Science.gov

Sample records for brain infarction model

  1. Longitudinal changes in resting-state brain activity in a capsular infarct model.

    PubMed

    Kim, Donghyeon; Kim, Ra Gyung; Kim, Hyung-Sun; Kim, Jin-Myung; Jun, Sung Chan; Lee, Boreom; Jo, Hang Joon; Neto, Pedro R; Lee, Min-Cheol; Kim, Hyoung-Ihl

    2015-01-01

    Strokes attributable to subcortical infarcts have been increasing recently in elderly patients. To gain insight how this lesion influences the motor outcome and responds to rehabilitative training, we used circumscribed photothrombotic capsular infarct models on 36 Sprague-Dawley rats (24 experimental and 12 sham-operated). We used 2-deoxy-2-[(18)F]-fluoro-D-glucose-micro positron emission tomography (FDG-microPET) to assess longitudinal changes in resting-state brain activity (rs-BA) and daily single-pellet reaching task (SPRT) trainings to evaluate motor recovery. Longitudinal FDG-microPET results showed that capsular infarct resulted in a persistent decrease in rs-BA in bilateral sensory and auditory cortices, and ipsilesional motor cortex, thalamus, and inferior colliculus (P<0.0025, false discovery rate (FDR) q<0.05). The decreased rs-BA is compatible with diaschisis and contributes to manifest the malfunctions of lesion-specific functional connectivity. In contrast, capsular infarct resulted in increase of rs-BA in the ipsilesional internal capsule, and contralesional red nucleus and ventral hippocampus in recovery group (P<0.0025, FDR q<0.05), implying that remaining subcortical structures have an important role in conducting the recovery process in capsular infarct. The SPRT training facilitated motor recovery only in rats with an incomplete destruction of the posterior limb of the internal capsule (PLIC) (Pearson's correlation, P<0.05). Alternative therapeutic interventions are required to enhance the potential for recovery in capsular infarct with complete destruction of PLIC. PMID:25352047

  2. Changes in Brain Swelling and Infarction Volume over Four Days After Hypoxia Ischemia in Neonatal Rats.

    PubMed

    McBride, Devin W; Jacob, Christine; Doycheva, Desislava; Dixon, Brandon J; Malaguit, Jay; Lekic, Tim; Tang, Jiping; Zhang, John H

    2016-01-01

    The leading cause of morbidity and mortality in infants is hypoxia-ischemia (HI). The current therapies for HI have limited success, in part due to a lack of understanding of HI pathophysiology and underlying mechanisms. Herein, a neonatal rat model of HI was used to examine the changes in brain swelling and infarct volume over 4 days after HI. Forty-four P10 rat pups were sacrificed at 2, 3, or 4 days post-HI. After sacrifice, the brains were removed, sliced, and stained with TTC (2,3,5-triphenyl-2H-tetrazolium chloride). Images of TTC-stained brains were used for measurement of the ipsilateral hemisphere brain volumes and infarct volumes, calculated using standard equations. The hemispheric brain volumes of HI animals in all groups was lower than that of sham animals and decreased as the post-HI sacrifice time increased. The infarct volume of HI animals was larger than that of sham animals. Infarct volumes tended to decrease over the days post-HI. The change in infarct volume is likely the result of a combination of brain growth and repair mechanisms. However, changes in the hemispheric brain volume may include tissue growth and repair mechanism, so also may be a limitation of the current algorithm used for calculating ipsilateral hemisphere brain volume. PMID:26463932

  3. Chromium supplementation improved post-stroke brain infarction and hyperglycemia.

    PubMed

    Chen, Wen-Ying; Mao, Frank Chiahung; Liu, Chia-Hsin; Kuan, Yu-Hsiang; Lai, Nai-Wei; Wu, Chih-Cheng; Chen, Chun-Jung

    2016-04-01

    Hyperglycemia is common after acute stroke and is associated with a worse outcome of stroke. Thus, a better understanding of stress hyperglycemia is helpful to the prevention and therapeutic treatment of stroke. Chromium is an essential nutrient required for optimal insulin activity and normal carbohydrate and lipid metabolism. Beyond its nutritional effects, dietary supplement of chromium causes beneficial outcomes against several diseases, in particular diabetes-associated complications. In this study, we investigated whether post-stroke hyperglycemia involved chromium dynamic mobilization in a rat model of permanent focal cerebral ischemia and whether dietary supplement of chromium improved post-stroke injury and alterations. Stroke rats developed brain infarction, hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance. Post-stroke hyperglycemia was accompanied by elevated secretion of counter-regulatory hormones including glucagon, corticosterone, and norepinephrine, decreased insulin signaling in skeletal muscles, and increased hepatic gluconeogenesis. Correlation studies revealed that counter-regulatory hormone secretion showed a positive correlation with chromium loss and blood glucose increased together with chromium loss. Daily chromium supplementation increased tissue chromium levels, attenuated brain infarction, improved hyperglycemia, and decreased plasma levels of glucagon and corticosterone in stroke rats. Our findings suggest that stroke rats show disturbance of tissue chromium homeostasis with a net loss through urinary excretion and chromium mobilization and loss might be an alternative mechanism responsible for post-stroke hyperglycemia. PMID:26477944

  4. 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

  5. Local carboxyfullerene protects cortical infarction in rat brain.

    PubMed

    Lin, Anya Maan-Yuh; Fang, Su-Feng; Lin, Shin-Zong; Chou, Cheng-Kong; Luh, Tieng-Yau; Ho, Low-Tone

    2002-08-01

    The neuroprotective effect of carboxyfullerene, a water-soluble derivative of fullerene, on the transient focal ischemia-reperfusion injury was investigated in rat brain. A focal infarction in the cerebral cortex was consistently observed 24 h after a 60-min transient ischemia by occlusion of the right middle cerebral artery and bilateral common carotid arteries. The fluorescent end products of lipid peroxidation were increased in the infarcted cortical area. Furthermore, the GSH level was decreased in the infarcted cortex. Carboxyfullerene was either intravenously (6 mg/kg) or intracerebroventricularly (0.1, 0.3 mg per rat) infused to the chloral hydrate-anesthetized Sprague-Dawley rats 30 min prior to transient ischemia-reperfusion. No protection of cortical infarction was observed after intravenous administration of carboxyfullerene. In contrast, intracerebroventricular infusion of carboxyfullerene not only attenuated cortical infarction but also prevented both the elevated lipid peroxidation and the depleted GSH level induced by transient ischemia-reperfusion. Adverse behavioral changes were simultaneously observed in rats receiving intracerebroventricular infusion of carboxyfullerene (0.3 mg per rat), including writhing accompanied by trunk stretch and even death. Our data suggest that intracerebroventricular infusion of carboxyfullerene may attenuate oxidative injuries by transient ischemia-reperfusion. Nevertheless, undesired side effects may limit the usefulness of carboxyfullerene in biological organisms. PMID:12135775

  6. Persistent Asymmetric Brain MIBG Activity Related to a Cerebrovascular Infarct.

    PubMed

    Bai, Xia; Zhuang, Hongming

    2016-04-01

    A 13-year-old woman with a history of left malignant carotid body paraganglioma status postsurgical resection underwent I-MIBG scan for staging. The images demonstrated no definite evidence of MIBG-avid disease. However, there was asymmetric activity in the region of the brain with relatively less activity on the left compared with the contralateral right side on the head images, which was related to prior infarct revealed from the patient's history. This asymmetric MIBG activity persisted 8 years later. PMID:26571441

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

    PubMed

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

    2016-01-01

    Stroke disproportionally affects diabetic and hyperglycemic patients with increased incidence and is associated with higher morbidity and mortality due to brain swelling. In this study, the intraluminal suture middle cerebral artery occlusion (MCAO) model was used to examine the effects of blood glucose on brain swelling and infarct volume in acutely hyperglycemic rats and normo-glycemic controls. Fifty-four rats were distributed into normo-glycemic sham surgery, hyperglycemic sham surgery, normo-glycemic MCAO, and hyperglycemic MCAO. To induce hyperglycemia, 15 min before MCAO surgery, animals were injected with 50 % dextrose. Animals were subjected to 90 min of MCAO and sacrificed 24 h after reperfusion for hemispheric brain swelling and infarct volume calculations using standard equations. While normo-glycemic and hyperglycemic animals after MCAO presented with significantly higher brain swelling and larger infarcts than their respective controls, no statistical difference was observed for either brain swelling or infarct volume between normo-glycemic shams and hyperglycemic shams or normo-glycemic MCAO animals and hyperglycemic MCAO animals. The findings of this study suggest that blood glucose does not have any significant effect on hemispheric brain swelling or infarct volume after MCAO in rats. PMID:26463957

  8. Development of an Infarct Volume Algorithm to Correct for Brain Swelling After Ischemic Stroke in Rats.

    PubMed

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

    2016-01-01

    The primary measure for experimental stroke studies, infarct volume, can be affected by brain swelling. The algorithm by Lin et al. was developed to correct for brain swelling, however, the correction is not adequate. This chapter presents a new infarct volume algorithm that more appropriately corrects for brain hemisphere volume changes (swelling and stunted growth). Fifty-one adult rats were sacrificed 24 h after middle cerebral artery occlusion (MCAO). Forty-four P10 rat pups were sacrificed 48 h after hypoxia-ischemia (HI). Infarct volumes for 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) stained brains were calculated using our algorithm and that of Lin and colleagues. For MCAO animals, the algorithm of Lin et al. computed smaller infarct volumes than those of our algorithm. For HI animals, Lin et al.'s algorithm's infarct volumes were greater than those of our algorithm. For sham animals, Lin et al.'s algorithm's computed infarct volumes were significantly different from those of our algorithm. Our algorithm produces a more robust estimation of infarct volume than Lin et al.'s algorithm because the effects of ipsilesional hemisphere volume changes are minimized. Herein, our algorithm yields an infarct volume that better corrects for brain swelling and stunted brain growth compared with the algorithm of Lin et al. PMID:26463931

  9. The allometric model in chronic myocardial infarction

    PubMed Central

    2012-01-01

    Background An allometric relationship between different electrocardiogram (ECG) parameters and infarcted ventricular mass was assessed in a myocardial infarction (MI) model in New Zealand rabbits. Methods A total of fifteen animals were used, out of which ten underwent left anterior descending coronary artery ligation to induce infarction (735% area). Myocardial infarction (MI) evolved and stabilized during a three month-period, after which, rabbits were sacrificed and the injured area was histologically confirmed. Right before sacrifice, ECGs were obtained to correlate several of its parameters to the infarcted mass. The latter was normalized after combining data from planimetry measurements and heart weight. The following ECG parameters were studied: RR and PR intervals, P-wave duration (PD), QRS duration (QRSD) and amplitude (QRSA), Q-wave (QA), R-wave (RA) and S-wave (SA) amplitudes, T-wave peak amplitude (TA), the interval from the peak to the end of the T-wave (TPE), ST-segment deviation (STA), QT interval (QT), corrected QT and JT intervals. Corrected QT was analyzed with different correction formulae, i.e., Bazett (QTB), Framingham (QTFRA), Fridericia (QTFRI), Hodge (QTHO) and Matsunaga (QTMA) and compared thereafter. The former variables and infarcted ventricular mass were then fitted to the allometric equation in terms of deviation from normality, in turn derived after ECGs in 5 healthy rabbits. Results Six variables (JT, QTB, QA, SA, TA and STA) presented statistical differences among leads. QT showed the best allometric fit (r?=?0.78), followed by TA (r?=?0.77), STA (r?=?0.75), QTFRA (r?=?0.72), TPE (r?=?0.69), QTFRI (r?=?0.68) and QTMA (r?=?0.68). Corrected QTs (QTFRA, QTFRI and QTMA) performed worse than the uncorrected counterpart (QT), the former scaling allometrically with similar goodness of fits. Conclusions QT, TA, STA and TPE could possibly be used to assess infarction extent in an old MI event through the allometric model as a first approach. Moreover, the TPE also produced a good allometric scaling, leading to the potential existence of promising allometric indexes to diagnose malignant arrhythmias. PMID:22578057

  10. Analysis of Small Ischemic Lesions in the Examinees of a Brain Dock and Neurological Examination of Animals Subjected to Cortical or Basal Ganglia Photothrombotic Infarction.

    PubMed

    Kuroiwa, Toshihiko; Tabata, Hitoshi; Xi, Guohua; Hua, Ya; Schallert, Timothy; Keep, Richard F

    2016-01-01

    We analyzed cases of small brain ischemic lesions found in examinees of a brain dock (neurological health screening center). Small cerebral infarction was found in 17 % of the examinees (733 cases). White matter lesions were found in 24 %. Infarctions were located in the cortex or subcortical white matter in 31 % and in the basal ganglia in 44 % of cases. Infratentorial infarction was found in 1.6 %. We have developed an animal model of small infarction in the cortex or basal ganglia induced by photothrombosis in rodents. Sprague-Dawley rats or Mongolian gerbils were anesthetized and photothrombotic infarction was induced in the left caudate nucleus or parietal cortex by light exposure via an optic fiber and intravenous Rose Bengal dye injection. Histological examination revealed development of a small spherical infarction surrounding the tip of the optic fiber. The lesion turned to a cyst by 6 weeks after lesioning. Neurological deficits were found in animals both with cortical and caudate infarction. Behavioral changes in an open field test differed with the lesion site. Neurological deficits were sustained longer in animals with larger infarctions. Thus, photothrombotic infarction is useful for analyzing location-dependent and size-dependent neurological and neuropathological changes after cerebral infarction. PMID:26463929

  11. Brain natriuretic peptide release in acute myocardial infarction

    PubMed Central

    Durak-Nalbanti?, Azra; Dubur, Alen; Dili?, Mirza; Pozderac, ana; Mujanovi?-Naran?i?, Alma; Kuli?, Mehmed; Hodi?, Enisa; Resi?, Nerma; Brdjanovi?, Sneana; Zvizdi?, Faris

    2012-01-01

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

  12. Effect of Ginkgo biloba extract on apoptosis of brain tissues in rats with acute cerebral infarction and related gene expression.

    PubMed

    Wu, C; Zhao, X; Zhang, X; Liu, S; Zhao, H; Chen, Y

    2015-01-01

    We investigated the effect of Ginkgo biloba extract on apoptosis of brain tissues in rats with acute cerebral infarction and apoptosis-related gene expression. Rat models of acute cerebral infarction were constructed using the suture method, and randomly divided into the control group, model, and treatment groups. In the treatment group, 4 mg/kg G. biloba extract was intravenously injected into the rat tail vein. Phosphate-buffered saline solution was injected in the model group. Seventy-two hours after treatment, rats were euthanized, and brain tissues were removed to analyze the changes in caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) mRNA and protein levels, and variation in brain tissue cells' apoptosis indices was measured. Compared with the control group, the model and treatment groups showed significantly upregulated caspase-3, Bcl-2, and Bax mRNA and protein levels in brain tissues, but remarkably downregulated Bcl-2 mRNA and protein levels (P < 0.05). After treatment, in treatment group brain tissues, caspase-3 and Bax mRNA and protein levels were significantly lower than those in the model group, while Bcl-2 mRNA and protein levels were higher than that in the model group (P < 0.05). The model and treatment groups showed increased cell apoptosis indices of brain tissues compared to the control group; after treatment, the apoptosis index in the treatment group was significantly downregulated compared with that in the model group (P < 0.05). In conclusion, G. biloba extract significantly reduced apoptosis in rat brain tissue cells with acute cerebral infarction and thus protected brain tissues. PMID:26125843

  13. 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.

  14. 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.…

  15. Prognostic Value of Troponin I for Infarct Size to Improve Preclinical Myocardial Infarction Small Animal Models

    PubMed Central

    Frobert, Aurélien; Valentin, Jérémy; Magnin, Jean-Luc; Riedo, Erwin; Cook, Stéphane; Giraud, Marie-Noëlle

    2015-01-01

    Coronary artery ligations to induce myocardial infarction (MI) in mice and rats are widely used in preclinical investigation. However, myocardial ischemic damage and subsequent infarct size are highly variable. The lack of standardization of the model impairs the probability of effective translation to the clinic. Cardiac Troponin I (cTnI) is a major clinically relevant biomarker. Aim: In the present study, we investigated the prognostic value of cTnI for early estimation of the infarct size. Methods and Results: Infarcts of different sizes were induced in mice and rats by ligation, at a random site, of the coronary artery. Kinetics of the plasma levels of cTnI were measured. Heart function was evaluated by echocardiography, the percentage of infarcted left ventricle and infarct expansion index were assessed from histological section. We observed that plasma cTnI level peaked at 24 h in the infarcted rats and between 24 and 48 h in mice. Sham operated animals had a level of cTnI below 15 ng/mL. Infarct expansion index (EI) assessed 4 weeks after ligation showed a large variation coefficient of 63 and 71% in rats and mice respectively. We showed a significative correlation between cTnI level and the EI demonstrating its predictive value for myocardial injury in small animal models. Conclusion: we demonstrated the importance of cTnI plasma level as a major early marker to assist in the optimal and efficient management of MI in laboratory animals model. The presented results stress the need for comparable biomarkers in the animal model and clinical trials for improved translation. PMID:26640441

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  18. Nicardipine in models of myocardial infarction

    PubMed Central

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

    1985-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

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

    PubMed

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

    2014-07-01

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

  1. Intravenous Treatment With Coenzyme Q10 Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Brain Ischemia in Rats.

    PubMed

    Belousova, Margarita; Tokareva, Olga G; Gorodetskaya, Evgeniya; Kalenikova, Elena I; Medvedev, Oleg S

    2016-02-01

    Coenzyme Q10 (CoQ10) crosses the blood-brain barrier when administered intravenously and accumulates in the brain. In this study, we investigated whether CoQ10 protects against ischemia-reperfusion injury by measuring neurological function and brain infarct volumes in a rat model of transient focal cerebral ischemia. In male Wistar rats, we performed transient middle cerebral artery occlusion (tMCAO) for 60 minutes, followed by reperfusion for 24 hours or 7 days. Forty-five minutes after the onset of occlusion (or 15 minutes before reperfusion), rats received a single intravenous injection of solubilized CoQ10 (30 mgmLkg) or saline (2 mL/kg). Sensory and motor function scores and body weights were obtained before the rats were killed by decapitation, and brain infarct volumes were calculated using tetrazolium chloride staining. CoQ10 brain levels were measured by high-performance liquid chromatography with electrochemical detection. CoQ10 significantly improved neurological behavior and reduced weight loss up to 7 days after tMCAO (P < 0.05). Furthermore, CoQ10 reduced cerebral infarct volumes by 67% at 24 hours after tMCAO and 35% at 7 days (P < 0.05). Cerebral ischemia resulted in a significant reduction in endogenous CoQ10 in both hemispheres (P < 0.05). However, intravenous injection of solubilized CoQ10 resulted in its increase in both hemispheres at 24 hours and in the contralateral hemisphere at 7 days (P < 0.05). Our results demonstrate that CoQ10 is a robust neuroprotective agent against ischemia-reperfusion brain injury in rats, improving both functional and morphological indices of brain damage. PMID:26371950

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  3. Bilateral borderzone brain infarctions in association with heroin abuse.

    PubMed

    Niehaus, L; Meyer, B U

    1998-10-01

    A 25-year-old drug abuser who developed an unusual pattern of cerebral ischemic lesions is presented. Cerebral magnetic resonance imaging revealed bilateral borderzone infarctions which were attributed to a heroin-associated vasculitis of the basal cerebral arteries. Under probatory corticosteroid medication the mild neurological deficits completely disappeared. PMID:9849803

  4. Devastating recurrent brain ischemic infarctions and retinal disease in pediatric patients with CD59 deficiency.

    PubMed

    Ben-Zeev, Bruria; Tabib, Adi; Nissenkorn, Andreea; Garti, Ben-Zion; Gomori, John Moshe; Nass, Dvora; Goldshmidt, Hanoch; Fellig, Yakov; Anikster, Yair; Nevo, Yoram; Elpeleg, Orly; Mevorach, Dror

    2015-11-01

    Identification of CD59 p.Cys89Tyr mutation in 5 patients from North-African Jewish origin presenting with chronic inflammatory demyelinating polyradiculoneuropathy like disease and chronic hemolysis, led us to reinvestigate an unsolved disease in 2 siblings from the same origin who died 17 years ago. The two patients carried the same CD59 gene mutation previously described by our group. These children had quiet similar disease course but in addition developed devastating recurrent brain infarctions, retinal and optic nerve involvement. Revising the brain autopsy of one of these patients confirmed the finding of multiple brain infarctions of different ages. CD59 protein expression was missing on brain endothelial cells by immunohistochemical staining. This new data expands the clinical spectrum of CD59 mutations and further emphasizes the need for its early detection and treatment. PMID:26233519

  5. A novel mouse model of subcortical infarcts with dementia.

    PubMed

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

    2015-03-01

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

  6. Epidemiology and characteristics of occipital brain infarcts in young adults in southwestern Finland.

    PubMed

    Martikainen, Mika H; Majamaa, Kari

    2010-02-01

    Occipital stroke and occipital epilepsy are possible manifestations of mitochondrial diseases. A previous study in northern Finland suggested a frequency of 10% for mitochondrial disorder in young patients with stroke. Here we studied the epidemiology of occipital brain infarcts in a defined population in southwestern Finland. Patients diagnosed with brain infarct or visual field defect with onset at the ages of 18-45 years were identified from the discharge files at the Turku University Hospital. We further ascertained those patients with an occipital brain infarct in brain imaging or homonymous hemianopia with no signs of other etiology in brain imaging. We reviewed the clinical data for known stroke risk factors and analyzed samples for the m.3243A > G and m.8344A > G mutations in mitochondrial DNA (mtDNA), and determined mtDNA haplogroups and five common mutations in the gene encoding polymerase gamma (POLG1). Migraine was more common in young patients with occipital brain infarct than in the general population, especially among women. None of the patients harboured the m.3243A > G or m.8344A > G mutation in mtDNA or any of the five common mutations in POLG1. Interestingly, 17% of the men and 33% of the women belonged to the mtDNA haplogroup Uk, while its frequency in the general population is 17%. Our results suggest that mtDNA haplogroup Uk is associated with increased risk of occipital stroke in young women. POLG1 mutations have been associated with occipital epilepsy, but we did not find the common mutations in patients with occipital stroke. PMID:19730927

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

    PubMed

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

    1995-03-01

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

  8. [Activity of enzymes of tricarboxylic and pentose-phosphate cycles in dog brain with myocardial infarction].

    PubMed

    Zanozdra, M M; Khmelevs'ki?, Iu V

    1977-01-01

    Under conditions of experimental myocardium infarction caused in dogs by ligation of the anterior descending branch of the left coronary artery, the activity of alpha-ketoglutarate dehydrogenase and succinate dehydrogenase in mitochondria of the cortex, cerebellum and medulla ablongata lowers most intensively on the first and fifth day after the appearance of acute myocardium infarction. Activation of the most important enzymes of the pentose-phosphate cycle (glucose-6-phosphate dehydrogenase and transketolase) which is clearly pronounced on the fifth day is observed in the mentioned sections. In the authors' opinions the above changes in the activity of the enzymes are due to the brain hypoxia which may be the main reason of disturbance in the function of the central nervous system under this disease. PMID:888227

  9. Invasive surgery reduces infarct size and preserves cardiac function in a porcine model of myocardial infarction

    PubMed Central

    van Hout, Gerardus PJ; Teuben, Michel PJ; Heeres, Marjolein; de Maat, Steven; de Jong, Renate; Maas, Coen; Kouwenberg, Lisanne HJA; Koenderman, Leo; van Solinge, Wouter W; de Jager, Saskia CA; Pasterkamp, Gerard; Hoefer, Imo E

    2015-01-01

    Reperfusion injury following myocardial infarction (MI) increases infarct size (IS) and deteriorates cardiac function. Cardioprotective strategies in large animal MI models often failed in clinical trials, suggesting translational failure. Experimentally, MI is induced artificially and the effect of the experimental procedures may influence outcome and thus clinical applicability. The aim of this study was to investigate if invasive surgery, as in the common open chest MI model affects IS and cardiac function. Twenty female landrace pigs were subjected to MI by transluminal balloon occlusion. In 10 of 20 pigs, balloon occlusion was preceded by invasive surgery (medial sternotomy). After 72hrs, pigs were subjected to echocardiography and Evans blue/triphenyl tetrazoliumchloride double staining to determine IS and area at risk. Quantification of IS showed a significant IS reduction in the open chest group compared to the closed chest group (IS versus area at risk: 50.95.4% versus 69.93.4%, P=0.007). End systolic LV volume and LV ejection fraction measured by echocardiography at follow-up differed significantly between both groups (515ml versus 653ml, P=0.033; 47.52.6% versus 38.81.2%, P=0.005). The inflammatory response in the damaged myocardium did not differ between groups. This study indicates that invasive surgery reduces IS and preserves cardiac function in a porcine MI model. Future studies need to elucidate the effect of infarct induction technique on the efficacy of pharmacological therapies in large animal cardioprotection studies. PMID:26282710

  10. Surgical Porcine Myocardial Infarction Model through Permanent Coronary Occlusion

    PubMed Central

    Munz, Maria R; Faria, Miguel A; Monteiro, Joana R; guas, Artur P; Amorim, Mrio J

    2011-01-01

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

  11. MRI and PET in Mouse Models of Myocardial Infarction

    PubMed Central

    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

  12. 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 β-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

  13. Modeling Myocardial Infarction in Mice: Methodology, Monitoring, Pathomorphology

    PubMed Central

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

    2011-01-01

    Myocardial infarction is one of the most serious and widespread diseases in the world. In this work, a minimally invasive method for simulating myocardial infarction in mice is described in the Russian Federation for the very first time; the procedure is carried out by ligation of the coronary heart artery or by controlled electrocoagulation. As a part of the methodology, a series of anesthetic, microsurgical and revival protocols are designed, owing to which a decrease in the postoperational mortality from the initial 94.6 to 13.6% is achieved. ECG confirms the development of large-focal or surface myocardial infarction. Postmortal histological examination confirms the presence of necrosis foci in the heart muscles of 87.5% of animals. Altogether, the medical data allow us to conclude that an adequate mouse model for myocardial infarction was generated. A further study is focused on the standardization of the experimental procedure and the use of genetically modified mouse strains, with the purpose of finding the most efficient therapeutic approaches for this disease. PMID:22649679

  14. Anticoagulation management of myocardial infarction after deep brain stimulation: a comparison of two cases.

    PubMed

    Polanski, Witold; Koy, Jan; Juratli, Tareq; Wolz, Martin; Klingelhfer, Lisa; Fauser, Mareike; Storch, Alexander; Schackert, Gabriele; Sobottka, Stephan B

    2013-09-01

    Deep brain stimulation (DBS) is an established treatment of various diseases, particularly used for idiopathic Parkinson's disease. Frequently, DBS patients are multimorbid and managing them may be challenging, since postoperative complications can become more likely with age. In this article, we present two cases of myocardial infarction after DBS with different therapeutic strategies. Case 1 was anticoagulated with a heparin infusion with a target partial thromboplastine time (PTT) between 50 and 60 s after the myocardial infarction and showed 3 days later, after an initial postoperative inconspicuous cranial computer tomography, an intracerebral haematoma, which was evacuated without explanting the DBS lead. Case 2 was only treated with enoxaparine 40 mg s.c. twice a day after the myocardial infarction without any further complications. Both cases benefited from the DBS with respect to the motor fluctuations, but case 1 continued to suffer from psychomotor slowdown, mild hemiparesis of the left side, visual neglect and a gaze paresis. Unfortunately, there are no established guidelines or therapy recommendations for the management of such patients. An individual therapy regime is necessary for this patient population regarding the bleeding risk, the cardial risk and the symptoms of the patient. Retrospectively, the rejection of the intravenous application of heparin in case 2 seems to be the right decision. But regarding the small number of cases, it remains still an individual therapy. Further experience will help us to develop optimal therapy strategies for this patient population. PMID:23563744

  15. Predictors of malignant brain edema in middle cerebral artery infarction observed on CT angiography.

    PubMed

    Kim, Hoon; Jin, Seon Tak; Kim, Young Woo; Kim, Seong Rim; Park, Ik Seong; Jo, Kwang Wook

    2015-03-01

    Patients with middle cerebral artery (MCA) infarction accompanied by MCA occlusion with or without internal carotid artery (ICA) occlusion have a poor prognosis, as a result of brain cell damage caused by both the infarction and by space-occupying and life-threatening edema formation. Multiple treatments can reduce the likelihood of edema formation, but tend to show limited efficacy. Decompressive hemicraniectomy with duroplasty has been promising for improving functional outcomes and reducing mortality, particularly improved functional outcomes can be achieved with early decompressive surgery. Therefore, identifying patients at risk for developing fatal edema is important and should be performed as early as possible. Sixty-four patients diagnosed with major MCA infarction with MCA occlusion within 8 hours of symptom onset were retrospectively reviewed. Early clinical, laboratory, and computed tomography angiography (CTA) parameters were analyzed for malignant brain edema (MBE). Twenty of the 64 patients (31%) had MBE, and the clinical outcome was poor (3month modified Rankin Scale >2) in 95% of them. The National Institutes of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early Computed Tomography Score, Clot Burden Score, and Collateral Score (CS) showed statically significant differences in both groups. Multivariable analyses adjusted for age and sex identified the independent predictors of MBE: NIHSS score >18 (odds ratio [OR]: 4.4, 95% confidence interval [CI]: 1.2-16.0, p=0.023) and CS on CTA <2 (OR: 7.28, 95% CI: 1.7-30.3,p=0.006). Our results provide useful information for selecting patients in need of aggressive treatment such as decompressive surgery. PMID:25510537

  16. Oxygen Mapping within Healthy and Acutely Infarcted Brain Tissue in Humans Using the NMR Relaxation of Lipids: A Proof-Of-Concept Translational Study

    PubMed Central

    Magat, Julie; Joudiou, Nicolas; Peeters, Andr P.; Jordan, Bndicte F.; Gallez, Bernard; Duprez, Thierry

    2015-01-01

    The clinical applicability of brain oxygenation mapping using the MOBILE (Mapping of Oxygen By Imaging Lipids relaxation Enhancement) magnetic resonance (MR) technique was assessed in the clinical setting of normal brain and of acute cerebral ischemia as a founding proof-of-concept translational study. Changes in the oxygenation level within healthy brain tissue can be detected by analyzing the spin-lattice proton relaxation (Global T1 combining water and lipid protons) because of the paramagnetic properties of molecular oxygen. It was hypothesized that selective measurement of the relaxation of the lipid protons (Lipids T1) would result in enhanced sensitivity of pO2 mapping because of higher solubility of oxygen in lipids than in water, and this was demonstrated in pre-clinical models using the MOBILE technique. In the present study, 12 healthy volunteers and eight patients with acute (4872 hours) brain infarction were examined with the same clinical 3T MR system. Both Lipids R1 (R1 = 1/T1) and Global R1 were significantly different in the infarcted area and the contralateral unaffected brain tissue, with a higher statistical significance for Lipids R1 (median difference: 0.408 s-1; p<0.0001) than for Global R1 (median difference: 0.154 s-1; p = 0.027). Both Lipids R1 and Global R1 values in the unaffected contralateral brain tissue of stroke patients were not significantly different from the R1 values calculated in the brain tissue of healthy volunteers. The main limitations of the present prototypic version of the MOBILE sequence are the long acquisition time (4 min), hampering robustness of data in uncooperative patients, and a 2 mm slice thickness precluding accurate measurements in small infarcts because of partial volume averaging effects. PMID:26267901

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

    NASA Astrophysics Data System (ADS)

    Kuliha, Martin; Školoudík, David; Martin Roubec, Martin; Herzig, Roman; Procházka, Václav; Jonszta, Tomáš; Krajča, Jan; Czerný, Dan; Hrbáč, Tomáš; Otáhal, David; Langová, Kateřina

    2012-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2001-08-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    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-hour transient MCAO produced by intraluminal suture blockade followed by 23 hours of reperfusion. In nine AQP4+/+ and nine AQP4?/? mice, infarct volume was significantly reduced by an average of 39 4 % at 24 hours 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

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

    PubMed

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

    2010-08-01

    Tissue plasminogen activator (TPA) showed brain-protective activity within the first 15 min after cerebral ischemia in rats. To understand its molecular mechanism, TPA derivates were intracerebroventricularly administered at 15 min before, and 15, 90, 120 min after middle cerebral artery occlusion (MCAO) in rats. The reduction in mortality and cerebral infarction at 24 h was seen only with TPA administered at 15 min after MCAO. The down-regulation of endogenous TPA by the intracerebroventricular injection of TPA was found to be responsible for the protective effect on the integrity of blood-brain barrier after MCAO, as well as for the reduction in mortality and cerebral infarction. Moreover, for the first time we have found that the Kringle-2 domain is essential for the brain-protective activity of TPA. PMID:20596602

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

    PubMed Central

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

    2014-01-01

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

  3. Brain MR: pathologic correlation with gross and histopathology. 1. Lacunar infarction and Virchow-Robin spaces.

    PubMed

    Braffman, B H; Zimmerman, R A; Trojanowski, J Q; Gonatas, N K; Hickey, W F; Schlaepfer, W W

    1988-09-01

    MR imaging was performed on 36 formalin-fixed brain specimens. For three of these specimens, in vivo MR studies had also been performed before death. Changes that take place in the MR appearance of the brain after fixation are discussed. Gross and microscopic pathology revealed 14 lacunar infarctions in seven cases and enlarged Virchow-Robin spaces (tat cribl) in four. Both types of lesion were seen in specimens from predominantly elderly, hypertensive patients. Eight lacunae were in the deep gray-matter nuclei (four in the putamen with variable involvement of the internal capsule and caudate nuclei, two in the thalami, and two in the dentate nuclei), five were in the supratentorial white matter, and one was in the brainstem. Enlarged Virchow-Robin spaces were identified in the basal ganglia. All lesions were detected on MR. CT failed to disclose the brainstem and dentate lacunae and the enlarged Virchow-Robin spaces. On MR, all lacunae were slitlike or ovoid, except one that was round. They were less than 1 cm in greatest diameter in all but two cases. The lacunae were hyperintense relative to brain parenchyma on both long TR sequences (short and long TEs) in all cases except that of a chronic infarct that underwent cystic change and was isointense relative to CSF on all pulse sequences. In contrast, dilated Virchow-Robin spaces were isointense relative to CSF in vivo or to fluid in the subarachnoid space in the postmortem state on all pulse sequences in all four cases. They were round or linear, and in general were smaller than the lacunae, although some overlap in size did occur. They were seen at the level immediately above the bifurcation of the internal carotid into the middle and anterior cerebral arteries and were seen on successive axial sections in the putamen (most prominent along its lateral margin) and in the internal capsule. MR studies of gross and microscopic pathology of lacunae and dilated Virchow-Robin spaces are useful in correlating MR and pathologic findings. However, changes resulting from the fixation process must be considered when postmortem and in vivo MR findings are correlated. PMID:3261517

  4. AAV-mediated targeting of gene expression to the peri-infarct region in rat cortical stroke model

    PubMed Central

    Mtlik, Kert; Abo-Ramadan, Usama; Harvey, Brandon K.; Arume, Urmas; Airavaara, Mikko

    2014-01-01

    Background For stroke patients the recovery of cognitive and behavioral functions is often incomplete. Functional recovery is thought to be mediated largely by connectivity rearrangements in the peri-infarct region. A method for manipulating gene expression in this region would be useful for identifying new recovery-enhancing treatments. New Method We have characterized a way of targeting adeno-associated virus (AAV) vectors to the peri-infarct region of cortical ischemic lesion in rats two days after middle cerebral artery occlusion (MCAo). Results We used magnetic resonance imaging (MRI) to show that the altered properties of post-ischemic brain tissue facilitate the spreading of intrastriatally injected nanoparticles towards the infarct. We show that subcortical injection of green fluorescent protein-encoding dsAAV7-GFP resulted in transduction of cells in and around the white matter tract underlying the lesion, and in the cortex proximal to the lesion. A similar result was achieved with dsAAV7 vector encoding the cerebral dopamine neurotrophic factor (CDNF), a protein with therapeutic potential. Comparison with existing methods Viral-vector mediated intracerebral gene delivery has been used before in rodent models of ischemic injury. However, the method of targeting gene expression to the peri-infarct region, after the initial phase of ischemic cell death, has not been described before. Conclusions We demonstrate a straightforward and robust way to target AAV vector-mediated over-expression of genes to the peri-infarct region in a rat stroke model. This method will be useful for studying the action of specific proteins in peri-infarct region during the recovery process. PMID:25152446

  5. 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 1.011.38; P = .03 and OR, 0.73, 95% CI 0.450.99; 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

  6. Altered expression of V1a receptors mRNA in the brain and kidney after myocardial infarction and chronic stress.

    PubMed

    Milik, E; Szczepanska-Sadowska, E; Dobruch, J; Cudnoch-Jedrzejewska, A; Maslinski, W

    2014-10-01

    Vasopressin released during myocardial infarction and in response to stress regulates blood pressure through multiple actions exerted in the brain, cardiovascular system and kidney. The aim of the present study was to determine whether myocardial infarction influences expression of vasopressin V1a receptor (V1aR) mRNA and protein in the brain and kidney and whether stress has an impact on expression of these parameters during the post-infarct state. Male, adult Sprague Dawley rats were subjected to myocardial infarction or sham surgery. Seven days later some rats were exposed to mild stress for 4weeks whereas other stayed at rest. Tissue fragments were harvested from four groups of rats (control, infarct, stress, infarct+stress). Expression of V1aR mRNA (Real time PCR) was determined in the preoptic, diencephalic, mesencephalopontine and medullary regions of the brain and in the renal cortex and medulla. Protein V1aR expression (Western blotting) was determined in the brain mesencephalopontine region and in the kidney medulla. In the preoptic, diencephalic, and mesencephalopontine regions, V1aR mRNA expression was significantly lower in the infarcted rats than in the sham-operated unstressed controls. The infarcted rats manifested also lower expression of V1aR protein in the mesencephalopontine region than the other groups. The stressed group demonstrated significantly higher V1aR mRNA expression in the brain medulla and in the renal cortex and renal medulla than the control group. In all brain regions and in the kidney, V1aR mRNA expression was significantly higher in the stressed rats than in the infarcted rats. The stressed rats showed also higher expression of V1aR protein in the renal medulla than the other groups. It is concluded that myocardial infarction and chronic stress cause significant but differential changes in the regulation of V1a receptors expression in the brain and the kidney. PMID:25169016

  7. Brain infarction with a predilection for cerebellum in a patient with double-outlet left ventricle and vascular malformations.

    PubMed

    Inoue, Yasuteru; Watanabe, Masaki; Ando, Yukio

    2014-01-01

    Double-outlet left ventricle (DOLV) is a rare congenital heart disease characterized by the origin of the great arteries arising predominantly or completely from the left ventricle. In this report, we describe a case with brain infarction with a predilection for cerebellum in a patient with DOLV and vascular malformations. The cerebellar predilection of ischemic lesions appeared to have been caused by hemodynamic effects related to the specific anatomy of the brachiocephalic trunk. This is further supported by our observation that the mean flow velocity was significantly higher in the vertebral arteries than in the common carotid arteries. PMID:24139408

  8. Complete cardiac regeneration in a mouse model of myocardial infarction.

    PubMed

    Haubner, Bernhard Johannes; Adamowicz-Brice, Martyna; Khadayate, Sanjay; Tiefenthaler, Viktoria; Metzler, Bernhard; Aitman, Tim; Penninger, Josef M

    2012-12-01

    Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, complete cardiac regeneration has been demonstrated in fish and newborn mice following resection of the cardiac apex. However, it remained entirely unclear whether the mammalian heart can also completely regenerate following a complex cardiac ischemic injury. We established a protocol to induce a severe heart attack in one-day-old mice using left anterior descending artery (LAD) ligation. LAD ligation triggered substantial cardiac injury in the left ventricle defined by Caspase 3 activation and massive cell death. Ischemia-induced cardiomyocyte death was also visible on day 4 after LAD ligation. Remarkably, 7 days after the initial ischemic insult, we observed complete cardiac regeneration without any signs of tissue damage or scarring. This tissue regeneration translated into long-term normal heart functions as assessed by echocardiography. In contrast, LAD ligations in 7-day-old mice resulted in extensive scarring comparable to adult mice, indicating that the regenerative capacity for complete cardiac healing after heart attacks can be traced to the first week after birth. RNAseq analyses of hearts on day 1, day 3, and day 10 and comparing LAD-ligated and sham-operated mice surprisingly revealed a transcriptional programme of major changes in genes mediating mitosis and cell division between days 1, 3 and 10 postnatally and a very limited set of genes, including genes regulating cell cycle and extracellular matrix synthesis, being differentially regulated in the regenerating hearts. We present for the first time a mammalian model of complete cardiac regeneration following a severe ischemic cardiac injury. This novel model system provides the unique opportunity to uncover molecular and cellular pathways that can induce cardiac regeneration after ischemic injury, findings that one day could be translated to human heart attack patients. PMID:23425860

  9. Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain.

    PubMed

    Petro, Marianne; Jaffer, Hayder; Yang, Jun; Kabu, Shushi; Morris, Viola B; Labhasetwar, Vinod

    2016-03-01

    Inherent neuronal and circulating progenitor cells play important roles in facilitating neuronal and functional recovery post stroke. However, this endogenous repair process is rather limited, primarily due to unfavorable conditions in the infarcted brain involving reactive oxygen species (ROS)-mediated oxidative stress and inflammation following ischemia/reperfusion injury. We hypothesized that during reperfusion, effective delivery of antioxidants to ischemic brain would create an environment without such oxidative stress and inflammation, thus promoting activation and mobilization of progenitor cells in the infarcted brain. We administered recombinant human tissue-type plasminogen activator (tPA) via carotid artery at 3 h post stroke in a thromboembolic rat model, followed by sequential administration of the antioxidants catalase (CAT) and superoxide dismutase (SOD), encapsulated in biodegradable nanoparticles (nano-CAT/SOD). Brains were harvested at 48 h post stroke for immunohistochemical analysis. Ipsilateral brain slices from animals that had received tPA + nano-CAT/SOD showed a widespread distribution of glial fibrillary acidic protein-positive cells (with morphology resembling radial glia-like neural precursor cells) and nestin-positive cells (indicating the presence of immature neurons); such cells were considerably fewer in untreated animals or those treated with tPA alone. Brain sections from animals receiving tPA + nano-CAT/SOD also showed much greater numbers of SOX2- and nestin-positive progenitor cells migrating from subventricular zone of the lateral ventricle and entering the rostral migratory stream than in t-PA alone treated group or untreated control. Further, animals treated with tPA + nano-CAT/SOD showed far fewer caspase-positive cells and fewer neutrophils than did other groups, as well as an inhibition of hippocampal swelling. These results suggest that the antioxidants mitigated the inflammatory response, protected neuronal cells from undergoing apoptosis, and inhibited edema formation by protecting the blood-brain barrier from ROS-mediated reperfusion injury. A longer-term study would enable us to determine if our approach would assist progenitor cells to undergo neurogenesis and to facilitate neurological and functional recovery following stroke and reperfusion injury. PMID:26735970

  10. Predicting the ischemic infarct volume at the first minute after occlusion in rodent stroke model by laser speckle imaging of cerebral blood flow.

    PubMed

    Li, Yao; Zhu, Shuping; Yuan, Lu; Lu, Hongyang; Li, Hangdao; Tong, Shanbao

    2013-07-01

    Stroke is a worldwide medical emergency and an important issue in stroke research is looking for the early pathophysiological markers which can predict the severity of brain injury. Decreased cerebral blood flow (CBF) has been serving as the most important indicator of ischemic stroke. Particular attention is paid to study the spatio-temporal CBF changes immediately after the onset of stroke in a rat intraluminal filament middle cerebral artery occlusion (MCAO) model and investigation of its correlation with brain infarct volume after 24 h. We implement an on-line laser speckle imaging (LSI) system, which could provide real time high spatio-temporal resolution CBF information before, during, and immediately after the rat MCAO surgery. We found a significant correlation between the affected area with 50% CBF reduction (CBF50) at the first minute after occlusion with the infarct volume. To the best of our knowledge, this is the earliest CBF marker for infarct volume prediction. Based on such a CBF-infarct volume correlation, LSI may be used as a real time guidance for improving the consistency of intraluminal filament MCAO model since the depth of filament insertion could be adjusted promptly and those unsuccessful models could be excluded in the earliest stage. PMID:23887483

  11. Dronedarone does not affect infarct volume as assessed by magnetic resonance imaging in a porcine model of myocardial infarction.

    PubMed

    Linke, Josefine; Utpatel, Kirsten; Wolke, Carmen; Evert, Matthias; Khn, Jens-Peter; Bukowska, Alicja; Goette, Andreas; Lendeckel, Uwe; Peters, Barbara

    2015-10-01

    Dronedarone has been demonstrated to be harmful in patients with recent decompensated heart failure. Furthermore, a PALLAS study reported that dronedarone therapy increases mortality rates in patients with permanent atrial fibrillation. Although a pathophysiological explanation for these finding remains to be elucidated, the long term effects of dronedarone on myocardial structure and stability have been suggested. The aim of the present study was to determine whether dronedarone therapy affects left ventricular (LV) function in a chronic model of myocardial infarction (MI). An anterior MI was induced in 16 pigs. Of these animals, eight pigs were then treated with dronedarone for 1 week prior to, and 4 weeks following MI, the remaining pigs served as controls. LV angiography was performed 4 weeks after MI to determine the LV ejection fraction (LVEF). A post?mortem magnetic resonance imaging scan of the LV was then performed on the two groups (n=6) to determine the volume and size of the induced MI. Dronedarone therapy did not affect systemic and intracardiac hemodynamic parameters or LVEF during the follow?up assessment. Of note, dronedarone had no negative effect on the total infarct volume and size and did not induce lethal proarrhythmic effects following the induced anterior MI. Therefore, the results suggested that dronedarone did not increase the volume or size of induced anterior MI and did not affect LV performance. Thus, dronedarone therapy was observed to be safe in a porcine model of anterior MI. PMID:26179812

  12. Effect of Inducible Co-Stimulatory Molecule siRNA in Cerebral Infarction Rat Models

    PubMed Central

    Luo, Yingquan; Yang, Yu; Zhang, Hui; Zhang, Ting; Wang, Yina; Tan, Shengyu; Xu, Yan; Li, Dan; Ye, Ling; Chen, Ping

    2015-01-01

    Background T cell-induced inflammatory response and related cytokine secretion at the injury site may participate in the pathogenesis of cerebral infarction. Recent studies established inducible co-stimulatory molecule (ICOS) as a novel T cell-related factor for its activation and functions. We thus investigate the role of ICOS in cerebral infarction. Material/Methods The siRNA of ICOS was first used to suppress the gene expression in cultured lymphocytes. An in vivo study was then performed by intravenous application of ICOS siRNA in cerebral infarction rats. Survival rates, neurological scores, serum tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-17 levels were observed. Results The expression of ICOS in cultured lymphocytes was significantly suppressed by siRNA. In the in vivo study, the application of siRNA effectively lowered mortality rates of rats, in addition to the improvement of neurological behaviors and amelioration of cerebral tissue damage. Serum levels of TNF-α, IL-1 and IL-17 were all significantly suppressed after siRNA injection. Conclusions ICOS siRNA can protect brain tissues from ischemia injuries after cerebral infarction, improve limb movement and coordination, lower the mortality rate of rats, and inhibit T cell-induced cytokines. These results collectively suggest the potential treatment efficacy of ICOS siRNA against cerebral infarction. PMID:26436531

  13. A Right Brain/Left Brain Model of Acting.

    ERIC Educational Resources Information Center

    Bowlen, Clark

    Using current right brain/left brain research, this paper develops a model that explains acting's underlying quality--the actor is both himself and the character. Part 1 presents (1) the background of the right brain/left brain theory, (2) studies showing that propositional communication is a left hemisphere function while affective communication

  14. Coupled agent-based and finite-element models for predicting scar structure following myocardial infarction.

    PubMed

    Rouillard, Andrew D; Holmes, Jeffrey W

    2014-08-01

    Following myocardial infarction, damaged muscle is gradually replaced by collagenous scar tissue. The structural and mechanical properties of the scar are critical determinants of heart function, as well as the risk of serious post-infarction complications such as infarct rupture, infarct expansion, and progression to dilated heart failure. A number of therapeutic approaches currently under development aim to alter infarct mechanics in order to reduce complications, such as implantation of mechanical restraint devices, polymer injection, and peri-infarct pacing. Because mechanical stimuli regulate scar remodeling, the long-term consequences of therapies that alter infarct mechanics must be carefully considered. Computational models have the potential to greatly improve our ability to understand and predict how such therapies alter heart structure, mechanics, and function over time. Toward this end, we developed a straightforward method for coupling an agent-based model of scar formation to a finite-element model of tissue mechanics, creating a multi-scale model that captures the dynamic interplay between mechanical loading, scar deformation, and scar material properties. The agent-based component of the coupled model predicts how fibroblasts integrate local chemical, structural, and mechanical cues as they deposit and remodel collagen, while the finite-element component predicts local mechanics at any time point given the current collagen fiber structure and applied loads. We used the coupled model to explore the balance between increasing stiffness due to collagen deposition and increasing wall stress due to infarct thinning and left ventricular dilation during the normal time course of healing in myocardial infarcts, as well as the negative feedback between strain anisotropy and the structural anisotropy it promotes in healing scar. The coupled model reproduced the observed evolution of both collagen fiber structure and regional deformation following coronary ligation in the rat, and suggests that fibroblast alignment in the direction of greatest stretch provides negative feedback on the level of anisotropy in a scar forming under load. In the future, this coupled model may prove useful in computational design and screening of novel therapies to influence scar formation in mechanically loaded tissues. PMID:25009995

  15. Ultrastructural analysis of blood-brain barrier breakdown in the peri-infarct zone in young adult and aged mice.

    PubMed

    Nahirney, Patrick C; Reeson, Patrick; Brown, Craig E

    2016-02-01

    Following ischemia, the blood-brain barrier is compromised in the peri-infarct zone leading to secondary injury and dysfunction that can limit recovery. Currently, it is uncertain what structural changes could account for blood-brain barrier permeability, particularly with aging. Here we examined the ultrastructure of early and delayed changes (3 versus 72?h) to the blood-brain barrier in young adult and aged mice (3-4 versus 18 months) subjected to photothrombotic stroke. At both time points and ages, permeability was associated with a striking increase in endothelial caveolae and vacuoles. Tight junctions were generally intact although small spaces were detected in a few cases. In young mice, ischemia led to a significant increase in pericyte process area and vessel coverage whereas these changes were attenuated with aging. Stroke led to an expansion of the basement membrane region that peaked at 3?h and partially recovered by 72?h in both age groups. Astrocyte endfeet and their mitochondria were severely swollen at both times points and ages. Our results suggest that blood-brain barrier permeability in young and aged animals is mediated by transcellular pathways (caveolae/vacuoles), rather than tight junction loss. Further, our data indicate that the effects of ischemia on pericytes and basement membrane are affected by aging. PMID:26661190

  16. 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 (2.5104 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

  17. Decreased brain infarct following focal ischemia in mice lacking the transcription factor E2F1.

    PubMed

    MacManus, J P; Koch, C J; Jian, M; Walker, T; Zurakowski, B

    1999-09-01

    E2F1+/- mice subjected to 2 h middle cerebral artery occlusion developed an infarct of 77.0 +/- 3.2 mm3 (mean +/- s.e.m., n = 15) in the ischemic hemisphere after 24 h reperfusion. A significantly smaller infarct of 58.8 +/- 4.8 mm3 (n = 15; p < 0.01) was found in E2F1-/- animals. Both deficient and normal mice had similar cerebral angioarchitecture and intra-ischemic decreases in regional blood flow. Similar areas of hypoxia in both groups of ischemic animals were demonstrated directly by immunohistochemical detection of nitroimidazole adducts. It was concluded that all animals received the same ischemic insult, yet the subsequent damage was different in the mutant mice. This is the first indication that the E2F1 gene plays a role in ischemic death of post-mitotic neurons. PMID:10511428

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

    PubMed Central

    Lückl, Janos; Dreier, Jens P.; Szabados, Tamas; Wiesenthal, Dirk; Bari, Ferenc; Greenberg, Joel H.

    2012-01-01

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

  19. Exploring diagnostic potentials of radioiodinated sennidin A in rat model of reperfused myocardial infarction.

    PubMed

    Jiang, Cuihua; Gao, Meng; Li, Yue; Huang, Dejian; Yao, Nan; Ji, Yun; Liu, Xuejiao; Zhang, Dongjian; Wang, Xiaoning; Yin, Zhiqi; Jing, Su; Ni, Yicheng; Zhang, Jian

    2015-11-10

    Non-invasive "hot spot imaging" and localization of necrotic tissue may be helpful for definitive diagnosis of myocardial viability, which is essential for clinical management of ischemic heart disease. We labeled Sennidin A (SA), a naturally occurring median dianthrone compound, with (131)I and evaluated (131)I SA as a potential necrosis-avid diagnostic tracer agent in rat model of reperfused myocardial infarction. Magnetic resonance imaging (MRI) was performed to determine the location and dimension of infarction. (131)I-SA was evaluated in rat model of 24-hour old reperfused myocardial infarction using single-photon emission computed tomography/computed tomography (SPECT/CT), biodistribution, triphenyltetrazolium chloride (TTC) histochemical staining, serial sectional autoradiography and microscopy. Gamma counting revealed high uptake and prolonged retention of (131)I SA in necrotic myocardium and fast clearance from non-targeted tissues. On SPECT/CT images, myocardial infarction was persistently visualized as well-defined hotspots over 24h, which was confirmed by perfect matches of images from post-mortem TTC staining and autoradiography. Radioactivity concentration in infarcted myocardium was over 9 times higher than that of the normal myocardium at 24h. With favorable hydrophilicity and stability, radioiodinated SA may serve as a necrosis-avid diagnostic agent for assessment of myocardial viability. PMID:26302863

  20. 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

  1. Silent brain infarcts in two patients with zeta chain-associated protein 70 kDa (ZAP70) deficiency.

    PubMed

    Akar, H Haluk; Patiroglu, Turkan; Akyildiz, Basak N; Tekerek, Nazan U; Do?an, M Sait; Do?anay, Selim; van der Burg, Mirjam; Dusunsel, Ruhan

    2015-05-01

    Zeta-chain associated protein 70 kDa deficiency (ZAP70) is a form of severe combined immunodeficiency (SCID). It is caused by defects in the signaling pathways associated with T-lymphocyte activation. ZAP70 deficiency is characterized by a marked reduction in peripheral CD8+ T-cells. In this report, we described two patients with ZAP70 deficiency who presented with recurrent infections, lung tuberculosis (TBC), congenital nephrotic syndrome (CNS), and silent brain infarcts (SBIs) as a common feature. The first patient initially presented with recurrent infections and TBC as in a classic SCID patient. At the age of 4, he was interned with febrile seizure. Cranial magnetic resonance imaging (MRI) showed SBIs. The second patient, an 8-month-old boy, presented with congenital nephrotic syndrome caused by cytomegalovirus (CMV) and he had also SBIs. PMID:25805655

  2. 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

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

    PubMed Central

    Armstead, Stephen C.

    2013-01-01

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

  4. 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.

  5. Feeding the human brain model.

    PubMed

    Tiesinga, Paul; Bakker, Rembrandt; Hill, Sean; Bjaalie, Jan G

    2015-06-01

    The goal of the Human Brain Project is to develop, during the next decade, an infrastructure capable of simulating a draft human brain model based on available experimental data. One of the key issues is therefore to integrate and make accessible the experimental data necessary to constrain and fully specify this model. The required data covers many different spatial scales, ranging from the molecular scale to the whole brain and these data are obtained using a variety of techniques whose measurements may not be directly comparable. Furthermore, these data are incomplete, and will remain so at least for the coming decade. Here we review new neuroinformatics techniques that need to be developed and applied to address these issues. PMID:25725212

  6. [Increased circulating Ly6C(high); monocyte subsets are correlated with cerebral infarct size in cerebral ischemia/reperfusion mouse models].

    PubMed

    Zhang, Xin; Li, Hongxia; Li, Yuxiu; Ma, Yongqiang; Luo, Yanwei; Ji, Wenjie; Zhou, Xin; Li, Yuming

    2016-03-01

    Objective To investigate the dynamic changes of monocyte subsets after cerebral ischemia/reperfusion in mice and their correlations with infarct size and neurological defects. Methods Thirty male C57BL/6 mice were randomly divided into two groups: middle cerebral artery occlusion/reperfusion (MCAO/R) group and Sham group. MCAO/R mouse models were induced via the intraluminal suture technique (so called filament or suture model). The modified Neurological Severity Scores (mNSS) was used to assess neurological function 6, 12 hours, 1, 2, 3 days after MCAO/R. Blood samples were collected 1, 2 and 3 days after surgery to determine the dynamic changes of Ly6C(high); and Ly6C(low); subsets by flow cytometry. Triphenyltetrazolium chloride (TTC) staining and HE staining of the brains were also performed on day 1, 2 and 3. The relationships between the changes of monocyte subsets and the cerebral infarct size and neurological scores were studied by correlation analysis. Results Compared with the baseline, the proportion of Ly6C(high); monocytes significantly increased 1 day after MCAO/R surgery, reached the peak level on the following day and then declined. Compared with the Sham group, the proportion of Ly6C(high); monocytes went up obviously at each time point. TTC staining revealed that the infarct size increased markedly 2 days after surgery. The proportion of Ly6C(high); monocytes in the MCAO/R group was positively associated with the percentage of cerebral infarct size, and it also showed a positive correlation with neurological function deficit scores. Conclusion The dynamic changes of monocyte subsets after MCAO/R modeling revealed that Ly6C(high); subset peaked on day 2 after the operation and was correlated with cerebral infarct size. PMID:26927544

  7. Experimental model of small subcortical infarcts in mice with long-lasting functional disabilities.

    PubMed

    Uchida, Hiroki; Sakata, Hiroyuki; Fujimura, Miki; Niizuma, Kuniyasu; Kushida, Yoshihiro; Dezawa, Mari; Tominaga, Teiji

    2015-12-10

    Small subcortical infarcts account for 25% of all ischemic strokes. Although once considered to be a small vessel disease with a favorable outcome, recent studies have reported relatively poor long-term prognoses following small subcortical infarcts. Limited pre-clinical modeling has hampered understanding of the etiology and development of treatments for this disease. Therefore, we attempted to develop a new experimental model of small subcortical infarcts in mice to investigate pathophysiological changes in the corticospinal tract and assess long-term behavioral performance. The vasoconstrictor peptide, endothlin-1 (ET-1), in combination with the nitric oxide synthase inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME), were injected into the internal capsule of mice. Histological and behavioral tests were performed 0-8 weeks after the injection. The ET-1/l-NAME injection resulted in severe neurological deficits that continued for up to 8 weeks. The loss of axons and myelin surrounded by reactive gliosis was identified in the region of the injection, in which the vasoconstriction of microvessels was also observed. Moreover, a tract-tracing study revealed an interruption in axonal flow at the internal capsule. The present model of small subcortical infarcts is unique and novel due to the reproduction of neurological deficits that continue for a long period, up to 8 weeks, as well as the use of mice as experimental animals. The reproducibility, simplicity, and easy adoptability make the present model highly appealing for use in further pre-clinical studies on small subcortical infarcts. PMID:26522346

  8. Comparative Analysis of Methods to Induce Myocardial Infarction in a Closed-Chest Rabbit Model

    PubMed Central

    Isorni, Marc-Antoine; Casanova, Amaury; Piquet, Julie; Bellamy, Valérie; Pignon, Charly; Puymirat, Etienne; Menasche, Philippe

    2015-01-01

    Objective. To develop a rabbit model of closed-chest catheter-induced myocardial infarction. Background. Limitations of rodent and large animal models justify the search for clinically relevant alternatives. Methods. Microcatheterization of the heart was performed in 47 anesthetized 3-4 kg New Zealand rabbits to test five techniques of myocardial ischemia: free coils (n = 4), interlocking coils (n = 4), thrombogenic gelatin sponge (n = 4), balloon occlusion (n = 4), and alcohol injection (n = 8). In order to limit ventricular fibrillation, an antiarrhythmic protocol was implemented, with beta-blockers/amiodarone before and xylocaine infusion during the procedure. Clinical, angiographic, and echographic data were gathered. End points included demonstration of vessel occlusion (TIMI flow grades 0 and 1 on the angiogram), impairment of left ventricular function at 2 weeks after procedure (by echocardiography), and pathologically confirmed myocardial infarction. Results. The best arterial access was determined to be through the right carotid artery. The internal mammary guiding catheter 4-Fr was selected as the optimal device for selective intracoronary injection. Free coils deployed prematurely and tended to prolapse into the aorta. Interlocking coils did not deploy completely and failed to provide reliable results. Gelatin sponge was difficult to handle, adhered to the catheter, and could not be clearly visualized by fluoroscopy. Balloon occlusion yielded inconsistent results. Alcohol injection was the most efficient and reproducible method for inducing myocardial infarction (4 out of 6 animals), the extent of which could be fine-tuned by using a coaxial balloon catheter as a microcatheter (0.52 mm) to achieve a superselective injection of 0.2 mL of alcohol. This approach resulted in a 20% decrease in LVEF and infarcted myocardium was confirmed histologically. Conclusions. By following a stepwise approach, a minimally invasive, effective, and reproducible rabbit model of catheter-induced myocardial infarction has been developed which addresses the limitations of rodent experiments while avoiding the logistical and cost issues associated with large animal models. PMID:26504843

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

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

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

    2012-08-01

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

  11. Therapy with recombinant T-cell receptor ligand reduces infarct size and infiltrating inflammatory cells in brain after middle cerebral artery occlusion in mice.

    PubMed

    Dziennis, Suzan; Mader, Sarah; Akiyoshi, Kozaburo; Ren, Xuefang; Ayala, Patricia; Burrows, Gregory G; Vandenbark, Arthur A; Herson, Paco S; Hurn, Patricia D; Offner, Halina A

    2011-06-01

    Stroke induces a biphasic effect on the peripheral immune response that involves early activation of peripheral leukocytes followed by severe immunosuppression and atrophy of the spleen. Peripheral immune cells, including T lymphocytes, migrate to the brain and exacerbate the developing infarct. Recombinant T-cell receptor (TCR) Ligand (RTL)551 is designed as a partial TCR agonist for myelin oligodendrocyte glycoprotein (MOG)-reactive T cells and has demonstrated the capacity to limit infarct volume and inflammation in brain when administered to mice undergoing middle cerebral artery occlusion (MCAO). The goal of this study was to determine if RTL551 could retain protection when given within the therapeutically relevant 4 h time window currently in clinical practice for stroke patients. RTL551 was administered subcutaneously 4 h after MCAO, with repeated doses every 24 h until the time of euthanasia. Cell numbers were assessed in the brain, blood, spleen and lymph nodes and infarct size was measured after 24 and 96 h reperfusion. RTL551 reduced infarct size in both cortex and striatum at 24 h and in cortex at 96 h after MCAO and inhibited the accumulation of inflammatory cells in brain at both time points. At 24 h post-MCAO, RTL551 reduced the frequency of the activation marker, CD44, on T-cells in blood and in the ischemic hemisphere. Moreover, RTL551 reduced expression of the chemokine receptors, CCR5 in lymph nodes and spleen, and CCR7 in the blood and lymph nodes. These data demonstrate effective treatment of experimental stroke with RTL551 within a therapeutically relevant 4 h time window through immune regulation of myelin-reactive inflammatory T-cells. PMID:21472429

  12. Tubastatin A, an HDAC6 inhibitor, alleviates stroke-induced brain infarction and functional deficits: potential roles of ?-tubulin acetylation and FGF-21 up-regulation.

    PubMed

    Wang, Zhifei; Leng, Yan; Wang, Junyu; Liao, Hsiao-Mei; Bergman, Joel; Leeds, Peter; Kozikowski, Alan; Chuang, De-Maw

    2016-01-01

    Histone deacetylase (HDAC) 6 exists exclusively in cytoplasm and deacetylates cytoplasmic proteins such as ?-tubulin. HDAC6 dysfunction is associated with several pathological conditions in the central nervous system. This study investigated the beneficial effects of tubastatin A (TubA), a novel specific HDAC6 inhibitor, in a rat model of transient middle cerebral artery occlusion (MCAO) and an in vitro model of excitotoxicity. Post-ischemic TubA treatment robustly improved functional outcomes, reduced brain infarction, and ameliorated neuronal cell death in MCAO rats. These beneficial effects lasted at least three days after MCAO. Notably, when given at 24?hours after MCAO, TubA still exhibited significant protection. Levels of acetylated ?-tubulin were decreased in the ischemic hemisphere on Days 1 and 3 after MCAO, and were significantly restored by TubA. MCAO markedly downregulated fibroblast growth factor-21 (FGF-21) and TubA significantly reversed this downregulation. TubA also mitigated impaired FGF-21 signaling in the ischemic hemisphere, including up-regulating ?-Klotho, and activating ERK and Akt/GSK-3? signaling pathways. In addition, both TubA and exogenous FGF-21 conferred neuroprotection and restored mitochondrial trafficking in rat cortical neurons against glutamate-induced excitotoxicity. Our findings suggest that the neuroprotective effects of TubA likely involve HDAC6 inhibition and the subsequent up-regulation of acetylated ?-tubulin and FGF-21. PMID:26790818

  13. Tubastatin A, an HDAC6 inhibitor, alleviates stroke-induced brain infarction and functional deficits: potential roles of α-tubulin acetylation and FGF-21 up-regulation

    PubMed Central

    Wang, Zhifei; Leng, Yan; Wang, Junyu; Liao, Hsiao-Mei; Bergman, Joel; Leeds, Peter; Kozikowski, Alan; Chuang, De-Maw

    2016-01-01

    Histone deacetylase (HDAC) 6 exists exclusively in cytoplasm and deacetylates cytoplasmic proteins such as α-tubulin. HDAC6 dysfunction is associated with several pathological conditions in the central nervous system. This study investigated the beneficial effects of tubastatin A (TubA), a novel specific HDAC6 inhibitor, in a rat model of transient middle cerebral artery occlusion (MCAO) and an in vitro model of excitotoxicity. Post-ischemic TubA treatment robustly improved functional outcomes, reduced brain infarction, and ameliorated neuronal cell death in MCAO rats. These beneficial effects lasted at least three days after MCAO. Notably, when given at 24 hours after MCAO, TubA still exhibited significant protection. Levels of acetylated α-tubulin were decreased in the ischemic hemisphere on Days 1 and 3 after MCAO, and were significantly restored by TubA. MCAO markedly downregulated fibroblast growth factor-21 (FGF-21) and TubA significantly reversed this downregulation. TubA also mitigated impaired FGF-21 signaling in the ischemic hemisphere, including up-regulating β-Klotho, and activating ERK and Akt/GSK-3β signaling pathways. In addition, both TubA and exogenous FGF-21 conferred neuroprotection and restored mitochondrial trafficking in rat cortical neurons against glutamate-induced excitotoxicity. Our findings suggest that the neuroprotective effects of TubA likely involve HDAC6 inhibition and the subsequent up-regulation of acetylated α-tubulin and FGF-21. PMID:26790818

  14. Synergistic effects of nitric oxide and exercise on revascularisation in the infarcted ventricle in a murine model of myocardial infarction

    PubMed Central

    Ranjbar, Kamal; Nazem, Farzad; Nazari, Afshin; Gholami, Mohammadreza; Nezami, Ali Reza; Ardakanizade, Malihe; Sohrabi, Maryam; Ahmadvand, Hasan; Mottaghi, Mohammad; Azizi, Yaser

    2015-01-01

    It has been shown that density of microvessels decreases in the left ventricular after myocardial infarction (MI). The change of angiogenic and angiostatic factors as the main factors in revascularisation after exercise training in area at risk is not determined yet in MI. Therefore, the aim of the present study was the effect of exercise training and L-arginine supplementation on area at risk angiogenesis in myocardial infarction rat. Four weeks after surgery (Left Anterior Descending Coronary artery Ligation), myocardial infarction rats were divided into 4 groups: Sedentary rats (Sed-MI); L-arginine supplementation (La-MI); Exercise training (Ex-MI) and Exercise + L-arginine (Ex+La). Exercise training (ET) lasted for 10 weeks at 17 m/min for 10-50 min day?1. Rats in the L-arginine-treated groups drank water containing 4 % L-arginine. After ET and L-arginine supplementation, ventricular function was evaluated and angiogenic and angiostatic indices were measured at ~1 mm from the edge of scar tissue (area at risk). Statistical analysis revealed that gene expression of VEGF as an angiogenic factor, angiostatin as an angiostatic factor and caspase-3 at area at risk decrease significantly in response to exercise training compared to the sedentary group. The capillary and arteriolar density in the Ex groups were significantly higher than those of the Sed groups. Compared to the Ex-MI group, the Ex+La group showed a markedly increase in capillary to fiber ratio. No significant differences were found in infarct size among the four groups, but cardiac function increased in response to exercise. Exercise training increases revascularization at area at risk by reduction of angiostatin. L-arginine supplementation causes additional effects on exercise-induced angiogenesis by preventing more reduction of VEGF gene expression in response to exercise. These improvements, in turn, increase left ventricular systolic function and decrease mortality in myocardial infarction rats. PMID:26869868

  15. Moderate hypothermia and brain temperature in patients with severe middle cerebral artery infarction.

    PubMed

    Schwab, S; Schwarz, S; Aschoff, A; Keller, E; Hacke, W

    1998-01-01

    Elevated temperature is known to facilitate neuronal injury after ischemia. After head injury a gradient between temperature and body temperature of up to 3 degrees C higher in the brain has been reported. Hypothermia may limit some of the deleterious metabolic consequences of such increased temperature. In 20 patients who had suffered severe ischemic stroke in the middle cerebral artery (MCA) territory, intracerebral temperature combined with ICP monitoring was recorded using two different thermocouples, with epidural, and parenchymatous measurements. Mild hypothermia was induced using cooling blankets. Patients were kept at 33 degrees C core temperature for 48 to 72 hours. In all patients brain temperature exceeded body-core temperature by at least up to 1 degree C (range 1.0-2.1 degrees C). Systemic cooling was effective and sustained hypothermic (33-34 degrees C) brain temperatures. With mild hypothermia critically elevated ICP values could be controlled. 12 patients survived the hemispheric stroke with a mean Barthel index of 70. Severe side effects of hypothermia were not detected. After MCA stroke, human intracerebral temperature is higher than central body-core temperature. Mild hypothermia in the treatment of severe cerebral ischemia using cooling blankets is safe and does not lead to severe side effects. Mild hypothermia can help to control critically elevated ICP values in severe space-occupying stroke and may improve clinical outcome in these patients. PMID:9779165

  16. 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

  17. Extracorporeal shock wave effectively attenuates brain infarct volume and improves neurological function in rat after acute ischemic stroke

    PubMed Central

    Yuen, Chun-Man; Chung, Sheng-Ying; Tsai, Tzu-Hsien; Sung, Pei-Hsun; Huang, Tien-Hung; Chen, Yi-Ling; Chen, Yung-Lung; Chai, Han-Tan; Zhen, Yen-Yi; Chang, Meng-Wei; Wang, Ching-Jen; Chang, Hsueh-Wen; Sun, Cheuk-Kwan; Yip, Hon-Kan

    2015-01-01

    Background: To investigate the effect of shock wave (SW) on brain-infarction volume (BIV) and neurological function in acute ischemic stroke (AIS) by left internal carotid artery occlusion in rats. Methods and results: SD rats (n=48) were divided into group 1 [sham-control (SC)], group 2 [SC-ECSW (energy dosage of 0.15 mJ/mm2/300 impulses)], group 3 (AIS), and group 4 (AIS-ECSW) and sacrificed by day 28 after IS induction. In normal rats, caspase-3, Bax and TNF-? biomarkers did not differ between animals with and without ECSW therapy, whereas Hsp70 was activated post-ECSW treatment. By day 21 after AIS, Sensorimotor-functional test identified a higher frequency of turning movement to left in group 3 than that in group 4 (P<0.05). By day 28, brain MRI demonstrated lager BIV in group 3 than that in group 4 (P<0.001). Angiogenesis biomarkers at cellular (CD31, ?-SMA+) and protein (eNOS) levels and number of neuN+ cells were higher in groups 1 and 2 than those in groups 3 and 4, and higher in group 4 than those in group 3, whereas VEGF and Hsp70 levels were progressively increased from groups 1 and 2 to group 4 (all P<0.001). Protein expressions of apoptosis (Bax, caspase 3, PARP), inflammation (MMP-9, TNF-?), oxidative stress (NOX-1, NOX-2, oxidized protein) and DNA-damage marker (?-H2AX), and expressions of ?-H2AX+, GFAP+, AQP-4+ cells showed an opposite pattern compared to that of angiogenesis among the four groups (all P<0.001). Conclusion: ECSW therapy was safe and effective in reducing BIV and improved neurological function. PMID:26279744

  18. A model of prehospital death from ventricular fibrillation following myocardial infarction.

    PubMed Central

    Cretin, S; Willemain, T R

    1979-01-01

    Current efforts to reduce prehospital cardiac mortality focus more on deployment of specially equipped ambulances than on reduction of patient or ambulance delays. To evaluate this strategy, we needed to find a method that would isolate the separate effects of patient delay, ambulance delay, and the resuscitative capability of the ambulance. Using published data, we have generated a mathematical model of death from ventricular fibrillation following myocardial infarction that shows the relationship among these three factors. Analyses based on the model indicate that the potential life saving impact of a defibrillation-equipped ambulance is severely limited due to typical patient response patterns. If the ambulance arrives ten minutes after the onset of infarction, defibrillation capabilities will reduce prehospital mortality from 6 percent to 2 percent. After a more typical delay of 60 minutes, the mortality rises sharply to 13 percent for an unequipped ambulance. With a delay of this length, defibrillation capabilities reduce mortality only to about 12 percent. PMID:521294

  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. 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.

  1. Anaerobic Threshold by Mathematical Model in Healthy and Post-Myocardial Infarction Men.

    PubMed

    Novais, L D; Silva, E; Simões, R P; Sakabe, D I; Martins, L E B; Oliveira, L; Diniz, C A R; Gallo, L; Catai, A M

    2016-02-01

    The aim of this study was to determine the anaerobic threshold (AT) in a population of healthy and post-myocardial infarction men by applying Hinkley's mathematical method and comparing its performance to the ventilatory visual method. This mathematical model, in lieu of observer-dependent visual determination, can produce more reliable results due to the uniformity of the procedure. 17 middle-aged men (55±3 years) were studied in 2 groups: 9 healthy men (54±2 years); and 8 men with previous myocardial infarction (57±3 years). All subjects underwent an incremental ramp exercise test until physical exhaustion. Breath-by-breath ventilatory variables, heart rate (HR), and vastus lateralis surface electromyography (sEMG) signal were collected throughout the test. Carbon dioxide output (V˙CO2), HR, and sEMG were studied, and the AT determination methods were compared using correlation coefficients and Bland-Altman plots. Parametric statistical tests were applied with significance level set at 5%. No significant differences were found in the HR, sEMG, and ventilatory variables at AT between the different methods, such as the intensity of effort relative to AT. Moreover, important concordance and significant correlations were observed between the methods. We concluded that the mathematical model was suitable for detecting the AT in both healthy and myocardial infarction subjects. PMID:26509383

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

    PubMed Central

    Muetn-Gmez, Vilma C.; Doncel-Prez, Ernesto; Fernandez, Ana P.; Serrano, Julia; Pozo-Rodriglvarez, Andrea; Vellosillo-Huerta, Lara; Taylor, Julian S.; Cardona-Gmez, Gloria P.; Nieto-Sampedro, Manuel; Martnez-Murillo, Ricardo

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. Defibrotide reduces infarct size in a rabbit model of experimental myocardial ischaemia and reperfusion.

    PubMed Central

    Thiemermann, C.; Thomas, G. R.; Vane, J. R.

    1989-01-01

    1. Defibrotide, a single-stranded polydeoxyribonucleotide obtained from bovine lungs, has significant anti-thrombotic, pro-fibrinolytic and prostacyclin-stimulating properties. 2. The present study was designed to evaluate the effects of defibrotide on infarct size and regional myocardial blood flow in a rabbit model of myocardial ischaemia and reperfusion. 3. Defibrotide (32 mg kg-1 bolus + 32 mg kg-1 h-1, i.v.) either with or without co-administration of indomethacin (5 mg kg-1 x 2, i.v.) was administered 5 min after occlusion of the left anterior-lateral coronary artery and continued during the 60 min occlusion and subsequent 3 h reperfusion periods. 4. Defibrotide significantly attenuated the ischaemia-induced ST-segment elevation and abolished the reperfusion-related changes (R-wave reduction and Q-wave development) in the electrocardiogram. In addition, defibrotide significantly improved myocardial blood flow in normal and in ischaemic, but not in infarcted sections of the heart. The improvement in blood flow in normal perfused myocardium, but not in the ischaemic area was prevented by indomethacin. 5. Although the area at risk was similar in all animal groups studied, defibrotide treatment resulted in a 51% reduction of infarct size. Indomethacin treatment abolished the reduction of infarct size seen with defibrotide alone. 6. The data demonstrate a considerable cardioprotective effect of defibrotide in the reperfused ischaemic rabbit myocardium. This effect may be related, at least in part, to a stimulation of endogenous prostaglandin formation. Other possible mechanisms are discussed. PMID:2758223

  5. Predictors of Pulmonary Infarction.

    PubMed

    Miniati, Massimo; Bottai, Matteo; Ciccotosto, Cesario; Roberto, Luca; Monti, Simonetta

    2015-10-01

    In the setting of acute pulmonary embolism (PE), pulmonary infarction is deemed to occur primarily in individuals with compromised cardiac function.The current study was undertaken to establish the prevalence of pulmonary infarction in patients with acute PE, and the relationship between infarction and: age, body height, body mass index (BMI), smoking habits, clot burden, and comorbidities.The authors studied prospectively 335 patients with acute PE diagnosed by computed tomographic angiography (CT) in 18 hospitals throughout central Italy. The diagnosis of pulmonary infarction on CT was based on Hampton and Castleman's criteria (cushion-like or hemispherical consolidation lying along the visceral pleura). Multivariable logistic regression was used to model the relationship between covariates and the probability of pulmonary infarction.The prevalence of pulmonary infarction was 31%. Patients with infarction were significantly younger and with significantly lower prevalence of cardiovascular disease than those without (P?infarction increased linearly with increasing height, and decreased with increasing BMI. In logistic regression, the covariates significantly associated with the probability of infarction were age, body height, BMI, and current smoking. The risk of infarction grew with age, peaked at approximately age 40, and decreased afterwards. Increasing body height and current smoking were significant amplifiers of the risk of infarction, whereas increasing BMI appeared to confer some protection.Our data indicate that pulmonary infarction occurs in nearly one-third of the patients with acute PE. Those with infarction are often young and otherwise healthy. Increasing body height and active smoking are predisposing risk factors. PMID:26469892

  6. Predictors of Pulmonary Infarction

    PubMed Central

    Miniati, Massimo; Bottai, Matteo; Ciccotosto, Cesario; Roberto, Luca; Monti, Simonetta

    2015-01-01

    Abstract In the setting of acute pulmonary embolism (PE), pulmonary infarction is deemed to occur primarily in individuals with compromised cardiac function. The current study was undertaken to establish the prevalence of pulmonary infarction in patients with acute PE, and the relationship between infarction and: age, body height, body mass index (BMI), smoking habits, clot burden, and comorbidities. The authors studied prospectively 335 patients with acute PE diagnosed by computed tomographic angiography (CT) in 18 hospitals throughout central Italy. The diagnosis of pulmonary infarction on CT was based on Hampton and Castleman's criteria (cushion-like or hemispherical consolidation lying along the visceral pleura). Multivariable logistic regression was used to model the relationship between covariates and the probability of pulmonary infarction. The prevalence of pulmonary infarction was 31%. Patients with infarction were significantly younger and with significantly lower prevalence of cardiovascular disease than those without (P?infarction increased linearly with increasing height, and decreased with increasing BMI. In logistic regression, the covariates significantly associated with the probability of infarction were age, body height, BMI, and current smoking. The risk of infarction grew with age, peaked at approximately age 40, and decreased afterwards. Increasing body height and current smoking were significant amplifiers of the risk of infarction, whereas increasing BMI appeared to confer some protection. Our data indicate that pulmonary infarction occurs in nearly one-third of the patients with acute PE. Those with infarction are often young and otherwise healthy. Increasing body height and active smoking are predisposing risk factors. PMID:26469892

  7. Inhomogeneity of collagen organization within the fibrotic scar after myocardial infarction: results in a swine model and in human samples.

    PubMed

    Hervas, Arantxa; Ruiz-Sauri, Amparo; de Dios, Elena; Forteza, Maria Jose; Minana, Gema; Nunez, Julio; Gomez, Cristina; Bonanad, Clara; Perez-Sole, Nerea; Gavara, Jose; Chorro, Francisco Javier; Bodi, Vicente

    2016-01-01

    We aimed to characterize the organization of collagen within a fibrotic scar in swine and human samples from patients with chronic infarctions. Swine were subjected to occlusion of the left anterior descending artery followed by reperfusion 1 week (acute myocardial infarction group) or 1 month (chronic myocardial infarction group) after infarction. The organization of the collagen fibers (Fast Fourier Transform of samples after picrosirius staining; higher values indicate more disorganization) was studied in 100 swine and 95 human samples. No differences in collagen organization were found between the acute and chronic groups in the core area of the scar in the experimental model. In the chronic group, the endocardium [0.90 (0.84-0.94); median (interquartile range)], epicardium [0.84 (0.79-0.91)] and peripheral area [0.73 (0.63-0.83)] displayed a much more disorganized pattern than the core area of the fibrotic scar [0.56 (0.45-0.64)]. Similarly, in human samples, the collagen fibers were more disorganized in all of the outer areas than in the core of the fibrotic scar (P<0.0001). Both in a highly controlled experimental model and in patient samples, collagen fibers exhibited an organized pattern in the core of the infarction, whereas the outer areas displayed a high level of inhomogeneity. This finding contributes pathophysiological information regarding the healing process and may lead to a clearer understanding of the genesis and invasive treatment of arrhythmias after acute myocardial infarction. PMID:26510481

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2012-01-01

    Objective This study sought to test the hypothesis that virtual electrophysiologic studies (EPS) on an anatomic platform generated by 3D MRI reconstruction of the left ventricle (LV) can reproduce the reentrant circuits of induced ventricular tachycardia (VT) in a porcine model of myocardial infarction (MI). Background Delayed-enhancement MRI has been used to characterize MI and gray zones, which are thought to reflect heterogeneous regions of viable and non-viable myocytes. Methods MI by coronary artery occlusion was induced in eight pigs. After a recovery period, 3D cardiac MRIs were obtained from each pig in-vivo. Normal areas, gray zones, and infarct cores were classified based on voxel intensity. In the computer model, gray zones were assigned slower conduction and longer action potential durations than those for normal myocardium. Virtual EPS was performed and was compared to results of actual in vivo programmed stimulation and non-contact mapping. Results The LV volumes ranged from 97.8 to 166.2 cm3 with 4.9 to 17.5% of voxels classified as infarct zones. Six of the seven pigs that developed VT during actual EPS were also inducible with virtual EPS. Four of the six pigs that had simulated VT had reentrant circuits that approximated the circuits seen with non-contact mapping, while the remaining two had similar circuits but propagating in opposite directions. Conclusions This initial study demonstrates the feasibility of applying a mathematical model to MRI reconstructions of the LV to predict VT circuits. Virtual EPS may be helpful to plan catheter ablation strategies or to identify patients who are at risk for future episodes of VT. PMID:22633654

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

    PubMed

    Chrastina, Adrian; Pokreisz, Peter; Schnitzer, Jan E

    2014-01-15

    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

  11. Brain Excitability in Stroke

    PubMed Central

    Carmichael, S. Thomas

    2015-01-01

    There is no current medical therapy for stroke recovery. Principles of physiological plasticity have been identified during recovery in both animal models and human stroke. Stroke produces a loss of physiological brain maps in adjacent peri-infarct cortex and then a remapping of motor and sensory functions in this region. This remapping of function in peri-infarct cortex correlates closely with recovery. Recent studies have shown that the stroke produces abnormal conditions of excitability in neuronal circuits adjacent to the infarct that may be the substrate for this process of brain remapping and recovery. Stroke causes a hypo-excitability in peri-infarct motor cortex that stems from increased tonic ?-aminobutyric acid activity onto neurons. Drugs that reverse this ?-aminobutyric acid signaling promote recovery after stroke. Stroke also increases the sensitivity of glutamate receptor signaling in peri-infarct cortex well after the stroke event, and stimulating ?-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate glutamate receptors in peri-infarct cortex promotes recovery after stroke. Both blocking tonic ?-aminobutyric acid currents and stimulating ?-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors promote recovery after stroke when initiated at quite a delay, more than 3 to 5 days after the infarct. These changes in the excitability of neuronal circuits in peri-infarct cortex after stroke may underlie the process of remapping motor and sensory function after stroke and may identify new therapeutic targets to promote stroke recovery. PMID:21987395

  12. Potential economic consequences of a cardioprotective agent for patients with myocardial infarction: modelling study

    PubMed Central

    Verhoef, Talitha I; Morris, Stephen; Mathur, Anthony; Singer, Mervyn

    2015-01-01

    Objective To investigate the cost-effectiveness of a hypothetical cardioprotective agent used to reduce infarct size in patients undergoing percutaneous coronary intervention (PCI) after anterior ST-elevation myocardial infarction. Methods Design: A cost-utility analysis using a Markov model. Setting: The National Health Service in the UK. Patients: Patients undergoing PCI after anterior ST-elevation myocardial infarction. Interventions: A cardioprotective agent given at the time of reperfusion compared to no cardioprotection. We assumed the cardioprotective agent (given at the time of reperfusion) would reduce the risk and severity of heart failure (HF) after PCI and the risk of mortality after PCI (with a relative risk ranging from 0.6 to 1). The costs of the cardioprotective agent were assumed to be in the range £1000–4000. Main outcome measures: The incremental costs per quality-adjusted life-year (QALY) gained, using 95% CIs from 1000 simulations. Results Incremental costs ranged from £933 to £3820 and incremental QALYs from 0.04 to 0.38. The incremental cost-effectiveness ratio (ICER) ranged from £3311 to £63 480 per QALY gained. The results were highly dependent on the costs of a cardioprotective agent, patient age, and the relative risk of HF after PCI. The ICER was below the willingness-to-pay threshold of £20 000 per QALY gained in 71% of the simulations. Conclusions A cardioprotective agent that can reduce the risk of HF and mortality after PCI has a high chance of being cost-effective. This chance depends on the price of the agent, the age of the patient and the relative risk of HF after PCI. PMID:26567251

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

    PubMed Central

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

    2014-01-01

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

  14. 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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  17. Analysis of the Influence of the Electrical Asynchrony on Regional Mechanics of the Infarcted Left Ventricle Using Electromechanical Heart Models

    NASA Astrophysics Data System (ADS)

    Liu, Feng; Xia, Ling; Zhang, Xin

    Asynchronous electrical activation, as induced by myocardial infarction, causes various abnormalities in left ventricle function. The influence of the electrical asynchrony on regional mechanics of the left ventricle is simulated using a mechanical heart model and an electrical heart model. The mechanical model accounts for the ventricular geometry, the fiber nature of the myocardial tissue, and the dependency of the activation sequence of the ventricular wall. The electrical model is based on a heart-torso model with realistic geometry, and different action potential waveforms with variables in duration are used to simulate the abnormal electrical activation after myocardial infarction. Regional deformation, strain and stress are calculated during systole phase. The preliminary results show that asynchronous electrical activation, as an important factor, significantly affects regional mechanical performance of the infarcted left ventricle, it indicates heterogeneous contraction pattern and elevated systolic stresses near the injured region. The simulated results are compared with solutions obtained in the literature. This simulation suggests that such coupled heart models can be used to assess the mechanical function of the left ventricle with diseases such as myocardial infarction, and more realistic models of cardiac function are essential for clinical evaluation of heart disease.

  18. Sesamin attenuates neurotoxicity in mouse model of ischemic brain stroke.

    PubMed

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

    2014-12-01

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

  19. Simple models of human brain functional networks.

    PubMed

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

    2012-04-10

    Human brain functional networks are embedded in anatomical space and have topological properties--small-worldness, modularity, fat-tailed degree distributions--that are comparable to many other complex networks. Although a sophisticated set of measures is available to describe the topology of brain networks, the selection pressures that drive their formation remain largely unknown. Here we consider generative models for the probability of a functional connection (an edge) between two cortical regions (nodes) separated by some Euclidean distance in anatomical space. In particular, we propose a model in which the embedded topology of brain networks emerges from two competing factors: a distance penalty based on the cost of maintaining long-range connections; and a topological term that favors links between regions sharing similar input. We show that, together, these two biologically plausible factors are sufficient to capture an impressive range of topological properties of functional brain networks. Model parameters estimated in one set of functional MRI (fMRI) data on normal volunteers provided a good fit to networks estimated in a second independent sample of fMRI data. Furthermore, slightly detuned model parameters also generated a reasonable simulation of the abnormal properties of brain functional networks in people with schizophrenia. We therefore anticipate that many aspects of brain network organization, in health and disease, may be parsimoniously explained by an economical clustering rule for the probability of functional connectivity between different brain areas. PMID:22467830

  20. 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

  1. [Bilateral caudate head infarcts].

    PubMed

    Kuriyama, N; Yamamoto, Y; Akiguchi, I; Oiwa, K; Nakajima, K

    1997-11-01

    We reported a 67-year-old woman with bilateral caudate head infarcts. She developed sudden mutism followed by abulia. She was admitted to our hospital 2 months after ictus for further examination. She showed prominent abulia and was inactive, slow and apathetic. Spontaneous activity and speech, immediate response to queries, spontaneous word recall and attention and persistence to complex programs were disturbed. Apparent motor disturbance, gait disturbance, motor aphasia, apraxia and remote memory disturbance were not identified. She seemed to be depressed but not sad. Brain CT and MRI revealed bilateral caudate head hemorrhagic infarcts including bilateral anterior internal capsules, in which the left lesion was more extensive than right one and involved the part of the left putamen. These infarct locations were thought to be supplied by the area around the medial striate artery including Heubner's arteries and the A1 perforator. Digital subtraction angiography showed asymptomatic right internal carotid artery occlusion. She bad had hypertension, diabetes mellitus and atrial fibrillation and also had a left atrium with a large diameter. The infarcts were thought to be caused by cardioembolic occlusion to the distal portion of the left internal carotid artery. Although some variations of vasculature at the anterior communicating artery might contribute to bilateral medial striate artery infarcts, we could not demonstrate such abnormalities by angiography. Bilateral caudate head infarcts involving the anterior internal capsule may cause prominent abulia. The patient did not improve by drug and rehabilitation therapy and died suddenly a year after discharge. PMID:9503974

  2. Modeling human brain development with cerebral organoids.

    PubMed

    Muzio, Luca; Consalez, G Giacomo

    2013-01-01

    The recent discovery of a new three-dimensional culture system for the derivation of cerebral organoids from human induced pluripotent stem cells provides developmental neurobiologists with the first example of a three-dimensional framework for the study of human brain development. This innovative approach permits the in vitro assembly of a human embryonic brain rudiment that recapitulates the developing human cerebrum. Organoids contain progenitor populations that develop to yield mature cortical neuron subtypes, potentially allowing investigators to study complex brain diseases that lack appropriate animal models. PMID:24367992

  3. Traumatic brain injury using mouse models.

    PubMed

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

    2014-08-01

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

  4. Effect of ranolazine on infarct size in a canine model of regional myocardial ischemia/reperfusion.

    PubMed

    Black, S C; Gralinski, M R; McCormack, J G; Driscoll, E M; Lucchesi, B R

    1994-12-01

    We assessed ranolazine's potential to reduce myocardial injury resulting from 90-min occlusion and 18-h reperfusion of left circumflex coronary artery (LCX) in anesthetized dogs. Ranolazine, a putative antianginal agent, has exhibited positive results in a variety of experimental models associated with the ischemic myocardium. Previous studies demonstrated that ranolazine possesses a mechanism of action involving increases in the amount of active pyruvate dehydrogenase during ischemia, suggesting that the compound may act to promote glucose utilization. Ranolazine was administered as a bolus of 3.3 mg/kg, followed by a constant infusion of 7.2 mg/kg/h for 20 h. The loading dose was administered 30 min before LCX occlusion. Control animals received appropriate volumes of vehicles (loading and infusion). Hemodynamics were unchanged between ranolazine and vehicle groups. Three animals in each group were excluded because of ventricular fibrillation (VF). There was no difference in degree of ST segment change between control and ranolazine-treated groups at any time during LCX occlusion. The area at risk (AAR) of infarct was 40.1 +/- 1.7 and 38.9 +/- 1.3% in control-treated (n = 13) and randolazine-treated (n = 8) animals, respectively (p = 0.631). Myocardial infarct size (IS) was 31.7 +/- 5.2 and 36.6 +/- 8.5% in control and ranolazine-treated animals, respectively (p = 0.603). No significant changes were observed in plasma content of enzymatic markers at 0.5, 2.0, and 18.0 h of reperfusion. The results of this in vivo study indicate that ranolazine did not provide protection from injury to regionally ischemic and reperfused myocardium despite its reported antiischemic activity. PMID:7898075

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

    PubMed Central

    Crisstomo, Vernica; Maestre, Juan; Maynar, Manuel; Sun, Fei; Bez-Daz, Claudia; Usn, Jess; Snchez-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

  6. An Ultrasound-Driven Kinematic Model for Deformation of the Infarcted Mouse Left Ventricle Incorporating A Near-Incompressibility Constraint

    PubMed Central

    Lin, Dan; French, Brent A.; Xu, Yaqin; Hossack, John A.; Holmes, Jeffrey W.

    2014-01-01

    Mathematical models of varying complexity have proved useful in fitting and interpreting regional cardiac displacements obtained from imaging methods such as ultrasound speckle tracking or MRI tagging. Simpler models, such as the classic thick-walled cylinder model of the left ventricle (LV), solve quickly and are easy to implement, but they ignore regional geometric variations and are difficult to adapt to the study of regional pathologies such as myocardial infarction. Complex, anatomically accurate finite-element models work well but are computationally intensive and require specialized expertise to implement. We developed a kinematic model that offers a compromise between these two traditional approaches, assuming only that displacements in the left ventricle are polynomial functions of initial position and that the myocardium is nearly incompressible, while allowing myocardial motion to vary spatially as would be expected in an ischemic or dyssynchronous left ventricle. Model parameters were determined using an objective function with adjustable weights to account for confidence in individual displacement components and desired strength of the incompressibility constraint. The model accurately represented the motion of both normal and infarcted mouse left ventricles during the cardiac cycle, with normalized root mean square errors in predicted deformed positions of 8.2 2.3% and 7.4 2.1% for normal and infarcted hearts, respectively. PMID:25542490

  7. MALDI Mass Spectrometric Imaging of Cardiac Tissue Following Myocardial Infarction in a Rat Coronary Artery Ligation Model

    PubMed Central

    Menger, Robert F.; Stutts, Whitney L.; Anbukumar, Dhanam S.; Bowden, John A.; Ford, David A.; Yost, Richard A.

    2011-01-01

    Although acute myocardial infarction (MI) is consistently among the top causes of death in the United States, the spatial distribution of lipids and metabolites following MI remains to be elucidated. This work presents the investigation of an in vivo rat model of MI using mass spectrometric imaging (MSI) and multivariate data analysis. MSI was conducted on cardiac tissue following a 24-hour left anterior descending coronary artery ligation in order to analyze multiple compound classes. First, the spatial distribution of a small metabolite, creatine, was used to identify areas of infarcted myocardium. Second, multivariate data analysis and tandem mass spectrometry were used to identify phospholipid (PL) markers of MI. A number of lysophospholipids demonstrated increased ion signal in areas of infarction. In contrast, select intact PLs demonstrated decreased ion signal in the area of infarction. The complementary nature of these two lipid classes suggest increased activity of phospholipase A2, an enzyme that has been implicated in coronary heart disease and inflammation. PMID:22141424

  8. Twenty-four hours hypothermia has temporary efficacy in reducing brain infarction and inflammation in aged rats.

    PubMed

    Sandu, Raluca Elena; Buga, Ana-Maria; Balseanu, Adrian Tudor; Moldovan, Mihai; Popa-Wagner, Aurel

    2016-02-01

    Stroke is a major cause of disability for which no neuroprotective measures are available. Age is the principal nonmodifiable risk factor for this disease. Previously, we reported that exposure to hydrogen sulfide for 48 hours after stroke lowers whole body temperature and confers neuroprotection in aged animals. Because the duration of hypothermia in most clinical trials is between 24 and 48 hours, we questioned whether 24 hours exposure to gaseous hypothermia confers the same neuroprotective efficacy as 48 hours exposure. We found that a shorter exposure to hypothermia transiently reduced both inflammation and infarct size. However, after 1 week, the infarct size became even larger than in controls and after 2 weeks there was no beneficial effect on regenerative processes such as neurogenesis. Behaviorally, hypothermia also had a limited beneficial effect. Finally, after hydrogen sulfide-induced hypothermia, the poststroke aged rats experienced a persistent sleep impairment during their active nocturnal period. Our data suggest that cellular events that are delayed by hypothermia in aged rats may, in the long term, rebound, and diminish the beneficial effects. PMID:26827651

  9. 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; Kekul, Alexander; Paulsen, Friedrich; Maronde, Erik; Bruer, 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

  10. Compact continuum brain model for human electroencephalogram

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

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

    PubMed Central

    2010-01-01

    Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 3.4 vs control: 74.1 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 1.2 vs control: 5.3 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability. PMID:20875134

  12. 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. Supported by NSF CDI-Type II grant IOS-1124804, Computational resource by XSEDE NSF grant TG-CTS100002.

  13. Ventricular Arrhythmias and Mortality Associated with Isoflurane and Sevoflurane in a Porcine Model of Myocardial Infarction

    PubMed Central

    Regueiro-Purriños, Marta; Fernández-Vázquez, Felipe; de Prado, Armando Perez; Altónaga, Jose R; Cuellas-Ramón, Carlos; Ajenjo-Silverio, Jose M; Orden, Asuncion; Gonzalo-Orden, Jose M

    2011-01-01

    Ischemia of the myocardium can lead to reversible or irreversible injury depending on the severity and duration of the preceding ischemia. Here we compared sevoflurane and isoflurane with particular reference to their hemodynamic effects and ability to modify the effects of acute severe myocardial ischemia and reperfusion on ventricular arrhythmias and mortality in a porcine model of myocardial infarction. Female Large White pigs were premedicated with ketamine, midazolam, and atropine. Propofol was given intravenously for the anesthetic induction, and anesthesia was maintained with isoflurane or sevoflurane. Endovascular, fluoroscopy-guided, coronary procedures were performed to occlude the midleft anterior descending artery by using a coronary angioplasty balloon. After 75 min, the balloon catheter system was withdrawn and the presence of adequate reperfusion flow was verified. The pigs were followed for 2 mo, and overall mortality rate was calculated. The isoflurane group showed lower arterial pressure throughout the procedure, with the difference reaching statistical significance after induction of myocardial ischemia. The ventricular fibrillation rate was higher in isoflurane group (81.3%) than the sevoflurane group (51.7%; relative risk, 1.57 [1.03 to 2.4]). Overall survival was lower in the isoflurane group (75%) than the sevoflurane group (96.4%). In conclusion, in this porcine model of myocardial ischemia and reperfusion, sevoflurane was associated with higher hemodynamic stability and fewer ventricular arrhythmias and mortality than was isoflurane. PMID:21333167

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

    PubMed Central

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

    2008-01-01

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

  15. A swine model of infarct-related reentrant ventricular tachycardia: Electroanatomic, magnetic resonance, and histopathological characterization

    PubMed Central

    Tschabrunn, Cory M.; Roujol, Sbastien; Nezafat, Reza; Faulkner-Jones, Beverly; Buxton, Alfred E.; Josephson, Mark E.; Anter, Elad

    2016-01-01

    BACKGROUND Human ventricular tachycardia (VT) after myocardial infarction usually occurs because of subendocardial reentrant circuits originating in scar tissue that borders surviving myocardial bundles. Several preclinical large animal models have been used to further study postinfarct reentrant VT, but with varied experimental methodologies and limited evaluation of the underlying substrate or induced arrhythmia mechanism. OBJECTIVE We aimed to develop and characterize a swine model of scar-related reentrant VT. METHODS Thirty-five Yorkshire swine underwent 180-minute occlusion of the left anterior descending coronary artery. Thirty-one animals (89%) survived the 68-week survival period. These animals underwent cardiac magnetic resonance imaging followed by electrophysiology study, detailed electroanatomic mapping, and histopathological analysis. RESULTS Left ventricular (LV) ejection fraction measured using CMR imaging was 36% 6.6% with anteroseptal wall motion abnormality and late gadolinium enhancement across 12.5% 4.1% of the LV surface area. Low voltage measured using endocardial electroanatomic mapping encompassed 11.1% 3.5% of the LV surface area (bipolar voltage ?1.5 mV) with anterior, anteroseptal, and anterolateral involvement. Reentrant circuits mapped were largely determined by functional rather than fix anatomical barriers, consistent with pseudo-block due to anisotropic conduction. Sustained monomorphic VT was induced in 28 of 31 swine (90%) (67 VTs; 2.4 1.1; range 14) and characterized as reentry. VT circuits were subendocardial, with an arrhythmogenic substrate characterized by transmural anterior scar with varying degrees of fibrosis and myocardial fiber disarray on the septal and lateral borders. CONCLUSION This is a well-characterized swine model of scar-related subendocardial reentrant VT. This model can serve as the basis for further investigation in the physiology and therapeutics of humanlike postinfarction reentrant VT. PMID:26226214

  16. Neurodynamical model of collective brain

    NASA Technical Reports Server (NTRS)

    Zak, Michail

    1992-01-01

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

  17. The body surface isopotential maps of the non-transmural infarctions--a simulation study of excitation spread in a ventricular model.

    PubMed

    Ishikawa, T; Okajima, M; Nimi, N; Koike, Y; Toyama, J; Yamada, K

    1980-02-01

    Simulation by a digital computer of excitation spread in a human ventricular model produced displays of body surface isopotential maps. Localization of model myocardial infarctions to non-transmural and transmural sites produced distinctive differences in these displayed isopotential maps. The body surface directly over the infarcted lesion was negative in potential only in the first half period of the QRS complex and then became positive. The model demonstrated that this later positive potential was due to delayed arrival of excitation to the subepicardial layer outside of the subendocardial lesion. While, in transmural infarction, the overlying body surface remained negative in potential throughout the QRS complex. It is expected that body surface isopotential maps will become clinically available and will permit helpful differential diagnoses between non-transumral and transmural myocardial infarctions. PMID:7365984

  18. Detection and evaluation of renal biomarkers in a swine model of acute myocardial infarction and reperfusion.

    PubMed

    Duan, Su-Yan; Xing, Chang-Ying; Zhang, Bo; Chen, Yan

    2015-01-01

    The prevalence of type 1 cardiorenal syndrome (CRS) is increasing and strongly associated with long-term mortality. However, lack of reliable animal models and well-defined measures of renoprotection, made early diagnosis and therapy difficult. We previously successfully established the swine acute myocardial infarction (AMI) model of ischemia-reperfusion by blocking left anterior descending branch (LAD). Reperfusion was performed after 90-minute occlusion of the LAD. AMI was confirmed by ECG and left ventricular angiography (LVG). Then those 52 survived AMI reperfusion swine, including ventricular fibrillation-cardiac arrest after restoration of blood flow, were randomly divided into four groups (four/group) according to different interventions: resuscitation in room temperature, resuscitation with 500 ml saline in room temperature, resuscitation with 4°C 500 ml saline and normal control (with no intervention of resuscitation). Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias: 1, 3, 5, 10-minute reperfusion after ventricular arrhythmias. Plasma and random urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury (AKI). Our swine AMI model of ischemia-reperfusion provoked subclinical AKI with the elevation of the tubular damage biomarker, NGAL, IL-18 and L-FABP. Renal damage rapidly observed after hemodynamic instability, rather than observation after several hours as previously reported. The increasing rate of biological markers declined after interventions, however, its impact on the long-term prognosis remains to be further studied. These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS. PMID:26339403

  19. Detection and evaluation of renal biomarkers in a swine model of acute myocardial infarction and reperfusion

    PubMed Central

    Duan, Su-Yan; Xing, Chang-Ying; Zhang, Bo; Chen, Yan

    2015-01-01

    The prevalence of type 1 cardiorenal syndrome (CRS) is increasing and strongly associated with long-term mortality. However, lack of reliable animal models and well-defined measures of renoprotection, made early diagnosis and therapy difficult. We previously successfully established the swine acute myocardial infarction (AMI) model of ischemia-reperfusion by blocking left anterior descending branch (LAD). Reperfusion was performed after 90-minute occlusion of the LAD. AMI was confirmed by ECG and left ventricular angiography (LVG). Then those 52 survived AMI reperfusion swine, including ventricular fibrillation-cardiac arrest after restoration of blood flow, were randomly divided into four groups (four/group) according to different interventions: resuscitation in room temperature, resuscitation with 500 ml saline in room temperature, resuscitation with 4°C 500 ml saline and normal control (with no intervention of resuscitation). Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias: 1, 3, 5, 10-minute reperfusion after ventricular arrhythmias. Plasma and random urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury (AKI). Our swine AMI model of ischemia-reperfusion provoked subclinical AKI with the elevation of the tubular damage biomarker, NGAL, IL-18 and L-FABP. Renal damage rapidly observed after hemodynamic instability, rather than observation after several hours as previously reported. The increasing rate of biological markers declined after interventions, however, its impact on the long-term prognosis remains to be further studied. These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS. PMID:26339403

  20. Targeted Delivery of Vascular Endothelial Growth Factor Improves Stem Cell Therapy in a Rat Myocardial Infarction Model

    PubMed Central

    Tang, Yuan; Gan, Xiaoliang; Cheheltani, Rabee; Curran, Elizabeth; Lamberti, Giuseppina; Krynska, Barbara; Kiani, Mohammad F.; Wang, Bin

    2014-01-01

    Rebuilding of infarcted myocardium by mesenchymal stem cells (MSCs) has not been successful because of poor cell survival due in part to insufficient blood supply after myocardial infarction (MI). We hypothesize that targeted delivery of vascular endothelial growth factor (VEGF) to MI can help regenerate vasculature in support of MSC therapy in a rat model of MI. VEGF-encapsulated immunoliposomes targeting overexpressed P-selectin in MI tissue were infused by tail vein immediately after MI. One week later, MSCs were injected intramyocardially. The cardiac function loss was moderated slightly by targeted delivery of VEGF or MSC treatment, while targeted VEGF + MSC combination treatment showed highest attenuation in cardiac function loss. The combination treatment also markedly increased blood vessel density (80%) and decreased the collagen content in post-MI tissue (33%). Engraftment of MSCs in the combination treatment group was significantly increased and the engrafted cells contributed to the restoration of blood vessels. PMID:24941463

  1. Stem cell-loaded nanofibrous patch promotes the regeneration of infarcted myocardium with functional improvement in rat model.

    PubMed

    Kai, Dan; Wang, Qiang-Li; Wang, Hai-Jie; Prabhakaran, Molamma P; Zhang, Yanzhong; Tan, Yu-Zhen; Ramakrishna, Seeram

    2014-06-01

    Myocardial infarction (MI) leads to the loss of cardiomyocytes, followed by left ventricular (LV) remodeling and cardiac dysfunction. The authors hypothesize that an elastic, biodegradable nanofibrous cardiac patch loaded with mesenchymal stem cells (MSC) could restrain LV remodeling and improve cardiac function after MI. Poly(?-caprolactone)/gelatin (PG) nanofibers were fabricated by electrospinning, and the nanofibers displayed a porous and uniform nanofibrous structure with a diameter of 24451nm. An MI model was established by ligation of the left anterior descending coronary artery of female Sprague-Dawley rats. The PG nanofibrous patch seeded with MSC, isolated from rat bone marrow, was implanted on the epicardium of the infarcted region of the LV wall of the heart. After transplantation, the PG-cell patch restricted the expansion of the LV wall effectively and reduced the scar size, and the density of the microvessels increased. Cells within the patch were able to migrate towards the scar tissue, and promoted new blood vessel formation at the infarct site. Angiogenesis and the cardiac functions improved significantly after 4weeks of implantation. The MSC-seeded PG nanofibrous patches are demonstrated to provide sufficient mechanical support, to induce angiogenesis and to accelerate cardiac repair in a rat model of MI. The study highlights the positive impact of implantation of an MSC-seeded PG nanofibrous patch as a novel constituent for MI repair. PMID:24576580

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

    SciTech Connect

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

    1986-07-01

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

  3. Neuroimaging of animal models of brain disease.

    PubMed

    Lythgoe, Mark F; Sibson, Nicola R; Harris, Neil G

    2003-01-01

    The main aim of this review is to describe some of the many animal models that have proved to be valuable from a neuroimaging perspective. This paper complements other articles in this volume, with a focus on animal models of the pathology of human brain disorders for investigations with modern non-invasive neuroimaging techniques. The use of animal model systems forms a fundamental part of neuroscience research efforts to improve the prevention, diagnosis, understanding and treatment of neurological conditions. Without such models it would be impossible to investigate such topics as the underlying mechanisms of neuronal cell damage and death, or to screen compounds for possible anticonvulsant properties. The adequacy of any one particular model depends on the suitability of information gained during experimental conditions. It is important, therefore, to understand the various types of animal model available and choose an appropriate model for the research question. PMID:12697629

  4. Plasma von Willebrand factor level is transiently elevated in a rat model of acute myocardial infarction

    PubMed Central

    LI, YAN; LI, LIQUN; DONG, FENGYUN; GUO, LING; HOU, YINGLONG; HU, HESHENG; YAN, SUHUA; ZHOU, XIAOJUN; LIAO, LIN; ALLEN, THADDEUS D.; LIU, JU

    2015-01-01

    The von Willebrand factor (vWF) is a plasma glycoprotein that plays an essential role in hemostasis by supporting platelet adhesion and thrombus formation in response to vascular injury. Plasma levels of vWF are an independent risk factor for patients with acute myocardial infarction (AMI); however, clinical data have demonstrated a marked variation of vWF levels in patients with AMI, the reason for which has not yet been identified. In the present study, a rat model of ST-segment elevation AMI was established, and cardiac and peripheral blood was collected for a time-course examination of the plasma levels of vWF and tumor necrosis factor-? (TNF-?). The level of vWF in the blood plasma increased, peaked at 1 h and decreased to normal levels by day 7 following AMI, while the level of TNF-? peaked at 24 h and remained elevated until day 7. The effects of TNF-? on vWF secretion and expression were examined in cultured human umbilical vascular endothelial cells (HUVECs). TNF-? treatment increased vWF secretion from the HUVECs but inhibited the mRNA and protein expression of vWF in the HUVECs. These results indicate that vWF secretion from endothelial cells is transiently elevated following AMI, and then decreases as the expression of vWF is inhibited by TNF-?. The present study increases the understanding of the pathophysiology of vWF and indicates that the determination of vWF levels may be useful in the clinical evaluation of AMI. PMID:26640545

  5. Convergent models of handedness and brain lateralization

    PubMed Central

    Sainburg, Robert L.

    2014-01-01

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

  6. Asiatic acid inhibits left ventricular remodeling and improves cardiac function in a rat model of myocardial infarction

    PubMed Central

    HUO, LIANYING; SHI, WENBING; CHONG, LING; WANG, JINLONG; ZHANG, KAI; LI, YUFENG

    2016-01-01

    Left ventricular remodeling results in cardiac dysfunction and accounts for the majority of the morbidity and mortality following myocardial infarction (MI). The aim of the present study was to investigate the effect of asiatic acid (AA) on cardiac function and left ventricular remodeling in a rat model of MI and explore the underlying mechanisms. Rats were subjected to coronary artery ligation to model MI and orally treated with AA. After 4 weeks, cardiac function was assessed by echocardiography. Cardiomyocyte cross-sectional area was recorded, and the expression levels of a number of inflammatory cytokines were detected using ELISA. The degree of interstitial fibrosis was determined by evaluating the mRNA expression levels of collagen II and III. Western blot analysis was performed to detect the expression levels of total and phosphorylated p38 MAPK and ERK1/2, to investigate whether they are involved in the mechanism underlying the effect of AA on the heart. Rats subjected to MI displayed significantly impaired cardiac function compared with those subjected to a sham procedure, while this change was reversed by treatment with AA. Furthermore, AA markedly inhibited cardiac hypertrophy, reduced the mRNA expression levels of inflammatory cytokines and decreased interstitial fibrosis in the infarct border zone of MI model rats compared with those in vehicle-treated MI model rats. Furthermore, the phosphorylation of p38 MAPK and ERK1/2 was blocked by AA in the MI rats but not in the sham rats. In summary, AA treatment preserved cardiac function and inhibited left ventricular remodeling, potentially by blocking the phosphorylation of p38 MAPK and ERK1/2 in the infarct border zone of the ischemic myocardium, indicating that AA may be a novel candidate for development as a therapy for MI. PMID:26889217

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

    PubMed

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

    2012-08-01

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

  8. Analyzing the Release of Copeptin from the Heart in Acute Myocardial Infarction Using a Transcoronary Gradient Model.

    PubMed

    Boeckel, Jes-Niels; Oppermann, Jana; Anadol, Remzi; Fichtlscherer, Stephan; Zeiher, Andreas M; Keller, Till

    2016-01-01

    Copeptin is the C-terminal end of pre-provasopressin released equimolar to vasopressin into circulation and recently discussed as promising cardiovascular biomarker amendatory to established markers such as troponins. Vasopressin is a cytokine synthesized in the hypothalamus. A direct release of copeptin from the heart into the circulation is implied by data from a rat model showing a cardiac origin in hearts put under cardiovascular wall stress. Therefore, evaluation of a potential release of copeptin from the human heart in acute myocardial infarction (AMI) has been done. PMID:26864512

  9. Analyzing the Release of Copeptin from the Heart in Acute Myocardial Infarction Using a Transcoronary Gradient Model

    PubMed Central

    Boeckel, Jes-Niels; Oppermann, Jana; Anadol, Remzi; Fichtlscherer, Stephan; Zeiher, Andreas M.; Keller, Till

    2016-01-01

    Copeptin is the C-terminal end of pre-provasopressin released equimolar to vasopressin into circulation and recently discussed as promising cardiovascular biomarker amendatory to established markers such as troponins. Vasopressin is a cytokine synthesized in the hypothalamus. A direct release of copeptin from the heart into the circulation is implied by data from a rat model showing a cardiac origin in hearts put under cardiovascular wall stress. Therefore, evaluation of a potential release of copeptin from the human heart in acute myocardial infarction (AMI) has been done. PMID:26864512

  10. 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

  11. Pretreatment with pentoxifylline has antidepressant-like effects in a rat model of acute myocardial infarction.

    PubMed

    Bah, Thierno Madjou; Kaloustian, Svan; Rousseau, Guy; Godbout, Roger

    2011-12-01

    We have observed that, after myocardial infarction (MI), rats display apoptosis in the limbic system that can be prevented by pentoxifylline (PTX), a proinflammatory cytokine inhibitor. We have hypothesized that reduction of apoptosis in the limbic system can attenuate the depressive behaviour occurring post-MI. The present study was, therefore, designed to assess the outcome of PTX on depressive behaviour manifesting after MI. Myocardial ischaemia, induced for 40 min in male Sprague-Dawley rats, was followed by reperfusion (MI groups). Sham groups were subjected to the same protocol without occlusion. PTX (10 mg/kg/day) or saline was administered intraperitoneally 15 min before ischaemia, and then every day until sacrifice. Two weeks after ischaemia, depression was evaluated by the forced swim test and the sucrose preference test. At the end of the experiment, the animals were sacrificed, and myocardial infarct size was examined along with plasma IL-1? concentrations. MI rats drank less sucrose in the sucrose preference test and were more immobile in the forced swim test than the sham controls. PTX reversed these behaviours in the MI group to a level similar to that in the untreated sham group, without affecting infarct size. PTX reduced plasma IL-1? concentrations in both sham and MI rats. We conclude that PTX administration significantly reverses the depressive-like behaviour seen after MI in rats. PMID:21971020

  12. Animal models of traumatic brain injury

    PubMed Central

    Xiong, Ye; Mahmood, Asim; Chopp, Michael

    2014-01-01

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

  13. 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.

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

    PubMed

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

    2015-05-01

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

  15. Experimental models of repetitive brain injuries.

    PubMed

    Weber, John T

    2007-01-01

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

  16. Development of an assisting detection system for early infarct diagnosis

    SciTech Connect

    Sim, K. S.; Nia, M. E.; Ee, C. S.

    2015-04-24

    In this paper, a detection assisting system for early infarct detection is developed. This new developed method is used to assist the medical practitioners to diagnose infarct from computed tomography images of brain. Using this assisting system, the infarct could be diagnosed at earlier stages. The non-contrast computed tomography (NCCT) brain images are the data set used for this system. Detection module extracts the pixel data from NCCT brain images, and produces the colourized version of images. The proposed method showed great potential in detecting infarct, and helps medical practitioners to make earlier and better diagnoses.

  17. Very Mild Hypothermia (35C) Postischemia Reduces Infarct Volume and Blood/Brain Barrier Breakdown Following tPA Treatment in the Mouse.

    PubMed

    Cechmanek, Brian K; Tuor, Ursula I; Rushforth, David; Barber, Philip A

    2015-12-01

    Reperfusion therapies for stroke diminish in effectiveness and safety as time to treatment increases. Hypothermia neuroprotection for stroke is established, but its clinical translation has been hampered by uncertainties regarding optimal temperature and complications associated with moderate hypothermia. Also, hypothermia targeting temperatures of 32-33C is associated with clinical and logistical problems related to induction and adverse side effects. We hypothesized that ischemic damage and tPA-exacerbated blood/brain barrier (BBB) breakdown produced following 30 minutes of middle cerebral artery occlusion and either 1 hour of saline or tPA infusion would be reduced by treatment with very mild cooling of 1.5C for 48 hours followed by 24 hours of gradual rewarming. Infarct volume was reduced by 29.6% (p<0.001) and 41.9% (p<0.001) in hypothermic-tPA (Hypo_tPA)-treated and hypothermic-saline (Hypo_Sal)-treated animals compared to normothermic-tPA (Norm_tPA) and saline (Norm_Sal)-treated animals, respectively. Hypothermia also reduced IgG extravasation in tPA-treated, but not saline-treated groups compared to their normothermic controls (p<0.001). The ipsilateral-contralateral changes in optical density for IgG extravasation were 18.4% greater in the Norm_tPA than Norm_Sal (p<0.001) group. The ipsilateral-contralateral changes in optical density for IgG extravasation were reduced by 17.8% (p<0.001) in the Hypo_tPA compared to Norm_tPA group. No significant mean difference in IgG extravasation was seen between Hypo_tPA and Hypo_Sal groups (p>0.05). Very modest hypothermia to reduce the BBB breakdown could improve the availability and safety of reperfusion treatments for stroke. PMID:26075540

  18. Brain-skull boundary conditions in a computational deformation model

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

    Brain shift poses a significant challenge to accurate image-guided neurosurgery. To this end, finite element (FE) brain models have been developed to estimate brain motion during these procedures. The significance of the brain-skull boundary conditions (BCs) for accurate predictions in these models has been explored in dynamic impact and inertial rotation injury computational simulations where the results have shown that the brain mechanical response is sensitive to the type of BCs applied. We extend the study of brain-skull BCs to quasi-static brain motion simulations which prevail in neurosurgery. Specifically, a frictionless brain-skull BC using a contact penalty method master-slave paradigm is incorporated into our existing deformation forward model (forced displacement method). The initial brain-skull gap (CSF thickness) is assumed to be 2mm for demonstration purposes. The brain surface nodes are assigned as either fixed (at bottom along the gravity direction), free (at brainstem), with prescribed displacement (at craniotomy) or as slave nodes potentially in contact with the skull (all the remaining). Each slave node is assigned a penalty parameter (?=5) such that when the node penetrates the rigid body skull inner-surface (master surface), a contact force is introduced proportionally to the penetration. Effectively, brain surface nodes are allowed to move towards or away from the cranium wall, but are ultimately restricted from penetrating the skull. We show that this scheme improves the model's ability to represent the brain-skull interface.

  19. Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study.

    PubMed

    Ehlert, Angelika; Schmidt, Christoph; Wlfer, Johannes; Manthei, Gerd; Jacobs, Andreas H; Brning, Roland; Heindel, Walter; Ringelstein, E Bernd; Stummer, Walter; Pluta, Ryszard M; Hesselmann, Volker

    2016-01-01

    OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study. PMID:26162034

  20. Posttraumatic Hemicerebral Infarction in a Four-Year-Old Girl

    PubMed Central

    Faridaalaee, Gholamreza; Taghian, Alireza; Sattarzadeh Ghadim, Tannaz

    2014-01-01

    Introduction: Brain infarction after trauma is uncommon. Injury of the carotid and vertebrobasilar arteries can cause brain infarction due to occlusion of brain blood flow. Case Presentation: Emergency medical service (EMS) brought a 4-year-old girl involved in a car accident to the emergency room. She had had seizure controlled by diazepam. She was unconscious and her Glasgow coma scale (GCS) score was eight. Early vital signs were stable. Her first brain CT scan showed a subdural hematoma (SDH). One day after admission to ICU, her GCS decreased to five; hence, a control brain CT was performed. The brain CT scan showed a brain infarction. Six days after admission, her status worsened and her GCS dropped to three and her pupils became dilated bilaterally and unresponsive to light; she was pronounced dead. Discussion: We present an uncommon case of posttraumatic brain infarction and synchronous SDH. PMID:25717443

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

    PubMed Central

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

    2013-01-01

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

  2. A Culture-Behavior-Brain Loop Model of Human Development.

    PubMed

    Han, Shihui; Ma, Yina

    2015-11-01

    Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model. PMID:26440111

  3. Permanent ligation of the left anterior descending coronary artery in mice: a model of post-myocardial infarction remodelling and heart failure.

    PubMed

    Muthuramu, Ilayaraja; Lox, Marleen; Jacobs, Frank; De Geest, Bart

    2014-01-01

    Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure. Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload. Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure. A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion. In contrast, the infarct area at 24 hr after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling. Besides the model of permanent ligation of the left anterior descending coronary artery, the technique of invasive hemodynamic measurements in mice is presented in detail. PMID:25489995

  4. One-staged aptamer-based isolation and application of endothelial progenitor cells in a porcine myocardial infarction model.

    PubMed

    Haller, Christoph; Sobolewska, Bianka; Schibilsky, David; Avci-Adali, Meltem; Schlensak, Christian; Wendel, Hans-Peter; Walker, Tobias

    2015-02-01

    A multitude of stem cell types has been extensively studied and used for myocardial regenerative therapy. Amongst these endothelial progenitor cells form a promising source. In our present study, we investigated a one-staged approach for isolation and application of autologous endothelial progenitor cells in a pig model of myocardial infarction. Endothelial progenitor cell isolation was performed by immediately preprocedural bone marrow aspiration and consecutive positive selection by aptamer-based magnetic cell sorting. Animals were divided in three groups receiving endothelial progenitor cells, saline, or no intramyocardial injection respectively. Postprocedural follow-up consisted of weekly echocardiographic evaluations. Postmortem histological analysis after four weeks focused on detection of transplanted PKH26-positive endothelial progenitor cells and neovascularization within the infarcted myocardium. A significant difference in left ventricular ejection fraction could not be shown between the three groups. PKH26-stained endothelial progenitor cells could be found in the endothelial progenitor cells transplanted group, although detection was scarce. Large-sized capillaries were found to be significantly more in endothelial progenitor cells treated myocardium. The one-stage approach of endothelial progenitor cells isolation and application presented herein offers a new therapeutic concept. Even though a beneficial impact on myocardial function could not be assessed, increased neovascularization may indicate positive effects on remodeling processes. Being able to harvest endothelial progenitor cells right before application provides a wider scope of action in urgent cases. PMID:25494449

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

    2014-01-01

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

  7. Modeling Brain Resonance Phenomena Using a Neural Mass Model

    PubMed Central

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

    2011-01-01

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

  8. 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

  9. Virtual reality in brain intervention: models and applications.

    PubMed

    Nowinski, Wieslaw

    2005-01-01

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

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

    PubMed

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

    2015-02-01

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

  11. Mathematical modeling of human brain physiological data

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

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

    PubMed Central

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

    2009-01-01

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

  13. Brain repair after stroke--a novel neurological model.

    PubMed

    Small, Steven L; Buccino, Giovanni; Solodkin, Ana

    2013-12-01

    Following stroke, patients are commonly left with debilitating motor and speech impairments. This article reviews the state of the art in neurological repair for stroke and proposes a new model for the future. We suggest that stroke treatment--from the time of the ictus itself to living with the consequences--must be fundamentally neurological, from limiting the extent of injury at the outset, to repairing the consequent damage. Our model links brain and behaviour by targeting brain circuits, and we illustrate the model though action observation treatment, which aims to enhance brain network connectivity. The model is based on the assumptions that the mechanisms of neural repair inherently involve cellular and circuit plasticity, that brain plasticity is a synaptic phenomenon that is largely stimulus-dependent, and that brain repair required both physical and behavioural interventions that are tailored to reorganize specific brain circuits. We review current approaches to brain repair after stroke and present our new model, and discuss the biological foundations, rationales, and data to support our novel approach to upper-extremity and language rehabilitation. We believe that by enhancing plasticity at the level of brain network interactions, this neurological model for brain repair could ultimately lead to a cure for stroke. PMID:24217509

  14. Brainstem infarction and sleep-disordered breathing in the BASIC Sleep Apnea Study

    PubMed Central

    Brown, Devin L.; McDermott, Mollie; Mowla, Ashkan; De Lott, Lindsey; Morgenstern, Lewis B.; Kerber, Kevin A.; Hegeman, Garnett; Smith, Melinda A.; Garcia, Nelda M.; Chervin, Ronald D.; Lisabeth, Lynda D.

    2014-01-01

    Background Association between cerebral infarction site and post-stroke sleep-disordered breathing (SDB) has important implications for SDB screening and the pathophysiology of post-stroke SDB. Within a large, population-based study, we assessed whether brainstem infarction location is associated with SDB presence and severity. Methods Cross-sectional study of ischemic stroke patients in the Brain Attack Surveillance in Corpus Christi (BASIC) project. Subjects underwent SDB screening (median 13 days after stroke) with a well-validated cardiopulmonary sleep apnea testing device (n=355). Acute infarction location was determined based on review of radiology reports and dichotomized into brainstem involvement or none. Logistic and linear regression models were used to test the associations between brainstem involvement and SDB or apnea/hypopnea index (AHI) in unadjusted and adjusted models. Results Thirty-eight (11%) had acute infarction involving the brainstem. Of those without brainstem infarction, 59% had significant SDB (AHI?10); the median AHI was 13 (interquartile range (IQR) 6, 26). Of those with brainstem infarction, 84% had SDB; median AHI was 20 (IQR 11, 38). In unadjusted analysis, brainstem involvement was associated with over three times the odds of SDB (OR 3.71 (95% CI: 1.52, 9.13)). In a multivariable model, adjusted for demographics, BMI, hypertension, diabetes, coronary artery disease, atrial fibrillation, prior stroke/TIA, and stroke severity, results were similar (OR 3.76 (95% CI: 1.44, 9.81)). Brainstem infarction was also associated with AHI (continuous) in unadjusted (p=0.004) and adjusted models (p=0.004). Conclusions Data from this population-based stroke study show that acute infarction involving the brainstem is associated with both presence and severity of SDB. PMID:24916097

  15. On a Mathematical Model of Brain Activities

    SciTech Connect

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

    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.

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

    NASA Astrophysics Data System (ADS)

    Chao, Tsi-chian; Xu, X. George

    2004-11-01

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

  17. Accuracy of prediction of infarct-related arrhythmic circuits from image-based models reconstructed from low and high resolution MRI

    PubMed Central

    Deng, Dongdong; Arevalo, Hermenegild; Pashakhanloo, Farhad; Prakosa, Adityo; Ashikaga, Hiroshi; McVeigh, Elliot; Halperin, Henry; Trayanova, Natalia

    2015-01-01

    Identification of optimal ablation sites in hearts with infarct-related ventricular tachycardia (VT) remains difficult to achieve with the current catheter-based mapping techniques. Limitations arise from the ambiguities in determining the reentrant pathways location(s). The goal of this study was to develop experimentally validated, individualized computer models of infarcted swine hearts, reconstructed from high-resolution ex-vivo MRI and to examine the accuracy of the reentrant circuit location prediction when models of the same hearts are instead reconstructed from low clinical-resolution MRI scans. To achieve this goal, we utilized retrospective data obtained from four pigs ~10 weeks post infarction that underwent VT induction via programmed stimulation and epicardial activation mapping via a multielectrode epicardial sock. After the experiment, high-resolution ex-vivo MRI with late gadolinium enhancement was acquired. The Hi-res images were downsampled into two lower resolutions (Med-res and Low-res) in order to replicate image quality obtainable in the clinic. The images were segmented and models were reconstructed from the three image stacks for each pig heart. VT induction similar to what was performed in the experiment was simulated. Results of the reconstructions showed that the geometry of the ventricles including the infarct could be accurately obtained from Med-res and Low-res images. Simulation results demonstrated that induced VTs in the Med-res and Low-res models were located close to those in Hi-res models. Importantly, all models, regardless of image resolution, accurately predicted the VT morphology and circuit location induced in the experiment. These results demonstrate that MRI-based computer models of hearts with ischemic cardiomyopathy could provide a unique opportunity to predict and analyze VT resulting for from specific infarct architecture, and thus may assist in clinical decisions to identify and ablate the reentrant circuit(s). PMID:26528188

  18. The Modeling and Functional Connectivity of the Brain

    NASA Astrophysics Data System (ADS)

    Kim, Seunghwan

    2008-12-01

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

  19. Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

    PubMed Central

    Lee, Hye Won; Park, Jong Ha; Kim, Bo Won; Ahn, Jinhee; Kim, Jin Hee; Park, Jin Sup; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Park, Tae Sik; Kim, Sang-Pil; Song, Seunghwan; Kim, Ji Yeon; Park, Mi Hwa; Jung, Jin Sup

    2015-01-01

    Purpose Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. Materials and Methods ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBI-SPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. Results Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0±10.0 vs. -2.6±12.0, p=0.019; LVEF, -8.0±15.4 vs. -15.9±14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. Conclusion Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model. PMID:26446632

  20. A revised dosimetric model of the adult head and brain

    SciTech Connect

    Bouchet, L.G.; Bolch, W.E.; Weber, D.A.

    1996-06-01

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

  1. Volumetric Intraoperative Brain Deformation Compensation: Model Development and Phantom Validation

    PubMed Central

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

    2012-01-01

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

  2. Viability assessment after conventional coronary angiography using a novel cardiovascular interventional therapeutic CT system: Comparison with gross morphology in a subacute infarct swine model

    PubMed Central

    Hartaigh, Brain W..; Park, Se-Il; Hong, Youngtaek; Shin, Sanghoon; Ha, Seongmin; Jeon, Byunghwan; Jung, Hoyup; Shim, Hackjoon; Min, James K.; Chang, Hyuk-Jae; Jang, Yangsoo; Chung, Namsik

    2015-01-01

    Background Given the lack of promptness and inevitable use of additional contrast agents, the myocardial viability imaging procedures have not been used widely for determining the need to performing revascularization. Objective This study is aimed to evaluate the feasibility of myocardial viability assessment, consecutively with diagnostic invasive coronary angiography (ICA) without use of additional contrast agent, using a novel hybrid system comprising ICA and multislice CT (MSCT). Methods In all, 14 Yucatan miniature swine models (female; age, 3 months; weight, 2830 kg) were subjected to ICA followed by balloon occlusion (90 minutes) and reperfusion of the left anterior descending coronary artery. Two weeks after induction of myocardial infarction, delayed hyperenhancement (DHE) images were obtained, using a novel combined machine comprising ICA and 320-channel MSCT scanner (Aquilion ONE, Toshiba), after 2, 5, 7, 10, 15, and 20 minutes after conventional ICA. The heart was sliced in 10-mm consecutive sections in the short-axis plane and was embedded in a solution of 1% triphenyltetrazolium chloride (TTC). Infarct size was determined as TTC-negative areas as a percentage of total left ventricular area. On MSCT images, infarct size per slice was calculated by dividing the DHE area by the total slice area (%) and compared with histochemical analyses. Results Serial MSCT scans revealed a peak CT attenuation of the infarct area (222.5 36.5 Hounsfield units) with a maximum mean difference in CT attenuation between the infarct areas and normal myocardium of at 2 minutes after contrast injection (106.4; P for difference = 0.002). Furthermore, the percentage difference of infarct size by MSCT vs histopathologic specimen was significantly lower at 2 (8.5% 1.8%) and 5 minutes (9.5% 1.9%) than those after 7 minutes. Direct comparisons of slice-matched DHE area by MSCT demonstrated excellent correlation with TTC-derived infarct size (r = 0.952; P < .001). Bland-Altman plots of the differences between DHE by MSCT and TTC-derived infarct measurements plotted against their means showed good agreement between the 2 methods. Conclusion The feasibility of myocardial viability assessment by DHE using MSCT after conventional ICA was proven in experimental models, and the optimal viability images were obtained after 2 to 5 minutes after the final intracoronary injection of contrast agent for conventional ICA. PMID:26088379

  3. Tc-99m HMDP (hydroxymethylene diphosphonate): a radiopharmaceutical for skeletal and acute myocardial infarct imaging. II. comparison of Tc-99m hydroxymethylene diphosphonate (HMDP) with other technetium-labeled bone-imaging agents in a canine model

    SciTech Connect

    Bevan, J.A.; Tofe, A.J.; Benedict, J.J.; Francis, M.D.; Barnett, B.L.

    1980-10-01

    Technetium-99m hydroxymethylene diphosphonate (Tc-HMDP) was compared with the two other diphosphonates (Tc-MDP and Tc-HEDP) and Tc-99m pyrophosphate (Tc-PPi) in a canine model of acute myocardial infarction. The Tc-HMDP showed higher uptake in infarcted myocardium than the other two diphosphonates, and uptake equivalent to that of Tc-PPi.

  4. Prasugrel reduces ischaemic infarct volume and ameliorates neurological deficits in a non-human primate model of middle cerebral artery thrombosis.

    PubMed

    Tomizawa, Atsuyuki; Ohno, Kousaku; Jakubowski, Joseph A; Mizuno, Makoto; Sugidachi, Atsuhiro

    2015-12-01

    Several clinical trials have demonstrated the benefits of thienopyridine monotherapy in ischaemic stroke patients. Non-human primate models of ischaemic stroke have been used for various antithrombotic agents; however, to the best of our knowledge, there is no data on the effects of P2Y12 antagonists in models, such as the thrombotic middle cerebral artery occlusion (MCAO) monkey model. Accordingly, it remains unclear what level of inhibition of platelet aggregation (IPA) is required for optimal treatment of ischaemic stroke. In the present study, we investigated the effects of prasugrel, a third-generation thienopyridine antiplatelet drug, on platelet aggregation, thrombus formation and cerebral infarct volume in a non-human primate model. Daily oral administration of prasugrel resulted in significant and stable platelet inhibitory effects on Day 3, with IPA values ranging from 31% to 36% at 0.3mg/kg/day and from 44% to 50% at 1mg/kg/day. These IPA levels encompassed values observed in clinical trials of clopidogrel, and were thus selected for further study. In the thrombotic MCAO model, prasugrel increased MCA patency in a dose-dependent manner and significantly reduced ischaemic infarct volume by approximately 70% at 0.3mg/kg/day and 90% at 1mg/kg/day without increasing haemorrhagic infarction. Prasugrel also significantly reduced neurological deficit scores by 60% at 0.3mg/kg/day and 80% at 1mg/kg/day. In conclusion, prasugrel treatment resulted in effective reduction of ischaemic infarction and an associated improvement in neurological function without increasing haemorrhagic infarction. These data suggest that prasugrel monotherapy would be effective for the prevention of thrombotic stroke. PMID:26388120

  5. Brain

    MedlinePLUS

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

  6. Intramuscular Transplantation of Pig Amniotic Fluid-Derived Progenitor Cells Has Therapeutic Potential in a Mouse Model of Myocardial Infarction.

    PubMed

    Peng, Shao-Yu; Chou, Chih-Jen; Cheng, Po-Jen; Tseng, Tse-Yang; Cheng, Winston Teng-Kui; Shaw, S W Steven; Wu, Shinn-Chih

    2015-01-01

    Acute myocardial infarction (MI) is a fatal event that causes a large number of deaths worldwide. MI results in pathological remodeling and decreased cardiac function, which could lead to heart failure and fatal arrhythmia. Cell therapy is a potential strategy to repair the damage through enhanced angiogenesis or by modulation of the inflammatory process via paracrine signaling. Amniotic fluid-derived progenitor cells (AFPCs) have been reported to differentiate into several lineages and can be used without ethical concerns or risk of teratoma formation. Since pigs are anatomically, physiologically, and genetically similar to humans, and pregnant pigs can be an abundant source of AFPCs, we used porcine AFPCs (pAFPCs) as our target cells. Intramyocardial injection of AFPCs has been shown to cure MI in animal models. However, intramuscular transplantation of cells has not been extensively investigated. In this study, we investigated the therapeutic potential of intramuscular injection of pAFPCs on acute MI. MI mice were divided into 1) PBS control, 2) medium cell dose (1 × 10(6) cells per leg; cell-M), and 3) high cell dose (4 × 10(6) cells per leg; cell-H) groups. Cells or PBS were directly injected into the hamstring muscle 20 min after MI surgery. Four weeks after MI surgery, the cell-M and cell-H groups exhibited significantly better ejection fraction, significantly greater wall thickness, smaller infarct scar sizes, and lower LV expansion index compared to the PBS group. Using in vivo imaging, we showed that the hamstring muscles from animals in the cell-M and cell-H groups had RFP-positive signals. In summary, intramuscular injection of porcine AFPCs reduced scar size, reduced pathological remodeling, and preserved heart function after MI. PMID:24667157

  7. 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

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

    PubMed Central

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

    2014-01-01

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

  9. Multislice first-pass cardiac perfusion MRI: validation in a model of myocardial infarction.

    PubMed

    Epstein, Frederick H; London, James F; Peters, Dana C; Goncalves, Lino M; Agyeman, Kwabena; Taylor, Joni; Balaban, Robert S; Arai, Andrew E

    2002-03-01

    The purpose of this study was to validate a first-pass MRI method for imaging myocardial perfusion with multislice coverage and relatively small analyzable regions of interest (ROIs). A fast gradient-echo (FGRE) sequence with an echo-train (ET) readout was used to achieve multislice coverage, and a high dose of a contrast agent (CA) was used to achieve a high signal-to-noise ratio (SNR). Dogs (N = 6) were studied 1 day after reperfused myocardial infarction, and fluorescent microspheres were used as a standard for perfusion. First-pass MRI correlated well vs. microsphere flow, achieving mean R values of 0.87 (range = 0.82-0.93), 0.71 (range = 0.46-0.85), and 0.72 (range = 0.49-0.95) for subendocardial ROIs, transmural ROIs, and the endocardial-epicardial ratio, respectively. Additionally, analysis of myocardial time-intensity curves (TICs) indicated that 15.8 +/- 6 sectors, corresponding to 260 microl of endocardium, can be analyzed (R(2) > 0.95). PMID:11870835

  10. MCARD-Mediated Gene Transfer of GRK2 Inhibitor in Ovine Model of Acute Myocardial Infarction

    PubMed Central

    Swain, JaBaris D.; Fargnoli, Anthony S.; Katz, Michael G.; Tomasulo, Catherine E.; Sumaroka, Marina; Richardville, Kyle C.; Koch, Walter J.; Rabinowitz, Joseph E.; Bridges, Charles R.

    2013-01-01

    ?-adrenergic receptor (?AR) dysfunction in acute myocardial infarction (MI) is associated with elevated levels of the G protein-coupled receptor kinase-2 (GRK2), which plays a key role in heart failure progression. Inhibition of GRK2 via expression of a peptide ?ARKct transferred by molecular cardiac surgery with recirculating delivery (MCARD) may be a promising intervention. Five sheep underwent scAAV6-mediated MCARD delivery of ?ARKct and five received no treatment (control). After a 3 week period, the branch of the circumflex artery (OM1) was ligated. Quantitative PCR data showed intense ?ARKct expression in the left ventricle (LV). Circumferential fractional shortening was 23.47.1% (baseline) vs. ?2.95.2% (p<0.05) in the control at 10 weeks. In the MCARD-?ARKct group this parameter was close to baseline. The same trend was observed with LV wall thickening. Cardiac index fully recovered in the MCARD-?ARKct group. LV end-diastolic volume and LV end-diastolic pressure did not differ in both groups. MCARD-mediated ?ARKct gene expression results in preservation of regional and global systolic function after acute MI without arresting progressive ventricular remodeling. PMID:23208013

  11. 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.

  12. Valproic Acid Pretreatment Reduces Brain Edema in a Rat Model of Surgical Brain Injury.

    PubMed

    Huang, Lei; Woo, Wendy; Sherchan, Prativa; Khatibi, Nikan H; Krafft, Paul; Rolland, William; Applegate, Richard L; Martin, Robert D; Zhang, John

    2016-01-01

    Surgically induced brain injury (SBI) results in brain edema and neurological decline. Valproic acid (VA) has been shown to be neuroprotective in several experimental brain diseases. In this study, we investigated the pretreatment effect of VA in a rat model of SBI. A total of 57 male Sprague-Dawley rats were use in four groups: sham, SBI?+?vehicle, SBI?+?low dose (100 mg/kg) VA, and SBI?+?high dose (300 mg/kg) VA. SBI was induced by partially resecting right frontal lobes. Shams underwent identical surgical procedures without brain resection. VA or vehicle was administered subcutaneously 30 min prior to SBI. At 24 and 72 h post SBI, neurobehavior and brain water content were assessed as well as matrix metalloproteinases (MMPs) activities. There was significantly higher brain water content within the right frontal lobe in SBI rats than in shams. Without neurobehavioral improvements, the low-dose but not high-dose VA significantly reduced brain edema at 24 h post SBI. The protection tends to persist to 72 h post SBI. At 24 h post SBI, low-dose VA did not significantly reduce the elevated MMP-9 activity associated with SBI. In conclusion, VA pretreatment attenuated brain edema at 24 h after SBI but lacked MMP inhibition. The single dose VA was not associated with neurobehavioral benefits. PMID:26463966

  13. Zebrafish as an emerging model for studying complex brain disorders

    PubMed Central

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

    2014-01-01

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

  14. Zebrafish as an emerging model for studying complex brain disorders.

    PubMed

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

    2014-02-01

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

  15. 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

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

    PubMed

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

    2013-08-01

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

  17. Controlling ferrofluid permeability across the blood-brain barrier model

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  18. Controlling ferrofluid permeability across the bloodbrain barrier model.

    PubMed

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

    2014-02-21

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

  19. Model of unidirectional block formation leading to reentrant ventricular tachycardia in the infarct border zone of postinfarction canine hearts

    PubMed Central

    Ciaccio, Edward J.; Coromilas, James; Ashikaga, Hiroshi; Cervantes, Daniel O.; Wit, Andrew L.; Peters, Nicholas S.; McVeigh, Elliot R.; Garan, Hasan

    2015-01-01

    Background When the infarct border zone is stimulated prematurely, a unidirectional block line (UBL) can form and lead to double-loop (figure-of-eight) reentrant ventricular tachycardia (VT) with a central isthmus. The isthmus is composed of an entrance, center, and exit. It was hypothesized that for certain stimulus site locations and coupling intervals, the UBL would coincide with the isthmus entrance boundary, where infarct border zone thickness changes from thin-to-thick in the travel direction of the premature stimulus wavefront. Method A quantitative model was developed to describe how thin-to-thick changes in the border zone result in critically convex wavefront curvature leading to conduction block, which is dependent upon coupling interval. The model was tested in 12 retrospectively analyzed postinfarction canine experiments. Electrical activation was mapped for premature stimulation and for the first reentrant VT cycle. The relationship of functional conduction block forming during premature stimulation to functional block during reentrant VT was quantified. Results For an appropriately placed stimulus, in accord with model predictions: (1) The UBL and reentrant VT isthmus lateral boundaries overlapped (error: 4.85.7mm). (2) The UBL leading edge coincided with the distal isthmus where the center-entrance boundary would be expected to occur. (3) The mean coupling interval was 164.611.0ms during premature stimulation and 190.720.4ms during the first reentrant VT cycle, in accord with model calculations, which resulted in critically convex wavefront curvature with functional conduction block, respectively, at the location of the isthmus entrance boundary and at the lateral isthmus edges. Discussion Reentrant VT onset following premature stimulation can be explained by the presence of critically convex wavefront curvature and unidirectional block at the isthmus entrance boundary when the premature stimulation interval is sufficiently short. The double-loop reentrant circuit pattern is a consequence of wavefront bifurcation around this UBL followed by coalescence, and then impulse propagation through the isthmus. The wavefront is blocked from propagating laterally away from the isthmus by sharp increases in border zone thickness, which results in critically convex wavefront curvature at VT cycle lengths. PMID:25966920

  20. Human adipose stem cell and ASC-derived cardiac progenitor cellular therapy improves outcomes in a murine model of myocardial infarction

    PubMed Central

    Davy, Philip MC; Lye, Kevin D; Mathews, Juanita; Owens, Jesse B; Chow, Alice Y; Wong, Livingston; Moisyadi, Stefan; Allsopp, Richard C

    2015-01-01

    Background Adipose tissue is an abundant and potent source of adult stem cells for transplant therapy. In this study, we present our findings on the potential application of adipose-derived stem cells (ASCs) as well as induced cardiac-like progenitors (iCPs) derived from ASCs for the treatment of myocardial infarction. Methods and results Human bone marrow (BM)-derived stem cells, ASCs, and iCPs generated from ASCs using three defined cardiac lineage transcription factors were assessed in an immune-compromised mouse myocardial infarction model. Analysis of iCP prior to transplant confirmed changes in gene and protein expression consistent with a cardiac phenotype. Endpoint analysis was performed 1 month posttransplant. Significantly increased endpoint fractional shortening, as well as reduction in the infarct area at risk, was observed in recipients of iCPs as compared to the other recipient cohorts. Both recipients of iCPs and ASCs presented higher myocardial capillary densities than either recipients of BM-derived stem cells or the control cohort. Furthermore, mice receiving iCPs had a significantly higher cardiac retention of transplanted cells than all other groups. Conclusion Overall, iCPs generated from ASCs outperform BM-derived stem cells and ASCs in facilitating recovery from induced myocardial infarction in mice. PMID:26604802

  1. MRI quantification of left ventricular function in microinfarct versus large infarct in swine model.

    PubMed

    Saeed, Maythem; Hetts, Steve W; Do, Loi; Sullivan, Sammir M; Wilson, Mark W

    2013-01-01

    To quantify, using MRI, the acute impacts of defined volume and sizes of coronary microemboli on myocardial viability and left ventricular (LV) function and to use LAD occlusion/reperfusion, as a reference. A total of 28 farm pigs were used in this study. Eight animals were used as controls. Successful coronary interventions were performed under X-ray fluoroscopy in 16 pigs to induce microinfarct (delivery of 16 mm(3) of 40-120 ?m) and large infarct (90 min LAD occlusion/reperfusion). On day 3, animals were imaged using contrast enhanced (in beating and non-beating hearts) and cine MRI for evaluating LV viability and function, respectively. Microscopy and cardiac injury enzymes were used to confirm the presence of necrosis. Myocardial damage was smaller after microembolization than occlusion/reperfusion (6.5 0.6%LV mass vs. 12.6 1.2%, P < 0.001). The increase in LV end-systolic volume and decreases in ejection fraction, cardiac output and regional systolic wall thickening, however, were comparable between groups, but significantly differed from controls. MRI also demonstrated microvascular obstruction after microembolization and occlusion/reperfusion as hyperenhanced and hypoenhanced regions, respectively. Microscopic examination revealed patchy necrosis, inflammatory cell infiltration, but no intramyocardial hemorrhage after microembolization and extensive intramyocardial hemorrhage and transmural damage in the occlusion/reperfusion group. Cardiac injury enzymes confirmed presence of myocardial damage in animals with interventions. Coronary microemboli have acute impact on LV function compared to control animals. Despite the difference in myocardial damage, global and regional LV dysfunction after microembolization was comparable to occlusion/reperfusion. This MR study suggests that the pattern of myocardial damage plays a role in LV dysfunction. PMID:23065097

  2. Erythropoietin as a Neuroprotectant for Neonatal Brain Injury: Animal Models

    PubMed Central

    Traudt, Christopher M.; Juul, Sandra E.

    2016-01-01

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

  3. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, reduces infarction volume and neurological deficits in an embolic model of stroke.

    PubMed

    Allahtavakoli, Mohammad; Shabanzadeh, Alireza P; Sadr, Seyed Shahabeddin; Parviz, Mohsen; Djahanguiri, Bijan

    2006-11-01

    1. Stroke is accompanied by a robust inflammatory response, glutamate-mediated excitotoxicity, release of reactive oxygen species and apoptosis. Thiazolidinediones, which target the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-g, have been reported recently to exhibit potent anti-inflammatory and anti-oxidant actions and inhibit both neural excitotoxicity and apoptosis. 2. The present study was conducted to determine whether rosiglitazone, a potent thiazolidinedione for PPAR-g, would show efficacy against the cerebral infarction and neurological dysfunctions induced by embolic middle cerebral artery (MCA) occlusion in the rat. 3. Focal ischaemic injury was induced by embolizing a preformed clot into the MCA. Rosiglitazone was dissolved in dimethyl sulphoxide and injected i.p. 1 h before MCA occlusion at doses of 0.33, 0.1, 0.3 or 1 mg/kg. In addition, 1 mg/kg rosiglitazone was used immediately or 4 h after embolization. Forty-eight hours after MCA occlusion, brains were removed, sectioned and stained with a 2% solution of 2,3,5-triphenyltetrazolum chloride and analysed using a commercial image-processing software program. 4. When rosiglitazone was administered 1 h before embolization, it significantly reduced infarct volume by 48.2, 68.4% and 70.3% at doses of 0.1, 0.3 and 1 mg/kg, respectively (P < 0.001). Administration of rosiglitazone (1 mg/kg) immediately or 4 h after stroke also reduced infarct volume by 67 and 50.8%, respectively (P < 0.001). Rosiglitazone-treated rats also demonstrated improved neurological functions. However, there were no statistically significant differences between control and treated groups in terms of brain oedema at 48 h after ischaemic injury. 5. The findings of the present study may support the idea of a potential benefit of thiazolidinediones in the management of ischaemic stroke. PMID:17042914

  4. Functional principal component model for high-dimensional brain imaging.

    PubMed

    Zipunnikov, Vadim; Caffo, Brian; Yousem, David M; Davatzikos, Christos; Schwartz, Brian S; Crainiceanu, Ciprian

    2011-10-01

    We explore a connection between the singular value decomposition (SVD) and functional principal component analysis (FPCA) models in high-dimensional brain imaging applications. We formally link right singular vectors to principal scores of FPCA. This, combined with the fact that left singular vectors estimate principal components, allows us to deploy the numerical efficiency of SVD to fully estimate the components of FPCA, even for extremely high-dimensional functional objects, such as brain images. As an example, a FPCA model is fit to high-resolution morphometric (RAVENS) images. The main directions of morphometric variation in brain volumes are identified and discussed. PMID:21798354

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

    PubMed Central

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

    2011-01-01

    BACKGROUND Small animal models have been used in traumatic brain injury (TBI) research to investigate the basic mechanisms and pathology of TBI. Unfortunately, successful TBI investigations in small animal models have not resulted in marked improvements in clinical outcomes of TBI patients. OBJECTIVE To develop a clinically relevant immature large animal model of pediatric neurocritical care following TBI. METHODS Eleven 4 week old piglets were randomized to either rapid axial head rotation without impact (N=6) or instrumented sham (N=5). All animals had an intracranial pressure monitor, brain tissue oxygen (PbtO2) probe, and cerebral microdialysis probe placed in the frontal lobe and data collected for 6 h following injury. RESULTS Injured animals had sustained elevations in intracranial pressure and lactate-pyruvate ratio (LPR), and decreased PbtO2 compared to sham. PbtO2 and LPR from separate frontal lobes had strong linear correlation in both sham and injured animals. Neuropathologic examination demonstrated significant axonal injury and infarct volumes in injured animals compared to sham at 6 hours post-injury. Averaged over time, PbtO2 in both injured and sham animals had a strong inverse correlation with total injury volume. Average LPR had a strong correlation with total injury volume. CONCLUSION LPR and PbtO2 can be utilized as serial non-terminal secondary markers in our injury model for neuropathology, and as evaluation metrics for novel interventions and therapeutics in the acute post-injury period. This translational model bridges a vital gap in knowledge between TBI studies in small animal models and clinical trials in the pediatric TBI population. PMID:21670716

  6. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in a Chinese pedigree: A case report using brain magnetic resonance imaging and biospy.

    PubMed

    Xu, Erhe; Dong, Huiqing; Zhang, Milan; Xu, Min

    2012-01-25

    The present study enrolled a Chinese family that comprised 34 members and spanned three generations. Eight members were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and disease diagnoses corresponded with autosomal incomplete dominance inheritance. The primary clinical manifestations included paralysis, dysarthria, and mild cognitive deficits. Magnetic resonance imaging revealed diffuse leukoencephalopathy with involvement of bilateral anterior temporal lobes, in particular the pons. In addition, multiple cerebral infarction was identified in the proband. Sural nerve biopsy findings of the proband revealed granular osmophilic material deposits in the extracellular matrix, which were adjacent to smooth muscle cells of dermal arterioles. Screening exons 2-4 for NOTCH 3 mutations by direct sequencing did not reveal any abnormalities. PMID:25767504

  7. Brain tumor modeling: glioma growth and interaction with chemotherapy

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

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

  8. Improve Myocardial T1 Measurement in Rats with a New Regression Model: Application to Myocardial Infarction and Beyond

    PubMed Central

    Zhang, Haosen; Ye, Qing; Zheng, Jie; Schelbert, Erik B; Hitchens, T. Kevin; Ho, Chien

    2013-01-01

    Purpose To improve myocardial and blood T1 measurements with a multi-variable T1 fitting model specifically modified for a segmented multi-shot FLASH sequence. Methods The proposed method was first evaluated in a series of phantoms simulating realistic tissues, and then in healthy rats (n = 8) and rats with acute myocardial infarction (MI) induced by coronary artery ligation (n = 8). Results By accounting for the saturation effect caused by sampling ?-train pulses, and the longitudinal magnetization recovery between readouts, our model provided more accurate T1 estimate than the conventional three-parameter fit in phantoms under realistic gating procedures (error of ?0.42 1.73% vs. ?3.40 1.46%, respectively, when using the measured inversion efficiency, ?). The baseline myocardial T1 values in healthy rats was 1636.3 23.4 ms at 7 T. One day post ligation, the T1 values in the remote and proximal myocardial areas were 1637.5 62.6 ms and 1740.3 70.5 ms, respectively. In rats with acute MI, regional differences in myocardial T1 values were observed both before and after the administration of gadolinium. Conclusion The proposed method has improved T1 estimate in phantoms and could advance applications utilizing quantitative myocardial T1 mapping in rodents. PMID:24142881

  9. Cerebral organoids model human brain development and microcephaly

    PubMed Central

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

    2013-01-01

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

  10. 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 (200250 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 (20.209.32 V vs 14.671.85 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

  11. 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

  12. Fuzzy object models for newborn brain MR image segmentation

    NASA Astrophysics Data System (ADS)

    Kobashi, Syoji; Udupa, Jayaram K.

    2013-03-01

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

  13. Development of a Model for Whole Brain Learning of Physiology

    ERIC Educational Resources Information Center

    Eagleton, Saramarie; Muller, Anton

    2011-01-01

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

  14. Development of a Model for Whole Brain Learning of Physiology

    ERIC Educational Resources Information Center

    Eagleton, Saramarie; Muller, Anton

    2011-01-01

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

  15. Image guided constitutive modeling of the silicone brain phantom

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  16. A hierarchical model of the evolution of human brain specializations.

    PubMed

    Barrett, H Clark

    2012-06-26

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

  17. Brain-derived neurotrophic factor blood levels in two models of transient brain ischemia in rats.

    PubMed

    Gottlieb, Miroslav; Bonova, Petra; Danielisova, Viera; Nemethova, Miroslava; Burda, Jozef; Cizkova, Dasa

    2013-03-01

    We monitored possible influence of transient focal and global brain ischemia on BDNF blood level. In both models noticeable fluctuation of BDNF concentration mainly in reperfusion was observed. During the first 90 min, BDNF in total blood and in blood cells continuously decreased in both models but plasma BDNF raised at 40 min and peaked at 90 min of reperfusion. Our data confirm the impact of transient brain ischemia on BDNF levels in the circulatory system, suggest blood cells as a possible source of BDNF and demonstrate the interdependence of blood compartments and physiological state of an affected organism. PMID:23531843

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

    PubMed Central

    Higa, Jason K; Matsui, Takashi

    2014-01-01

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

  19. Models of the Aging Brain Structure and Individual Decline

    PubMed Central

    Ziegler, Gabriel; Dahnke, Robert; Gaser, Christian

    2012-01-01

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

  20. Melatonin protects ADSCs from ROS and enhances their therapeutic potency in a rat model of myocardial infarction

    PubMed Central

    Zhu, Ping; Liu, Jianfeng; Shi, Jinxin; Zhou, Qian; Liu, Jie; Zhang, Xianwei; Du, Zhiyan; Liu, Qiaowei; Guo, Yuanyuan

    2015-01-01

    Myocardial infarction (MI) is a major cause of death and disability worldwide. In the last decade, mesenchymal stem cells (MSCs) based cell therapy has emerged as a promising therapeutic strategy. Although great advance have been made using MSCs to treat MI, the low viability of transplanted MSCs severely limits the efficiency of MSCs therapy. Here, we show evidence that exvivo pre-treatment with melatonin, an endogenous hormone with newly found anti-oxidative activity, could improve survival and function of adipose tissue derived MSCs (ADSCs) invitro as well as invivo. ADSCs with 5?M melatonin pre-treatment for 24hrs showed increased expression of the antioxidant enzyme catalase and Cu/Zn superoxide dismutase (SOD-1), as well as pro-angiogenic and mitogenic factors like insulin-like growth factor 1, basic fibroblast growth factor, hepatocyte growth factor (HGF), epidermal growth factor. Furthermore, melatonin pre-treatment protected MSCs from reactive oxygen species (ROS) induced apoptosis both directly by promoting anti-apoptosis kinases like p-Akt as well as blocking caspase cascade, and indirectly by restoring the ROS impaired cell adhesion. Using a rat model of MI, we found that melatonin pre-treatment enhanced the viability of engrafted ADSCs, and promoted their therapeutic potency. Hopefully, our results may shed light on the design of more effective therapeutic strategies treating MI by MSCs in clinic. PMID:26081690

  1. An anthelmintic drug, pyrvinium pamoate, thwarts fibrosis and ameliorates myocardial contractile dysfunction in a mouse model of myocardial infarction.

    PubMed

    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

  2. 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

  3. A revised dosimetric model of the adult head and brain

    SciTech Connect

    Bouchet, L.G.; Bolch, W.E.; Weber, D.A.; Atkins, H.L.; Poston, J.W. ||

    1996-07-01

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

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

    PubMed Central

    Rengifo Valbuena, Carlos Augusto; vila Rodrguez, Marco Fidel; Cspedes Rubio, Angel

    2013-01-01

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

  5. 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.

  6. Corticonic models of brain mechanisms underlying cognition and intelligence

    NASA Astrophysics Data System (ADS)

    Farhat, Nabil H.

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

  7. 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.

  8. Realistic modeling of neurons and networks: towards brain simulation

    PubMed Central

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

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

  9. 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

  10. Cognitive Models as Bridge between Brain and Behavior.

    PubMed

    Love, Bradley C

    2016-04-01

    How can disparate neural and behavioral measures be integrated? Turner and colleagues propose joint modeling as a solution. Joint modeling mutually constrains the interpretation of brain and behavioral measures by exploiting their covariation structure. Simultaneous estimation allows for more accurate prediction than would be possible by considering these measures in isolation. PMID:26947873

  11. Dynamic changes of magnetic resonance imaging abnormalities in relation to inflammation and glial responses after photothrombotic cerebral infarction in the rat brain.

    PubMed

    Schroeter, M; Franke, C; Stoll, G; Hoehn, M

    2001-02-01

    This investigation analyzed the potential of high-resolution magnetic resonance imaging (MRI) at a field strength of 7T to depict leukocyte infiltration and glial responses after focal cerebral ischemia induced by photothrombotic occlusion of cerebral microvessels. For this purpose we superimposed multiparametric MRI (apparent diffusion coefficient, T2, perfusion-weighted, and gadolinium-DTPA-enhanced T1-weighted imaging) on tissue sections stained for phagocytes and astrocytes and, moreover, assessed the regional distribution of tissue pH and ATP content by invasive biochemical methods. Comparing the histological data with the various MRI parameters, high-resolution MRI did not allow a spatial discrimination between distinct areas of phagocyte accumulation or astroglial scar formation, based on image contrast or even quantitative parameter value differences. However, MRI parameters underwent characteristic changes and differentiated distinct stages of tissue remodeling between days 3 and 14 after photothrombosis. Low apparent diffusion coefficient (ADC) and high T2 values indicated an early stage (3 days) with necrosis and beginning glial activation. Normal ADC and reduced T2 elevation characterized an infarct with advanced glial activation and infiltration of hematogenous cells at 7 days after photothrombosis. Heterogeneous ADC together with T2 elevation reflected a late infarct stage (14 days) when pseudocystic degeneration and scar formation had occurred. PMID:11271365

  12. 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.

  13. [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. PMID:26155312

  14. 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.

  15. Modeling and detecting deep brain activity with MEG & EEG.

    PubMed

    Attal, Yohan; Bhattacharjee, Manik; Yelnik, Jerome; Cottereau, Benoit; Lefèvre, Julien; Okada, Yoshio; Bardinet, Eric; Chupin, Marie; Baillet, Sylvain

    2007-01-01

    We introduce an anatomical and electrophysiological model of deep brain structures dedicated to magnetoencephalography (MEG) and electroencephalography (EEG) source imaging. So far, most imaging inverse models considered that MEG/EEG surface signals were predominantly produced by cortical, hence superficial, neural currents. Here we question whether crucial deep brain structures such as the basal ganglia and the hippocampus may also contribute to distant, scalp MEG and EEG measurements. We first design a realistic anatomical and electrophysiological model of these structures and subsequently run Monte-Carlo experiments to evaluate the respective sensitivity of the MEG and EEG to signals from deeper origins. Results indicate that MEG/EEG may indeed localize these deeper generators, which is confirmed here from experimental MEG data reporting on the modulation of alpha brain waves. PMID:18003114

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

    PubMed Central

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

    2016-01-01

    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 EndoIIIs vehicle nor an enzymatically inactive EndoIII mutant (K120Q) offered any protection. The magnitude of EndoIIIs 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 todays patient with acute myocardial infarction. PMID:25595210

  17. 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 scalingin 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

  18. 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

  19. Enhanced angiogenesis mediated by vascular endothelial growth factor plasmid-loaded thermo-responsive amphiphilic polymer in a rat myocardial infarction model.

    PubMed

    Kwon, Jin Sook; Park, In Kyu; Cho, Ae Shin; Shin, Sun Mi; Hong, Moon Hwa; Jeong, Seo Yeon; Kim, Yong Sook; Min, Jung-Joon; Jeong, Myung Ho; Kim, Won Jong; Jo, Seongbong; Pun, Suzie H; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee; Ahn, Youngkeun

    2009-09-01

    Thermo-responsive hydrogel-mediated gene transfer may be preferred for the muscle, because the release of DNA into the surrounding tissue can be controlled by the 3-dimensional structure of the hydrogel. Such a system for the controlled release of a therapeutic gene may extend the duration of gene expression. Here, a thermo-responsive, biodegradable polymeric hydrogel was synthesized for local gene transfer in the heart. Initially, the luciferase gene was delivered into mouse heart. The intensity of gene expression assessed by optical imaging was closely correlated with the expressed protein concentration measured by luciferase assay in homogenized heart. Polymeric hydrogel-based gene transfer enhanced gene expression up to 4 fold, compared with naked plasmid, and displayed 2 bi-modal expression profiles with peaks at 2 days and around 25 days after local injection. Histological analyses showed that gene expression was initially highest in the myocardium, whereas lower and longer expression was seen mainly in fibrotic or inflammatory cells that infiltrated the injury site during injection. Next, a rat myocardial infarction model was made for 1 week, and human vascular endothelial growth factor (hVEGF) plasmid was injected into the infarct area with an amphiphilic thermo-responsive polymer. Enhanced and sustained hVEGF expression in the infarct region mediated by amphiphilic thermo-responsive polymer increased capillary density and larger vessel formation, thus enabling effective angiogenesis. PMID:19465071

  20. 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; Feng Yi; Wu Yanping; Jin Qindi; Wang Yu; Wang Zhen; Lu Qin; Jiang Yibo; Wang Shengqi; Chen Feng; Marchal, Guy; Ni Yicheng

    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.

  1. 5?-Adenosine Monophosphate-Induced Hypothermia Attenuates Brain Ischemia/Reperfusion Injury in a Rat Model by Inhibiting the Inflammatory Response

    PubMed Central

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

    2015-01-01

    Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5?-adenosine monophosphate (5?-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5?-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5?-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia. PMID:25873763

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

    PubMed Central

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

    2006-01-01

    Background Magnetic resonance imaging (MRI) permits 3-dimensional (3D) cardiac imaging with high soft tissue contrast. X-ray fluoroscopy provides high-resolution, 2-dimensional (2D) projection imaging. We have developed real-time x-ray fused with MRI (XFM) to guide invasive procedures that combines the best features of both imaging modalities. We tested the accuracy of XFM using external fiducial markers to guide endomyocardial cell injections in infarcted swine hearts. Methods and Results Endomyocardial injections of iron-labeled mesenchymal stromal cells admixed with tissue dye were performed in previously infarcted hearts of 12 Yucatan miniswine (weight, 33 to 67 kg). Features from cardiac MRI were displayed combined with x-ray in real time to guide injections. During 130 injections, operators were provided with 3D surfaces of endocardium, epicardium, myocardial wall thickness (range, 2.6 to 17.7 mm), and infarct registered with live x-ray images to facilitate device navigation and choice of injection location. XFM-guided injections were compared with postinjection MRI and with necropsy specimens obtained 24 hours later. Visual inspection of the pattern of dye staining on 2,3,5-triphenyltetrazolium chloridestained heart slices agreed (?=0.69) with XFM-derived injection locations mapped onto delayed hyperenhancement MRI and the susceptibility artifacts seen on the postinjection T2*-weighted gradient echo MRI. The distance between the predicted and actual injection locations in vivo was 3.22.6 mm (n=64), and 75% of injections were within 4.1 mm of the predicted location. Conclusions Three-dimensional to two-dimensional registration of x-ray and MR images with the use of external fiducial markers accurately targets endomyocardial injection in a swine model of myocardial infarction. PMID:17101858

  3. A revised dosimetric model of the head and brain

    SciTech Connect

    Bolch, W.E.; Poston, J.W. Sr.

    1995-05-01

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

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

    PubMed

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

    2014-02-01

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

  5. 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

    2015-01-01

    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

  6. Astragalosides promote angiogenesis via vascular endothelial growth factor and basic fibroblast growth factor in a rat model of myocardial infarction

    PubMed Central

    YU, JUN-MIN; ZHANG, XIAO-BO; JIANG, WEN; WANG, HUI-DONG; ZHANG, YI-NA

    2015-01-01

    The aim of the present study was to evaluate the effect of astragalosides (ASTs) on angiogenesis, as well as the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) following myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Twenty-four hours after surgery, the rats were divided into low-dose, high-dose, control and sham surgery groups (n=8 per group). The low- and high-dose groups were treated with ASTs (2.5 and 10 mg/kg/day, respectively, via intraperitoneal injection), while, the control and sham surgery group rats received saline. Serum levels, and mRNA and protein expression levels of VEGF and bFGF, as well as the microvessel density (MVD) were determined four weeks post-treatment. Twenty-four hours post-surgery, VEGF and bFGF serum levels were observed to be comparable between the groups; while at four weeks, the VEGF and bFGF levels were higher in the AST-treated rats (P<0.01). Similarly, VEGF and bFGF mRNA and protein expression levels were higher following AST treatment (P<0.05). No difference in VEGF mRNA expression between the low- and high-dose groups was noted, however, an increase in the bFGF expression levels was detected in the high-dose group. Newly generated blood vessels were observed following MI, with a significant increase in MVD observed in the AST-treated groups (P<0.05). AST promotes angiogenesis of the heart and increases VEGF and bFGF expression levels. Thus, it is hypothesized that increased VEGF and bFGF levels may contribute to the AST-induced increase in angiogenesis in rat models of MI. PMID:26352430

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

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

    PubMed Central

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

    2012-01-01

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

  9. Animal Models of Brain Maldevelopment Induced by Cycad Plant Genotoxins

    PubMed Central

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

    2014-01-01

    Cycads are long-lived tropical and subtropical plants that contain azoxyglycosides (e.g., cycasin, macrozamin) and neurotoxic amino acids (notably β-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. 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

  11. Temporally-patterned deep brain stimulation in a mouse model of multiple traumatic brain injury.

    PubMed

    Tabansky, Inna; Quinkert, Amy Wells; Rahman, Nadera; Muller, Salomon Zev; Lofgren, Jesper; Rudling, Johan; Goodman, Alyssa; Wang, Yingping; Pfaff, Donald W

    2014-10-15

    We report that mice with closed-head multiple traumatic brain injury (TBI) show a decrease in the motoric aspects of generalized arousal, as measured by automated, quantitative behavioral assays. Further, we found that temporally-patterned deep brain stimulation (DBS) can increase generalized arousal and spontaneous motor activity in this mouse model of TBI. This arousal increase is input-pattern-dependent, as changing the temporal pattern of DBS can modulate its effect on motor activity. Finally, an extensive examination of mouse behavioral capacities, looking for deficits in this model of TBI, suggest that the strongest effects of TBI in this model are found in the initiation of any kind of movement. PMID:25072520

  12. Temporally-Patterned Deep Brain Stimulation in a Mouse Model of Multiple Traumatic Brain Injury

    PubMed Central

    Tabansky, Inna; Quinkert, Amy Wells; Rahman, Nadera; Muller, Salomon Zev; Löfgren, Jesper; Rudling, Johan; Goodman, Alyssa; Wang, Yingping; Pfaff, Donald W.

    2014-01-01

    We report that mice with closed-head multiple traumatic brain injury (TBI) show a decrease in the motoric aspects of generalized arousal, as measured by automated, quantitative behavioral assays. Further, we found that temporally-patterned deep brain stimulation (DBS) can increase generalized arousal and spontaneous motor activity in this mouse model of TBI. This arousal increase is input-pattern-dependent, as changing the temporal pattern of DBS can modulate its effect on motor activity. Finally, an extensive examination of mouse behavioral capacities, looking for deficits in this model of TBI, suggest that the strongest effects of TBI in this model are found in the initiation of any kind of movement. PMID:25072520

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

    SciTech Connect

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

    1984-07-01

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

  14. Optical projection tomography permits efficient assessment of infarct volume in the murine heart postmyocardial infarction.

    PubMed

    Zhao, X; Wu, J; Gray, C D; McGregor, K; Rossi, A G; Morrison, H; Jansen, M A; Gray, G A

    2015-08-15

    The extent of infarct injury is a key determinant of structural and functional remodeling following myocardial infarction (MI). Infarct volume in experimental models of MI can be determined accurately by in vivo magnetic resonance imaging (MRI), but this is costly and not widely available. Experimental studies therefore commonly assess injury by histological analysis of sections sampled from the infarcted heart, an approach that is labor intensive, can be subjective, and does not fully assess the extent of injury. The present study aimed to assess the suitability of optical projection tomography (OPT) for identification of injured myocardium and for accurate and efficient assessment of infarct volume. Intact, perfusion-fixed, optically cleared hearts, collected from mice 7 days after induction of MI by coronary artery occlusion, were scanned by a tomograph for autofluorescence emission after UV excitation, generating >400 transaxial sections for reconstruction. Differential autofluorescence permitted discrimination between viable and injured myocardium and highlighted the heterogeneity within the infarct zone. Two-dimensional infarct areas derived from OPT imaging and Masson's trichrome staining of slices from the same heart were highly correlated (r(2) = 0.99, P < 0.0001). Infarct volume derived from reconstructed OPT sections correlated with volume derived from in vivo late gadolinium enhancement MRI (r(2) = 0.7608, P < 0.005). Tissue processing for OPT did not compromise subsequent immunohistochemical detection of endothelial cell and inflammatory cell markers. OPT is thus a nondestructive, efficient, and accurate approach for routine in vitro assessment of murine myocardial infarct volume. PMID:26071543

  15. Optical projection tomography permits efficient assessment of infarct volume in the murine heart postmyocardial infarction

    PubMed Central

    Zhao, X.; Wu, J.; Gray, C. D.; McGregor, K.; Rossi, A. G.; Morrison, H.; Jansen, M. A.

    2015-01-01

    The extent of infarct injury is a key determinant of structural and functional remodeling following myocardial infarction (MI). Infarct volume in experimental models of MI can be determined accurately by in vivo magnetic resonance imaging (MRI), but this is costly and not widely available. Experimental studies therefore commonly assess injury by histological analysis of sections sampled from the infarcted heart, an approach that is labor intensive, can be subjective, and does not fully assess the extent of injury. The present study aimed to assess the suitability of optical projection tomography (OPT) for identification of injured myocardium and for accurate and efficient assessment of infarct volume. Intact, perfusion-fixed, optically cleared hearts, collected from mice 7 days after induction of MI by coronary artery occlusion, were scanned by a tomograph for autofluorescence emission after UV excitation, generating >400 transaxial sections for reconstruction. Differential autofluorescence permitted discrimination between viable and injured myocardium and highlighted the heterogeneity within the infarct zone. Two-dimensional infarct areas derived from OPT imaging and Masson's trichrome staining of slices from the same heart were highly correlated (r2 = 0.99, P < 0.0001). Infarct volume derived from reconstructed OPT sections correlated with volume derived from in vivo late gadolinium enhancement MRI (r2 = 0.7608, P < 0.005). Tissue processing for OPT did not compromise subsequent immunohistochemical detection of endothelial cell and inflammatory cell markers. OPT is thus a nondestructive, efficient, and accurate approach for routine in vitro assessment of murine myocardial infarct volume. PMID:26071543

  16. Computational modeling of an endovascular approach to deep brain stimulation

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  17. Characterisation and modelling of brain tissue for surgical simulation.

    PubMed

    Mendizabal, A; Aguinaga, I; Snchez, E

    2015-05-01

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

  18. Assessment of C-phycocyanin effect on astrocytes-mediated neuroprotection against oxidative brain injury using 2D and 3D astrocyte tissue model

    PubMed Central

    Min, Seul Ki; Park, Jun Sang; Luo, Lidan; Kwon, Yeo Seon; Lee, Hoo Cheol; Jung Shim, Hyun; Kim, Il-Doo; Lee, Ja-Kyeong; Shin, Hwa Sung

    2015-01-01

    Drugs are currently being developed to attenuate oxidative stress as a treatment for brain injuries. C-phycocyanin (C-Pc) is an antioxidant protein of green microalgae known to exert neuroprotective effects against oxidative brain injury. Astrocytes, which compose many portions of the brain, exert various functions to overcome oxidative stress; however, little is known about how C-Pc mediates the antioxidative effects of astrocytes. In this study, we revealed that C-Pc intranasal administration to the middle cerebral artery occlusion (MCAO) rats ensures neuroprotection of ischemic brain by reducing infarct size and improving behavioral deficits. C-Pc also enhanced viability and proliferation but attenuated apoptosis and reactive oxygen species (ROS) of oxidized astrocytes, without cytotoxicity to normal astrocytes and neurons. To elucidate how C-Pc leads astrocytes to enhance neuroprotection and repair of ischemia brain, we firstly developed 3D oxidized astrocyte model. C-Pc had astrocytes upregulate antioxidant enzymes such as SOD and catalase and neurotrophic factors BDNF and NGF, while alleviating inflammatory factors IL-6 and IL-1β and glial scar. Additionally, C-Pc improved viability of 3D oxidized neurons. In summary, C-Pc was concluded to activate oxidized astrocytes to protect and repair the ischemic brain with the combinatorial effects of improved antioxidative, neurotrophic, and anti-inflammatory mechanisms. PMID:26399322

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

    PubMed

    Wilhelm, Imola; Fazakas, Csilla; Krizbai, Istvan A

    2011-01-01

    The blood-brain barrier (BBB) is an active interface between the circulation and the central nervous system (CNS) with a dual function: the barrier function restricts the transport from the blood to the brain of potentially toxic or harmful substances; the carrier function is responsible for the transport of nutrients to the brain and removal of metabolites. The BBB plays a crucial role in the clinical practice as well. On the one side there is a large number of neurological disorders including cerebral ischemia, brain trauma and tumors, neurodegenerative disorders, in which the permeability of the BBB is increased. On the other hand due to the relative impermeability of the barrier many drugs are unable to reach the CNS in therapeutically relevant concentration, making the BBB one of the major impediments in the treatment of CNS disorders. The significant scientific and industrial interest in the physiology and pathology of the BBB led to the development of several in vitro models of the BBB. These models are mainly based on the culture of cerebral endothelial cells. The best in vitro models which mimic the best way the in vivo anatomical conditions are the co-culture models in which brain endothelial cells are co-cultured with astrocytes and/or pericytes. Our in vitro BBB model is characterized by high transendothelial electrical resistance (TEER regularily above 200 Ohm x cm(2)), low permeability and expression of several transporters. Our experiments have proven that the model is suitable for basic research and for testing the interaction between the BBB and potential drug candidates (toxicity, permeability, interaction with efflux transporters) as well. PMID:21499332

  20. Coronary artery ligation and intramyocardial injection in a murine model of infarction.

    PubMed

    Virag, Jitka A I; Lust, Robert M

    2011-01-01

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

  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. 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…

  3. Experimental model for civilian ballistic brain injury biomechanics quantification.

    PubMed

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

    2007-01-01

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

  4. Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification.

    PubMed

    Subhash, N; Sriram, R; Kurian, Gino A

    2015-11-01

    Vascular bed calcification is a common feature of ends stage renal disease that may lead to a complication in cardiovascular and cerebrovascular beds, which is a promoting cause of myocardial infarction, stroke, dementia and aneurysms. Sodium thiosulfate (STS) due to its multiple properties such as antioxidant and calcium chelation has been reported to prevent vascular calcification in uremic rats, without mentioning its impact on cerebral function. Moreover, the previous studies have not explored the effect of STS on the mitochondrial dysfunction, one of the main pathophysiological features associated with the disease and the main site for STS metabolism. The present study addresses this limitation by using a rat model where 0.75% adenine was administered to induce vascular calcification and 400mg/kgbwt. of STS was given as preventive and curative agent. The blood and urine chemistries along with histopathology of aorta confirms the renal protective effect of STS in two modes of administration. The brain oxidative stress assessment was made through TBARS level, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, found to be in the near normal level. STS administration not only reduced the mitochondrial oxidative stress (measured by TBARS, SOD, GPx and CAT) but also preserved the mitochondrial respiratory enzyme activities (NADH dehydrogenase, Succinate dehydrogenase and Malate dehydrogenase) and its physiology (measured by P/O ratio and RCR). In fact, the protective effect of STS was prominent, when it was administered as a curative agent, where low H2S and high thiosulfate level was observed along with low cystathionine ? synthase activity, confirms thiosulfate mediated renal protection. In conclusion, STS when given after induction of calcification is protective to the brain by preserving its mitochondria, compared to the treatment given concomitantly. PMID:26363090

  5. Effects of exercise on brain functions in diabetic animal models.

    PubMed

    Yi, Sun Shin

    2015-05-15

    Human life span has dramatically increased over several decades, and the quality of life has been considered to be equally important. However, diabetes mellitus (DM) characterized by problems related to insulin secretion and recognition has become a serious health problem in recent years that threatens human health by causing decline in brain functions and finally leading to neurodegenerative diseases. Exercise is recognized as an effective therapy for DM without medication administration. Exercise studies using experimental animals are a suitable option to overcome this drawback, and animal studies have improved continuously according to the needs of the experimenters. Since brain health is the most significant factor in human life, it is very important to assess brain functions according to the different exercise conditions using experimental animal models. Generally, there are two types of DM; insulin-dependent type 1 DM and an insulin-independent type 2 DM (T2DM); however, the author will mostly discuss brain functions in T2DM animal models in this review. Additionally, many physiopathologic alterations are caused in the brain by DM such as increased adiposity, inflammation, hormonal dysregulation, uncontrolled hyperphagia, insulin and leptin resistance, and dysregulation of neurotransmitters and declined neurogenesis in the hippocampus and we describe how exercise corrects these alterations in animal models. The results of changes in the brain environment differ according to voluntary, involuntary running exercises and resistance exercise, and gender in the animal studies. These factors have been mentioned in this review, and this review will be a good reference for studying how exercise can be used with therapy for treating DM. PMID:25987956

  6. 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

  7. Effects of exercise on brain functions in diabetic animal models

    PubMed Central

    Yi, Sun Shin

    2015-01-01

    Human life span has dramatically increased over several decades, and the quality of life has been considered to be equally important. However, diabetes mellitus (DM) characterized by problems related to insulin secretion and recognition has become a serious health problem in recent years that threatens human health by causing decline in brain functions and finally leading to neurodegenerative diseases. Exercise is recognized as an effective therapy for DM without medication administration. Exercise studies using experimental animals are a suitable option to overcome this drawback, and animal studies have improved continuously according to the needs of the experimenters. Since brain health is the most significant factor in human life, it is very important to assess brain functions according to the different exercise conditions using experimental animal models. Generally, there are two types of DM; insulin-dependent type 1 DM and an insulin-independent type 2 DM (T2DM); however, the author will mostly discuss brain functions in T2DM animal models in this review. Additionally, many physiopathologic alterations are caused in the brain by DM such as increased adiposity, inflammation, hormonal dysregulation, uncontrolled hyperphagia, insulin and leptin resistance, and dysregulation of neurotransmitters and declined neurogenesis in the hippocampus and we describe how exercise corrects these alterations in animal models. The results of changes in the brain environment differ according to voluntary, involuntary running exercises and resistance exercise, and gender in the animal studies. These factors have been mentioned in this review, and this review will be a good reference for studying how exercise can be used with therapy for treating DM. PMID:25987956

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

    PubMed

    Noreikiene, Kristina; Herczeg, Gbor; Gonda, Abigl; Balzs, Gergely; Husby, Arild; Meril, 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

  9. 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

  10. Insight into Pre-Clinical Models of Traumatic Brain Injury Using Circulating Brain Damage Biomarkers: Operation Brain Trauma Therapy.

    PubMed

    Mondello, Stefania; Shear, Deborah A; Bramlett, Helen M; Dixon, C Edward; Schmid, Kara E; Dietrich, W Dalton; Wang, Kevin K W; Hayes, Ronald L; Glushakova, Olena; Catania, Michael; Richieri, Steven P; Povlishock, John T; Tortella, Frank C; Kochanek, Patrick M

    2016-03-15

    Operation Brain Trauma Therapy (OBTT) is a multicenter pre-clinical drug screening consortium testing promising therapies for traumatic brain injury (TBI) in three well-established models of TBI in rats-namely, parasagittal fluid percussion injury (FPI), controlled cortical impact (CCI), and penetrating ballistic-like brain injury (PBBI). This article presents unique characterization of these models using histological and behavioral outcomes and novel candidate biomarkers from the first three treatment trials of OBTT. Adult rats underwent CCI, FPI, or PBBI and were treated with vehicle (VEH). Shams underwent all manipulations except trauma. The glial marker glial fibrillary acidic protein (GFAP) and the neuronal marker ubiquitin C-terminal hydrolase (UCH-L1) were measured by enzyme-linked immunosorbent assay in blood at 4 and 24 h, and their delta 24-4 h was calculated for each marker. Comparing sham groups across experiments, no differences were found in the same model. Similarly, comparing TBI + VEH groups across experiments, no differences were found in the same model. GFAP was acutely increased in injured rats in each model, with significant differences in levels and temporal patterns mirrored by significant differences in delta 24-4 h GFAP levels and neuropathological and behavioral outcomes. Circulating GFAP levels at 4 and 24 h were powerful predictors of 21 day contusion volume and tissue loss. UCH-L1 showed similar tendencies, albeit with less robust differences between sham and injury groups. Significant differences were also found comparing shams across the models. Our findings (1) demonstrate that TBI models display specific biomarker profiles, functional deficits, and pathological consequence; (2) support the concept that there are different cellular, molecular, and pathophysiological responses to TBI in each model; and (3) advance our understanding of TBI, providing opportunities for a successful translation and holding promise for theranostic applications. Based on our findings, additional studies in pre-clinical models should pursue assessment of GFAP as a surrogate histological and/or theranostic end-point. PMID:26671651

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

    NASA Astrophysics Data System (ADS)

    Wang, Zhihui; Deisboeck, Thomas S.

    2008-04-01

    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 silicobrain 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.

  12. Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model.

    PubMed

    Ostrowski, Robert P; Schulte, Reinhard W; Nie, Ying; Ling, Ted; Lee, Timothy; Manaenko, Anatol; Gridley, Daila S; Zhang, John H

    2012-12-01

    Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen's inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO), then CT scanned for spleen localization and irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8 hrs after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia the rats were euthanized, and brains recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 hrs after start of ischemia significantly reduced cerebral infarction volumes measured at 48 hrs and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 hours offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain. PMID:23956805

  13. Models to Tailor Brain Stimulation Therapies in Stroke.

    PubMed

    Plow, E B; Sankarasubramanian, V; Cunningham, D A; Potter-Baker, K; Varnerin, N; Cohen, L G; Sterr, A; Conforto, A B; Machado, A G

    2016-01-01

    A great challenge facing stroke rehabilitation is the lack of information on how to derive targeted therapies. As such, techniques once considered promising, such as brain stimulation, have demonstrated mixed efficacy across heterogeneous samples in clinical studies. Here, we explain reasons, citing its one-type-suits-all approach as the primary cause of variable efficacy. We present evidence supporting the role of alternate substrates, which can be targeted instead in patients with greater damage and deficit. Building on this groundwork, this review will also discuss different frameworks on how to tailor brain stimulation therapies. To the best of our knowledge, our report is the first instance that enumerates and compares across theoretical models from upper limb recovery and conditions like aphasia and depression. Here, we explain how different models capture heterogeneity across patients and how they can be used to predict which patients would best respond to what treatments to develop targeted, individualized brain stimulation therapies. Our intent is to weigh pros and cons of testing each type of model so brain stimulation is successfully tailored to maximize upper limb recovery in stroke. PMID:27006833

  14. Models to Tailor Brain Stimulation Therapies in Stroke

    PubMed Central

    Plow, E. B.; Sankarasubramanian, V.; Cunningham, D. A.; Potter-Baker, K.; Varnerin, N.; Cohen, L. G.; Sterr, A.; Conforto, A. B.; Machado, A. G.

    2016-01-01

    A great challenge facing stroke rehabilitation is the lack of information on how to derive targeted therapies. As such, techniques once considered promising, such as brain stimulation, have demonstrated mixed efficacy across heterogeneous samples in clinical studies. Here, we explain reasons, citing its one-type-suits-all approach as the primary cause of variable efficacy. We present evidence supporting the role of alternate substrates, which can be targeted instead in patients with greater damage and deficit. Building on this groundwork, this review will also discuss different frameworks on how to tailor brain stimulation therapies. To the best of our knowledge, our report is the first instance that enumerates and compares across theoretical models from upper limb recovery and conditions like aphasia and depression. Here, we explain how different models capture heterogeneity across patients and how they can be used to predict which patients would best respond to what treatments to develop targeted, individualized brain stimulation therapies. Our intent is to weigh pros and cons of testing each type of model so brain stimulation is successfully tailored to maximize upper limb recovery in stroke. PMID:27006833

  15. Cerebral organoids model human brain development and microcephaly.

    PubMed

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

    2013-09-19

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

  16. Creating Physical 3D Stereolithograph Models of Brain and Skull

    PubMed Central

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

    2007-01-01

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

  17. Dosha brain-types: A neural model of individual differences

    PubMed Central

    Travis, Frederick T.; Wallace, Robert Keith

    2015-01-01

    This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations. PMID:26834428

  18. Dosha brain-types: A neural model of individual differences.

    PubMed

    Travis, Frederick T; Wallace, Robert Keith

    2015-01-01

    This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations. PMID:26834428

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

    PubMed Central

    2014-01-01

    Background Optimal fluid resuscitation strategy following combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remain controversial and the effect of resuscitation infusion speed on outcome is not well known. We have previously reported that bolus infusion of fresh frozen plasma (FFP) protects the brain compared with bolus infusion of 0.9% normal saline (NS). We now hypothesize reducing resuscitation infusion speed through a stepwise infusion speed increment protocol using either FFP or NS would provide neuroprotection compared with a high speed resuscitation protocol. Methods 23 Yorkshire swine underwent a protocol of computer controlled TBI and 40% hemorrhage. Animals were left in shock (mean arterial pressure of 35 mmHg) for two hours prior to resuscitation with bolus FFP (n = 5, 50 ml/min) or stepwise infusion speed increment FFP (n = 6), bolus NS (n = 5, 165 ml/min) or stepwise infusion speed increment NS (n = 7). Hemodynamic variables over a 6-hour observation phase were recorded. Following euthanasia, brains were harvested and lesion size as well as brain swelling was measured. Results Bolus FFP resuscitation resulted in greater brain swelling (22.36 ± 1.03% vs. 15.58 ± 2.52%, p = 0.04), but similar lesion size compared with stepwise resuscitation. This was associated with a lower cardiac output (CO: 4.81 ± 1.50 l/min vs. 5.45 ± 1.14 l/min, p = 0.03). In the NS groups, bolus infusion resulted in both increased brain swelling (37.24 ± 1.63% vs. 26.74 ± 1.33%, p = 0.05) as well as lesion size (3285.44 ± 130.81 mm3 vs. 2509.41 ± 297.44 mm3, p = 0.04). This was also associated with decreased cardiac output (NS: 4.37 ± 0.12 l/min vs. 6.35 ± 0.10 l/min, p < 0.01). Conclusions In this clinically relevant model of combined TBI and HS, stepwise resuscitation protected the brain compared with bolus resuscitation. PMID:25116886

  20. Arginase inhibition improves coronary microvascular function and reduces infarct size following ischemia-reperfusion in a rat model

    PubMed Central

    Grnros, Julia; Kiss, Attila; Palmr, Malin; Jung, Christian; Berkowitz, Dan; Pernow, John

    2013-01-01

    Aim Ischemia-reperfusion injury is associated with reduced bioavailability of nitric oxide and microvascular dysfunction. One emerging mechanism behind reduced nitric oxide bioavailability is upregulation of arginase which metabolizes the nitric oxide synthase substrate L-arginine. This study investigated the effects of arginase inhibition on coronary flow velocity and infarct size during reperfusion. Methods Anaesthetized rats, subjected to 30 min coronary artery ligation and reperfusion up to 8 days, were treated with vehicle or the arginase inhibitor N?-hydroxy-nor-L-arginine (nor-NOHA; 100 mg/kg) intravenously 15 min before ischemia. Coronary flow velocity was determined repeatedly during reperfusion. Results Arginase activity in the ischemic-reperfused myocardium was increased already at 20 min of reperfusion and maintained at 8 days. Infarct size was reduced by arginase inhibition at 2 h (39 3% of the area at risk vs. 51 2% in the vehicle group, P<0.01) and at 8 days of reperfusion (13 2% of the left ventricle vs. 22 2%, P<0.05). Basal coronary flow velocity was higher during reperfusion in the group given nor-NOHA and it correlated inversely to infarct size (P<0.01, r=?0.60). Hyperemic coronary flow velocity was also increased in the nor-NOHA treated group compared to vehicle at 24 h and at day 8 (P<0.05). Conclusion It is concluded that arginase activity is increased already during early reperfusion. Arginase inhibition increases coronary flow velocity and reduces infarct size that is sustained 8 days after reperfusion. Inhibition of arginase may thus be a promising therapeutic target to prevent the development of microvascular dysfunction and myocardial injury following ischemia-reperfusion. PMID:23497275

  1. Evaluation of Engraftment of Superparamagnetic Iron Oxide-Labeled Mesenchymal Stem Cells Using Three-Dimensional Reconstruction of Magnetic Resonance Imaging in Photothrombotic Cerebral Infarction Models of Rats

    PubMed Central

    Shim, Jaehyun; Jung, Jisung; Park, Serah

    2015-01-01

    Objective To evaluate engraftment by visualizing the location of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) three-dimensionally in photothrombotic cerebral infarction (PTCI) models of rats. Materials and Methods Magnetic resonance imaging (MRI) of an agarose block containing superparamagnetic iron oxide (SPIO)-labeled hBM-MSCs was performed using a 3.0-T MRI, T2-(T2WI), T2*-(T2*WI), and susceptibility-weighted images (SWI). PTCI was induced in 6 rats, and 2.5 105 SPIO-labeled hBM-MSCs were infused through the ipsilateral internal carotid artery (ICA group) or tail vein (IV group). MRI was performed on days 1, 3, 7, and 14 after stem cell injection. Dark signal regions were confirmed using histology. Three-dimensional MRI reconstruction was performed using the clinical workflow solution to evaluate the engraftment of hBM-MSCs. Volumetric analysis of the engraftment was also performed. Results The volumes of SPIO-labeled hBM-MSCs in the phantom MRI were 129.3, 68.4, and 25.9 L using SWI, T2*WI, and T2WI, respectively. SPIO-labeled hBM-MSCs appeared on day 1 after injection, encircling the cerebral infarction from the ventral side. Dark signal regions matched iron positive cells and human origin (positive) cells. The volume of the engraftment was larger in the ICA group on days 1, 3, and 7, after stem cell injection (p < 0.05 on SWI). SWI was the most sensitive MRI pulse sequence (p < 0.05). The volume of infarction decreased until day 14. Conclusion The engraftment of SPIO-labeled hBM-MSCs can be visualized and evaluated three-dimensionally in PTCI models of rats. The engraftment volume was larger in the ICA group than IV group on early stage within one week. PMID:25995687

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

    PubMed Central

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

    2012-01-01

    Background There is an increasing need for animal disease models for pathophysiological research and efficient drug screening. However, one of the technical barriers to the effective use of the models is the difficulty of non-invasive and sequential monitoring of the same animals. Micro-CT is a powerful tool for serial diagnostic imaging of animal models. However, soft tissue contrast resolution, particularly in the brain, is insufficient for detailed analysis, unlike the current applications of CT in the clinical arena. We address the soft tissue contrast resolution issue in this report. Methodology We performed contrast-enhanced CT (CECT) on mouse models of experimental cerebral infarction and hepatic ischemia. Pathological changes in each lesion were quantified for two weeks by measuring the lesion volume or the ratio of high attenuation area (%HAA), indicative of increased vascular permeability. We also compared brain images of stroke rats and ischemic mice acquired with micro-CT to those acquired with 11.7-T micro-MRI. Histopathological analysis was performed to confirm the diagnosis by CECT. Principal Findings In the models of cerebral infarction, vascular permeability was increased from three days through one week after surgical initiation, which was also confirmed by Evans blue dye leakage. Measurement of volume and %HAA of the liver lesions demonstrated differences in the recovery process between mice with distinct genetic backgrounds. Comparison of CT and MR images acquired from the same stroke rats or ischemic mice indicated that accuracy of volumetric measurement, as well as spatial and contrast resolutions of CT images, was comparable to that obtained with MRI. The imaging results were also consistent with the histological data. Conclusions This study demonstrates that the CECT scanning method is useful in rodents for both quantitative and qualitative evaluations of pathologic lesions in tissues/organs including the brain, and is also suitable for longitudinal observation of the same animals. PMID:22384223

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

    PubMed Central

    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

    2014-01-01

    Summary 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. Tri-lineage 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

  4. Mesh Smoothing Algorithm Applied to a Finite Element Model of the Brain for Improved Brain-Skull Interface.

    PubMed

    Kelley, Mireille E; Miller, Logan E; Urban, Jillian E; Stitzel, Joel D

    2015-01-01

    The brain-skull interface plays an important role in the strain and pressure response of the brain due to impact. In this study, a finite element (FE) model was developed from a brain atlas, representing an adult brain, by converting each 1mm isotropic voxel into a single element of the same size using a custom code developed in MATLAB. This model includes the brain (combined cerebrum and cerebellum), cerebrospinal fluid (CSF), ventricles, and a rigid skull. A voxel-based approach to develop a FE model causes the outer surface of each part to be stair-stepped, which may affect the stress and strain measurements at interfaces between parts. To improve the interaction between the skull, CSF, and brain surfaces, a previously developed mesh smoothing algorithm based on a Laplacian non-shrinking smoothing algorithm was applied to the FE model. This algorithm not only applies smoothing to the surface of the model, but also to the interfaces between the brain, CSF, and skull, while preserving volume and element quality. Warpage, jacobian, aspect ratio, and skew were evaluated and reveal that >99% of the elements retain good element quality. Future work includes implementation of contact definitions to accurately represent the brain-skull interface and to ultimately better understand and predict head injury. PMID:25996716

  5. Unilateral watershed cerebral infarcts.

    PubMed

    Bogousslavsky, J; Regli, F

    1986-03-01

    We studied 51 patients with symptomatic unilateral watershed (WS) cerebral infarct on CT. In 22 patients, the infarct was between the superficial territory of the anterior and middle cerebral arteries, 20 had an infarct between the superficial territory of the middle and posterior cerebral arteries, and 9 had an infarct between the superficial and deep territory of the middle cerebral arteries. Each type had a characteristic neurologic picture. Syncope at onset (37%) and focal limb shaking (12%) were frequent. Thirty-eight patients (75%) had internal carotid artery occlusion or tight stenosis associated with a hemodynamically significant cardiopathy, increased hematocrit, or acute hypotension. Embolic infarction was probable in only two patients (4%) who had only atrial fibrillation. PMID:3951705

  6. Controlled cortical impact model for traumatic brain injury.

    PubMed

    Romine, Jennifer; Gao, Xiang; Chen, Jinhui

    2014-01-01

    Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI. PMID:25145417

  7. Avoiding Boltzmann Brain domination in holographic dark energy models

    NASA Astrophysics Data System (ADS)

    Horvat, R.

    2015-11-01

    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 dimensionless model 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 latter case, the bound on c is exponentially stronger, and seemingly at odds with those bounds on c obtained from various observational tests.

  8. 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

  9. Imatinib treatment reduces brain injury in a murine model of traumatic brain injury.

    PubMed

    Su, Enming J; Fredriksson, Linda; Kanzawa, Mia; Moore, Shannon; Folestad, Erika; Stevenson, Tamara K; Nilsson, Ingrid; Sashindranath, Maithili; Schielke, Gerald P; Warnock, Mark; Ragsdale, Margaret; Mann, Kris; Lawrence, Anna-Lisa E; Medcalf, Robert L; Eriksson, Ulf; Murphy, Geoffrey G; Lawrence, Daniel A

    2015-01-01

    Current therapies for Traumatic brain injury (TBI) focus on stabilizing individuals and on preventing further damage from the secondary consequences of TBI. A major complication of TBI is cerebral edema, which can be caused by the loss of blood brain barrier (BBB) integrity. Recent studies in several CNS pathologies have shown that activation of latent platelet derived growth factor-CC (PDGF-CC) within the brain can promote BBB permeability through PDGF receptor ? (PDGFR?) signaling, and that blocking this pathway improves outcomes. In this study we examine the efficacy for the treatment of TBI of an FDA approved antagonist of the PDGFR?, Imatinib. Using a murine model we show that Imatinib treatment, begun 45 min after TBI and given twice daily for 5 days, significantly reduces BBB dysfunction. This is associated with significantly reduced lesion size 24 h, 7 days, and 21 days after TBI, reduced cerebral edema, determined from apparent diffusion co-efficient (ADC) measurements, and with the preservation of cognitive function. Finally, analysis of cerebrospinal fluid (CSF) from human TBI patients suggests a possible correlation between high PDGF-CC levels and increased injury severity. Thus, our data suggests a novel strategy for the treatment of TBI with an existing FDA approved antagonist of the PDGFR?. PMID:26500491

  10. Imatinib treatment reduces brain injury in a murine model of traumatic brain injury

    PubMed Central

    Su, Enming J.; Fredriksson, Linda; Kanzawa, Mia; Moore, Shannon; Folestad, Erika; Stevenson, Tamara K.; Nilsson, Ingrid; Sashindranath, Maithili; Schielke, Gerald P.; Warnock, Mark; Ragsdale, Margaret; Mann, Kris; Lawrence, Anna-Lisa E.; Medcalf, Robert L.; Eriksson, Ulf; Murphy, Geoffrey G.; Lawrence, Daniel A.

    2015-01-01

    Current therapies for Traumatic brain injury (TBI) focus on stabilizing individuals and on preventing further damage from the secondary consequences of TBI. A major complication of TBI is cerebral edema, which can be caused by the loss of blood brain barrier (BBB) integrity. Recent studies in several CNS pathologies have shown that activation of latent platelet derived growth factor-CC (PDGF-CC) within the brain can promote BBB permeability through PDGF receptor α (PDGFRα) signaling, and that blocking this pathway improves outcomes. In this study we examine the efficacy for the treatment of TBI of an FDA approved antagonist of the PDGFRα, Imatinib. Using a murine model we show that Imatinib treatment, begun 45 min after TBI and given twice daily for 5 days, significantly reduces BBB dysfunction. This is associated with significantly reduced lesion size 24 h, 7 days, and 21 days after TBI, reduced cerebral edema, determined from apparent diffusion co-efficient (ADC) measurements, and with the preservation of cognitive function. Finally, analysis of cerebrospinal fluid (CSF) from human TBI patients suggests a possible correlation between high PDGF-CC levels and increased injury severity. Thus, our data suggests a novel strategy for the treatment of TBI with an existing FDA approved antagonist of the PDGFRα. PMID:26500491

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

    PubMed

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

    2015-04-01

    The transplantation of adipose tissue-derived stem cells (ADSCs) improves cardiac contractility after myocardial infarction (MI); however, little is known about the electrophysiological consequences of transplantation. The purpose of this study was to clarify whether the transplantation of ADSCs increases or decreases the incidence of ventricular tachyarrhythmias (VT) in a rat model of MI. MI was induced experimentally by permanent occlusion of the left anterior descending artery of Lewis rats. ADSCs were harvested from GFP-transgenic rats, and were cultured until passage four. ADSCs (1010(6)) resuspended in 100?L saline or pro-survival cocktail (PSC), which enhances cardiac graft survival, were injected directly into syngeneic rat hearts 1week after MI. The recipients of ADSCs suspended in PSC had a larger graft area compared with those receiving ASDCs suspended in saline at 1week post-transplantation (number of graft cells/section: 148.710.6 vs. 22.43.4, p<0.05, n=5/group). Thereafter, all ADSC recipients were transplanted with ASDCs in PSC. ADSCs were transplanted into infarcted hearts, and the mechanical and electrophysiological functions were assessed. Echocardiography revealed that ADSC recipients had improved contractile function compared with those receiving PSC vehicle (fractional shortening: 21.10.9 vs. 14.11.2, p<0.05, n?12/group). Four weeks post-transplantation, VT was induced via in vivo programmed electrical stimulation. The recipients of ADSCs showed a significantly lower incidence of induced VT compared with the control (31.3% vs. 83.3%, p<0.05, n?12/group). To understand the electrical activity following transplantation, we performed ex vivo optical mapping using a voltage sensitive dye, and found that ADSC transplantation decreased conduction velocity and its dispersion in the peri-infarct area. These results suggest that ADSC transplantation improved cardiac mechanical and electrophysiological functions in subacute MI. PMID:25724725

  12. Developing better and more valid animal models of brain disorders.

    PubMed

    Stewart, Adam Michael; Kalueff, Allan V

    2015-01-01

    Valid sensitive animal models are crucial for understanding the pathobiology of complex human disorders, such as anxiety, autism, depression and schizophrenia, which all have the 'spectrum' nature. Discussing new important strategic directions of research in this field, here we focus i) on cross-species validation of animal models, ii) ensuring their population (external) validity, and iii) the need to target the interplay between multiple disordered domains. We note that optimal animal models of brain disorders should target evolutionary conserved 'core' traits/domains and specifically mimic the clinically relevant inter-relationships between these domains. PMID:24384129

  13. 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

  14. Self-organization in a simple brain model

    SciTech Connect

    Stassinopoulos, D.; Bak, P.; Alstroem, P.

    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.

  15. [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

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

    PubMed Central

    Feng, Yuanbo; Bogaert, Jan; Oyen, Raymond

    2014-01-01

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

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

    PubMed Central

    Gerth, Sabrina; Vasishth, Shravan

    2008-01-01

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

  18. Signal transmission competing with noise in model excitable brains

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

  19. [Acute myocardial infarction with neurological symptoms: clinical and pathologic aspects].

    PubMed

    Manea, Paloma; Cosovanu, A; Stefanache, Felicia; Hodorog, Diana; Logof?tu, Stefania; Dumitrescu, Gabriela

    2004-01-01

    A variety neurological symptoms can be the onset of an acute myocardial infarction. The study includes 96 patients who have undergone necropsies (from 1978 to 2003), hospitalized at the "Sfnta Treime" University Hospital, Ia?i, in the Neurology Clinic. They were admitted for various neurological manifestations: hemiparesis, hemiplegia, aphasia, coma of the 1st degree up to the 4th. Death of these patients was due to acute myocardial infarction in the cases of most of them, even those with significant brain damage. We have taken into account the anatomic pathology of the heart, brain, kidneys and lungs. The prevalence of the factors of cardiovascular risk was considered in our study, as well as the topography of the myocardial infarction. Patients with acute myocardial infarction can present major neurological symptoms with no significant cardiovascular clinical symptoms. PMID:15832969

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

    PubMed Central

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

    2014-01-01

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

  1. Functional Consequences of a Tissue-Engineered Myocardial Patch for Cardiac Repair in a Rat Infarct Model

    PubMed Central

    Wendel, Jacqueline S.; Ye, Lei; Zhang, Pengyuan

    2014-01-01

    Cell therapies have emerged as a promising treatment for the prevention of heart failure after myocardial infarction (MI). This study evaluated the capacity of an aligned, fibrin-based, stretch-conditioned cardiac patch consisting of either the native population or a cardiomyocyte (CM)depleted population (i.e., CM+ or CM? patches) of neonatal rat heart cells to ameliorate left ventricular (LV) remodeling in the acute-phase postinfarction in syngeneic, immunocompetent rats. Patches were exposed to 7 days of static culture and 7 days of cyclic stretching prior to implantation. Within 1 week of implantation, both patches became vascularized, and non-CMs began migrating from CM+ patches. By week 4, patches had been remodeled into collagenous tissue, and live, elongated, donor CMs were found within grafted CM+ patches. Significant improvement in cardiac contractile function was seen with the administration of the CM+ patch (ejection fraction increased from 35.1%4.0% for MI only to 58.8%7.3% with a CM+ patch, p<0.05) associated with a 77% reduction in infarct size (61.3%7.9% for MI only, 13.9%10.8% for CM+ patch, p<0.05), and the elimination of LV free-wall thinning. Decreased infarct size and reduced wall thinning also occurred with the administration of the CM? patch (infarct size 36.9%10.2%, LV wall thickness: 1058.2135.4??m for CM? patch, 661.337.4??m for MI only, p<0.05), but without improvements in cardiac function. Approximately 36.5% of the transplanted CMs survived at 4 weeks; however, they remained separated and electrically uncoupled from the host myocardium by a layer of CM-free tissue, which suggests that the benefits of CM+ patch transplantation resulted from paracrine mechanisms originating from CMs. Collectively, these observations suggest that the transplantation of CM-containing engineered heart tissue patches can lead to dramatic improvements in cardiac function and remodeling after acute MI. PMID:24295499

  2. Amelioration of ischemic brain damage by peritoneal dialysis

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Egea, J; Parada, E; Gmez-Rangel, V; Buendia, I; Negredo, P; Montell, E; Ruh, R; Vergs, J; Roda, J M; Garca, A G; Lpez, 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. Fluid-percussioninduced traumatic brain injury model in rats

    PubMed Central

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

    2013-01-01

    Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Various attempts have been made to replicate clinical TBI using animal models. The fluid-percussion model (FP) is one of the oldest and most commonly used models of experimentally induced TBI. Both central (CFP) and lateral (LFP) variations of the model have been used. Developed initially for use in larger species, the standard FP device was adapted more than 20 years ago to induce consistent degrees of brain injury in rodents. Recently, we developed a microprocessor-controlled, pneumatically driven instrument, micro-FP (MFP), to address operational concerns associated with the use of the standard FP device in rodents. We have characterized the MFP model with regard to injury severity according to behavioral and histological outcomes. In this protocol, we review the FP models and detail surgical procedures for LFP. The surgery involves tracheal intubation, craniotomy and fixation of Luer fittings, and induction of injury. The surgical procedure can be performed within 4550 min. PMID:20725070

  5. 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.

  6. A theoretical model of phase transitions in the human brain.

    PubMed

    Jirsa, V K; Friedrich, R; Haken, H; Kelso, J A

    1994-01-01

    An experiment using a multisensor SQUID (superconducting quantum interference device) array was performed by Kelso and colleagues (1992) which combined information from three different sources: perception, motor response, and brain signals. When an acoustic stimulus frequency is changed systematically, a spontaneous transition in coordination occurs at a critical frequency in both motor behavior and brain signals. Qualitatively analogous transitions are known for physical and biological systems such as changes in the coordination of human hand movements (Kelso 1981, 1984). In this paper we develop a theoretical model based on methods from the interdisciplinary field of synergetics (Haken 1983, 1987) and nonlinear oscillator theory that reproduces the main experimental features very well and suggests a formulation of a fundamental biophysical coupling. PMID:8054384

  7. Brain glioma growth model using reaction-diffusion equation with viscous stress tensor on brain MR images.

    PubMed

    Yuan, Jianjun; Liu, Lipei

    2016-02-01

    In this paper, a new reaction-diffusion model with viscous stress tensor is proposed for modeling the diffusion and invasion of brain glioma cells, which is based on the model in Yuan J.J., Liu L., Hu Q.M. Mathematical modeling of brain glioma growth using modified reaction-diffusion equation on brain MR images. Comput Biol Med 2013;43:2007-2013. The corresponding parameters are computed. The viscous stress tensor is introduced into reaction-diffusion equation, and can describe more accurately the adhesion of gliomas and normal cells. The experimental results demonstrate the effectiveness and accuracy of the proposed reaction-diffusion equation with viscous stress tensor for real brain glioma MR images. PMID:26518060

  8. High-tech brains: a history of technology-based analogies and models of nerve and brain function.

    PubMed

    Kirkland, Kyle L

    2002-01-01

    This article reviews some of the technological devices and ideas which have been used over the years to answer the question, how does the brain work? It describes some of the early technology-based analogies and models of nerve fibers, and then discusses other analogies and models of the brain based on mechanical and electrical technologies. There are also short sections on cybernetics, telephone exchanges, and computers. Although all of these ideas are flawed to some extent, this article offers a brief argument on the usefulness of analogy and abstraction in brain science. PMID:11919380

  9. Biothermal Model of Patient for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Wakamatsu, Hidetoshi; Gaohua, Lu

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

  10. 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

  11. Thrombolytics and myocardial infarction.

    PubMed

    Kunadian, Vijayalakshmi; Gibson, C Michael

    2012-04-01

    Coronary artery disease is the single leading cause of death in the United States. Occlusion of the coronary artery was identified to be the cause of myocardial infarction almost a century ago. Following a series of investigations, streptokinase was discovered and demonstrated to be beneficial for the treatment of patients with acute myocardial infarction in terms of reducing short- and long-term mortality. Newer agents including tissue plasminogen activators such as alteplase, reteplase, tenecteplase were developed subsequently. In the present era, thrombolytic therapy and primary percutaneous coronary intervention has revolutionized the way patients with acute myocardial infarction are managed resulting in significant reduction in cardiovascular death. This article provides an overview of the various thrombolytic agents utilized in the management of patients with acute myocardial infarction. PMID:21070617

  12. Organotypic brain slice cultures as a model to study angiogenesis of brain vessels.

    PubMed

    Hutter-Schmid, Bianca; Kniewallner, Kathrin M; Humpel, Christian

    2015-01-01

    Brain vessels are the most important structures in the brain to deliver energy and substrates to neurons. Brain vessels are composed of a complex interaction between endothelial cells, pericytes, and astrocytes, controlling the entry of substrates into the brain. Damage of brain vessels and vascular impairment are general pathologies observed in different neurodegenerative disorders including e.g., Alzheimer's disease. In order to study remodeling of brain vessels, simple 3-dimensional in vitro systems need to be developed. Organotypic brain slices of mice provide a potent tool to explore angiogenic effects of brain vessels in a complex 3-dimensional structure. Here we show that organotypic brain slices can be cultured from 110 ?m thick sections of postnatal and adult mice brains. The vessels are immunohistochemically stained for laminin and collagen IV. Co-stainings are an appropriate method to visualize interaction of brain endothelial cells with pericytes and astrocytes in these vessels. Different exogenous stimuli such as fibroblast growth factor-2 or vascular endothelial growth factor induce angiogenesis or re-growth, respectively. Hyperthermia or acidosis reduces the vessel density in organotypic slices. In conclusion, organotypic brain slices exhibit a strong vascular network which can be used to study remodeling and angiogenesis of brain vessels in a 3-dimensional in vitro system. PMID:26389117

  13. Organotypic brain slice cultures as a model to study angiogenesis of brain vessels

    PubMed Central

    Hutter-Schmid, Bianca; Kniewallner, Kathrin M.; Humpel, Christian

    2015-01-01

    Brain vessels are the most important structures in the brain to deliver energy and substrates to neurons. Brain vessels are composed of a complex interaction between endothelial cells, pericytes, and astrocytes, controlling the entry of substrates into the brain. Damage of brain vessels and vascular impairment are general pathologies observed in different neurodegenerative disorders including e.g., Alzheimer's disease. In order to study remodeling of brain vessels, simple 3-dimensional in vitro systems need to be developed. Organotypic brain slices of mice provide a potent tool to explore angiogenic effects of brain vessels in a complex 3-dimensional structure. Here we show that organotypic brain slices can be cultured from 110 ?m thick sections of postnatal and adult mice brains. The vessels are immunohistochemically stained for laminin and collagen IV. Co-stainings are an appropriate method to visualize interaction of brain endothelial cells with pericytes and astrocytes in these vessels. Different exogenous stimuli such as fibroblast growth factor-2 or vascular endothelial growth factor induce angiogenesis or re-growth, respectively. Hyperthermia or acidosis reduces the vessel density in organotypic slices. In conclusion, organotypic brain slices exhibit a strong vascular network which can be used to study remodeling and angiogenesis of brain vessels in a 3-dimensional in vitro system. PMID:26389117

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

    PubMed

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

    2012-01-20

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

  15. Experimental myocardial infarction

    PubMed Central

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

    1970-01-01

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

  16. [A brain shift correction model based on the fuzzy support vector machines with different constant term].

    PubMed

    Wang, Wei; Zhang, Chenxi

    2010-12-01

    Brain shift contributes mostly to the error of prediction in Image-Guided Neurosurgery (IGNS). In order to solve this problem, we build a statistical learning model between the quantity of the brain shift and we factors that impinge on the brain shift, and we predict the brain shift by using this model. The prediction of the brain shift can be regarded as an approach to estimation of regression function, the quantity of the brain shift is the output value of the function, while the corresponding factors that affect the brain shift can be taken as the input value of the function. In this study, we employ the fuzzy support vector machines (FSVM) with different constant term to build a brain shift correction model between the quantity of the brain shift and the factors that affect the brain shift. By taking 10 clinical data sets and employing the novel predicting method, we trained the relational model of the multi-dimensional data for the brain tissue displacement, the direction of surgical operation, and the operative site, etc. The results of validating the model by the leave-one-out method unveil that the approach recapitulated 90% of the shift, thus indicating that the correction model based on the FSVM with different constant term can be used to predict the brain shift with clinically acceptable accuracy. Therefore, the model can be applied to IGNS. PMID:21374995

  17. Multiscale modeling and simulation of brain blood flow

    NASA Astrophysics Data System (ADS)

    Perdikaris, Paris; Grinberg, Leopold; Karniadakis, George Em

    2016-02-01

    The aim of this work is to present an overview of recent advances in multi-scale modeling of brain blood flow. In particular, we present some approaches that enable the in silico study of multi-scale and multi-physics phenomena in the cerebral vasculature. We discuss the formulation of continuum and atomistic modeling approaches, present a consistent framework for their concurrent coupling, and list some of the challenges that one needs to overcome in achieving a seamless and scalable integration of heterogeneous numerical solvers. The effectiveness of the proposed framework is demonstrated in a realistic case involving modeling the thrombus formation process taking place on the wall of a patient-specific cerebral aneurysm. This highlights the ability of multi-scale algorithms to resolve important biophysical processes that span several spatial and temporal scales, potentially yielding new insight into the key aspects of brain blood flow in health and disease. Finally, we discuss open questions in multi-scale modeling and emerging topics of future research.

  18. Experimental modeling of explosive blast-related traumatic brain injuries.

    PubMed

    Alley, Matthew D; Schimizze, Benjamin R; Son, Steven F

    2011-01-01

    This study aims to characterize the interaction of explosive blast waves through simulated anatomical systems. We have developed physical models and a systematic approach for testing traumatic brain injury (TBI) mechanisms and occurrences. A simplified series of models consisting of spherical poly(methyl methacrylate) (PMMA) shells housing synthetic gelatins as brain simulants have been utilized. A series of experiments was conducted to compare the sensitivity of the system response to mechanical properties of the simulants under high strain-rate explosive blasts. Small explosive charges were directed at the models to produce a realistic blast wave in a scaled laboratory setting. Blast profiles were measured and analyzed to compare system response severity. High-speed shadowgraph imaging captured blast wave interaction with the head model while particle tracking captured internal response for displacement and strain correlation. The results suggest amplification of shock waves inside the head near material interfaces due to impedance mismatches. In addition, significant relative displacement was observed between the interacting materials suggesting large strain values of nearly 5%. Further quantitative results were obtained through shadowgraph imaging of the blasts confirming a separation of time scales between blast interaction and bulk movement. These results lead to a conclusion that primary blast effects may potentially contribute significantly to the occurrence of military associated TBI. PMID:20580931

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

    SciTech Connect

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

    2009-09-15

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

  20. Therapeutic Hypothermia for Cardioprotection in Acute Myocardial Infarction

    PubMed Central

    Kang, In Sook; Fumiaki, Ikeno

    2016-01-01

    Mild therapeutic hypothermia of 32–35℃ improved neurologic outcomes in outside hospital cardiac arrest survivor. Furthermore, in experimental studies on infarcted model and pilot studies on conscious patients with acute myocardial infarction, therapeutic hypothermia successfully reduced infarct size and microvascular resistance. Therefore, mild therapeutic hypothermia has received an attention as a promising solution for reduction of infarction size after acute myocardial infarction which are not completely solved despite of optimal reperfusion therapy. Nevertheless, the results from randomized clinical trials failed to prove the cardioprotective effects of therapeutic hypothermia or showed beneficial effects only in limited subgroups. In this article, we reviewed rationale for therapeutic hypothermia and possible mechanisms from previous studies, effective methods for clinical application to the patients with acute myocardial infarction, lessons from current clinical trials and future directions. PMID:26847278

  1. Therapeutic Hypothermia for Cardioprotection in Acute Myocardial Infarction.

    PubMed

    Kang, In Sook; Fumiaki, Ikeno; Pyun, Wook Bum

    2016-03-01

    Mild therapeutic hypothermia of 32-35C improved neurologic outcomes in outside hospital cardiac arrest survivor. Furthermore, in experimental studies on infarcted model and pilot studies on conscious patients with acute myocardial infarction, therapeutic hypothermia successfully reduced infarct size and microvascular resistance. Therefore, mild therapeutic hypothermia has received an attention as a promising solution for reduction of infarction size after acute myocardial infarction which are not completely solved despite of optimal reperfusion therapy. Nevertheless, the results from randomized clinical trials failed to prove the cardioprotective effects of therapeutic hypothermia or showed beneficial effects only in limited subgroups. In this article, we reviewed rationale for therapeutic hypothermia and possible mechanisms from previous studies, effective methods for clinical application to the patients with acute myocardial infarction, lessons from current clinical trials and future directions. PMID:26847278

  2. A rodent model of mild traumatic brain blast injury.

    PubMed

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

    2015-04-01

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

  3. Ekbom syndrome occurring with multi infarct dementia.

    PubMed

    Bhatia, M S; Gautam, Priyanka; Kaur, Jaswinder

    2015-04-01

    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

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

    PubMed Central

    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

  5. 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

  6. Multispectral brain tumor segmentation based on histogram model adaptation

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

  7. Brain glucose metabolism in an animal model of depression.

    PubMed

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

    2015-06-01

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

  8. A Mixed Approach for Modeling Blood Flow in Brain Microcirculation

    NASA Astrophysics Data System (ADS)

    Peyrounette, M.; Sylvie, L.; Davit, Y.; Quintard, M.

    2014-12-01

    We have previously demonstrated [1] that the vascular system of the healthy human brain cortex is a superposition of two structural components, each corresponding to a different spatial scale. At small-scale, the vascular network has a capillary structure, which is homogeneous and space-filling over a cut-off length. At larger scale, veins and arteries conform to a quasi-fractal branched structure. This structural duality is consistent with the functional duality of the vasculature, i.e. distribution and exchange. From a modeling perspective, this can be viewed as the superposition of: (a) a continuum model describing slow transport in the small-scale capillary network, characterized by a representative elementary volume and effective properties; and (b) a discrete network approach [2] describing fast transport in the arterial and venous network, which cannot be homogenized because of its fractal nature. This problematic is analogous to modeling problems encountered in geological media, e.g, in petroleum engineering, where fast conducting channels (wells or fractures) are embedded in a porous medium (reservoir rock). An efficient method to reduce the computational cost of fractures/continuum simulations is to use relatively large grid blocks for the continuum model. However, this also makes it difficult to accurately couple both structural components. In this work, we solve this issue by adapting the "well model" concept used in petroleum engineering [3] to brain specific 3-D situations. We obtain a unique linear system of equations describing the discrete network, the continuum and the well model coupling. Results are presented for realistic geometries and compared with a non-homogenized small-scale network model of an idealized periodic capillary network of known permeability. [1] Lorthois & Cassot, J. Theor. Biol. 262, 614-633, 2010. [2] Lorthois et al., Neuroimage 54 : 1031-1042, 2011. [3] Peaceman, SPE J. 18, 183-194, 1978.

  9. Asynchronous brain computer interface using hidden semi-Markov models.

    PubMed

    Oliver, Gareth; Sunehag, Peter; Gedeon, Tom

    2012-01-01

    Ideal Brain Computer Interfaces need to perform asynchronously and at real time. We propose Hidden Semi-Markov Models (HSMM) to better segment and classify EEG data. The proposed HSMM method was tested against a simple windowed method on standard datasets. We found that our HSMM outperformed the simple windowed method. Furthermore, due to the computational demands of the algorithm, we adapted the HSMM algorithm to an online setting and demonstrate that this faster version of the algorithm can run in real time. PMID:23366489

  10. The musician's brain as a model of neuroplasticity.

    PubMed

    Mnte, Thomas F; Altenmller, Eckart; Jncke, Lutz

    2002-06-01

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

  11. 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

  12. In vivo animal models for studying brain metastasis: value and limitations.

    PubMed

    Daphu, Inderjit; Sundstrm, Terje; Horn, Sindre; Huszthy, Peter C; Niclou, Simone P; Sakariassen, Per ; Immervoll, Heike; Miletic, Hrvoje; Bjerkvig, Rolf; Thorsen, Frits

    2013-06-01

    Brain metastasis is associated with a particular poor prognosis. Novel insight into the brain metastatic process is therefore warranted. Several preclinical models of brain tumor metastasis have been developed during the last 60 years, and they have in part revealed some of the mechanisms underlying the metastatic process. This review discusses mechanisms of brain metastasis with a key focus of the development of animal model systems. This includes the use of rodent, syngeneic brain metastasis models (spontaneous, chemically induced and genetically engineered models) and human xenotransplantation models (ectopic inoculation and orthotopic models). Current information indicates that none of these fully reflect tumor development seen in patients with metastatic disease. The various model systems used, however, have provided important insight into specific mechanisms of the metastatic process related to the brain. By combining the knowledge obtained from animal models, new important information on the molecular mechanisms behind metastasis will be obtained, leading to the future development of new therapeutic strategies. PMID:23322381

  13. Optimized Heart Sampling and Systematic Evaluation of Cardiac Therapies in Mouse Models of Ischemic Injury: Assessment of Cardiac Remodeling and Semi-Automated Quantification of Myocardial Infarct Size.

    PubMed

    Valente, Mariana; Arajo, Ana; Esteves, Tiago; Laundos, Tiago L; Freire, Ana G; Quelhas, Pedro; Pinto-do-, Perptua; Nascimento, Diana S

    2015-01-01

    Cardiac therapies are commonly tested preclinically in small-animal models of myocardial infarction. Following functional evaluation, post-mortem histological analysis is essential to assess morphological and molecular alterations underlying the effectiveness of treatment. However, non-methodical and inadequate sampling of the left ventricle often leads to misinterpretations and variability, making direct study comparisons unreliable. Protocols are provided for representative sampling of the ischemic mouse heart followed by morphometric analysis of the left ventricle. Extending the use of this sampling to other types of in situ analysis is also illustrated through the assessment of neovascularization and cellular engraftment in a cell-based therapy setting. This is of interest to the general cardiovascular research community as it details methods for standardization and simplification of histo-morphometric evaluation of emergent heart therapies. 2015 by John Wiley & Sons, Inc. PMID:26629776

  14. Acute simultaneous multiple lacunar infarcts as the initial presentation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

    PubMed

    Hsiao, Cheng-Tsung; Chen, Yun-Chung; Liu, Yo-Tsen; Soong, Bing-Wen; Lee, Yi-Chung

    2015-07-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset, dominantly inherited small-vessel disease of the brain caused by NOTCH3 mutations and characterized by recurrent subcortical infarctions, dementia, migraine with aura, and mood disturbance. We report a patient with unusual presentation of CADASIL with acute simultaneous multiple subcortical lacunar infarcts as the first manifestation. A 69-year-old man developed confusion, drowsiness, right hemiparesis, and slurred speech following orthopedic surgeries. Brain magnetic resonance imaging revealed diffuse leukoencephalopathy and multiple acute subcortical lacunar infarcts. Brain magnetic resonance angiography, echocardiography and 24-hour electrocardiography were unremarkable. The symptoms improved quickly after treatment with fluid hydration and antiplatelet agent, and his consciousness and mentality totally recovered within 3 days. The NOTCH3 genetic testing showed a heterozygous missense mutation, c.1630C>T (p. Arg544Cys). The experience in this case suggests that brain imaging is important in managing postoperative confusion, and any patient with diffuse leukoencephalopathy of unknown etiology may need to be tested for NOTCH3 mutations. Surgery is an important factor of encephalopathy and acute infarction in individuals with NOTCH3 mutations. Comprehensive presurgical evaluations and proactive perioperative precautions to avoid dehydration and anemia are necessary for patients with CADASIL who are about to receive anesthesia and surgery. PMID:25959358

  15. Brain Anatomical Structure Segmentation by Hybrid Discriminative/Generative Models

    PubMed Central

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

    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 discriminative 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 multi-class discriminative models that combine hundreds of features across different scales. On the generative model side, both global and local shape models are used to capture the shape information about each anatomical structure. The parameters to combine the discriminative appearance and generative shape models are also automatically learned. Thus low-level and high-level information is learned and integrated in a hybrid model. Segmentations are obtained by minimizing an energy function associated with the proposed hybrid model. Finally, a grid-face structure is designed to explicitly represent the 3D region topology. This representation handles an arbitrary number of regions and facilitates fast surface evolution. Our system was trained and tested on a set of 3D MRI volumes and the results obtained are encouraging. PMID:18390346

  16. Brain anatomical structure segmentation by hybrid discriminative/generative models.

    PubMed

    Tu, Z; Narr, K L; Dollar, P; Dinov, I; Thompson, P M; Toga, A W

    2008-04-01

    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 discriminative 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 that combine hundreds of features across different scales. On the generative model side, both global and local shape models are used to capture the shape information about each anatomical structure. The parameters to combine the discriminative appearance and generative shape models are also automatically learned. Thus, low-level and high-level information is learned and integrated in a hybrid model. Segmentations are obtained by minimizing an energy function associated with the proposed hybrid model. Finally, a grid-face structure is designed to explicitly represent the 3-D region topology. This representation handles an arbitrary number of regions and facilitates fast surface evolution. Our system was trained and tested on a set of 3-D magnetic resonance imaging (MRI) volumes and the results obtained are encouraging. PMID:18390346

  17. Cluster imaging of multi-brain networks (CIMBN): a general framework for hyperscanning and modeling a group of interacting brains

    PubMed Central

    Duan, Lian; Dai, Rui-Na; Xiao, Xiang; Sun, Pei-Pei; Li, Zheng; Zhu, Chao-Zhe

    2015-01-01

    Studying the neural basis of human social interactions is a key topic in the field of social neuroscience. Brain imaging studies in this field usually focus on the neural correlates of the social interactions between two participants. However, as the participant number further increases, even by a small amount, great difficulties raise. One challenge is how to concurrently scan all the interacting brains with high ecological validity, especially for a large number of participants. The other challenge is how to effectively model the complex group interaction behaviors emerging from the intricate neural information exchange among a group of socially organized people. Confronting these challenges, we propose a new approach called “Cluster Imaging of Multi-brain Networks” (CIMBN). CIMBN consists of two parts. The first part is a cluster imaging technique with high ecological validity based on multiple functional near-infrared spectroscopy (fNIRS) systems. Using this technique, we can easily extend the simultaneous imaging capacity of social neuroscience studies up to dozens of participants. The second part of CIMBN is a multi-brain network (MBN) modeling method based on graph theory. By taking each brain as a network node and the relationship between any two brains as a network edge, one can construct a network model for a group of interacting brains. The emergent group social behaviors can then be studied using the network's properties, such as its topological structure and information exchange efficiency. Although there is still much work to do, as a general framework for hyperscanning and modeling a group of interacting brains, CIMBN can provide new insights into the neural correlates of group social interactions, and advance social neuroscience and social psychology. PMID:26283906

  18. Focal brain trauma in the cryogenic lesion model in mice

    PubMed Central

    2012-01-01

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

  19. Focal brain trauma in the cryogenic lesion model in mice.

    PubMed

    Raslan, Furat; Albert-Weienberger, Christiane; Ernestus, Ralf-Ingo; Kleinschnitz, Christoph; Sirn, Anna-Leena

    2012-01-01

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

  20. A mouse model of human repetitive mild traumatic brain injury

    PubMed Central

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

    2011-01-01

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

  1. Modeling the brain-pituitary-gonad axis in salmon

    SciTech Connect

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

    2006-08-24

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

  2. Right ventricular infarction mimicking anterior infarction: a case report.

    PubMed

    Vives, M A; Bonet, L A; Soriano, J R; Lalaguna, L A; Sez, A O; de Arellano, A R; Prez, M P

    1999-10-01

    Right ventricular infarction usually occurs in association with inferior infarction, with no remarkable electrocardiographic signs in conventional leads. This report describes a patient with a previous inferior acute myocardial infarction who developed right ventricular infarction with significant anterior lead ST segment elevation (V1-V4) caused by the loss of two large right ventricular branches during a coronary angioplasty of the right coronary artery. The case is discussed and the literature is reviewed. PMID:10549912

  3. 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

  4. Multistability in Large Scale Models of Brain Activity.

    PubMed

    Golos, Mathieu; Jirsa, Viktor; Dauc, Emmanuel

    2015-12-01

    Noise driven exploration of a brain network's dynamic repertoire has been hypothesized to be causally involved in cognitive function, aging and neurodegeneration. The dynamic repertoire crucially depends on the network's capacity to store patterns, as well as their stability. Here we systematically explore the capacity of networks derived from human connectomes to store attractor states, as well as various network mechanisms to control the brain's dynamic repertoire. Using a deterministic graded response Hopfield model with connectome-based interactions, we reconstruct the system's attractor space through a uniform sampling of the initial conditions. Large fixed-point attractor sets are obtained in the low temperature condition, with a bigger number of attractors than ever reported so far. Different variants of the initial model, including (i) a uniform activation threshold or (ii) a global negative feedback, produce a similarly robust multistability in a limited parameter range. A numerical analysis of the distribution of the attractors identifies spatially-segregated components, with a centro-medial core and several well-delineated regional patches. Those different modes share similarity with the fMRI independent components observed in the "resting state" condition. We demonstrate non-stationary behavior in noise-driven generalizations of the models, with different meta-stable attractors visited along the same time course. Only the model with a global dynamic density control is found to display robust and long-lasting non-stationarity with no tendency toward either overactivity or extinction. The best fit with empirical signals is observed at the edge of multistability, a parameter region that also corresponds to the highest entropy of the attractors. PMID:26709852

  5. Evaluation of Left Ventricle Function by Regional Fractional Area Change (RFAC) in a Mouse Model of Myocardial Infarction Secondary to Valsartan Treatment

    PubMed Central

    Castiglioni, Laura; Colazzo, Francesca; Fontana, Lucia; Colombo, Gualtiero I.; Piacentini, Luca; Bono, Elisa; Milano, Giuseppina; Paleari, Serena; Palermo, Annamaria; Guerrini, Uliano; Tremoli, Elena; Sironi, Luigi

    2015-01-01

    Aim Left ventricle (LV) regional fractional area change (RFAC) measured by cardiac magnetic resonance (CMR) allows the non-invasive localization and quantification of the degree of myocardial infarction (MI), and could be applied to assess the effectiveness of pharmacological or regenerative therapies. Here we investigate the ability of RFAC to identify regional dysfunction and discriminate the effect of pharmacological treatment with valsartan, a selective antagonist of angiotensin II type 1 receptor, in a model of MI. Methods and Results C57BL/6N mice, undergoing coronary artery ligation, were divided into two groups: untreated (MI) or treated with valsartan (MI+Val). Sham-operated mice were used as a control. Cardiac dimensions and function were assessed at baseline, 24 hours, 1 and 4 weeks post surgery by CMR and echocardiography. At sacrifice histology and whole-genome gene expression profiling were performed. RFAC was able to detect significant differences between treatment groups whereas the global ejection fraction was not. RFAC showed greater loss of regional contraction in remote non-infarcted myocardium in MI group than in MI+Val group. Consistently, in the same region MI+Val mice showed reduced myocyte hypertrophy, fibroblast proliferation, and fibrosis and modulation of target genes; in addition, left atrium volumes, appendage length and duct contraction were preserved. Conclusion In this study, RFAC effectively estimated the degree of systolic dysfunction and discriminated the regions preserved by pharmacological treatment. RFAC index is a promising tool to monitor changes in LV contraction and to assess the effectiveness of therapeutic regimens in clinical settings. PMID:26291973

  6. Language Model Applications to Spelling with Brain-Computer Interfaces

    PubMed Central

    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. Myocardial infarction accelerates atherosclerosis

    PubMed Central

    Dutta, Partha; Courties, Gabriel; Wei, Ying; Leuschner, Florian; Gorbatov, Rostic; Robbins, Clinton; Iwamoto, Yoshiko; Thompson, Brian; Carlson, Alicia L.; Heidt, Timo; Majmudar, Maulik D.; Lasitschka, Felix; Etzrodt, Martin; Waterman, Peter; Waring, Michael T.; Chicoine, Adam T.; van der Laan, Anja M.; Niessen, Hans W.M.; Piek, Jan J.; Rubin, Barry B.; Butany, Jagdish; Stone, James; Katus, Hugo A.; Murphy, Sabina A.; Morrow, David A.; Sabatine, Marc S.; Vinegoni, Claudio; Moskowitz, Michael A.; Pittet, Mikael J.; Libby, Peter; Lin, Charles P.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

    2012-01-01

    SUMMARY During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaque in the arterial wall and cause its rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, apoE?/? mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. When seeking the source of surplus monocytes in plaque, we found that myocardial infarction liberated hematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signaling. The progenitors then seeded the spleen yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression. PMID:22763456

  8. Myocardial infarction accelerates atherosclerosis.

    PubMed

    Dutta, Partha; Courties, Gabriel; Wei, Ying; Leuschner, Florian; Gorbatov, Rostic; Robbins, Clinton S; Iwamoto, Yoshiko; Thompson, Brian; Carlson, Alicia L; Heidt, Timo; Majmudar, Maulik D; Lasitschka, Felix; Etzrodt, Martin; Waterman, Peter; Waring, Michael T; Chicoine, Adam T; van der Laan, Anja M; Niessen, Hans W M; Piek, Jan J; Rubin, Barry B; Butany, Jagdish; Stone, James R; Katus, Hugo A; Murphy, Sabina A; Morrow, David A; Sabatine, Marc S; Vinegoni, Claudio; Moskowitz, Michael A; Pittet, Mikael J; Libby, Peter; Lin, Charles P; Swirski, Filip K; Weissleder, Ralph; Nahrendorf, Matthias

    2012-07-19

    During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression. PMID:22763456

  9. Regional brain metabolism in a murine systemic lupus erythematosus model.

    PubMed

    Vo, An; Volpe, Bruce T; Tang, Chris C; Schiffer, Wynne K; Kowal, Czeslawa; Huerta, Patricio T; Ulu?, Aziz M; Dewey, Stephen L; Eidelberg, David; Diamond, Betty

    2014-08-01

    Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb+ mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood-brain barrier (BBB) breach. In DNRAb+ mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb- mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb+ animals with hippocampal BBB breach and altered fear conditioning in DNRAb+ mice with amygdala BBB breach. In DNRAb+ mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb- mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects. PMID:24824914

  10. 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

  11. Longitudinal Study of Cardiac Remodeling in Rabbits Following Infarction

    PubMed Central

    Wang, Yves T.; Popovi?, Zoran B.; Efimov, Igor R.; Cheng, Yuanna

    2016-01-01

    Background Cardiac remodeling following myocardial infarction (MI) is a complex, dynamic process. There have been few longitudinal studies of these changes. Methods Two-dimensional transthoracic echocardiography was performed on 20 rabbits: before and 1, 2, 4, 8, and 12 weeks after MI (n=14) and twice for controls (n=6). Chronic left ventricular (LV) infarct size was histologically characterized and correlated with mechanical function. A linear mixed model was used to analyze longitudinal and infarct size related changes in LV end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF), sphericity, circumferential strain, and wall motion score index (WMSI). Results Mean LV infarct size was 28.99.3%. After MI, rapid remodeling occurred in LVESV, LVEF, and sphericity for 2 weeks and LVEDV for 4 weeks, with slower changes afterwards. LV infarct size correlated with LVESV (r=0.76), LVEDV (r=0.71), and LVEF (r=0.69). Larger infarcts resulted in greater LVESV dilation (p=0.04) and faster LVEDV (p<0.01), LVEF (p<0.01) and sphericity (p<0.01) remodeling. Apical global circumferential strain and WMSI increased for 1 week then stabilized, regardless of infarct size, and apical global circumferential strain was correlated with apical infarction (r=0.58). Additionally, regional circumferential strain decreased in segments with severe (>80%) infarction more quickly (p<0.01) and by a greater degree (p=0.04) compared to segments with minor (<20%) infarction. Conclusions The most dynamic remodeling of cardiac function in this model occurred during the first 4 weeks, stabilizing thereafter, with changes maintained up to 12 weeks. Infarct size affected both the early rate and long-term extent of mechanical remodeling. PMID:22265993

  12. 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 Parkinsons 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

  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. Prioritizing the development of mouse models for childhood brain disorders.

    PubMed

    Ogden, Kevin K; Ozkan, Emin D; Rumbaugh, Gavin

    2016-01-01

    Mutations in hundreds of genes contribute to cognitive and behavioral dysfunction associated with developmental brain disorders (DBDs). Due to the sheer number of risk factors available for study combined with the cost of developing new animal models, it remains an open question how genes should be prioritized for in-depth neurobiological investigations. Recent reviews have argued that priority should be given to frequently mutated genes commonly found in sporadic DBD patients. Intrigued by this idea, we explored to what extent "high priority" risk factors have been studied in animals in an effort to assess their potential for generating valuable preclinical models capable of advancing the neurobiological understanding of DBDs. We found that in-depth whole animal studies are lacking for many high priority genes, with relatively few neurobiological studies performed in construct valid animal models aimed at understanding the pathological substrates associated with disease phenotypes. However, some high priority risk factors have been extensively studied in animal models and they have generated novel insights into DBD patho-neurobiology while also advancing early pre-clinical therapeutic treatment strategies. We suggest that prioritizing model development toward genes frequently mutated in non-specific DBD populations will accelerate the understanding of DBD patho-neurobiology and drive novel therapeutic strategies. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'. PMID:26231830

  15. A model for traumatic brain injury using laser induced shockwaves

    NASA Astrophysics Data System (ADS)

    Selfridge, A.; Preece, D.; Gomez, V.; Shi, L. Z.; Berns, M. W.

    2015-08-01

    Traumatic brain injury (TBI) represents a major treatment challenge in both civilian and military medicine; on the cellular level, its mechanisms are poorly understood. As a method to study the dysfunctional repair mechanisms following injury, laser induced shock waves (LIS) are a useful way to create highly precise, well characterized mechanical forces. We present a simple model for TBI using laser induced shock waves as a model for damage. Our objective is to develop an understanding of the processes responsible for neuronal death, the ways in which we can manipulate these processes to improve cell survival and repair, and the importance of these processes at different levels of biological organization. The physics of shock wave creation has been modeled and can be used to calculate forces acting on individual neurons. By ensuring that the impulse is in the same regime as that occurring in practical TBI, the LIS model can ensure that in vitro conditions and damage are similar to those experienced in TBI. This model will allow for the study of the biochemical response of neurons to mechanical stresses, and can be combined with microfluidic systems for cell growth in order to better isolate areas of damage.

  16. 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 7.3mg.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 0.16min?1 and efflux from the shallow brain compartment (kout) of 0.019min?1 and the fluvoxamine concentration at which 50% of the maximum active efflux (C50) is reached of 710ng.ml?1. The proposed brain distribution model constitutes a basis for precise characterization of the PKPD correlation of fluvoxamine by taking into account the non-linearity in brain distribution. PMID:17710515

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    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-1α in rats' brain was detected by real-time RT-PCR, immunohistochmeistry method and western blot. No cerebral infarction and significant expression of HIF-1α in Group sham. Compared with Group IR, there was smaller infarct volume and stronger HIF-1α 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-1α. PMID:25796156

  20. An automatic rat brain extraction method based on a deformable surface model.

    PubMed

    Li, Jiehua; Liu, Xiaofeng; Zhuo, Jiachen; Gullapalli, Rao P; Zara, Jason M

    2013-08-15

    The extraction of the brain from the skull in medical images is a necessary first step before image registration or segmentation. While pre-clinical MR imaging studies on small animals, such as rats, are increasing, fully automatic imaging processing techniques specific to small animal studies remain lacking. In this paper, we present an automatic rat brain extraction method, the Rat Brain Deformable model method (RBD), which adapts the popular human brain extraction tool (BET) through the incorporation of information on the brain geometry and MR image characteristics of the rat brain. The robustness of the method was demonstrated on T2-weighted MR images of 64 rats and compared with other brain extraction methods (BET, PCNN, PCNN-3D). The results demonstrate that RBD reliably extracts the rat brain with high accuracy (>92% volume overlap) and is robust against signal inhomogeneity in the images. PMID:23684784

  1. Phase lagging model of brain response to external stimuli-modeling of single action potential.

    PubMed

    Seetharaman, Karthik; Namazi, Hamidreza; Kulish, Vladimir V; Kulsih, Vladimir V

    2012-08-01

    In this paper we detail a phase lagging model of brain response to external stimuli. The model is derived using the basic laws of physics like conservation of energy law. This model eliminates the paradox of instantaneous propagation of the action potential in the brain. The solution of this model is then presented. The model is further applied in the case of a single neuron and is verified by simulating a single action potential. The results of this modeling are useful not only for the fundamental understanding of single action potential generation, but also they can be applied in case of neuronal interactions, where the results can be verified against the real EEG signal. PMID:22795226

  2. Comparison of conventional risk factors in middle-aged versus elderly diabetic and nondiabetic patients with myocardial infarction: prediction with decisionanalytic model

    PubMed Central

    Mahmoodi, Mohammad Reza; Baneshi, Mohammad Reza; Rastegari, Azam

    2015-01-01

    Background: We sought to predict occurrence of myocardial infarction (MI) by means of a classification and regression tree (CART) model by conventional risk factors in middle-aged versus elderly (age ?65years) diabetic and nondiabetic patients from the Modares Heart Study. Method: A total of 469 patients were randomly selected and categorized into two groups according to clinical diabetes status. Group I consisted of 238 diabetic patients and group II consisted of 231 nondiabetic patients. Our population was MI positive. The outcome investigated was diabetes mellitus. We used a decisionanalytic model to predict the diagnosis of patients with suspected MI. Results: We constructed 4 predictive patterns using 12 input variables and 1 output variable in terms of their sensitivity, specificity and risk. The differences among patterns were due to inclusion of predictor variables. The CART model suggested different variables of hypertension, mean cell volume, fasting blood sugar, cholesterol, triglyceride and uric acid concentration based on middle-aged and elderly patients at high risk for MI. Levels of biochemical measurements identified as best risk cutoff points. In evaluating the precision of different patterns, sensitivity and specificity were 47.984.0% and 56.393.0%, respectively. Conclusions: The CART model is capable of symbolizing interpretable clinical data for confirming and better prediction of MI occurrence in clinic or in hospital. Therefore, predictor variables in pattern could affect the outcome based on age group variable. Hyperglycemia, hypertension, hyperlipidemia and hyperuricemia were serious predictors for occurrence of MI in diabetics. PMID:26623003

  3. Formal and informal prediction of recurrent stroke and myocardial infarction after stroke: a systematic review and evaluation of clinical prediction models in a new cohort

    PubMed Central

    2014-01-01

    Background The objective of this study was to: (1) systematically review the reporting and methods used in the development of clinical prediction models for recurrent stroke or myocardial infarction (MI) after ischemic stroke; (2) to meta-analyze their external performance; and (3) to compare clinical prediction models to informal clinicians prediction in the Edinburgh Stroke Study (ESS). Methods We searched Medline, EMBASE, reference lists and forward citations of relevant articles from 1980 to 19 April 2013. We included articles which developed multivariable clinical prediction models for the prediction of recurrent stroke and/or MI following ischemic stroke. We extracted information to assess aspects of model development as well as metrics of performance to determine predictive ability. Model quality was assessed against a pre-defined set of criteria. We used random-effects meta-analysis to pool performance metrics. Results We identified twelve model development studies and eleven evaluation studies. Investigators often did not report effective sample size, regression coefficients, handling of missing data; typically categorized continuous predictors; and used data dependent methods to build models. A meta-analysis of the area under the receiver operating characteristic curve (AUROCC) was possible for the Essen Stroke Risk Score (ESRS) and for the Stroke Prognosis Instrument II (SPI-II); the pooled AUROCCs were 0.60 (95% CI 0.59 to 0.62) and 0.62 (95% CI 0.60 to 0.64), respectively. An evaluation among minor stroke patients in the ESS demonstrated that clinicians discriminated poorly between those with and those without recurrent events and that this was similar to clinical prediction models. Conclusions The available models for recurrent stroke discriminate poorly between patients with and without a recurrent stroke or MI after stroke. Models had a similar discrimination to informal clinicians' predictions. Formal prediction may be improved by addressing commonly encountered methodological problems. PMID:24708686

  4. Agraphia caused by acute right parietal infarction.

    PubMed

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

    2015-04-01

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

  5. Binding of radiolabeled misonidazole in cerebral infarction

    SciTech Connect

    Rasey, J.S.; Hoffman, J.; Spence, A.M.; Krohn, K.A.

    1985-05-01

    The metabolic trapping of the radiolabeled nitroimidazole, misonidazole, in viable hypoxic tissue may form the basis for the nuclear imaging of ischemia in cerebral infarction. Misonidazole congeners could be labeled with /sup 75/Br, /sup 18/F, or /sup 11/C and detected with PET. Infarction was induced in male Mongolian gerbils by ligation of the right common carotid artery. Severity of the lesions was determined by scoring neurological symptoms with a stroke index, in which scores >10, out of a possible 25, indicate presence of a severe infarct. Gerbils with scores ranging from 0 (asymptomatic) to 13 as well as control (unligated) animals received 3 injections (50 ..mu..Moles/kg) of /sup 3/H-misonidazole in 2 hours and % injected dose/g (% I.D./g) was determined 2 hours after the final injection. Uptake into whole brain of control animals averaged 0.137 +- 0.0168 % I.D./g. The cerebral hemispheres of ligated gerbils were divided into 7, 2 mm-thick coronal sections which were then bisected. In the right half of slide number3 (midparietal region) the % I.D./g increased with increasing stroke index. For animals with a stroke index = 0, uptake was 0.159 % I.D./g, and right/left R/L ratio was 1.07. For 2 animals with a score = 13, uptake in the same region ws 0.752 and 0.717 and I.D./g with R/L ratios of 3.29 and 2.3l, respectively. Animals with intermediate scores had moderately elevated uptake. The authors conclude that the uptake of /sup 3/H-misonidazole in the right hemisphere positively correlates with the severity of infarction. Studies are underway to determine whether the regions of highest uptake correlate with histological evidence of infarction and reduced oxygen availability.

  6. 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

  7. Informing Pedagogy Through the Brain-Targeted Teaching Model

    PubMed Central

    Hardiman, Mariale

    2012-01-01

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

  8. Reprint of 'Model of unidirectional block formation leading to reentrant ventricular tachycardia in the infarct border zone of postinfarction canine hearts'

    PubMed Central

    Ciaccio, Edward J.; Coromilas, James; Ashikaga, Hiroshi; Cervantes, Daniel O.; Wit, Andrew L.; Peters, Nicholas S.; McVeigh, Elliot R.; Garan, Hasan

    2015-01-01

    Background When the infarct border zone is stimulated prematurely, a unidirectional block line (UBL) can form and lead to double-loop (figure-of-eight) reentrant ventricular tachycardia (VT) with a central isthmus. The isthmus is composed of an entrance, center, and exit. It was hypothesized that for certain stimulus site locations and coupling intervals, the UBL would coincide with the isthmus entrance boundary, where infarct border zone thickness changes from thin-to-thick in the travel direction of the premature stimulus wavefront. Method A quantitative model was developed to describe how thin-to-thick changes in the border zone result in critically convex wavefront curvature leading to conduction block, which is dependent upon coupling interval. The model was tested in 12 retrospectively analyzed postinfarction canine experiments. Electrical activation was mapped for premature stimulation and for the first reentrant VT cycle. The relationship of functional conduction block forming during premature stimulation to functional block during reentrant VT was quantified. Results For an appropriately placed stimulus, in accord with model predictions: 1. The UBL and reentrant VT isthmus lateral boundaries overlapped (error: 4.85.7mm). 2. The UBL leading edge coincided with the distal isthmus where the center-entrance boundary would be expected to occur. 3. The mean coupling interval was 164.611.0ms during premature stimulation and 190.720.4ms during the first reentrant VT cycle, in accord with model calculations, which resulted in critically convex wavefront curvature and functional conduction block, respectively, at the location of the isthmus entrance boundary and at the lateral isthmus edges. Discussion Reentrant VT onset following premature stimulation can be explained by the presence of critically convex wavefront curvature and unidirectional block at the isthmus entrance boundary when the premature stimulation interval is sufficiently short. The double-loop reentrant circuit pattern is a consequence of wavefront bifurcation around this UBL followed by coalescence, and then impulse propagation through the isthmus. The wavefront is blocked from propagating laterally away from the isthmus by sharp increases in border zone thickness, which results in critically convex wavefront curvature at VT cycle lengths. PMID:26372420

  9. Training in Brain Retraction Using a Self-Made Three-Dimensional Model.

    PubMed

    Mashiko, Toshihiro; Konno, Takehiko; Kaneko, Naoki; Watanabe, Eiju

    2015-08-01

    A hollow brain model was created using soft urethane. A tube passing through the hollow was attached for use as a water inlet and manometer. Water sufficient in quantity to realize the intended initial pressure was infused through the tube. The brain model was retracted with a brain spatula and the surgical corridor was opened. By measuring local force with a sensor set on the brain spatula, the model could be used for training in brain retraction. At the same time, the water column of the manometer was measured and the relationship with the force of the brain spatula was investigated. A positive correlation between the water column and local force was confirmed. This indicated that it was possible to use this model without a force sensor for the same training using water column measurements. PMID:25862113

  10. Misdiagnosis of Cerebellar Infarctions

    PubMed Central

    Sangha, Navdeep; Albright, Karen C.; Peng, Hui; Vahidy, Farhaan; Boehme, Amelia; Chen, Zhongxue; Savitz, Sean I.

    2015-01-01

    Background This retrospective study addresses for the first time the differences in clinical features and outcomes between those individuals with a cerebellar infarct who were correctly diagnosed on initial presentation compared to those who experienced delayed diagnosis. Methods A retrospective review was conducted of our stroke registry from 09/2003 to 02/2011. Forty seven patients had an isolated cerebellar infarction confirmed by MRI. Misdiagnosis was defined as the diagnosis given by the first physician. Results Among 47 patients identified, 59.6% had delayed diagnosis. Five patients in the correct diagnosis group received intravenous tissue plasminogen activator, compared to none in the delayed diagnosis group. Complaints of weakness were protective from delayed diagnosis (OR 0.087, 95% CI 0.019-0.393, p = 0.001). Conclusion Patients with an isolated cerebellar infarction need to be considered when patients present with acute non-specific symptoms. Critical components of the neurological examination are omitted which are imperative to diagnose cerebellar infarcts. A thorough neurological examination may increase clinical suspicion of an ischemic stroke. PMID:25373805

  11. Bilateral renal infarction.

    PubMed

    Chung, Shiu-Dong; Yu, Hong-Jeng; Huang, Kuo-How

    2009-02-01

    A 34-year-old man was admitted for acute onset of left lower abdominal pain associated with fever. His medical history was unremarkable, and the physical examination revealed bilateral flank tenderness. Bilateral renal infarction was diagnosed and demonstrated by computed tomography. PMID:18829084

  12. 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; Mllmann, 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

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

    PubMed Central

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

    2015-01-01

    Background. Novel therapies need to be evaluated in a relevant large animal model that mimics the clinical course and treatment in a reasonable time frame. To reliably assess therapeutic efficacy, knowledge regarding the translational model and the course of disease is needed. Methods. Landrace pigs were subjected to a transient occlusion of the proximal left circumflex artery (LCx) (n = 6) or mid-left anterior descending artery (LAD) (n = 6) for 150 min. Cardiac function was evaluated before by 2D echocardiography or 3D echocardiography and pressure-volume loop analysis. At 12 weeks of follow-up the heart was excised for histological analysis and infarct size calculations. Results. Directly following AMI, LVEF was severely reduced compared to baseline in the LAD group (−17.1 ± 1.6%, P = 0.009) compared to only a moderate reduction in the LCx group (−5.9 ± 1.5%, P = 0.02) and this effect remained unchanged during 12 weeks of follow-up. Conclusion. Two models of chronic MI, representative for different patient groups, can reproducibly be created through clinically relevant ischemia-reperfusion of the mid-LAD and proximal LCx. PMID:25802838

  14. Localized radiation necrosis model in mouse brain using proton ion beams.

    PubMed

    Kondo, Natsuko; Sakurai, Yoshinori; Takata, Takushi; Takai, Nobuhiko; Nakagawa, Yosuke; Tanaka, Hiroki; Watanabe, Tsubasa; Kume, Kyo; Toho, Taichiro; Miyatake, Shin-ichi; Suzuki, Minoru; Masunaga, Shin-ichiro; Ono, Koji

    2015-12-01

    Brain radiation necrosis is the most serious late adverse event that occurs after 6 months following radiation therapy. Effective treatment for this irreversible brain necrosis has not been established yet. This study tries to establish brain radiation necrosis mouse model using proton or helium beam. The right cerebral hemispheres of C57BL/6J mouse brains were irradiated at doses of 40, 50, 60 Gy with charged particles. In 60 Gy group, brain necrosis that recapitulates human disease was detected after 8 months. PMID:26260449

  15. A typical example of cerebral watershed infarct.

    PubMed

    Juergenson, Ina; Mazzucco, Sara; Tinazzi, Michele

    2011-09-28

    Watershed infarcts (WI) evolve in hemodynamic risk zones. Clinical picture of WI can be associated to partial epileptic seizures. Diffusion weighted brain magnetic resonance imaging (MRI) allows a clear diagnosis. WI pathogenesis involves either embolic or hemodynamic mechanism. A 69-year old patient presented with sub-acute occurrence of right hemiparesis and partial epileptic seizures of the right arm. Carotid ultrasounds demonstrated occlusion of the right extra-cranial internal carotid artery (ICA) and tight stenosis of the contralateral ICA. Brain Diffusion-Weighted magnetic resonance revealed acute ischemic lesions within the watershed area of the left hemisphere. Our case supports the hypothesis of impaired washout of emboli in low-perfusion brain areas as the mechanism underlying cortical WI. PMID:24765355

  16. Traumatic Brain Injury Modeling Neuropsychiatric Symptoms in Rodents

    PubMed Central

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

    2013-01-01

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

  17. Neuropathological basis of age-associated brain atrophy

    PubMed Central

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

    2013-01-01

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

  18. Stretch in Brain Microvascular Endothelial Cells (cEND) as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

    PubMed Central

    Salvador, Ellaine; Neuhaus, Winfried; Foerster, Carola

    2013-01-01

    Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying mechanisms involved in it are useful for treatment. There are both in vivo and in vitro methods available for this purpose. In vivo models can mimic actual head injury as it occurs during TBI. However, in vivo techniques may not be exploited for studies at the cell physiology level. Hence, in vitro methods are more advantageous for this purpose since they provide easier access to the cells and the extracellular environment for manipulation. Our protocol presents an in vitro model of TBI using stretch injury in brain microvascular endothelial cells. It utilizes pressure applied to the cells cultured in flexible-bottomed wells. The pressure applied may easily be controlled and can produce injury that ranges from low to severe. The murine brain microvascular endothelial cells (cEND) generated in our laboratory is a well-suited model for the blood brain barrier (BBB) thus providing an advantage to other systems that employ a similar technique. In addition, due to the simplicity of the method, experimental set-ups are easily duplicated. Thus, this model can be used in studying the cellular and molecular mechanisms involved in TBI at the BBB. PMID:24193450

  19. Intermedin attenuates myocardial infarction through activation of autophagy in a rat model of ischemic heart failure via both cAMP and MAPK/ERK1/2 pathways

    PubMed Central

    Wei, Peng; Yang, Xiang-Jun; Fu, Qiang; Han, Bing; Ling, Lin; Bai, Jie; Zong, Bin; Jiang, Chun-Ying

    2015-01-01

    Intermedin is a proopiomelanocortin-derived peptide before opioid promoting cortical hormone, its main function embodies in mononuclear macrophages and neutrophilic granulocytes to inhibit the proinflammatory cytokines. The aim of this study is to determine intermedin attenuates myocardial infarction and its related mechanisms in a rat model of ischemic heart failure. After rat model of ischemic heart failure was set up, myocardial infarction, blood levels of activities of creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) were effectively reduced by treatment with intermedin. Tumor necrosis factor (TNF-?) and interleukin-6 (IL-6) in a rat model of ischemic heart failure were recovered by pretreatment with intermedin. Administrate of intermedin availably promoted cAMP contents and suppressed caspase-3 protein in ischemic heart failure rat. ERK1/2 and LC3 protein expression were significantly activated and autophagy was significantly promoted by intermedin in a rat model of ischemic heart failure. These results indicate that intermedin protected rat heart, attenuates myocardial infarction from ischemic heart failure in the rat model. The underlying mechanisms may include upregulation of cAMP, ERK1/2 and LC3 protein expression and activating of autophagy. PMID:26617693

  20. Infantile Tubercular Meningitis With Brain Infarct.

    PubMed

    Kratimenos, Panagiotis; Koutroulis, Ioannis; Fruscione, Mike; Adigun, Hazeez; DeGroote, Richard; Fisher, Margaret C

    2016-02-01

    A previously healthy 6-month-old Asian girl presented to the emergency department (ED) after 7 to 10 days of fever of 101 to 102F, cough, and intermittent vomiting. Pneumonia was diagnosed and successfully treated, and the patient was discharged. She returned to the ED after her mother noticed mild facial asymmetry, left upper extremity weakness, and an episode of jerkiness. The mother then revealed that both she and the child's maternal grandmother, who also lived with the patient, had suffered chronic coughs in recent months. The mother's previous chest radiograph showed pulmonary tuberculosis. The patient's magnetic resonance imaging findings were consistent with a cerebrovascular event. Positive results on cerebrospinal fluid analysis, the mother's suspicious tuberculosis-like history, and the patient's clinical symptoms pointed heavily toward a diagnosis of tuberculous meningitis. A 4-drug antituberculosis regimen with dexamethasone was instituted and scheduled to continue for 12 months. However, the patient returned to the ED 2 months later after developing an obstructive hydrocephalus. PMID:26087442

  1. 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

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

    SciTech Connect

    Dietrich, W.D.; Busto, R.; Ginsberg, M.D. )

    1989-12-01

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

  3. Longitudinal monitoring adipose-derived stem cell survival by PET imaging hexadecyl-4-{sup 124}I-iodobenzoate in rat myocardial infarction model

    SciTech Connect

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

    2015-01-02

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

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

    PubMed Central

    Reilly, Karlyne M.

    2009-01-01

    Brain tumors are relatively rare but deadly cancers, and present challenges in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain, with surgery, radiation and chemotherapy options carrying potentially lasting morbidity for patients and incomplete cure of the tumor. The development of methods to prevent or detect brain tumors at an early stage is extremely important to reduce damage to the brain from the tumor and the therapy. Developing effective prevention or early detection methods requires a deep understanding of the risk factors for brain tumors. This review explores the difficulties in assessing risk factors in rare diseases such as brain tumors, and discusses how mouse models of cancer can aid in a better understanding of genetic risk factors for brain tumors. PMID:19076777

  5. 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

  6. 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.

  7. 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

  8. Monitoring the injured brain: registered, patient specific atlas models to improve accuracy of recovered brain saturation values

    NASA Astrophysics Data System (ADS)

    Clancy, Michael; Belli, Antonio; Davies, David; Lucas, Samuel J. E.; Su, Zhangjie; Dehghani, Hamid

    2015-07-01

    The subject of superficial contamination and signal origins remains a widely debated topic in the field of Near Infrared Spectroscopy (NIRS), yet the concept of using the technology to monitor an injured brain, in a clinical setting, poses additional challenges concerning the quantitative accuracy of recovered parameters. Using high density diffuse optical tomography probes, quantitatively accurate parameters from different layers (skin, bone and brain) can be recovered from subject specific reconstruction models. This study assesses the use of registered atlas models for situations where subject specific models are not available. Data simulated from subject specific models were reconstructed using the 8 registered atlas models implementing a regional (layered) parameter recovery in NIRFAST. A 3-region recovery based on the atlas model yielded recovered brain saturation values which were accurate to within 4.6% (percentage error) of the simulated values, validating the technique. The recovered saturations in the superficial regions were not quantitatively accurate. These findings highlight differences in superficial (skin and bone) layer thickness between the subject and atlas models. This layer thickness mismatch was propagated through the reconstruction process decreasing the parameter accuracy.

  9. Multistability in Large Scale Models of Brain Activity

    PubMed Central

    Golos, Mathieu; Jirsa, Viktor; Daucé, Emmanuel

    2015-01-01

    Noise driven exploration of a brain network’s dynamic repertoire has been hypothesized to be causally involved in cognitive function, aging and neurodegeneration. The dynamic repertoire crucially depends on the network’s capacity to store patterns, as well as their stability. Here we systematically explore the capacity of networks derived from human connectomes to store attractor states, as well as various network mechanisms to control the brain’s dynamic repertoire. Using a deterministic graded response Hopfield model with connectome-based interactions, we reconstruct the system’s attractor space through a uniform sampling of the initial conditions. Large fixed-point attractor sets are obtained in the low temperature condition, with a bigger number of attractors than ever reported so far. Different variants of the initial model, including (i) a uniform activation threshold or (ii) a global negative feedback, produce a similarly robust multistability in a limited parameter range. A numerical analysis of the distribution of the attractors identifies spatially-segregated components, with a centro-medial core and several well-delineated regional patches. Those different modes share similarity with the fMRI independent components observed in the “resting state” condition. We demonstrate non-stationary behavior in noise-driven generalizations of the models, with different meta-stable attractors visited along the same time course. Only the model with a global dynamic density control is found to display robust and long-lasting non-stationarity with no tendency toward either overactivity or extinction. The best fit with empirical signals is observed at the edge of multistability, a parameter region that also corresponds to the highest entropy of the attractors. PMID:26709852

  10. (-) Epicatechin prevents alterations in lysosomal glycohydrolases, cathepsins and reduces myocardial infarct size in isoproterenol-induced myocardial infarcted rats.

    PubMed

    Prince, Ponnian Stanely Mainzen

    2013-04-15

    The preventive effects of (-) epicatechin on oxidative stress, cardiac mitochondrial damage, altered membrane bound adenosine triphosphatases and minerals were reported previously in isoproterenol-induced myocardial infarction model. Leakage of lysosomal glycohydrolases and cathepsins play an important role in the pathology of myocardial infarction. This study was aimed to evaluate the preventive effects of (-) epicatechin on alterations in lysosomal glycohydrolases, cathepsins and myocardial infarct size in isoproterenol-induced myocardial infarcted rats. Male albino Wistar rats were pretreated with (-) epicatechin (20mg/kg body weight) daily for a period of 21 days. After the pretreatment period, isoproterenol (100mg/kg body weight) was injected subcutaneously into the rats at an interval of 24h for two days to induce myocardial infarction. The levels of serum cardiac troponin-I and the activities of serum and heart lysosomal enzymes (?-glucuronidase, ?-N-acetyl glucosaminidase, ?-galactosidase, cathepsin-B and cathepsin-D) were increased significantly (P<0.05) and the activities of ?-glucuronidase and cathepsin-D in the heart lysosomal fractions were significantly (P<0.05) decreased in isoproterenol-induced myocardial infarcted rats. The in vitro study revealed the potent antioxidant action of (-) epicatechin. Pretreatment with (-) epicatechin daily for a period of 21 days prevented the leakage of cardiac marker, lysosomal glycohydrolases, cathepsins, and reduced infarct size, thereby protecting the lysosomal membranes in isoproterenol-induced myocardial infarcted rats, by virtue of its membrane stabilizing property. PMID:23454557

  11. Stratified mixture modeling for segmentation of white-matter lesions in brain MR images.

    PubMed

    Galimzianova, Alfiia; Pernu, Franjo; Likar, Botjan; piclin, iga

    2016-01-01

    Accurate characterization of white-matter lesions from magnetic resonance (MR) images has increasing importance for diagnosis and management of treatment of certain neurological diseases, and can be performed in an objective and effective way by automated lesion segmentation. This usually involves modeling the whole-brain MR intensity distribution, however, capturing various sources of MR intensity variability and lesion heterogeneity results in highly complex whole-brain MR intensity models, thus their robust estimation on a large set of MR images presents a huge challenge. We propose a novel approach employing stratified mixture modeling, where the main premise is that the otherwise complex whole-brain model can be reduced to a tractable parametric form in small brain subregions. We show on MR images of multiple sclerosis (MS) patients with different lesion loads that robust estimators enable accurate mixture modeling of MR intensity in small brain subregions even in the presence of lesions. Recombination of the mixture models across strata provided an accurate whole-brain MR intensity model. Increasing the number of subregions and, thereby, the model complexity, consistently improved the accuracy of whole-brain MR intensity modeling and segmentation of normal structures. The proposed approach was incorporated into three unsupervised lesion segmentation methods and, compared to original and three other state-of-the-art methods, the proposed modeling approach significantly improved lesion segmentation according to increased Dice similarity indices and lower number of false positives on real MR images of 30 patients with MS. PMID:26427644

  12. Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat model of traumatic brain injury.

    PubMed

    Sarkaki, Alireza; Farbood, Yaghoub; Gharib-Naseri, Mohammad Kazem; Badavi, Mohammad; Mansouri, Mohammad Taghi; Haghparast, Abbas; Mirshekar, Mohammad Ali

    2015-08-01

    Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. In the clinic it is essential to limit the development of cognitive impairment after TBI. In this study, the effects of gallic acid (GA; 100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on neurological score, passive avoidance memory, long-term potentiation (LTP) deficits, and levels of proinflammatory cytokines including interleukin-1 beta (IL-1?), interleukin 6 (IL-6), and tumor necrosis factor-? (TNF-?) in the brain have been evaluated. Brain injury was induced following Marmarou's method. Data were analyzed by one-way and repeated measures ANOVA followed by Tukey's post-hoc test. The results indicated that memory was significantly impaired (p < 0.001) in the group treated with TBI + vehicle, together with deterioration of the hippocampal LTP and increased brain tissue levels of IL-1?, IL-6, and TNF-?. GA treatment significantly improved memory and LTP in the TBI rats. The brain tissue levels of IL-1?, IL-6, and TNF-? were significantly reduced (p < 0.001) in the group treated with GA. The results suggest that GA has neuroprotective properties against TBI-induced behavioral, electrophysiological, and inflammatory disorders, probably via the decrease of cerebral proinflammatory cytokines. PMID:26222320

  13. 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.

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

    NASA Astrophysics Data System (ADS)

    Liley, David T. J.; Frascoli, Federico

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

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

    NASA Astrophysics Data System (ADS)

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

    1999-05-01

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

  16. 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

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

    PubMed Central

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

    2015-01-01

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

  18. Synchronization Tomography: Modeling and Exploring Complex Brain Dynamics

    NASA Astrophysics Data System (ADS)

    Fieseler, Thomas

    2002-03-01

    Phase synchronization (PS) plays an important role both under physiological and pathological conditions. With standard averaging techniques of MEG data, it is difficult to reliably detect cortico-cortical and cortico-muscular PS processes that are not time-locked to an external stimulus. For this reason, novel synchronization analysis techniques were developed and directly applied to MEG signals. Of course, due to the lack of an inverse modeling (i.e. source localization), the spatial resolution of this approach was limited. To detect and localize cerebral PS, we here present the synchronization tomography (ST): For this, we first estimate the cerebral current source density by means of the magnetic field tomography (MFT). We then apply the single-run PS analysis to the current source density in each voxel of the reconstruction space. In this way we study simulated PS, voxel by voxel in order to determine the spatio-temporal resolution of the ST. To this end different generators of ongoing rhythmic cerebral activity are simulated by current dipoles at different locations and directions, which are modeled by slightly detuned chaotic oscillators. MEG signals for these generators are simulated for a spherical head model and a whole-head MEG system. MFT current density solutions are calculated from these simulated signals within a hemispherical source space. We compare the spatial resolution of the ST with that of the MFT. Our results show that adjacent sources which are indistinguishable for the MFT, can nevertheless be separated with the ST, provided they are not strongly phase synchronized. This clearly demonstrates the potential of combining spatial information (i.e. source localization) with temporal information for the anatomical localization of phase synchronization in the human brain.

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

    PubMed Central

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

    2014-01-01

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

  20. Perceived Neighborhood Social Cohesion and Myocardial Infarction

    PubMed Central

    Kim, Eric S.; Hawes, Armani M.; Smith, Jacqui

    2015-01-01

    Background The main strategy for alleviating heart disease has been to target individuals and encourage them to change their health behaviors. Though important, emphasis on individuals has diverted focus and responsibility away from neighborhood characteristics, which also strongly influence peoples behaviors. Although a growing body of research has repeatedly demonstrated strong associations between neighborhood characteristics and cardiovascular health, it has typically focused on negative neighborhood characteristics. Only a few studies have examined the potential health enhancing effects of positive neighborhood characteristics, such as perceived neighborhood social cohesion. Methods Using multiple logistic regression models, we tested whether higher perceived neighborhood social cohesion was associated with lower incidence of myocardial infarction. Prospective data from the Health and Retirement Studya nationally representative panel study of American adults over the age of 50were used to analyze 5,276 participants with no history of heart disease. Respondents were tracked for four years and analyses adjusted for relevant sociodemographic, behavioral, biological, and psychosocial factors. Results In a model that adjusted for age, gender, race, marital status, education, and total wealth, each standard deviation increase in perceived neighborhood social cohesion was associated with a 22% reduced odds of myocardial infarction (OR = 0.78, 95% CI, 0.630.94. The association between perceived neighborhood social cohesion and myocardial infarction remained even after adjusting for behavioral, biological, and psychosocial covariates. Conclusions Higher perceived neighborhood social cohesion may have a protective effect against myocardial infarction. PMID:25135074

  1. Noise in the brain: a physical network model.

    PubMed

    Haken, H

    1996-09-01

    In the brain as in any other open physical systems, noise is inevitable. We present an explicit model of an active physical system that is borrowed from laser physics and allows us to establish the properties of the fluctuating forces that cause noise in the system. It is shown how the cooperation of the individual parts of a system (atoms or neurons) can considerably reduce the noise level. In particular we determine the correlation function between the individual parts. The basic equations can be transformed in such a way that a close analogy with typical equations of neural nets are obtained. In particular, the nonlinear properties of neurons described by the sigmoid function are well captured. Propagation of excitation in axons and dendrites is represented by a linear equation, where we consider both a bandwidth filter and more or less free propagation. In the latter case, a close analogy with an equation for neural activity in the sense of Nunez and established by Jirsa and Haken is pointed out. PMID:8968847

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  3. [Bonsai induced acute myocardial infarction].

    PubMed

    Ayhan, Hüseyin; Aslan, Abdullah Nabi; Süygün, Hakan; Durmaz, Tahir

    2014-09-01

    Incidences of drug abuse and cannabis have increased in young adults, recently. Cannabis induced myocardial infarction has rarely been reported in these people. There is no any literature about a synthetic cannabinoid, being recently most popular Bonsai, to cause myocardial infarction. In this case report we presented a 33-year-old male patient who developed acute myocardial infarction after taking high doses of Bonsai. PMID:25362948

  4. Secondary SUNCT syndrome caused by dorsolateral medullary infarction.

    PubMed

    Jin, Di; Lian, Ya-Jun; Zhang, Hai-Feng

    2016-12-01

    Short-lasting unilateral neuralgiform headaches with conjunctival injection and tearing (SUNCT) is a rare headache syndrome which belongs to trigeminal autonomic cephalalgias. Though the majority of SUNCT syndrome is idiopathic, more and more cases of secondary SUNCT syndrome have been reported recently. In this study, we present a case of symptomatic SUNCT syndrome caused by acute dorsolateral medullary infarction which was verified by brain MRI(magnetic resonance imaging). Up to now, there is not absolutely effective treatment for SUNCT syndrome. However, in our case, SUNCT was completely resolved after conventional treatment for cerebral infarction without specific drug intervention. PMID:26885826

  5. STRIATOCAPSULAR INFARCTION; A SINGLE INSTITUTIONAL EXPERIENCE

    PubMed Central

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

    2012-01-01

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

  6. 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

  7. 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

  8. Neuroimaging of cortical development and brain connectivity in human newborns and animal models

    PubMed Central

    Lodygensky, Gregory A; Vasung, Lana; Sizonenko, Stéphane V; Hüppi, Petra S

    2010-01-01

    Significant human brain growth occurs during the third trimester, with a doubling of whole brain volume and a fourfold increase of cortical gray matter volume. This is also the time period during which cortical folding and gyrification take place. Conditions such as intrauterine growth restriction, prematurity and cerebral white matter injury have been shown to affect brain growth including specific structures such as the hippocampus, with subsequent potentially permanent functional consequences. The use of 3D magnetic resonance imaging (MRI) and dedicated postprocessing tools to measure brain tissue volumes (cerebral cortical gray matter, white matter), surface and sulcation index can elucidate phenotypes associated with early behavior development. The use of diffusion tensor imaging can further help in assessing microstructural changes within the cerebral white matter and the establishment of brain connectivity. Finally, the use of functional MRI and resting-state functional MRI connectivity allows exploration of the impact of adverse conditions on functional brain connectivity in vivo. Results from studies using these methods have for the first time illustrated the structural impact of antenatal conditions and neonatal intensive care on the functional brain deficits observed after premature birth. In order to study the pathophysiology of these adverse conditions, MRI has also been used in conjunction with histology in animal models of injury in the immature brain. Understanding the histological substrate of brain injury seen on MRI provides new insights into the immature brain, mechanisms of injury and their imaging phenotype. PMID:20979587

  9. Development of an autofluorescent probe designed to help brain tumor removal: study on an animal model

    NASA Astrophysics Data System (ADS)

    Siebert, R.; Leh, B.; Charon, Y.; Collado-Hilly, M.; Duval, M.-A.; Menard, L.; Monnet, F. P.; Varlet, P.

    2010-02-01

    The complete resection of the brain tumour is crucial to the patient life quality and prognosis. An autofluorescence probe aiming at helping the surgeon to improve the completeness of the removal is being developed. Autofluorescence spectroscopy is a promising approach to define whether the tissue is cancerous or not. First ex vivo measurements have been realised on an animal model. After tumorous cell injection in rat brain, autofluorescence intensity is revealed from the extracted brain. These autofluorescence data are compared to results from a histological analysis of same brains. First indicators are identified that may have the ability to differentiate tumorous and healthy tissues.

  10. 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 bloodbrain 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 bloodbrain barrier (BBB). Our previous studies provided evidence that the BBB NaKCl 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 NaKCl cotransporter activity. PMID:23149557

  11. 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

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

    ERIC Educational Resources Information Center

    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

  13. Genetic deletion of neuronal pentraxin 1 expression prevents brain injury in a neonatal mouse model of cerebral hypoxia-ischemia

    PubMed Central

    Thatipamula, Shabarish; Rahim, Md Al; Zhang, Jiangyang; Hossain, Mir Ahamed

    2015-01-01

    Neonatal hypoxic-ischemic (HI) brain injury is a leading cause of mortality and morbidity in infants and children for which there is no promising therapy at present. Previously, we reported induction of neuronal pentraxin 1 (NP1), a novel neuronal protein of the long-pentraxin family, following HI injury in neonatal brain. Here, we report that genetic deletion of NP1 expression prevents HI injury in neonatal brain. Elevated expression of NP1 was observed in neurons, not in astrocytes, of the ipsilateral cortical layers (I–IV) and in the hippocampal CA1 and CA3 areas of WT brains following hypoxia-ischemia; brain areas that developed infarcts (at 24–48 h), showed significantly increased numbers of TUNEL-(+) cells and tissue loss (at 7 d). In contrast, NP1-KO mice showed no evidence of brain infarction and tissue loss after HI. The immunofluorescence staining of brain sections with mitochondrial protein COX IV and subcellular fractionation analysis showed increased accumulation of NP1 in mitochondria, pro-death protein Bax activation and NP1 co-localization with activated caspase-3 in WT, but not in the NP1-KO brains; corroborating NP1 interactions with the mitochondria-derived pro-death pathways. Disruption of NP1 translocation to mitochondria by NP1-siRNA in primary cortical cultures significantly reduced ischemic neuronal death. NP1 was immunoprecipitated with activated Bax[6A7] proteins; HI caused increased interactions of NP1 with Bax, thereby, facilitating Bax translocation to mitochondrial and neuronal death. To further delineate the specificity of NPs, we found that NP1 but not the NP2 induction is specifically involved in brain injury mechanisms and that knockdown of NP1 only results in neuroprotection. Furthermore, live in vivo T2-weighted magnetic resonance imaging (MRI) including fractional anisotropy (FA) mapping showed no sign of delayed brain injury or tissue loss in the NP1-KO mice as compared to the WT at different post-HI periods (4–24 weeks), examined; indicating a long-term neuroprotective efficacy of NP1 gene deletion. Collectively, our results demonstrate a novel mechanism of neuronal death and predict that inhibition of NP1 expression is a promising strategy to prevent hypoxic-ischemic injury in immature brain. PMID:25554688

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

    PubMed Central

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

    2013-01-01

    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. PMID:23546385

  15. Parallel optimization of tumor model parameters for fast registration of brain tumor images

    NASA Astrophysics Data System (ADS)

    Zacharaki, Evangelia I.; Hogea, Cosmina S.; Shen, Dinggang; Biros, George; Davatzikos, Christos

    2008-03-01

    The motivation of this work is to register MR brain tumor images with a brain atlas. Such a registration method can make possible the pooling of data from different brain tumor patients into a common stereotaxic space, thereby enabling the construction of statistical brain tumor atlases. Moreover, it allows the mapping of neuroanatomical brain atlases into the patient's space, for segmenting brains and thus facilitating surgical or radiotherapy treatment planning. However, the methods developed for registration of normal brain images are not directly applicable to the registration of a normal atlas with a tumor-bearing image, due to substantial dissimilarity and lack of equivalent image content between the two images, as well as severe deformation or shift of anatomical structures around the tumor. Accordingly, a model that can simulate brain tissue death and deformation induced by the tumor is considered to facilitate the registration. Such tumor growth simulation models are usually initialized by placing a small seed in the normal atlas. The shape, size and location of the initial seed are critical for achieving topological equivalence between the atlas and patient's images. In this study, we focus on the automatic estimation of these parameters, pertaining to tumor simulation. In particular, we propose an objective function reflecting feature-based similarity and elastic stretching energy and optimize it with APPSPACK (Asynchronous Parallel Pattern Search), for achieving significant reduction of the computational cost. The results indicate that the registration accuracy is high in areas around the tumor, as well as in the healthy portion of the brain.

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

    SciTech Connect

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

    2009-03-10

    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.

  17. Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling

    PubMed Central

    Hagmann, Patric; Deco, Gustavo

    2015-01-01

    How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI) signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model’s prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information. PMID:26317432

  18. 3D brain atlas reconstructor service--online repository of three-dimensional models of brain structures.

    PubMed

    Majka, Piotr; Kowalski, Jakub M; Chlodzinska, Natalia; Wjcik, 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

  19. 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

  20. 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

  1. Admittance?based pressurevolume 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 pressurevolume 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

  2. 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

  3. MicroRNA-214 Inhibits Left Ventricular Remodeling in an Acute Myocardial Infarction Rat Model by Suppressing Cellular Apoptosis via the Phosphatase and Tensin Homolog (PTEN).

    PubMed

    Yang, Xingwei; Qin, Yanjun; Shao, Suxia; Yu, Yueqing; Zhang, Chongyang; Dong, Hua; Lv, Guangwei; Dong, Shimin

    2016-03-22

    The aims of the present study were to determine the role of miR-214 on left ventricular remodeling of rat heart with acute myocardial infarction (AMI) and to further investigate the underlying mechanism of miR-214-mediated myocardial protection. AMI was induced in which adenovirus-expressing miR-214 (Ad-miR-214), anti-miR-214, or Ad-GFP had been delivered into rats hearts 4 days prior, while a phosphatase and tensin homolog (PTEN) inhibitor was administered via intra-peritoneal injection 30 minutes prior to AMI. Changes in hemodynamic parameters were detected and recorded. Left ventricular (LV) dimensions and LV/BW were measured. Quantitative RT-PCR was used to determine the miR-214 expression levels of the myocytes in the infarcted, border, and non-infarcted areas of the LV. Myocardial infarct size was also measured. Flow cytometry analysis was performed to examine cellular apoptosis. Western blot analysis was performed to examine PTEN expression. The results showed that miR-214 was upregulated in both border and infarcted areas. Myocardial cell apoptosis was decreased in the Ad-miR-214 group, but was increased in the anti-miR-214 group, while there were no differences among the Ad-GFP-group, PTEN-ad-miR-214 group, or PTEN-anti-miR-214 group. Myocardial infarct size, LV dimensions, heart rate (HR), and LV end-diastolic pressure (LVEDP) were decreased while the maximal rates of rise or decline in blood pressure in the ventricular chamber (± dp/dt) and LV systolic pressure (LVSP) were increased in the Ad-miR-214 group, all of which exhibited opposite changes in the anti-miR-214 group. PTEN was downregulated in the Ad-miR-214 group and upregulated in the anti-miR-214 group. PTEN was decreased in both the border and infarcted areas compared with non-infarcted areas. The study results suggest that Ad-miR-214 improves LV remodeling and decreases the apoptosis of myocardial cells through PTEN, suggesting a possible mechanism by which Ad-miR-214 functions in protecting against AMI injury. PMID:26973267

  4. 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.

  5. Brain-derived microparticles induce systemic coagulation in a murine model of traumatic brain injury.

    PubMed

    Tian, Ye; Salsbery, Breia; Wang, Min; Yuan, Hengjie; Yang, Jing; Zhao, Zilong; Wu, Xiaoping; Zhang, Yanjun; Konkle, Barbara A; Thiagarajan, Perumal; Li, Min; Zhang, Jianning; Dong, Jing-Fei

    2015-03-26

    Traumatic brain injury (TBI) is associated with coagulopathy, although it often lacks 2 key risk factors: severe bleeding and significant fluid resuscitation associated with hemorrhagic shock. The pathogenesis of TBI-associated coagulopathy remains poorly understood. We tested the hypothesis that brain-derived microparticles (BDMPs) released from an injured brain induce a hypercoagulable state that rapidly turns into consumptive coagulopathy. Here, we report that mice subjected to fluid percussion injury (1.9 0.1 atm) developed a BDMP-dependent hypercoagulable state, with peak levels of plasma glial cell and neuronal BDMPs reaching 17?496 4833/?L and 18?388 3657/?L 3 hours after TBI, respectively. Uninjured mice injected with BDMPs developed a dose-dependent hyper-turned hypocoagulable state measured by a progressively prolonged clotting time, fibrinogen depletion, and microvascular fibrin deposition in multiple organs. The BDMPs were 50 to 300 nm with intact membranes, expressing neuronal or glial cell markers and procoagulant phosphatidylserine and tissue factor. Their procoagulant activity was greater than platelet microparticles and was dose-dependently blocked by lactadherin. Microparticles were produced from injured hippocampal cells, transmigrated through the disrupted endothelial barrier in a platelet-dependent manner, and activated platelets. These data define a novel mechanism of TBI-associated coagulopathy in mice, identify early predictive markers, and provide alternative therapeutic targets. PMID:25628471

  6. An in vitro model for the assessment of stem cell fate following implantation within the infarct microenvironment identifies ISL-1 expression as the strongest predictor of c-Kit(+) cardiac progenitor cells' therapeutic potential.

    PubMed

    Sullivan, Kelly E; Burns, Laura J; Black, Lauren D

    2015-11-01

    Cell therapy has the potential to drastically improve clinical outcomes for the 1.45 million patients suffering from a myocardial infarction (MI) each year in the U.S. However, the limitations associated with this treatment - including poor engraftment, significant cell death and poor differentiation potential - have prevented its widespread application clinically. To optimize functional improvements provided by transplanted cells, there is a need to develop methods that increase cellular retention and viability, while supporting differentiation and promoting paracrine signaling. Current in vivo models are expensive, difficult to access and manipulate and are time consuming. We have developed an in vitro model of MI which allows for a straightforward, consistent and relatively accurate prediction of cell fate following injection in vivo. The model demonstrated how the infarct environment impairs cellular engraftment and differentiation, but identified an implantation strategy which enhanced cell fate in vitro. Multivariate linear regression identified variables within the model that regulated vascular differentiation potential including oxygen tension, stiffness and cytokine presence, while cardiac differentiation was more accurately predicted by Isl-1 expression in the original cell isolate than any other variable present within the model system. The model highlighted how the cells' sensitivity to the infarct variables varied from line to line, which emphasizes the importance of the model system for the prediction of cell fate on a patient specific basis. Further development of this model system could help predict the clinical efficacy of cardiac progenitor cell therapy at the patient level as well as identify the optimal strategy for cell delivery. PMID:26393440

  7. Computational model of an infant brain subjected to periodic motion simplified modelling and Bayesian sensitivity analysis.

    PubMed

    Batterbee, D C; Sims, N D; Becker, W; Worden, K; Rowson, J

    2011-11-01

    Non-accidental head injury in infants, or shaken baby syndrome, is a highly controversial and disputed topic. Biomechanical studies often suggest that shaking alone cannot cause the classical symptoms, yet many medical experts believe the contrary. Researchers have turned to finite element modelling for a more detailed understanding of the interactions between the brain, skull, cerebrospinal fluid (CSF), and surrounding tissues. However, the uncertainties in such models are significant; these can arise from theoretical approximations, lack of information, and inherent variability. Consequently, this study presents an uncertainty analysis of a finite element model of a human head subject to shaking. Although the model geometry was greatly simplified, fluid-structure-interaction techniques were used to model the brain, skull, and CSF using a Eulerian mesh formulation with penalty-based coupling. Uncertainty and sensitivity measurements were obtained using Bayesian sensitivity analysis, which is a technique that is relatively new to the engineering community. Uncertainty in nine different model parameters was investigated for two different shaking excitations: sinusoidal translation only, and sinusoidal translation plus rotation about the base of the head. The level and type of sensitivity in the results was found to be highly dependent on the excitation type. PMID:22292202

  8. p-Hydroxybenzyl alcohol prevents brain injury and behavioral impairment by activating Nrf2, PDI, and neurotrophic factor genes in a rat model of brain ischemia.

    PubMed

    Kam, Kyung-Yoon; Yu, Seong Jin; Jeong, Nahee; Hong, Jeong Hwa; Jalin, Angela M A Anthony; Lee, Sungja; Choi, Yong Won; Lee, Chae Kwan; Kang, Sung Goo

    2011-03-01

    The therapeutic goal in treating cerebral ischemia is to reduce the extent of brain injury and thus minimize neurological impairment. We examined the effects of p-hydroxybenzyl alcohol (HBA), an active component of Gastrodia elata Blume, on transient focal cerebral ischemia-induced brain injury with respect to the involvement of protein disulphide isomerase (PDI), nuclear factor-E2-related factor 2 (Nrf2), and neurotrophic factors. All animals were ovariectomized 14 days before ischemic injury. Ischemic injury was induced for 1 h by middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion. Three days before MCAO, the vehicle-treated and the HBA-treated groups received intramuscular sesame oil and HBA (25 mg/kg BW), respectively. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed decreased infarct volume in the ischemic lesion of HBA-treated animals. HBA pretreatment also promoted functional recovery, as measured by the modified neurological severity score (mNSS; p < 0.05). Moreover, expression of PDI, Nrf2, BDNF, GDNF, and MBP genes increased by HBA treatment. In vitro, H(2)O(2)-induced PC12 cell death was prevented by 24 h HBA treatment, but bacitracin, a PDI inhibitor, attenuated this cytoprotective effect in a dose-dependent manner. HBA treatment for 2 h also induced nuclear translocation of Nrf2, possibly activating the intracellular antioxidative system. These results suggest that HBA protects against brain damage by modulating cytoprotective genes, such as Nrf2 and PDI, and neurotrophic factors. PMID:21347705

  9. From animal model to human brain networking: dynamic causal modeling of motivational systems.

    PubMed

    Gonen, Tal; Admon, Roee; Podlipsky, Ilana; Hendler, Talma

    2012-05-23

    An organism's behavior is sensitive to different reinforcements in the environment. Based on extensive animal literature, the reinforcement sensitivity theory (RST) proposes three separate neurobehavioral systems to account for such context-sensitive behavior, affecting the tendency to react to punishment, reward, or goal-conflict stimuli. The translation of animal findings to complex human behavior, however, is far from obvious. To examine whether the neural networks underlying humans' motivational processes are similar to those proposed by the RST model, we conducted a functional MRI study, in which 24 healthy subjects performed an interactive game that engaged the different motivational systems using distinct time periods (states) of punishment, reward, and conflict. Crucially, we found that the different motivational states elicited activations in brain regions that corresponded exactly to the brain systems underlying RST. Moreover, dynamic causal modeling of each motivational system confirmed that the coupling strengths between the key brain regions of each system were enabled selectively by the appropriate motivational state. These results may shed light on the impairments that underlie psychopathologies associated with dysfunctional motivational processes and provide a translational validity for the RST. PMID:22623666

  10. [Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)].

    PubMed

    Chen, Yun-Chung; Hsiao, Cheng-Tsung; Soong, Bing-Wen; Lee, Yi-Chung

    2014-06-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most prevalent monogenic cerebral small vessel diseases caused by a mutation in the NOTCH3 gene. The clinical manifestations of CADASIL range from single or multiple lacunar infarcts, transient ischemic attacks, dementia, migraine with aura to psychiatric disorders. The features of brain MRI of CADASIL include multiple lacunar infarcts and diffuse leukoencephalopathy, which frequently involves external capsules and anterior temporal regions. Almost all patients with CADASIL harbor cysteine-involving mutations in NOTCH3. In Taiwan, two thirds of CADASIL patients carry NOTCH3 p.R544C mutations, and only approximately 56% of patients with CADASIL have leukoencephalopathy with anterior temporal regions involvement. PMID:26035923

  11. Infarction in the territory of the anterior cerebral artery: clinical study of 51 patients

    PubMed Central

    Arboix, Adri; Garca-Eroles, Luis; Sellars, Nria; Raga, Agns; Oliveres, Montserrat; Massons, Joan

    2009-01-01

    Background Little is known about clinical features and prognosis of patients with ischaemic stroke caused by infarction in the territory of the anterior cerebral artery (ACA). This single centre, retrospective study was conducted with the following objectives: a) to describe the clinical characteristics and short-term outcome of stroke patients with ACA infarction as compared with that of patients with ischaemic stroke due to middle cerebral artery (MCA) and posterior cerebral artery (PCA) infarctions, and b) to identify predictors of ACA stroke. Methods Fifty-one patients with ACA stroke were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 19 years (19862004). Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The characteristics of these 51 patients with ACA stroke were compared with those of the 1355 patients with MCA infarctions and 232 patients with PCA infarctions included in the registry. Results Infarctions of the ACA accounted for 1.3% of all cases of stroke (n = 3808) and 1.8% of cerebral infarctions (n = 2704). Stroke subtypes included cardioembolic infarction in 45.1% of patients, atherothrombotic infarction in 29.4%, lacunar infarct in 11.8%, infarct of unknown cause in 11.8% and infarction of unusual aetiology in 2%. In-hospital mortality was 7.8% (n = 4). Only 5 (9.8%) patients were symptom-free at hospital discharge. Speech disturbances (odds ratio [OR] = 0.48) and altered consciousness (OR = 0.31) were independent variables of ACA stroke in comparison with MCA infarction, whereas limb weakness (OR = 9.11), cardioembolism as stroke mechanism (OR = 2.49) and sensory deficit (OR = 0.35) were independent variables associated with ACA stroke in comparison with PCA infarction. Conclusion Cardioembolism is the main cause of brain infarction in the territory of the ACA. Several clinical features are more frequent in stroke patients with ACA infarction than in patients with ischaemic stroke due to infarction in the MCA and PCA territories. PMID:19589132

  12. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  15. Combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces post-myocardial infarction depression symptoms and restores intestinal permeability in a rat model.

    PubMed

    Arseneault-Brard, Jessica; Rondeau, Isabelle; Gilbert, Kim; Girard, Stphanie-Anne; Tompkins, Thomas A; Godbout, Roger; Rousseau, Guy

    2012-06-01

    Myocardial infarction (MI) in rats is accompanied by apoptosis in the limbic system and a behavioural syndrome similar to models of depression. We have already shown that probiotics can reduce post-MI apoptosis and designed the present study to determine if probiotics can also prevent post-MI depressive behaviour. We also tested the hypothesis that probiotics achieve their central effects through changes in the intestinal barrier. MI was induced in anaesthetised rats via 40-min transient occlusion of the left anterior coronary artery. Sham rats underwent the same surgical procedure without actual coronary occlusion. For 7 d before MI and between the seventh post-MI day and euthanasia, half the MI and sham rats were given one billion live bacterial cells of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 per d dissolved in water, while the remaining animals received only the vehicle (maltodextrin). Depressive behaviour was evaluated 2 weeks post-MI in social interaction, forced swimming and passive avoidance step-down tests. Intestinal permeability was evaluated by oral administration with fluorescein isothiocyanate-dextran, 4 h before euthanasia. MI rats displayed less social interaction and impaired performance in the forced swimming and passive avoidance step-down tests compared to the sham controls (P < 005). Probiotics reversed the behavioural effects of MI (P < 005), but did not alter the behaviour of sham rats. Intestinal permeability was increased in MI rats and reversed by probiotics. In conclusion, L. helveticus R0052 and B. longum R0175 combination interferes with the development of post-MI depressive behaviour and restores intestinal barrier integrity in MI rats. PMID:21933458

  16. Development of a cerebral circulation model for the automatic control of brain physiology.

    PubMed

    Utsuki, T

    2015-08-01

    In various clinical guidelines of brain injury, intracranial pressure (ICP), cerebral blood flow (CBF) and brain temperature (BT) are essential targets for precise management for brain resuscitation. In addition, the integrated automatic control of BT, ICP, and CBF is required for improving therapeutic effects and reducing medical costs and staff burden. Thus, a new model of cerebral circulation was developed in this study for integrative automatic control. With this model, the CBF and cerebral perfusion pressure of a normal adult male were regionally calculated according to cerebrovascular structure, blood viscosity, blood distribution, CBF autoregulation, and ICP. The analysis results were consistent with physiological knowledge already obtained with conventional studies. Therefore, the developed model is potentially available for the integrative control of the physiological state of the brain as a reference model of an automatic control system, or as a controlled object in various control simulations. PMID:26736651

  17. Material and physical model for evaluation of deep brain activity contribution to EEG recordings

    NASA Astrophysics Data System (ADS)

    Ye, Yan; Li, Xiaoping; Wu, Tiecheng; Li, Zhe; Xie, Wenwen

    2015-12-01

    Deep brain activity is conventionally recorded with surgical implantation of electrodes. During the neurosurgery, brain tissue damage and the consequent side effects to patients are inevitably incurred. In order to eliminate undesired risks, we propose that deep brain activity should be measured using the noninvasive scalp electroencephalography (EEG) technique. However, the deeper the neuronal activity is located, the noisier the corresponding scalp EEG signals are. Thus, the present study aims to evaluate whether deep brain activity could be observed from EEG recordings. In the experiment, a three-layer cylindrical head model was constructed to mimic a human head. A single dipole source (sine wave, 10 Hz, altering amplitudes) was embedded inside the model to simulate neuronal activity. When the dipole source was activated, surface potential was measured via electrodes attached on the top surface of the model and raw data were recorded for signal analysis. Results show that the dipole source activity positioned at 66 mm depth in the model, equivalent to the depth of deep brain structures, is clearly observed from surface potential recordings. Therefore, it is highly possible that deep brain activity could be observed from EEG recordings and deep brain activity could be measured using the noninvasive scalp EEG technique.

  18. [Occupational stress and myocardial infarction].

    PubMed

    Consoli, Silla M

    2015-01-01

    Besides the best-known role of depressed mood, occupational stress deserves to be taken as a coronary risk factor. There are two basic models to define occupational stress: Karasek's model (high job psychological demands associated with low decision latitude, or even low social support at work) and Siegrist's model (imbalance between efforts and rewards received). The combination of the two models better reflects the coronary risk than each model alone. Occupational stress appears both as a risk factor and a prognostic factor after the occurrence of myocardial infarction. The relevance of the models is best in men or in younger age subjects. In women, role conflicts (occupational/domestic), the existence of excessive "intrinsic" efforts (job over investment) and association with marital stress provide more specific information. Burnout, particularly among health professionals, and bullying at work are also linked to cardiovascular risk. Occupational stress is a collective indicator of health at work, valuable to the employer. At an individual level, it can lead to therapeutic preventive approaches. PMID:26150284

  19. Epsilon Aminocaproic Acid Pretreatment Provides Neuroprotection Following Surgically Induced Brain Injury in a Rat Model.

    PubMed

    Komanapalli, Esther S; Sherchan, Prativa; Rolland, William; Khatibi, Nikan; Martin, Robert D; Applegate, Richard L; Tang, Jiping; Zhang, John H

    2016-01-01

    Neurosurgical procedures can damage viable brain tissue unintentionally by a wide range of mechanisms. This surgically induced brain injury (SBI) can be a result of direct incision, electrocauterization, or tissue retraction. Plasmin, a serine protease that dissolves fibrin blood clots, has been shown to enhance cerebral edema and hemorrhage accumulation in the brain through disruption of the blood brain barrier. Epsilon aminocaproic acid (EAA), a recognized antifibrinolytic lysine analogue, can reduce the levels of active plasmin and, in doing so, potentially can preserve the neurovascular unit of the brain. We investigated the role of EAA as a pretreatment neuroprotective modality in a SBI rat model, hypothesizing that EAA therapy would protect brain tissue integrity, translating into preserved neurobehavioral function. Male Sprague-Dawley rats were randomly assigned to one of four groups: sham (n?=?7), SBI (n?=?7), SBI with low-dose EAA, 150 mg/kg (n?=?7), and SBI with high-dose EAA, 450 mg/kg (n?=?7). SBI was induced by partial right frontal lobe resection through a frontal craniotomy. Postoperative assessment at 24 h included neurobehavioral testing and measurement of brain water content. Results at 24 h showed both low- and high-dose EAA reduced brain water content and improved neurobehavioral function compared with the SBI groups. This suggests that EAA may be a useful pretherapeutic modality for SBI. Further studies are needed to clarify optimal therapeutic dosing and to identify mechanisms of neuroprotection in rat SBI models. PMID:26463967

  20. 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

  1. Application of Random Forest Survival Models to Increase Generalizability of Decision Trees: A Case Study in Acute Myocardial Infarction

    PubMed Central

    Yosefian, Iman; Mosa Farkhani, Ehsan; Baneshi, Mohammad Reza

    2015-01-01

    Background. Tree models provide easily interpretable prognostic tool, but instable results. Two approaches to enhance the generalizability of the results are pruning and random survival forest (RSF). The aim of this study is to assess the generalizability of saturated tree (ST), pruned tree (PT), and RSF. Methods. Data of 607 patients was randomly divided into training and test set applying 10-fold cross-validation. Using training sets, all three models were applied. Using Log-Rank test, ST was constructed by searching for optimal cutoffs. PT was selected plotting error rate versus minimum sample size in terminal nodes. In construction of RSF, 1000 bootstrap samples were drawn from the training set. C-index and integrated Brier score (IBS) statistic were used to compare models. Results. ST provides the most overoptimized statistics. Mean difference between C-index in training and test set was 0.237. Corresponding figure in PT and RSF was 0.054 and 0.007. In terms of IBS, the difference was 0.136 in ST, 0.021 in PT, and 0.0003 in RSF. Conclusion. Pruning of tree and assessment of its performance of a test set partially improve the generalizability of decision trees. RSF provides results that are highly generalizable.

  2. Localized dose delivering by ion beam irradiation for experimental trial of establishing brain necrosis model.

    PubMed

    Takata, Takushi; Kondo, Natsuko; Sakurai, Yoshinori; Tanaka, Hiroki; Hasegawa, Takashi; Kume, Kyo; Suzuki, Minoru

    2015-11-01

    Localized dose delivery techniques to establish a brain radiation necrosis model are described. An irradiation field was designed by using accelerated protons or helium ions with a spread-out Bragg peak. Measurement of the designed field confirmed that a high dose can be confined to a local volume of an animal brain. The irradiation techniques described here are very useful for establishing a necrosis model without existence of extraneous complications. PMID:26454176

  3. Trauma induced myocardial infarction.

    PubMed

    Lolay, Georges A; Abdel-Latif, Ahmed K

    2016-01-15

    Chest Trauma in athletes is a common health problem. However, myocardial infarction secondary to coronary dissection in the setting of blunt chest trauma is extremely rare. We report a case of acute inferior wall myocardial infarction following blunt chest trauma. A 32-year-old male with no relevant medical problems was transferred to our medical center for retrosternal chest pain after being elbowed in the chest during a soccer game. Few seconds later, he started experiencing sharp retrosternal chest pain that was severe to that point where he called the emergency medical service. Upon arrival to the trauma department patient was still complaining of chest pain. ECG demonstrated ST segment elevation in the inferior leads with reciprocal changes in the lateral leads all consistent with active ischemia. After rolling out aortic dissection, patient was loaded with ASA, ticagerlor, heparin and was emergently taken to the cardiac catheterization lab. Coronary angiography demonstrated 100% thrombotic occlusion in the distal right coronary artery with TIMI 0 flow distally. After thrombus aspiration, a focal dissection was noted on the angiogram that was successfully stented. Two days after admission patient was discharged home. Echocardiography prior to discharge showed inferior wall akinesis, normal right ventricular systolic function and normal overall ejection fraction. PMID:26490501

  4. A Triple Culture Model of the Blood-Brain Barrier Using Porcine Brain Endothelial cells, Astrocytes and Pericytes

    PubMed Central

    Thomsen, Louiza Bohn; Burkhart, Annette; Moos, Torben

    2015-01-01

    In vitro blood-brain barrier (BBB) models based on primary brain endothelial cells (BECs) cultured as monoculture or in co-culture with primary astrocytes and pericytes are useful for studying many properties of the BBB. The BECs retain their expression of tight junction proteins and efflux transporters leading to high trans-endothelial electric resistance (TEER) and low passive paracellular permeability. The BECs, astrocytes and pericytes are often isolated from small rodents. Larger species as cows and pigs however, reveal a higher yield, are readily available and have a closer resemblance to humans, which make them favorable high-throughput sources for cellular isolation. The aim of the present study has been to determine if the preferable combination of purely porcine cells isolated from the 6 months old domestic pigs, i.e. porcine brain endothelial cells (PBECs) in co-culture with porcine astrocytes and pericytes, would compare with PBECs co-cultured with astrocytes and pericytes isolated from newborn rats with respect to TEER value and low passive permeability. The astrocytes and pericytes were grown both as contact and non-contact co-cultures as well as in triple culture to examine their effects on the PBECs for barrier formation as revealed by TEER, passive permeability, and expression patterns of tight junction proteins, efflux transporters and the transferrin receptor. This syngenic porcine in vitro BBB model is comparable to triple cultures using PBECs, rat astrocytes and rat pericytes with respect to TEER formation, low passive permeability, and expression of hallmark proteins signifying the brain endothelium (tight junction proteins claudin 5 and occludin, the efflux transporters P-glycoprotein (PgP) and breast cancer related protein (BCRP), and the transferrin receptor). PMID:26241648

  5. Vitexin reduces hypoxia-ischemia neonatal brain injury by the inhibition of HIF-1alpha in a rat pup model.

    PubMed

    Min, Jia-Wei; Hu, Jiang-Jian; He, Miao; Sanchez, Russell M; Huang, Wen-Xian; Liu, Yu-Qiang; Bsoul, Najeeb Bassam; Han, Song; Yin, Jun; Liu, Wan-Hong; He, Xiao-Hua; Peng, Bi-Wen

    2015-12-01

    Previous studies have demonstrated that the early suppression of HIF-1α after hypoxia-ischemia (HI) injury provides neuroprotection. Vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), an HIF-1α inhibitor, is a c-glycosylated flavone that has been identified in medicinal plants. Therefore, we hypothesized that treatment with vitexin would protect against HI brain injury. Newborn rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O2 at 37 °C). Vitexin (30, 45 or 60 mg/kg) was administered intraperitoneally at 5 min or 3 h after HI. Vitexin, administered 5 min after HI, was neuroprotective as seen by decreased infarct volume evaluated at 48 h post-HI. This neuroprotection was removed when vitexin was administered 3 h after HI. Neuronal cell death, blood-brain barrier (BBB) integrity, brain edema, HIF-1α and VEGF protein levels were evaluated using a combination of Nissl staining, IgG staining, brain water content, immunohistochemistry and Western blot at 24 and 48 h after HI. The long-term effects of vitexin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests. Vitexin (45 mg/kg) ameliorated brain edema, BBB disruption and neuronal cell death; Upregulation of HIF-1α by dimethyloxalylglycine (DMOG) increased the BBB permeability and brain edema compared to HI alone. Vitexin attenuated the increase in HIF-1α and VEGF. Vitexin also had long-term effects of protecting against the loss of ipsilateral brain and improveing neurobehavioral outcomes. In conclusion, our data indicate early HIF-1α inhibition with vitexin provides both acute and long-term neuroprotection in the developing brain after neonatal HI injury. PMID:26187393

  6. 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…

  7. 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

  8. 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

  9. Energy metabolism in neuronal/glial induction and in iPSC models of brain disorders.

    PubMed

    Mlody, Barbara; Lorenz, Carmen; Inak, Gizem; Prigione, Alessandro

    2016-04-01

    The metabolic switch associated with the reprogramming of somatic cells to pluripotency has received increasing attention in recent years. However, the impact of mitochondrial and metabolic modulation on stem cell differentiation into neuronal/glial cells and related brain disease modeling still remains to be fully addressed. Here, we seek to focus on this aspect by first addressing brain energy metabolism and its inter-cellular metabolic compartmentalization. We then review the findings related to the mitochondrial and metabolic reconfiguration occurring upon neuronal/glial specification from pluripotent stem cells (PSCs). Finally, we provide an update of the PSC-based models of mitochondria-related brain disorders and discuss the challenges and opportunities that may exist on the road to develop a new era of brain disease modeling and therapy. PMID:26877213

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

    PubMed Central

    Pellicer, Begoa; Herraiz, Sonia; Leal, Antonio; Simn, 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

  11. Atomistic modeling of the structural components of the blood-brain barrier

    NASA Astrophysics Data System (ADS)

    Glukhova, O. E.; Grishina, O. A.; Slepchenkov, M. M.

    2015-03-01

    Blood-brain barrier, which is a barrage system between the brain and blood vessels, plays a key role in the "isolation" of the brain of unnecessary information, and reduce the "noise" in the interneuron communication. It is known that the barrier function of the BBB strictly depends on the initial state of the organism and changes significantly with age and, especially in developing the "vascular accidents". Disclosure mechanisms of regulation of the barrier function will develop new ways to deliver neurotrophic drugs to the brain in the newborn. The aim of this work is the construction of atomistic models of structural components of the blood-brain barrier to reveal the mechanisms of regulation of the barrier function.

  12. 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.

  13. Stochastic modelling of PTEN regulation in brain tumors: A model for glioblastoma multiforme.

    PubMed

    Carletti, Margherita; Montani, Matteo; Meschini, Valentina; Bianchi, Marzia; Radici, Lucia

    2015-10-01

    This work is the outcome of the partnership between the mathematical group of Department DISBEF and the biochemical group of Department DISB of the University of Urbino "Carlo Bo" in order to better understand some crucial aspects of brain cancer oncogenesis. Throughout our collaboration we discovered that biochemists are mainly attracted to the instantaneous behaviour of the whole cell, while mathematicians are mostly interested in the evolution along time of small and different parts of it. This collaboration has thus been very challenging. Starting from [23,24,25], we introduce a competitive stochastic model for post-transcriptional regulation of PTEN, including interactions with the miRNA and concurrent genes. Our model also covers protein formation and the backward mechanism going from the protein back to the miRNA. The numerical simulations show that the model reproduces the expected dynamics of normal glial cells. Moreover, the introduction of translational and transcriptional delays offers some interesting insights for the PTEN low expression as observed in brain tumor cells. PMID:26280182

  14. A Graphical Model for Estimating Stimulus-Evoked Brain Responses from Magnetoencephalography Data with Large Background Brain Activity

    PubMed Central

    Nagarajan, Srikantan S.; Attias, Hagai T.; Hild, Kenneth E.; Sekihara, Kensuke

    2014-01-01

    This paper formulates a novel probabilistic graphical model for noisy stimulus-evoked MEG and EEG sensor data obtained in the presence of large background brain activity. The model describes the observed data in terms of unobserved evoked and background factors with additive sensor noise. We present an Expectation-Maximization (EM) algorithm that estimates the model parameters from data. Using the model, the algorithm cleans the stimulus-evoked data by removing interference from background factors and noise artifacts, and separates those data into contributions from independent factors. We demonstrate on real and simulated data that the algorithm outperforms benchmark methods for denoising and separation. We also show that the algorithm improves the performance of localization with beamforming algorithms. PMID:16360320

  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. 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. 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. 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. 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

  17. 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

  18. 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…

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

    PubMed

    Batalle, Dafnis; Muoz-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

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

    SciTech Connect

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

    1983-11-01

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

  1. Excision of Zenker's diverticulum to treat dysphagia associated with acute-phase cerebral infarction.

    PubMed

    Abe, Arata; Harada-Abe, Mina; Takayama, Yohei; Toda, Yusuke; Ueda, Masayuki; Katayama, Yasuo

    2014-01-01

    A 75-year-old man was admitted to our hospital with dysphagia shortly after the onset of a brainstem infarction. Videofluorography indicated the presence of a Zenker's diverticulum with a bolus at the esophageal orifice; endoscopy 5 years earlier had not shown a Zenker's diverticulum and suggests that the diverticulum had formed because of an increase in the hypopharyngeal pressure caused by the brainstem infarction. Surgical excision successfully facilitated transport of the bolus to the esophageal orifice. In the present report, we describe a case of dysphagia caused by a Zenker's diverticulum following and associated with a brain infarction. PMID:24998963

  2. Managing Malignant Cerebral Infarction

    PubMed Central

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

    2011-01-01

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

  3. Masquerades of myocardial infarction.

    PubMed Central

    Bean, W. B.

    1976-01-01

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

  4. An unusual myocardial infarction

    PubMed Central

    Di Michele, Sara; Mirabelli, Francesca; Mankad, Sunil

    2014-01-01

    Summary We present a 74-year-old male with a chondrosarcoma, who presented with chest pain. The history, electrocardiogram (ECG), and biomarkers established the diagnosis of myocardial infarction (MI); angiography did not show coronary atherosclerosis and, both initial transthoracic echocardiogram and chest computed tomography (CT), did not demonstrate any cardiac abnormalities. A second echocardiogram following a routine ECG showed presence of a mass involving the right ventricle and the cardiac apex that was confirmed by chest CT scan. We underline the importance of considering cardiac tumors in the clinical arena of MI management. Learning points Cardiac tumors cause ECG changes similar to ischemic heart diseases.Keep in mind cardiac tumors when performing transthoracic echocardiogram (TTE) in the setting of suspected MI.TTE is the technique of choice in detecting cardiac tumors.

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

    PubMed Central

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

    2014-01-01

    In earlier studies insects were proposed as suitable models for vertebrate bloodbrain 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 2C and 30C 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 brainbarrier 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

  6. BOLD-based Techniques for Quantifying Brain Hemodynamic and Metabolic Properties Theoretical Models and Experimental Approaches

    PubMed Central

    Yablonskiy, Dmitriy A.; Sukstanskii, Alexander L.; He, Xiang

    2012-01-01

    Quantitative evaluation of brain hemodynamics and metabolism, particularly the relationship between brain function and oxygen utilization, is important for understanding normal human brain operation as well as pathophysiology of neurological disorders. It can also be of great importance for evaluation of hypoxia within tumors of the brain and other organs. A fundamental discovery by Ogawa and co-workers of the BOLD (Blood Oxygenation Level Dependent) contrast opened a possibility to use this effect to study brain hemodynamic and metabolic properties by means of MRI measurements. Such measurements require developing theoretical models connecting MRI signal to brain structure and functioning and designing experimental techniques allowing MR measurements of salient features of theoretical models. In our review we discuss several such theoretical models and experimental methods for quantification brain hemodynamic and metabolic properties. Our review aims mostly at methods for measuring oxygen extraction fraction, OEF, based on measuring blood oxygenation level. Combining measurement of OEF with measurement of CBF allows evaluation of oxygen consumption, CMRO2. We first consider in detail magnetic properties of blood magnetic susceptibility, MR relaxation and theoretical models of intravascular contribution to MR signal under different experimental conditions. Then, we describe a through-space effect the influence of inhomogeneous magnetic fields, created in the extravascular space by intravascular deoxygenated blood, on the MR signal formation. Further we describe several experimental techniques taking advantage of these theoretical models. Some of these techniques - MR susceptometry, and T2-based quantification of oxygen OEF utilize intravascular MR signal. Another technique qBOLD evaluates OEF by making use of through-space effects. In this review we targeted both scientists just entering the MR field and more experienced MR researchers interested in applying advanced BOLD-based techniques to study brain in health and disease. PMID:22927123

  7. 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

  8. 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

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

    PubMed

    Direito, Bruno; Teixeira, Csar; Ribeiro, Bernardete; Castelo-Branco, Miguel; Sales, Francisco; Dourado, Antnio

    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

  10. 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

  11. Reduced energy utilization in the brain is a feature of an animal model of fatigue.

    PubMed

    Tanaka, Masaaki; Watanabe, Yasuyoshi

    2008-05-01

    Recently, the authors established an animal model of fatigue. The fatigued animals showed reduced 2-[18F]fluoro-2-deoxy-D-glucose uptake in their brain, although their blood glucose level did not differ from that of the control animals. For further clarification, the study measured regional cerebral blood flow, ATP level, and the ability of mitochondria to produce ATP in the brain of the fatigued and control rats. The fatigued animals showed almost equal regional cerebral blood flow, a significantly higher ATP level, and almost equal mitochondria ability to produce ATP. These data suggest that decreased energy utilization in the brain is a feature of fatigue. PMID:18446584

  12. Modeling invasion of brain tissue by glioblastoma cells: ECM alignment and motility

    NASA Astrophysics Data System (ADS)

    Sander, L. M.

    2013-03-01

    A key stage in the development of highly malignant brain tumors (Glioblastoma Multiforme) is invasion of normal brain tissue by motile cells moving through a crowded, complex environment. Evidence from in vitro experiments suggests the cell motion is accompanied by considerable deformation and alignment of the extra-cellular matrix (ECM) of the brain. In the case of breast cancer, alignment effects of this sort have been seen in vivo. We have modeled features of this system including stress confinement in the non-linear elasticity of the ECM and contact guidance of the cell motion.

  13. Psychosis post corona radiata and lentiform nucleus infarction.

    PubMed

    Abdullah, Khadijah Hasanah Abang; Saini, Suriati Mohamed; Sharip, Shalisah; Rahman, Abdul Hamid Abdul

    2015-01-01

    Complications of stroke