes to worsening of the neurologic outcome. The authors show that, after transient ischemic injury to the rat brain, systemic application of interferon-beta (IFN-?), a cytokine with antiinflammatory properties, attenuated the development of brain infarction. Serial magnetic resonance imaging (MRI)

  17. Positron emission tomography imaging of CD105 expression in a rat myocardial infarction model with 64Cu-NOTA-TRC105

    PubMed Central

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

    2014-01-01

    Biological changes following myocardial infarction (MI) lead to increased secretion of angiogenic factors that subsequently stimulate the formation of new blood vessels as a compensatory mechanism to reverse ischemia. The goal of this study was to assess the role of CD105 expression during MI-induced angiogenesis by positron emission tomography (PET) imaging using 64Cu-labeled TRC105, an anti-CD105 monoclonal antibody. MI was induced by ligation of the left anterior descending (LAD) artery in female rats. Echocardiography and 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET scans were performed on post-operative day 3 to confirm the presence of MI in the infarct group and intact heart in the sham group, respectively. Ischemia-induced angiogenesis was non-invasively monitored with 64Cu-NOTA-TRC105 (an extensively validated PET tracer in our previous studies) PET on post-operative days 3, 10, and 17. Tracer uptake in the infarct zone was highest on day 3 following MI, which was significantly higher than that in the sham group (1.41 ± 0.45 %ID/g vs 0.57 ± 0.07 %ID/g; n=3, p<0.05). Subsequently, tracer uptake in the infarct zone decreased over time to the background level on day 17, whereas tracer uptake in the heart of sham rats remained low at all time points examined. Histopathology documented increased CD105 expression following MI, which corroborated in vivo findings. This study indicated that PET imaging of CD105 can be a useful tool for MI-related research, which can potentially improve MI patient management in the future upon clinical translation of the optimized PET tracers. PMID:24380040

  18. Activation of peripheral ? opioid receptors eliminates cardiac electrical instability in a rat model of post-infarction cardiosclerosis via mitochondrial ATP-dependent K + channels

    Microsoft Academic Search

    L. N. Maslov; Yu. B. Lishmanov; N. V. Solenkova; G. J. Gross; G. B. Stefano; S. W. Tam

    2003-01-01

    The effects of the selective delta-1 (?1) opioid receptor agonist, DPDPE, and the selective ?2 opioid receptor agonist, DSLET, have been studied on the ventricular fibrillation threshold (VFT) in rats with an experimental post-infarction cardiosclerosis (CS). It has been found that CS induced a significant decrease in VFT. This CS-induced decrease in VFT was significantly reversed by intravenous administration of

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

    E-print Network

    Kamp, Tim

    ) cells following myocardial infarction (MI) in animal models is beneficial; however, the mechanismBrief Communication Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types Dinender K. Singla a,b, , Timothy A. Hacker a , Lining Ma a,b , Pamela S

  20. Core modular blood and brain biomarkers in social defeat mouse model for post traumatic stress disorder

    PubMed Central

    2013-01-01

    Background Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects a substantial portion of combat veterans and poses serious consequences to long-term health. Consequently, the identification of diagnostic and prognostic blood biomarkers for PTSD is of great interest. Previously, we assessed genome-wide gene expression of seven brain regions and whole blood in a social defeat mouse model subjected to various stress conditions. Results To extract biological insights from these data, we have applied a new computational framework for identifying gene modules that are activated in common across blood and various brain regions. Our results, in the form of modular gene networks that highlight spatial and temporal biological functions, provide a systems-level molecular description of response to social stress. Specifically, the common modules discovered between the brain and blood emphasizes molecular transporters in the blood-brain barrier, and the associated genes have significant overlaps with known blood signatures for PTSD, major depression, and bipolar disease. Similarly, the common modules specific to the brain highlight the components of the social defeat stress response (e.g., fear conditioning pathways) in each brain sub-region. Conclusions Many of the brain-specific genes discovered are consistent with previous independent studies of PTSD or other mental illnesses. The results from this study further our understanding of the mechanism of stress response and contribute to a growing list of diagnostic biomarkers for PTSD. PMID:23962043

  1. Neuroimaging diagnosis for cerebral infarction

    PubMed Central

    Du, Yan; Yang, Xiaoxia; Song, Hong; Chen, Bo; Li, Lin; Pan, Yue; Wu, Qiong; Li, Jia

    2012-01-01

    Objective: To identify global research trends in neuroimaging diagnosis for cerebral infarction using a bibliometric analysis of the Web of Science. Data Retrieval: We performed a bibliometric analysis of data retrieval for neuroimaging diagnosis for cerebral infarction containing the key words “CT, magnetic resonance imaging, MRI, transcranial Doppler, transvaginal color Doppler, digital subtraction angiography, and cerebral infarction” using the Web of Science. Selection Criteria: Inclusion criteria were: (a) peer-reviewed articles on neuroimaging diagnosis for cerebral infarction which were published and indexed in the Web of Science; (b) original research articles and reviews; and (c) publication between 2004–2011. Exclusion criteria were: (a) articles that required manual searching or telephone access; and (b) corrected papers or book chapters. Main Outcome Measures: (1) Annual publication output; (2) distribution according to country; (3) distribution according to institution; (4) top cited publications; (5) distribution according to journals; and (6) comparison of study results on neuroimaging diagnosis for cerebral infarction. Results: Imaging has become the predominant method used in diagnosing cerebral infarction. The most frequently used clinical imaging methods were digital subtraction angiography, CT, MRI, and transcranial color Doppler examination. Digital subtraction angiography is used as the gold standard. However, it is a costly and time-consuming invasive diagnosis that requires some radiation exposure, and is poorly accepted by patients. As such, it is mostly adopted in interventional therapy in the clinic. CT is now accepted as a rapid, simple, and reliable non-invasive method for use in diagnosis of cerebrovascular disease and preoperative appraisal. Ultrasonic Doppler can be used to reflect the hardness of the vascular wall and the nature of the plaque more clearly than CT and MRI. Conclusion: At present, there is no unified standard of classification of cerebral infarction imaging. Detection of clinical super-acute cerebral infarction remains controversial due to its changes on imaging, lack of specificity, and its similarity to a space-occupying lesion. Neuroimaging diagnosis for cerebral infarction remains a highly active area of research and development. PMID:25538765

  2. Implications of sodium hydrogen exchangers in various brain diseases.

    PubMed

    Verma, Vivek; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

    2015-09-01

    Na+/H+ exchangers (NHEs) are the transporter proteins that play an important role in intracellular pH (pHi) regulation, cell differentiation and cell volume and that mediate transepithelial Na+ and HCO3- absorption on the basis of chemical gradients across the plasma membrane. Its activation causes an increase in intracellular Na+, which further leads to Ca+ overload and cell death. The pharmacological inhibition of these transporter proteins prevents myocardial infarction and other heart diseases like congestive heart failure in experimental animal models as well as in clinical situations. The more recent studies have implicated the role of these exchangers in the pathophysiology of brain diseases. Out of nine NHE isoforms, NHE-1 is the major isoform present in the brain and regulates the trans-cellular ion transport through blood-brain barrier membrane, and alteration in their function leads to severe brain abnormalities. NHEs were shown to be involved in pathophysiologies of many brain diseases like epilepsy, Alzheimer's disease, neuropathic pain and ischemia/reperfusion-induced cerebral injury. Na+/H+-exchanger inhibitors (e.g., amiloride and cariporide) produce protective effects on ischemia/reperfusion-induced brain injury (e.g., stroke), exhibit good antiepileptic potential and attenuate neuropathic pain in various animal models. The present review focuses on the pathophysiological role of these ion exchangers in different brain diseases with possible mechanisms. PMID:26020555

  3. Mathematical modeling for evolution of heterogeneous modules in the brain.

    PubMed

    Yamaguti, Yutaka; Tsuda, Ichiro

    2015-02-01

    Modular architecture has been found in most cortical areas of mammalian brains, but little is known about its evolutionary origin. It has been proposed by several researchers that maximizing information transmission among subsystems can be used as a principle for understanding the development of complex brain networks. In this paper, we study how heterogeneous modules develop in coupled-map networks via a genetic algorithm, where selection is based on maximizing bidirectional information transmission. Two functionally differentiated modules evolved from two homogeneous systems with random couplings, which are associated with symmetry breaking of intrasystem and intersystem couplings. By exploring the parameter space of the network around the optimal parameter values, it was found that the optimum network exists near transition points, at which the incoherent state loses its stability and an extremely slow oscillatory motion emerges. PMID:25124068

  4. Cell Therapy for Models of Pain and Traumatic Brain Injury

    Microsoft Academic Search

    Mary Eaton; Jacqueline Sagen

    This chapter reviews the cell transplantation strategies that have been explored as potential options in the treatment of\\u000a pain and traumatic brain injury (TBI). As the goals of these two therapeutic targets are widely disparate, approaches have\\u000a evolved along distinctive paths. Thus, although the provision of a local cellular source of pharmacologic analgesic molecules\\u000a may be most appropriate in the

  5. Microwave spectroscopy of myocardial ischemia and infarction. 2. Biophysical reconstruction.

    PubMed

    Semenov, S Y; Svenson, R H; Bulyshev, A E; Souvorov, A E; Nazarov, A G; Sizov, Y E; Posukh, V G; Pavlovsky, A; Tatsis, G P

    2000-01-01

    The proposed dielectrical relaxation model of the myocardium in the microwave spectrum has been verified both on test solutions and on normal canine myocardium. Furthermore, the model was utilized to reconstruct the changes in tissue properties (including myocardial bulk resistance and water content) following myocardial acute ischemia and chronic infarction. It was shown that the reconstructed myocardial resistance and water content correlate dynamically with the process of the development of acute myocardial ischemic injury. In chronic cases the reconstructed resistance and water content of infarcted myocardium are significantly different from that of normal myocardium: the resistance is lower and water content is higher than in normal myocardium. PMID:10645788

  6. Protracted brain development in a rodent model of extreme longevity.

    PubMed

    Penz, Orsolya K; Fuzik, Janos; Kurek, Aleksandra B; Romanov, Roman; Larson, John; Park, Thomas J; Harkany, Tibor; Keimpema, Erik

    2015-01-01

    Extreme longevity requires the continuous and large-scale adaptation of organ systems to delay senescence. Naked mole rats are the longest-living rodents, whose nervous system likely undergoes life-long adaptive reorganization. Nevertheless, neither the cellular organization of their cerebral cortex nor indices of structural neuronal plasticity along extreme time-scales have been established. We find that adult neurogenesis and neuronal migration are not unusual in naked mole rat brains. Instead, we show the prolonged expression of structural plasticity markers, many recognized as being developmentally controlled, and multi-year-long postnatal neuromorphogenesis and spatial synapse refinement in hippocampal and olfactory structures of the naked mole rat brain. Neurophysiological studies on identified hippocampal neurons demonstrated that morphological differentiation is disconnected from the control of excitability in all neuronal contingents regardless of their ability to self-renew. Overall, we conclude that naked mole rats show an extremely protracted period of brain maturation that may permit plasticity and resilience to neurodegenerative processes over their decades-long life span. This conclusion is consistent with the hypothesis that naked mole rats are neotenous, with retention of juvenile characteristics to permit survival in a hypoxic environment, with extreme longevity a consequence of greatly retarded development. PMID:26118676

  7. Protracted brain development in a rodent model of extreme longevity

    PubMed Central

    Penz, Orsolya K.; Fuzik, Janos; Kurek, Aleksandra B.; Romanov, Roman; Larson, John; Park, Thomas J.; Harkany, Tibor; Keimpema, Erik

    2015-01-01

    Extreme longevity requires the continuous and large-scale adaptation of organ systems to delay senescence. Naked mole rats are the longest-living rodents, whose nervous system likely undergoes life-long adaptive reorganization. Nevertheless, neither the cellular organization of their cerebral cortex nor indices of structural neuronal plasticity along extreme time-scales have been established. We find that adult neurogenesis and neuronal migration are not unusual in naked mole rat brains. Instead, we show the prolonged expression of structural plasticity markers, many recognized as being developmentally controlled, and multi-year-long postnatal neuromorphogenesis and spatial synapse refinement in hippocampal and olfactory structures of the naked mole rat brain. Neurophysiological studies on identified hippocampal neurons demonstrated that morphological differentiation is disconnected from the control of excitability in all neuronal contingents regardless of their ability to self-renew. Overall, we conclude that naked mole rats show an extremely protracted period of brain maturation that may permit plasticity and resilience to neurodegenerative processes over their decades-long life span. This conclusion is consistent with the hypothesis that naked mole rats are neotenous, with retention of juvenile characteristics to permit survival in a hypoxic environment, with extreme longevity a consequence of greatly retarded development. PMID:26118676

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

    PubMed Central

    Fyshe, Alona; Talukdar, Partha P; Murphy, Brian; Mitchell, Tom M

    2015-01-01

    Vector space models (VSMs) represent word meanings as points in a high dimensional space. VSMs are typically created using a large text corpora, and so represent word semantics as observed in text. We present a new algorithm (JNNSE) that can incorporate a measure of semantics not previously used to create VSMs: brain activation data recorded while people read words. The resulting model takes advantage of the complementary strengths and weaknesses of corpus and brain activation data to give a more complete representation of semantics. Evaluations show that the model 1) matches a behavioral measure of semantics more closely, 2) can be used to predict corpus data for unseen words and 3) has predictive power that generalizes across brain imaging technologies and across subjects. We believe that the model is thus a more faithful representation of mental vocabularies.

  9. Neuroprotective activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in rodent models of brain ischemia.

    PubMed

    Martins, A H; Hu, J; Xu, Z; Mu, C; Alvarez, P; Ford, B D; El Sayed, K; Eterovic, V A; Ferchmin, P A; Hao, J

    2015-04-16

    (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is a precursor to key flavor ingredients in leaves of Nicotiana species. The present study shows 4R decreased brain damage in rodent ischemic stroke models. The 4R-pretreated mice had lower infarct volumes (26.2±9.7 mm3) than those in control groups (untreated: 63.4±4.2 mm3, DMSO: 60.2±14.2 mm3). The 4R-posttreated rats also had less infarct volumes (120±65 mm3) than those in the rats of the DMSO group (291±95 mm3). The results from in vitro experiments indicate that 4R decreased neuro2a cell (neuroblastoma cells) apoptosis induced by oxygen-glucose deprivation (OGD), and improved the population spikes' (PSs) recovery in rat acute hippocampal slices under OGD; a phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, abolished the effect of 4R on PSs recovery. Furthermore, 4R also inhibited monocyte adhesion to murine brain-derived endothelial (bEND5) cells and upregulation of intercellular adhesion molecule-1(ICAM-1) induced by OGD/reoxygenation (OGD/R), and restored the p-Akt level to pre-OGD/R values in bEND5 cells. In conclusion, the present study indicates that 4R has a protective effect in rodent ischemic stroke models. Inhibition of ICAM-1 expression and restoration of Akt phosphorylation are the possible mechanisms involved in cellular protection by 4R. PMID:25677097

  10. Quantum-like model of processing of information in the brain based on classical electromagnetic field

    E-print Network

    Andrei Khrennikov

    2010-11-28

    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.

  11. Ontogenetic ritualization of primate gesture as a case study in dyadic brain modeling.

    PubMed

    Gasser, Brad; Cartmill, Erica A; Arbib, Michael A

    2014-01-01

    This paper introduces dyadic brain modeling - the simultaneous, computational modeling of the brains of two interacting agents - to explore ways in which our understanding of macaque brain circuitry can ground new models of brain mechanisms involved in ape interaction. Specifically, we assess a range of data on gestural communication of great apes as the basis for developing an account of the interactions of two primates engaged in ontogenetic ritualization, a proposed learning mechanism through which a functional action may become a communicative gesture over repeated interactions between two individuals (the 'dyad'). The integration of behavioral, neural, and computational data in dyadic (or, more generally, social) brain modeling has broad application to comparative and evolutionary questions, particularly for the evolutionary origins of cognition and language in the human lineage. We relate this work to the neuroinformatics challenges of integrating and sharing data to support collaboration between primatologists, neuroscientists and modelers that will help speed the emergence of what may be called comparative neuro-primatology. PMID:23608958

  12. 2-Vessel Occlusion/Hypotension: A Rat Model of Global Brain Ischemia

    PubMed Central

    Sanderson, Thomas H.; Wider, Joseph M.

    2013-01-01

    Cardiac arrest followed by resuscitation often results in dramatic brain damage caused by ischemia and subsequent reperfusion of the brain. Global brain ischemia produces damage to specific brain regions shown to be highly sensitive to ischemia 1. Hippocampal neurons have higher sensitivity to ischemic insults compared to other cell populations, and specifically, the CA1 region of the hippocampus is particularly vulnerable to ischemia/reperfusion 2. The design of therapeutic interventions, or study of mechanisms involved in cerebral damage, requires a model that produces damage similar to the clinical condition and in a reproducible manner. Bilateral carotid vessel occlusion with hypotension (2VOH) is a model that produces reversible forebrain ischemia, emulating the cerebral events that can occur during cardiac arrest and resuscitation. We describe a model modified from Smith et al. (1984) 2, as first presented in its current form in Sanderson, et al. (2008) 3, which produces reproducible injury to selectively vulnerable brain regions 3-6. The reliability of this model is dictated by precise control of systemic blood pressure during applied hypotension, the duration of ischemia, close temperature control, a specific anesthesia regimen, and diligent post-operative care. An 8-minute ischemic insult produces cell death of CA1 hippocampal neurons that progresses over the course of 6 to 24 hr of reperfusion, while less vulnerable brain regions are spared. This progressive cell death is easily quantified after 7-14 days of reperfusion, as a near complete loss of CA1 neurons is evident at this time. In addition to this brain injury model, we present a method for CA1 damage quantification using a simple, yet thorough, methodology. Importantly, quantification can be accomplished using a simple camera-mounted microscope, and a free ImageJ (NIH) software plugin, obviating the need for cost-prohibitive stereology software programs and a motorized microscopic stage for damage assessment. PMID:23851591

  13. Microwave Spectroscopy of Myocardial Ischemia and Infarction. 2. Biophysical Reconstruction

    Microsoft Academic Search

    Serguei Y. Semenov; Robert H. Svenson; Alexander E. Bulyshev; Alexander E. Souvorov; Alexei G. Nazarov; Yuri E. Sizov; Vitaly G. Posukh; Andrey Pavlovsky; George P. Tatsis

    2000-01-01

    The proposed dielectrical relaxation model of the myocardium in the microwave spectrum has been verified both on test solutions and on normal canine myocardium. Furthermore, the model was utilized to reconstruct the changes in tissue properties (including myocardial bulk resistance and water content) following myocardial acute ischemia and chronic infarction. It was shown that the reconstructed myocardial resistance and water

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

    PubMed Central

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

    2014-01-01

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

  15. Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients

    PubMed Central

    2008-01-01

    Objective To develop and validate practical prognostic models for death at 14 days and for death or severe disability six months after traumatic brain injury. Design Multivariable logistic regression to select variables that were independently associated with two patient outcomes. Two models designed: “basic” model (demographic and clinical variables only) and “CT” model (basic model plus results of computed tomography). The models were subsequently developed for high and low-middle income countries separately. Setting Medical Research Council (MRC) CRASH Trial. Subjects 10?008 patients with traumatic brain injury. Models externally validated in a cohort of 8509. Results The basic model included four predictors: age, Glasgow coma scale, pupil reactivity, and the presence of major extracranial injury. The CT model also included the presence of petechial haemorrhages, obliteration of the third ventricle or basal cisterns, subarachnoid bleeding, midline shift, and non-evacuated haematoma. In the derivation sample the models showed excellent discrimination (C statistic above 0.80). The models showed good calibration graphically. The Hosmer-Lemeshow test also indicated good calibration, except for the CT model in low-middle income countries. External validation for unfavourable outcome at six months in high income countries showed that basic and CT models had good discrimination (C statistic 0.77 for both models) but poorer calibration. Conclusion Simple prognostic models can be used to obtain valid predictions of relevant outcomes in patients with traumatic brain injury. PMID:18270239

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

    E-print Network

    E. Alfinito; G. Vitiello

    2000-02-03

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

  17. Dynamics of the brain: Mathematical models and non-invasive experimental studies

    NASA Astrophysics Data System (ADS)

    Toronov, V.; Myllylä, T.; Kiviniemi, V.; Tuchin, V. V.

    2013-10-01

    Dynamics is an essential aspect of the brain function. In this article we review theoretical models of neural and haemodynamic processes in the human brain and experimental non-invasive techniques developed to study brain functions and to measure dynamic characteristics, such as neurodynamics, neurovascular coupling, haemodynamic changes due to brain activity and autoregulation, and cerebral metabolic rate of oxygen. We focus on emerging theoretical biophysical models and experimental functional neuroimaging results, obtained mostly by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS). We also included our current results on the effects of blood pressure variations on cerebral haemodynamics and simultaneous measurements of fast processes in the brain by near-infrared spectroscopy and a very novel functional MRI technique called magnetic resonance encephalography. Based on a rapid progress in theoretical and experimental techniques and due to the growing computational capacities and combined use of rapidly improving and emerging neuroimaging techniques we anticipate during next decade great achievements in the overall knowledge of the human brain.

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

    NASA Astrophysics Data System (ADS)

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

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

  19. Skull-stripping magnetic resonance brain images using a model-based level set.

    PubMed

    Zhuang, Audrey H; Valentino, Daniel J; Toga, Arthur W

    2006-08-01

    The segmentation of brain tissue from nonbrain tissue in magnetic resonance (MR) images, commonly referred to as skull stripping, is an important image processing step in many neuroimage studies. A new mathematical algorithm, a model-based level set (MLS), was developed for controlling the evolution of the zero level curve that is implicitly embedded in the level set function. The evolution of the curve was controlled using two terms in the level set equation, whose values represented the forces that determined the speed of the evolving curve. The first force was derived from the mean curvature of the curve, and the second was designed to model the intensity characteristics of the cortex in MR images. The combination of these forces in a level set framework pushed or pulled the curve toward the brain surface. Quantitative evaluation of the MLS algorithm was performed by comparing the results of the MLS algorithm to those obtained using expert segmentation in 29 sets of pediatric brain MR images and 20 sets of young adult MR images. Another 48 sets of elderly adult MR images were used for qualitatively evaluating the algorithm. The MLS algorithm was also compared to two existing methods, the brain extraction tool (BET) and the brain surface extractor (BSE), using the data from the Internet brain segmentation repository (IBSR). The MLS algorithm provides robust skull-stripping results, making it a promising tool for use in large, multi-institutional, population-based neuroimaging studies. PMID:16697666

  20. STRUCTURE AND MECHANICS OF HEALING MYOCARDIAL INFARCTS

    Microsoft Academic Search

    Jeffrey W. Holmes; Thomas K. Borg; James W. Covell

    2005-01-01

    ? Abstract Therapies for myocardial,infarction have historically been developed by trial and error, rather than from an understanding of the structure and function of the healing infarct. With exciting new,bioengineering,therapies for myocardial,infarction on the horizon, we have reviewed the time course of structural and mechanical changes in the healing infarct in an attempt to identify key structural determinants,of mechanics at

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

    Microsoft Academic Search

    A. G. Zaraisky

    2004-01-01

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

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

    Microsoft Academic Search

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

    1999-01-01

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

  3. Rat Brain Tumor Models to Assess the Efficacy of Boron Neutron Capture Therapy: A Critical Evaluation

    Microsoft Academic Search

    Rolf F. Barth; Weilian Yang; Jeffrey A. Coderre

    2003-01-01

    Development of any therapeutic modality can be facilitated by the use of the appropriate animal models to assess its efficacy. This report primarily will focus on our studies using the F98 and 9L rat glioma models to evaluate the effectiveness of boron neutron capture therapy (BNCT) of brain tumors. Following intracerebral implantation the biological behavior of each tumor resembles that

  4. MULTIVARIATE MODELING OF LONGITUDINAL MRI IN EARLY BRAIN DEVELOPMENT WITH CONFIDENCE MEASURES

    E-print Network

    Gerig, Guido

    MULTIVARIATE MODELING OF LONGITUDINAL MRI IN EARLY BRAIN DEVELOPMENT WITH CONFIDENCE MEASURES Neda accurately captures development as compared to cross-sectional analysis. Growth modeling of longitudinal data in structural and diffusion MRI of healthy subjects with repeated scans. We provide a frame- work for joint

  5. A two-part mixed-effects modeling framework for analyzing whole-brain network data.

    PubMed

    Simpson, Sean L; Laurienti, Paul J

    2015-06-01

    Whole-brain network analyses remain the vanguard in neuroimaging research, coming to prominence within the last decade. Network science approaches have facilitated these analyses and allowed examining the brain as an integrated system. However, statistical methods for modeling and comparing groups of networks have lagged behind. Fusing multivariate statistical approaches with network science presents the best path to develop these methods. Toward this end, we propose a two-part mixed-effects modeling framework that allows modeling both the probability of a connection (presence/absence of an edge) and the strength of a connection if it exists. Models within this framework enable quantifying the relationship between an outcome (e.g., disease status) and connectivity patterns in the brain while reducing spurious correlations through inclusion of confounding covariates. They also enable prediction about an outcome based on connectivity structure and vice versa, simulating networks to gain a better understanding of normal ranges of topological variability, and thresholding networks leveraging group information. Thus, they provide a comprehensive approach to studying system level brain properties to further our understanding of normal and abnormal brain function. PMID:25796135

  6. Impact of brain tissue filtering on neurostimulation fields: a modeling study

    PubMed Central

    Wagner, Tim; Eden, Uri; Rushmore, Jarrett; Russo, Christopher J.; Dipietro, Laura; Fregni, Felipe; Simon, Stephen; Rotman, Stephen; Pitskel, Naomi B.; Ramos-Estebanez, Ciro; Pascual-Leone, Alvaro; Grodzinsky, Alan J.; Zahn, Markus; Valero-Cabre, Antoni

    2013-01-01

    Electrical neurostimulation techniques, such as deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), are increasingly used in the neurosciences, e.g., for studying brain function, and for neurotherapeutics, e.g., for treating depression, epilepsy, and Parkinson’s disease. The characterization of electrical properties of brain tissue has guided our fundamental understanding and application of these methods, from electrophysiologic theory to clinical dosing-metrics. Nonetheless, prior computational models have primarily relied on ex-vivo impedance measurements. We recorded the in-vivo impedances of brain tissues during neurosurgical procedures and used these results to construct MRI guided computational models of TMS and DBS neurostimulatory fields and conductance-based models of neurons exposed to stimulation. We demonstrated that tissues carry neurostimulation currents through frequency dependent resistive and capacitive properties not typically accounted for by past neurostimulation modeling work. We show that these fundamental brain tissue properties can have significant effects on the neurostimulatory-fields (capacitive and resistive current composition and spatial/temporal dynamics) and neural responses (stimulation threshold, ionic currents, and membrane dynamics). These findings highlight the importance of tissue impedance properties on neurostimulation and impact our understanding of the biological mechanisms and technological potential of neurostimulatory methods. PMID:23850466

  7. Magnesium therapy for acute myocardial infarction

    Microsoft Academic Search

    LeRoy E. Rabbani

    1995-01-01

    The use of magnesium therapy for acute myocardial infarction remains controversial despite recent clinical trials such as ISIS-4. Magnesium has numerous beneficial effects in the setting of myocardial infarction, including inhibitory effects on platelet aggregation. Clinical trials of magnesium therapy for myocardial infarction have yielded conflicting results that may be related to the difference in the timing of magnesium administration.

  8. [Myocardial infarction as complication of acute pancreatitis].

    PubMed

    Asfalou, I; Miftah, F; Kendoussi, M; Raissouni, M; Benyass, A; Moustaghfir, A; Zbir, E; Hda, A; Hamani, A

    2011-01-01

    We report a case of an acute pancreatitis complicated by myocardial infarction with normal coronary arteries on angiography. This observation presents a double interest. First, it illustrates unusual forms of coronary disease represented by the non-atherosclerotic infarction. On the other hand, it shows that the multiple visceral damage associated with acute pancreatitis can include myocardial infarction which complications aggravate prognosis. PMID:21232905

  9. [Intestinal infarction in the elderly].

    PubMed

    De Santis, L; Bruttocao, A; Ciardo, L; Militello, C; Terranova, O

    2003-01-01

    The bowel infarction is till affected by high mortality in spite of new diagnostic methods and therapy. In our experience was observed about 45 patients with bowel infarction by different etiology; fast diagnosis and therapy are necessary for a good prognosis. The arteriography, at the light of this experience, is the gold standard but it is still performed in a low number of patients. The laparoscopy, in the advanced pathologies, is able to avoid an ineffectual laparotomy and permits a better diagnosis in borderline cases. PMID:14677278

  10. Favorable left ventricular remodeling following large myocardial infarction by exercise training. Effect on ventricular morphology and gene expression.

    PubMed Central

    Orenstein, T L; Parker, T G; Butany, J W; Goodman, J M; Dawood, F; Wen, W H; Wee, L; Martino, T; McLaughlin, P R; Liu, P P

    1995-01-01

    Continued adverse remodeling of myocardium after infarction may lead to progressive ventricular dilation and heart failure. We tested the hypothesis that exercise training in a healed myocardial infarction-dysfunction rat model can favorably modify the adverse effects of ventricular remodeling including attenuation of abnormal myosin gene expression. Sprague-Dawley rats were subjected to either proximal LAD ligation or sham operation. At 5 wk after the operation, animals were randomly assigned to sedentary conditions or 6 wk of graduated swim training, creating four experimental groups: infarct sedentary (IS), infarct exercise (IE), sham sedentary (SS), and sham exercise (SE). At 11 wk all rats were sacrificed and analyzed. Compared to sedentary infarct controls, exercise training attenuated left ventricular (LV) dilation and allowed more hypertrophy of the non infarct wall. The exercise-trained hearts also showed a reduction in the estimated peak wall tension. Northern blot analysis showed an increase in beta-myosin heavy chain expression in the hearts of the sedentary infarction group soon after infarction when compared to sham controls. However, with exercise training, there was a significant attenuation of the beta-myosin heavy chain expression in the myocardium. Exercise training in a model of left ventricular dysfunction after healed myocardial infarction can improve the adverse remodeling process by attenuating ventricular dilation and reducing wall tension. The abnormal beta-myosin expression was also attenuated in the exercise trained group. This is evidence that abnormal gene expression following severe myocardial infarction dysfunction can be favorably modified by an intervention. Images PMID:7635980

  11. Network diffusion accurately models the relationship between structural and functional brain connectivity networks

    PubMed Central

    Abdelnour, Farras; Voss, Henning U.; Raj, Ashish

    2014-01-01

    The relationship between anatomic connectivity of large-scale brain networks and their functional connectivity is of immense importance and an area of active research. Previous attempts have required complex simulations which model the dynamics of each cortical region, and explore the coupling between regions as derived by anatomic connections. While much insight is gained from these non-linear simulations, they can be computationally taxing tools for predicting functional from anatomic connectivities. Little attention has been paid to linear models. Here we show that a properly designed linear model appears to be superior to previous non-linear approaches in capturing the brain’s long-range second order correlation structure that governs the relationship between anatomic and functional connectivities. We derive a linear network of brain dynamics based on graph diffusion, whereby the diffusing quantity undergoes a random walk on a graph. We test our model using subjects who underwent diffusion MRI and resting state fMRI. The network diffusion model applied to the structural networks largely predicts the correlation structures derived from their fMRI data, to a greater extent than other approaches. The utility of the proposed approach is that it can routinely be used to infer functional correlation from anatomic connectivity. And since it is linear, anatomic connectivity can also be inferred from functional data. The success of our model confirms the linearity of ensemble average signals in the brain, and implies that their long-range correlation structure may percolate within the brain via purely mechanistic processes enacted on its structural connectivity pathways. PMID:24384152

  12. Interobserver Agreement in Assessing Early CT Signs of Middle Cerebral Artery Infarction

    Microsoft Academic Search

    Rudiger von Kummer; Rolf Holle; Ulrich Grzyska; Erich Hofmann; Olav Jansen; Dirk Petersen; Martin Schumacher; Klaus Sartor

    PURPOSE: To assess the reliability of detecting signs of hemispheric infarction on CT scans obtained within 6 hours of the onset of symptoms. METHODS: A neuroradiologist selected 12 normal and 33 abnormal CT studies showing the hyperdense middle cerebral artery sign (HMCAS) (n 5 10), brain swelling (n 5 22), and parenchymal hypodensity (n 5 33) from two series of

  13. Computed Tomographic Parameters Predicting Fatal Outcome in Large Middle Cerebral Artery Infarction

    Microsoft Academic Search

    Philip A. Barber; Andrew M. Demchuk; Jinjin Zhang; Scott E. Kasner; Michael D. Hill; Jorg Berrouschot; Erich Schmutzhard; Lutz Harms; Piero Verro; Derk Krieger

    2003-01-01

    Background: Large middle cerebral artery (MCA) ischaemic stroke when associated with extensive mass effect can result in brain herniation and neurological death. As yet there are few guidelines to aid the selection of patients for aggressive interventional therapies, such as decompression hemicraniectomy and\\/or hypothermia. Methods: We studied a cohort of patients from seven centres with large MCA infarction requiring neurocritical

  14. Acute myocardial infarction

    PubMed Central

    Domes, Trustin; Szafran, Olga; Bilous, Cheryl; Olson, Odell; Spooner, G. Richard

    2006-01-01

    OBJECTIVE To assess the quality of care of acute myocardial infarction (AMI) in a rural health region. DESIGN Clinical audit employing multiple explicit criteria of care elements for emergency department and in-hospital AMI management. The audit was conducted using retrospective chart review. SETTING Twelve acute care health centres and hospitals in the East Central Health Region, a rural health region in Alberta, where medical and surgical services are provided almost entirely by family physicians. PARTICIPANTS Hospital inpatients with a confirmed discharge diagnosis of AMI (ICD-9-CM codes 410.xx) during the period April 1, 2001, to March 31, 2002, were included (177 confirmed cases). MAIN OUTCOME MEASURES Quality of AMI care was assessed using guidelines from the American College of Cardiology and the American Heart Association and the Canadian Cardiovascular Outcomes Research Team and Canadian Cardiovascular Society. Quality of care indicators at three stages of patient care were assessed: at initial recognition and AMI management in the emergency department, during in-hospital AMI management, and at preparation for discharge from hospital. RESULTS In the emergency department, the quality of care was high for most procedural and therapeutic audit elements, with the exception of rapid electrocardiography, urinalysis, and provision of nitroglycerin and morphine. Average door-to-needle time for thrombolysis was 102.5 minutes. The quality of in-hospital care was high for most elements, but low for nitroglycerin and angiotensin-converting enzyme (ACE) inhibitors, daily electrocardiography, and counseling regarding smoking cessation and diet. Few patients received counseling for lifestyle changes at hospital discharge. Male and younger patients were treated more aggressively than female and older patients. Sites that used care protocols achieved better results in initial AMI management than sites that did not. Stress testing was not readily available in the rural region studied. CONCLUSION Quality of care for patients with AMI in this rural health region was high for most guideline elements. Standing orders, protocols, and checklists could improve care. Training and resource issues will need to be addressed to improve access to stress testing for rural patients. Clinical audit should be at the core of a system for local monitoring of quality of care. PMID:16926968

  15. Effects of zoledronate in the repair of chronically infarcted rat myocardium.

    PubMed

    Hwang, Hyosook; Hale, Sharon L; Leeka, Justin; Kloner, Robert A

    2010-12-01

    Zoledronate (Zol), one of the class of bisphophonate drugs, is commonly used to treat postmenopausal osteoporosis. Treatment of liposomal bisphosphonates has been shown to worsen myocardial infarct repair in an experimental model. The purpose of this study was to investigate the effect of Zol in the repair of chronically infarcted myocardium without liposomal encapsulation to mimic the clinical setting. Zol (20 ?g/kg, a dose known to treat experimental osteoporosis in rats, n = 15) was administered subcutaneously to female Sprague-Dawley rats 1 day before coronary artery ligation. Rats receiving phosphate-buffered saline (n = 12) were used as controls. Left ventricular function, infarct size, and remodeling were studied at 4 weeks postinfarction. Zol pretreatment did not affect left ventricular ejection fraction in hearts with myocardial infarction (49.5 ± 1.4% in Zol; 50.6 ± 2.1% in phosphate-buffered saline). Infarct size was similar in Zol versus untreated hearts (34.2% ± 2.9% in Zol; 33.4% ± 2.9% in phosphate-buffered saline). Left ventricular cavity volume and circumference, infarct thickness, and expansion index were comparable between the groups. To investigate a potential effect of Zol on tissue macrophage infiltration after myocardial infarction, heart specimens were harvested 48 hours postinfarction and sections were immunostained with CD68 antibody, a macrophage-specific marker. Results of macrophage immunostaining revealed that the level of tissue macrophage infiltration was similar between groups. In conclusion, administration of Zol before myocardial infarction had no adverse effects on cardiac contractile function, infarct size, or remodeling. These results suggest that treatment of Zol given before the onset of myocardial infarction does not cause worsening of infarct repair. PMID:21052019

  16. How does the motor relearning program improve neurological function of brain ischemia monkeys??

    PubMed Central

    Yin, Yong; Gu, Zhen; Pan, Lei; Gan, Lu; Qin, Dongdong; Yang, Bo; Guo, Jin; Hu, Xintian; Wang, Tinghua; Feng, Zhongtang

    2013-01-01

    The motor relearning program can significantly improve various functional disturbance induced by ischemic cerebrovascular diseases. However, its mechanism of action remains poorly understood. In injured brain tissues, glial fibrillary acidic protein and neurofilament protein changes can reflect the condition of injured neurons and astrocytes, while vascular endothelial growth factor and basic fibroblast growth factor changes can indicate angiogenesis. In the present study, we induced ischemic brain injury in the rhesus macaque by electrocoagulation of the M1 segment of the right middle cerebral artery. The motor relearning program was conducted for 60 days from the third day after model establishment. Immunohistochemistry and single-photon emission CT showed that the numbers of glial fibrillary acidic protein-, neurofilament protein-, vascular endothelial growth factor- and basic fibroblast growth factor-positive cells were significantly increased in the infarcted side compared with the contralateral hemisphere following the motor relearning program. Moreover, cerebral blood flow in the infarcted side was significantly improved. The clinical rating scale for stroke was used to assess neurological function changes in the rhesus macaque following the motor relearning program. Results showed that motor function was improved, and problems with consciousness, self-care ability and balance function were significantly ameliorated. These findings indicate that the motor relearning program significantly promoted neuronal regeneration, repair and angiogenesis in the surroundings of the infarcted hemisphere, and improve neurological function in the rhesus macaque following brain ischemia. PMID:25206440

  17. A mechanical model predicts morphological abnormalities in the developing human brain

    NASA Astrophysics Data System (ADS)

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-01

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

  18. Reverse brain drain in South Korea: state-led model.

    PubMed

    Yoon, B L

    1992-01-01

    Korea's reverse brain drain (RBD) has been an organized government effort, rather than a spontaneous social phenomenon, in that various policies and the political support of President Park, Chung-Hee were instrumental in laying the groundwork for its success. Particular features of Korea's RBD policies are the creation of a conducive domestic environment (i.e., government-sponsored strategic R & D institution-building, legal, and administrative reforms), and importantly, the empowerment of returnees (via, i.e., exceptionally good maternal benefits, guarantees of research autonomy). President Park played the cardinal role in empowering repatriates at the expense of his own civil bureaucracy, and his capacity for such patronage derived from Korea's bureaucratic-authoritarian political system. Returning scientists and engineers directly benefitted from this political system as well as Park's personal guardianship. For Park, empowerment of returning "brains" was necessary to accomplish his national industrialization plan, thereby enhancing his political legitimacy in domestic politics. An alliance with the R & D cadre was functionally necessary to successfully consolidate strong presidential power, and politically nonthreatening due to the particular form of "pact of domination" in Korea's power structure. RBD in Korea will continue in the near future given Korea's drive for high technology, and the remarkable expansion of local industrial and educational sectors. Korea's future RBD, however, needs to pay closer attention to the following 4 problems: research autonomy; equality issues; skill-based repatriation of technicians and engineers rather than Ph.Ds; and subsidies to small and medium industry for RBD. PMID:12285392

  19. Wharton's Jelly Transplantation Improves Neurologic Function in a Rat Model of Traumatic Brain Injury.

    PubMed

    Cheng, Tian; Yang, Bo; Li, Dongpeng; Ma, Shanshan; Tian, Yi; Qu, Ruina; Zhang, Wenjin; Zhang, Yanting; Hu, Kai; Guan, Fangxia; Wang, Jian

    2015-07-01

    Traumatic brain injury (TBI), which can lead to disability, dysfunction, and even death, is a prominent health problem worldwide. Effective therapy for this serious and debilitating condition is needed. Human umbilical cord matrix, known as Wharton's jelly (WJ), provides a natural, interface scaffold that is enriched in mesenchymal stem cells. In this study, we tested the efficacy of WJ tissue transplantation in a weight-drop model of TBI in rats. WJ tissue was cultured and transplanted into the injury site 24 h after TBI. The modified neurologic severity score, body weight, brain edema, and lesion volume were evaluated at various time points after TBI. Cognitive behavior was assessed by the novel object recognition test and the Morris water maze test. Expression of brain-derived neurotrophic factor (BDNF) in the perilesional brain area was measured at day 14 after TBI. We found that WJ tissue transplantation lessened TBI-induced brain edema (day 3), reduced lesion volume (day 28), improved neurologic function (days 21-28), and promoted memory and cognitive recovery. Additionally, expression of BDNF mRNA and protein was higher in WJ tissue-treated rats than in sham-operated or vehicle-treated rats. These data suggest that WJ tissue transplantation can reduce TBI-induced brain injury and may have therapeutic potential for the treatment of TBI. PMID:25638565

  20. Brain Changes Differ by Race with Alzheimer's Disease

    MedlinePLUS

    ... strokes, the researchers explained. They also might contain Lewy bodies -- another form of abnormal protein build-up in ... mix of brain changes that included infarcts and Lewy bodies, the researchers said. But among 41 black patients ...

  1. Construction of a Physiologically Based Pharmacokinetic Model for 2,4-Dichlorophenoxyacetic Acid Dosimetry in the Developing Rabbit Brain

    Microsoft Academic Search

    C. S. Kim; Z. Binienda; J. A. Sandberg

    1996-01-01

    A physiologically based pharmacokinetic (PBPK) model that describes the kinetics of organic anions by using 2,4-dichlorophenoxyacetic acid (2,4-D) as a representative compound was constructed for the developing rabbit brain at near-term pregnancy (Gestation Day 30). The model consisted of brain, body, and venous and arterial compartments for the mother which were linked to the fetus by a placenta. Maternal brain

  2. A multimodal approach for determining brain networks by jointly modeling functional and structural connectivity.

    PubMed

    Xue, Wenqiong; Bowman, F DuBois; Pileggi, Anthony V; Mayer, Andrew R

    2015-01-01

    Recent innovations in neuroimaging technology have provided opportunities for researchers to investigate connectivity in the human brain by examining the anatomical circuitry as well as functional relationships between brain regions. Existing statistical approaches for connectivity generally examine resting-state or task-related functional connectivity (FC) between brain regions or separately examine structural linkages. As a means to determine brain networks, we present a unified Bayesian framework for analyzing FC utilizing the knowledge of associated structural connections, which extends an approach by Patel et al. (2006a) that considers only functional data. We introduce an FC measure that rests upon assessments of functional coherence between regional brain activity identified from functional magnetic resonance imaging (fMRI) data. Our structural connectivity (SC) information is drawn from diffusion tensor imaging (DTI) data, which is used to quantify probabilities of SC between brain regions. We formulate a prior distribution for FC that depends upon the probability of SC between brain regions, with this dependence adhering to structural-functional links revealed by our fMRI and DTI data. We further characterize the functional hierarchy of functionally connected brain regions by defining an ascendancy measure that compares the marginal probabilities of elevated activity between regions. In addition, we describe topological properties of the network, which is composed of connected region pairs, by performing graph theoretic analyses. We demonstrate the use of our Bayesian model using fMRI and DTI data from a study of auditory processing. We further illustrate the advantages of our method by comparisons to methods that only incorporate functional information. PMID:25750621

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

    PubMed Central

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

    2014-01-01

    The present study assessed the impact of sample size on the power and fit of structural equation modeling applied to functional brain connectivity hypotheses. The data consisted of time-constrained minimum norm estimates of regional brain activity during performance of a reading task obtained with magnetoencephalography. Power analysis was first conducted for an autoregressive model with 5 latent variables (brain regions), each defined by 3 indicators (successive activity time bins). A series of simulations were then run by generating data from an existing pool of 51 typical readers (aged 7.5-12.5 years). Sample sizes ranged between 20 and 1,000 participants and for each sample size 1,000 replications were run. Results were evaluated using chi-square Type I errors, model convergence, mean RMSEA (root mean square error of approximation) values, confidence intervals of the RMSEA, structural path stability, and D-Fit index values. Results suggested that 70 to 80 participants were adequate to model relationships reflecting close to not so close fit as per MacCallum et al.'s recommendations. Sample sizes of 50 participants were associated with satisfactory fit. It is concluded that structural equation modeling is a viable methodology to model complex regional interdependencies in brain activation in pediatric populations. PMID:25435589

  4. Prolongation and enhancement of the anti-apoptotic effects of PTD-Hsp27 fusion proteins using an injectable thermo-reversible gel in a rat myocardial infarction model.

    PubMed

    Won, Young-Wook; Kim, Jang-Kyung; Cha, Min-Ji; Hwang, Ki-Chul; Choi, Donghoon; Kim, Yong-Hee

    2010-06-01

    Ischemic heart disease has emerged as a leading cause of death worldwide. Conventional surgery-based therapy for this disease, especially myocardial infarction, requires additional pharmaceutical agents using heart's endogenous protective mechanism to suppress the progress and recurrence of the disease. Heat shock protein 27 (Hsp27) has been considered to be a potentially therapeutic protein for the treatment of ischemic heart disease due to its anti-apoptotic and protective effects on cardiomyocytes under stressful conditions. Despite the potency of Hsp27, low transduction efficiency, protein instability, and a short half-life in the body have limited its in vivo applications. Protein transduction domains (PTD) were recombinantly fused with Hsp27 to enhance transduction efficiency. Although the intracellular delivery of the PTD-Hsp27 fusion proteins was significantly enhanced compared with Hsp27, the instability and short half-life of the PTD-Hsp27 fusion proteins still need to be improved for in vivo applications. Injectable thermo-reversible gel system was developed and found to be effective in stabilizing and retarding the release of the PTD-Hsp27 fusion proteins both in vitro and in vivo. PTD-Hsp27-loaded thermo-reversible gels were locally administered to the heart muscle in a ligation/reperfused rat myocardial infarction model and the long-term therapeutic efficacy was observed by measuring the inhibition of apoptosis and the area of fibrosis. PMID:20153787

  5. Catalpol Increases Brain Angiogenesis and Up-Regulates VEGF and EPO in the Rat after Permanent Middle Cerebral Artery Occlusion

    PubMed Central

    Zhu, Hui-Feng; Wan, Dong; Luo, Yong; Zhou, Jia-Li; Chen, Li; Xu, Xiao-Yu

    2010-01-01

    To investigate the role and mechanism of catalpol in brain angiogenesis in a rat model of stroke, the effect of catalpol (5 mg/kg; i.p) or vehicle administered 24 hours after permanent middle cerebral artery occlusion (pMCAO) on behavior, angiogenesis, ultra-structural integrity of brain capillary endothelial cells, and expression of EPO and VEGF were assessed. Repeated treatments with Catalpol reduced neurological deficits and significantly improved angiogenesis, while significantly increasing brain levels of EPO and VEGF without worsening BBB edema. These results suggested that catalpol might contribute to infarcted-brain angiogenesis and ameliorate the edema of brain capillary endothelial cells (BCECs) by upregulating VEGF and EPO coordinately. PMID:20827397

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

    PubMed

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

    2013-01-01

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

  7. Multimodality imaging of pulmonary infarction.

    PubMed

    Bray, T J P; Mortensen, K H; Gopalan, D

    2014-12-01

    The impact of absent pulmonary arterial and venous flow on the pulmonary parenchyma depends on a host of factors. These include location of the occlusive insult, the speed at which the occlusion develops and the ability of the normal dual arterial supply to compensate through increased bronchial arterial flow. Pulmonary infarction occurs when oxygenation is cut off secondary to sudden occlusion with lack of recruitment of the dual supply arterial system. Thromboembolic disease is the commonest cause of such an insult but a whole range of disease processes intrinsic and extrinsic to the pulmonary arterial and venous lumen may also result in infarcts. Recognition of the presence of infarction can be challenging as imaging manifestations often differ from the classically described wedge shaped defect and a number of weighty causes need consideration. This review highlights aetiologies and imaging appearances of pulmonary infarction, utilising cases to illustrate the essential role of a multimodality imaging approach in order to arrive at the appropriate diagnosis. PMID:25241050

  8. JAMA Patient Page: Myocardial Infarction

    MedlinePLUS

    ... Heart Blocked Coronary Artery Insertion of Stent After Balloon Angioplasty Stent in Place and Blood Flow Restored Aorta Femoral artery Catheter for stent insertion H E A R T D I S E A S E The Journal of the American Medical Association JAMA PATIENT PAGE Myocardial Infarction M yocardial ...

  9. Paroxysmal Rhinorrhea after Medullary Infarct

    PubMed Central

    Uchino, Ken; Lu, Mei

    2012-01-01

    Lateral medullary infarction, known as Wallenberg syndrome, can be accompanied by sympathetic dysfunction. We report a case of unilateral intermittent rhinorrhea that started after an ischemic stroke in the ipsilateral lateral medulla and cerebellum. Rhinorrhea might be mediated by dysfunction of the sympathetic autonomic system. PMID:22393323

  10. Neuroprotective effect of lentivirus mediated VEGF on rat model with cerebral ischemic injury

    PubMed Central

    Zhang, Junhe; Li, Xiaojuan; Chai, Shujie; Wang, Xiaoyin

    2015-01-01

    This study aimed to investigate the neuroprotective effect and its mechanism of lentivirus mediated VEGF on rat model with cerebral ischemic injury. 45 rats with cerebral ischemic injury constructed by the suture method were randomly divided into sham group, model group, vector group and VEGF group. The packaged vector lentivirus and lentivirus carrying VEGF gene were injected into the lateral ventricular of rats in vector group and VEGF group respectively. The equal volume of PBS buffer was injected in sham group and model group respectively. The expression of VEGF and protein in brain tissue were detected by real-time fluorescence quantitative PCR and Western blot. The change of brain tissue vascular density was analyzed by immunohistochemistry. The brain infarction area and the degree of nervous functional defect of the rats were analyzed. VEGF mRNA and protein levels were significantly higher in brain tissue of rats in VEGF group than those in model group and vector group (P < 0.05). The brain tissue vascular density increased significantly in VEGF group (P < 0.05). Compared with sham group, the infarction area of brain tissue and the degree of nervous functional defect increased significantly in model group, vector group and VEGF group, but the VEGF group was significantly lower than those in model group and vector group (P < 0.05). In conclusion, the overexpression of VEGF in cerebral ischemia injury contributed to the angiogenesis in brain tissues, reduced the brain injury caused by cerebral ischemia and protected brain neuronal function. PMID:26064315

  11. Human and rat glioma growth, invasion, and vascularization in a novel chick embryo brain tumor model.

    PubMed

    Cretu, Alexandra; Fotos, Joseph S; Little, Brian W; Galileo, Deni S

    2005-01-01

    The mechanisms that control the insidiously invasive nature of malignant gliomas are poorly understood, and their study would be facilitated by an in vivo model that is easy to manipulate and inexpensive. The developing chick embryo brain was assessed as a new xenograft model for the production, growth, and study of human and rat glioma cell lines. Three established glioma lines (U-87 MG, C6, and 9L) were injected into chick embryo brain ventricles on embryonic day (E) 5 and brains were examined after several days to two weeks after injection. All glioma lines survived, produced vascularized intraventricular tumors, and invaded the brain in a manner similar to that in rodents. Rat C6 glioma cells spread along vasculature and also invaded the neural tissue. Human U-87 glioma cells migrated along vasculature and exhibited slight invasion of neural tissue. Rat 9L gliosarcoma cells were highly motile, but migrated only along the vasculature. A derivative of 9L cells that stably expressed the cell surface adhesion molecule NgCAM/L1 was produced and also injected into chick embryo brain ventricles to see if this protein could facilitate tumor cell migration away from the vasculature into areas such as axonal tracts. 9L/NgCAM cells, however, did not migrate away from the vasculature and, thus, this protein alone cannot be responsible for diffuse invasiveness of some gliomas. 9L/NgCAM cell motility was assessed in vitro using sophisticated time-lapse microscopy and quantitative analysis, and was significantly altered compared to parental 9L cells. These studies demonstrate that the chick embryo brain is a successful and novel xenograft model for mammalian gliomas and demonstrate the potential usefulness of this new model for studying glioma tumor cell growth, vascularization, and invasiveness. PMID:16158250

  12. ¹H MRS characterization of neurochemical profiles in orthotopic mouse models of human brain tumors.

    PubMed

    Hulsey, Keith M; Mashimo, Tomoyuki; Banerjee, Abhishek; Soesbe, Todd C; Spence, Jeffrey S; Vemireddy, Vamsidhara; Maher, Elizabeth A; Bachoo, Robert M; Choi, Changho

    2015-01-01

    Glioblastoma (GBM), the most common primary brain tumor, is resistant to currently available treatments. The development of mouse models of human GBM has provided a tool for studying mechanisms involved in tumor initiation and growth as well as a platform for preclinical investigation of new drugs. In this study we used (1) H MR spectroscopy to study the neurochemical profile of a human orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to evaluate differences in metabolite concentrations in the GBM HOT mice when compared with normal mouse brain in order to determine if MRS could reliably differentiate tumor from normal brain. A TE =19?ms PRESS sequence at 9.4?T was used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels for 12 metabolites and for lipids/macromolecules at 0.9?ppm and at 1.3?ppm were reliably detected in all mouse spectra. The tumors had significantly lower concentrations of total creatine, GABA, glutamate, total N-acetylaspartate, aspartate, lipids/macromolecules at 0.9?ppm, and lipids/macromolecules at 1.3?ppm than did the brains of normal mice. The concentrations of glycine and lactate, however, were significantly higher in tumors than in normal brain. PMID:25394324

  13. Responses to model songs of auditory neurons in the thoracic ganglia and brain of the locust

    Microsoft Academic Search

    Heiner Römer; Ulrich Seikowski

    1985-01-01

    1.Locust interneurons in the ventral nerve cord and the brain were tested with models of the stridulatory song. These models had the conspecific frequency composition (Fig. 1) but were varied with respect to the duration of the interchirp-interval.2.In most ascending interneurons such model songs elicited complex responses comprising EPSP and IPSP of different thresholds and amplitude. As a consequence of

  14. A GENETIC ALGORITHM FOR CONTROLLING AN AGENT-BASED MODEL OF THE FUNCTIONAL HUMAN BRAIN

    PubMed Central

    Joyce, Karen E; Hayasaka, Satoru; Laurienti, Paul J

    2013-01-01

    Recently, we introduced a dynamic functional model of the human brain. This model, representing functional connectivity in the brain, is generated from subject-specific physiological data collected using functional magnetic resonance imaging (fMRI). The dynamics of this model are examined using agent-based modeling techniques, wherein a collection of binary agents are embedded as nodes in the network. This model is capable of producing a wide variety of complex behaviors. In this work, we use machine learning techniques to drive the model to produce desired behaviors. The solution space of the model is unreasonably large for a brute-force approach, but we demonstrate that genetic algorithms (GAs) are able to locate optimal model parameters within this space to achieve the desired behavior. We detail the design of a GA specifically suited for this model, and discuss the relevant issues that arise in GA design. Specifically, we explore several fitness functions to accurately quantify the suitability of each potential solution. We examine their strengths and weaknesses, and identify an optimal fitness function for this system. We validate the GA with the optimal fitness function by showing that it can drive the system to produce pre-defined behaviors. The ability of the model to produce pre-defined behaviors indicates that it may be possible to produce physiologically relevant outputs. The model may be very useful for studying the changes in brain dynamics due to neurological diseases or conditions. Additionally, this powerful dynamic brain model may be instrumental in many artificial intelligence settings. PMID:22846285

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

    Microsoft Academic Search

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

    2005-01-01

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

  16. Relationship between angiographic vasospasm, cerebral blood flow, and cerebral infarction after subarachnoid hemorrhage.

    PubMed

    Dhar, Rajat; Diringer, Michael N

    2015-01-01

    Delayed cerebral ischemia (DCI) and cerebral infarction are major contributors to poor functional recovery after subarachnoid hemorrhage (SAH). Cerebral vasospasm, the narrowing of proximal intracranial arteries after SAH, has long been assumed to be the primary cause of DCI, and has therefore been the primary therapeutic target in attempts to diminish disability after SAH. However, emerging evidence has questioned the strength and causality of the relationship between vasospasm and DCI. To address this fundamental question, we performed two parallel studies assessing the relationship between the presence of vasospasm in a vascular territory and both regional reductions in cerebral blood flow (CBF) and development of cerebral infarction.In a cohort of SAH patients at high-risk for DCI, we identified regions of hypoperfusion using positron emission tomography (PET) and compared their distribution with territories exhibiting vasospasm on concurrent angiography. We found that regional hypoperfusion was common in the absence of proximal vasospasm and that some patients without any significant vasospasm still could have hypoperfused brain regions. Similarly, our parallel study demonstrated that both patients and brain territories without vasospasm could develop delayed cerebral infarction, and that such vasospasm-independent infarcts account for more than a quarter of the infarct burden from DCI. These findings suggest that other processes, perhaps at a microvascular level, contribute at least part of the burden of DCI and future interventions should also address these other pathophysiologic processes. PMID:25366617

  17. Isolated rotational nystagmus may be the only clue to the early diagnosis of dorsolateral medullary infarction.

    PubMed

    Tseng, Chun-Hsiang; Chiu, Wen-Yi

    2014-07-01

    The medulla contains complex nervous structures related to motor, sensory, coordination, and visceral autonomic functions. The medullary infarctions cause various symptoms and signs depending on the location of the lesion. Lateral medullary infarction is caused by a vascular event in the territory of the posterior inferior cerebellar artery or the vertebral artery. We report a case of a patient with falling tendency and whirling sensation. He reported no facial drop, arm drift, slurred speech, difficulty of swallowing, or weakness of his limbs. The neurologic examination revealed no decreased muscle power, dysarthria, dysphagia, or other relevant neurologic deficits. Urgent noncontrast brain computed tomography detected no acute hemorrhage or ischemic lesion. On admission, the oculomotor examination revealed conjugated rotational nystagmus with clockwise direction. The magnetic resonance imaging of the brain demonstrated acute infarct in the medulla oblongata approximately 0.8 × 0.5 cm. The infarct appears bright on diffusion-weighted images (Fig.). A diagnosis of dorsolateral medulla infarction was established, and the patient was started on a therapy of 100 mg aspirin once daily. After standard therapies, the patient's recovery was uneventful. PMID:24462398

  18. Study of Protein Expresion in Peri-Infarct Tissue after Cerebral Ischemia

    PubMed Central

    Brea, David; Agulla, Jesús; Staes, An; Gevaert, Kris; Campos, Francisco; Sobrino, Tomás; Blanco, Miguel; Dávalos, Antoni; Castillo, José; Ramos-Cabrer, Pedro

    2015-01-01

    In this work, we report our study of protein expression in rat peri-infarct tissue, 48?h after the induction of permanent focal cerebral ischemia. Two proteomic approaches, gel electrophoresis with mass spectrometry and combined fractional diagonal chromatography (COFRADIC), were performed using tissue samples from the periphery of the induced cerebral ischemic lesions, using tissue from the contra-lateral hemisphere as a control. Several protein spots (3408) were identified by gel electrophoresis, and 11 showed significant differences in expression between peri-infarct and contra-lateral tissues (at least 3-fold, p?infarct tissue. Further studies by 1D and 2D western blotting and immunohistochemistry revealed that only one member of this family (the inducible form, HSP72 or HSP70i) is specifically expressed by the peri-infarct tissue, while the majority of this family (the constitutive form, HSC70 or HSP70c) is expressed in the whole brain. Our data support that HSP72 is a suitable biomarker of peri-infarct tissue in the ischemic brain. PMID:26153530

  19. Chemokine receptor-like 2 is involved in ischemic brain injury

    PubMed Central

    Douglas, Robert M.; Chen, Alice H.; Iniguez, Alejandra; Wang, Juan; Fu, Zhengxing; Powell, Frank L.; Haddad, Gabriel G.; Yao, Hang

    2013-01-01

    We examined the role of CCRL2 in ischemic brain injury using both in vitro and in vivo mouse stroke models. The expression of CCRL2 was enhanced at both the RNA and protein levels in cultured brain slices under ischemic conditions. Ischemia-induced cell death was reduced in brain slices derived from CCRL2 knockout (KO) mice in comparison with those from wild type (WT) mice. The infarct volume was smaller and neurological deficits were attenuated in CCRL2 KO mice when compared to WT mice subjected to a transient middle cerebral artery occlusion. Our data suggest that CCRL2 is involved in ischemia-induced brain injury in mice. PMID:23847708

  20. A Simple Method for Assessing Free Brain/Free Plasma Ratios Using an In Vitro Model of the Blood Brain Barrier

    PubMed Central

    Sevin, Emmanuel; Szorath, Erica; Martinsson, Stefan; Renftel, Mila; Hongmei, Yan; Cecchelli, Romeo; Lundquist, Stefan

    2013-01-01

    Historically, the focus has been to use in vitro BBB models to optimize rate of drug delivery to the CNS, whereas total in vivo brain/plasma ratios have been used for optimizing extent. However, these two parameters do not necessarily show good correlations with receptor occupancy data or other pharmacological readouts. In line with the free drug hypothesis, the use of unbound brain concentrations (Cu,br) has been shown to provide the best correlations with pharmacological data. However, typically the determination of this parameter requires microdialysis, a technique not ideally suited for screening in early drug development. Alternative, and less resource-demanding methodologies to determine Cu,br employ either equilibrium dialysis of brain homogenates or incubations of brain slices in buffer to determine fraction unbound brain (fu,br), which is subsequently multiplied by the total brain concentration to yield Cu,br. To determine Cu,br/Cu,pl ratios this way, still requires both in vitro and in vivo experiments that are quite time consuming. The main objective of this study was to explore the possibility to directly generate Cu,br/Cu,pl ratios in a single in vitro model of the BBB, using a co-culture of brain capillary endothelial and glial cells in an attempt to mimick the in vivo situation, thereby greatly simplifying existing experimental procedures. Comparison to microdialysis brain concentration profiles demonstrates the possibility to estimate brain exposure over time in the BBB model. A stronger correlation was found between in vitro Cu,br/Cu,pl ratios and in vivo Cu,br/Cu,pl obtained using fu,br from brain slice than with fu,br from brain homogenate for a set of 30 drugs. Overall, Cu,br/Cu,pl ratios were successfully predicted in vitro for 88% of the 92 studied compounds. This result supports the possibility to use this methodology for identifying compounds with a desirable in vivo response in the CNS early on in the drug discovery process. PMID:24312489

  1. Probabilistic graphical models for effective connectivity extraction in the brain using FMRI data.

    PubMed

    Ali Safari, Mohammad; Mohammadbeigi, Majid

    2012-01-01

    In this study using Bayesian network method to learn the structure of effective connectivity among brain regions involved in a functional MRI. The approach is exploratory in the sense that it does not require a priori model as in the earlier approaches, such as the Structural Equation Modeling or Dynamic Causal Modeling, which can only affirm or refute the connectivity of a previously known anatomical model or a hypothesized model. The conditional probabilities that render the interactions among brain regions in Bayesian networks represent the connectivity in the complete statistical sense. This method is applicable even when the number of regions involved in the cognitive network is large or unknown. In this study, we demonstrated the present approach using synthetic data and fMRI data collected in attention to motion in the visual system task. PMID:22874167

  2. Modeling adolescent nicotine exposure: effects on cholinergic systems in rat brain regions

    Microsoft Academic Search

    Jennifer A Trauth; Everett C McCook; Frederic J Seidler; Theodore A Slotkin

    2000-01-01

    Smoking among teenagers is increasing and the initiation of tobacco use during adolescence is associated with subsequently higher cigarette consumption and lower rates of quitting. Few animal studies have addressed whether adolescent nicotine exposure exerts unique or lasting effects on brain structure or function. Initial investigations with a rat model of adolescent nicotine exposure have demonstrated that the vulnerable developmental

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    E-print Network

    Tian, Jie

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

  5. Action and Language Mechanisms in the Brain: Data, Models and Neuroinformatics

    PubMed Central

    Bonaiuto, James J.; Bornkessel-Schlesewsky, Ina; Kemmerer, David; MacWhinney, Brian; Nielsen, Finn Årup; Oztop, Erhan

    2014-01-01

    We assess the challenges of studying action and language mechanisms in the brain, both singly and in relation to each other to provide a novel perspective on neuroinformatics, integrating the development of databases for encoding – separately or together – neurocomputational models and empirical data that serve systems and cognitive neuroscience. PMID:24234916

  6. Bridging Levels: Using a Cognitive Model to Connect Brain and Behavior in Category Learning

    E-print Network

    Love, Bradley C.

    Bridging Levels: Using a Cognitive Model to Connect Brain and Behavior in Category Learning Todd M to a learning circuit involving the hip- pocampus, perirhinal, and prefrontal cortex. Results from groups varying in function along this circuit (e.g., infants, amnesics, older adults) are successfully simu

  7. Optogenetic investigation of neural circuits underlying brain disease in animal models

    Microsoft Academic Search

    Kay M. Tye; Karl Deisseroth

    2012-01-01

    Optogenetic tools have provided a new way to establish causal relationships between brain activity and behaviour in health and disease. Although no animal model captures human disease precisely, behaviours that recapitulate disease symptoms may be elicited and modulated by optogenetic methods, including behaviours that are relevant to anxiety, fear, depression, addiction, autism and parkinsonism. The rapid proliferation of optogenetic reagents

  8. Morphometrical Characterization of Two Glioma Models in the Brain of Immunocompetent and Immunodeficient Rats

    Microsoft Academic Search

    Marco Saini; Mattia Bellinzona; Frerk Meyer; Gaetano Cali‘; Madjid Samii

    1999-01-01

    Although several glioma models exist, systematic morphometrical studies on such experimental tumors are lacking. The purpose of this study was the quantitative assessment of how rat strains, cell lines, injection techniques and location affect tumors reproducibility and histopathological features. Glioma cells were implanted in 3 brain locations, with different injection techniques (free hand, stereotactic, water-tight device), variable volumes, cell concentrations

  9. Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia

    Microsoft Academic Search

    A. Y. Estevez; S. Pritchard; K. Harper; J. W. Aston; A. Lynch; J. J. Lucky; J. S. Ludington; P. Chatani; W. P. Mosenthal; J. C. Leiter; S. Andreescu; J. S. Erlichman

    2011-01-01

    Cerium oxide nanoparticles (nanoceria) are widely used as catalysts in industrial applications because of their potent free radical-scavenging properties. Given that free radicals play a prominent role in the pathology of many neurological diseases, we explored the use of nanoceria as a potential therapeutic agent for stroke. Using a mouse hippocampal brain slice model of cerebral ischemia, we show here

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

    E-print Network

    E. Alfinito; G. Vitiello

    2000-06-14

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

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

    Microsoft Academic Search

    Eleonora Alfinito; Giuseppe Vitiello

    2000-01-01

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

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

    E-print Network

    Alfinito, E

    2000-01-01

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

  13. LPA signaling initiates schizophrenia-like brain and behavioral changes in a mouse model of prenatal brain hemorrhage

    PubMed Central

    Mirendil, H; Thomas, E A; De Loera, C; Okada, K; Inomata, Y; Chun, J

    2015-01-01

    Genetic, environmental and neurodevelopmental factors are thought to underlie the onset of neuropsychiatric disorders such as schizophrenia. How these risk factors collectively contribute to pathology is unclear. Here, we present a mouse model of prenatal intracerebral hemorrhage—an identified risk factor for schizophrenia—using a serum-exposure paradigm. This model exhibits behavioral, neurochemical and schizophrenia-related gene expression alterations in adult females. Behavioral alterations in amphetamine-induced locomotion, prepulse inhibition, thigmotaxis and social interaction—in addition to increases in tyrosine hydroxylase-positive dopaminergic cells in the substantia nigra and ventral tegmental area and decreases in parvalbumin-positive cells in the prefrontal cortex—were induced upon prenatal serum exposure. Lysophosphatidic acid (LPA), a lipid component of serum, was identified as a key molecular initiator of schizophrenia-like sequelae induced by serum. Prenatal exposure to LPA alone phenocopied many of the schizophrenia-like alterations seen in the serum model, whereas pretreatment with an antagonist against the LPA receptor subtype LPA1 prevented many of the behavioral and neurochemical alterations. In addition, both prenatal serum and LPA exposure altered the expression of many genes and pathways related to schizophrenia, including the expression of Grin2b, Slc17a7 and Grid1. These findings demonstrate that aberrant LPA receptor signaling associated with fetal brain hemorrhage may contribute to the development of some neuropsychiatric disorders. PMID:25849980

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

    NASA Astrophysics Data System (ADS)

    Schwartz, Jon A.; Shetty, Anil M.; Price, Roger E.; Stafford, R. Jason; Wang, James C.; Uthamanthil, Rajesh K.; Pham, Kevin; McNichols, Roger J.; Coleman, Chris L.; Payne, J. Donald

    2009-02-01

    We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8+/-4.1ºC. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of 48.6+/-1.1ºC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

  15. An integrative dynamic model of brain energy metabolism using in vivo neurochemical measurements.

    PubMed

    Cloutier, Mathieu; Bolger, Fiachra B; Lowry, John P; Wellstead, Peter

    2009-12-01

    An integrative, systems approach to the modelling of brain energy metabolism is presented. Mechanisms such as glutamate cycling between neurons and astrocytes and glycogen storage in astrocytes have been implemented. A unique feature of the model is its calibration using in vivo data of brain glucose and lactate from freely moving rats under various stimuli. The model has been used to perform simulated perturbation experiments that show that glycogen breakdown in astrocytes is significantly activated during sensory (tail pinch) stimulation. This mechanism provides an additional input of energy substrate during high consumption phases. By way of validation, data from the perfusion of 50 microM propranolol in the rat brain was compared with the model outputs. Propranolol affects the glucose dynamics during stimulation, and this was accurately reproduced in the model by a reduction in the glycogen breakdown in astrocytes. The model's predictive capacity was verified by using data from a sensory stimulation (restraint) that was not used for model calibration. Finally, a sensitivity analysis was conducted on the model parameters, this showed that the control of energy metabolism and transport processes are critical in the metabolic behaviour of cerebral tissue. PMID:19396534

  16. Protective effect of tanshinone IIA on the brain and its therapeutic time window in rat models of cerebral ischemia-reperfusion

    PubMed Central

    TANG, QIQIANG; HAN, RUODONG; XIAO, HAN; LI, JUN; SHEN, JILONG; LUO, QINGLI

    2014-01-01

    The aims of the present study were to investigate the protective effect of tanshinone IIA on the brain and its therapeutic time window in a rat model of cerebral ischemia-reperfusion. The rat model of cerebral ischemia-reperfusion was established by suture occlusion. In an initial experiment, male Sprague-Dawley (SD) rats were randomly divided into control cerebral ischemia-reperfusion rat model, tanshinone IIA1 (TSA1), tanshinone IIA4 (TSA4), tanshinone IIA6 (TSA6) and tanshinone IIA12 (TSA12) groups (n=8 per group). The rats in the control group were given 4 ml phosphate-buffered saline (PBS) intraperitoneally following suture occlusion. The other groups were respectively treated with 25 mg/kg tanshinone IIA intraperitoneally at 1, 4, 6 and 12 h following the initiation of reperfusion and once a day for a total of three days. The grades of neurologic impairment and volume of cerebral infarction of each group were measured 72 h after suture occlusion. In another experiment, 16 male SD rats were randomly divided into a 6 h reperfusion group and a 24 h reperfusion group following drug administration. The rats in each group were further divided into a control subgroup (4 ml PBS) and a tanshinone IIA subgroup (25 mg/kg). The rats were immediately administered their respective treatments following the establishment of the model. The rats were decapitated 6 and 24 h after the initiation of reperfusion. The expression levels of cytoplasmic thioredoxin (Trx-1) and mitochondrial thioredoxin (Trx-2) in the ischemic penumbra were determined by western blot analysis. The nitric oxide (NO) levels, and total NO synthase (tNOS) and inducible NO synthase (iNOS) activities in the rat blood were measured using a reagent kit. The changes in cerebral blood flow were evaluated by Doppler imaging. The grade of neurological impairment of the TSA1 group was statistically lower than that of the other groups (P<0.05). The cerebral infarction volume results showed that the volumes of infarction in the TSA1 and TSA4 groups were lower than those in the other groups (P<0.05). Tanshinone IIA significantly increased cerebral blood flow compared with that of the control group (P<0.05). Moreover, tanshinone IIA significantly increased the expression levels of Trx-1 and Trx-2 compared with those in the control group (P<0.05). Tanshinone IIA significantly decreased the NO levels and iNOS and tNOS activities compared with those of the control group (P<0.05). However, the iNOS activity in the rats in the 6 h reperfusion group was not statistically significantly different from that of the respective control group (P>0.05). Tanshinone IIA has a protective effect on the cranial nerves when administered during the initial stages of cerebral ischemia. This protective effect is associated with an improvement of cerebral blood flow as well as an increase in anti-oxygen radical and anti-inflammatory activities. PMID:25289069

  17. In defense of brain-inspired cognitive models

    E-print Network

    Kanan, Christopher

    the contextual— guidance model when their performance ongood performance. Our re—implementation of the ContextualContextual Guidance model (Ehinger et al. , 2009) incorporates object ap- pearance, and they ?nd its performance

  18. Computational modeling of high-level cognition and brain function

    Microsoft Academic Search

    Marcel Adam Just; Patricia A. Carpenter; Sashank Varma

    1999-01-01

    This article describes a computational modeling architecture, 4CAPS, which is consistent with key properties of cortical function and makes good contact with functional neuroimaging results. Like earlier cognitive models such as SOAR, ACT-R, 3CAPS, and EPIC, the proposed cognitive model is implemented in a computer simulation that predicts observable variables such as human response times and error patterns. In addition,

  19. Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

    PubMed

    Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

    2014-06-01

    Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48?h of reperfusion. The effects of rapamycin (250??g/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin. PMID:24773551

  20. Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease.

    PubMed

    Cotrina, Maria Luisa; Chen, Michael; Han, Xiaoning; Iliff, Jeffrey; Ren, Zeguang; Sun, Wei; Hagemann, Tracy; Goldman, James; Messing, Albee; Nedergaard, Maiken

    2014-09-25

    Alexander disease (AxD) is the only known human pathology caused by mutations in an astrocyte-specific gene, glial fibrillary acidic protein (GFAP). These mutations result in abnormal GFAP accumulations that promote seizures, motor delays and, ultimately, death. The exact contribution of increased, abnormal levels of astrocytic mutant GFAP in the development and progression of the epileptic phenotype is not clear, and we addressed this question using two mouse models of AxD. Comparison of brain seizure activity spontaneously and after traumatic brain injury (TBI), an effective way to trigger seizures, revealed that abnormal GFAP accumulation contributes to anomalous brain activity (increased non-convulsive hyperactivity) but is not a risk factor for the development of epilepsy after TBI. These data highlight the need to further explore the complex and heterogeneous response of astrocytes towards injury and the involvement of GFAP in the progression of AxD. PMID:25069089

  1. Gaussian mixture models and semantic gating improve reconstructions from human brain activity

    PubMed Central

    Schoenmakers, Sanne; Güçlü, Umut; van Gerven, Marcel; Heskes, Tom

    2015-01-01

    Better acquisition protocols and analysis techniques are making it possible to use fMRI to obtain highly detailed visualizations of brain processes. In particular we focus on the reconstruction of natural images from BOLD responses in visual cortex. We expand our linear Gaussian framework for percept decoding with Gaussian mixture models to better represent the prior distribution of natural images. Reconstruction of such images then boils down to probabilistic inference in a hybrid Bayesian network. In our set-up, different mixture components correspond to different character categories. Our framework can automatically infer higher-order semantic categories from lower-level brain areas. Furthermore, the framework can gate semantic information from higher-order brain areas to enforce the correct category during reconstruction. When categorical information is not available, we show that automatically learned clusters in the data give a similar improvement in reconstruction. The hybrid Bayesian network leads to highly accurate reconstructions in both supervised and unsupervised settings. PMID:25688202

  2. Copper-amyloid-? complex may catalyze peroxynitrite production in brain: evidence from molecular modeling.

    PubMed

    Giacovazzi, Roberto; Ciofini, Ilaria; Rao, Li; Amatore, Christian; Adamo, Carlo

    2014-06-01

    Rationalization of the origin of peroxynitrite-related damages in the brain of Alzheimer's disease (AD) patients linking to functional hyperemia, inexplicable on the basis of the accepted hydrogen peroxide catalytic route, is here provided by molecular modeling. The present theoretical work indeed strongly supports the facile occurrence of an A?-catalyzed generation of peroxynitrite in the brain, alternative to the already accepted H2O2-route, whenever ascorbate, dioxygen and nitric oxide are present near Cu-A? complexes without the necessity of generating short-lived superoxide ions. The proposed route requires nitric oxide and dioxygen to be simultaneously present at sufficiently high concentrations near Cu-A? complexes, requirement which is frequently fulfilled in brain during functional hyperemia. Conversely, hydrogen peroxide would be produced during resting phases. PMID:24616909

  3. Migration and fate of therapeutic stem cells in different brain disease models.

    PubMed

    Carney, B J; Shah, K

    2011-12-01

    Stem cells have a number of properties, which make them excellent candidates for the treatment of various neurologic disorders, the most important of which being their ability to migrate to and differentiate predictably at sites of pathology in the brain. The disease-directed migration and well-characterized differentiation patterns of stem cells may eventually provide a powerful tool for the treatment of both localized and diffuse disease processes within the human brain. A thorough understanding of the molecular mechanisms governing their migratory properties and their choice between different differentiation programs is essential if these cells are to be used therapeutically in humans. This review focuses on summarizing the migration and differentiation of therapeutic neural and mesenchymal stem cells in different disease models in the brain and also discusses the promise of these cells to eventually treat various forms of neurologic disease. PMID:21946010

  4. MIGRATION AND FATE OF THERAPEUTIC STEM CELLS IN DIFFERENT BRAIN DISEASE MODELS

    PubMed Central

    CARNEY, B. J.; SHAH, K.

    2013-01-01

    Stem cells have a number of properties, which make them excellent candidates for the treatment of various neurologic disorders, the most important of which being their ability to migrate to and differentiate predictably at sites of pathology in the brain. The disease-directed migration and well-characterized differentiation patterns of stem cells may eventually provide a powerful tool for the treatment of both localized and diffuse disease processes within the human brain. A thorough understanding of the molecular mechanisms governing their migratory properties and their choice between different differentiation programs is essential if these cells are to be used therapeutically in humans. This review focuses on summarizing the migration and differentiation of therapeutic neural and mesenchymal stem cells in different disease models in the brain and also discusses the promise of these cells to eventually treat various forms of neurologic disease. PMID:21946010

  5. Correlation between subacute sensorimotor deficits and brain edema in two mouse models of intracerebral hemorrhage.

    PubMed

    Krafft, Paul R; McBride, Devin W; Lekic, Tim; Rolland, William B; Mansell, Charles E; Ma, Qingyi; Tang, Jiping; Zhang, John H

    2014-05-01

    Formation of brain edema after intracerebral hemorrhage (ICH) is highly associated with its poor outcome. However, the relationship between cerebral edema and behavioral deficits has not been thoroughly examined in the preclinical setting. Hence, this study aimed to evaluate the ability of common sensorimotor tests to predict the extent of brain edema in two mouse models of ICH. One hundred male CD-1 mice were subjected to sham surgery or ICH induction via intrastriatal injection of either autologous blood (30 ?L) or bacterial collagenase (0.0375U or 0.075U). At 24 and 72 h after surgery, animals underwent a battery of behavioral tests, including the modified Garcia neuroscore (Neuroscore), corner turn test (CTT), forelimb placing test (FPT), wire hang task (WHT) and beam walking (BW). Brain edema was evaluated via the wet weight/dry weight method. Intrastriatal injection of autologous blood or bacterial collagenase resulted in a significant increase in brain water content and associated sensorimotor deficits (p<0.05). A significant correlation between brain edema and sensorimotor deficits was observed for all behavioral tests except for WHT and BW. Based on these findings, we recommend implementing the Neuroscore, CTT and/or FPT in preclinical studies of unilateral ICH in mice. PMID:24518201

  6. Correlation of CD34+ cells with tissue angiogenesis after traumatic brain injury in a rat model.

    PubMed

    Guo, Xinbin; Liu, Li; Zhang, Ming; Bergeron, Angela; Cui, Zhuang; Dong, Jing-Fei; Zhang, Jianning

    2009-08-01

    Increasing evidence suggests that circulating endothelial progenitor cells, which are a subpopulation of hematopoietic progenitor CD34(+) cells, play a critical role in neovascularization and tissue repair. We have tested the hypothesis that traumatic brain injury (TBI) could mobilize CD34(+) cells to peripheral blood and brain tissue, a process critical for vascular repair, in a rat model of TBI. Male Wistar rats were subjected to controlled fluid percussion. Blood and brain tissue were collected before and after TBI to measure the levels of CD34(+) cells in peripheral blood and to detect their accumulation in the damaged cerebral tissue. Compared with surgery controls, CD34(+) cells significantly increased in the peripheral blood and accumulated in the brain tissue of TBI rats. Immunohistochemistry detected new vessels with incomplete CD34(+) endothelial-like cell lining and an increased number of microvessels in the injured and surrounding tissue. The results demonstrate a close correlation between an increase in circulating CD34(+) cells in response to traumatic injury and angiogenesis in TBI rat brain. They also suggest that transplantation of CD34(+) cells or augmentation of endogenous CD34(+) cells may be a novel therapeutic approach for patients with TBI. PMID:19226208

  7. Estimating passive mechanical properties in a myocardial infarction using MRI and finite element simulations.

    PubMed

    Mojsejenko, Dimitri; McGarvey, Jeremy R; Dorsey, Shauna M; Gorman, Joseph H; Burdick, Jason A; Pilla, James J; Gorman, Robert C; Wenk, Jonathan F

    2015-06-01

    Myocardial infarction (MI) triggers a series of maladaptive events that lead to structural and functional changes in the left ventricle. It is crucial to better understand the progression of adverse remodeling, in order to develop effective treatment. In addition, being able to assess changes in vivo would be a powerful tool in the clinic. The goal of the current study is to quantify the in vivo material properties of infarcted and remote myocardium 1 week after MI, as well as the orientation of collagen fibers in the infarct. This will be accomplished by using a combination of magnetic resonance imaging (MRI), catheterization, finite element modeling, and numerical optimization to analyze a porcine model ([Formula: see text]) of posterolateral myocardial infarction. Specifically, properties will be determined by minimizing the difference between in vivo strains and volume calculated from MRI and finite element model predicted strains and volume. The results indicate that the infarct region is stiffer than the remote region and that the infarct collagen fibers become more circumferentially oriented 1 week post-MI. These findings are consistent with previous studies, which employed ex vivo techniques. The proposed methodology will ultimately provide a means of predicting remote and infarct mechanical properties in vivo at any time point post-MI. PMID:25315521

  8. Automatic segmentation of brain MR images using an adaptive balloon snake model with fuzzy classification.

    PubMed

    Liu, Hung-Ting; Sheu, Tony W H; Chang, Herng-Hua

    2013-10-01

    Skull-stripping in magnetic resonance (MR) images is one of the most important preprocessing steps in medical image analysis. We propose a hybrid skull-stripping algorithm based on an adaptive balloon snake (ABS) model. The proposed framework consists of two phases: first, the fuzzy possibilistic c-means (FPCM) is used for pixel clustering, which provides a labeled image associated with a clean and clear brain boundary. At the second stage, a contour is initialized outside the brain surface based on the FPCM result and evolves under the guidance of an adaptive balloon snake model. The model is designed to drive the contour in the inward normal direction to capture the brain boundary. The entire volume is segmented from the center slice toward both ends slice by slice. Our ABS algorithm was applied to numerous brain MR image data sets and compared with several state-of-the-art methods. Four similarity metrics were used to evaluate the performance of the proposed technique. Experimental results indicated that our method produced accurate segmentation results with higher conformity scores. The effectiveness of the ABS algorithm makes it a promising and potential tool in a wide variety of skull-stripping applications and studies. PMID:23744446

  9. Differences in amyloid-? clearance across mouse and human blood-brain barrier models: Kinetic analysis and mechanistic modeling

    PubMed Central

    Qosa, Hisham; Abuasal, Bilal S.; Romero, Ignacio A.; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N.; Kaddoumi, Amal

    2014-01-01

    Alzheimer’s disease (AD) has a characteristic hallmark of amyloid-? (A?) accumulation in the brain. This accumulation of A? has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate A? clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient A? clearance. However, the contribution of each process to A? clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect A? clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to A? clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected 125I-A?40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare A? clearance between mouse and human BBB models. Kinetic studies for A?40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of 125I-A?40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of 125I-A?40 and the rate of each process. Established mechanistic model suggested significantly higher rates of A? uptake and degradation in bEnd3 cells as rationale for the observed differences in 125I-A?40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of A? from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to A? clearance and offer, for the first time, a mathematical model that describes A? clearance across BBB. PMID:24467845

  10. The interaction of carbon nanotubes with an in vitro blood-brain barrier model and mouse brain in vivo

    PubMed Central

    Kafa, Houmam; Wang, Julie Tzu-Wen; Rubio, Noelia; Venner, Kerrie; Anderson, Glenn; Pach, Elzbieta; Ballesteros, Belén; Preston, Jane E.; Abbott, N. Joan; Al-Jamal, Khuloud T.

    2015-01-01

    Carbon nanotubes (CNTs) are a novel nanocarriers with interesting physical and chemical properties. Here we investigate the ability of amino-functionalized multi-walled carbon nanotubes (MWNTs-NH3+) to cross the Blood-Brain Barrier (BBB) in vitro using a co-culture BBB model comprising primary porcine brain endothelial cells (PBEC) and primary rat astrocytes, and in vivo following a systemic administration of radiolabelled f-MWNTs. Transmission Electron microscopy (TEM) confirmed that MWNTs-NH3+ crossed the PBEC monolayer via energy-dependent transcytosis. MWNTs-NH3+ were observed within endocytic vesicles and multi-vesicular bodies after 4 and 24 h. A complete crossing of the in vitro BBB model was observed after 48 h, which was further confirmed by the presence of MWNTs-NH3+ within the astrocytes. MWNT-NH3+ that crossed the PBEC layer was quantitatively assessed using radioactive tracers. A maximum transport of 13.0 ± 1.1% after 72 h was achieved using the co-culture model. f-MWNT exhibited significant brain uptake (1.1  ±  0.3% injected dose/g) at 5 min after intravenous injection in mice, after whole body perfusion with heparinized saline. Capillary depletion confirmed presence of f-MWNT in both brain capillaries and parenchyma fractions. These results could pave the way for use of CNTs as nanocarriers for delivery of drugs and biologics to the brain, after systemic administration. PMID:25890741

  11. Effects of progesterone administration on infarct volume and functional deficits following permanent focal cerebral ischemia in rats.

    PubMed

    Ishrat, Tauheed; Sayeed, Iqbal; Atif, Fahim; Stein, Donald G

    2009-02-27

    Recent experimental evidence indicates that progesterone (PROG) protects against various models of brain injury, including ischemic stroke. Most human studies of pharmacologic treatments for acute cerebral stroke have failed despite initial success in animal models. To simulate better the typical human stroke without reperfusion, the present study was conducted to examine the efficacy of PROG on infarct volume and functional outcome in a permanent model of stroke, using direct cauterization of the middle cerebral artery (MCA). Twenty-four male adult Sprague-Dawley rats underwent pMCAO by electro-coagulation and sham operation. After induction of permanent MCA occlusion (pMCAO), the rats received an initial intraperitoneal injection of PROG (8 mg/kg) or vehicle at 1 h post-occlusion followed by subcutaneous injections at 6, 24 and 48 h. Functional deficits were tested on the rotarod and grip-strength meter at 24, 48 and 72 h after pMCAO. The rats were killed 72 h after surgery and isolated brain was sectioned into coronal slices and stained with 2, 3, 5-triphenyltetrazolium chloride (TTC). PROG-treated rats showed a substantial reduction (54.05%) in the volume of the infarct (% contralateral hemisphere) compared to vehicle controls. In addition there was a significant improvement in ability to remain on an accelerating rotarod and increased grip strength observed in the pMCAO rats treated with PROG compared to vehicle. Taken together, these data indicate that PROG is beneficial in one of the best-characterized models of stroke, and may warrant further testing in future clinical trials for human stroke. PMID:19135987

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

    E-print Network

    Shahmirzadi, Danial

    2005-11-01

    Page 1 Anatomical view of the Brain Limbic System ????????????... 11 2 Connections of Amygdala with other components of the Limbic System ??. 11 3 Block Diagram of the Simplified Limbic Model (BEL) ????????? 17 4 Sensory (upper) and Emotional (lower...) signals for ACQ 1 experiment ??? 22 5 Model output in ACQ 1 experiment ????????????????... 22 6 Amygdala (upper) and Orbitofrontal Cortex (lower) learning through ACQ 1 experiment ??????????????????????????.. 23 7 Sensory (upper) and Emotional...

  13. Human and Rat Glioma Growth, Invasion, and Vascularization in a Novel Chick Embryo Brain Tumor Model

    Microsoft Academic Search

    Alexandra Cretu; Joseph S. Fotos; Brian W. Little; Deni S. Galileo

    2005-01-01

    The mechanisms that control the insidiously invasive nature of malignant gliomas are poorly understood, and their study would\\u000a be facilitated by an in vivo model that is easy to manipulate and inexpensive. The developing chick embryo brain was assessed as a new xenograft model\\u000a for the production, growth, and study of human and rat glioma cell lines. Three established glioma

  14. Sampling DTI fibers in the human brain based on DWI forward modeling

    Microsoft Academic Search

    Song Zhang; David H. Laidlaw

    2006-01-01

    We present a forward-modeling-based sampling of diffusion-tensor imaging (DTI) integral curves. This work has the potential to generate accurate brain neural fiber models that fit the data well with an economic number of curves. DTI integral curves are integrated from the first eigenvector field of the DTI field. Usually the seed points are generated randomly or from a regular grid

  15. Rat brain tumor models to assess the efficacy of boron neutron capture therapy: a critical evaluation

    Microsoft Academic Search

    Rolf F. Barth; Weilian Yang; Jeffrey A. Coderre

    2003-01-01

    Summary  Development of any therapeutic modality can be facilitated by the use of the appropriate animal models to assess its efficacy.\\u000a This report primarily will focus on our studies using the F98 and 9L rat glioma models to evaluate the effectiveness of boron\\u000a neutron capture therapy (BNCT) of brain tumors. Following intracerebral implantation the biological behavior of each tumor\\u000a resembles that

  16. Blood-brain barrier in vitro model: A tissue engineering approach and validation

    Microsoft Academic Search

    Zhiqi Zhang

    2010-01-01

    This dissertation evaluated the feasibility of using commercially available immortalized cell lines in building a tissue engineered in vitro blood-brain barrier (BBB) co-culture model for preliminary drug development studies. Mouse endothelial cell line and rat astrocyte cell lines purchased from American Type Culture Collections (ATCC) were the building blocks of the co-culture model. An astrocyte derived acellular extracellular matrix (aECM)

  17. Blood-Brain Barrier in vitro Model: A Tissue Engineering Approach and Validation

    Microsoft Academic Search

    Zhiqi Zhang

    2010-01-01

    This dissertation evaluated the feasibility of using commercially available immortalized cell lines in building a tissue engineered in vitro blood-brain barrier (BBB) co-culture model for preliminary drug development studies. Mouse endothelial cell line and rat astrocyte cell lines purchased from American Type Culture Collections (ATCC) were the building blocks of the co-culture model. An astrocyte derived acellular extracellular matrix (aECM)

  18. The mathematical research for the Kuramoto model of the describing neuronal synchrony in the brain

    Microsoft Academic Search

    Chang Lin; Mai-Mai Lin

    2009-01-01

    The Kuramoto model of the describing neuronal synchrony is mathematically investigated in the brain. A general analytical solutions (the most sententious description) for the Kuramoto model, incorporating the inclusion of a Ki,j(t) term to represent time-varying coupling strengths, have been obtained by using the precise mathematical approach. We derive an exact analytical expression, opening out the connotative and latent linear

  19. Concise Review: Are Stimulated Somatic Cells Truly Reprogrammed into an ES/iPS-Like Pluripotent State? Better Understanding by Ischemia-Induced Multipotent Stem Cells in a Mouse Model of Cerebral Infarction

    PubMed Central

    Nakagomi, Takayuki; Nakano-Doi, Akiko; Narita, Aya; Matsuyama, Tomohiro

    2015-01-01

    Following the discovery of pluripotent stem (PS) cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells, there has been a great hope that injured tissues can be repaired by transplantation of ES/iPS-derived various specific types of cells such as neural stem cells (NSCs). Although PS cells can be induced by ectopic expression of Yamanaka's factors, it is known that several stimuli such as ischemia/hypoxia can increase the stemness of somatic cells via reprogramming. This suggests that endogenous somatic cells acquire stemness during natural regenerative processes following injury. In this study, we describe whether somatic cells are converted into pluripotent stem cells by pathological stimuli without ectopic expression of reprogramming factors based on the findings of ischemia-induced multipotent stem cells in a mouse model of cerebral infarction. PMID:25945100

  20. Ex vivo molecular rejuvenation improves the therapeutic activity of senescent human cardiac stem cells in a mouse model of myocardial infarction.

    PubMed

    Avolio, Elisa; Gianfranceschi, Giuseppe; Cesselli, Daniela; Caragnano, Angela; Athanasakis, Emmanouil; Katare, Rajesh; Meloni, Marco; Palma, Anita; Barchiesi, Arianna; Vascotto, Carlo; Toffoletto, Barbara; Mazzega, Elisa; Finato, Nicoletta; Aresu, Giuseppe; Livi, Ugolino; Emanueli, Costanza; Scoles, Giacinto; Beltrami, Carlo Alberto; Madeddu, Paolo; Beltrami, Antonio Paolo

    2014-09-01

    Cardiac stem cells (CSC) from explanted decompensated hearts (E-CSC) are, with respect to those obtained from healthy donors (D-CSC), senescent and functionally impaired. We aimed to identify alterations in signaling pathways that are associated with CSC senescence. Additionally, we investigated if pharmacological modulation of altered pathways can reduce CSC senescence in vitro and enhance their reparative ability in vivo. Measurement of secreted factors showed that E-CSC release larger amounts of proinflammatory cytokine IL1? compared with D-CSC. Using blocking antibodies, we verified that IL1? hampers the paracrine protective action of E-CSC on cardiomyocyte viability. IL1? acts intracranially inducing IKK? signaling, a mechanism that via nuclear factor-?B upregulates the expression of IL1? itself. Moreover, E-CSC show reduced levels of AMP protein kinase (AMPK) activating phosphorylation. This latter event, together with enhanced IKK? signaling, increases TORC1 activity, thereby impairing the autophagic flux and inhibiting the phosphorylation of Akt and cAMP response element-binding protein. The combined use of rapamycin and resveratrol enhanced AMPK, thereby restoring downstream signaling and reducing IL1? secretion. These molecular corrections reduced E-CSC senescence, re-establishing their protective activity on cardiomyocytes. Moreover ex vivo treatment with rapamycin and resveratrol improved E-CSC capacity to induce cardiac repair upon injection in the mouse infarcted heart, leading to reduced cardiomyocyte senescence and apoptosis and increased abundance of endogenous c-Kit(+) CSC in the peri-infarct area. Molecular rejuvenation of patient-derived CSC by short pharmacologic conditioning boosts their in vivo reparative abilities. This approach might prove useful for refinement of CSC-based therapies. PMID:24801508

  1. Activation of peripheral delta opioid receptors eliminates cardiac electrical instability in a rat model of post-infarction cardiosclerosis via mitochondrial ATP-dependent K+ channels.

    PubMed

    Maslov, L N; Lishmanov, Yu B; Solenkova, N V; Gross, G J; Stefano, G B; Tam, S W

    2003-07-01

    The effects of the selective delta-1 (delta(1)) opioid receptor agonist, DPDPE, and the selective delta(2) opioid receptor agonist, DSLET, have been studied on the ventricular fibrillation threshold (VFT) in rats with an experimental post-infarction cardiosclerosis (CS). It has been found that CS induced a significant decrease in VFT. This CS-induced decrease in VFT was significantly reversed by intravenous administration of DPDPE (0.1 mg/kg) 10 min before VFT measurement. On the contrary, intravenous injection of DSLET (0.5 mg/kg) exacerbated the CS-induced cardiac electrical instability. Pretreatment with the selective delta opioid receptor antagonist, ICI 174,864 (0.5 mg/kg), completely abolished the changes in VFT produced by both DPDPE and DSLET. Previous administration of a nonselective peripherally acting opioid receptor antagonist, naloxone methiodide (5 mg/kg) also completely reversed the antifibrillatory action of DPDPE. Naloxone methiodide and ICI 174,864 alone had no effect on VFT. Pretreatment with the nonselective K(ATP) channel blocker, glibenclamide (0.3 mg/kg), or with the mitochondrial selective K(ATP) channel blocker, 5-hydroxydecanoic acid (5-HD, 5 mg/kg), completely abolished the DPDPE-induced increase in cardiac electrical stability. Glibenclamide and 5-HD alone had no effect on VFT. These results demonstrate that the delta opioid receptor plays an important role in the regulation of electrical stability in rats with post-infarction cardiosclerosis. We propose that peripheral delta(1) opioid receptor stimulation reverses CS-induced electrical instability via mitochondrial K(ATP) channels. On the contrary, delta(2) opioid receptor stimulation may exacerbate the CS-induced decrease in VFT. Further studies are necessary to determine the delta opioid receptor subtype which mediates the antifibrillatory effect of DPDPE and pro-fibrillatory effect of DSLET. PMID:12798419

  2. Neuropeptides and the social brain: potential rodent models of autism

    Microsoft Academic Search

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

    2005-01-01

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

  3. A Novel Brain Neurovascular Unit Model with Neurons, Astrocytes and Microvascular Endothelial Cells of Rat

    PubMed Central

    Xue, Qiang; Liu, Yang; Qi, Hongyi; Ma, Qiang; Xu, Ling; Chen, Weihai; Chen, Gang; Xu, Xiaoyu

    2013-01-01

    A novel triple cell neurovascular unit (NVU) model co-culturing with neurons, brain microvascular endothelial cells (BMECs) and astrocytes was established in this study for investigating the cerebral diseases and screening the candidates of therapeutic drug. We have first performed the cell identification and morphological characterization, analyzed the specific protein expression and determined the blood-brain barrier (BBB) function of the co-culture model under normal condition. Then, we further determined the BBB function, inflammation, cell injury and the variation of neuroprotective factor in this model after anoxia-reoxygenation. The results suggest that this model exhibited a better BBB function and significantly increased expression of P-glycoprotein (Pg-P) and ZO-1 compared with BMECs only or co-culture with astrocytes or neurons. After anoxia-reoxygenation, the pathological changes of this model were basically resemblance to the pathological changes of brain cells and BBB in vivo. And nimodipine, an antagonist of calcium, could reverse those changes as well. According to our observations, we deduce that this triple cell co-culture model exhibits the basic structure, function and cell-cell interaction of NVU, which may offer a more proper in vitro system of NVU for the further investigation of cerebral diseases and drug screening. PMID:23412420

  4. Characterization of a novel rat model of penetrating traumatic brain injury.

    PubMed

    Plantman, Stefan; Ng, Kian Chye; Lu, Jia; Davidsson, Johan; Risling, Mårten

    2012-04-10

    A penetrating traumatic brain injury (pTBI) occurs when an object impacts the head with sufficient force to penetrate the skin, skull, and meninges, and inflict injury directly to the brain parenchyma. This type of injury has been notoriously difficult to model in small laboratory animals such as rats or mice. To this end, we have established a novel non-fatal model for pTBI based on a modified air rifle that accelerates a pellet, which in turn impacts a small probe that then causes the injury to the experimental animal's brain. In the present study, we have focused on the acute phase and characterized the tissue destruction, including increasing cavity formation, white matter degeneration, hemorrhage, edema, and gliosis. We also used a battery of behavioral models to examine the neurological outcome, with the most noteworthy finding being impairment of reference memory function. In conclusion, we have described a number of events taking place after pTBI in our model. We expect this model will prove useful in our efforts to unravel the biological events underlying injury and regeneration after pTBI and possibly serve as a useful animal model in the development of novel therapeutic and diagnostic approaches. PMID:22181060

  5. Modeling the variability in brain morphology and lesion distribution in multiple sclerosis by deep learning.

    PubMed

    Brosch, Tom; Yoo, Youngjin; Li, David K B; Traboulsee, Anthony; Tam, Roger

    2014-01-01

    Changes in brain morphology and white matter lesions are two hallmarks of multiple sclerosis (MS) pathology, but their variability beyond volumetrics is poorly characterized. To further our understanding of complex MS pathology, we aim to build a statistical model of brain images that can automatically discover spatial patterns of variability in brain morphology and lesion distribution. We propose building such a model using a deep belief network (DBN), a layered network whose parameters can be learned from training images. In contrast to other manifold learning algorithms, the DBN approach does not require a prebuilt proximity graph, which is particularly advantageous for modeling lesions, because their sparse and random nature makes defining a suitable distance measure between lesion images challenging. Our model consists of a morphology DBN, a lesion DBN, and a joint DBN that models concurring morphological and lesion patterns. Our results show that this model can automatically discover the classic patterns of MS pathology, as well as more subtle ones, and that the parameters computed have strong relationships to MS clinical scores. PMID:25485412

  6. Genetics of premature myocardial infarction

    Microsoft Academic Search

    Robert Roberts

    2008-01-01

    Common multigene disorders account for 80% of deaths in the world and all have significant genetic predisposition. Coronary\\u000a artery disease and myocardial infarction (MI) account for more than 40% of these deaths. The genetic component is due to multiple\\u000a genes, each contributing only minimally to the phenotype. Linkage analysis, which has been successful in identifying rare\\u000a disorders that cause MI,

  7. Magnetic Resonance Imaging Criteria for Thrombolysis in Hyperacute Cerebral Infarction

    PubMed Central

    AHMETGJEKAJ, ILIR; KABASHI-MUÇAJ, SERBEZE; LASCU, LUANA CORINA; KABASHI, ANTIGONA; BONDARI, A.; BONDARI, SIMONA; DEDUSHI-HOTI, KRESHNIKE; BIÇAKU, ARDIAN; SHATRI, JETON

    2014-01-01

    Purpose: Selection of patients with cerebral infarction for MRI that is suitable for thrombolytic therapy as an emerging application. Although the efficiency of the therapy with i.v. tissue plasminogen activator (tPA) within 3 hours after onset of symptoms has been proven in selected patients with CT, now these criteria are determined by MRI, as the data we gather are fast and accurate in the first hours. Material and methods: MRI screening in patients with acute cerebral infarction before application of thrombolytic therapy was done in a UCC Mannheim in Germany. Unlike trials with CT, MRI studies demonstrated the benefits of therapy up to 6 hours after the onset of symptoms. We studied 21 patients hospitalized in Clinic of Neuroradiology at University Clinical Centre in Mannheim-Germany. They all undergo brain MRI evaluation for stroke. This article reviews literature that has followed application of thrombolysis in patients with cerebral infarction based on MRI. Results: We have analyzed the MRI criteria for i.v. application of tPA at this University Centre. Alongside the personal viewpoints of clinicians, survey reveals a variety of clinical aspects and MRI features that are opened for further more exploration: therapeutic effects, the use of the MRI angiography, dynamics, and other. Conclusions: MRI is a tested imaging method for rapid evaluation of patients with hyperacute cerebral infarction, replacing the use of CT imaging and clinical features. MRI criteria for thrombolytic therapy are being applied in some cerebral vascular centres. In Kosovo, the application of thrombolytic therapy has not started yet. PMID:25729591

  8. Random-Walk Model of Diffusion in Three Dimensions in Brain Extracellular Space: Comparison with Microfiberoptic Photobleaching Measurements

    PubMed Central

    Jin, Songwan; Zador, Zsolt; Verkman, A. S.

    2008-01-01

    Diffusion through the extracellular space (ECS) in brain is important in drug delivery, intercellular communication, and extracellular ionic buffering. The ECS comprises ?20% of brain parenchymal volume and contains cell-cell gaps ?50 nm. We developed a random-walk model to simulate macromolecule diffusion in brain ECS in three dimensions using realistic ECS dimensions. Model inputs included ECS volume fraction (?), cell size, cell-cell gap geometry, intercellular lake (expanded regions of brain ECS) dimensions, and molecular size of the diffusing solute. Model output was relative solute diffusion in water versus brain ECS (Do/D). Experimental Do/D for comparison with model predictions was measured using a microfiberoptic fluorescence photobleaching method involving stereotaxic insertion of a micron-size optical fiber into mouse brain. Do/D for the small solute calcein in different regions of brain was in the range 3.0–4.1, and increased with brain cell swelling after water intoxication. Do/D also increased with increasing size of the diffusing solute, particularly in deep brain nuclei. Simulations of measured Do/D using realistic ?, cell size and cell-cell gap required the presence of intercellular lakes at multicell contact points, and the contact length of cell-cell gaps to be least 50-fold smaller than cell size. The model accurately predicted Do/D for different solute sizes. Also, the modeling showed unanticipated effects on Do/D of changing ECS and cell dimensions that implicated solute trapping by lakes. Our model establishes the geometric constraints to account quantitatively for the relatively modest slowing of solute and macromolecule diffusion in brain ECS. PMID:18469079

  9. Progressive Brain Damage, Synaptic Reorganization and NMDA Activation in a Model of Epileptogenic Cortical Dysplasia

    PubMed Central

    Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano

    2014-01-01

    Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity. PMID:24587109

  10. WONOEP APPRAISAL: NEW SYSTEMIC FUNCTIONAL IMAGING TECHNOLOGIES TO STUDY THE BRAIN IN EXPERIMENTAL MODELS OF EPILEPSY

    PubMed Central

    Dedeurwaerdere, Stefanie; Shultz, Sandy R.; Federico, Paolo; Engel, Jerome

    2014-01-01

    Summary Objectives Modern functional neuroimaging provides opportunities to visualize activity of the entire brain, making it an indispensable diagnostic tool for epilepsy. Various forms of non-invasive functional neuroimaging are now also being performed as research tools in animal models of epilepsy and provide opportunities for parallel animal/human investigations into fundamental mechanisms of epilepsy and identification of epilepsy biomarkers. Methods Recent animal studies of epilepsy using positron emission tomography, tractography, and functional magnetic resonance imaging were reviewed. Results Epilepsy is an abnormal emergent property of disturbances in neuronal networks which, even for epilepsies characterized by focal seizures, involve widely distributed systems, often in both hemispheres. Functional neuroimaging in animal models now provides opportunities to examine neuronal disturbances in the whole brain that underlie generalized and focal seizure generation as well as various types of epileptogenesis. Significance Tremendous advances in understanding the contribution of specific properties of widely distributed neuronal networks to both normal and abnormal human behavior have been provided by current functional neuroimaging methodologies. Successful application of functional neuroimaging of the whole brain in the animal laboratory now permits investigations during epileptogenesis and correlation with deep brain EEG activity. With the continuing development of these techniques and analytical methods, the potential for future translational research on epilepsy is enormous. PMID:24836499

  11. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer’s disease

    PubMed Central

    Bajo, R.; Pusil, S.; López, M. E.; Canuet, L.; Pereda, E.; Osipova, D.; Maestú, F.; Pekkonen, E.

    2015-01-01

    Scopolamine administration may be considered as a psychopharmacological model of Alzheimer’s disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD. PMID:26130273

  12. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer's disease.

    PubMed

    Bajo, R; Pusil, S; López, M E; Canuet, L; Pereda, E; Osipova, D; Maestú, F; Pekkonen, E

    2015-01-01

    Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD. PMID:26130273

  13. Development of a skull/brain model for military wound ballistics studies.

    PubMed

    Carr, Debra; Lindstrom, Anne-Christine; Jareborg, Andreas; Champion, Stephen; Waddell, Neil; Miller, David; Teagle, Michael; Horsfall, Ian; Kieser, Jules

    2015-05-01

    Reports on penetrating ballistic head injuries in the literature are dominated by case studies of suicides; the penetrating ammunition usually being .22 rimfire or shotgun. The dominating cause of injuries in modern warfare is fragmentation and hence, this is the primary threat that military helmets protect the brain from. When helmets are perforated, this is usually by bullets. In combat, 20% of penetrating injuries occur to the head and its wounding accounts for 50% of combat deaths. A number of head simulants are described in the academic literature, in ballistic test methods for helmets (including measurement of behind helmet blunt trauma, BHBT) and in the 'open' and 'closed' government literature of several nations. The majority of these models are not anatomically correct and are not assessed with high-velocity rifle ammunition. In this article, an anatomically correct 'skull' (manufactured from polyurethane) and 'brain' (manufactured from 10%, by mass, gelatine) model for use in military wound ballistic studies is described. Filling the cranium completely with gelatine resulted in a similar 'skull' fracture pattern as an anatomically correct 'brain' combined with a representation of cerebrospinal fluid. In particular, posterior cranial fossa and occipital fractures and brain ejection were observed. This pattern of injury compared favourably to reported case studies of actual incidents in the literature. PMID:25194710

  14. Traumatic brain injury caused by laser-induced shock wave in rats: a novel laboratory model for studying blast-induced traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Hatano, Ben; Matsumoto, Yoshihisa; Otani, Naoki; Saitoh, Daizoh; Tokuno, Shinichi; Satoh, Yasushi; Nawashiro, Hiroshi; Matsushita, Yoshitaro; Sato, Shunichi

    2011-03-01

    The detailed mechanism of blast-induced traumatic brain injury (bTBI) has not been revealed yet. Thus, reliable laboratory animal models for bTBI are needed to investigate the possible diagnosis and treatment for bTBI. In this study, we used laser-induced shock wave (LISW) to induce TBI in rats and investigated the histopathological similarities to actual bTBI. After craniotomy, the rat brain was exposed to a single shot of LISW with a diameter of 3 mm at various laser fluences. At 24 h after LISW exposure, perfusion fixation was performed and the extracted brain was sectioned; the sections were stained with hematoxylin-eosin. Evans blue (EB) staining was also used to evaluate disruption of the blood brain barrier. At certain laser fluence levels, neural cell injury and hemorrhagic lesions were observed in the cortex and subcortical region. However, injury was limited in the tissue region that interacted with the LISW. The severity of injury increased with increasing laser fluence and hence peak pressure of the LISW. Fluorescence originating from EB was diffusively observed in the injuries at high fluence levels. Due to the grade and spatial controllability of injuries and the histological observations similar to those in actual bTBI, brain injuries caused by LISWs would be useful models to study bTBI.

  15. Brain in flames – animal models of psychosis: utility and limitations

    PubMed Central

    Mattei, Daniele; Schweibold, Regina; Wolf, Susanne A

    2015-01-01

    The neurodevelopmental hypothesis of schizophrenia posits that schizophrenia is a psychopathological condition resulting from aberrations in neurodevelopmental processes caused by a combination of environmental and genetic factors which proceed long before the onset of clinical symptoms. Many studies discuss an immunological component in the onset and progression of schizophrenia. We here review studies utilizing animal models of schizophrenia with manipulations of genetic, pharmacologic, and immunological origin. We focus on the immunological component to bridge the studies in terms of evaluation and treatment options of negative, positive, and cognitive symptoms. Throughout the review we link certain aspects of each model to the situation in human schizophrenic patients. In conclusion we suggest a combination of existing models to better represent the human situation. Moreover, we emphasize that animal models represent defined single or multiple symptoms or hallmarks of a given disease.

  16. Allostasis and the human brain: Integrating models of stress from the social and life sciences

    PubMed Central

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

    2009-01-01

    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 the neural focus of “wear and tear” due to ongoing adaptation. This mediation, in turn, allows us to model the interplay over time between context, current stressor exposure, internal regulation of bodily processes, and health outcomes. We illustrate how this approach facilitates the integration of current findings in human neuroscience and genetics with key constructs from stress models from the social and life sciences, with implications for future research and the design of interventions targeting individuals at risk. PMID:20063966

  17. Evaluation of an intraoperative ultrasound training model based on a cadaveric sheep brain

    PubMed Central

    Vavruska, Jan; Buhl, Ralf; Petridis, Athanasios K.; Maslehaty, Homajoun; Scholz, Martin

    2014-01-01

    Background: The present study evaluates the effectiveness of an ultrasound (US) practice course based on a sheep brain cadaver. Neurosurgical education is considerably restrained following patient safety objections and work time restrictions. It is therefore of vital importance to offer residents an opportunity to practice certain US techniques in a controlled environment without ethical or legal restrictions. We developed an US training model based on a sheep brain cadaver in order to demonstrate the feasibility of such a model, facilitate crucial anatomic knowledge, and demonstrate a learning curve from it. Methods: Over the course of 2 months from December 2012-January 2013, a total of 13 residents took part in a three part training session, each consisting of 20-30 min of individual US-training and performance evaluation based on a biological phantom. The first cadaver was a physiologic sheep brain. After initial familiarization with the US, the residents performed an US on a second cadaveric brain and tried to find a 0.5 cm big (in diameter) echogenic structure. In a third brain they were asked to identify a cyst (Fogarty catheter filled with water). Results: Thirteen neurosurgical residents participated in the study. After the first training session, the learning curve improved significantly in the second and the third session. The ability to actuate the US device, the time needed to display crucial anatomic landmarks, and to locate the two different artificial masses increased, and respectively decreased remarkably by up to 80%. Conclusion: After 2 months and three training sessions, the handling of the US from the residents was excellent in the operating room. The accuracy and the dexterity in use of the US improved significantly. The participants found the model to be realistic and agreed on the need for further promotion of such courses. PMID:24818053

  18. Transport of treosulfan and temozolomide across an in-vitro blood-brain barrier model.

    PubMed

    Linz, Ute; Hupert, Michelle; Santiago-Schübel, Beatrix; Wien, Sascha; Stab, Julia; Wagner, Sylvia

    2015-08-01

    In vitro, treosulfan (TREO) has shown high effectiveness against malignant gliomas. However, a first clinical trial for newly diagnosed glioblastoma did not show any positive effect. Even though dosing and timing might have been the reasons for this failure, it might also be that TREO does not reach the brain in sufficient amount. Surprisingly, there are no published data on TREO uptake into the brain of patients, despite extensive research on this compound. An in-vitro blood-brain barrier (BBB) model consisting of primary porcine brain capillary endothelial cells was used to determine the transport of TREO across the cell monolayer. Temozolomide (TMZ), the most widely used cytotoxic drug for malignant gliomas, served as a reference. An HPLC-ESI-MS/MS procedure was developed to detect TREO and TMZ in cell culture medium. Parallel to the experimental approach, the permeability of TREO and the reference substance across the in-vitro BBB was estimated on the basis of their physicochemical properties. The detection limit was 30?nmol/l for TREO and 10?nmol/l for TMZ. Drug transport was measured in two directions: influx, apical-to-basolateral (A-to-B), and efflux, basolateral-to-apical (B-to-A). For TREO, the A-to-B permeability was lower (1.6%) than the B-to-A permeability (3.0%). This was in contrast to TMZ, which had higher A-to-B (13.1%) than B-to-A (7.2%) permeability values. The in-vitro BBB model applied simulated the human BBB properly for TMZ. It is, therefore, reasonable to assume that the values for TREO are also meaningful. Considering the lack of noninvasive, significant alternative methods to study transport across the BBB, the porcine brain capillary endothelial cell model was efficient to collect first data for TREO that explain the disappointing clinical results for this drug against cerebral tumors. PMID:25919318

  19. Application of radiosurgical techniques to produce a primate model of brain lesions

    PubMed Central

    Kunimatsu, Jun; Miyamoto, Naoki; Ishikawa, Masayori; Shirato, Hiroki; Tanaka, Masaki

    2015-01-01

    Behavioral analysis of subjects with discrete brain lesions provides important information about the mechanisms of various brain functions. However, it is generally difficult to experimentally produce discrete lesions in deep brain structures. Here we show that a radiosurgical technique, which is used as an alternative treatment for brain tumors and vascular malformations, is applicable to create non-invasive lesions in experimental animals for the research in systems neuroscience. We delivered highly focused radiation (130–150 Gy at ISO center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear accelerator (LINAC). The effects of irradiation were assessed by analyzing oculomotor performance along with magnetic resonance (MR) images before and up to 8 months following irradiation. In parallel with tissue edema indicated by MR images, deficits in saccadic and smooth pursuit eye movements were observed during several days following irradiation. Although initial signs of oculomotor deficits disappeared within a month, damage to the tissue and impaired eye movements gradually developed during the course of the subsequent 6 months. Postmortem histological examinations showed necrosis and hemorrhages within a large area of the white matter and, to a lesser extent, in the adjacent gray matter, which was centered at the irradiated target. These results indicated that the LINAC system was useful for making brain lesions in experimental animals, while the suitable radiation parameters to generate more focused lesions need to be further explored. We propose the use of a radiosurgical technique for establishing animal models of brain lesions, and discuss the possible uses of this technique for functional neurosurgical treatments in humans. PMID:25964746

  20. Bilateral adrenal infarction in Crohn's disease

    PubMed Central

    Khandelwal, Ashish; Krishna, J. Sateesh; Khandelwal, Kanika; Virmani, Vivek; Ryan, John

    2013-01-01

    Adrenal infarction is an uncommon cause of adrenal insufficiency. We herein present unique occurrence of bilateral adrenal infarction detected on imaging in a young female with known history of Crohn's disease. The patient responded well to steroids and is on follow up. To our knowledge, this is the first case reported in English literature of adrenal infarct associated with Crohn's disease as extraintestinal manifestation. PMID:24083186

  1. In vivo MRI tracking of exogenous monocytes/macrophages targeting brain tumours in a rat model of glioma

    E-print Network

    Paris-Sud XI, Université de

    1 In vivo MRI tracking of exogenous monocytes/macrophages targeting brain tumours in a rat model and efficiently with large, green-fluorescent, micron-sized particles of iron-oxide (MPIO). Neither size nor. The labelled Mo/Ma were shown to target the brain tumours, a process that could be monitored non invasively

  2. AAV9-mediated erythropoietin gene delivery into the brain protects nigral dopaminergic neurons in a rat model of Parkinson's disease

    Microsoft Academic Search

    Y-Q Xue; B-F Ma; L-R Zhao; J B Tatom; B Li; L-X Jiang; R L Klein; W-M Duan

    2010-01-01

    We have recently shown that intrastriatal injection of recombinant human erythropoietin (EPO) protects dopaminergic (DA) neurons in the substantia nigra (SN) from 6-hydroxydopamine (6-OHDA) toxicity in a rat model of Parkinson's disease. However, systemic administration of EPO did not protect nigral DA neurons, suggesting that the blood–brain barrier limits the passage of EPO protein into the brain. In the present

  3. Murine in vitro model of the blood-brain barrier for evaluating drug transport.

    PubMed

    Shayan, Gilda; Choi, Yong Seok; Shusta, Eric V; Shuler, Michael L; Lee, Kelvin H

    2011-01-18

    In vitro blood-brain barrier (BBB) models help predict brain uptake of potential central nervous system drug candidates. Current in vitro models are composed of brain microvascular endothelial cells (BMEC) that are isolated from rat, bovine, or porcine. However, most in vivo studies on drug transport through the BBB are performed in small laboratory animals, specially mouse and thus murine in vitro BBB models serve as better surrogates to correlate with these studies. Here we describe the functional characterization of a reproducible in vitro model composed of murine BMEC co-cultured with rat primary astrocytes in the presence of biochemical inducing agents. The co-cultures presented high TEER and low sodium fluorescein permeability. Expression of specific BBB tight junction proteins (occludin, claudin-5, ZO-1) and the functionality of transporters (Pgp, GLUT1) were detected by immunocytochemistry and Western blotting. These results indicated a 2.5-fold increase in the expression levels of these proteins in the presence of astrocytes. In addition, a high correlation coefficient (0.98) was obtained between the permeability of a series of hydrophobic and hydrophilic drugs and their corresponding in vivo values. These results together establish the utility of this murine model for future drug transport, pathological, and pharmacological characterizations of the BBB. PMID:21078386

  4. Investigation of the best model to characterize diffuse correlation spectroscopy measurements acquired directly on the brain

    NASA Astrophysics Data System (ADS)

    Verdecchia, K.; Diop, M.; St. Lawrence, K.

    2015-03-01

    Diffuse correlation spectroscopy (DCS) is a non-invasive optical technique capable of monitoring tissue perfusion changes, particularly in the brain. The normalized temporal intensity autocorrelation function generated by DCS is typically characterized by assuming that the movement of erythrocytes can be modeled as a Brownian diffusion-like process instead of the expected random flow model. Carp et al. [Biomedical Optics Express, 2011] proposed a hybrid model, referred to as the hydrodynamic diffusion model, to capture both the random ballistic and diffusive nature of erythrocyte motion. The purpose of this study was to compare how well the Brownian diffusion and the hydrodynamic diffusion models characterized DCS data acquired directly on the brain, avoiding the confounding effects of scalp and skull. Data were acquired from seven pigs during normocapnia (39.9 +/- 0.7 mmHg) and hypocapnia (22.1 +/- 1.6 mmHg) with the DCS fibers placed 7 mm apart, directly on the cerebral cortex. The hydrodynamic diffusion model was found to provide a consistently better fit to the autocorrelation functions compared to the Brownian diffusion model and was less sensitive to the chosen start and end time points used in the fitting. However, the decrease in cerebral blood flow from normocapnia to hypocapnia determined was similar for the two models (-42.6 +/- 8.6 % for the Brownian model and -42.2 +/- 10.2 % for the hydrodynamic model), suggesting that the latter is reasonable for monitoring flow changes.

  5. Cardiac remodeling and physical training post myocardial infarction

    PubMed Central

    Garza, Michael A; Wason, Emily A; Zhang, John Q

    2015-01-01

    After myocardial infarction (MI), the heart undergoes extensive myocardial remodeling through the accumulation of fibrous tissue in both the infarcted and noninfarcted myocardium, which distorts tissue structure, increases tissue stiffness, and accounts for ventricular dysfunction. There is growing clinical consensus that exercise training may beneficially alter the course of post-MI myocardial remodeling and improve cardiac function. This review summarizes the present state of knowledge regarding the effect of post-MI exercise training on infarcted hearts. Due to the degree of difficulty to study a viable human heart at both protein and molecular levels, most of the detailed studies have been performed by using animal models. Although there are some negative reports indicating that post-MI exercise may further cause deterioration of the wounded hearts, a growing body of research from both human and animal experiments demonstrates that post-MI exercise may beneficially alter the course of wound healing and improve cardiac function. Furthermore, the improved function is likely due to exercise training-induced mitigation of renin-angiotensin-aldosterone system, improved balance between matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, favorable myosin heavy chain isoform switch, diminished oxidative stress, enhanced antioxidant capacity, improved mitochondrial calcium handling, and boosted myocardial angiogenesis. Additionally, meta-analyses revealed that exercise-based cardiac rehabilitation has proven to be effective, and remains one of the least expensive therapies for both the prevention and treatment of cardiovascular disease, and prevents re-infarction. PMID:25717353

  6. Fulminant cerebral infarction of anterior and posterior cerebral circulation after ascending type of facial necrotizing fasciitis.

    PubMed

    Lee, Jun Ho; Choi, Hui-Chul; Kim, Chulho; Sohn, Jong Hee; Kim, Heung Cheol

    2014-01-01

    Necrotizing fasciitis is a soft tissue infection that is characterized by extensive necrosis of the subcutaneous fat, neurovascular structures, and fascia. Cerebral infarction after facial necrotizing fasciitis has been rarely reported. A 61-year-old woman with diabetes was admitted with painful swelling of her right cheek. One day later, she was stuporous and quadriplegic. A computed tomographic scan of her face revealed right facial infection in the periorbital soft tissue, parotid, buccal muscle, and maxillary sinusitis. A computed tomographic scan of the brain revealed cerebral infarction in the right hemisphere, left frontal area, and both cerebellum. Four days later, she died from cerebral edema and septic shock. Involvement of the cerebral vasculature, such as the carotid or vertebral artery by necrotizing fasciitis, can cause cerebral infarction. Facial necrotizing fasciitis should be treated early with surgical treatment and the appropriate antibiotic therapy. PMID:22939195

  7. Brain investigation and brain conceptualization

    PubMed Central

    Redolfi, Alberto; Bosco, Paolo; Manset, David; Frisoni, Giovanni B.

    Summary The brain of a patient with Alzheimer’s disease (AD) undergoes changes starting many years before the development of the first clinical symptoms. The recent availability of large prospective datasets makes it possible to create sophisticated brain models of healthy subjects and patients with AD, showing pathophysiological changes occurring over time. However, these models are still inadequate; representations are mainly single-scale and they do not account for the complexity and interdependence of brain changes. Brain changes in AD patients occur at different levels and for different reasons: at the molecular level, changes are due to amyloid deposition; at cellular level, to loss of neuron synapses, and at tissue level, to connectivity disruption. All cause extensive atrophy of the whole brain organ. Initiatives aiming to model the whole human brain have been launched in Europe and the US with the goal of reducing the burden of brain diseases. In this work, we describe a new approach to earlier diagnosis based on a multimodal and multiscale brain concept, built upon existing and well-characterized single modalities. PMID:24139654

  8. A Novel Three-Phase Model of Brain Tissue Microstructure

    E-print Network

    Torquato, Salvatore

    , peptides, neurohormones and molecules of the extracellular matrix (ECM) [2]. Using current imaging-phase models, we explore the previously proposed hypothesis that the extracellular matrix is an important, we support this hypothesis by showing that the incorporation of the extracellular matrix as the third

  9. Foundational model of neuroanatomy: implications for the Human Brain Project.

    PubMed Central

    Martin, R. F.; Mejino, J. L.; Bowden, D. M.; Brinkley, J. F.; Rosse, C.

    2001-01-01

    In order to meet the need for a controlled terminology in neuroinformatics, we have integrated the extensive terminology of NeuroNames into the Foundational Model of anatomy. We illustrate the application of foundational principles for the establishment of an inheritance hierarchy, which accommodates anatomical attributes of neuroanatomical concepts and provides the foundation to which other information may be linked. PMID:11825226

  10. Computational Modeling of High-Level Cognition and Brain Function

    E-print Network

    development of integrative cogni- tive theories. Such theoretical frameworks cannot only integrate many assumptions of the theory and task models. We report one of the first attempts to apply some of the types in Contract grant sponsor: Office of Naval Research; Contract grant number: N00014-96-1-0322; Contract grant

  11. The brain's code and its canonical computational motifs. From sensory cortex to the default mode network: A multi-scale model of brain function in health and disease.

    PubMed

    Turkheimer, Federico E; Leech, Robert; Expert, Paul; Lord, Louis-David; Vernon, Anthony C

    2015-08-01

    A variety of anatomical and physiological evidence suggests that the brain performs computations using motifs that are repeated across species, brain areas, and modalities. The computational architecture of cortex, for example, is very similar from one area to another and the types, arrangements, and connections of cortical neurons are highly stereotyped. This supports the idea that each cortical area conducts calculations using similarly structured neuronal modules: what we term canonical computational motifs. In addition, the remarkable self-similarity of the brain observables at the micro-, meso- and macro-scale further suggests that these motifs are repeated at increasing spatial and temporal scales supporting brain activity from primary motor and sensory processing to higher-level behaviour and cognition. Here, we briefly review the biological bases of canonical brain circuits and the role of inhibitory interneurons in these computational elements. We then elucidate how canonical computational motifs can be repeated across spatial and temporal scales to build a multiplexing information system able to encode and transmit information of increasing complexity. We point to the similarities between the patterns of activation observed in primary sensory cortices by use of electrophysiology and those observed in large scale networks measured with fMRI. We then employ the canonical model of brain function to unify seemingly disparate evidence on the pathophysiology of schizophrenia in a single explanatory framework. We hypothesise that such a framework may also be extended to cover multiple brain disorders which are grounded in dysfunction of GABA interneurons and/or these computational motifs. PMID:25956253

  12. Blast-Associated Shock Waves Result in Increased Brain Vascular Leakage and Elevated ROS Levels in a Rat Model of Traumatic Brain Injury

    PubMed Central

    Petro, Marianne; Dudzinski, Dave; Stewart, Desiree; Courtney, Amy; Courtney, Michael; Labhasetwar, Vinod

    2015-01-01

    Blast-associated shock wave-induced traumatic brain injury (bTBI) remains a persistent risk for armed forces worldwide, yet its detailed pathophysiology remains to be fully investigated. In this study, we have designed and characterized a laboratory-scale shock tube to develop a rodent model of bTBI. Our blast tube, driven by a mixture of oxygen and acetylene, effectively generates blast overpressures of 20–130 psi, with pressure-time profiles similar to those of free-field blast waves. We tested our shock tube for brain injury response to various blast wave conditions in rats. The results show that blast waves cause diffuse vascular brain damage, as determined using a sensitive optical imaging method based on the fluorescence signal of Evans Blue dye extravasation developed in our laboratory. Vascular leakage increased with increasing blast overpressures and mapping of the brain slices for optical signal intensity indicated nonhomogeneous damage to the cerebral vasculature. We confirmed vascular leakage due to disruption in the blood-brain barrier (BBB) integrity following blast exposure. Reactive oxygen species (ROS) levels in the brain also increased with increasing blast pressures and with time post-blast wave exposure. Immunohistochemical analysis of the brain sections analyzed at different time points post blast exposure demonstrated astrocytosis and cell apoptosis, confirming sustained neuronal injury response. The main advantages of our shock-tube design are minimal jet effect and no requirement for specialized equipment or facilities, and effectively generate blast-associated shock waves that are relevant to battle-field conditions. Overall data suggest that increased oxidative stress and BBB disruption could be the crucial factors in the propagation and spread of neuronal degeneration following blast injury. Further studies are required to determine the interplay between increased ROS activity and BBB disruption to develop effective therapeutic strategies that can prevent the resulting cascade of neurodegeneration. PMID:26024446

  13. Silent infarction as a risk factor for overt stroke in children with sickle cell anemia: A report from the Cooperative Study of Sickle Cell Disease

    Microsoft Academic Search

    Scott T. Miller; Eric A. Macklin; Charles H. Pegelow; Thomas R. Kinney; Lynn A. Sleeper; Jacqueline A. Bello; L. Dana DeWitt; Dianne M. Gallagher; Ludovico Guarini; Franklin G. Moser; Kwaku Ohene-Frempong; Nelson Sanchez; Elliott P. Vichinsky; Winfred C. Wang; Doris L. Wethers; Donald P. Younkin; Robert A. Zimmerman; Michael R. DeBaun

    2001-01-01

    Objective: To determine whether children with homozygous sickle cell anemia (SCD) who have silent infarcts on magnetic resonance imaging (MRI) of the brain are at increased risk for overt stroke. Methods: We selected patients with homozygous SCD who (1) enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) before age 6 months, (2) had at least 1 study-mandated brain

  14. A mathematical model of endovascular heat transfer for human brain cooling

    NASA Astrophysics Data System (ADS)

    Salsac, Anne-Virginie; Lasheras, Juan Carlos; Yon, Steven; Magers, Mike; Dobak, John

    2000-11-01

    Selective cooling of the brain has been shown to exhibit protective effects in cerebral ischemia, trauma, and spinal injury/ischemia. A multi-compartment, unsteady thermal model of the response of the human brain to endovascular cooling is discussed and its results compared to recent experimental data conducted with sheep and other mammals. The model formulation is based on the extension of the bioheat equation, originally proposed by Pennes(1) and later modified by Wissler(2), Stolwijk(3) and Werner and Webb(4). The temporal response of the brain temperature and that of the various body compartments to the cooling of the blood flowing through the common carotid artery is calculated under various scenarios. The effect of the boundary conditions as well as the closure assumptions used in the model, i.e. perfusion rate, metabolism heat production, etc. on the cooling rate of the brain are systematically investigated. (1) Pennes H. H., “Analysis of tissue and arterial blood temperature in the resting forearm.” J. Appl. Physiol. 1: 93-122, 1948. (2) Wissler E. H., “Steady-state temperature distribution in man”, J. Appl. Physiol., 16: 764-740, 1961. (3) Stolwick J. A. J., “Mathematical model of thermoregulation” in “Physiological and behavioral temperature regulation”, edited by J. D. Hardy, A. P. Gagge and A. J. Stolwijk, Charles C. Thomas Publisher, Springfiels, Ill., 703-721, 1971. (4) Werner J., Webb P., “A six-cylinder model of human thermoregulation for general use on personal computers”, Ann. Physiol. Anthrop., 12(3): 123-134, 1993.

  15. Assessing the direct effects of deep brain stimulation using embedded axon models

    NASA Astrophysics Data System (ADS)

    Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

    2007-06-01

    To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.

  16. In Vitro Blood–Brain Barrier Models: Current and Perspective Technologies

    PubMed Central

    NAIK, POOJA; CUCULLO, LUCA

    2012-01-01

    Even in the 21st century, studies aimed at characterizing the pathological paradigms associated with the development and progression of central nervous system diseases are primarily performed in laboratory animals. However, limited translational significance, high cost, and labor to develop the appropriate model (e.g., transgenic or inbred strains) have favored parallel in vitro approaches. In vitro models are of particular interest for cerebrovascular studies of the blood–brain barrier (BBB), which plays a critical role in maintaining the brain homeostasis and neuronal functions. Because the BBB dynamically responds to many events associated with rheological and systemic impairments (e.g., hypoperfusion), including the exposure of potentially harmful xenobiotics, the development of more sophisticated artificial systems capable of replicating the vascular properties of the brain microcapillaries are becoming a major focus in basic, translational, and pharmaceutical research. In vitro BBB models are valuable and easy to use supporting tools that can precede and complement animal and human studies. In this article, we provide a detailed review and analysis of currently available in vitro BBB models ranging from static culture systems to the most advanced flow-based and three-dimensional coculture apparatus. We also discuss recent and perspective developments in this ever expanding research field. PMID:22213383

  17. Comparison of Long-Term Clinical Outcomes after Drug-Eluting Stent Implantation in Patients with Coronary Artery Disease with and without Prior Cerebral Infarction

    PubMed Central

    Fujiwara, Hidetoshi; Horiuchi, Naruyoshi; Shirasaki, Shuichi; Sakai, Ichiro; Tsuchida, Kazuyuki; Murai, Hiroshi

    2015-01-01

    Objective: To compare the clinical and angiographic outcomes after implantation of drug-eluting stents (DESs) in patients with coronary artery disease (CAD) with or without prior cerebral infarction. Materials and Methods: Ninety-eight consecutive patients (130 lesions) who underwent successful coronary DES implantation were prospectively classified into two groups: those with a clinical history of symptomatic cerebral infarction (cerebral infarction group, 49 patients, 69 lesions) and those without a clinical history of symptomatic cerebral infarction (noncerebral infarction group, 49 patients, 61 lesions). The primary endpoint was defined as death, nonfatal myocardial infarction, and cerebrovascular events. Results: The Kaplan–Meier method was used to create a primary endpoint curves to determine the time-dependent cumulative primary endpoint-free rate, which were compared using the log-rank test. The incidence of primary endpoints was higher in the cerebral infarction group than in the noncerebral infarction group (p = 0.0075). The Cox proportional hazards regression model for primary endpoint identified prior cerebral infarction (p = 0.0331, hazard ratio = 2.827) and patients with peripheral artery disease (p = 0.0271, hazard ratio = 2.757) as explanatory factors. Conclusion: The results showed that clinical outcomes were poorer in patients with CAD who had prior cerebral infarctions than in those who did not have infarction.

  18. The immune system and the remodeling infarcted heart: cell biological insights and therapeutic opportunities

    PubMed Central

    Frangogiannis, Nikolaos G

    2014-01-01

    Extensive necrosis of ischemic cardiomyocytes in the infarcted myocardium activates the innate immune response triggering an intense inflammatory reaction. Release of danger signals from dying cells and damaged matrix activates the complement cascade and stimulates Toll-Like Receptor (TLR)/Interleukin (IL)-1 signaling, resulting in activation of the Nuclear Factor (NF)-?B system and induction of chemokines, cytokines and adhesion molecules. Subsequent infiltration of the infarct with neutrophils and mononuclear cells serves to clear the wound from dead cells and matrix debris, while stimulating reparative pathways. In addition to its role in repair of the infarcted heart and formation of a scar, the immune system is also involved in adverse remodeling of the infarcted ventricle. Overactive immune responses and defects in suppression, containment and resolution of the post-infarction inflammatory reaction accentuate dilative remodeling in experimental models and may be associated with chamber dilation, systolic dysfunction and heart failure in patients surviving a myocardial infarction. Interventions targeting the inflammatory response to attenuate adverse remodeling may hold promise in patients with myocardial infarction that exhibit accentuated, prolonged, or dysregulated immune responses to the acute injury. PMID:24072174

  19. Early radionuclide scans for risk assessment in suspected acute myocardial infarction.

    PubMed Central

    Norris, S. L.; Haywood, L. J.; Sobel, E.; Hung, G. L.; deGuzman, M.; Siegel, M.

    1997-01-01

    First-day thallium-201 myocardial perfusion scans and technetium-99m RBC gated scintiangiography were performed during the initial clinical and prognostic evaluation of 69 patients with suspected acute myocardial infarction. Patients were monitored for clinical course, diagnosis confirmation, and use of specialty services (cardiac catheterization, percutaneous balloon angioplasty, and cardiac surgery) during hospitalization. Myocardial infarction, confirmed in 20 patients, was associated with significantly more left ventricular dilatation, lower ejection fractions, lower peak left ventricular filling rates, wall motion abnormalities, and thallium-201 perfusion defects than nonmyocardial infarction patients. Among all patients, left ventricular dilatation carried a relative risk of myocardial infarction of 5.8; low ejection fraction and right ventricular dilatation were strongly associated with myocardial infarction. A logistic model for congestive heart failure included: left ventricular dilation, lower mean left ventricular filling rates and time to peak filling rates, and abnormal thallium-201 lung:heart uptakes. Among nonmyocardial infarction patients, subsequent cardiac catheterization was predicted by the presence of anterior thallium-201 perfusion defects, Killip functional class II-III, and ischemia on ECG. These findings suggest that early detection of myocardial perfusion defects and cardiac dysfunction by radionuclide scans enhances initial evaluation of suspected acute myocardial infarction patients. Additional studies are needed to confirm these findings. PMID:9433058

  20. Effects of angiotensin-converting enzyme inhibition and bradykinin peptides in rats with myocardial infarction

    PubMed Central

    Qu, Zhe; Xu, Hongxin; Tian, Yihao

    2015-01-01

    Background and objective: Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease myocardial remodeling and faciliate cardiac function improvement in the setting myocardial infarction by affecting bradykinin. The purpose of this study was to evaluate the combination effects of perindopril and bradykinin (BK) in rats with myocardial infarction. Methods: Wistar Rats underwent to left anterior descending (LAD) coronary artery ligation were allocated into MI group (n = 6); Perindopril group (n = 7); Perindopril + BK group (n = 7). An additional sham operation group (Sham group, n = 6) were also established. After 4 weeks, the left ventricle function, myocardial tissue morphology, myocardial collagen volume faction, infracted ventricular wall thickness, myocardial infarction area and neovascular formation were evaluated. Results: Combination treatment with perindopril and BK were showed significant improvement on LVEDV, LVEF and LVFS than MI group. Moreover, a significant improvement on LVEF was found in Perindopril + BK group than Perindopril group but not on LVEDV and LVFS between these two groups. Furthermore, neo-vessel density was significantly increased in Perindopril + BK group than other groups while no significant improvement on vessel density was found after the treatment of perindopril. In addition, myocardial infarction thickness improvement was found in Perindopril and group than MI group while combination treatment with perindopril and BK can significant improve the myocardial infarction thickness than perindopril only. Conclusions: Combination treatment with ACE inhibitor perindopril and BK can significantly improve the ventricle function in the rat model of myocardial infarction. Our data suggest BK can serve as adjuvant treatment in myocardial infarction treatment.