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Sample records for brain infarction model

  1. 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

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

    PubMed

    Norrving, Bo

    2008-08-01

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

  3. Caspase-3 inhibitor prevents the apoptosis of brain tissue in rats with acute cerebral infarction

    PubMed Central

    SUN, YUHUA; XU, YUMING; GENG, LIJIAO

    2015-01-01

    The aim of the present study was to investigate the effect of the caspase-3 inhibitor z-DEVD-fmk on the apoptosis of the brain tissues of rats with acute cerebral infarction. Middle cerebral artery occlusion was used to establish a rat model of infarction, and the rats were randomly divided into a sham group (n=15), model group (n=15) and treatment group (n=15). z-DEVD-fmk (2.5 µg/kg) was injected into the intracranial artery of rats in the treatment group, while the same volume of phosphate-buffered saline solution was administered to the rats of the sham and model groups. After 48 h, all rats were sacrificed and their brain tissues were removed. The caspase-3 mRNA level, protein level and activity, brain cell apoptosis index and infarction scope of the three groups were analyzed. Neurological impairment was also assessed. At 48 h after model establishment, the caspase-3 mRNA and protein levels in the brain tissues of the model group were significantly higher than those of the sham group, and those in the treatment group were significantly lower than those in the model group (P<0.05); however, they remained significantly higher than those in the sham group. Caspase-3 activity in the model group was significantly higher than that in the sham group, and treatment with the caspase-3 inhibitor significantly reduced caspase-3 activity compared with that in the model group (P<0.05). The apoptosis index and infarction scope in the model and treatment groups were significantly increased compared with those in the sham group, and were significantly lower in the treatment group than in the model group (P<0.05). The neurological impairment of rats in the model and treatment groups was increased significantly compared with that in the sham group, and the treatment group exhibited a significantly lower level of neurological impairment than the model group (P<0.05). In conclusion, the caspase-3 inhibitor z-DEVD-fmk effectively inhibited apoptosis and delayed the necrosis of brain tissue cells in rats with acute cerebral infarction, and had certain protective effects on brain tissue. PMID:26170924

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

    PubMed

    McBride, Devin W; Matei, Nathanael; Câmara, Justin R; Louis, Jean-Sébastien; 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

  5. 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

  6. 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

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

  8. 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

  9. 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.…

  10. [Generalized brain edema and cerebral infarct in ergotamine abuse: imaging by computerized tomography, magnetic resonance tomography and angiography].

    PubMed

    Toedt, C; Hötzinger, H; Salbeck, R; Beyer, H K

    1989-09-01

    Abuse of ergotamine can release a generalised brain edema and brain infarctions. This can be visualized by CT, MR and angiography. The reason, however, can only be found in the patients history. PMID:2591142

  11. 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.

  12. 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

  13. 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.

  14. 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

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

    NASA Astrophysics Data System (ADS)

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

    2005-03-01

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

  16. Multiple microembolic brain infarctions in Clonorchis sinensis infestation.

    PubMed

    Hwang, Kyoung Jin; Heo, Sung Hyuk; Chang, Dae-Il

    2012-08-15

    We report a case of multiple cerebral infarctions as the first symptom of hypereosinophilia with Clonorchis sinensis infestation. The patient showed hypereosinophilia and elevated cardiac enzyme, and the egg test of C. sinensis was positive. CT scans of the chest and the abdomen revealed eosinophilic infiltration in both lung and liver. Over a period of six weeks after praziquantel medication, he recovered. C. sinensis infestation which is endemic in East Asian countries should be considered as a cause of multiple microembolic stroke associated with idiopathic hypereosinophilic syndrome. PMID:22656183

  17. 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

  18. [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

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

    PubMed Central

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

    2013-01-01

    Background Stroke is a major cause of death and severe disability, but effective treatments are limited. Neuroglobin, a neuronal heme-globin, has been advocated as a novel pharmacological target in combating stroke and neurodegenerative disorders based on cytoprotective properties. Using thoroughly validated antibodies and oligos, we give a detailed brain anatomical characterization of transgenic mice over expressing Neuroglobin. Moreover, using permanent middle artery occlusion the effect of elevated levels of Neuroglobin on ischemic damage was studied. Lastly, the impact of mouse strain genetic background on ischemic damage was investigated. Principal Findings A four to five fold increase in Neuroglobin mRNA and protein expression was seen in the brain of transgenic mice. A ?-actin promoter was used to drive Neuroglobin over expression, but immunohistochemistry and in situ hybridization showed over expression to be confined to primarily the cortex, hippocampus, cerebellum, and only in neurons. The level and expression pattern of endogenous Neuroglobin was unaffected by insertion of the over expressing Ngb transgene. Neuroglobin over expression resulted in a significant reduction in infarct volume 24 hours after ischemia. Immunohistochemistry showed no selective sparing of Neuroglobin expressing cells in the ischemic core or penumbra. A significant difference in infarct volume was found between mice of the same strain, but from different colonies. Significance In contrast to some previous reports, Neuroglobin over expression is not global but confined to a few well-defined brain regions, and only in neurons. This study confirms previous reports showing a correlation between reduced infarct volume and elevated Neuroglobin levels, but underlines the need to study the likely contribution from compensatory mechanisms to the phenotype following a genetic perturbation. We also stress, that care should be taken when comparing results where different mouse strains and colonies have been used due to large genetic background contribution to the observed phenotype. PMID:24098534

  20. 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 72 hrs, 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: 50.9 ± 5.4% versus 69.9 ± 3.4%, P = 0.007). End systolic LV volume and LV ejection fraction measured by echocardiography at follow-up differed significantly between both groups (51 ± 5 ml versus 65 ± 3 ml, P = 0.033; 47.5 ± 2.6% versus 38.8 ± 1.2%, 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

  1. 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, André P.; Jordan, Bénédicte 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 (48–72 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

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

    PubMed

    Colliez, Florence; Safronova, Marta M; Magat, Julie; Joudiou, Nicolas; Peeters, André P; Jordan, Bénédicte 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 (48-72 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

  3. 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; Kraj?a, Jan; Czerný, Dan; Hrbá?, Tomáš; Otáhal, David; Langová, Kate?ina

    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.

  4. 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.

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

    PubMed Central

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

    1988-01-01

    The role of preceding infection as a risk factor for ischaemic stroke was investigated in a case-control study of 54 consecutive patients under 50 years of age with brain infarction and 54 randomly selected controls from the community matched for sex and age. Information about previous illnesses, smoking, consumption of alcohol, and use of drugs was taken. A blood sample was analysed for standard biochemical variables and serum cholesterol, high density lipoprotein cholesterol, triglyceride, and fasting blood glucose concentrations determined. Titres of antimicrobial antibodies against various bacteria, including Staphylococcus, Streptococcus, Yersinia, and Salmonella and several viruses were determined. Febrile infection was found in patients during the month before the brain infarction significantly more often than in controls one month before their examination (19 patients v three controls; estimated relative risk 9·0 (95% confidence interval 2·2 to 80·0)). The most common preceding febrile infection was respiratory infection (80%). Infections preceding brain infarction were mostly of bacterial origin based on cultural, serological, and clinical data. In conditional logistic regression analysis for matched pairs the effect of preceding febrile infection remained significant (estimated relative risk 14·5 (95% confidence interval 1·9 to 112·3)) when tested with triglyceride concentration, hypertension, smoking, and preceding intoxication with alcohol. Although causality cannot be inferred from these data and plausible underlying mechanisms remain undetermined, preceding febrile infection may play an important part in the development of brain infarction in young and middle aged patients. PMID:3132245

  6. Spatiotemporal brain imaging and modeling

    E-print Network

    Lin, Fa-Hsuan, 1972-

    2004-01-01

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

  7. Novel mouse model of left ventricular pressure overload and infarction causing predictable ventricular remodelling and progression to heart failure.

    PubMed

    Weinheimer, Carla J; Lai, Ling; Kelly, Daniel P; Kovacs, Attila

    2015-01-01

    Mouse surgical models are important tools for evaluating mechanisms of human cardiac disease. The clinically relevant comorbidities of hypertension and ischaemia have not been explored in mice. We have developed a surgical approach that combines transverse aortic constriction and distal left anterior coronary ligation (MI) to produce a gradual and predictable progression of adverse left ventricular (LV) remodelling that leads to heart failure (HF). Mice received either sham, MI alone, transverse aortic constriction alone or HF surgery. Infarct size and LV remodelling were evaluated by serial 2-D echocardiograms. Transverse aortic constriction gradients were measured by the Doppler velocity-time integral ratio between constricted and proximal aortic velocities. At 4 weeks, hearts were weighed and analysed for histology and brain natriuretic peptide, a molecular marker of HF. Echocardiographic analysis of segmental wall motion scores showed similarly small apical infarct sizes in the MI and HF groups at day 1 postsurgery. MI alone showed little change in infarct size over 4 weeks (0.26 ± 0.02 to 0.27 ± 0.04, P = 0.77); however, HF mice showed infarct expansion (0.25 ± 0.06 to 0.39 ± 0.09, P < 0.05). HF mice also showed LV remodelling with increases in LV volumes (1 day = 36.5 ± 5.2 mL, 28 days = 89.1 ± 16.0 mL) versus no significant changes in the other groups. Furthermore, systolic function progressively deteriorated in the HF group only (ejection fraction, 1 day = 55.6 ± 3.6%, 28 days = 17.6 ± 4.1%, P < 0.05) with an increase of brain natriuretic peptide by 3.5-fold. This surgical model of pressure overload in the setting of a small infarction causes progressive deterioration of cardiac structural and functional properties, and provides a clinically relevant tool to study adverse LV remodelling and heart failure. PMID:25311547

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

    PubMed Central

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

    2015-01-01

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

  9. 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

  10. Spatiotemporal evolution of blood brain barrier damage and tissue infarction within the first 3h after ischemia onset.

    PubMed

    Jin, Xinchun; Liu, Jie; Yang, Yi; Liu, Ke J; Yang, Yirong; Liu, Wenlan

    2012-12-01

    Blood brain barrier (BBB) damage that occurs within the thrombolytic time window is increasingly appreciated to negatively impact the safety and efficacy profiles of thrombolytic therapy for ischemic stroke. However, the spatiotemporal evolution of BBB damage in this early stroke stage and the underlying mechanisms remain unclear. Here, we investigated the topographical distribution of BBB damage and its association with tissue injury within the first 3 h after ischemia onset and the roles of matrix metalloproteinase (MMP)-2/9 in this process. Rats were subjected to 1, 2, or 3 h of middle cerebral artery occlusion (MCAO) followed by 10 min reperfusion with fluorescence-labeled dextran as BBB permeability marker. Acute tissue infarction was evidenced by staining defect with triphenyltetrazolium chloride (TTC). Cerebral blood flow (CBF) was measured by magnetic resonance imaging. MMP-2/9 were assessed by gel and in situ zymography. After 2-h MCAO, dextran leakage was seen in the ischemic ventromedial striatum and the preoptic area which showed ~70% CBF reduction, and expanded to other MCA regions including the cortex after 3-h MCAO. Interestingly, high (2000 kDa) and low (70 kDa) molecular weight dextrans displayed almost identical leakage patterns. Different from BBB damage, tissue infarction was first seen in the ischemic dorsal striatum and the parietal/insular cortex which experienced ~90% CBF reduction. Increased gelatinolytic activity colocalized with dextran leakage, and MMP-2 was found to be the major enzymatic source on gelatin zymograms. Pretreatment with MMP inhibitor GM6001 significantly reduced dextran leakage induced by 2-h and 3-h MCAO. Taken together, our findings reveal substantial differences in the topographic distribution of BBB damage and tissue infarction within the first 3 h after MCAO onset. Unlike ischemic neuronal damage, BBB damage appears to develop faster in brain regions with moderately severe ischemia, and MMP-2 contributes to this early ischemic BBB damage. PMID:22813865

  11. Increased Silent Brain Infarction Accompanied With High Prevalence of Diabetes and Dyslipidemia in Psychiatric Inpatients: A Cross-Sectional Study

    PubMed Central

    Uju, Yoriyasu; Sekine, Keisuke; Ishii, Yukihiro; Yoshimi, Taro; Yasui, Reiko; Yasukawa, Asuka; Sato, Mamoru; Okamoto, Seiko; Hisaoka, Tetsuya; Miura, Masafumi; Kusanishi, Shun; Murakami, Kanako; Nakano, Chieko; Mizuta, Yasuhiko; Mimori, Seisuke; Mishima, Shunichi; Igarashi, Kazuei; Takizawa, Tsuyoshi; Hayakawa, Tatsuro; Tsukada, Kazumi

    2015-01-01

    Objective: Patients with schizophrenia have increased risk of atherosclerotic diseases. It is already known that lifestyle-related disorders and the use of antipsychotics are closely related with the progression of atherosclerosis in psychiatric patients. Stroke as well as coronary heart disease play an important role in the cause of death in Asia and Japan. Thus, we studied the prevalence of cerebrovascular disease in psychiatric inpatients in Japan using brain magnetic resonance imaging (MRI). Method: This cross-sectional study was performed from January 2012 to December 2013. Study participants were 152 hospitalized patients (61 men and 91 women) in the Department of Psychiatry at Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa City, Japan. Mean ages were 50.0 and 57.1 years old for men and women, respectively. The diagnoses (DSM-IV-TR criteria) of participants were schizophrenia (69.1%), mood disorder (18.4%), and other mental disorders (12.5%). We checked physical status, metabolic status of glucose and lipid levels, and brain MRI within 1 week of admission. Results: The study group showed a significantly high prevalence of diabetes and low high-density lipoprotein (HDL) cholesterolemia in both sexes (n = 61 in men, n = 91 in women, P < .05). In the study group, serum fasting plasma glucose and hemoglobin A1c levels were significantly high (n = 152, P < .05), but serum HDL cholesterol and total cholesterol were significantly low in both sexes (n = 61 in men, n = 90 in women, P < .05), and triglycerides were low in men (n = 61, P < .05). Silent brain infarction was recognized at a higher rate (n = 98, P < .05) compared with healthy controls. Conclusions: Participants in this study had an increased ratio of silent brain infarction compared with Japanese healthy controls, accompanied with higher ratios of diabetes and low HDL cholesterol. PMID:26445690

  12. Antiphospholipid antibodies, brain infarcts, and cognitive and motor decline in aging (ABICMA): design of a community-based, longitudinal, clinical-pathological study.

    PubMed

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

    2013-01-01

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

  13. The Role of the PI3K Pathway in the Regeneration of the Damaged Brain by Neural Stem Cells after Cerebral Infarction

    PubMed Central

    Lo, Eng H.

    2015-01-01

    Neurologic deficits resulting from stroke remain largely intractable, which has prompted thousands of studies aimed at developing methods for treating these neurologic sequelae. Endogenous neurogenesis is also known to occur after brain damage, including that due to cerebral infarction. Focusing on this process may provide a solution for treating neurologic deficits caused by cerebral infarction. The phosphatidylinositol-3-kinase (PI3K) pathway is known to play important roles in cell survival, and many studies have focused on use of the PI3K pathway to treat brain injury after stroke. Furthermore, since the PI3K pathway may also play key roles in the physiology of neural stem cells (NSCs), eliciting the appropriate activation of the PI3K pathway in NSCs may help to improve the sequelae of cerebral infarction. This review describes the PI3K pathway, its roles in the brain and NSCs after cerebral infarction, and the therapeutic possibility of activating the pathway to improve neurologic deficits after cerebral infarction. PMID:26320845

  14. 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)-?, 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-?, 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

  15. Downregulation of serum brain specific microRNA is associated with inflammation and infarct volume in acute ischemic stroke.

    PubMed

    Liu, Yanping; Zhang, Junjian; Han, Rongfei; Liu, Hanxing; Sun, Dong; Liu, Xuan

    2015-02-01

    Cerebral ischemic injury activates a robust inflammatory response, exacerbating neurological deficit. Several brain specific microRNA (miRNA) molecules have been reported to mediate functioning of the immune system, referred to as NeurimmiR. We aimed to explore possible associations between serum miRNA levels and stroke severity and their involvement in the regulation of inflammatory responses after stroke. Blood samples were obtained from 31 patients with acute ischemic stroke and 11 healthy controls. We evaluated infarct volume using diffusion weighted imaging and neurological deficit using the National Institutes of Health Stroke Scale. Serum levels of three NeurimmiR, miR-124, miR-9 and miR-219 were detected by real-time polymerase chain reaction and serum levels of metalloproteinase-9 (MMP-9), a proinflammation marker in brain injury, were examined by enzyme-linked immunosorbent assay. We found that serum miR-124 was significantly decreased within 24 hours after stroke onset and serum miR-9 was decreased in patients with larger stroke. There were no significant changes in serum miR-219. Both serum miR-124 and miR-9 levels within 24 hours were negatively correlated with infarct volume and plasma high-sensitivity C-reactive protein levels. All three NeurimmiR negatively correlated with MMP-9 levels. Our preliminary findings indicate that serum miR-124, miR-9 and miR-219 are suppressed in acute ischemic stroke thus facilitating neuroinflammation and brain injury. PMID:25257664

  16. Effect of decellularized tissue powders on a rat model of acute myocardial infarction.

    PubMed

    Tabuchi, Masaki; Negishi, Jun; Yamashita, Akitatsu; Higami, Tetsuya; Kishida, Akio; Funamoto, Seiichi

    2015-11-01

    Many research groups are currently investigating new treatment modalities for myocardial infarction. Numerous aspects need to be considered for the clinical application of these therapies, such as low cell integration and engraftment rates of cell injection techniques. Decellularized tissues are considered good materials for promoting regeneration of traumatic tissues. The properties of the decellularized tissues are sustained after processing to powder form. In this study, we examined the use of decellularized tissue powder in a rat model of acute myocardial infarction. The decellularized tissue powders, especially liver powder, promoted cell integration and neovascularization both in vitro and in vivo. Decellularized liver powder induced neovascularization in the infarct area, resulting in the suppression of myocardial necrosis. The results of this study suggest that decellularized liver powder has good potential for application as a blood supply material for the treatment of myocardial infarction. PMID:26249619

  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. Incorporation of a left ventricle finite element model defining infarction into the XCAT imaging phantom.

    PubMed

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

    2011-04-01

    The 4D extended cardiac-torso (XCAT) phantom was developed to provide a realistic and flexible model of the human anatomy and cardiac and respiratory motions for use in medical imaging research. A prior limitation to the phantom was that it did not accurately simulate altered functions of the heart that result from cardiac pathologies such as coronary artery disease (CAD). We overcame this limitation in a previous study by combining the phantom with a finite-element (FE) mechanical model of the left ventricle (LV) capable of more realistically simulating regional defects caused by ischemia. In the present work, we extend this model giving it the ability to accurately simulate motion abnormalities caused by myocardial infarction (MI), a far more complex situation in terms of altered mechanics compared with the modeling of acute ischemia. The FE model geometry is based on high resolution CT images of a normal male subject. An anterior region was defined as infarcted and the material properties and fiber distribution were altered, according to the bio-physiological properties of two types of infarction, i.e., fibrous and remodeled infarction (30% thinner wall than fibrous case). Compared with the original, surface-based 4D beating heart model of the XCAT, where regional abnormalities are modeled by simply scaling down the motion in those regions, the FE model was found to provide a more accurate representation of the abnormal motion of the LV due to the effects of fibrous infarction as well as depicting the motion of remodeled infarction. In particular, the FE models allow for the accurate depiction of dyskinetic motion. The average circumferential strain results were found to be consistent with measured dyskinetic experimental results. Combined with the 4D XCAT phantom, the FE model can be used to produce realistic multimodality sets of imaging data from a variety of patients in which the normal or abnormal cardiac function is accurately represented. PMID:21041157

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

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

    PubMed

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

    2014-02-01

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

  9. 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

  10. 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

  11. 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.

  12. Combination of cyclosporine and erythropoietin improves brain infarct size and neurological function in rats after ischemic stroke

    PubMed Central

    2011-01-01

    Background This study tested the superiority of combined cyclosporine A (CsA)-erythropoietin (EPO) therapy compared with either one in limiting brain infarction area (BIA) and preserving neurological function in rat after ischemic stroke (IS). Methods Fifty adult-male SD rats were equally divided into sham control (group 1), IS plus intra-peritoneal physiological saline (at 0.5/24/48 h after IS) (group 2), IS plus CsA (20.0 mg/kg at 0.5/24h, intra-peritoneal) (group 3), IS plus EPO (5,000IU/kg at 0.5/24/48h, subcutaneous) (group 4), combined CsA and EPO (same route and dosage as groups 3 and 4) treatment (group 5) after occlusion of distal left internal carotid artery. Results BIA on day 21 after acute IS was higher in group 2 than in other groups and lowest in group 5 (all p < 0.01). The sensorimotor functional test showed higher frequency of left turning in group 2 than in other groups and lowest in group 5 (all p < 0.05). mRNA and protein expressions of apoptotic markers and number of apoptotic nuclei on TUNEL were higher in group 2 than in other groups and lowest in group 1 and 5, whereas the anti-apoptotic markers exhibited an opposite trend (all p < 0.05). The expressions of inflammatory and oxidized protein were higher in group 2 than in other groups and lowest in group 1 and 5, whereas anti-inflammatory markers showed reversed changes in group 1 and other groups (all p < 0.05). The number of aquaporin-4+ and glial fibrillary acid protein+ stained cells were higher in group 2 as compared to other groups and lowest in groups 1 and 5 (all p < 0.01). Conclusion combined treatment with CsA and EPO was superior to either one alone in protecting rat brain from ischemic damage after IS. PMID:21864394

  13. 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.

  14. Left Brain, Right Brain, Super Brain: The Holistic Model.

    ERIC Educational Resources Information Center

    Yellin, David

    Recent discoveries about the whole brain seem to call for a holistic approach to learning, one in which educators would teach the whole person, including physical and emotional states as well as cognitive abilities. Three holistic techniques are particularly relevant to education: (1) biofeedback; (2) yoga; and (3) the Lozanov method. Biofeedback…

  15. 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

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

    PubMed

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

    2011-05-01

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

  17. 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

  18. 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

  19. 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

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

    E-print Network

    Cimino, James J.

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

  1. 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

  2. Cryoinjury as a myocardial infarction model for the study of cardiac regeneration in the zebrafish.

    PubMed

    González-Rosa, Juan Manuel; Mercader, Nadia

    2012-04-01

    The zebrafish heart has the capacity to regenerate after ventricular resection. Although this regeneration model has proved useful for the elucidation of certain regeneration mechanisms, it is based on the removal of heart tissue rather than on tissue damage. We recently characterized the cellular response and regenerative capacity of the zebrafish heart after cryoinjury (CI), an alternative procedure that more closely models the pathophysiological process undergone by the human heart after myocardial infarction (MI). After anesthesia, localized CI with a liquid nitrogen-cooled copper probe induced damage in 25% of the ventricle, in a procedure requiring <5 min. Here we present a detailed description of the technique, which provides a valuable system for the study of the mechanisms of heart regeneration and scar removal after MI in a versatile vertebrate model. PMID:22461067

  3. 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

  4. Psychosocial work environment and myocardial infarction: improving risk estimation by combining two complementary job stress models in the SHEEP Study

    PubMed Central

    Peter, R; Siegrist, J; Hallqvist, J; Reuterwall, C; Theorell, T

    2002-01-01

    Objectives: Associations between two alternative formulations of job stress derived from the effort-reward imbalance and the job strain model and first non-fatal acute myocardial infarction were studied. Whereas the job strain model concentrates on situational (extrinsic) characteristics the effort-reward imbalance model analyses distinct person (intrinsic) characteristics in addition to situational ones. In view of these conceptual differences the hypothesis was tested that combining information from the two models improves the risk estimation of acute myocardial infarction. Methods: 951 male and female myocardial infarction cases and 1147 referents aged 45–64 years of The Stockholm Heart Epidemiology (SHEEP) case-control study underwent a clinical examination. Information on job stress and health adverse behaviours was derived from standardised questionnaires. Results: Multivariate analysis showed moderately increased odds ratios for either model. Yet, with respect to the effort-reward imbalance model gender specific effects were found: in men the extrinsic component contributed to risk estimation, whereas this was the case with the intrinsic component in women. Controlling each job stress model for the other in order to test the independent effect of either approach did not show systematically increased odds ratios. An improved estimation of acute myocardial infarction risk resulted from combining information from the two models by defining groups characterised by simultaneous exposure to effort-reward imbalance and job strain (men: odds ratio 2.02 (95% confidence intervals (CI) 1.34 to 3.07); women odds ratio 2.19 (95% CI 1.11 to 4.28)). Conclusions: Findings show an improved risk estimation of acute myocardial infarction by combining information from the two job stress models under study. Moreover, gender specific effects of the two components of the effort-reward imbalance model were observed. PMID:11896138

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

    PubMed Central

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

    2014-01-01

    Large animal studies are an important step toward clinical translation of novel therapeutic approaches. We aimed to establish an ischemic heart failure (HF) model with a larger myocardial infarction (MI) relative to previous studies, and characterize the functional and structural features of this model. An MI was induced by occluding the proximal left anterior descending artery (LAD; n = 15) or the proximal left circumflex artery (LCx; n = 6) in Yorkshire pigs. Three pigs with sham procedures were also included. All pigs underwent hemodynamic and echocardiographic assessments before MI, at 1 mo, and 3 mo after MI. Analyses of left ventricular (LV) myocardial mechanics by means of strains and torsion were performed using speckle-tracking echocardiography and compared between the groups. The proximal LAD MI approach induced larger infarct sizes (14.2 ± 3.2% vs. 10.6 ± 1.9%, P = 0.03), depressed systolic function (LV ejection fraction; 39.8 ± 7.5% vs. 54.1 ± 4.6%, P < 0.001), and more LV remodeling (end-systolic volume index; 82 ± 25 ml/m2 vs. 51 ± 18 ml/m2, P = 0.02, LAD vs. LCx, respectively) compared with the LCx MI approach without compromising the survival rate. At the papillary muscle level, echocardiographic strain analysis revealed no differences in radial and circumferential strain between LAD and LCx MIs. However, in contrast with the LCx MI, the LAD MI resulted in significantly decreased longitudinal strain. The proximal LAD MI model induces more LV remodeling and depressed LV function relative to the LCx MI model. Location of MI significantly impacts the severity of HF, thus careful consideration is required when choosing an MI model for preclinical HF studies. PMID:25217654

  6. Modeling premature brain injury and recovery

    PubMed Central

    Scafidi, Joey; Fagel, Devon M.; Ment, Laura R.; Vaccarino, Flora M.

    2009-01-01

    Premature birth is a growing and significant public health problem because of the large number of infants that survive with neurodevelopmental sequelae from brain injury. Recent advances in neuroimaging have shown that although some neuroanatomical structures are altered, others improve over time. This review outlines recent insights into brain structure and function in these preterm infants at school age and relevant animal models. These animal models have provided scientists with an opportunity to explore in depth the molecular and cellular mechanisms of injury as well as the potential of the brain for recovery. The endogenous potential that the brain has for neurogenesis and gliogenesis, and how environment contributes to recovery, are also outlined. These preclinical models will provide important insights into the genetic and epigenetic mechanisms responsible for variable degrees of injury and recovery, permitting the exploration of targeted therapies to facilitate recovery in the developing preterm brain. PMID:19482072

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

    PubMed Central

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

    2013-01-01

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

  8. UNCORRECTEDPROOF Optimization in Brain? Modeling Human

    E-print Network

    Wu, Changxu (Sean)

    ]. With these computational models, researchers are able to validate, test, and up- date psychological theories in ways and the psychological refractory period (PRP). This model also proposes brain changes that may accompany the typing and PRP practice effects that could be tested empirically with neuroimaging. All of the modeled phenomena

  9. An ultrasound-driven kinematic model for deformation of the infarcted mouse left ventricle incorporating a near-incompressibility constraint.

    PubMed

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

    2015-02-01

    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), can be solved quickly and are easy to implement, but they ignore regional geometric variations and are difficult to adapt to the study of regional pathologies like myocardial infarctions. 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 LV. 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 LVs 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

  10. 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

  11. Models in the Brain Naturalizing Human Intentionality

    E-print Network

    Ryder, Dan

    Models in the Brain Naturalizing Human Intentionality Dan Ryder University of British Columbia it is shown how this idea can be natural- ized, and how the representational contents of our internal models, and proper- ties that form the objects of human perception and thought. It is then shown how this account

  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. Computational Modeling of Brain Dynamics during Repetitive Head Motions

    E-print Network

    Burtscher, Martin

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

  14. Aquaporin-4 gene silencing protects injured neurons after early cerebral infarction

    PubMed Central

    He, Zhan-ping; Lu, Hong

    2015-01-01

    Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cellular edema after early cerebral infarction. Cellular edema and aquaporin-4 expression can be determined by measuring cerebral infarct area and apparent diffusion coefficient using diffusion-weighted imaging (DWI). We examined the effects of silencing aquaporin-4 on cerebral infarction. Rat models of cerebral infarction were established by occlusion of the right middle cerebral artery and siRNA-aquaporin-4 was immediately injected via the right basal ganglia. In control animals, the area of high signal intensity and relative apparent diffusion coefficient value on T2-weighted imaging (T2WI) and DWI gradually increased within 0.5–6 hours after cerebral infarction. After aquaporin-4 gene silencing, the area of high signal intensity on T2WI and DWI reduced, relative apparent diffusion coefficient value was increased, and cellular edema was obviously alleviated. At 6 hours after cerebral infarction, the apparent diffusion coefficient value was similar between treatment and model groups, but angioedema was still obvious in the treatment group. These results indicate that aquaporin-4 gene silencing can effectively relieve cellular edema after early cerebral infarction; and when conducted accurately and on time, the diffusion coefficient value and the area of high signal intensity on T2WI and DWI can reflect therapeutic effects of aquaporin-4 gene silencing on cellular edema. PMID:26330830

  15. 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.

  16. 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

  17. 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

  18. SABANCI UNIVERSITY Probabilistic Graphical Models for Brain

    E-print Network

    Çetin, Müjdat

    , and would think that it continued in motion solely because of its own wish. This is that human freedomSABANCI UNIVERSITY Probabilistic Graphical Models for Brain Computer Interfaces by Jaime F. Delgado #12;"Further conceive, I beg, that a stone, while continuing in motion, should be capable of thinking

  19. Chlorogenic acid ameliorates brain damage and edema by inhibiting matrix metalloproteinase-2 and 9 in a rat model of focal cerebral ischemia.

    PubMed

    Lee, Kyungjin; Lee, Jeong-Sook; Jang, Hyeung-Jin; Kim, Sung-Moo; Chang, Mun Seog; Park, Si Hyung; Kim, Kwan Su; Bae, Jinhyun; Park, Jae-Woo; Lee, Bumjun; Choi, Ho-Young; Jeong, Chang-Hyun; Bu, Youngmin

    2012-08-15

    Chlorogenic acid (CGA) has been reported to have various beneficial effects on the cardiovascular and central nervous systems. The purpose of the current study was to investigate whether CGA has protective effects against cerebral ischemia and whether these effects are due to modification of brain edema-related vascular factors. In a rat model of transient middle cerebral artery occlusion (MCAo, 2h of occlusion followed by 22 h of reperfusion), we measured infarct volume and performed behavioral test to evaluate the effects of CGA on brain damage and sensory-motor functional deficits. Brain water content and Evans blue extravasation were measured to evaluate brain edema and blood brain barrier (BBB) damage. Lipid peroxidation (LPO) and the expressions and activities of matrix metalloproteinase (MMP)-2 and MMP-9 were measured to investigate the mechanisms of action. Intraperitoneal injection of CGA (3, 10, and 30 mg/kg) at 0 h and 2h after MCAo dose-dependently reduced infarct volume and sensory-motor functional deficits. It also reduced brain water content and Evans blue extravasation. Mechanistically, CGA reduced LPO and MMPs expressions and activities. These results suggest that CGA reduces brain damage, BBB damage and brain edema by radical scavenging activity and the inhibitory effects on MMP-2 and MMP-9. PMID:22659584

  20. 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.

  1. Zebrafish as an alternative model for hypoxic-ischemic brain damage.

    PubMed

    Yu, Xinge; Li, Yang V

    2011-01-01

    Acute cerebral ischemia is one of the leading causes of mortality and chronic disability. Animal models provide an essential tool for understanding the complex cellular and molecular pathophysiology of hypoxic-ischemia and for testing novel neuroprotective drugs in the pre-clinical setting. In this study we tested zebrafish as a novel model for hypoxic-ischemic brain damage. We built an air-proof chamber where water inside had a low oxygen concentration (0.6-0.8 mg/L) proximate to complete hypoxia. Each zebrafish was placed individually in the hypoxia chamber and was subjected to hypoxia treatment until it became motionless, lying on its side on the bottom of the chamber (time to hypoxia = 679.52 ± 90 seconds, mean ± SD, n =23), followed by transferring into a recovery beaker. Overall, 60.87% of subjects did not recover from hypoxia while 39% survived. The size and distribution of brain injury were determined by triphenyltetrazolium chloride (TTC) staining. Bilateral, moderate to complete TTC decoloration or demarcation of the infarct after 10 minutes of hypoxic treatment was clearly visible in the optic tectum of the optic lobe. The size of the infarct expanded to the deep structure of the optic lobe with longer hypoxic treatments. The zebrafish that survived hypoxia experienced initial twitching followed by unbalanced erratic movements until they regained coordinated, balanced swimming ability. These data indicate that zebrafish are susceptible to hypoxic attack and suggest that the model we present in this study can be used as an alternative model to evaluate hypoxia-induced brain damage. PMID:21760967

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

    PubMed

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

    2010-04-01

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

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

    PubMed Central

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

    2010-01-01

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

  4. Modelling of Brain Consciousness based on Collaborative Adaptive Filters

    E-print Network

    Kent, University of

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

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

    PubMed Central

    Providência, Rui; Paiva, Luís; Caetano, Francisca; Almeida, Inês; Gomes, Pedro; Marques, António Leitão

    2012-01-01

    Background: Thrombolysis In Myocardial Infarction (TIMI), Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (PURSUIT) and Global Registry of Acute Coronary Events (GRACE) scores have been developed for risk stratification in myocardial infarction (MI). The latter is the most validated score, yet active research is ongoing for improving prognostication in MI. Aim: Derivation and validation of a new model for intrahospital, post-discharge and combined/total all-cause mortality prediction – ACHTUNG-Rule – and comparison with the GRACE algorithm. Methods: 1091 patients admitted for MI (age 68.4 ± 13.5, 63.2% males, 41.8% acute MI with ST-segment elevation (STEMI)) and followed for 19.7 ± 6.4 months were assigned to a derivation sample. 400 patients admitted at a later date at our institution (age 68.3 ± 13.4, 62.7% males, 38.8% STEMI) and followed for a period of 7.2 ± 4.0 months were assigned to a validation sample. Three versions of the ACHTUNG-Rule were developed for the prediction of intrahospital, post-discharge and combined (intrahospital plus post-discharge) all-cause mortality prediction. All models were evaluated for their predictive performance using the area under the receiver operating characteristic (ROC) curve, calibration through the Hosmer–Lemeshow test and predictive utility within each individual patient through the Brier score. Comparison through ROC curve analysis and measures of risk reclassification – net reclassification improvement index (NRI) or Integrated Discrimination Improvement (IDI) – was performed between the ACHTUNG versions for intrahospital, post-discharge and combined mortality prediction and the equivalent GRACE score versions for intrahospital (GRACE-IH), post-discharge (GRACE-6PD) and post-admission 6-month mortality (GRACE-6). Results: Assessment of calibration and overall performance of the ACHTUNG-Rule demonstrated a good fit (p value for the Hosmer–Lemeshow goodness-of-fit test of 0.258, 0.101 and 0.550 for ACHTUNG-IH, ACHTUNG-T and ACHTUNG-R, respectively) and high discriminatory power in the validation cohort for all the primary endpoints (intrahospital mortality: AUC ACHTUNG-IH 0.886 ± 0.035 vs. AUC GRACE-IH 0.906 ± 0.026; post-discharge mortality: AUC ACHTUNG-R 0.827 ± 0.036 vs. AUC GRACE-6PD 0.811 ± 0.034; combined/total mortality: AUC ACHTUNG-T 0.831 ± 0.028 vs. AUC GRACE-6 0.815 ± 0.033). Furthermore, all versions of the ACHTUNG-Rule accurately reclassified a significant number of patients in different, more appropriate, risk categories (NRI ACHTUNG-IH 17.1%, p (2-sided) = 0.0021; NRI ACHTUNG-R 22.0%, p = 0.0002; NRI ACHTUNG-T 18.6%, p = 0.0012). The prognostic performance of the ACHTUNG-Rule was similar in both derivation and validation samples. Conclusions: All versions of the ACHTUNG-Rule have shown excellent discriminative power and good calibration for predicting intrahospital, post-discharge and combined in-hospital plus post-discharge mortality. The ACHTUNG version for intrahospital mortality prediction was not inferior to its equivalent GRACE model, and ACHTUNG versions for post-discharge and combined/total mortality demonstrated apparent superiority. External validation in wider, independent, preferably multicentre, registries is warranted before its potential clinical implementation. PMID:24062923

  6. 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.

  7. 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.

  8. 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

  9. A Hierarchical Coevolutionary Method to Support Brain-Lesion Modelling

    E-print Network

    Trahanias, Panos

    A Hierarchical Coevolutionary Method to Support Brain-Lesion Modelling Michail Maniadakis and Panos. In our approach, neural network- based agent structures are employed to represent distinct brain areas cooperating agents. Thus, partial brain models consisting of many substructures can be designed. Replication

  10. Construction of Anatomically Correct Models of Mouse Brain Networks 1

    E-print Network

    Choe, Yoonsuck

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

  11. Spinal Cord Infarction

    MedlinePLUS

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

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

    PubMed Central

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

    2014-01-01

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

  13. 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

  14. Epicardial delivery of collagen patches with adipose-derived stem cells in rat and minipig models of chronic myocardial infarction.

    PubMed

    Araña, Miriam; Gavira, Juan J; Peña, Estefanía; González, Arantxa; Abizanda, Gloria; Cilla, Myriam; Pérez, Marta M; Albiasu, Edurne; Aguado, Natalia; Casado, Mayte; López, Begoña; González, Susana; Soriano, Mario; Moreno, Cristina; Merino, Juana; García-Verdugo, José M; Díez, Javier; Doblaré, Manuel; Pelacho, Beatriz; Prosper, Felipe

    2014-01-01

    Although transplantation of adipose-derived stem cells (ADSC) in chronic myocardial infarction (MI) models is associated with functional improvement, its therapeutic value is limited due to poor long-term cell engraftment and survival. Thus, the objective of this study was to examine whether transplantation of collagen patches seeded with ADSC could enhance cell engraftment and improve cardiac function in models of chronic MI. With that purpose, chronically infarcted Sprague-Dawley rats (n = 58) were divided into four groups and transplanted with media, collagen scaffold (CS), rat ADSC, or CS seeded with rat ADSC (CS-rADSC). Cell engraftment, histological changes, and cardiac function were assessed 4 months after transplantation. In addition, Göttingen minipigs (n = 18) were subjected to MI and then transplanted 2 months later with CS or CS seeded with autologous minipig ADSC (CS-pADSC). Functional and histological assessments were performed 3 months post-transplantation. Transplantation of CS-rADSC was associated with increased cell engraftment, significant improvement in cardiac function, myocardial remodeling, and revascularization. Moreover, transplantation of CS-pADSC in the pre-clinical swine model improved cardiac function and was associated with decreased fibrosis and increased vasculogenesis. In summary, transplantation of CS-ADSC resulted in enhanced cell engraftment and was associated with a significant improvement in cardiac function and myocardial remodeling. PMID:24119456

  15. Diffusion Based Modeling of Human Brain Response to External Stimuli

    E-print Network

    Namazi, Hamidreza

    2012-01-01

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

  16. 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

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

    E-print Network

    Hammock, Bruce D.

    inhibitors Myocardial infarction Epoxyeicosatrienoic acids Oxylipin profiling Myocardial infarction (MIOriginal article Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: Insight gained using metabolomic approaches Ning Li a , Jun-Yan Liu c , Valeriy Timofeyev

  18. 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

  19. 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.

  20. 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

  1. 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

  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. Neuroprotective mechanism of the novel melatonin derivative Neu-P11 in brain ischemia related models.

    PubMed

    Buendia, Izaskun; Gómez-Rangel, Vanessa; González-Lafuente, Laura; Parada, Esther; León, Rafael; Gameiro, Isabel; Michalska, Patrycja; Laudon, Moshe; Egea, Javier; López, Manuela G

    2015-12-01

    Stopping the ischemic cascade by targeting its components is a potential strategy for acute ischemic stroke treatment. During ischemia and especially over reperfusion, oxidative stress plays a major role in causing neuronal cell death. Melatonin has been previously reported to provide neuroprotective effects in in vivo models of stroke by a mechanism that implicates melatonin receptors. In this context, this study was planned to test the potential neuroprotective effects of the novel melatonin MT1/MT2 receptor agonist, Neu-P11, against brain ischemia in in vitro and in vivo models, and to elucidate its underlying mechanism of action. Neu-P11 proved to be a good antioxidant, to protect against glutamate-induced excitotoxicity and oxygen and glucose deprivation in hippocampal slices, and to reduce infarct volume in an in vivo stroke model. Regarding its mechanism of action, the protective effect of Neu-P11 was reverted by luzindole (melatonin receptor antagonist), AG490 (JAK2 inhibitor), LY294002 (PI3/AKT inhibitor) and PD98059 (MEK/ERK1/2 inhibitor). In conclusion, Neu-P11 affords neuroprotection against brain ischemia in in vitro and in vivo models by activating a pro-survival signaling pathway that involves melatonin receptors, JAK/STAT, PI3K/Akt and MEK/ERK1/2. PMID:26188145

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

    PubMed Central

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

    2013-01-01

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

  5. 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

  6. 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

  7. 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 ...

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

    PubMed Central

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

    2013-01-01

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

  9. 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

  10. Diffusion Modeling in BrainSuite13 Justin P. Haldar

    E-print Network

    Leahy, Richard M.

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

  11. 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.

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

    PubMed Central

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

    2013-01-01

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

  13. 77 FR 13578 - Disability and Rehabilitation Research Project; Traumatic Brain Injury Model Systems Centers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-07

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

  14. 77 FR 34363 - Disability and Rehabilitation Research Projects and Centers Program; Traumatic Brain Injury Model...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

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

  15. 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 23.4±7.1% (baseline) vs. ?2.9±5.2% (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

  16. 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

  17. On a Mathematical Model of Brain Activities

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

  18. 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.

  19. Preclinical Evaluation of the Engineered Stem Cell Chemokine Stromal Cell-Derived Factor 1–alpha Analogue in a Translational Ovine Myocardial Infarction Model

    PubMed Central

    MacArthur, John W.; Cohen, Jeffrey E.; McGarvey, Jeremy R.; Shudo, Yasuhiro; Patel, Jay B.; Trubelja, Alen; Fairman, Alexander S.; Edwards, Bryan B.; Hung, George; Hiesinger, William; Goldstone, Andrew B.; Atluri, Pavan; Wilensky, Robert L.; Pilla, James J.; Gorman, Joseph H.; Gorman, Robert C.; Woo, Y. Joseph

    2014-01-01

    Rationale Following myocardial infarction (MI) there is an inadequate blood supply to the myocardium and the surrounding borderzone becomes hypocontractile. Objective To develop a clinically translatable therapy, we hypothesized that in a preclinical ovine model of MI, the modified endothelial progenitor stem cell (EPC) chemokine, engineered stromal cell-derived factor 1-alpha analogue (ESA), would induce EPC chemotaxis, limit adverse ventricular remodeling, and preserve borderzone contractility. Methods and Results Thirty six adult male Dorset sheep underwent permanent ligation of the left anterior descending coronary artery, inducing an anteroapical infarction and were randomized to borderzone injection of saline (n=18) or ESA (n=18). Ventricular function, geometry, and regional strain were assessed using cardiac magnetic resonance imaging and pressure-volume catheter transduction. Bone marrow was harvested for in-vitro analysis, and myocardial biopsies were taken for mRNA, protein and immunohistochemical analysis. ESA induced greater chemotaxis of EPCs compared to saline (p<0.01), and was equivalent to recombinant stromal cell-derived factor 1-alpha (p=0.27). Analysis of mRNA expression and protein levels in ESA treated animals revealed reduced MMP-2 in the borderzone (p<0.05), with elevated levels of TIMP-1 and elastin in the infarct (p<0.05), while immunohistochemical analysis of borderzone myocardium showed increased capillary and arteriolar density in the ESA group (p<0.01). Animals in the ESA treatment group also had significant reductions in infarct size (p<0.01), increased maximal principle strain in the borderzone (p<0.01), and a steeper slope of the end systolic pressure volume relationship (p=0.01). Conclusions The novel, biomolecularly-designed peptide ESA induces chemotaxis of EPCs, stimulates neovasculogenesis, limits infarct expansion, and preserves contractility in an ovine model of MI. PMID:24366171

  20. 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

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

    SciTech Connect

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

    1988-01-01

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

  2. Clinical characteristics and long-term outcome of patients in whom congestive heart failure develops after thrombolytic therapy for acute myocardial infarction: development of a predictive model.

    PubMed

    O'Connor, C M; Hathaway, W R; Bates, E R; Leimberger, J D; Sigmon, K N; Kereiakes, D J; George, B S; Samaha, J K; Abbottsmith, C W; Candela, R J; Topol, E J; Califf, R M

    1997-06-01

    Ischemic heart disease is the most common cause of congestive heart failure, which often begins after acute myocardial infarction. To better delineate the clinical characteristics and outcomes of patients in whom congestive heart failure develops after acute myocardial infarction in the thrombolytic era, we prospectively evaluated patients enrolled in six of the TAMI trials. The study cohort comprised 1619 consecutive patients who had at least 1 mm of ST-segment elevation in two contiguous electrocardiographic leads within 6 hours of the onset of acute myocardial infarction and who received intravenous thrombolytic therapy. We prospectively collected clinical characteristics, baseline demographics, acute and 1-week angiographic variables, and in-hospital and 1-year outcome data. We performed stepwise multivariable regression analysis to determine the noninvasive and invasive predictors of the development of in-hospital congestive heart failure. Congestive heart failure developed in 301 patients in the hospital (19% of 1521 patients admitted were not in heart failure). These patients were likely to be older and female, have diabetes mellitus and previous myocardial infarction, and have an anterior wall myocardial infarction. On acute angiography, they had lower ejection fractions and a higher incidence of multivessel disease. Patency at 90 minutes was lower in the patients with congestive heart failure, and acute mitral regurgitation occurred in 1.6% versus 0.21% of patients without congestive heart failure. Patients with congestive heart failure had higher mortality, more in-hospital complications, and longer hospitalizations. At 1-year follow up, 21% of the patients in whom congestive heart failure developed had died versus 5% in the group without congestive heart failure. Predictors of new congestive heart failure included increased age, anterior wall myocardial infarction, lower pulse pressure and systolic blood pressure, diabetes mellitus, and the presence of rales on admission. The acute angiographic variables of reduced ejection fraction, increased number of diseased vessels, and attempted percutaneous intervention improved the concordance of the predictive model by 6%. Congestive heart failure remains a common clinical problem after acute myocardial infarction and is associated with a twofold increase in in-hospital morbidity and a fourfold increase in in-hospital and 1-year mortality. The development of congestive heart failure in the hospital can be predicted from noninvasive and invasive baseline characteristics. We present a simple table to predict congestive heart failure from baseline characteristics and invasive information. PMID:9200394

  3. 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

  4. The Virtual Brain Integrates Computational Modeling and Multimodal Neuroimaging

    PubMed Central

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

    2013-01-01

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

  5. 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

  6. 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).

  7. DISTINGUISHING EPICARDIAL FAT FROM SCAR: ANALYSIS OF ELECTROGRAMS USING HIGH DENSITY ELECTROANATOMIC MAPPING IN A NOVEL PORCINE INFARCT MODEL

    PubMed Central

    Tung, Roderick; Nakahara, Shiro; Ramirez, Rafael; Lai, Chi; Fishbein, Michael C.; Shivkumar, Kalyanam

    2013-01-01

    Background The presence of epicardial fat can confound the quantification of scar during transpericardial electroanatomic mapping. The electrogram (EGM) characteristics of epicardial fat have not been systematically compared with infarct scar using gross and histopathologic analysis as a gold standard. Methods A closed-chest infarction was created in 40–50 kg pigs by occlusion of the circumflex artery for 150 minutes using an angioplasty balloon. This artery was chosen to minimize any potential overlap of epicardial fat with infarct and to spare any septal involvement. After 4–12 weeks of infarct healing, epicardial mapping was performed. EGMs in low voltage regions (<1.5mV) were analyzed and bipolar amplitude, duration, number of deflections, and the presence of late potentials were recorded. Statistical analysis was performed using unpaired t-test and chi square analysis. Gross and histopathologic examination was used to confirm areas of fat and infarct scar. Results Seven porcine hearts were analyzed after high-density epicardial mapping (364±92 points) was performed 48±19 days after infarction. The mean bipolar EGM amplitude was similar in fat and scar (0.77±0.34 vs 0.75±0.38mV; P=NS). The mean EGM duration was longer in scar than fat (68.8±18.9 vs 50.1±11.6 ms; P<0.0001) and exhibited more fractionation (8.5±3.1 vs 4.7±1.8 deflections; P<0.0001). The presence of late potentials was 99% specific for scar. Further, areas of fat >4 mm in thickness registered low voltage bipolar EGMs. Conclusion Scar from healed myocardial infarction exhibits more fractionation and longer EGM duration when compared to fat. Late potentials are highly specific for locating infarct scars. PMID:20185114

  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. Action of acetylstrophanthidin on experimental myocardial infarction.

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. ["Heart attack in humans"--the health belief model in comparison with the health reality of patients with myocardial infarction].

    PubMed

    Sitnik, Katarzyna; Trzcieniecka-Green, Anna; Jakubowski, Daniel; Gasior, Zbigniew

    2004-01-01

    Myocardial infarction (MI) is the direct cause of 40% of all deaths, independently of the high standard of medical treatment. The main aim of the study was to define the relationship between the declarative health model (declarations) and the real health activity of the sufferers (realization). The research was performed on 107 patients after acute MI, hospitalized in the Cardiology Department Medical University of Silesia. They were questioned in direct interviews. In addition, the modified form of Shalit's circle was applied. The results indicated the coexistence of two health models of patients. In declarations, there is a model of person with interior attribution of MI (90.65%) that has a feeling of ability to influence his/her health (e.g. through the lifestyle: 63.55%; an individual's character: 41.12%). In realization, there is a model of sick patient with exterior attribution of heart attack (e.g. political and economic crisis, innate predisposition). A similar tendency in the perception of health factors and planning of changes after MI was observed. For instance, 50.47% patients talked about "the increase caution" or "slowing down" as a new planned form of activity. Moreover, of 92% patients who have the social support only 33.64% consider that as an important factor for health. The results suggest a divergence between declarations and real health activity. The launched health model of beliefs seems to be too costly and not attractive enough. Taking into consideration the complete risk factors in MI and making the proposed health belief system more accessible seem to be essential for creating an adequate prevention program. PMID:15884259

  12. Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction

    PubMed Central

    Song, Guixian; Gu, Weijuan; Chen, Minglong; Yang, Bing; Li, Dianfu; Wang, Daowu; Cao, Kejiang

    2013-01-01

    Induced pluripotent stem (iPS) cells have the potential to differentiate to various types of cardiovascular cells to repair an injured heart. The potential therapeutic benefits of iPS cell based treatment have been established in small-animal models of myocardial infarction (MI). We?hypothesize that porcine iPS (piPS) cell transplantation may be an effective treatment for MI. After a 90-minute occlusion of the left anterior descending artery in a porcine model, undifferentiated piPS cells or PBS were injected into the ischemic myocardium. Cardiac function, myocardial perfusion and cell differentiation were investigated. One week after piPS cell delivery, global left ventricular ejection fraction (LVEF) significantly decreased in both the iPS group and the PBS group compared to the Sham group (p<0.05, respectively). Six weeks after piPS cell delivery, LVEF of the iPS group significantly improved compared to the PBS group (56.68% vs. 50.93%, p?=?0.04) but was still lower than the Sham group. Likewise, the piPS cell transplantation improved the regional perfusion compared to the PBS injection (19.67% vs. 13.67%, p?=?0.02). The infarct area was significantly smaller in the iPS group than the PBS group (12.04% vs. 15.98% p?=?0.01). PiPS cells engrafted into the myocardium can differentiate into vessel cells, which result in increased formation of new vessels in the infarcted heart. Direct intramyocardial injection of piPS cells can decrease infarct size and improve left ventricular function and perfusion for an immunosuppressed porcine AMI model. PMID:23805264

  13. 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 ex vivo pre-treatment with melatonin, an endogenous hormone with newly found anti-oxidative activity, could improve survival and function of adipose tissue derived MSCs (ADSCs) in vitro as well as in vivo. ADSCs with 5 ?M melatonin pre-treatment for 24 hrs 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

  14. 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.

  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. 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

  17. A Bayesian model of category-specific emotional brain responses.

    PubMed

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

    2015-04-01

    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

  18. [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

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

    PubMed Central

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

    2014-01-01

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

  20. 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.

  1. 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…

  2. Kidney Modeling molecular dockingBrain Analysis Visualization

    E-print Network

    Buyya, Rajkumar

    in research on kidney physiology. A large number of mathematical models and resources describing aspects1 Researcher Kidney Modeling molecular dockingBrain Analysis Visualization e-Research Platform User Environment Globus Condor Alchemi UNICORE XGrid PBS ResearcherResearcher Kidney Modeling molecular docking

  3. Bayes in the Brain--On Bayesian Modelling in Neuroscience

    E-print Network

    Lin, Kevin K.

    Bayes in the Brain--On Bayesian Modelling in Neuroscience Matteo Colombo and Peggy Serie`s ABSTRACT According to agrowing trend intheoretical neuroscience, the humanperceptual system is akin to a Bayesian are Bayesian models used in theoretical neuroscience? (ii) From the use of Bayesian models in theoretical

  4. 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

  5. 5'-adenosine monophosphate-induced hypothermia attenuates brain ischemia/reperfusion injury in a rat model by inhibiting the inflammatory response.

    PubMed

    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

  6. 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.

  7. 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

  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. 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

  10. 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.

  11. 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-1? 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

  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. Activation of the phosphatidylinositol 3-kinase pathway plays important roles in reduction of cerebral infarction by cilnidipine.

    PubMed

    Son, Jeong-Woo; Choi, Hojin; Yoo, Arum; Park, Hyun-Hee; Kim, Young-Seo; Lee, Kyu-Yong; Lee, Young Joo; Koh, Seong-Ho

    2015-10-01

    Cerebral infarction causes permanent neuronal loss inducing severe morbidity and mortality. Because hypertension is the main risk factor for cerebral infarction and most patients with hypertension take antihypertensive drugs daily, the neuroprotective effects and mechanisms of anti-hypertensive drugs need to be investigated. Cilnidipine, a long-acting, new generation 1,4-dihydropyridine inhibitor of both L- and N-type calcium channels, was reported to reduce oxidative stress. In this study, we investigated whether cilnidipine has therapeutic effects in an animal model of cerebral infarction. After determination of the most effective dose of cilnidipine, a total of 128 rats were subjected to middle cerebral artery occlusion. Neurobehavioral function test and brain MRI were performed, and rats with similar sized infarcts were randomized to either the cilnidipine group or the control group. Cilnidipine treatment was performed with reperfusion after 2-h occlusion. Western blots and immunohistochemistry were also performed after 24-h occlusion. Initial infarct volume on diffusion-weighted MRI was not different between the cilnidipine group and the control group; however, fluid-attenuated inversion recovery MRI at 24 h showed significantly reduced infarct volume in the cilnidipine group compared with the control group. Cilnidipine treatment significantly decreased the number of triphosphate nick end labeling-positive cells compared to the control group. Western blot and immunohistochemistry showed increased expression of phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase-3?, and Bcl-2 and decreased expression of Bax and cleaved caspase-3. These results suggest that cilnidipine, which is used for the treatment of hypertension, has neuroprotective effects in the ischemic brain through activation of the PI3K pathway. We investigated whether cilnidipine has neuroprotective effects on ischemic stroke in an animal model. We have demonstrated that the neuroprotective effect of cilnidipine is associated with the activation of the PI3K pathway. Considering the daily use of antihypertensive drugs for patients with hypertension, cilnidipine could be beneficial for patients with ischemic stroke. PMID:26222278

  14. 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

  15. Kidney Modeling molecular dockingBrain Analysis Visualization

    E-print Network

    Melbourne, University of

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

  16. Predictive modeling of neuroanatomic structures for brain atrophy detection

    NASA Astrophysics Data System (ADS)

    Hu, Xintao; Guo, Lei; Nie, Jingxin; Li, Kaiming; Liu, Tianming

    2010-03-01

    In this paper, we present an approach of predictive modeling of neuroanatomic structures for the detection of brain atrophy based on cross-sectional MRI image. The underlying premise of applying predictive modeling for atrophy detection is that brain atrophy is defined as significant deviation of part of the anatomy from what the remaining normal anatomy predicts for that part. The steps of predictive modeling are as follows. The central cortical surface under consideration is reconstructed from brain tissue map and Regions of Interests (ROI) on it are predicted from other reliable anatomies. The vertex pair-wise distance between the predicted vertex and the true one within the abnormal region is expected to be larger than that of the vertex in normal brain region. Change of white matter/gray matter ratio within a spherical region is used to identify the direction of vertex displacement. In this way, the severity of brain atrophy can be defined quantitatively by the displacements of those vertices. The proposed predictive modeling method has been evaluated by using both simulated atrophies and MRI images of Alzheimer's disease.

  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 scaling—in addition to several summary statistics, including the mean clustering coefficient, the shortest path-length, and the network diameter. The models are investigated in a progressive, branching sequence, aimed at capturing different elements thought to be important in the brain, and range from simple random and regular networks, to models that incorporate specific growth rules and constraints. We find that synthetic models that constrain the network nodes to be physically embedded in anatomical brain regions tend to produce distributions that are most similar to the corresponding measurements for the brain. We also find that network models hardcoded to display one network property (e.g., assortativity) do not in general simultaneously display a second (e.g., hierarchy). This relative independence of network properties suggests that multiple neurobiological mechanisms might be at play in the development of human brain network architecture. Together, the network models that we develop and employ provide a potentially useful starting point for the statistical inference of brain network structure from neuroimaging data. PMID:24675546

  18. Resolving structural variability in network models and the brain.

    PubMed

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

    2014-03-01

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

  19. 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 ?-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

  20. 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

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

    PubMed

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

    2015-07-01

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

  2. Constitutive model for brain tissue under finite compression.

    PubMed

    Laksari, Kaveh; Shafieian, Mehdi; Darvish, Kurosh

    2012-02-23

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

  3. 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 400 mg/kg b wt. 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

  4. 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

  5. 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.

  6. Modeling the blood–brain barrier using stem cell sources

    PubMed Central

    2013-01-01

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

  7. 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 µL 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

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

    PubMed Central

    Grönros, Julia; Kiss, Attila; Palmér, 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

  9. Restoring blood-brain barrier P-glycoprotein reduces brain amyloid-beta in a mouse model of Alzheimer's disease.

    PubMed

    Hartz, Anika M S; Miller, David S; Bauer, Björn

    2010-05-01

    Reduced clearance of amyloid-beta (Abeta) from brain partly underlies increased Abeta brain accumulation in Alzheimer's disease (AD). The mechanistic basis for this pathology is unknown, but recent evidence suggests a neurovascular component in AD etiology. We show here that the ATP-driven pump, P-glycoprotein, specifically mediates efflux transport of Abeta from mouse brain capillaries into the vascular space, thus identifying a critical component of the Abeta brain efflux mechanism. We demonstrate in a transgenic mouse model of AD [human amyloid precursor protein (hAPP)-overexpressing mice; Tg2576 strain] that brain capillary P-glycoprotein expression and transport activity are substantially reduced compared with wild-type control mice, suggesting a mechanism by which Abeta accumulates in the brain in AD. It is noteworthy that dosing 12-week-old, asymptomatic hAPP mice over 7 days with pregnenolone-16alpha-carbonitrile to activate the nuclear receptor pregnane X receptor restores P-glycoprotein expression and transport activity in brain capillaries and significantly reduces brain Abeta levels compared with untreated control mice. Thus, targeting intracellular signals that up-regulate blood-brain barrier P-glycoprotein in the early stages of AD has the potential to increase Abeta clearance from the brain and reduce Abeta brain accumulation. This mechanism suggests a new therapeutic strategy in AD. PMID:20101004

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

    PubMed Central

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

    2010-01-01

    Reduced clearance of amyloid-? (A?) from brain partly underlies increased A? brain accumulation in Alzheimer's disease (AD). The mechanistic basis for this pathology is unknown, but recent evidence suggests a neurovascular component in AD etiology. We show here that the ATP-driven pump, P-glycoprotein, specifically mediates efflux transport of A? from mouse brain capillaries into the vascular space, thus identifying a critical component of the A? brain efflux mechanism. We demonstrate in a transgenic mouse model of AD [human amyloid precursor protein (hAPP)-overexpressing mice; Tg2576 strain] that brain capillary P-glycoprotein expression and transport activity are substantially reduced compared with wild-type control mice, suggesting a mechanism by which A? accumulates in the brain in AD. It is noteworthy that dosing 12-week-old, asymptomatic hAPP mice over 7 days with pregnenolone-16?-carbonitrile to activate the nuclear receptor pregnane X receptor restores P-glycoprotein expression and transport activity in brain capillaries and significantly reduces brain A? levels compared with untreated control mice. Thus, targeting intracellular signals that up-regulate blood-brain barrier P-glycoprotein in the early stages of AD has the potential to increase A? clearance from the brain and reduce A? brain accumulation. This mechanism suggests a new therapeutic strategy in AD. PMID:20101004

  11. 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…

  12. 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

  13. 3D SEGMENTATION OF RODENT BRAIN STRUCTURES USING ACTIVE VOLUME MODEL WITH SHAPE PRIORS

    E-print Network

    Huang, Junzhou

    3D SEGMENTATION OF RODENT BRAIN STRUCTURES USING ACTIVE VOLUME MODEL WITH SHAPE PRIORS Shaoting of the rodent brain from MR images, and the proposed method performed better than the original AVM. Index Terms-- Segmentation, deformable models, Ac- tive Volume Model, Active Shape Model, Shape prior, rodent brain 1

  14. 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 1? was significantly decreased compared with controls. Further analysis revealed that hNSCs poorly withstand physiological shear stress, and their ability is further decreased following fucosylation. In addition, fhNSCs demonstrated a higher frequency of cellular aggregate formation as well as a tendency for removal of fucose from the cell surface. In summary, our findings suggest that the behavior of hNSCs in circulation is different from that observed with other cell types and that, at least for stroke, intravenous administration is a suboptimal route, even when the in vitro rolling ability of hNSCs is optimized by enforced fucosylation. PMID:24396034

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

    PubMed Central

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

    2013-01-01

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

  17. 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

  18. 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

  19. 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

  20. Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

    PubMed Central

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

    2011-01-01

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

  1. 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 ? (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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2015-08-01

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

  4. Aetiological considerations and risk factors for multi-infarct dementia.

    PubMed Central

    Meyer, J S; McClintic, K L; Rogers, R L; Sims, P; Mortel, K F

    1988-01-01

    One hundred and seventy five multi-infarct dementia (MID) patients were evaluated for risk factors for stroke as well as for the types of cerebrovascular lesions that were present. The incidence of associated risk factors for stroke were as follows: hypertension (66%), heart disease (47%), cigarette smoking (37%), diabetes mellitus (20%), moderate alcohol consumption (19%) and hyperlipidaemia (21%). The most frequently occurring type of lesions were multiple lacunar infarctions of the brain (43%). These were combined with other types of stroke in an additional 21%. Atherosclerotic occlusive disease of the carotid and vertebrobasilar arteries occurred alone in 18% and was associated with other types of stroke in another 25%. Embolic cerebral infarctions were present alone in 8% and were combined with other types of stroke in 15%. MID was more frequent in men (62%) than women (p less than 0.002). Mean bihemispheric gray matter cerebral blood flow (CBF) values showed a fluctuating course and when results were pooled and compared between different types of MID, extracranial occlusive disease and/or multiple lacunar infarctions resulted in lowest CBF values. The location of cerebral infarctions was more importantly related to cognitive impairments than was the total volume of infarcted brain. Mortality rates among 125 MID patients followed for 31 months has been 5%. Correct clinical classification of the types of cerebrovascular lesions was confirmed in three necropsied cases. PMID:3221215

  5. Theoretic Impact of Infarct Compliance on Left Ventricular Function

    PubMed Central

    Pilla, James J.; Gorman, Joseph H.; Gorman, Robert C.

    2011-01-01

    Background After coronary occlusion, the infarct region loses contractile function immediately and then undergoes a progressive healing process. This causes complex and time-dependent changes in infarct material properties that have not been well described experimentally. We used a theoretic approach to assess how infarct compliance effects left ventricular (LV) size and function after myocardial infarction. Methods We used a closed-loop lumped-parameter model of the ovine cardiovascular system developed to study the effect of infarct size and compliance on cardiovascular function. The time-varying LV function was partitioned into infarct and noninfarct regions where the parameters of each could be adjusted separately. The model incorporated an adaptive compensatory mechanism to maintain stroke volume by varying the total blood volume. Results For the preinfarction heart, the model produced pressure, volume, and functional results that were consistent with normal values for large animals. When infarcts of progressively larger size (5% to 25%) were introduced and stroke volume adaptation was permitted, the model produced pressure, volume, and functional results that were consistent with postinfarction values measured experimentally in large animals. Infarct size was held at 20% as infarct compliance decreased from 7 to 1 mL/mm Hg. This stiffening of the infarct resulted in reduced LV end-diastolic volume (200 to 60 mL), increased ejection fraction (0.10 to 0.30), and reduced LV end-diastolic pressure (14 to 5 mm Hg). Estimated LV oxygen consumption was also improved in the stiffer infracts. Conclusion Stiffer infarcts are associated with less LV dilatation, reduced filling pressures and better global LV function. PMID:19231393

  6. 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

  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. Rapamycin up-regulation of autophagy reduces infarct size and improves outcomes in both permanent MCAL, and embolic MCAO, murine models of stroke

    PubMed Central

    2014-01-01

    Background and purpose The role of autophagy in response to ischemic stroke has been confusing with reports that both enhancement and inhibition of autophagy decrease infarct size and improve post-stroke outcomes. We sought to clarify this by comparing pharmacologic modulation of autophagy in two clinically relevant murine models of stroke. Methods We used rapamycin to induce autophagy, and chloroquine to block completion of autophagy, by treating mice immediately after stroke and at 24 hours post-stroke in two different models; permanent Middle Cerebral Artery Ligation (MCAL), which does not allow for reperfusion of distal trunk of middle cerebral artery, and Embolic Clot Middle Cerebral Artery Occlusion (eMCAO) which allows for a slow reperfusion similar to that seen in most human stroke patients. Outcome measures at 48 hours post-stroke included infarct size analysis, behavioral assessment using Bederson neurological scoring, and survival. Results Chloroquine treatment reduced the lesion size by approximately 30% and was significant only in the eMCAO model, where it also improved the neurological score, but did not increase survival. Rapamycin reduced lesion size by 44% and 50% in the MCAL and eMCAO models, respectively. Rapamycin also improved the neurological score to a greater degree than chloroquine and improved survival. Conclusions While both inhibition and enhancement of autophagy by pharmacological intervention decreased lesion size and improved neurological scores, the enhancement with rapamycin showed a greater degree of improvement in outcomes as well as in survival. The protective action seen with chloroquine may be in part due to off-target effects on apoptosis separate from blocking lysosomal activity in autophagy. We conclude pharmacologic induction of autophagy is more advantageous than its blockade in physiologically-relevant permanent and slow reperfusion stroke models. PMID:24991402

  9. 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.

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

    PubMed

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

    2014-04-18

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

  11. 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

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

    PubMed

    Vives, M A; Bonet, L A; Soriano, J R; Lalaguna, L A; Sáez, A O; de Arellano, A R; Pérez, 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

  13. 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

  14. Avoiding Boltzmann Brain domination in holographic dark energy models

    E-print Network

    Horvat, R

    2015-01-01

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

  15. Avoiding Boltzmann Brain domination in holographic dark energy models

    E-print Network

    R. Horvat

    2015-09-14

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

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

    E-print Network

    Frey, Pascal

    Brain Shift Correction Based on a Boundary Element Biomechanical Model with Different Material to inaccuracy due to intraoperative changes like brain shift or tumor resection. In order to correct for these deformations a biomechanical model of the brain is proposed. Not only elastic tissues, but also fluids

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

    E-print Network

    Durikovic, Roman

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

  18. Design and Integration of Partial Brain Models Using Hierarchical Cooperative CoEvolution

    E-print Network

    Trahanias, Panos

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

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

    E-print Network

    Golland, Polina

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

  20. 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.

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

    E-print Network

    Batte, David Allan

    1997-01-01

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

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

    E-print Network

    Atalar, Ergin

    In Vivo Magnetic Resonance Imaging of Mesenchymal Stem Cells in Myocardial Infarction Dara L-MSCs) in a swine myocardial infarction (MI) model. Methods and Results--Adult farm pigs (n 5) were subjected;107:2290-2293.) Key Words: magnetic resonance imaging myocardial infarction cells contrast media Because

  3. 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

  4. 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

  5. Fluid-percussion–induced 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 45–50 min. PMID:20725070

  6. 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

  7. 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.

  8. Longitudinal diffusion tensor imaging in a rat brain glioma model.

    PubMed

    Lope-Piedrafita, Silvia; Garcia-Martin, Maria L; Galons, Jean-Philippe; Gillies, Robert J; Trouard, Theodore P

    2008-10-01

    In order to investigate the properties of water motion within and around brain tumors as a function of tumor growth, longitudinal diffusion tensor imaging (DTI) was carried out in a rat brain glioma (C6) model. As tumors grew in size, significant anisotropy of water diffusion was seen both within and around the tumor. The tissue water surrounding the tumor exhibited high planar anisotropy, as opposed to the linear anisotropy normally seen in white matter, indicating that cells were experiencing stress in a direction normal to the tumor border. When tumors were sufficiently large, significant anisotropy was also seen within the tumor because of longer-range organization of cancer cells within the tumor borders. These findings have important implications for diffusion-weighted MRI experiments examining tumor growth and response to therapy. PMID:18470959

  9. 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

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

    PubMed

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

    2012-01-01

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

  11. 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

  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. Inhibition of immunoproteasome reduces infarction volume and attenuates inflammatory reaction in a rat model of ischemic stroke

    PubMed Central

    Chen, X; Zhang, X; Wang, Y; Lei, H; Su, H; Zeng, J; Pei, Z; Huang, R

    2015-01-01

    The detailed knowledge about the contribution of immunoproteasome to the neuroinflammation in ischemic stroke is still not available. The immunoreactivity of low molecular mass peptide 2 (LMP2) and low molecular mass peptide 7 (LMP7) was evident in the ipsilateral ischemic cerebral cortex and striatum following transient middle cerebral artery occlusion (MCAO). Both LMP2 and LMP7 increased as early as 4?h after the MCAO, further increased at 24?h, peaked at 72?h and decreased 7 days later. LMP2 and LMP7 were mainly present in astrocytes and microglia/macrophage cells, respectively. LMP2 knockdown by shRNA (short hairpin RNA) markedly reduced the levels of LMP2 and LMP7 protein and caused 75.5 and 78.6% decrease in the caspase-like (C-L) and chymotrypsin-like (CT-L) activities, respectively. Compared with cont-shRNA group (39.7%, infarction volumes/total ipsilateral hemisphere), the infarction volumes were reduced to 22.5% in LMP2-shRNA group. Additionally, LMP2 knockdown significantly reduced activated astrocytes and microglia, the expression nuclear factor kappa B (NF-?B) p65, tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?) and caused less accumulation of ischemia-induced protein ubiquitination compared with MG132. These findings demonstrate that inhibition of LMP2 significantly attenuates inflammatory reaction and offers neuroprotection against focal cerebral ischemia in rats, suggesting that selective immunoproteasome inhibitors may be a promising strategy for stroke treatment. PMID:25633295

  14. Sinoatrial Node Reentry in a Canine Chronic Left Ventricular Infarct Model: The Role of Intranodal Fibrosis and Heterogeneity of Refractoriness

    PubMed Central

    Glukhov, Alexey V.; Hage, Lori T.; Hansen, Brian J.; Pedraza-Toscano, Adriana; Vargas-Pinto, Pedro; Hamlin, Robert L.; Weiss, Raul; Carnes, Cynthia A.; Billman, George E.; Fedorov, Vadim V.

    2014-01-01

    Background Reentrant arrhythmias involving the sinoatrial node (SAN), namely, SAN reentry, remain one of the most intriguing enigmas of cardiac electrophysiology. The goal of the present study was to elucidate the mechanism of SAN micro-reentry in canine hearts with post myocardial infarction (MI) structural remodeling. Methods and Results In vivo, Holter monitoring revealed ventricular arrhythmias and SAN dysfunctions in post left ventricular MI (6–15 wks) dogs (n=5) compared to control dogs (n=4). In vitro, high resolution near-infrared optical mapping of intramural SAN activation was performed in coronary perfused atrial preparations from MI (n=5) and controls (n=4). Both SAN macro- (slow-fast; 16–28 mm) and micro-reentries (1–3 mm) were observed in 60% of the MI preparations during moderate autonomic stimulation (acetylcholine (0.1 µM) or isoproterenol (0.01-0.1 µM)) after termination of atrial tachypacing (5–8 Hz), a finding not seen in controls. The autonomic stimulation induced heterogeneous changes in the SAN refractoriness; thus, competing atrial and/or SAN pacemaker waves could produce unidirectional blocks and initiate intranodal micro-reentries. The micro-reentry pivot waves were anchored to the longitudinal block region and produced both tachycardia and paradoxical bradycardia (due to exit block), despite an atrial ECG morphology identical to regular sinus rhythm. Intranodal longitudinal conduction blocks coincided with interstitial fibrosis strands that were exaggerated in the MI SAN pacemaker complex (fibrosis density 37±7% MI vs. 23±6% control, P<0.001). Conclusions Both tachy- and bradyarrhythmias can result from SAN micro-reentries. Post-infarction remodeling, including increased intranodal fibrosis and heterogeneity of refractoriness, provides substrates for SAN reentry. PMID:23960214

  15. 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; Araújo, Ana; Esteves, Tiago; Laundos, Tiago L; Freire, Ana G; Quelhas, Pedro; Pinto-do-Ó, Perpétua; 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    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. 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

  19. Apocynum venetum leaf extract attenuates disruption of the blood-brain barrier and upregulation of matrix metalloproteinase-9/-2 in a rat model of cerebral ischemia-reperfusion injury.

    PubMed

    Xiang, Jun; Lan, Rui; Tang, Yu-Ping; Chen, Yi-Ping; Cai, Ding-Fang

    2012-08-01

    We investigated the neuroprotective effects of Apocynum venetum leaf extract (AVLE) on a rat model of cerebral ischemia-reperfusion injury and explored the underlying mechanisms. Rats were randomly divided into five groups: sham, ischemia-reperfusion, AVLE125, AVLE250, and AVLE500. Cerebral ischemia was induced by 1.5 h of occlusion of the middle cerebral artery. Cerebral infarct area was measured by tetrazolium staining at 24 and 72 h after reperfusion, and neurological function was evaluated at 24, 48 and 72 h after reperfusion. Pathological changes on the ultrastructure of the blood-brain barrier (BBB) were observed by transmission electron microscopy. BBB permeability was assessed by detecting leakage of Evan's blue (EB) dye in brain tissue. The expression and activities of matrix metalloproteinase (MMP)-9/-2 were measured by western blot analyses and gelatin zymography at 24 h after reperfusion. AVLE (500 mg/kg/day) significantly reduced cerebral infarct area, improved recovery of neurological function, relieved morphological damage to the BBB, reduced water content and EB leakage in the brain, and downregulated the expression and activities of MMP-9/-2. These findings suggest that AVLE protects against cerebral ischemia-reperfusion-induced injury by alleviating BBB disruption. This action may be due to its inhibitory effects on the expression and activities of MMP-9/-2. PMID:22592643

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

    E-print Network

    Gao, Jianbo

    ORIGINAL ARTICLE Assessing a signal model and identifying brain activity from fMRI data is to develop simple and reliable methods to correlate brain regions with functionality. In this paper, we brain activity from fMRI data. We perform three tasks: (a) Estimating noise level from experimental f

  1. Distributed Brain Modelling by means of Hierarchical Collaborative CoEvolution

    E-print Network

    Trahanias, Panos

    Distributed Brain Modelling by means of Hierarchical Collaborative CoEvolution Michail Maniadakis-based agent structures are employed to represent distinct brain areas. We in- troduce a Hierarchical Collaborative CoEvolutionary (HCCE) approach to design autonomous, yet cooper- ating agents. Thus, partial brain

  2. 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

  3. 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

  4. 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.

  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. 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

  7. 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

  8. Comparison of conventional risk factors in middle-aged versus elderly diabetic and nondiabetic patients with myocardial infarction: prediction with decision–analytic 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 decision–analytic 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 47.9–84.0% and 56.3–93.0%, 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

  9. 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

  10. A mathematical model for brain tumor response to radiation therapy

    PubMed Central

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

    2013-01-01

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

  11. 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

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

    PubMed

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

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

    PubMed

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

    2004-05-01

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

  14. 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: 4.8±5.7 mm). 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 164.6±11.0 ms during premature stimulation and 190.7±20.4 ms 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

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

    PubMed Central

    Arbib, Michael; Ganesh, Varsha; Gasser, Brad

    2014-01-01

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

  16. On the unimportance of constitutive models in computing brain deformation for image-guided surgery

    PubMed Central

    Wittek, Adam; Hawkins, Trent; Miller, Karol

    2011-01-01

    Imaging modalities that can be used intra-operatively do not provide sufficient details to confidently locate the abnormalities and critical healthy areas that have been identified from high-resolution pre-operative scans. However, as we have shown in our previous work, high quality pre-operative images can be warped to the intra-operative position of the brain. This can be achieved by computing deformations within the brain using a biomechanical model. In this paper, using a previously developed patient-specific model of brain undergoing craniotomy-induced shift, we conduct a parametric analysis to investigate in detail the influences of constitutive models of the brain tissue. We conclude that the choice of the brain tissue constitutive model, when used with an appropriate finite deformation solution, does not affect the accuracy of computed displacements, and therefore a simple linear elastic model for the brain tissue is sufficient. PMID:18246376

  17. 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

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

    PubMed Central

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

    2007-01-01

    Introduction A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine. Materials and methods Rats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1, 3.7 or 7.3 mg.kg?1 of fluvoxamine. Analysis With increasing dose a disproportional increase in brain concentrations was observed. The kinetics of brain distribution was estimated by simultaneous analysis of plasma, free brain ECF and total brain tissue concentrations. The PK model consists of three compartments for fluvoxamine concentrations in plasma in combination with a catenary two compartment model for distribution into the brain. In this catenary model, the mass exchange between a shallow perfusion-limited and a deep brain compartment is described by a passive diffusion term and a saturable active efflux term. Results The model resulted in precise estimates of the parameters describing passive influx into (kin) of 0.16 min?1 and efflux from the shallow brain compartment (kout) of 0.019 min?1 and the fluvoxamine concentration at which 50% of the maximum active efflux (C50) is reached of 710 ng.ml?1. The proposed brain distribution model constitutes a basis for precise characterization of the PK–PD correlation of fluvoxamine by taking into account the non-linearity in brain distribution. PMID:17710515

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

    PubMed

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

    2014-01-01

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

  20. 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.

  1. Modeling Brain Responses in an Arithmetic Working Memory Task

    NASA Astrophysics Data System (ADS)

    Hamid, Aini Ismafairus Abd; Yusoff, Ahmad Nazlim; Mukari, Siti Zamratol-Mai Sarah; Mohamad, Mazlyfarina; Manan, Hanani Abdul; Hamid, Khairiah Abdul

    2010-07-01

    Functional magnetic resonance imaging (fMRI) was used to investigate brain responses due to arithmetic working memory. Nine healthy young male subjects were given simple addition and subtraction instructions in noise and in quiet. The general linear model (GLM) and random field theory (RFT) were implemented in modelling the activation. The results showed that addition and subtraction evoked bilateral activation in Heschl's gyrus (HG), superior temporal gyrus (STG), inferior frontal gyrus (IFG), supramarginal gyrus (SG) and precentral gyrus (PCG). The HG, STG, SG and PCG activate higher number of voxels in noise as compared to in quiet for addition and subtraction except for IFG that showed otherwise. The percentage of signal change (PSC) in all areas is higher in quiet as compared to in noise. Surprisingly addition (not subtraction) exhibits stronger activation.

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

    ERIC Educational Resources Information Center

    Bump, Jerome

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

  3. 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…

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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, 60Gy with charged particles. In 60Gy group, brain necrosis that recapitulates human disease was detected after 8 months. PMID:26260449

  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. 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

  12. 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

  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. 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.

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

    PubMed Central

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

    2014-01-01

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

  16. 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

  17. 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

  18. [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

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

    E-print Network

    Piatkowski, Jakub Przemyslaw

    2014-06-27

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

  20. 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

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

    PubMed

    Galimzianova, Alfiia; Pernuš, Franjo; Likar, Boštjan; Špiclin, Žiga

    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

  2. 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

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Moualhi, Wafa; Ezzeddine, Zagrouba

    2015-02-01

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

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

    PubMed

    Weston, Eleanor M; Lister, Adrian M

    2009-05-01

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

  6. 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

  7. 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

  8. [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

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

    PubMed

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

    2015-06-01

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

  10. 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

  11. 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.

  12. 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.

  13. 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.

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

    PubMed Central

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

    2011-01-01

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

  15. Palatal tremor as a manifestation of epilepsia partialis continua caused by acute precentral gyral infarction.

    PubMed

    Jung, Hyun-Jung; Choi, Seong-Min; Lee, Jong-Kyung; Lee, Seung-Han; Kim, Byeong C

    2013-10-01

    We describe a patient with palatal tremor (PT) as a manifestation of focal seizure caused by acute cortical infarction. Brain MRI showed acute infarction in the left precentral gyrus without evidence of brainstem lesions or hypertrophy of the inferior olivary nucleus. We discuss the differences between our patient and previous reports of symptomatic PT and the mechanisms involved in the development of PT associated with cortical lesions. PMID:23647708

  16. Neural Modeling n The brain and its neurons

    E-print Network

    Olufsen, Mette Sofie

    ): Integration of sensory perception and motor control n Hypothalamus: Links the nervous system to the endocrine system via the pituitary gland #12;Brain regions n Pituitary gland: Part of the endocrine system in the cortex n Ventricles:Cerebrospinal fluid is produced in the ventricular system. Protects the brain from

  17. Efficient Multilevel Brain Tumor Segmentation with Integrated Bayesian Model Classification

    E-print Network

    Krovi, Venkat

    algorithm, and apply the technique to the task of detecting and segmenting brain tumor and edema are the tumor itself, comprising a necrotic (dead) part and an active part, the edema or swelling in the nearby. On the right, we outline the different heterogeneous regions of the brain tumor and label them as edema, active

  18. 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

  19. Myocardin-related transcription factor-A-overexpressing bone marrow stem cells protect cardiomyocytes and alleviate cardiac damage in a rat model of acute myocardial infarction.

    PubMed

    Zhong, Ze; Hu, Jia-Qing; Wu, Xin-Dong; Sun, Yong; Jiang, Jun

    2015-09-01

    Myocardin-related transcription factor-A (MRTF-A) can transduce biomechanical and humoral signals, which can positively modulate cardiac damage induced by acute myocardial infarction (AMI). In the clinic, bone marrow stem cell (BMSC) therapy is being increasingly utilized for AMI; however, the effects of BMSC transplantation remain to be optimized. Therefore, a novel strategy to enhance BMSC?directed myocardial repair is particularly important. The present study was performed to assess the efficacy of MRTF?A-overexpressing BMSCs in a rat model of AMI. Primary cardiomyocytes were prepared from neonatal Sprague-Dawley rats and BMSCs were isolated from male Sprague-Dawley rats (aged 8-12 weeks). Annexin V-phycoerythrin/7-actinomycin D staining was used to evaluate BMSC and cardiomyocyte survival after exposure to hydrogen peroxide in vitro. B-cell lymphoma 2 (Bcl-2) protein expression was measured by flow cytometric and western blot analyses. The effects of MRTF-A?overexpressing BMSCs in a rat model of AMI were investigated by hematoxylin and eosin staining and western blot analysis of Bcl-2 expression in myocardial tissue sections. MRTF-A enhanced the migration of BMSCs, and overexpression of MRTF-A in BMSCs prevented hydrogen peroxide-induced apoptosis in primary cardiomyocytes ex vivo. In addition, co-culture of cardiomyocytes with MRTF?A-overexpressing BMSCs inhibited hydrogen peroxide-induced apoptosis and the enhanced expression of Bcl-2. Furthermore, in vivo, enhanced cell survival was observed in the MRTF-A-modified BMSC group compared with that in the control group. These observations indicated that MRTF-A-overexpressing BMSCs have the potential to exert cardioprotective effects against hydrogen peroxide-induced injury and that treatment with MRTF?A?modified BMSCs is able to reverse cardiac dysfunction after AMI. PMID:26135208

  20. 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

  1. 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…

  2. Submitted to Neuroimage, April 2004 Variational, geometric and statistical methods for modeling brain anatomy

    E-print Network

    Faugeras, Olivier

    brain anatomy and function Olivier Faugeras, Geoffray Adde, Guillaume Charpiat, Christophe Chefd of models for studying brain anatomy and function. We start with the problem of reconstructing sourcesMRI to the anatomy. The paper ends with a dis- cussion of a new theory of random shapes that may prove useful

  3. Structural Modelling of the Whole Head for Electrical Impedance Imaging and Deep Brain Stimulation

    E-print Network

    Duffy, Ken

    models of the whole human head to simulate the dynamic electrical field distribution during deep brain this electrical stimulation acts on neuronal activity is unclear. Experimental in situ investigation the effects of DBS in a defined region of the brain. To address this problem we have adapted a bio imaging

  4. 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.

  5. A General Purpose Brain Model For Developmental Robots: The Spatial Brain for Any Temporal Lengths

    E-print Network

    @cse.msu.edu In fact, they all correspond to an "skull-open approach" to the brain -- it is the human teacher who's" internal representation through its open "skull". Among many limitations of such "skull-open" approaches development. It cannot explain the following process: With his "skull closed," a child autonomously interacts

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

    E-print Network

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

    1992-01-01

    transport systems for nucleic acid precursors. Biochim Biophys Acta 394:211-21 9, 1975. Dehouck, M.-P.; Meresse, S.; Delorme, P.; Fruchart, J.-C.; and Cecchelli, R. An easier, reproducible, and mass-production method to study the blood- brain barrier...

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

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

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

  8. 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.

  9. 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

  10. Highlighting the structure-function relationship of the brain with the Ising model and graph theory.

    PubMed

    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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Brain Slices as Models for Neurodegenerative Disease and Screening Platforms to Identify Novel Therapeutics

    PubMed Central

    Cho, Seongeun; Wood, Andrew; Bowlby, Mark R

    2007-01-01

    Recent improvements in brain slice technology have made this biological preparation increasingly useful for examining pathophysiology of brain diseases in a tissue context. Brain slices maintain many aspects of in vivo biology, including functional local synaptic circuitry with preserved brain architecture, while allowing good experimental access and precise control of the extracellular environment, making them ideal platforms for dissection of molecular pathways underlying neuronal dysfunction. Importantly, these ex vivo systems permit direct treatment with pharmacological agents modulating these responses and thus provide surrogate therapeutic screening systems without recourse to whole animal studies. Virus or particle mediated transgenic expression can also be accomplished relatively easily to study the function of novel genes in a normal or injured brain tissue context. In this review we will discuss acute brain injury models in organotypic hippocampal and co-culture systems and the effects of pharmacological modulation on neurodegeneration. The review will also cover the evidence of developmental plasticity in these ex vivo models, demonstrating emergence of injury-stimulated neuronal progenitor cells, and neurite sprouting and axonal regeneration following pathway lesioning. Neuro-and axo-genesis are emerging as significant factors contributing to brain repair following many acute and chronic neurodegenerative disorders. Therefore brain slice models may provide a critical contextual experimental system to explore regenerative mechanisms in vitro. PMID:18615151

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

    PubMed Central

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

    2012-01-01

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

  17. Multi-modal approach for investigating brain and behavior changes in an animal model of traumatic brain injury.

    PubMed

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

    2013-06-01

    Use of novel approaches in imaging modalities is needed for enhancing diagnostic and therapeutic outcomes of persons with a traumatic brain injury (TBI). This study explored the feasibility of using functional magnetic resonance imaging (fMRI) in conjunction with behavioral measures to target dynamic changes in specific neural circuitries in an animal model of TBI. Wistar rats were randomly assigned to one of two groups (traumatic brain injury/sham operation). TBI rats were subjected to the closed head injury (CHI) model. Any observable motor deficits and cognitive deficits associated with the injury were measured using beam walk and Morris water maze tests, respectively. fMRI was performed to assess the underlying post-traumatic cerebral anatomy and function in acute (24 hours after the injury) and chronic (7 and 21 days after the injury) phases. Beam walk test results detected no significant differences in motor deficits between groups. The Morris water maze test indicated that cognitive deficits persisted for the first week after injury and, to a large extent, resolved thereafter. Resting state functional connectivity (rsFC) analysis detected initially diminished connectivity between cortical areas involved in cognition for the TBI group; however, the connectivity patterns normalized at 1 week and remained so at the 3 weeks post-injury time point. Taken together, we have demonstrated an objective in vivo marker for mapping functional brain changes correlated with injury-associated cognitive behavior deficits and offer an animal model for testing potential therapeutic interventions options. PMID:23294038

  18. Computational modeling of primary blast effects on the human brain

    E-print Network

    Nyein, Michelle K. (Michelle Kyaw)

    2013-01-01

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

  19. Generative models of brain connectivity for population studies

    E-print Network

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

    2012-01-01

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

  20. Weighted Functional Brain Network Modeling via Network Filtration

    E-print Network

    Chung, Moo K.

    the local and global differences of the brain networks of 24 attention deficit hyperactivity disorder (ADHD), 26 autism spectrum disorder (ASD) and 11 pediatric control (PedCon) children ob- tained through

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

    PubMed Central

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

    2012-01-01

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

  2. Effect of Prolonged Moderate Exercise on the Changes of Nonneuronal Cells in Early Myocardial Infarction

    PubMed Central

    Rinaldi, Barbara; Guida, Francesca; Furiano, Anna; Donniacuo, Maria; Luongo, Livio; Gritti, Giulia; Urbanek, Konrad; Messina, Giovanni; Maione, Sabatino; Rossi, Francesco; de Novellis, Vito

    2015-01-01

    Myocardial infarction (MI) is one of the leading causes of death in developed countries and it is characterized by several associated symptomatologies and poor quality of life. Recent data showed a possible interaction between infarction and brain inflammation and activity. Previous studies have demonstrated the beneficial effect of exercise training on deterioration in cardiac function after MI. In this study we analyzed in sedentary and trained rats the microglia and astrocytes 48 hours after MI in PVN, thalamus, prefrontal cortex, and hippocampus through immunofluorescence approach. We found significant changes in specific microglia phenotypes in the brain areas analyzed together with astrocytes activation. Prolonged exercise normalized these morphological changes of microglia and astrocytes in the prefrontal cortex, hippocampus, and thalamus but not in the PVN. Our data suggest that there is an early brain reaction to myocardial infarction induction, involving nonneuronal cells, that is attenuated by the prolonged exercise. PMID:26266053

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

    PubMed Central

    Tait, Matthew J.; Saadoun, Samira; Bell, B. Anthony; Verkman, Alan S.; Papadopoulos, Marios C.

    2010-01-01

    We investigated the role of the glial water channel protein aquaporin-4 in brain edema in a mouse model of subarachnoid haemorrhage in which thirty microliters of blood was injected into the basal cisterns. Brain water content, intracranial pressure and neurological score were compared in wildtype and aquaporin-4 null mice. We also measured blood-brain barrier permeability, and the osmotic permeability of the glia limitans, one of the routes of edema elimination. Wildtype and aquaporin-4 null mice had comparable baseline brain water content, intracranial pressure and neurological score. At six hours after blood injection, aquaporin-4 null mice developed more brain swelling than wildtype mice. Brain water content increased by 1.5 ± 0.1 vs. 0.5 ± 0.2 % (Mean ± Standard Error, P < 0.0005) and intracranial pressure by 36 ± 5 vs. 21 ± 3 mmHg (P < 0.05) above pre-injection baseline, and neurological score was worse at 18.0 vs. 24.5 (median, P < 0.05), respectively. Although subarachnoid hemorrhage produced comparable increases in blood-brain barrier permeability in wildtype and aquaporin-4 null mice, aquaporin-4 null mice had a twofold reduction in glia limitans osmotic permeability. We conclude that aquaporin-4 null mice manifest increased brain edema following subarachnoid hemorrhage as a consequence of reduced elimination of excess brain water. PMID:20132873

  4. 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.

  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-1? after hypoxia-ischemia (HI) injury provides neuroprotection. Vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), an HIF-1? 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-1? 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-1? by dimethyloxalylglycine (DMOG) increased the BBB permeability and brain edema compared to HI alone. Vitexin attenuated the increase in HIF-1? 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-1? inhibition with vitexin provides both acute and long-term neuroprotection in the developing brain after neonatal HI injury. PMID:26187393

  6. Heroin abuse and myocardial infarction.

    PubMed

    Sztajzel, J; Karpuz, H; Rutishauser, W

    1994-12-01

    A young woman developed an acute transmural infarction due to an acute thrombosis of the left anterior descending coronary artery, probably induced by a previous abuse of intravenous heroin. PMID:7721488

  7. Small intestinal ischemia and infarction

    MedlinePLUS

    ... are reconnected. In some cases, a colostomy or ileostomy is needed. The blockage of arteries to the ... Intestinal infarction may require a colostomy or ileostomy, which ... these cases. People who have a large amount of tissue death in ...

  8. Aberrant white matter networks mediate cognitive impairment in patients with silent lacunar infarcts in basal ganglia territory.

    PubMed

    Tang, Jinfu; Zhong, Suyu; Chen, Yaojing; Chen, Kewei; Zhang, Junying; Gong, Gaolang; Fleisher, Adam S; He, Yong; Zhang, Zhanjun

    2015-09-01

    Silent lacunar infarcts, which are present in over 20% of healthy elderly individuals, are associated with subtle deficits in cognitive functions. However, it remains largely unclear how these silent brain infarcts lead to cognitive deficits and even dementia. Here, we used diffusion tensor imaging tractography and graph theory to examine the topological organization of white matter networks in 27 patients with silent lacunar infarcts in the basal ganglia territory and 30 healthy controls. A whole-brain white matter network was constructed for each subject, where the graph nodes represented brain regions and the edges represented interregional white matter tracts. Compared with the controls, the patients exhibited a significant reduction in local efficiency and global efficiency. In addition, a total of eighteen brain regions showed significantly reduced nodal efficiency in patients. Intriguingly, nodal efficiency-behavior associations were significantly different between the two groups. The present findings provide new aspects into our understanding of silent infarcts that even small lesions in subcortical brain regions may affect large-scale cortical white matter network, as such may be the link between subcortical silent infarcts and the associated cognitive impairments. Our findings highlight the need for network-level neuroimaging assessment and more medical care for individuals with silent subcortical infarcts. PMID:25873426

  9. 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

  10. 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

  11. 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.

  12. Generation of an immortalized murine brain microvascular endothelial cell line as an in vitro blood brain barrier model.

    PubMed

    Burek, Malgorzata; Salvador, Ellaine; Förster, Carola Y

    2012-01-01

    Epithelial and endothelial cells (EC) are building paracellular barriers which protect the tissue from the external and internal environment. The blood-brain barrier (BBB) consisting of EC, astrocyte end-feet, pericytes and the basal membrane is responsible for the protection and homeostasis of the brain parenchyma. In vitro BBB models are common tools to study the structure and function of the BBB at the cellular level. A considerable number of different in vitro BBB models have been established for research in different laboratories to date. Usually, the cells are obtained from bovine, porcine, rat or mouse brain tissue (discussed in detail in the review by Wilhelm et al.). Human tissue samples are available only in a restricted number of laboratories or companies. While primary cell preparations are time consuming and the EC cultures can differ from batch to batch, the establishment of immortalized EC lines is the focus of scientific interest. Here, we present a method for establishing an immortalized brain microvascular EC line from neonatal mouse brain. We describe the procedure step-by-step listing the reagents and solutions used. The method established by our lab allows the isolation of a homogenous immortalized endothelial cell line within four to five weeks. The brain microvascular endothelial cell lines termed cEND (from cerebral cortex) and cerebEND (from cerebellar cortex), were isolated according to this procedure in the Förster laboratory and have been effectively used for explanation of different physiological and pathological processes at the BBB. Using cEND and cerebEND we have demonstrated that these cells respond to glucocorticoid- and estrogen-treatment as well as to pro-infammatory mediators, such as TNFalpha. Moreover, we have studied the pathology of multiple sclerosis and hypoxia on the EC-level. The cEND and cerebEND lines can be considered as a good tool for studying the structure and function of the BBB, cellular responses of ECs to different stimuli or interaction of the EC with lymphocytes or cancer cells. PMID:22951995

  13. 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

  14. Role of acetaminophen in acute myocardial infarction.

    PubMed

    Leshnower, Bradley G; Sakamoto, Hiroaki; Zeeshan, Ahmad; Parish, Landi M; Hinmon, Robin; Plappert, Theodore; Jackson, Benjamin M; Gorman, Joseph H; Gorman, Robert C

    2006-06-01

    Acetaminophen, the active ingredient in Tylenol, is a widely used drug that is well known for its analgesic and antipyretic properties. Acetaminophen is a commonly used alternative to nonsteroidal anti-inflammatory drugs, which have recently been demonstrated to increase mortality after acute myocardial infarction (AMI). The safety and potential cardioprotective properties of acetaminophen in the setting of AMI have recently been investigated; however, the results from these studies have been inconclusive. Using both large (ovine) and small (rabbit) collateral-deficient animal models, we studied the effects of acetaminophen in the setting of reperfused AMI. In both species we studied the effects of acetaminophen on myocardial salvage and ventricular function. Additionally, we studied the effects of acetaminophen on myocardial perfusion in sheep and on myocyte apoptosis in rabbits. Sixteen sheep and twenty-two rabbits were divided into two groups and administered acetaminophen or a vehicle before undergoing ischemia and reperfusion. The ischemic period was 60 min in sheep and 30 min in rabbits. All animals were reperfused for 3 h. There were no significant differences observed in myocardial perfusion, myocyte apoptosis, or infarct size in acetaminophen-treated animals. Acetaminophen increased cardiac output and mean arterial pressure before ischemia in sheep but had no effect on any other hemodynamic parameter. In rabbits, no effect on cardiac output or blood pressure was detected. These results support the role of acetaminophen as a safe drug in the postmyocardial infarction setting; however, no significant cardioprotective effect of the drug could be demonstrated. PMID:16687610

  15. In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia

    PubMed Central

    Agulla, Jesús; Brea, David; Campos, Francisco; Sobrino, Tomás; Argibay, Bárbara; Al-Soufi, Wajih; Blanco, Miguel; Castillo, José; Ramos-Cabrer, Pedro

    2014-01-01

    The use of theranostics in neurosciences has been rare to date because of the limitations imposed on the free delivery of substances to the brain by the blood-brain barrier. Here we report the development of a theranostic system for the treatment of stroke, a leading cause of death and disability in developed countries. We first performed a series of proteomic, immunoblotting and immunohistological studies to characterize the expression of molecular biomarkers for the so-called peri-infarct tissue, a key region of the brain for stroke treatment. We confirmed that the HSP72 protein is a suitable biomarker for the peri-infarct region, as it is selectively expressed by at-risk tissue for up to 7 days following cerebral ischemia. We also describe the development of anti-HSP72 vectorized stealth immunoliposomes containing imaging probes to make them traceable by conventional imaging techniques (fluorescence and MRI) that were used to encapsulate a therapeutic agent (citicoline) for the treatment of cerebral ischemia. We tested the molecular recognition capabilities of these nano-platforms in vitro together with their diagnostic and therapeutic properties in vivo, in an animal model of cerebral ischemia. Using MRI, we found that 80% of vectorized liposomes were located on the periphery of the ischemic lesion, and animals treated with citicoline encapsulated on these liposomes presented lesion volumes up to 30% smaller than animals treated with free (non-encapsulated) drugs. Our results show the potential of nanotechnology for the development of effective tools for the treatment of neurological diseases. PMID:24396517

  16. Minimal Invasive Surgical Procedure of Inducing Myocardial Infarction in Mice

    PubMed Central

    Curaj, Adelina; Simsekyilmaz, Sakine; Staudt, Mareike; Liehn, Elisa

    2015-01-01

    Myocardial infarction still remains the main cause of death in western countries, despite considerable progress in the stent development area in the last decades. For clarification of the underlying mechanisms and the development of new therapeutic strategies, the availability of valid animal models are mandatory. Since we need new insights into pathomechanisms of cardiovascular diseases under in vivo conditions to combat myocardial infarction, the validity of the animal model is a crucial aspect. However, protection of animals are highly relevant in this context. Therefore, we establish a minimally invasive and simple model of myocardial infarction in mice, which assures a high reproducibility and survival rate of animals. Thus, this models fulfils the requirements of the 3R principle (Replacement, Refinement and Reduction) for animal experiments and assure the scientific information needed for further developing of therapeutical strategies for cardiovascular diseases. PMID:25992740

  17. Early Cerebral Infarction after Aneurysmal Subarachnoid Hemorrhage.

    PubMed

    Wong, George Kwok Chu; Leung, Joyce Hoi Ying; Yu, Janice Wong Li; Lam, Sandy Wai; Chan, Emily Kit Ying; Poon, Wai Sang; Abrigo, Jill; Siu, Deyond Yun Woon

    2016-01-01

    Aneurysmal subarachnoid hemorrhage (SAH) is a serious disease with high case fatality and morbidity. Early cerebral infarction has been suggested as a risk factor for poor outcome. We aimed to assess the pattern of early and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage. We prospectively enrolled consecutive aneurysmal subarachnoid hemorrhage (SAH) patients presenting to an academic neurosurgical referral center (Prince of Wales Hospital, the Chinese University of Hong Kong) in Hong Kong. Cerebral infarction occurred in 24 (48 %) patients, in which 14 (28 %) had early cerebral infarction and 14 (28 %) had delayed cerebral infarction. Early anterior cerebral infarction occurred in a similar proportion of anterior and posterior circulation aneurysms (24 % vs. 21 %), whereas posterior circulation aneurysm patients had a higher proportion of early posterior cerebral infarction compared with anterior circulation aneurysm patients (18 % vs. 2 %). In conclusion, early cerebral infarction was common and different from delayed cerebral infarction. PMID:26463941

  18. MRI evaluation of injectable hyaluronic acid-based hydrogel therapy to limit ventricular remodeling after myocardial infarction.

    PubMed

    Dorsey, Shauna M; McGarvey, Jeremy R; Wang, Hua; Nikou, Amir; Arama, Leron; Koomalsingh, Kevin J; Kondo, Norihiro; Gorman, Joseph H; Pilla, James J; Gorman, Robert C; Wenk, Jonathan F; Burdick, Jason A

    2015-11-01

    Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non-invasive estimation of infarct material properties. Specifically, cine magnetic resonance imaging (MRI) assesses global LV structure and function, late-gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI. PMID:26280951

  19. 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.

  20. Conjugation of Functionalized SPIONs with Transferrin for Targeting and Imaging Brain Glial Tumors in Rat Model

    PubMed Central

    Ghoorah, Devina; Shang, Yalei; Shi, Haojun; Liu, Fang; Yang, Xiangliang; Xu, Haibo

    2012-01-01

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

  1. 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

  2. Effect of antihypertensive treatment on focal cerebral infarction.

    PubMed

    Fujii, K; Weno, B L; Baumbach, G L; Heistad, D D

    1992-06-01

    The goal of the current study was to determine whether treatment of hypertension reduces cerebral infarction after occlusion of the middle cerebral artery in stroke-prone spontaneously hypertensive rats (SHRSPs). Three-month-old SHRSPs received untreated drinking water or drinking water containing cilazapril, an angiotensin converting enzyme inhibitor, or hydralazine and hydrochlorothiazide. After 3 months of treatment, the left middle cerebral artery was occluded and neurological deficit was evaluated. Infarct volume was measured 3 days after occlusion using computer imaging techniques from brain slices. Cilazapril and hydralazine with hydrochlorothiazide were equally effective in reducing systolic blood pressure in SHRSPs. One day after occlusion of the middle cerebral artery, neurological deficit was decreased by both cilazapril and hydralazine with hydrochlorothiazide compared with untreated SHRSPs, and the deficit 3 days after occlusion was decreased significantly only by cilazapril. Infarct volume was 178 +/- 7 mm3 (mean +/- SEM) in untreated SHRSPs, and it was significantly reduced to 117 +/- 15 mm3 by hydralazine with hydrochlorothiazide and to 101 +/- 17 mm3 by cilazapril. Infarct volume in Wistar-Kyoto rats was 27 +/- 16 mm3. Thus, reduction in arterial pressure by hydralazine with hydrochlorothiazide or an angiotensin converting enzyme inhibitor is protective against focal cerebral ischemia in SHRSPs. PMID:1534316

  3. Allergic myocardial infarction.

    PubMed

    Sinkiewicz, W?adys?aw; Soba?ski, Piotr; Bartuzi, Zbigniew

    2008-01-01

    In the literature there are very few well-documented cases of myocardial ischemia with pathomechanism accompanying allergic reaction. It is defined as Kounis syndrome, i.e. angina pectoris or infarction with allergic etiology. It is suggested, that few few cases of myocardial ischemia after a Hymenoptera sting reported thus far represent only a minute percentage of the total number of allergic reactions which occur in the circulatory system. It is difficult to make a credible decision whether allergic mechanisms are responsible for a greater number of deaths than we suspect. In the light of the literature, this review deals with current views regarding pathomechanisms of myocardial ischemia in the course of anaphylactic reaction and presents the clinical manifestation of myocardial ischemia with an allergic background, pointing out that allergic reactions involving cardiac muscle are not limited to the development of ischemia. The term organ anaphylaxis, in relation to the heart, also comprises rhythm and contractility disturbances which are present after exposure to the allergen. At the same time, the authors touch upon therapeutic aspects of immunotherapy in patients with significant cardiovascular risk and draw attention to the possibility of an alternative treatment for patients with allergic history, not only during desensitization but also for long-term outpatient treatment. PMID:18651413

  4. Thalamic amnesia after infarct

    PubMed Central

    Barbeau, Emmanuel J.; Eustache, Pierre; Planton, Mélanie; Raposo, Nicolas; Sibon, Igor; Albucher, Jean-François; Bonneville, Fabrice; Peran, Patrice; Pariente, Jérémie

    2015-01-01

    Objective: To improve current understanding of the mechanisms behind thalamic amnesia, as it is unclear whether it is directly related to damage to specific nuclei, in particular to the anterior or mediodorsal nuclei, or indirectly related to lesions of the mammillothalamic tract (MTT). Methods: We recruited 12 patients with a left thalamic infarction and 25 healthy matched controls. All underwent a comprehensive neuropsychological assessment of verbal and visual memory, executive functions, language, and affect, and a high-resolution structural volumetric MRI scan. Thalamic lesions were manually segmented and automatically localized with a computerized thalamic atlas. As well as comparing patients with controls, we divided patients into subgroups with intact or damaged MTT. Results: Only one patient had a small lesion of the anterior nucleus. Most of the lesions included the mediodorsal (n = 11) and intralaminar nuclei (n = 12). Patients performed worse than controls on the verbal memory tasks, but the 5 patients with intact MTT who showed isolated lesions of the mediodorsal nucleus (MD) only displayed moderate memory impairment. The 7 patients with a damaged MTT performed worse on the verbal memory tasks than those whose MTT was intact. Conclusions: Lesions in the MTT and in the MD result in memory impairment, severely in the case of MTT and to a lesser extent in the case of MD, thus highlighting the roles played by these 2 structures in memory circuits. PMID:26567269

  5. MR images of mouse brain using clinical 3T MR scanner and 4CH-Mouse coil

    NASA Astrophysics Data System (ADS)

    Lim, Soo Mee; Park, Eun Mi; Lyoo, In Kyoon; Lee, Junghyun; Han, Bo Mi; Lee, Jeong Kyong; Lee, Su Bin

    2015-07-01

    Objectives: Although small-bore high-field magnets are useful for research in small rodent models,this technology, however, has not been easily accessible to most researchers. This current study, thus,tried to evaluate the usability of 4CH-Mouse coil (Philips Healthcare, Best, the Netherlands) forpreclinical investigations in clinical 3T MR scan environment. We evaluated the effects of ischemicpreconditioning (IP) in the mouse stroke model with clinical 3T MR scanner and 4CH-Mouse coil. Materials and Methods: Experiments were performed on male C57BL/6 mice that either received the IP or sham operation (control). Three different MR sequences including diffusion weighted images (DWI), T2-weighted images (T2WI), and fluid attenuated inversion recovery (FLAIR) were performed on the mouse brains following 24, 72 hours of middle cerebral artery occlusion (MCAO) and analyzed for infarct lesions. Results: The images showed that the IP-treated mouse brains had significantly smaller infarct volumes compared to the control group. Of the MR sequences employed, the T2WI showed the highest level of correlations with postmortem infarct volume measurements. Conclusions: The clinical 3T MR scanner turned out to have a solid potential as a practical tool for imaging small animal brains. MR sequences including DWI, T2WI, FLAIR were obtained with acceptable resolution and in a reasonable time constraint in evaluating a mouse stroke model brain.

  6. Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts

    PubMed Central

    Duering, Marco; Righart, Ruthger; Wollenweber, Frank Arne; Zietemann, Vera; Gesierich, Benno

    2015-01-01

    Objective: To study remote effects distant from acute ischemic infarcts by measuring longitudinal changes of cortical thickness in connected brain regions as well as changes in microstructural integrity in connecting fiber tracts. Methods: Thirty-two patients (mean age 71 years) underwent a standardized protocol including multimodal MRI and clinical assessment both at stroke onset and 6 months after the event. Cortex connected to acute infarcts was identified by probabilistic diffusion tensor tractography starting from the acute lesion. Changes of cortical thickness were measured using the longitudinal stream of FreeSurfer. Microstructural damage in white matter tracts was assessed by changes of mean diffusivity. Results: We found focal cortical thinning specifically in areas connected to acute infarcts (p < 0.001). Thinning was more pronounced in regions showing a high probability of connectivity to infarcts. Microstructural damage in white matter tracts connecting acute infarcts with distant cortex significantly correlated with thickness changes in that region (? = ?0.39, p = 0.028). There was no indication of an influence of cavitation status or infarct etiology on the observed changes in cortex and white matter. Conclusions: These findings identify secondary degeneration of connected white matter tracts and remote cortex as key features of acute ischemic infarcts. Our observations may have implications for the understanding of structural and functional reorganization after stroke. PMID:25809303

  7. Intravenous Followed by X-ray Fused with MRI-Guided Transendocardial Mesenchymal Stem Cell Injection Improves Contractility Reserve in a Swine Model of Myocardial Infarction.

    PubMed

    Schmuck, Eric G; Koch, Jill M; Hacker, Timothy A; Hatt, Charles R; Tomkowiak, Michael T; Vigen, Karl K; Hendren, Nicholas; Leitzke, Cathlyn; Zhao, Ying-Qi; Li, Zhanhai; Centanni, John M; Hei, Derek J; Schwahn, Denise; Kim, Jaehyup; Hematti, Peiman; Raval, Amish N

    2015-10-01

    The aim of this study is to determine the effects of early intravenous (IV) infusion later followed by transendocardial (TE) injection of allogeneic mesenchymal stem cells (MSCs) following myocardial infarction (MI). Twenty-four swine underwent balloon occlusion reperfusion MI and were randomized into 4 groups: IV MSC (or placebo) infusion (post-MI day 2) and TE MSC (or placebo) injection targeting the infarct border with 2D X-ray fluoroscopy fused to 3D magnetic resonance (XFM) co-registration (post-MI day 14). Continuous ECG recording, MRI, and invasive pressure-volume analyses were performed. IV MSC plus TE MSC treated group was superior to other groups for contractility reserve (p?=?0.02) and freedom from VT (p?=?0.03) but had more lymphocytic foci localized to the peri-infarct region (p?=?0.002). No differences were observed in post-MI remodeling parameters. IV followed by XFM targeted TE MSC therapy improves contractility reserve and suppresses VT but does not affect post-MI remodeling and may cause an immune response. PMID:26374144

  8. 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…

  9. Modeling Development and Disease in Our "Second" Brain

    E-print Network

    Balasuriya, Sanjeeva

    's Hospital, Parkville, Victoria 3052 Australia don.newgreen@mcri.edu.au Abstract. The enteric nervous system (ENS) in our gastrointestinal tract, nicknamed the "second brain", is responsible for normal gut func, Frontal Expan- sion, Stochastic, Hirschsprung disease. 1 Introduction The enteric nervous system (ENS

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

    PubMed Central

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

    2014-01-01

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

  11. 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

  12. Can pulsed ultrasound increase tissue damage during ischemia? A study of the effects of ultrasound on infarcted and non-infarcted myocardium in anesthetized pigs

    PubMed Central

    Olivecrona, Göran K; Härdig, Bjarne Madsen; Roijer, Anders; Block, Mattias; Grins, Edgars; Persson, Hans W; Johansson, Leif; Olsson, Bertil

    2005-01-01

    Background The same mechanisms by which ultrasound enhances thrombolysis are described in connection with non-beneficial effects of ultrasound. The present safety study was therefore designed to explore effects of beneficial ultrasound characteristics on the infarcted and non-infarcted myocardium. Methods In an open chest porcine model (n = 17), myocardial infarction was induced by ligating a coronary diagonal branch. Pulsed ultrasound of frequency 1 MHz and intensity 0.1 W/cm2 (ISATA) was applied during one hour to both infarcted and non-infarcted myocardial tissue. These ultrasound characteristics are similar to those used in studies of ultrasound enhanced thrombolysis. Using blinded assessment technique, myocardial damage was rated according to histopathological criteria. Results Infarcted myocardium exhibited a significant increase in damage score compared to non-infarcted myocardium: 6.2 ± 2.0 vs. 4.3 ± 1.5 (mean ± standard deviation), (p = 0.004). In the infarcted myocardium, ultrasound exposure yielded a further significant increase of damage scores: 8.1 ± 1.7 vs. 6.2 ± 2.0 (p = 0.027). Conclusion Our results suggest an instantaneous additive effect on the ischemic damage in myocardial tissue when exposed to ultrasound of stated characteristics. The ultimate damage degree remains to be clarified. PMID:15831106

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

    PubMed

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

    2015-01-01

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

  14. 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…

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

    E-print Network

    Gerber, Samuel

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

  16. Lacunar infarction and small vessel disease: pathology and pathophysiology.

    PubMed

    Caplan, Louis R

    2015-01-01

    Two major vascular pathologies underlie brain damage in patients with disease of small size penetrating brain arteries and arterioles; 1) thickening of the arterial media and 2) obstruction of the origins of penetrating arteries by parent artery intimal plaques. The media of these small vessels may be thickened by fibrinoid deposition and hypertrophy of smooth muscle and other connective tissue elements that accompanies degenerative changes in patients with hypertension and or diabetes or can contain foreign deposits as in amyloid angiopathy and genetically mediated conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These pathological changes lead to 2 different pathophysiologies: 1) brain ischemia in regions supplied by the affected arteries. The resultant lesions are deep small infarcts, most often involving the basal ganglia, pons, thalami and cerebral white matter. And 2) leakage of fluid causing edema and later gliosis in white matter tracts. The changes in the media and adventitia effect metalloproteinases and other substances within the matrix of the vessels and lead to abnormal blood/brain barriers in these small vessels. and chronic gliosis and atrophy of cerebral white matter. PMID:25692102

  17. Lacunar Infarction and Small Vessel Disease: Pathology and Pathophysiology

    PubMed Central

    2015-01-01

    Two major vascular pathologies underlie brain damage in patients with disease of small size penetrating brain arteries and arterioles; 1) thickening of the arterial media and 2) obstruction of the origins of penetrating arteries by parent artery intimal plaques. The media of these small vessels may be thickened by fibrinoid deposition and hypertrophy of smooth muscle and other connective tissue elements that accompanies degenerative changes in patients with hypertension and or diabetes or can contain foreign deposits as in amyloid angiopathy and genetically mediated conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These pathological changes lead to 2 different pathophysiologies: 1) brain ischemia in regions supplied by the affected arteries. The resultant lesions are deep small infarcts, most often involving the basal ganglia, pons, thalami and cerebral white matter. And 2) leakage of fluid causing edema and later gliosis in white matter tracts. The changes in the media and adventitia effect metalloproteinases and other substances within the matrix of the vessels and lead to abnormal blood/brain barriers in these small vessels. and chronic gliosis and atrophy of cerebral white matter. PMID:25692102

  18. Nanoparticles for targeting the infarcted heart

    E-print Network

    Dvir, Tal

    We report a nanoparticulate system capable of targeting the heart after myocardial infarction (MI). Targeting is based on overexpression of angiotensin II type 1 (AT1) receptor in the infarcted heart. Liposomes 142 nm in ...

  19. Brain Source Imaging in Preclinical Rat Models of Focal Epilepsy using High-Resolution EEG Recordings

    PubMed Central

    Bae, Jihye; Deshmukh, Abhay; Song, Yinchen; Riera, Jorge

    2015-01-01

    Electroencephalogram (EEG) has been traditionally used to determine which brain regions are the most likely candidates for resection in patients with focal epilepsy. This methodology relies on the assumption that seizures originate from the same regions of the brain from which interictal epileptiform discharges (IEDs) emerge. Preclinical models are very useful to find correlates between IED locations and the actual regions underlying seizure initiation in focal epilepsy. Rats have been commonly used in preclinical studies of epilepsy1; hence, there exist a large variety of models for focal epilepsy in this particular species. However, it is challenging to record multichannel EEG and to perform brain source imaging in such a small animal. To overcome this issue, we combine a patented-technology to obtain 32-channel EEG recordings from rodents2 and an MRI probabilistic atlas for brain anatomical structures in Wistar rats to perform brain source imaging. In this video, we introduce the procedures to acquire multichannel EEG from Wistar rats with focal cortical dysplasia, and describe the steps both to define the volume conductor model from the MRI atlas and to uniquely determine the IEDs. Finally, we validate the whole methodology by obtaining brain source images of IEDs and compare them with those obtained at different time frames during the seizure onset. PMID:26131755

  20. Learning Computational Models of Video Memorability from fMRI Brain Imaging.

    PubMed

    Han, Junwei; Chen, Changyuan; Shao, Ling; Hu, Xintao; Han, Jungong; Liu, Tianming

    2015-08-01

    Generally, various visual media are unequally memorable by the human brain. This paper looks into a new direction of modeling the memorability of video clips and automatically predicting how memorable they are by learning from brain functional magnetic resonance imaging (fMRI). We propose a novel computational framework by integrating the power of low-level audiovisual features and brain activity decoding via fMRI. Initially, a user study experiment is performed to create a ground truth database for measuring video memorability and a set of effective low-level audiovisual features is examined in this database. Then, human subjects' brain fMRI data are obtained when they are watching the video clips. The fMRI-derived features that convey the brain activity of memorizing videos are extracted using a universal brain reference system. Finally, due to the fact that fMRI scanning is expensive and time-consuming, a computational model is learned on our benchmark dataset with the objective of maximizing the correlation between the low-level audiovisual features and the fMRI-derived features using joint subspace learning. The learned model can then automatically predict the memorability of videos without fMRI scans. Evaluations on publically available image and video databases demonstrate the effectiveness of the proposed framework. PMID:25314715

  1. 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

  2. Blue Brain Project Brain Mind Institute

    E-print Network

    © Blue Brain Project Brain Mind Institute Prof. Henry Markram Dr. Felix Schürmann felix.schuermann@epfl.ch http://bluebrainproject.epfl.ch Reverse-Engineering the Brain #12;© Blue Brain Project The Electrophysiologist's View BBP BBPBBP #12;© Blue Brain Project Accurate Models that Relate to Experiment LBC PC SBC PC

  3. Mathematical modeling for evolution of heterogeneous modules in the brain.

    PubMed

    Yamaguti, Yutaka; Tsuda, Ichiro

    2015-02-01

    Modular architecture has been found in most cortical areas of mammalian brains, but little is known about its evolutionary origin. It has been proposed by several researchers that maximizing information transmission among subsystems can be used as a principle for understanding the development of complex brain networks. In this paper, we study how heterogeneous modules develop in coupled-map networks via a genetic algorithm, where selection is based on maximizing bidirectional information transmission. Two functionally differentiated modules evolved from two homogeneous systems with random couplings, which are associated with symmetry breaking of intrasystem and intersystem couplings. By exploring the parameter space of the network around the optimal parameter values, it was found that the optimum network exists near transition points, at which the incoherent state loses its stability and an extremely slow oscillatory motion emerges. PMID:25124068

  4. Ventricular Aneurysm Following Myocardial Infarction

    PubMed Central

    Walters, M. B.

    1966-01-01

    Cineradiographic examination appears to be the best method for the study of cardiac pulsations. Fifty consecutive patients, who had sustained transmural myocardial infarction at least six months previously, were studied by this technique. Thirty-six had some abnormality of pulsation and eight had dynamic ventricular aneurysm. Six of the eight had suffered severe infarct. Functional recovery in those with aneurysm was not as complete as in the rest of the group. Two made a poor functional recovery, two a fair recovery, and four a moderately good recovery. Clinically, there were no systemic emboli in the patients with dynamic aneurysms. Five of the 50 had persistent ST-segment elevation and “coving” of the T waves; three of these patients had aneurysms. There was no good correlation between the electrocardiographic site of the infarct and the site of the abnormal pulsation. ImagesFig. 1 PMID:5928534

  5. Acute Hyperglycemia Is Associated with Immediate Brain Swelling and Hemorrhagic Transformation After Middle Cerebral Artery Occlusion in Rats.

    PubMed

    McBride, Devin W; Legrand, Julia; Krafft, Paul R; Flores, Jerry; Klebe, Damon; Tang, Jiping; Zhang, John H

    2016-01-01

    Hemorrhagic transformation occurs in as many as 48 % of stroke patients and is a major contributor to post-insult morbidity and mortality. Experimental models of hemorrhagic transformation are utilized for understanding the mechanisms behind its development, as well as for investigating potential therapeutics for prevention and reduction of bleeding. Thoroughly studying animal models of hemorrhagic transformation is critically important for testing novel treatments. Thus far, no study has examined the progression of brain swelling and hemorrhagic transformation after transient middle cerebral artery occlusion (MCAO). Herein, we investigate the development of infarction, brain swelling, and hemorrhagic transformation following MCAO in hyperglycemic rats. Twenty-five Sprague-Dawley rats were subjected to either 1.5 h of MCAO or sham surgery 15 min after induction of hyperglycemia. Animals were sacrificed at 0.25, 1, 3, or 24 h after reperfusion for measurement of infarct volume, brain swelling, and hemoglobin volume. Within 15 min of reperfusion, the infarct volume was significantly larger than in sham animals and did not increase in size over the 24 h. However, both brain swelling and hemorrhagic transformation, which began immediately after reperfusion, increase over 24 h after reperfusion. PMID:26463955

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

    PubMed

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

    2013-01-01

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

  7. Core modular blood and brain biomarkers in social defeat mouse model for post traumatic stress disorder

    PubMed Central

    2013-01-01

    Background Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects a substantial portion of combat veterans and poses serious consequences to long-term health. Consequently, the identification of diagnostic and prognostic blood biomarkers for PTSD is of great interest. Previously, we assessed genome-wide gene expression of seven brain regions and whole blood in a social defeat mouse model subjected to various stress conditions. Results To extract biological insights from these data, we have applied a new computational framework for identifying gene modules that are activated in common across blood and various brain regions. Our results, in the form of modular gene networks that highlight spatial and temporal biological functions, provide a systems-level molecular description of response to social stress. Specifically, the common modules discovered between the brain and blood emphasizes molecular transporters in the blood-brain barrier, and the associated genes have significant overlaps with known blood signatures for PTSD, major depression, and bipolar disease. Similarly, the common modules specific to the brain highlight the components of the social defeat stress response (e.g., fear conditioning pathways) in each brain sub-region. Conclusions Many of the brain-specific genes discovered are consistent with previous independent studies of PTSD or other mental illnesses. The results from this study further our understanding of the mechanism of stress response and contribute to a growing list of diagnostic biomarkers for PTSD. PMID:23962043

  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. Mathematical Modeling of Human Glioma Growth Based on Brain Topological Structures: Study of Two Clinical Cases

    PubMed Central

    Suarez, Cecilia; Maglietti, Felipe; Colonna, Mario; Breitburd, Karina; Marshall, Guillermo

    2012-01-01

    Gliomas are the most common primary brain tumors and yet almost incurable due mainly to their great invasion capability. This represents a challenge to present clinical oncology. Here, we introduce a mathematical model aiming to improve tumor spreading capability definition. The model consists in a time dependent reaction-diffusion equation in a three-dimensional spatial domain that distinguishes between different brain topological structures. The model uses a series of digitized images from brain slices covering the whole human brain. The Talairach atlas included in the model describes brain structures at different levels. Also, the inclusion of the Brodmann areas allows prediction of the brain functions affected during tumor evolution and the estimation of correlated symptoms. The model is solved numerically using patient-specific parametrization and finite differences. Simulations consider an initial state with cellular proliferation alone (benign tumor), and an advanced state when infiltration starts (malign tumor). Survival time is estimated on the basis of tumor size and location. The model is used to predict tumor evolution in two clinical cases. In the first case, predictions show that real infiltrative areas are underestimated by current diagnostic imaging. In the second case, tumor spreading predictions were shown to be more accurate than those derived from previous models in the literature. Our results suggest that the inclusion of differential migration in glioma growth models constitutes another step towards a better prediction of tumor infiltration at the moment of surgical or radiosurgical target definition. Also, the addition of physiological/psychological considerations to classical anatomical models will provide a better and integral understanding of the patient disease at the moment of deciding therapeutic options, taking into account not only survival but also life quality. PMID:22761843

  10. Near Real-Time Computer Assisted Surgery for Brain Shift Correction Using Biomechanical Models

    PubMed Central

    SUN, KAY; PHEIFFER, THOMAS S.; SIMPSON, AMBER L.; WEIS, JARED A.; THOMPSON, REID C.; MIGA, MICHAEL I.

    2014-01-01

    Conventional image-guided neurosurgery relies on preoperative images to provide surgical navigational information and visualization. However, these images are no longer accurate once the skull has been opened and brain shift occurs. To account for changes in the shape of the brain caused by mechanical (e.g., gravity-induced deformations) and physiological effects (e.g., hyperosmotic drug-induced shrinking, or edema-induced swelling), updated images of the brain must be provided to the neuronavigation system in a timely manner for practical use in the operating room. In this paper, a novel preoperative and intraoperative computational processing pipeline for near real-time brain shift correction in the operating room was developed to automate and simplify the processing steps. Preoperatively, a computer model of the patient’s brain with a subsequent atlas of potential deformations due to surgery is generated from diagnostic image volumes. In the case of interim gross changes between diagnosis, and surgery when reimaging is necessary, our preoperative pipeline can be generated within one day of surgery. Intraoperatively, sparse data measuring the cortical brain surface is collected using an optically tracked portable laser range scanner. These data are then used to guide an inverse modeling framework whereby full volumetric brain deformations are reconstructed from precomputed atlas solutions to rapidly match intraoperative cortical surface shift measurements. Once complete, the volumetric displacement field is used to update, i.e., deform, preoperative brain images to their intraoperative shifted state. In this paper, five surgical cases were analyzed with respect to the computational pipeline and workflow timing. With respect to postcortical surface data acquisition, the approximate execution time was 4.5 min. The total update process which included positioning the scanner, data acquisition, inverse model processing, and image deforming was ~11–13 min. In addition, easily implemented hardware, software, and workflow processes were identified for improved performance in the near future. PMID:25914864

  11. A large left atrial myxoma causing multiple cerebral infarcts

    PubMed Central

    Kebede, Saba; Edmunds, Eiry; Raybould, Adrian

    2013-01-01

    A 52-year-old man presented with a history of sudden onset diplopia. On neurological examination, the only abnormality was a right-sided oculomotor (third nerve) palsy. A brain CT was performed and reported as showing no abnormality. He was discharged to be investigated as an outpatient. He presented 1?month later with a new expressive dysphasia and confusional state. MRI was performed which revealed multiple cerebral infarcts. He was discharged on secondary stroke prevention medication. Six months elapsed, before a transthoracic echocardiogram was performed. This showed a large left atrial myxoma. The patient underwent an emergency resection and made a good postoperative recovery. This case report showed the importance of considering a cardiogenic source of emboli in patients who present with cerebral infarcts. Performing echocardiography early will help to detect treatable conditions such as atrial myxoma, and prevent further complications. PMID:24285802

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

    PubMed Central

    Fyshe, Alona; Talukdar, Partha P; Murphy, Brian; Mitchell, Tom M

    2015-01-01

    Vector space models (VSMs) represent word meanings as points in a high dimensional space. VSMs are typically created using a large text corpora, and so represent word semantics as observed in text. We present a new algorithm (JNNSE) that can incorporate a measure of semantics not previously used to create VSMs: brain activation data recorded while people read words. The resulting model takes advantage of the complementary strengths and weaknesses of corpus and brain activation data to give a more complete representation of semantics. Evaluations show that the model 1) matches a behavioral measure of semantics more closely, 2) can be used to predict corpus data for unseen words and 3) has predictive power that generalizes across brain imaging technologies and across subjects. We believe that the model is thus a more faithful representation of mental vocabularies. PMID:26166940

  13. Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients

    PubMed Central

    2008-01-01

    Objective To develop and validate practical prognostic models for death at 14 days and for death or severe disability six months after traumatic brain injury. Design Multivariable logistic regression to select variables that were independently associated with two patient outcomes. Two models designed: “basic” model (demographic and clinical variables only) and “CT” model (basic model plus results of computed tomography). The models were subsequently developed for high and low-middle income countries separately. Setting Medical Research Council (MRC) CRASH Trial. Subjects 10?008 patients with traumatic brain injury. Models externally validated in a cohort of 8509. Results The basic model included four predictors: age, Glasgow coma scale, pupil reactivity, and the presence of major extracranial injury. The CT model also included the presence of petechial haemorrhages, obliteration of the third ventricle or basal cisterns, subarachnoid bleeding, midline shift, and non-evacuated haematoma. In the derivation sample the models showed excellent discrimination (C statistic above 0.80). The models showed good calibration graphically. The Hosmer-Lemeshow test also indicated good calibration, except for the CT model in low-middle income countries. External validation for unfavourable outcome at six months in high income countries showed that basic and CT models had good discrimination (C statistic 0.77 for both models) but poorer calibration. Conclusion Simple prognostic models can be used to obtain valid predictions of relevant outcomes in patients with traumatic brain injury. PMID:18270239

  14. The brain as a system of nested but partially overlapping networks. Heuristic relevance of the model for brain physiology and pathology.

    PubMed

    Agnati, L F; Guidolin, D; Fuxe, K

    2007-01-01

    A new model of the brain organization is proposed. The model is based on the assumption that a global molecular network enmeshes the entire central nervous system. Thus, brain extra-cellular and intra-cellular molecular networks are proposed to communicate at the level of special plasma membrane regions (e.g., the lipid rafts) where horizontal molecular networks can represent input/output regions allowing the cell to have informational exchanges with the extracellular environment. Furthermore, some "pervasive signals" such as field potentials, pressure waves and thermal gradients that affect large parts of the brain cellular and molecular networks are discussed. Finally, at least two learning paradigms are analyzed taking into account the possible role of Volume Transmission: the so-called model of "temporal difference learning" and the "Turing B-unorganised machine". The relevance of this new view of brain organization for a deeper understanding of some neurophysiological and neuropathological aspects of its function is briefly discussed. PMID:16906353

  15. Acute myocardial infarction

    PubMed Central

    Domes, Trustin; Szafran, Olga; Bilous, Cheryl; Olson, Odell; Spooner, G. Richard

    2006-01-01

    OBJECTIVE To assess the quality of care of acute myocardial infarction (AMI) in a rural health region. DESIGN Clinical audit employing multiple explicit criteria of care elements for emergency department and in-hospital AMI management. The audit was conducted using retrospective chart review. SETTING Twelve acute care health centres and hospitals in the East Central Health Region, a rural health region in Alberta, where medical and surgical services are provided almost entirely by family physicians. PARTICIPANTS Hospital inpatients with a confirmed discharge diagnosis of AMI (ICD-9-CM codes 410.xx) during the period April 1, 2001, to March 31, 2002, were included (177 confirmed cases). MAIN OUTCOME MEASURES Quality of AMI care was assessed using guidelines from the American College of Cardiology and the American Heart Association and the Canadian Cardiovascular Outcomes Research Team and Canadian Cardiovascular Society. Quality of care indicators at three stages of patient care were assessed: at initial recognition and AMI management in the emergency department, during in-hospital AMI management, and at preparation for discharge from hospital. RESULTS In the emergency department, the quality of care was high for most procedural and therapeutic audit elements, with the exception of rapid electrocardiography, urinalysis, and provision of nitroglycerin and morphine. Average door-to-needle time for thrombolysis was 102.5 minutes. The quality of in-hospital care was high for most elements, but low for nitroglycerin and angiotensin-converting enzyme (ACE) inhibitors, daily electrocardiography, and counseling regarding smoking cessation and diet. Few patients received counseling for lifestyle changes at hospital discharge. Male and younger patients were treated more aggressively than female and older patients. Sites that used care protocols achieved better results in initial AMI management than sites that did not. Stress testing was not readily available in the rural region studied. CONCLUSION Quality of care for patients with AMI in this rural health region was high for most guideline elements. Standing orders, protocols, and checklists could improve care. Training and resource issues will need to be addressed to improve access to stress testing for rural patients. Clinical audit should be at the core of a system for local monitoring of quality of care. PMID:16926968

  16. Ex vivo micro-CT imaging of murine brain models using non-ionic iodinated contrast

    NASA Astrophysics Data System (ADS)

    Salas Bautista, N.; Martínez-Dávalos, A.; Rodríguez-Villafuerte, M.; Murrieta-Rodríguez, T.; Manjarrez-Marmolejo, J.; Franco-Pérez, J.; Calvillo-Velasco, M. E.

    2014-11-01

    Preclinical investigation of brain tumors is frequently carried out by means of intracranial implantation of brain tumor xenografts or allografts, with subsequent analysis of tumor growth using conventional histopathology. However, very little has been reported on the use contrast-enhanced techniques in micro-CT imaging for the study of malignant brain tumors in small animal models. The aim of this study has been to test a protocol for ex vivo imaging of murine brain models of glioblastoma multiforme (GBM) after treatment with non-ionic iodinated solution, using an in-house developed laboratory micro-CT. We have found that the best compromise between acquisition time and image quality is obtained using a 50 kVp, 0.5 mAs, 1° angular step on a 360 degree orbit acquisition protocol, with 70 ?m reconstructed voxel size using the Feldkamp algorithm. With this parameters up to 4 murine brains can be scanned in tandem in less than 15 minutes. Image segmentation and analysis of three sample brains allowed identifying tumor volumes as small as 0.4 mm3.

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

    NASA Astrophysics Data System (ADS)

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

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

  18. Dynamics of the brain: Mathematical models and non-invasive experimental studies

    NASA Astrophysics Data System (ADS)

    Toronov, V.; Myllylä, T.; Kiviniemi, V.; Tuchin, V. V.

    2013-10-01

    Dynamics is an essential aspect of the brain function. In this article we review theoretical models of neural and haemodynamic processes in the human brain and experimental non-invasive techniques developed to study brain functions and to measure dynamic characteristics, such as neurodynamics, neurovascular coupling, haemodynamic changes due to brain activity and autoregulation, and cerebral metabolic rate of oxygen. We focus on emerging theoretical biophysical models and experimental functional neuroimaging results, obtained mostly by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS). We also included our current results on the effects of blood pressure variations on cerebral haemodynamics and simultaneous measurements of fast processes in the brain by near-infrared spectroscopy and a very novel functional MRI technique called magnetic resonance encephalography. Based on a rapid progress in theoretical and experimental techniques and due to the growing computational capacities and combined use of rapidly improving and emerging neuroimaging techniques we anticipate during next decade great achievements in the overall knowledge of the human brain.

  19. Implications of sodium hydrogen exchangers in various brain diseases.

    PubMed

    Verma, Vivek; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

    2015-09-01

    Na+/H+ exchangers (NHEs) are the transporter proteins that play an important role in intracellular pH (pHi) regulation, cell differentiation and cell volume and that mediate transepithelial Na+ and HCO3- absorption on the basis of chemical gradients across the plasma membrane. Its activation causes an increase in intracellular Na+, which further leads to Ca+ overload and cell death. The pharmacological inhibition of these transporter proteins prevents myocardial infarction and other heart diseases like congestive heart failure in experimental animal models as well as in clinical situations. The more recent studies have implicated the role of these exchangers in the pathophysiology of brain diseases. Out of nine NHE isoforms, NHE-1 is the major isoform present in the brain and regulates the trans-cellular ion transport through blood-brain barrier membrane, and alteration in their function leads to severe brain abnormalities. NHEs were shown to be involved in pathophysiologies of many brain diseases like epilepsy, Alzheimer's disease, neuropathic pain and ischemia/reperfusion-induced cerebral injury. Na+/H+-exchanger inhibitors (e.g., amiloride and cariporide) produce protective effects on ischemia/reperfusion-induced brain injury (e.g., stroke), exhibit good antiepileptic potential and attenuate neuropathic pain in various animal models. The present review focuses on the pathophysiological role of these ion exchangers in different brain diseases with possible mechanisms. PMID:26020555

  20. Multilevel Segmentation and Integrated Bayesian Model Classification with an Application to Brain Tumor Segmentation

    E-print Network

    Corso, Jason J.

    region membership: or Incorporate models as hidden variables and marginalize over them: brain edema tumor. Typical Example: T1 T1 w/ Contrast Flair T2 Results on Training Set Tumor Edema Algorithm Jac Prec Rec Jac% 76% Model-Based Extractor 62% 75% 81% 54% 66% 72% Results on Testing Set Tumor Edema Algorithm Jac

  1. OFF-CENTER SPHERICAL MODEL FOR DOSIMETRY CALCULATIONS IN CHICK BRAIN TISSUE

    EPA Science Inventory

    The paper presents calculations for the electric field and absorbed power density distribution in chick brain tissue inside a test tube, using an off-center spherical model. It is shown that the off-center spherical model overcomes many of the limitations of the concentric spheri...

  2. Analysis of Model-Updated MR Images to Correct for Brain Deformation Due to Tissue Retraction

    E-print Network

    Miga, Michael I.

    Analysis of Model-Updated MR Images to Correct for Brain Deformation Due to Tissue Retraction the accuracy of neuronavigation systems that use a preoperative image display. Computational modeling has by simulating surgical events and creating updated images. The success of simulating surgical events relies upon

  3. Behavioural Brain Research 179 (2007) 118 What's wrong with my mouse model?

    E-print Network

    Kalueff, Allan V.

    2007-01-01

    and strategies in animal modeling of anxiety and depression A.V. Kalueff, M. Wheaton, D.L. Murphy Laboratory plays a key role in pathogenesis of anxiety and depression. Animal models of these disorders are widely used in behavioral neuroscience to explore stress-evoked brain abnormalities, screen anxiolytic/antidepressant

  4. Self-organized Critical Model Based on Complex Brain Networks with Hierarchical Organization

    NASA Astrophysics Data System (ADS)

    Zhang, Ying-Yue; Zhang, Gui-Qing; Yang, Qiu-Ying; Chen, Tian-Lun

    2008-09-01

    The dynamical behavior in the cortical brain network of macaque is studied by modelling each cortical area with a subnetwork of interacting excitable neurons. We find that the avalanche of our model on different levels exhibits power-law. Furthermore the power-law exponent of the distribution and the average avalanche size are affected by the topology of the network.

  5. Extent of Contrast Enhancement on Non-Enhanced Computed Tomography after Intra-Arterial Thrombectomy for Acute Infarction on Anterior Circulation: As a Predictive Value for Malignant Brain Edema

    PubMed Central

    Song, Seung Yoon; Rhee, Jong Ju; Lee, Jong Won; Hur, Jin Woo; Lee, Hyun Koo

    2015-01-01

    Objective To determine whether the use of contrast enhancement (especially its extent) predicts malignant brain edema after intra-arterial thrombectomy (IAT) in patients with acute ischemic stroke. Methods We reviewed the records of patients with acute ischemic stroke who underwent IAT for occlusion of the internal carotid artery or the middle cerebral artery between January 2012 and March 2015. To estimate the extent of contrast enhancement (CE), we used the contrast enhancement area ratio (CEAR)-i.e., the ratio of the CE to the area of the hemisphere, as noted on immediate non-enhanced brain computed tomography (NECT) post-IAT. Patients were categorized into two groups based on the CEAR values being either greater than or less than 0.2. Results A total of 39 patients were included. Contrast enhancement was found in 26 patients (66.7%). In this subgroup, the CEAR was greater than 0.2 in 7 patients (18%) and less than 0.2 in the other 19 patients (48.7%). On univariate analysis, both CEAR ?0.2 and the presence of subarachnoid hemorrhage were significantly associated with progression to malignant brain edema (p<0.001 and p=0.004), but on multivariate analysis, only CEAR ?0.2 showed a statistically significant association (p=0.019). In the group with CEAR ?0.2, the time to malignant brain edema was shorter (p=0.039) than in the group with CEAR <0.2. Clinical functional outcomes, based on the modified Rankin scale, were also significantly worse in patients with CEAR ?0.2 (p=0.003) Conclusion The extent of contrast enhancement as noted on NECT scans obtained immediately after IAT could be predictive of malignant brain edema and a poor clinical outcome. PMID:26587184

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

    PubMed Central

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

    2010-01-01

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

  7. Pesticides and Myocardial Infarction Incidence and Mortality Among Male Pesticide Applicators in the Agricultural Health Study

    PubMed Central

    Mills, Katherine T.; Blair, Aaron; Freeman, Laura E. Beane; Sandler, Dale P.

    2009-01-01

    Acute organophosphate and carbamate pesticide poisonings result in adverse cardiac outcomes. The cardiac effects of chronic low-level pesticide exposure have not been studied. The authors analyzed self-reported lifetime use of pesticides reported at enrollment (1993–1997) and myocardial infarction mortality through 2006 and self-reported nonfatal myocardial infarction through 2003 among male pesticide applicators in the Agricultural Health Study. Using proportional hazard models, the authors estimated the association between lifetime use of 49 pesticides and fatal and nonfatal myocardial infarction. There were 476 deaths from myocardial infarction among 54,069 men enrolled in the study and 839 nonfatal myocardial infarctions among the 32,024 participants who completed the follow-up interview. Fatal and nonfatal myocardial infarctions were associated with commonly reported risk factors, including age and smoking. There was little evidence of an association between having used pesticides, individually or by class, and myocardial infarction mortality (e.g., insecticide hazard ratio (HR)?=?0.91, 95% confidence interval (CI): 0.67, 1.24; herbicide HR?=?0.74, 95% CI: 0.49, 1.10) or nonfatal myocardial infarction incidence (e.g., insecticide HR?=?0.85, 95% CI: 0.66, 1.09; herbicide HR?=?0.91, 95% CI: 0.61, 1.36). There was no evidence of a dose response with any pesticide measure. In a population with low risk for myocardial infarction, the authors observed little evidence of increased risk of myocardial infarction mortality or nonfatal myocardial infarction associated with the occupational use of pesticides. PMID:19700503

  8. Identifying functional subdivisions in the human brain using meta-analytic activation modeling-based parcellation.

    PubMed

    Yang, Yong; Fan, Lingzhong; Chu, Congying; Zhuo, Junjie; Wang, Jiaojian; Fox, Peter T; Eickhoff, Simon B; Jiang, Tianzi

    2016-01-01

    Parcellation of the human brain into fine-grained units by grouping voxels into distinct clusters has been an effective approach for delineating specific brain regions and their subregions. Published neuroimaging studies employing coordinate-based meta-analyses have shown that the activation foci and their corresponding behavioral categories may contain useful information about the anatomical-functional organization of brain regions. Inspired by these developments, we proposed a new parcellation scheme called meta-analytic activation modeling-based parcellation (MAMP) that uses meta-analytically obtained information. The raw meta data, including the experiments and the reported activation coordinates related to a brain region of interest, were acquired from the Brainmap database. Using this data, we first obtained the "modeled activation" pattern by modeling the voxel-wise activation probability given spatial uncertainty for each experiment that featured at least one focus within the region of interest. Then, we processed these "modeled activation" patterns across the experiments with a K-means clustering algorithm to group the voxels into different subregions. In order to verify the reliability of the method, we employed our method to parcellate the amygdala and the left Brodmann area 44 (BA44). The parcellation results were quite consistent with previous cytoarchitectonic and in vivo neuroimaging findings. Therefore, the MAMP proposed in the current study could be a useful complement to other methods for uncovering the functional organization of the human brain. PMID:26296500

  9. A two-part mixed-effects modeling framework for analyzing whole-brain network data.

    PubMed

    Simpson, Sean L; Laurienti, Paul J

    2015-06-01

    Whole-brain network analyses remain the vanguard in neuroimaging research, coming to prominence within the last decade. Network science approaches have facilitated these analyses and allowed examining the brain as an integrated system. However, statistical methods for modeling and comparing groups of networks have lagged behind. Fusing multivariate statistical approaches with network science presents the best path to develop these methods. Toward this end, we propose a two-part mixed-effects modeling framework that allows modeling both the probability of a connection (presence/absence of an edge) and the strength of a connection if it exists. Models within this framework enable quantifying the relationship between an outcome (e.g., disease status) and connectivity patterns in the brain while reducing spurious correlations through inclusion of confounding covariates. They also enable prediction about an outcome based on connectivity structure and vice versa, simulating networks to gain a better understanding of normal ranges of topological variability, and thresholding networks leveraging group information. Thus, they provide a comprehensive approach to studying system level brain properties to further our understanding of normal and abnormal brain function. PMID:25796135

  10. Recent advances in brain injury research: a new human head model development and validation.

    PubMed

    Zhang, L; Yang, K H; Dwarampudi, R; Omori, K; Li, T; Chang, K; Hardy, W N; Khalil, T B; King, A I

    2001-11-01

    Many finite element models have been developed by several research groups in order to achieve a better understanding of brain injury. Due to the lack of experimental data, validation of these models has generally been limited. Consequently, applying these models to investigate brain responses has also been limited. Over the last several years, several versions of the Wayne State University brain injury model (WSUBIM) were developed. However, none of these models is capable of simulating indirect impacts with an angular acceleration higher than 8,000 rad/s(2). Additionally, the density and quality of the mesh in the regions of interest are not detailed and sensitive enough to accurately predict the stress/strain level associated with a wide range of impact severities. In this study, WSUBIM version 2001, capable of simulating direct and indirect impacts with a combined translational and rotational acceleration of the head up to 200 g and 12,000 rad/s(2) has been developed. This new finely meshed model, consisting of more than 314,500 elements and 281,800 nodes, also simulates an anatomically detailed facial bone model. An additional new feature of the model is the damageable material property representation of the facial bone and the skull, allowing it to simulate bony fractures. The model was subjected to extensive validation using published cadaveric test data. These data include the intracranial and ventricular pressure data reported by Nahum et al. (1977) and Trosseille et al. (1992), the relative displacement data between the brain and the skull reported by King et al. (1999) and Hardy et al. (2001), and the facial impact data reported by Nyquist et al. (1986) and Allsop et al. (1988). With the enhanced accuracy of model predictions offered by this new model, along with new experimental data, it is hoped that it will become a powerful tool to further our understanding of the mechanisms of injury and the tolerance of the brain to blunt impact. PMID:17458754

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

    PubMed Central

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

    2014-01-01

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

  12. Spousal Adjustment to Myocardial Infarction.

    ERIC Educational Resources Information Center

    Ziglar, Elisa J.

    This paper reviews the literature on the stresses and coping strategies of spouses of patients with myocardial infarction (MI). It attempts to identify specific problem areas of adjustment for the spouse and to explore the effects of spousal adjustment on patient recovery. Chapter one provides an overview of the importance in examining the…

  13. Describing the Neuron Axons Network of the Human Brain by Continuous Flow Models

    NASA Astrophysics Data System (ADS)

    Hizanidis, J.; Katsaloulis, P.; Verganelakis, D. A.; Provata, A.

    2014-12-01

    The multifractal spectrum Dq (Rényi dimensions) is used for the analysis and comparison between the Neuron Axons Network (NAN) of healthy and pathological human brains because it conveys information about the statistics in many scales, from the very rare to the most frequent network configurations. Comparison of the Fractional Anisotropy Magnetic Resonance Images between healthy and pathological brains is performed with and without noise reduction. Modelling the complex structure of the NAN in the human brain is undertaken using the dynamics of the Lorenz model in the chaotic regime. The Lorenz multifractal spectra capture well the human brain characteristics in the large negative q's which represent the rare network configurations. In order to achieve a closer approximation in the positive part of the spectrum (q > 0) two independent modifications are considered: a) redistribution of the dense parts of the Lorenz model's phase space into their neighbouring areas and b) inclusion of additive uniform noise in the Lorenz model. Both modifications, independently, drive the Lorenz spectrum closer to the human NAN one in the positive q region without destroying the already good correspondence of the negative spectra. The modelling process shows that the unmodified Lorenz model in its full chaotic regime has a phase space distribution with high fluctuations in its dense parts, while the fluctuations in the human brain NAN are smoother. The induced modifications (phase space redistribution or additive noise) moderate the fluctuations only in the positive part of the Lorenz spectrum leading to a faithful representation of the human brain axons network in all scales.

  14. Supportive or detrimental roles of P2Y receptors in brain pathology?-The two faces of P2Y receptors in stroke and neurodegeneration detected in neural cell and in animal model studies.

    PubMed

    Förster, Daniel; Reiser, Georg

    2015-12-01

    This review describing the role of P2Y receptors in neuropathological conditions focuses on obvious differences between results demonstrating either a role in neuroprotection or in neurodegeneration, depending on in vitro and in vivo models. Such critical juxtaposition puts special emphasis on discussions of beneficial and detrimental effects of P2Y receptor agonists and antagonists in these models. The mechanisms reported to underlie the protection in vitro include increased expression of oxidoreductase genes, like carbonyl reductase and thioredoxin reductase; increased expression of inhibitor of apoptosis protein-2; extracellular signal-regulated kinase- and Akt-mediated antiapoptotic signaling; increased expression of Bcl-2 proteins, neurotrophins, neuropeptides, and growth factors; decreased Bax expression; non-amyloidogenic APP shedding; and increased neurite outgrowth in neuronal cells. Animal studies investigating the influence of P2Y receptors in middle cerebral artery occlusion (MCAO) models for stroke prove beneficial effects of P2Y receptor antagonists. In MCAO mice and rats, the application of broad-range P2 receptor antagonists decreased the infarct volume and improved neurological outcome. Moreover, antagonists of the P2Y1 receptor, one of the most abundant P2Y receptor subtypes in brain tissue, decreased neuronal loss and improved spatial memory in rats after traumatic brain injury (TBI). Currently available data show a discrepancy between in vitro and in vivo models concerning the benefits of P2Y receptor activation in pathological conditions. In vitro models demonstrate protection by P2Y receptor agonists, but in vivo P2Y receptor activation deteriorates the outcome after MCAO and controlled cortical impact brain injury, a TBI model. To broaden the scope of the review, we additionally discuss publications that demonstrate detrimental effects of P2Y receptor agonists in vitro and publications showing protective effects of agonists in vivo. All these studies help to better understand the significant role of P2Y receptors especially in stroke models and to develop pharmacological strategies for the treatment of stroke. PMID:26407872

  15. A mechanical model predicts morphological abnormalities in the developing human brain

    PubMed Central

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-01-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism. PMID:25008163

  16. A geometric network model of intrinsic grey-matter connectivity of the human brain

    PubMed Central

    Lo, Yi-Ping; O’Dea, Reuben; Crofts, Jonathan J.; Han, Cheol E.; Kaiser, Marcus

    2015-01-01

    Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuroscience is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections. PMID:26503036

  17. A geometric network model of intrinsic grey-matter connectivity of the human brain

    NASA Astrophysics Data System (ADS)

    Lo, Yi-Ping; O’Dea, Reuben; Crofts, Jonathan J.; Han, Cheol E.; Kaiser, Marcus

    2015-10-01

    Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuroscience is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections.

  18. A geometric network model of intrinsic grey-matter connectivity of the human brain.

    PubMed

    Lo, Yi-Ping; O'Dea, Reuben; Crofts, Jonathan J; Han, Cheol E; Kaiser, Marcus

    2015-01-01

    Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuroscience is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct 'shortcuts' through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections. PMID:26503036

  19. A mechanical model predicts morphological abnormalities in the developing human brain

    NASA Astrophysics Data System (ADS)

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-01

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

  20. [Climatologic parameters and myocardial infarction].

    PubMed

    Larcan, A; Gilgenkrantz, J M; Stoltz, J F; Lambert, H; Laprevote-Heully, M C; Evrard, D; Kempf, J B; Lambert, J

    1983-01-01

    535 patients admitted to hospital with myocardium infarct which was confirmed in a determined period and within a 80 kilometers radius from a city of the East of France were compared to the meteorological parameters of the day when the infarct occurred and of the day preceding its occurrence. On one hand, climatic parameters were selected: atmospheric pressure, temperature of the air under shelter, relative humidity, wind speed and wind direction, hydrometeors and electrometeors; on the other hand, parameters of solar and planetary activity: daily flare index, AA index, Ap index or daily planetary index, phases of the moon. The analytic study concerning all acute vascular accidents (infarcts and cerebral accidents all together) enabled to us to notice a higher frequency of vascular accidents in various meteorological circumstances: atmospheric pressure lower than 990 mb, temperature lower than 12 degrees, wind of sector North to South-South West, hoar-frost with fog, rain, snow, first quarter of the moon, daily flare index lower than 530, magnetic activity lower than 6. A factorial analysis of correspondence enabled to us to understand the problem better and to determine "an infarct area" in which main meteorological factors appeared: low or decreasing atmospheric pressure, relative or increasing humidity, clear or increasing solar activity, steady magnetic activity; other factors could play an apparently less important role: low temperature, snow, decrease of wind speed, full moon, wind of sector East to North-East, South-South West. Consequently it appeared in that study that the occurrence of myocardium infarct corresponded to a climatic tendency corresponding to cold, bad or deteriorating weather. PMID:6638893

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

    PubMed Central

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

    2014-01-01

    The present study assessed the impact of sample size on the power and fit of structural equation modeling applied to functional brain connectivity hypotheses. The data consisted of time-constrained minimum norm estimates of regional brain activity during performance of a reading task obtained with magnetoencephalography. Power analysis was first conducted for an autoregressive model with 5 latent variables (brain regions), each defined by 3 indicators (successive activity time bins). A series of simulations were then run by generating data from an existing pool of 51 typical readers (aged 7.5-12.5 years). Sample sizes ranged between 20 and 1,000 participants and for each sample size 1,000 replications were run. Results were evaluated using chi-square Type I errors, model convergence, mean RMSEA (root mean square error of approximation) values, confidence intervals of the RMSEA, structural path stability, and D-Fit index values. Results suggested that 70 to 80 participants were adequate to model relationships reflecting close to not so close fit as per MacCallum et al.'s recommendations. Sample sizes of 50 participants were associated with satisfactory fit. It is concluded that structural equation modeling is a viable methodology to model complex regional interdependencies in brain activation in pediatric populations. PMID:25435589

  2. A multimodal approach for determining brain networks by jointly modeling functional and structural connectivity

    PubMed Central

    Xue, Wenqiong; Bowman, F. DuBois; Pileggi, Anthony V.; Mayer, Andrew R.

    2015-01-01

    Recent innovations in neuroimaging technology have provided opportunities for researchers to investigate connectivity in the human brain by examining the anatomical circuitry as well as functional relationships between brain regions. Existing statistical approaches for connectivity generally examine resting-state or task-related functional connectivity (FC) between brain regions or separately examine structural linkages. As a means to determine brain networks, we present a unified Bayesian framework for analyzing FC utilizing the knowledge of associated structural connections, which extends an approach by Patel et al. (2006a) that considers only functional data. We introduce an FC measure that rests upon assessments of functional coherence between regional brain activity identified from functional magnetic resonance imaging (fMRI) data. Our structural connectivity (SC) information is drawn from diffusion tensor imaging (DTI) data, which is used to quantify probabilities of SC between brain regions. We formulate a prior distribution for FC that depends upon the probability of SC between brain regions, with this dependence adhering to structural-functional links revealed by our fMRI and DTI data. We further characterize the functional hierarchy of functionally connected brain regions by defining an ascendancy measure that compares the marginal probabilities of elevated activity between regions. In addition, we describe topological properties of the network, which is composed of connected region pairs, by performing graph theoretic analyses. We demonstrate the use of our Bayesian model using fMRI and DTI data from a study of auditory processing. We further illustrate the advantages of our method by comparisons to methods that only incorporate functional information. PMID:25750621

  3. Inflammation as a therapeutic target in myocardial infarction: learning from past failures to meet future challenges.

    PubMed

    Saxena, Amit; Russo, Ilaria; Frangogiannis, Nikolaos G

    2016-01-01

    In the infarcted myocardium, necrotic cardiomyocytes release danger signals, activating an intense inflammatory response. Inflammatory pathways play a crucial role in regulation of a wide range of cellular processes involved in injury, repair, and remodeling of the infarcted heart. Proinflammatory cytokines, such as tumor necrosis factor ? and interleukin 1, are markedly upregulated in the infarcted myocardium and promote adhesive interactions between endothelial cells and leukocytes by stimulating chemokine and adhesion molecule expression. Distinct pairs of chemokines and chemokine receptors are implicated in recruitment of various leukocyte subpopulations in the infarcted myocardium. For more than the past 30 years, extensive experimental work has explored the role of inflammatory signals and the contributions of leukocyte subpopulations in myocardial infarction. Robust evidence derived from experimental models of myocardial infarction has identified inflammatory targets that may attenuate cardiomyocyte injury or protect from adverse remodeling. Unfortunately, attempts to translate the promising experimental findings to clinical therapy have failed. This review article discusses the biology of the inflammatory response after myocardial infarction, attempts to identify the causes for the translational failures of the past, and proposes promising new therapeutic directions. Because of their potential involvement in injurious, reparative, and regenerative responses, inflammatory cells may hold the key for design of new therapies in myocardial infarction. PMID:26241027

  4. Random graph theory and neuropercolation for modeling brain oscillations at criticality.

    PubMed

    Kozma, Robert; Puljic, Marko

    2015-04-01

    Mathematical approaches are reviewed to interpret intermittent singular space-time dynamics observed in brain imaging experiments. The following aspects of brain dynamics are considered: nonlinear dynamics (chaos), phase transitions, and criticality. Probabilistic cellular automata and random graph models are described, which develop equations for the probability distributions of macroscopic state variables as an alternative to differential equations. The introduced modular neuropercolation model is motivated by the multilayer structure and dynamical properties of the cortex, and it describes critical brain oscillations, including background activity, narrow-band oscillations in excitatory-inhibitory populations, and broadband oscillations in the cortex. Input-induced and spontaneous transitions between states with large-scale synchrony and without synchrony exhibit brief episodes with long-range spatial correlations as observed in experiments. PMID:25460075

  5. Study of Protein Expresion in Peri-Infarct Tissue after Cerebral Ischemia

    PubMed Central

    Brea, David; Agulla, Jesús; Staes, An; Gevaert, Kris; Campos, Francisco; Sobrino, Tomás; Blanco, Miguel; Dávalos, Antoni; Castillo, José; Ramos-Cabrer, Pedro

    2015-01-01

    In this work, we report our study of protein expression in rat peri-infarct tissue, 48?h after the induction of permanent focal cerebral ischemia. Two proteomic approaches, gel electrophoresis with mass spectrometry and combined fractional diagonal chromatography (COFRADIC), were performed using tissue samples from the periphery of the induced cerebral ischemic lesions, using tissue from the contra-lateral hemisphere as a control. Several protein spots (3408) were identified by gel electrophoresis, and 11 showed significant differences in expression between peri-infarct and contra-lateral tissues (at least 3-fold, p?infarct tissue. Further studies by 1D and 2D western blotting and immunohistochemistry revealed that only one member of this family (the inducible form, HSP72 or HSP70i) is specifically expressed by the peri-infarct tissue, while the majority of this family (the constitutive form, HSC70 or HSP70c) is expressed in the whole brain. Our data support that HSP72 is a suitable biomarker of peri-infarct tissue in the ischemic brain. PMID:26153530

  6. A weighted cluster kernel PCA prediction model for multi-subject brain imaging data

    PubMed Central

    Guo, Ying

    2010-01-01

    SUMMARY Brain imaging data have shown great promise as a useful predictor for psychiatric conditions, cognitive functions and many other neural-related outcomes. Development of prediction models based on imaging data is challenging due to the high dimensionality of the data, noisy measurements, complex correlation structures among voxels, small sample sizes, and between-subject heterogeneity. Most existing prediction approaches apply a dimension reduction method such as PCA on whole brain images as a preprocessing step. These approaches usually do not take into account of the cluster structure among voxels and between-subject differences. We propose a weighted cluster kernel PCA predictive model that addresses the challenges in brain imaging data. We first divide voxels into clusters based on neuroanatomic parcellation or data-driven methods, then extract cluster-specific principal features using kernel PCA and define the prediction model based on the principal features. Finally, we propose a weighted estimation method for the prediction model where each subject is weighted according to the percent of variance explained by the principal features. The proposed method allows assessment of relative importance of various brain regions in prediction; captures nonlinearity in feature space; and helps guard against overfitting for outlying subjects in predictive model building. We evaluate the performance of our method through simulation studies. A real fMRI data example is also used to illustrate the method. PMID:20657752

  7. Neuroprotective effect of lentivirus mediated VEGF on rat model with cerebral ischemic injury

    PubMed Central

    Zhang, Junhe; Li, Xiaojuan; Chai, Shujie; Wang, Xiaoyin

    2015-01-01

    This study aimed to investigate the neuroprotective effect and its mechanism of lentivirus mediated VEGF on rat model with cerebral ischemic injury. 45 rats with cerebral ischemic injury constructed by the suture method were randomly divided into sham group, model group, vector group and VEGF group. The packaged vector lentivirus and lentivirus carrying VEGF gene were injected into the lateral ventricular of rats in vector group and VEGF group respectively. The equal volume of PBS buffer was injected in sham group and model group respectively. The expression of VEGF and protein in brain tissue were detected by real-time fluorescence quantitative PCR and Western blot. The change of brain tissue vascular density was analyzed by immunohistochemistry. The brain infarction area and the degree of nervous functional defect of the rats were analyzed. VEGF mRNA and protein levels were significantly higher in brain tissue of rats in VEGF group than those in model group and vector group (P < 0.05). The brain tissue vascular density increased significantly in VEGF group (P < 0.05). Compared with sham group, the infarction area of brain tissue and the degree of nervous functional defect increased significantly in model group, vector group and VEGF group, but the VEGF group was significantly lower than those in model group and vector group (P < 0.05). In conclusion, the overexpression of VEGF in cerebral ischemia injury contributed to the angiogenesis in brain tissues, reduced the brain injury caused by cerebral ischemia and protected brain neuronal function. PMID:26064315

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  9. Catalpol Increases Brain Angiogenesis and Up-Regulates VEGF and EPO in the Rat after Permanent Middle Cerebral Artery Occlusion

    PubMed Central

    Zhu, Hui-Feng; Wan, Dong; Luo, Yong; Zhou, Jia-Li; Chen, Li; Xu, Xiao-Yu

    2010-01-01

    To investigate the role and mechanism of catalpol in brain angiogenesis in a rat model of stroke, the effect of catalpol (5 mg/kg; i.p) or vehicle administered 24 hours after permanent middle cerebral artery occlusion (pMCAO) on behavior, angiogenesis, ultra-structural integrity of brain capillary endothelial cells, and expression of EPO and VEGF were assessed. Repeated treatments with Catalpol reduced neurological deficits and significantly improved angiogenesis, while significantly increasing brain levels of EPO and VEGF without worsening BBB edema. These results suggested that catalpol might contribute to infarcted-brain angiogenesis and ameliorate the edema of brain capillary endothelial cells (BCECs) by upregulating VEGF and EPO coordinately. PMID:20827397

  10. A Simple Method for Assessing Free Brain/Free Plasma Ratios Using an In Vitro Model of the Blood Brain Barrier

    PubMed Central

    Sevin, Emmanuel; Szorath, Erica; Martinsson, Stefan; Renftel, Mila; Hongmei, Yan; Cecchelli, Romeo; Lundquist, Stefan

    2013-01-01

    Historically, the focus has been to use in vitro BBB models to optimize rate of drug delivery to the CNS, whereas total in vivo brain/plasma ratios have been used for optimizing extent. However, these two parameters do not necessarily show good correlations with receptor occupancy data or other pharmacological readouts. In line with the free drug hypothesis, the use of unbound brain concentrations (Cu,br) has been shown to provide the best correlations with pharmacological data. However, typically the determination of this parameter requires microdialysis, a technique not ideally suited for screening in early drug development. Alternative, and less resource-demanding methodologies to determine Cu,br employ either equilibrium dialysis of brain homogenates or incubations of brain slices in buffer to determine fraction unbound brain (fu,br), which is subsequently multiplied by the total brain concentration to yield Cu,br. To determine Cu,br/Cu,pl ratios this way, still requires both in vitro and in vivo experiments that are quite time consuming. The main objective of this study was to explore the possibility to directly generate Cu,br/Cu,pl ratios in a single in vitro model of the BBB, using a co-culture of brain capillary endothelial and glial cells in an attempt to mimick the in vivo situation, thereby greatly simplifying existing experimental procedures. Comparison to microdialysis brain concentration profiles demonstrates the possibility to estimate brain exposure over time in the BBB model. A stronger correlation was found between in vitro Cu,br/Cu,pl ratios and in vivo Cu,br/Cu,pl obtained using fu,br from brain slice than with fu,br from brain homogenate for a set of 30 drugs. Overall, Cu,br/Cu,pl ratios were successfully predicted in vitro for 88% of the 92 studied compounds. This result supports the possibility to use this methodology for identifying compounds with a desirable in vivo response in the CNS early on in the drug discovery process. PMID:24312489

  11. The Virtual Brain: Modeling Biological Correlates of Recovery after Chronic Stroke

    PubMed Central

    Falcon, Maria Inez; Riley, Jeffrey D.; Jirsa, Viktor; McIntosh, Anthony R.; Shereen, Ahmed D.; Chen, E. Elinor; Solodkin, Ana

    2015-01-01

    There currently remains considerable variability in stroke survivor recovery. To address this, developing individualized treatment has become an important goal in stroke treatment. As a first step, it is necessary to determine brain dynamics associated with stroke and recovery. While recent methods have made strides in this direction, we still lack physiological biomarkers. The Virtual Brain (TVB) is a novel application for modeling brain dynamics that simulates an individual’s brain activity by integrating their own neuroimaging data with local biophysical models. Here, we give a detailed description of the TVB modeling process and explore model parameters associated with stroke. In order to establish a parallel between this new type of modeling and those currently in use, in this work we establish an association between a specific TVB parameter (long-range coupling) that increases after stroke with metrics derived from graph analysis. We used TVB to simulate the individual BOLD signals for 20 patients with stroke and 10 healthy controls. We performed graph analysis on their structural connectivity matrices calculating degree centrality, betweenness centrality, and global efficiency. Linear regression analysis demonstrated that long-range coupling is negatively correlated with global efficiency (P?=?0.038), but is not correlated with degree centrality or betweenness centrality. Our results suggest that the larger influence of local dynamics seen through the long-range coupling parameter is closely associated with a decreased efficiency of the system. We thus propose that the increase in the long-range parameter in TVB (indicating a bias toward local over global dynamics) is deleterious because it reduces communication as suggested by the decrease in efficiency. The new model platform TVB hence provides a novel perspective to understanding biophysical parameters responsible for global brain dynamics after stroke, allowing the design of focused therapeutic interventions. PMID:26579071

  12. Action and Language Mechanisms in the Brain: Data, Models and Neuroinformatics

    PubMed Central

    Bonaiuto, James J.; Bornkessel-Schlesewsky, Ina; Kemmerer, David; MacWhinney, Brian; Nielsen, Finn Årup; Oztop, Erhan

    2014-01-01

    We assess the challenges of studying action and language mechanisms in the brain, both singly and in relation to each other to provide a novel perspective on neuroinformatics, integrating the development of databases for encoding – separately or together – neurocomputational models and empirical data that serve systems and cognitive neuroscience. PMID:24234916

  13. Development and characterization of an ex-vivo brain slice culture model of chronic wasting disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases have long incubation times in vivo, therefore, modeling the diseases ex-vivo will advance the development of rationale-based therapeutic strategies. An organotypic slice culture assay (POSCA) was recently developed for scrapie prions by inoculating mouse cerebellar brain slices with R...

  14. Evaluation of three-dimensional anisotropic head model for mapping realistic electromagnetic fields of brain tissues

    NASA Astrophysics Data System (ADS)

    Jeong, Woo Chul; Wi, Hun; Sajib, Saurav Z. K.; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2015-08-01

    Electromagnetic fields provide fundamental data for the imaging of electrical tissue properties, such as conductivity and permittivity, in recent magnetic resonance (MR)-based tissue property mapping. The induced voltage, current density, and magnetic flux density caused by externally injected current are critical factors for determining the image quality of electrical tissue conductivity. As a useful tool to identify bio-electromagnetic phenomena, precise approaches are required to understand the exact responses inside the human body subject to an injected currents. In this study, we provide the numerical simulation results of electromagnetic field mapping of brain tissues using a MR-based conductivity imaging method. First, we implemented a realistic three-dimensional human anisotropic head model using high-resolution anatomical and diffusion tensor MR images. The voltage, current density, and magnetic flux density of brain tissues were imaged by injecting 1 mA of current through pairs of electrodes on the surface of our head model. The current density map of anisotropic brain tissues was calculated from the measured magnetic flux density based on the linear relationship between the water diffusion tensor and the electrical conductivity tensor. Comparing the current density to the previous isotropic model, the anisotropic model clearly showed the differences between the brain tissues. This originates from the enhanced signals by the inherent conductivity contrast as well as the actual tissue condition resulting from the injected currents.

  15. Thesis proposal CSF Brazil 2014 Ageing brain pathology : the marmoset monkey model.

    E-print Network

    Bordenave, Charles

    Thesis proposal CSF Brazil 2014 Title: Ageing brain pathology : the marmoset monkey model. Thesis imaging will explore anatomo-functional alterations in marmoset monkeys. Animals will be followed proximity to humans. More specifically, we will explore in the marmoset monkey (Callithrix Jacchus

  16. A random-effects model for group-level analysis of diffuse optical brain imaging

    PubMed Central

    Abdelnour, Farras; Huppert, Theodore

    2011-01-01

    Diffuse optical imaging is a non-invasive technique for measuring changes in blood oxygenation in the brain. This technique is based on the temporally and spatially resolved recording of optical absorption in tissue within the near-infrared range of light. Optical imaging can be used to study functional brain activity similar to functional MRI. However, group level comparisons of brain activity from diffuse optical data are difficult due to registration of optical sensors between subjects. In addition, optical signals are sensitive to inter-subject differences in cranial anatomy and the specific arrangement of optical sensors relative to the underlying functional region. These factors can give rise to partial volume errors and loss of sensitivity and therefore must be accounted for in combining data from multiple subjects. In this work, we describe an image reconstruction approach using a parametric Bayesian model that simultaneously reconstructs group-level images of brain activity in the context of a random-effects analysis. Using this model, we demonstrate that localization accuracy and the statistical effects size of group-level reconstructions can be improved when compared to individualized reconstructions. In this model, we use the Restricted Maximum Likelihood (ReML) method to optimize a Bayesian random-effects model. PMID:21326631

  17. Modeling Plus MRI Data Characterize Brain Tumors in Patients | Physical Sciences in Oncology

    Cancer.gov

    Patients diagnosed with glioblastoma, the most aggressive form of brain cancer, routinely undergo MRI scanning prior to receiving treatment. Now, an international team of investigators has developed a mathematical modeling technique that can translate the data from pretreatment MRI scans into patient-specific rates of tumor growth and metastasis that may find use in tailoring therapy to meet the needs of each patient.

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  19. An improved dosimetric model of the head and brain 

    E-print Network

    Bouchet, Lionel Gerard

    1995-01-01

    head model developed by Posion et al. in 1984. Some corrections and improvements were added to this head model such as the development of a new spinal region and a new cranium region in order to incorporate the cerebrospinal fluid. This model was used...

  20. LPA signaling initiates schizophrenia-like brain and behavioral changes in a mouse model of prenatal brain hemorrhage

    PubMed Central

    Mirendil, H; Thomas, E A; De Loera, C; Okada, K; Inomata, Y; Chun, J

    2015-01-01

    Genetic, environmental and neurodevelopmental factors are thought to underlie the onset of neuropsychiatric disorders such as schizophrenia. How these risk factors collectively contribute to pathology is unclear. Here, we present a mouse model of prenatal intracerebral hemorrhage—an identified risk factor for schizophrenia—using a serum-exposure paradigm. This model exhibits behavioral, neurochemical and schizophrenia-related gene expression alterations in adult females. Behavioral alterations in amphetamine-induced locomotion, prepulse inhibition, thigmotaxis and social interaction—in addition to increases in tyrosine hydroxylase-positive dopaminergic cells in the substantia nigra and ventral tegmental area and decreases in parvalbumin-positive cells in the prefrontal cortex—were induced upon prenatal serum exposure. Lysophosphatidic acid (LPA), a lipid component of serum, was identified as a key molecular initiator of schizophrenia-like sequelae induced by serum. Prenatal exposure to LPA alone phenocopied many of the schizophrenia-like alterations seen in the serum model, whereas pretreatment with an antagonist against the LPA receptor subtype LPA1 prevented many of the behavioral and neurochemical alterations. In addition, both prenatal serum and LPA exposure altered the expression of many genes and pathways related to schizophrenia, including the expression of Grin2b, Slc17a7 and Grid1. These findings demonstrate that aberrant LPA receptor signaling associated with fetal brain hemorrhage may contribute to the development of some neuropsychiatric disorders. PMID:25849980

  1. Sensitivity analysis of brain morphometry based on MRI-derived surface models

    NASA Astrophysics Data System (ADS)

    Klein, Gregory J.; Teng, Xia; Schoenemann, P. T.; Budinger, Thomas F.

    1998-07-01

    Quantification of brain structure is important for evaluating changes in brain size with growth and aging and for characterizing neurodegeneration disorders. Previous quantification efforts using ex vivo techniques suffered considerable error due to shrinkage of the cerebrum after extraction from the skull, deformation of slices during sectioning, and numerous other factors. In vivo imaging studies of brain anatomy avoid these problems and allow repetitive studies following progression of brain structure changes due to disease or natural processes. We have developed a methodology for obtaining triangular mesh models of the cortical surface from MRI brain datasets. The cortex is segmented from nonbrain tissue using a 2D region-growing technique combined with occasional manual edits. Once segmented, thresholding and image morphological operations (erosions and openings) are used to expose the regions between adjacent surfaces in deep cortical folds. A 2D region- following procedure is then used to find a set of contours outlining the cortical boundary on each slice. The contours on all slices are tiled together to form a closed triangular mesh model approximating the cortical surface. This model can be used for calculation of cortical surface area and volume, as well as other parameters of interest. Except for the initial segmentation of the cortex from the skull, the technique is automatic and requires only modest computation time on modern workstations. Though the use of image data avoids many of the pitfalls of ex vivo and sectioning techniques, our MRI-based technique is still vulnerable to errors that may impact the accuracy of estimated brain structure parameters. Potential inaccuracies include segmentation errors due to incorrect thresholding, missed deep sulcal surfaces, falsely segmented holes due to image noise and surface tiling artifacts. The focus of this paper is the characterization of these errors and how they affect measurements of cortical surface area and volume.

  2. Ex vivo molecular rejuvenation improves the therapeutic activity of senescent human cardiac stem cells in a mouse model of myocardial infarction.

    PubMed

    Avolio, Elisa; Gianfranceschi, Giuseppe; Cesselli, Daniela; Caragnano, Angela; Athanasakis, Emmanouil; Katare, Rajesh; Meloni, Marco; Palma, Anita; Barchiesi, Arianna; Vascotto, Carlo; Toffoletto, Barbara; Mazzega, Elisa; Finato, Nicoletta; Aresu, Giuseppe; Livi, Ugolino; Emanueli, Costanza; Scoles, Giacinto; Beltrami, Carlo Alberto; Madeddu, Paolo; Beltrami, Antonio Paolo

    2014-09-01

    Cardiac stem cells (CSC) from explanted decompensated hearts (E-CSC) are, with respect to those obtained from healthy donors (D-CSC), senescent and functionally impaired. We aimed to identify alterations in signaling pathways that are associated with CSC senescence. Additionally, we investigated if pharmacological modulation of altered pathways can reduce CSC senescence in vitro and enhance their reparative ability in vivo. Measurement of secreted factors showed that E-CSC release larger amounts of proinflammatory cytokine IL1? compared with D-CSC. Using blocking antibodies, we verified that IL1? hampers the paracrine protective action of E-CSC on cardiomyocyte viability. IL1? acts intracranially inducing IKK? signaling, a mechanism that via nuclear factor-?B upregulates the expression of IL1? itself. Moreover, E-CSC show reduced levels of AMP protein kinase (AMPK) activating phosphorylation. This latter event, together with enhanced IKK? signaling, increases TORC1 activity, thereby impairing the autophagic flux and inhibiting the phosphorylation of Akt and cAMP response element-binding protein. The combined use of rapamycin and resveratrol enhanced AMPK, thereby restoring downstream signaling and reducing IL1? secretion. These molecular corrections reduced E-CSC senescence, re-establishing their protective activity on cardiomyocytes. Moreover ex vivo treatment with rapamycin and resveratrol improved E-CSC capacity to induce cardiac repair upon injection in the mouse infarcted heart, leading to reduced cardiomyocyte senescence and apoptosis and increased abundance of endogenous c-Kit(+) CSC in the peri-infarct area. Molecular rejuvenation of patient-derived CSC by short pharmacologic conditioning boosts their in vivo reparative abilities. This approach might prove useful for refinement of CSC-based therapies. PMID:24801508

  3. Neurocomputational approaches to modelling multisensory integration in the brain: a review.

    PubMed

    Ursino, Mauro; Cuppini, Cristiano; Magosso, Elisa

    2014-12-01

    The Brain's ability to integrate information from different modalities (multisensory integration) is fundamental for accurate sensory experience and efficient interaction with the environment: it enhances detection of external stimuli, disambiguates conflict situations, speeds up responsiveness, facilitates processes of memory retrieval and object recognition. Multisensory integration operates at several brain levels: in subcortical structures (especially the Superior Colliculus), in higher-level associative cortices (e.g., posterior parietal regions), and even in early cortical areas (such as primary cortices) traditionally considered to be purely unisensory. Because of complex non-linear mechanisms of brain integrative phenomena, a key tool for their understanding is represented by neurocomputational models. This review examines different modelling principles and architectures, distinguishing the models on the basis of their aims: (i) Bayesian models based on probabilities and realizing optimal estimator of external cues; (ii) biologically inspired models of multisensory integration in the Superior Colliculus and in the Cortex, both at level of single neuron and network of neurons, with emphasis on physiological mechanisms and architectural schemes; among the latter, some models exhibit synaptic plasticity and reproduce development of integrative capabilities via Hebbian-learning rules or self-organizing maps; (iii) models of semantic memory that implement object meaning as a fusion between sensory-motor features (embodied cognition). This overview paves the way to future challenges, such as reconciling neurophysiological and Bayesian models into a unifying theory, and stimulates upcoming research in both theoretical and applicative domains. PMID:25218929

  4. Management of high-risk non-ST elevation myocardial infarction in the UK: need for alternative models of care to reduce length of stay and admission to angiography times.

    PubMed

    Koganti, Sudheer; Rakhit, Roby D

    2015-12-01

    The roll out of the primary percutaneous coronary intervention pathway as the default treatment for patients with ST elevation myocardial infarction (STEMI) across the NHS has led to a paradigm shift in the model of care resulting in a significant improvement in mortality. In comparison, a similar care plan does not exist for non-ST elevation acute coronary syndrome (NSTE-ACS) despite the fact that patients presenting with high-risk non-STEMI carry a similar if not higher mortality at six months in comparison to STEMI. In this article we focus on the contemporary management of NSTE-ACS in the NHS and also look at some of the dedicated pathways already developed and implemented successfully in expediting treatment and decreasing hospital stay without compromising the safety of patients. PMID:26621938

  5. Computational modeling of high-level cognition and brain function.

    PubMed

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

    1999-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Schwartz, Jon A.; Shetty, Anil M.; Price, Roger E.; Stafford, R. Jason; Wang, James C.; Uthamanthil, Rajesh K.; Pham, Kevin; McNichols, Roger J.; Coleman, Chris L.; Payne, J. Donald

    2009-02-01

    We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8+/-4.1ºC. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of 48.6+/-1.1ºC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

  7. Sexual differentiation of the brain: a model for drug-induced alterations of the reproductive system

    SciTech Connect

    Gorski, R.A.

    1986-12-01

    The process of the sexual differentiation of the brain represents a valuable model system for the study of the chemical modification of the mammalian brain. Although there are numerous functional and structural sex differences in the adult brain, these are imposed on an essentially feminine or bipotential brain by testicular hormones during a critical phase of perinatal development in the rat. It is suggested that a relatively marked structural sex difference in the rat brain, the sexually dimorphic nucleus of the preoptic area (SDN-POA), is a morphological signature of the permanent or organizational action of estradiol derived from the aromatization of testicular testosterone. The SDN-POA of the male rat is severalfold larger in volume and is composed of more neurons than that of the female. The observation that the mitotic formation of the neurons of the SDN-POA is specifically prolonged has enabled us to identify the time course and pathway of neuronal migration into the nucleus. Study of the development of the SDN-POA suggests that estradiol in the male increases the number of neurons which survive a phase of neuronal death by exerting a neurite growth promoting action and/or a direct neuronotrophic action. Finally, although it is clear that gonadal hormones have dramatic permanent effects on the brain during perinatal development, even after puberty and in adulthood gonadal steroids can alter neuronal structure and, perhaps as a corollary to this, have permanent effects on reproductive function. Although the brain may be most sensitive to gonadal hormones or exogenous chemical factors during perinatal development, such as sensitivity does not appear limited to this period.

  8. A GPU-based approach to compute the brain shift using a fully nonlinear biomechanical model

    NASA Astrophysics Data System (ADS)

    Tian, Ye; Shen, Xukun

    2015-07-01

    We present a brain shift prediction algorithm which is based on multi-GPU. Our algorithm can calculate on more complex mesh model. The proposed algorithm mainly includes two aspects. On the one hand, we present a grid-based algorithm for the generation of hexahedral element meshes. It can automatically divide the complex and high quality of hexahedral mesh without manual operation. On the other hand, we implementation a non-linear brain shift prediction algorithm. It is designed to run on a GPU server. The experiment results demonstrate that the proposed algorithm can quickly calculate the results on complex mesh.

  9. Vision Loss Caused by Retinal and Lateral Geniculate Nucleus Infarction in H1N1 Influenza.

    PubMed

    Breker, Dane A; Stacey, Andrew W; Srinivasan, Ashok; Bursztyn, Lulu L C D; Trobe, Jonathan D; Johnson, Mark W

    2015-09-01

    A 13-year-old girl developed encephalopathy and severe bilateral vision loss to the level of light perception within 24 hours of having fever and myalgias heralding H1N1 influenza A. Ophthalmoscopy demonstrated findings of confluent ischemic retinopathy. Brain MRI disclosed lateral geniculate body signal abnormalities indicative of hemorrhagic infarction. Despite aggressive treatment with intravenous corticosteroids, intravenous immunoglobulin, and plasmapheresis, vision did not substantially improve. This case demonstrates that H1N1 can cause simultaneous retinal and lateral geniculate body infarctions, a combination of findings not previously described in any condition. We postulate an immunologic response to the virus marked by occlusive damage to arteriolar endothelium. PMID:25887303

  10. Reconstruction of micron resolution mouse brain surface from large-scale imaging dataset using resampling-based variational model.

    PubMed

    Li, Jing; Quan, Tingwei; Li, Shiwei; Zhou, Hang; Luo, Qingming; Gong, Hui; Zeng, Shaoqun

    2015-01-01

    Brain surface profile is essential for brain studies, including registration, segmentation of brain structure and drawing neuronal circuits. Recent advances in high-throughput imaging techniques enable imaging whole mouse brain at micron spatial resolution and provide a basis for more fine quantitative studies in neuroscience. However, reconstructing micron resolution brain surface from newly produced neuronal dataset still faces challenges. Most current methods apply global analysis, which are neither applicable to a large imaging dataset nor to a brain surface with an inhomogeneous signal intensity. Here, we proposed a resampling-based variational model for this purpose. In this model, the movement directions of the initial boundary elements are fixed, the final positions of the initial boundary elements that form the brain surface are determined by the local signal intensity. These features assure an effective reconstruction of the brain surface from a new brain dataset. Compared with conventional typical methods, such as level set based method and active contour method, our method significantly increases the recall and precision rates above 97% and is approximately hundreds-fold faster. We demonstrated a fast reconstruction at micron level of the whole brain surface from a large dataset of hundreds of GB in size within 6 hours. PMID:26245266

  11. Subarachnoid hemorrhage mimicking myocardial infarction.

    PubMed

    Benninger, Felix; Raphaeli, Guy; Steiner, Israel

    2015-12-01

    We discuss a patient with an aneurysmal subarachnoid hemorrhage (SAH) presenting with chest pain, electrocardiogram changes compatible with myocardial infarction, and headache. SAH is a medical emergency but an initial misdiagnosis is common, and diagnosis can be delayed due to atypical presentations. The delay of diagnosis of SAH may endanger the life of the patient. Electrocardiogram abnormalities have been described previously in aneurysmal SAH, and can obscure the correct diagnosis. PMID:26183304

  12. FTY720 Reduces Post-Ischemic Brain Lymphocyte Influx but Does Not Improve Outcome in Permanent Murine Cerebral Ischemia

    PubMed Central

    Liesz, Arthur; Sun, Li; Zhou, Wei; Schwarting, Sönke; Mracsko, Eva; Zorn, Markus; Bauer, Henrike; Sommer, Clemens; Veltkamp, Roland

    2011-01-01

    Background The contribution of neuroinflammation and specifically brain lymphocyte invasion is increasingly recognised as a substantial pathophysiological mechanism after stroke. FTY720 is a potent treatment for primary neuroinflammatory diseases by inhibiting lymphocyte circulation and brain immigration. Previous studies using transient focal ischemia models showed a protective effect of FTY720 but did only partially characterize the involved pathways. We tested the neuroprotective properties of FTY720 in permanent and transient cortical ischemia and analyzed the underlying neuroimmunological mechanisms. Methodology/Principal Findings FTY720 treatment resulted in substantial reduction of circulating lymphocytes while blood monocyte counts were significantly increased. The number of histologically and flow cytometrically analyzed brain invading T- and B lymphocytes was significantly reduced in FTY720 treated mice. However, despite testing a variety of treatment protocols, infarct volume and behavioural dysfunction were not reduced 7d after permanent occlusion of the distal middle cerebral artery (MCAO). Additionally, we did not measure a significant reduction in infarct volume at 24h after 60 min filament-induced MCAO, and did not see differences in brain edema between PBS and FTY720 treatment. Analysis of brain cytokine expression revealed complex effects of FTY720 on postischemic neuroinflammation comprising a substantial reduction of delayed proinflammatory cytokine expression at 3d but an early increase of IL-1? and IFN-? at 24 h after MCAO. Also, serum cytokine levels of IL-6 and TNF-? were increased in FTY720 treated animals compared to controls. Conclusions/Significance In the present study we were able to detect a reduction of lymphocyte brain invasion by FTY720 but could not achieve a significant reduction of infarct volumes and behavioural dysfunction. This lack of neuroprotection despite effective lymphopenia might be attributed to a divergent impact of FTY720 on cytokine expression and possible activation of innate immune cells after brain ischemia. PMID:21701599

  13. Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease

    PubMed Central

    Cotrina, Maria Luisa; Chen, Michael; Han, Xiaoning; Iliff, Jeffrey; Ren, Zeguang; Sun, Wei; Hagemann, Tracy; Goldman, James; Messing, Albee; Nedergaard, Maiken

    2014-01-01

    Alexander disease (AxD) is the only known human pathology caused by mutations in an astrocyte-specific gene, glial fibrillary acidic protein (GFAP). These mutations result in abnormal GFAP accumulations that promote seizures, motor delays and, ultimately, death. The exact contribution of increased, abnormal levels of astrocytic mutant GFAP in the development and progression of the epileptic phenotype is not clear, and we addressed this question using two mouse models of AxD. Comparison of brain seizure activity spontaneously and after traumatic brain injury (TBI), an effective way to trigger seizures, revealed that abnormal GFAP accumulation contributes to abnormal brain activity (increased interictal discharges) but is not a risk factor for the development of epilepsy after TBI. These data highlight the need to further explore the complex and heterogeneous response of astrocytes towards injury and the involvement of GFAP in the progression of AxD. PMID:25069089

  14. Delayed hyperbaric oxygen therapy induces cell proliferation through stabilization of cAMP responsive element binding protein in the rat model of MCAo-induced ischemic brain injury

    PubMed Central

    Mu, Jun; Ostrowski, Robert P.; Soejima, Yoshiteru; Rolland, William B.; Krafft, Paul R.; Tang, Jiping; Zhang, John H.

    2012-01-01

    Treatments that could extend the therapeutic window of opportunity for stroke patients are urgently needed. Early administration of hyperbaric oxygen therapy (HBOT) has been proven neuroprotective in the middle cerebral artery occlusion (MCAo) in rodents. Our aim was to determine: 1) whether delayed HBOT after permanent MCAo (pMCAo) can still convey neuroprotection and restorative cell proliferation, and 2) whether these beneficial effects rely on HBO-induced activation of protein phosphatase-1? (PP1-?) leading to a decreased phosphorylation and ubiquitination of CREB and hence its stabilization. The experiments were performed in one hundred thirty-two male Sprague-Dawley rats with the body weight ranging from 240 to 270 g. Permanent MCAo was induced with the intraluminal filament occluding the right middle cerebral artery (MCA). In the first experiment, HBOT (2.5 ATA, 1 hr daily for 10 days) was started 48 hrs after pMCAo. Neurobehavioral deficits and infarct size as well as cyclic AMP response element-binding protein (CREB) expression and BrdU-DAB staining in the hippocampus and the peri-infarct region were evaluated on day 14 and day 28 post-MCAo. In the second experiment, HBOT (2.5 ATA, 1 hr) was started 3 hrs after pMCAo. The effects of CREB siRNA or PP1-? siRNA on HBO-induced infarct size alterations and target proteins expression were studied. HBOT started with 48 hr delay reduced infarct size, ameliorated neurobehavioral deficits and increased protein expression of CREB, resulting in increased cell proliferations in the hippocampus and peri-infarct region, on day 14 and day 28 post-MCAo. In the acute experiment pMCAo resulted in cerebral infarction and functional deterioration and reduced brainexpression of PP1-?, which led to increased phosphorylation and ubiquitination of CREB 24 hrs after MCAo. However HBOT administered 3 hrs after ischemia reversed these molecular events and resulted in CREB stabilization, infarct size reduction and neurobehavioral improvement. Gene silencing with CREB siRNA or PP1-? siRNA reduced acute beneficial effects of HBO. In conclusion, delayed daily HBOT presented as potent neuroprotectant in pMCAo rats, increased CREB expression and signaling activity, and bolstered regenerative type cell proliferation in the injured brain. As shown in the acute experiment these effects of HBO were likely to be mediated by reducing ubiquitin-dependent CREB degradation owing to HBO-induced activation of PP1?. PMID:23146993

  15. Multiplex Three-Dimensional Brain Gene Expression Mapping in a Mouse Model of Parkinson's Disease

    PubMed Central

    Brown, Vanessa M.; Ossadtchi, Alex; Khan, Arshad H.; Yee, Simon; Lacan, Goran; Melega, William P.; Cherry, Simon R.; Leahy, Richard M.; Smith, Desmond J.

    2002-01-01

    To facilitate high-throughput 3D imaging of brain gene expression, a new method called voxelation has been developed. Spatially registered voxels (cubes) are analyzed, resulting in multiple volumetric maps of gene expression analogous to the images reconstructed in biomedical imaging systems. Using microarrays, 40 voxel images for 9000 genes were acquired from brains of both normal mice and mice in which a pharmacological model of Parkinson's disease (PD) had been induced by methamphetamine. Quality-control analyses established the reproducibility of the voxelation procedure. The investigation revealed a common network of coregulated genes shared between the normal and PD brain, and allowed identification of putative control regions responsible for these networks. In addition, genes involved in cell/cell interactions were found to be prominently regulated in the PD brains. Finally, singular value decomposition (SVD), a mathematical method used to provide parsimonious explanations of complex data sets, identified gene vectors and their corresponding images that distinguished between normal and PD brain structures, most pertinently the striatum. [All study results and supplementary data are available on the web at http://www.pharmacology.ucla.edu/smithlab/genome_multiplex and at http://www.genome.org. Microarray data are also available at GEO, http://www.ncbi.nlm.nih.gov/geo, under the series accession no. GSE30.] PMID:12045141

  16. A Screening, Prevention, and Restoration Model for Saving the Injured Brain

    PubMed Central

    Vasilevskis, Eduard E.; Pandharipande, Pratik P.; Girard, Timothy D.; Ely, E. Wesley

    2013-01-01

    We face a profound and emerging public health problem in the form of acute and chronic brain dysfunction. This affects both young and elderly intensive care unit (ICU) survivors and is altering the landscape of society. Two-thirds of ICU patients develop delirium, and this is associated with longer stays, increased costs and excess mortality. In addition, over one-half of ICU survivors suffer a dementia-like illness that impacts their physical and cognitive functional abilities and which appears to be related to the duration of their ICU delirium. A new paradigm of how Intensivists handle the brain is required. We propose a 3-step approach to address this emerging epidemic, which includes Screening, Prevention, and Restoration of brain function (SPR). Screening combines risk factor identification and delirium assessment using validated instruments. Prevention of acute and chronic brain dysfunction requires implementation of a core model of care that combines evidence-based practices: awakening and breathing coordination with target -based sedation, delirium monitoring, and exercise / early mobility (ABCDE). Restoration introduces strategies of ongoing screening and treatment for ICU survivors at high risk of ongoing brain dysfunction. This practical system applying many evidence-based concepts, incorporates personalized medicine, systems based practice, and continuing research and development towards improving acute and chronic cognitive outcomes. PMID:21164415

  17. MRI characteristics of acute and subacute brainstem and thalamic infarctions: value of T2- and diffusion-weighted sequences.

    PubMed

    Küker, Wilhelm; Weise, Jens; Krapf, Hilmar; Schmidt, Friederike; Friese, Sigrid; Bähr, Mathias

    2002-01-01

    MRI including diffusion-weighted sequences (DW-MRI) has demonstrated its high sensitivity for acute supratentorial ischemic lesions. In this study we examined the sensitivity of different MRI sequences for the detection of acute brainstem and isolated thalamic infarctions. Diffusion- and T2-weighted MRI of 45 consecutive patients with signs and symptoms of infratentorial and thalamic infarction between 6/1997 and 1/2000 were analysed. The time between the onset of symptoms and the first MRI varied between 2 hours to 7 days with a median of 2 days. MRI repeats were performed in 4 patients in whom the clinical brainstem infarction had not been detected initially. Lesion detectability and size were evaluated for different brainstem and thalamic localizations. An acute brainstem or thalamic infarction as defined by the clinical condition could be identified in all patients by comparison of DW-MRI and T2-weighted images. Pons in farctions were the largest, followed by midbrain and thalamic lesions. Medulla oblongata infarctions were small in comparison. Pons, mid-brain and thalamic infarctions were reliably identified beginning 12 hours after the onset of symptoms. In contrast, detectability of medulla oblongata infarctions varied within the first 24 hours and their overall visibility was worse than that of other brainstem infarctions corresponding to their small size. However, regardless of loca tion, none of the 3 infarctions examined within the first 5 hours after the onset of symptoms could be identified. These lesions were demonstrated in follow-up examinations. In conclusion, pontine, midbrain and thalamic infarctions can reliably be visualized by a combination of DW-MRI and T2-weighted images beginning 12 hours after the ischemic attack. However, sensitivity seems to be lower earlier than 12 hours after ischemia and for medulla oblongata lesions. PMID:11954866

  18. Differences in amyloid-? clearance across mouse and human blood-brain barrier models: Kinetic analysis and mechanistic modeling

    PubMed Central

    Qosa, Hisham; Abuasal, Bilal S.; Romero, Ignacio A.; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N.; Kaddoumi, Amal

    2014-01-01

    Alzheimer’s disease (AD) has a characteristic hallmark of amyloid-? (A?) accumulation in the brain. This accumulation of A? has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate A? clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient A? clearance. However, the contribution of each process to A? clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect A? clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to A? clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected 125I-A?40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare A? clearance between mouse and human BBB models. Kinetic studies for A?40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of 125I-A?40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of 125I-A?40 and the rate of each process. Established mechanistic model suggested significantly higher rates of A? uptake and degradation in bEnd3 cells as rationale for the observed differences in 125I-A?40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of A? from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to A? clearance and offer, for the first time, a mathematical model that describes A? clearance across BBB. PMID:24467845

  19. Differences in amyloid-? clearance across mouse and human blood-brain barrier models: kinetic analysis and mechanistic modeling.

    PubMed

    Qosa, Hisham; Abuasal, Bilal S; Romero, Ignacio A; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N; Kaddoumi, Amal

    2014-04-01

    Alzheimer's disease (AD) has a characteristic hallmark of amyloid-? (A?) accumulation in the brain. This accumulation of A? has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate A? clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient A? clearance. However, the contribution of each process to A? clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect A? clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to A? clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected (125)I-A?40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare A? clearance between mouse and human BBB models. Kinetic studies for A?40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of (125)I-A?40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of (125)I-A?40 and the rate of each process. Established mechanistic model suggested significantly higher rates of A? uptake and degradation in bEnd3 cells as rationale for the observed differences in (125)I-A?40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of A? from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to A? clearance and offer, for the first time, a mathematical model that describes A? clearance across BBB. PMID:24467845

  20. Biological Principles in Self-Organization of Young Brain - Viewed from Kohonen Model

    E-print Network

    Pallaver, T; Parizeau, M; Pallaver, Tanguy; Kroger, Helmut; Parizeau, Marc

    2006-01-01

    Variants of the Kohonen model are proposed to study biological principles of self-organization in a model of young brain. We suggest a function to measure aquired knowledge and use it to auto-adapt the topology of neuronal connectivity, yielding substantial organizational improvement relative to the standard model. In the early phase of organization with most intense learning, we observe that neural connectivity is of Small World type, which is very efficient to organize neurons in response to stimuli. In analogy to human brain where pruning of neural connectivity (and neuron cell death) occurs in early life, this feature is present also in our model, which is found to stabilize neuronal response to stimuli.

  1. Task decomposition: a framework for comparing diverse training models in human brain plasticity studies

    PubMed Central

    Coffey, Emily B. J.; Herholz, Sibylle C.

    2013-01-01

    Training studies, in which the structural or functional neurophysiology is compared before and after expertise is acquired, are increasingly being used as models for understanding the human brain’s potential for reorganization. It is proving difficult to use these results to answer basic and important questions like how task training leads to both specific and general changes in behavior and how these changes correspond with modifications in the brain. The main culprit is the diversity of paradigms used as complex task models. An assortment of activities ranging from juggling to deciphering Morse code has been reported. Even when working in the same general domain, few researchers use similar training models. New ways to meaningfully compare complex tasks are needed. We propose a method for characterizing and deconstructing the task requirements of complex training paradigms, which is suitable for application to both structural and functional neuroimaging studies. We believe this approach will aid brain plasticity research by making it easier to compare training paradigms, identify “missing puzzle pieces,” and encourage researchers to design training protocols to bridge these gaps. PMID:24115927

  2. Prenatal pharmacotherapy rescues brain development in a Down's syndrome mouse model.

    PubMed

    Guidi, Sandra; Stagni, Fiorenza; Bianchi, Patrizia; Ciani, Elisabetta; Giacomini, Andrea; De Franceschi, Marianna; Moldrich, Randal; Kurniawan, Nyoman; Mardon, Karine; Giuliani, Alessandro; Calzà, Laura; Bartesaghi, Renata

    2014-02-01

    Intellectual impairment is a strongly disabling feature of Down's syndrome, a genetic disorder of high prevalence (1 in 700-1000 live births) caused by trisomy of chromosome 21. Accumulating evidence shows that widespread neurogenesis impairment is a major determinant of abnormal brain development and, hence, of intellectual disability in Down's syndrome. This defect is worsened by dendritic hypotrophy and connectivity alterations. Most of the pharmacotherapies designed to improve cognitive performance in Down's syndrome have been attempted in Down's syndrome mouse models during adult life stages. Yet, as neurogenesis is mainly a prenatal event, treatments aimed at correcting neurogenesis failure in Down's syndrome should be administered during pregnancy. Correction of neurogenesis during the very first stages of brain formation may, in turn, rescue improper brain wiring. The aim of our study was to establish whether it is possible to rescue the neurodevelopmental alterations that characterize the trisomic brain with a prenatal pharmacotherapy with fluoxetine, a drug that is able to restore post-natal hippocampal neurogenesis in the Ts65Dn mouse model of Down's syndrome. Pregnant Ts65Dn females were treated with fluoxetine from embryonic Day 10 until delivery. On post-natal Day 2 the pups received an injection of 5-bromo-2-deoxyuridine and were sacrificed after either 2 h or after 43 days (at the age of 45 days). Untreated 2-day-old Ts65Dn mice exhibited a severe neurogenesis reduction and hypocellularity throughout the forebrain (subventricular zone, subgranular zone, neocortex, striatum, thalamus and hypothalamus), midbrain (mesencephalon) and hindbrain (cerebellum and pons). In embryonically treated 2-day-old Ts65Dn mice, precursor proliferation and cellularity were fully restored throughout all brain regions. The recovery of proliferation potency and cellularity was still present in treated Ts65Dn 45-day-old mice. Moreover, embryonic treatment restored dendritic development, cortical and hippocampal synapse development and brain volume. Importantly, these effects were accompanied by recovery of behavioural performance. The cognitive deficits caused by Down's syndrome have long been considered irreversible. The current study provides novel evidence that a pharmacotherapy with fluoxetine during embryonic development is able to fully rescue the abnormal brain development and behavioural deficits that are typical of Down's syndrome. If the positive effects of fluoxetine on the brain of a mouse model are replicated in foetuses with Down's syndrome, fluoxetine, a drug usable in humans, may represent a breakthrough for the therapy of intellectual disability in Down's syndrome. PMID:24334313

  3. Experimental Models of Anxiety for Drug Discovery and Brain Research

    E-print Network

    Kalueff, Allan V.

    . Kalueff Abstract Animal models have been vital to recent advances in experimental neuroscience, including confronta- tion), these phenotypes have clear utility in testing the effects of psychotropic drugs differ- ent experimental models of mouse anxiety and discuss their utility for testing anxiolytic

  4. Neural mass modeling of power-line magnetic fields effects on brain activity.

    PubMed

    Modolo, J; Thomas, A W; Legros, A

    2013-01-01

    Neural mass models are an appropriate framework to study brain activity, combining a high degree of biological realism while being mathematically tractable. These models have been used, with a certain success, to simulate brain electric (electroencephalography, EEG) and metabolic (functional magnetic resonance imaging, fMRI) activity. However, concrete applications of neural mass models have remained limited to date. Motivated by experimental results obtained in humans, we propose in this paper a neural mass model designed to study the interaction between power-line magnetic fields (MFs) (60 Hz in North America) and brain activity. The model includes pyramidal cells; dendrite-projecting, slow GABAergic neurons; soma-projecting, fast GABAergic neurons; and glutamatergic interneurons. A simple phenomenological model of interaction between the induced electric field and neuron membranes is also considered, along with a model of post-synaptic calcium concentration and associated changes in synaptic weights Simulated EEG signals are produced in a simple protocol, both in the absence and presence of a 60 Hz MF. These results are discussed based on results obtained previously in humans. Notably, results highlight that (1) EEG alpha (8-12 Hz) power can be modulated by weak membrane depolarizations induced by the exposure; (2) the level of input noise has a significant impact on EEG power modulation; and (3) the threshold value in MF flux density resulting in a significant effect on the EEG depends on the type of neuronal populations modulated by the MF exposure. Results obtained from the model shed new light on the effects of power-line MFs on brain activity, and will provide guidance in future human experiments. This may represent a valuable contribution to international regulation agencies setting guidelines on MF values to which the general public and workers can be exposed. PMID:23596412

  5. The interaction of carbon nanotubes with an in vitro blood-brain barrier model and mouse brain in vivo

    PubMed Central

    Kafa, Houmam; Wang, Julie Tzu-Wen; Rubio, Noelia; Venner, Kerrie; Anderson, Glenn; Pach, Elzbieta; Ballesteros, Belén; Preston, Jane E.; Abbott, N. Joan; Al-Jamal, Khuloud T.

    2015-01-01

    Carbon nanotubes (CNTs) are a novel nanocarriers with interesting physical and chemical properties. Here we investigate the ability of amino-functionalized multi-walled carbon nanotubes (MWNTs-NH3+) to cross the Blood-Brain Barrier (BBB) in vitro using a co-culture BBB model comprising primary porcine brain endothelial cells (PBEC) and primary rat astrocytes, and in vivo following a systemic administration of radiolabelled f-MWNTs. Transmission Electron microscopy (TEM) confirmed that MWNTs-NH3+ crossed the PBEC monolayer via energy-dependent transcytosis. MWNTs-NH3+ were observed within endocytic vesicles and multi-vesicular bodies after 4 and 24 h. A complete crossing of the in vitro BBB model was observed after 48 h, which was further confirmed by the presence of MWNTs-NH3+ within the astrocytes. MWNT-NH3+ that crossed the PBEC layer was quantitatively assessed using radioactive tracers. A maximum transport of 13.0 ± 1.1% after 72 h was achieved using the co-culture model. f-MWNT exhibited significant brain uptake (1.1  ±  0.3% injected dose/g) at 5 min after intravenous injection in mice, after whole body perfusion with heparinized saline. Capillary depletion confirmed presence of f-MWNT in both brain capillaries and parenchyma fractions. These results could pave the way for use of CNTs as nanocarriers for delivery of drugs and biologics to the brain, after systemic administration. PMID:25890741

  6. New Predictive Models for Blood—Brain Barrier Permeability of Drug-like Molecules

    PubMed Central

    Kortagere, Sandhya; Chekmarev, Dmitriy; Welsh, William J.; Ekins, Sean

    2009-01-01

    Purpose The goals of the present study were to apply a generalized regression model and support vector machine (SVM) models with Shape Signatures descriptors, to the domain of blood—brain barrier (BBB) modeling. Materials and Methods The Shape Signatures method is a novel computational tool that was used to generate molecular descriptors utilized with the SVM classification technique with various BBB datasets. For comparison purposes we have created a generalized linear regression model with eight MOE descriptors and these same descriptors were also used to create SVM models. Results The generalized regression model was tested on 100 molecules not in the model and resulted in a correlation r2=0.65. SVM models with MOE descriptors were superior to regression models, while Shape Signatures SVM models were comparable or better than those with MOE descriptors. The best 2D shape signature models had 10-fold cross validation prediction accuracy between 80–83% and leave-20%-out testing prediction accuracy between 80–82% as well as correctly predicting 84% of BBB+ compounds (n=95) in an external database of drugs. Conclusions Our data indicate that Shape Signatures descriptors can be used with SVM and these models may have utility for predicting blood—brain barrier permeation in drug discovery. PMID:18415049

  7. Assessment of Regional Myocardial Strain using Cardiac Elastography: Distinguishing Infarcted from Non-Infarcted Myocardium

    E-print Network

    Konofagou, Elisa E.

    Assessment of Regional Myocardial Strain using Cardiac Elastography: Distinguishing Infarcted from in a patient with a known myocardial infarction. Envelope- detected sonographic data was used to estimate Non-Infarcted Myocardium Elisa E. Konofagou', Timothy Harrigan2 and Scott Solomon3 'Focused Ultrasound

  8. Brain in flames – animal models of psychosis: utility and limitations

    PubMed Central

    Mattei, Daniele; Schweibold, Regina; Wolf, Susanne A

    2015-01-01

    The neurodevelopmental hypothesis of schizophrenia posits that schizophrenia is a psychopathological condition resulting from aberrations in neurodevelopmental processes caused by a combination of environmental and genetic factors which proceed long before the onset of clinical symptoms. Many studies discuss an immunological component in the onset and progression of schizophrenia. We here review studies utilizing animal models of schizophrenia with manipulations of genetic, pharmacologic, and immunological origin. We focus on the immunological component to bridge the studies in terms of evaluation and treatment options of negative, positive, and cognitive symptoms. Throughout the review we link certain aspects of each model to the situation in human schizophrenic patients. In conclusion we suggest a combination of existing models to better represent the human situation. Moreover, we emphasize that animal models represent defined single or multiple symptoms or hallmarks of a given disease. PMID:26064050

  9. Ventrucci, M., Bowman, A. W., Miller, C., and Gross, J. (2014) Quasi-periodic spatiotemporal models of brain activation in single-trial MEG

    E-print Network

    2014-01-01

    models of brain activation in single-trial MEG experiments. Statistical Modelling, 14 (5). pp. 417-periodic spatiotemporal models of brain activation in single-trial MEG experiments Massimo Ventrucci,1 Adrian W Bowman,2 technique which measures neuronal activity in the brain. Even when a subject is in a resting state, meg data

  10. Cardiac remodeling and physical training post myocardial infarction

    PubMed Central

    Garza, Michael A; Wason, Emily A; Zhang, John Q

    2015-01-01

    After myocardial infarction (MI), the heart undergoes extensive myocardial remodeling through the accumulation of fibrous tissue in both the infarcted and noninfarcted myocardium, which distorts tissue structure, increases tissue stiffness, and accounts for ventricular dysfunction. There is growing clinical consensus that exercise training may beneficially alter the course of post-MI myocardial remodeling and improve cardiac function. This review summarizes the present state of knowledge regarding the effect of post-MI exercise training on infarcted hearts. Due to the degree of difficulty to study a viable human heart at both protein and molecular levels, most of the detailed studies have been performed by using animal models. Although there are some negative reports indicating that post-MI exercise may further cause deterioration of the wounded hearts, a growing body of research from both human and animal experiments demonstrates that post-MI exercise may beneficially alter the course of wound healing and improve cardiac function. Furthermore, the improved function is likely due to exercise training-induced mitigation of renin-angiotensin-aldosterone system, improved balance between matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, favorable myosin heavy chain isoform switch, diminished oxidative stress, enhanced antioxidant capacity, improved mitochondrial calcium handling, and boosted myocardial angiogenesis. Additionally, meta-analyses revealed that exercise-based cardiac rehabilitation has proven to be effective, and remains one of the least expensive therapies for both the prevention and treatment of cardiovascular disease, and prevents re-infarction. PMID:25717353

  11. MALDI Mass Spectrometric Imaging of Lipids in Rat Brain Injury Models

    NASA Astrophysics Data System (ADS)

    Hankin, Joseph A.; Farias, Santiago E.; Barkley, Robert M.; Heidenreich, Kim; Frey, Lauren C.; Hamazaki, Kei; Kim, Hee-Yong; Murphy, Robert C.

    2011-06-01

    Matrix-assisted laser desorption ionization/ionization imaging mass spectrometry (MALDI IMS) with a time-of-flight analyzer was used to characterize the distribution of lipid molecular species in the brain of rats in two injury models. Ischemia/reperfusion injury of the rat brain after bilateral occlusion of the carotid artery altered appearance of the phospholipids present in the hippocampal region, specifically the CA1 region. These brain regions also had a large increase in the ion abundance at m/z 548.5 and collisional activation supported identification of this ion as arising from ceramide (d18:1/18:0), a lipid known to be associated with cellular apoptosis. Traumatic brain injury model in the rat was examined by MALDI IMS and the area of damage also showed an increase in ceramide (d18:1/18:0) and a remarkable loss of signal for the potassium adduct of the most abundant phosphocholine molecular species 16:0/18:1 (PC) with a corresponding increase in the sodium adduct ion. This change in PC alkali attachment ion was suggested to be a result of edema and influx of extracellular fluid likely through a loss of Na/K-ATPase caused by the injury. These studies reveal the value of MALDI IMS to examine tissues for changes in lipid biochemistry and will provide data needed to eventually understand the biochemical mechanisms relevant to tissue injury.

  12. Propofol Pretreatment Fails to Provide Neuroprotection Following a Surgically Induced Brain Injury Rat Model.

    PubMed

    Pakkianathan, Colleen; Benggon, Michael; Khatibi, Nikan H; Chen, Hank; Marcantonio, Suzzanne; Applegate, Richard; Tang, Jiping; Zhang, John

    2016-01-01

    Neurosurgical procedures are associated with unintentional damage to the brain during surgery, known as surgically induced brain injuries (SBI), which have been implicated in orchestrating structural and neurobehavioral deterioration. Propofol, an established hypnotic anesthetic agent, has been shown to ameliorate neuronal injury when given after injury in a number of experimental brain studies. We tested the hypothesis that propofol pretreatment confers neuroprotection against SBI and will reduce cerebral edema formation and neurobehavioral deficits in our rat population. Sprague-Dawley rats were treated with low- and high-dose propofol 30 min before SBI. At 24 h post injury, brain water content and neurobehavioral assessment was conducted based on previously established models. In vehicle-treated rats, SBI resulted in significant cerebral edema and higher neurological deficit scores compared with sham-operated rats. Low- or high-dose propofol therapy neither reduced cerebral edema nor improved neurologic function. The results suggest that propofol pretreatment fails to provide neuroprotection in SBI rats. However, it is possible that a SBI model with less magnitude of injury or that propofol re-dosing, given the short-acting pharmacokinetic property of propofol, may be needed to provide definitive conclusions. PMID:26463969

  13. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer's disease.

    PubMed

    Bajo, R; Pusil, S; López, M E; Canuet, L; Pereda, E; Osipova, D; Maestú, F; Pekkonen, E

    2015-01-01

    Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD. PMID:26130273

  14. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer’s disease

    PubMed Central

    Bajo, R.; Pusil, S.; López, M. E.; Canuet, L.; Pereda, E.; Osipova, D.; Maestú, F.; Pekkonen, E.

    2015-01-01

    Scopolamine administration may be considered as a psychopharmacological model of Alzheimer’s disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD. PMID:26130273

  15. Development of a skull/brain model for military wound ballistics studies.

    PubMed

    Carr, Debra; Lindstrom, Anne-Christine; Jareborg, Andreas; Champion, Stephen; Waddell, Neil; Miller, David; Teagle, Michael; Horsfall, Ian; Kieser, Jules

    2015-05-01

    Reports on penetrating ballistic head injuries in the literature are dominated by case studies of suicides; the penetrating ammunition usually being .22 rimfire or shotgun. The dominating cause of injuries in modern warfare is fragmentation and hence, this is the primary threat that military helmets protect the brain from. When helmets are perforated, this is usually by bullets. In combat, 20% of penetrating injuries occur to the head and its wounding accounts for 50% of combat deaths. A number of head simulants are described in the academic literature, in ballistic test methods for helmets (including measurement of behind helmet blunt trauma, BHBT) and in the 'open' and 'closed' government literature of several nations. The majority of these models are not anatomically correct and are not assessed with high-velocity rifle ammunition. In this article, an anatomically correct 'skull' (manufactured from polyurethane) and 'brain' (manufactured from 10%, by mass, gelatine) model for use in military wound ballistic studies is described. Filling the cranium completely with gelatine resulted in a similar 'skull' fracture pattern as an anatomically correct 'brain' combined with a representation of cerebrospinal fluid. In particular, posterior cranial fossa and occipital fractures and brain ejection were observed. This pattern of injury compared favourably to reported case studies of actual incidents in the literature. PMID:25194710

  16. Allostasis and the human brain: Integrating models of stress from the social and life sciences

    PubMed Central

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

    2009-01-01

    We draw on the theory of allostasis to develop an integrative model of the current stress process that highlights the brain as a dynamically adapting interface between the changing environment and the biological self. We review evidence that the core emotional regions of the brain constitute the primary mediator of the well-established association between stress and health, as well as the neural focus of “wear and tear” due to ongoing adaptation. This mediation, in turn, allows us to model the interplay over time between context, current stressor exposure, internal regulation of bodily processes, and health outcomes. We illustrate how this approach facilitates the integration of current findings in human neuroscience and genetics with key constructs from stress models from the social and life sciences, with implications for future research and the design of interventions targeting individuals at risk. PMID:20063966

  17. A numerical model for the study of photoacoustic imaging of brain tumours

    E-print Network

    Firouzi, Kamyar

    2015-01-01

    Photoacoustic imaging has shown great promise for medical imaging, where optical energy absorption by blood haemoglobin is used as the contrast mechanism. A numerical method was developed for the in-silico assessment of the photoacoustic image reconstruction of the brain. Image segmentation techniques were used to prepare a digital phantom from MR images. Light transport through brain tissue was modelled using a Finite Element approach. The resulting acoustic pressure was then estimated by pulsed photoacoustics considerations. The forward acoustic wave propagation was modelled by the linearized coupled first order wave equations and solved by an acoustic k-space method. Since skull bone is an elastic solid and strongly attenuates ultrasound (due to both scattering and absorption), a k-space method was developed for elastic media. To model scattering effects, a new approach was applied based on propagation in random media. In addition, absorption effects were incorporated using a power law. Finally, the acoust...

  18. Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia–Reperfusion Model

    PubMed Central

    Dash, Rajesh; Kim, Paul J; Matsuura, Yuka; Ikeno, Fumiaki; Metzler, Scott; Huang, Ngan F; Lyons, Jennifer K; Nguyen, Patricia K; Ge, Xiaohu; Wong Po Foo, Cheryl; McConnell, Michael V; Wu, Joseph C; Yeung, Alan C; Harnish, Phillip; Yang, Phillip C

    2015-01-01

    Background The exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri-infarct region (PIR) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese-enhanced magnetic resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts. Methods and Results Twelve adult swine underwent ischemia–reperfusion injury. Digital subtraction of MEMRI-negative myocardium (intrainfarct region) from delayed gadolinium enhancement MRI–positive myocardium (PIR and intrainfarct region) clearly delineated the PIR in which the MEMRI-positive signal reflected PIR viability. Human amniotic mesenchymal stem cells (hAMSCs) represent a unique population of immunomodulatory mesodermal stem cells that restored the murine PIR. Immediately following hAMSC delivery, MEMRI demonstrated an increased PIR viability signal compared with control. Direct PIR viability remained higher in hAMSC-treated hearts for >6 weeks. Increased PIR viability correlated with improved regional contractility, left ventricular ejection fraction, infarct size, and hAMSC engraftment, as confirmed by immunocytochemistry. Increased MEMRI and positron emission tomography reporter gene signal in the intrainfarct region and the PIR correlated with sustained functional augmentation (global and regional) within the hAMSC group (mean change, left ventricular ejection fraction: hAMSC 85±60%, control 8±10%; P<0.05) and reduced chamber dilatation (left ventricular end-diastole volume increase: hAMSC 24±8%, control 110±30%; P<0.05). Conclusions The positron emission tomography reporter gene signal of hAMSC engraftment correlates with the improved MEMRI signal in the PIR. The increased MEMRI signal represents PIR viability and the restorative potential of the injured heart. This in vivo multimodality imaging platform represents a novel, real-time method of tracking PIR viability and stem cell engraftment while providing a mechanistic explanation of the therapeutic efficacy of cardiovascular stem cells. PMID:26215972

  19. Evaluation of an intraoperative ultrasound training model based on a cadaveric sheep brain

    PubMed Central

    Vavruska, Jan; Buhl, Ralf; Petridis, Athanasios K.; Maslehaty, Homajoun; Scholz, Martin

    2014-01-01

    Background: The present study evaluates the effectiveness of an ultrasound (US) practice course based on a sheep brain cadaver. Neurosurgical education is considerably restrained following patient safety objections and work time restrictions. It is therefore of vital importance to offer residents an opportunity to practice certain US techniques in a controlled environment without ethical or legal restrictions. We developed an US training model based on a sheep brain cadaver in order to demonstrate the feasibility of such a model, facilitate crucial anatomic knowledge, and demonstrate a learning curve from it. Methods: Over the course of 2 months from December 2012-January 2013, a total of 13 residents took part in a three part training session, each consisting of 20-30 min of individual US-training and performance evaluation based on a biological phantom. The first cadaver was a physiologic sheep brain. After initial familiarization with the US, the residents performed an US on a second cadaveric brain and tried to find a 0.5 cm big (in diameter) echogenic structure. In a third brain they were asked to identify a cyst (Fogarty catheter filled with water). Results: Thirteen neurosurgical residents participated in the study. After the first training session, the learning curve improved significantly in the second and the third session. The ability to actuate the US device, the time needed to display crucial anatomic landmarks, and to locate the two different artificial masses increased, and respectively decreased remarkably by up to 80%. Conclusion: After 2 months and three training sessions, the handling of the US from the residents was excellent in the operating room. The accuracy and the dexterity in use of the US improved significantly. The participants found the model to be realistic and agreed on the need for further promotion of such courses. PMID:24818053

  20. Transport of treosulfan and temozolomide across an in-vitro blood-brain barrier model.

    PubMed

    Linz, Ute; Hupert, Michelle; Santiago-Schübel, Beatrix; Wien, Sascha; Stab, Julia; Wagner, Sylvia

    2015-08-01

    In vitro, treosulfan (TREO) has shown high effectiveness against malignant gliomas. However, a first clinical trial for newly diagnosed glioblastoma did not show any positive effect. Even though dosing and timing might have been the reasons for this failure, it might also be that TREO does not reach the brain in sufficient amount. Surprisingly, there are no published data on TREO uptake into the brain of patients, despite extensive research on this compound. An in-vitro blood-brain barrier (BBB) model consisting of primary porcine brain capillary endothelial cells was used to determine the transport of TREO across the cell monolayer. Temozolomide (TMZ), the most widely used cytotoxic drug for malignant gliomas, served as a reference. An HPLC-ESI-MS/MS procedure was developed to detect TREO and TMZ in cell culture medium. Parallel to the experimental approach, the permeability of TREO and the reference substance across the in-vitro BBB was estimated on the basis of their physicochemical properties. The detection limit was 30?nmol/l for TREO and 10?nmol/l for TMZ. Drug transport was measured in two directions: influx, apical-to-basolateral (A-to-B), and efflux, basolateral-to-apical (B-to-A). For TREO, the A-to-B permeability was lower (1.6%) than the B-to-A permeability (3.0%). This was in contrast to TMZ, which had higher A-to-B (13.1%) than B-to-A (7.2%) permeability values. The in-vitro BBB model applied simulated the human BBB properly for TMZ. It is, therefore, reasonable to assume that the values for TREO are also meaningful. Considering the lack of noninvasive, significant alternative methods to study transport across the BBB, the porcine brain capillary endothelial cell model was efficient to collect first data for TREO that explain the disappointing clinical results for this drug against cerebral tumors. PMID:25919318

  1. Modeling an angiogenesis treatment after a myocardial Literature study

    E-print Network

    Vuik, Kees

    Modeling an angiogenesis treatment after a myocardial infarction Literature study L.Y.D. Crapts Biological background 3 2.1 Myocardial infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

  2. Baicalin attenuates brain edema in a rat model of intracerebral hemorrhage.

    PubMed

    Zhou, Qing-Bo; Jin, Yun-Ling; Jia, Qing; Zhang, Yuan; Li, Lu-Yang; Liu, Ping; Liu, Yuan-Tao

    2014-02-01

    Baicalin is a flavonoid compound purified from the roots of Scutellaria baicalensis, which possesses multiple biological activities. Previous studies have shown that baicalin is protective in ischemic cerebral diseases. The aim of the present study was to examine the effects of baicalin on brain injury in a rat model of intracerebral hemorrhage (ICH) and to explore the possible mechanisms. Intracerebral hemorrhage was induced in male Wistar rats by injection of 0.5 U collagenaseVII to the caudate nucleus. Sham operation rats were injected with equal volume of saline. After the induction of ICH, the rats were randomly divided into four groups and administered with different dose of baicalin (0, 25, 50, or 100 mg/kg in saline) through peritoneal injection. The brain tissues around the hemorrhage areas were collected on days 1, 3, and 5 after treatment. Brain edema was analyzed by desiccation method; the metalloproteinase-9 (MMP-9) protein and mRNA expression were determined by western blotting and real time RT-PCR, respectively. Nuclear factor-?B (NF-?B) protein expression was analyzed by western blotting. IL-1? and IL-6 levels were determined by enzyme-linked immunosorbent assay. Blood-brain barrier permeability was determined by Evans blue leakage method. The results showed that baicalin reduced brain edema following ICH in a dose-dependent manner, with concomitant inhibition of NF-?B activation and suppression of MMP-9 expression. In addition, baicalin also reduced IL-1? and IL-6 production, as well as blood-brain barrier permeability. The above results indicated that baicalin prevents against perihematomal edema development after intracerebral hemorrhage possibly through an anti-inflammatory mechanism. PMID:23974988

  3. Application of radiosurgical techniques to produce a primate model of brain lesions

    PubMed Central

    Kunimatsu, Jun; Miyamoto, Naoki; Ishikawa, Masayori; Shirato, Hiroki; Tanaka, Masaki

    2015-01-01

    Behavioral analysis of subjects with discrete brain lesions provides important information about the mechanisms of various brain functions. However, it is generally difficult to experimentally produce discrete lesions in deep brain structures. Here we show that a radiosurgical technique, which is used as an alternative treatment for brain tumors and vascular malformations, is applicable to create non-invasive lesions in experimental animals for the research in systems neuroscience. We delivered highly focused radiation (130–150 Gy at ISO center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear accelerator (LINAC). The effects of irradiation were assessed by analyzing oculomotor performance along with magnetic resonance (MR) images before and up to 8 months following irradiation. In parallel with tissue edema indicated by MR images, deficits in saccadic and smooth pursuit eye movements were observed during several days following irradiation. Although initial signs of oculomotor deficits disappeared within a month, damage to the tissue and impaired eye movements gradually developed during the course of the subsequent 6 months. Postmortem histological examinations showed necrosis and hemorrhages within a large area of the white matter and, to a lesser extent, in the adjacent gray matter, which was centered at the irradiated target. These results indicated that the LINAC system was useful for making brain lesions in experimental animals, while the suitable radiation parameters to generate more focused lesions need to be further explored. We propose the use of a radiosurgical technique for establishing animal models of brain lesions, and discuss the possible uses of this technique for functional neurosurgical treatments in humans. PMID:25964746

  4. Traumatic brain injury caused by laser-induced shock wave in rats: a novel laboratory model for studying blast-induced traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Hatano, Ben; Matsumoto, Yoshihisa; Otani, Naoki; Saitoh, Daizoh; Tokuno, Shinichi; Satoh, Yasushi; Nawashiro, Hiroshi; Matsushita, Yoshitaro; Sato, Shunichi

    2011-03-01

    The detailed mechanism of blast-induced traumatic brain injury (bTBI) has not been revealed yet. Thus, reliable laboratory animal models for bTBI are needed to investigate the possible diagnosis and treatment for bTBI. In this study, we used laser-induced shock wave (LISW) to induce TBI in rats and investigated the histopathological similarities to actual bTBI. After craniotomy, the rat brain was exposed to a single shot of LISW with a diameter of 3 mm at various laser fluences. At 24 h after LISW exposure, perfusion fixation was performed and the extracted brain was sectioned; the sections were stained with hematoxylin-eosin. Evans blue (EB) staining was also used to evaluate disruption of the blood brain barrier. At certain laser fluence levels, neural cell injury and hemorrhagic lesions were observed in the cortex and subcortical region. However, injury was limited in the tissue region that interacted with the LISW. The severity of injury increased with increasing laser fluence and hence peak pressure of the LISW. Fluorescence originating from EB was diffusively observed in the injuries at high fluence levels. Due to the grade and spatial controllability of injuries and the histological observations similar to those in actual bTBI, brain injuries caused by LISWs would be useful models to study bTBI.

  5. Interplay between pro-inflammatory cytokines and brain oxidative stress biomarkers: evidence of parallels between butyl paraben intoxication and the valproic acid brain physiopathology in autism rat model.

    PubMed

    Hegazy, Hoda G; Ali, Elham H A; Elgoly, Amany H Mahmoud

    2015-02-01

    Butyl paraben is a preservative used in food, drugs and cosmetics. Neurotoxic effect was reported recently beside the potential estrogenic activity of parabens. There is controversy as to the potential harmful effects of butyl parabens, which are suspected to contribute to autism and learning disabilities. The purpose of this study was to examine the similarities between paraben intoxication signs in the rat brain and brain markers in an autistic like rat model. This study provides evidence of many parallels between the two, including (1) oxidative stress, (2) decreased reduced glutathione levels and elevated oxidised glutathione, (3) mitochondrial dysfunction, and (4) neuroinflammation and increased pro-inflammatory cytokine levels in the brain (tumour necrosis factor-alpha, interleukin-1-beta, and interleukin-6). (5) Increased protein oxidation reported by a significant increase in 3-nitrotyrosine (3-NT)/tyrosine ratio. (6) A marked disturbance was found in the production of energy carriers (AMP, ATP and AMP/ATP ratio) in comparison with the control. The evidence suggests that paraben may, to some extent, either cause or contribute to the brain physiopathology in ASDs or pathogens that produce the brain pathology observed in the diagnosed rat model of ASD. PMID:25461396

  6. 3D active shape models of human brain structures: application to patient-specific mesh generation

    NASA Astrophysics Data System (ADS)

    Ravikumar, Nishant; Castro-Mateos, Isaac; Pozo, Jose M.; Frangi, Alejandro F.; Taylor, Zeike A.

    2015-03-01

    The use of biomechanics-based numerical simulations has attracted growing interest in recent years for computer-aided diagnosis and treatment planning. With this in mind, a method for automatic mesh generation of brain structures of interest, using statistical models of shape (SSM) and appearance (SAM), for personalised computational modelling is presented. SSMs are constructed as point distribution models (PDMs) while SAMs are trained using intensity profiles sampled from a training set of T1-weighted magnetic resonance images. The brain structures of interest are, the cortical surface (cerebrum, cerebellum & brainstem), lateral ventricles and falx-cerebri membrane. Two methods for establishing correspondences across the training set of shapes are investigated and compared (based on SSM quality): the Coherent Point Drift (CPD) point-set registration method and B-spline mesh-to-mesh registration method. The MNI-305 (Montreal Neurological Institute) average brain atlas is used to generate the template mesh, which is deformed and registered to each training case, to establish correspondence over the training set of shapes. 18 healthy patients' T1-weightedMRimages form the training set used to generate the SSM and SAM. Both model-training and model-fitting are performed over multiple brain structures simultaneously. Compactness and generalisation errors of the BSpline-SSM and CPD-SSM are evaluated and used to quantitatively compare the SSMs. Leave-one-out cross validation is used to evaluate SSM quality in terms of these measures. The mesh-based SSM is found to generalise better and is more compact, relative to the CPD-based SSM. Quality of the best-fit model instance from the trained SSMs, to test cases are evaluated using the Hausdorff distance (HD) and mean absolute surface distance (MASD) metrics.

  7. Feasibility of Transcranial, Localized Drug-delivery in the Brain of Alzheimers-model Mice Using Focused Ultrasound

    E-print Network

    Konofagou, Elisa E.

    Feasibility of Transcranial, Localized Drug-delivery in the Brain of Alzheimers-model Mice Using the BBB is the rate-limiting factor in brain drug delivery development [3]. The BBB is a specialized actively transported. A successful drug delivery system requires transient, localized, and non

  8. Patterns of cerebral glucose utilization in depression, multiple infarct dementia, and Alzheimer's disease

    SciTech Connect

    Kuhl, D.E.; Metter, E.J.; Riege, W.H.

    1983-01-01

    Patterns of local cerebral glucose utilization were determined in moderately to severely disabled patients with depression (n=7), multiple infarct dementia (n=6), and Alzheimer's disease (n=6), and in normal controls (n=6), using positron emission tomography with the /sup 18/F-fluorodeoxyglucose method. Average global metabolic rate was decreased 30% in patients with Alzheimer's disease, but overlap among the other groups reduced the discriminant value of this measure. In depressed patients, the cerebral metabolic pattern was normal, except for evidence of hypometabolic zone in the posterior-inferior frontal cortex which was of marginal statistical significance. In multiple infarct dementia, focal metabolic defects were scattered throughout the brain and exceeded the extent of infarction. In Alzheimer's disease, metabolism was markedly reduced in cortex, especially parietal cortex, but relatively preserved in caudate, thalamus, anterior cingulate gyrus, pre and post central gyrus, and calcarine occipital cortex, a pattern duplicating the degree and location of pathological and neurochemical alterations characteristic of this disorder.

  9. Diagnosis of Alzheimer's disease and multiple infarct dementia by tomographic imaging of iodine-123 IMP

    SciTech Connect

    Cohen, M.B.; Graham, L.S.; Lake, R.; Metter, E.J.; Fitten, J.; Kulkarni, M.K.; Sevrin, R.; Yamada, L.; Chang, C.C.; Woodruff, N.

    1986-06-01

    Tomographic imaging of the brain was performed using a rotating slant hole collimator and (/sup 123/I)N-isopropyl p-iodoamphetamine (IMP) in normal subjects (n = 6) and patients with either Alzheimer's disease (n = 5) or multiple infarct dementia (n = 3). Four blinded observers were asked to make a diagnosis from the images. Normal subjects and patients with multiple infarct dementia were correctly identified. Alzheimer's disease was diagnosed in three of the five patients with this disease. One patient with early Alzheimer's disease was classified as normal by two of the four observers. Another patient with Alzheimer's disease had an asymmetric distribution of IMP and was incorrectly diagnosed as multiple infarct dementia by all four observers. Limited angle tomography of the cerebral distribution of /sup 123/I appears to be a useful technique for the evaluation of demented patients.

  10. Comparison of Long-Term Clinical Outcomes after Drug-Eluting Stent Implantation in Patients with Coronary Artery Disease with and without Prior Cerebral Infarction

    PubMed Central

    Fujiwara, Hidetoshi; Horiuchi, Naruyoshi; Shirasaki, Shuichi; Sakai, Ichiro; Tsuchida, Kazuyuki; Murai, Hiroshi

    2015-01-01

    Objective: To compare the clinical and angiographic outcomes after implantation of drug-eluting stents (DESs) in patients with coronary artery disease (CAD) with or without prior cerebral infarction. Materials and Methods: Ninety-eight consecutive patients (130 lesions) who underwent successful coronary DES implantation were prospectively classified into two groups: those with a clinical history of symptomatic cerebral infarction (cerebral infarction group, 49 patients, 69 lesions) and those without a clinical history of symptomatic cerebral infarction (noncerebral infarction group, 49 patients, 61 lesions). The primary endpoint was defined as death, nonfatal myocardial infarction, and cerebrovascular events. Results: The Kaplan–Meier method was used to create a primary endpoint curves to determine the time-dependent cumulative primary endpoint-free rate, which were compared using the log-rank test. The incidence of primary endpoints was higher in the cerebral infarction group than in the noncerebral infarction group (p = 0.0075). The Cox proportional hazards regression model for primary endpoint identified prior cerebral infarction (p = 0.0331, hazard ratio = 2.827) and patients with peripheral artery disease (p = 0.0271, hazard ratio = 2.757) as explanatory factors. Conclusion: The results showed that clinical outcomes were poorer in patients with CAD who had prior cerebral infarctions than in those who did not have infarction. PMID:26131026

  11. Investigation of the best model to characterize diffuse correlation spectroscopy measurements acquired directly on the brain

    NASA Astrophysics Data System (ADS)

    Verdecchia, K.; Diop, M.; St. Lawrence, K.

    2015-03-01

    Diffuse correlation spectroscopy (DCS) is a non-invasive optical technique capable of monitoring tissue perfusion changes, particularly in the brain. The normalized temporal intensity autocorrelation function generated by DCS is typically characterized by assuming that the movement of erythrocytes can be modeled as a Brownian diffusion-like process instead of the expected random flow model. Carp et al. [Biomedical Optics Express, 2011] proposed a hybrid model, referred to as the hydrodynamic diffusion model, to capture both the random ballistic and diffusive nature of erythrocyte motion. The purpose of this study was to compare how well the Brownian diffusion and the hydrodynamic diffusion models characterized DCS data acquired directly on the brain, avoiding the confounding effects of scalp and skull. Data were acquired from seven pigs during normocapnia (39.9 +/- 0.7 mmHg) and hypocapnia (22.1 +/- 1.6 mmHg) with the DCS fibers placed 7 mm apart, directly on the cerebral cortex. The hydrodynamic diffusion model was found to provide a consistently better fit to the autocorrelation functions compared to the Brownian diffusion model and was less sensitive to the chosen start and end time points used in the fitting. However, the decrease in cerebral blood flow from normocapnia to hypocapnia determined was similar for the two models (-42.6 +/- 8.6 % for the Brownian model and -42.2 +/- 10.2 % for the hydrodynamic model), suggesting that the latter is reasonable for monitoring flow changes.

  12. Modeling distributed axonal delays in mean-field brain dynamics.

    PubMed

    Roberts, J A; Robinson, P A

    2008-11-01

    The range of conduction delays between connected neuronal populations is often modeled as a single discrete delay, assumed to be an effective value averaging over all fiber velocities. This paper shows the effects of distributed delays on signal propagation. A distribution acts as a linear filter, imposing an upper frequency cutoff that is inversely proportional to the delay width. Distributed thalamocortical and corticothalamic delays are incorporated into a physiologically based mean-field model of the cortex and thalamus to illustrate their effects on the electroencephalogram (EEG). The power spectrum is acutely sensitive to the width of the thalamocortical delay distribution, and more so than the corticothalamic distribution, because all input signals must travel along the thalamocortical pathway. This imposes a cutoff frequency above which the spectrum is overly damped. The positions of spectral peaks in the resting EEG depend primarily on the distribution mean, with only weak dependences on distribution width. Increasing distribution width increases the stability of fixed point solutions. A single discrete delay successfully approximates a distribution for frequencies below a cutoff that is inversely proportional to the delay width, provided that other model parameters are moderately adjusted. A pair of discrete delays together having the same mean, variance, and skewness as the distribution approximates the distribution over the same frequency range without needing parameter adjustment. Delay distributions with large fractional widths are well approximated by low-order differential equations. PMID:19113149

  13. Evidence that the EphA2 receptor exacerbates ischemic brain injury.

    PubMed

    Thundyil, John; Manzanero, Silvia; Pavlovski, Dale; Cully, Tanya R; Lok, Ker-Zhing; Widiapradja, Alexander; Chunduri, Prasad; Jo, Dong-Gyu; Naruse, Chie; Asano, Masahide; Launikonis, Bradley S; Sobey, Christopher G; Coulthard, Mark G; Arumugam, Thiruma V

    2013-01-01

    Ephrin (Eph) signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT) and EphA2-deficient (EphA2(-/-)) mice by middle cerebral artery occlusion (MCAO; 60 min), followed by reperfusion (24 or 72 h). Brain infarction was measured using triphenyltetrazolium chloride staining. Neurological deficit scores and brain infarct volumes were significantly less in EphA2(-/-) mice compared with WT controls. This protection by EphA2 deletion was associated with a comparative decrease in brain edema, blood-brain barrier damage, MMP-9 expression and leukocyte infiltration, and higher expression levels of the tight junction protein, zona occludens-1. Moreover, EphA2(-/-) brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3 and BAX, and higher levels of the anti-apoptotic protein, Bcl-2 as compared to WT group. We confirmed that isolated WT cortical neurons express the EphA2 receptor and its ligands (ephrin-A1-A3). Furthermore, expression of all four proteins was increased in WT primary cortical neurons following 24 h of glucose deprivation, and in the brains of WT mice following stroke. Glucose deprivation induced less cell death in primary neurons from EphA2(-/-) compared with WT mice. In conclusion, our data provide the first evidence that the EphA2 receptor directly contributes to blood-brain barrier damage and neuronal death following ischemic stroke. PMID:23308246

  14. Exercise enhanced functional recovery and expression of GDNF after photochemically induced cerebral infarction in the rat

    PubMed Central

    Ohwatashi, Akihiko; Ikeda, Satoshi; Harada, Katsuhiro; Kamikawa, Yurie; Yoshida, Akira

    2013-01-01

    Exercise has been considered to affect the functional recovery from central nervous damage. Neurotrophic factors have various effects on brain damage. However, the effects of exercise for expression of GDNF on functional recovery with brain damage are not well known. We investigated the difference in functional recovery between non-exercise and beam-walking exercise groups, and the expression of GDNF in both groups after photochemical infarction. Adult male Wistar rats (N = 64) were used. Animals were divided into two groups: non-exercise (N = 35), and beam-walking exercise (N = 29). All rats underwent surgical photochemical infarction. The rats of the beam-walking group were trained every day to walk on a narrow beam after a one-day recovery period and those of the non-exercise group were left to follow a natural course. Animals were evaluated for hind limb function every day using a beam-walking task with an elevated narrow beam. The number of GDNF-like immunoreactive cells in the temporal cortex surrounding the lesion was counted 1, 3, 5, and 7 days after the infarction. Functional recovery of the beam-walking exercise group was significantly earlier than that of the non-exercise group. At 3 days after infarction, the number of GDNF-positive cells in the temporal cortex surrounding the infarction was significantly increased in the beam-walking exercise group compared with that in the non-exercise group. In the exercise group, motor function was remarkably recovered with the increased expression of GDNF-like immunoreactive cells. Our results suggested that a rehabilitative approach increased the expression of GDNF and facilitated functional recovery from cerebral infarction.

  15. Blast-Associated Shock Waves Result in Increased Brain Vascular Leakage and Elevated ROS Levels in a Rat Model of Traumatic Brain Injury

    PubMed Central

    Petro, Marianne; Dudzinski, Dave; Stewart, Desiree; Courtney, Amy; Courtney, Michael; Labhasetwar, Vinod

    2015-01-01

    Blast-associated shock wave-induced traumatic brain injury (bTBI) remains a persistent risk for armed forces worldwide, yet its detailed pathophysiology remains to be fully investigated. In this study, we have designed and characterized a laboratory-scale shock tube to develop a rodent model of bTBI. Our blast tube, driven by a mixture of oxygen and acetylene, effectively generates blast overpressures of 20–130 psi, with pressure-time profiles similar to those of free-field blast waves. We tested our shock tube for brain injury response to various blast wave conditions in rats. The results show that blast waves cause diffuse vascular brain damage, as determined using a sensitive optical imaging method based on the fluorescence signal of Evans Blue dye extravasation developed in our laboratory. Vascular leakage increased with increasing blast overpressures and mapping of the brain slices for optical signal intensity indicated nonhomogeneous damage to the cerebral vasculature. We confirmed vascular leakage due to disruption in the blood-brain barrier (BBB) integrity following blast exposure. Reactive oxygen species (ROS) levels in the brain also increased with increasing blast pressures and with time post-blast wave exposure. Immunohistochemical analysis of the brain sections analyzed at different time points post blast exposure demonstrated astrocytosis and cell apoptosis, confirming sustained neuronal injury response. The main advantages of our shock-tube design are minimal jet effect and no requirement for specialized equipment or facilities, and effectively generate blast-associated shock waves that are relevant to battle-field conditions. Overall data suggest that increased oxidative stress and BBB disruption could be the crucial factors in the propagation and spread of neuronal degeneration following blast injury. Further studies are required to determine the interplay between increased ROS activity and BBB disruption to develop effective therapeutic strategies that can prevent the resulting cascade of neurodegeneration. PMID:26024446

  16. [Cardiac rehabilitation after myocardial infarction].

    PubMed

    Ghannem, M; Ghannem, L; Ghannem, L

    2015-12-01

    Although the proofs of the benefits of cardiac rehabilitation accumulate, many patients are not sent to rehabilitation units, especially younger and very elderly patients. As the length of stay in acute care units decreases, rehabilitation offers more time to fully assess the patients' conditions and needs. Meta-analyses of randomised trials suggest that mortality can be improved by as much as 20-30%. In addition, rehabilitation helps managing risk factors, including hyperlipidemia, diabetes, smoking and sedentary behaviours. Physical training also helps improving exercise capacity. Because of all of these effects, cardiac rehabilitation for post-myocardial infarction patients has been given a class IA recommendation in current guidelines. PMID:26548984

  17. Characteristics of an explosive blast-induced brain injury in an experimental model.

    PubMed

    de Lanerolle, Nihal C; Bandak, Faris; Kang, Dewey; Li, Alexander Y; Du, Fu; Swauger, Peter; Parks, Steven; Ling, Geoffrey; Kim, Jung H

    2011-11-01

    Mild traumatic brain injury resulting from exposure to an explosive blast is associated with significant neurobehavioral outcomes in soldiers. Little is known about the neuropathologic consequences of such an insult to the human brain. This study is an attempt to understand the effects of an explosive blast in a large animal gyrencephalic brain blast injury model. Anesthetized Yorkshire swine were exposed to measured explosive blast levels in 3 operationally relevant scenarios: simulated free field (blast tube), high-mobility multipurpose wheeled vehicle surrogate, and building (4-walled structure). Histologic changes in exposed animals up to 2 weeks after blast were compared to a group of naive and sham controls. The overall pathologic changes in all 3 blast scenarios were limited, with very little neuronal injury, fiber tract demyelination, or intracranial hemorrhage observed. However, there were 2 distinct neuropathologic changes observed: increased astrocyte activation and proliferation and periventricular axonal injury detected with ?-amyloid precursor protein immunohistochemistry. We postulate that the increased astrogliosis observed may have a longer-term potential for the exacerbation of brain injury and that the pattern of periventricular axonal injury may be related to a potential for cognitive and mood disorders. PMID:22002430

  18. Imagine all the people: how the brain creates and uses personality models to predict behavior.

    PubMed

    Hassabis, Demis; Spreng, R Nathan; Rusu, Andrei A; Robbins, Clifford A; Mar, Raymond A; Schacter, Daniel L

    2014-08-01

    The behaviors of other people are often central to envisioning the future. The ability to accurately predict the thoughts and actions of others is essential for successful social interactions, with far-reaching consequences. Despite its importance, little is known about how the brain represents people in order to predict behavior. In this functional magnetic resonance imaging study, participants learned the unique personality of 4 protagonists and imagined how each would behave in different scenarios. The protagonists' personalities were composed of 2 traits: Agreeableness and Extraversion. Which protagonist was being imagined was accurately inferred based solely on activity patterns in the medial prefrontal cortex using multivariate pattern classification, providing novel evidence that brain activity can reveal whom someone is thinking about. Lateral temporal and posterior cingulate cortex discriminated between different degrees of agreeableness and extraversion, respectively. Functional connectivity analysis confirmed that regions associated with trait-processing and individual identities were functionally coupled. Activity during the imagination task, and revealed by functional connectivity, was consistent with the default network. Our results suggest that distinct regions code for personality traits, and that the brain combines these traits to represent individuals. The brain then uses this "personality model" to predict the behavior of others in novel situations. PMID:23463340

  19. Human Brain Imaging of Tinnitus and Animal Models.

    PubMed

    Lobarinas, Edward; Sun, Wei; Stolzberg, Daniel; Lu, Jianzhong; Salvi, Richard

    2008-11-01

    Because subjective tinnitus is typically localized to the ear with hearing loss, tinnitus was traditionally thought to originate from neural hyperactivity in the damaged ear. However, most studies have found that hearing loss reduces the neural outputs from the damaged cochlea. These negative findings led to the hypothesis that rinnitus arises from aberrant neural activity in the central auditory system. Positron emission tomography imaging studies performed on tinnitus patients that could modulate their tinnitus provide evidence showing that the aberrant neural activity that gives rise to tinnitus resides in the central auditory pathway. To investigate the biological basis of tinnitus in more detail, an animal model was developed that allowed behavioral measures of tinnitus to be obtained from individual rats after inducing tinnitus with high doses of salicylate or high-intensity noise. This behavioral model was used to test the efficacy of memantine, an N-methyl-D-aspartate antagonist, and scopolamine, an anticholinergic, in suppressing salicylate-induced tinnitus. Neither drug completely suppressed salicylate-induced tinnitus. To detect the physiological changes associated with tinnitus, chronic microwire electrodes were implanted in the auditory cortex and measurements were obtained from the auditory cortex before and after salicylate and noise exposures known to induce tinnitus. High doses of salicylate or high-level noise exposure generally resulted in sound-evoked hyperactivity in the electrophysiological responses recorded from the auditory cortex of awake-animals. However, anesthetic tended to suppress or abolish the hyperactivity. PMID:19122834

  20. Role of Neuronal NADPH Oxidase 1 in the Peri-Infarct Regions after Stroke

    PubMed Central

    Choi, Dong-Hee; Kim, Ji-Hye; Lee, Kyoung-Hee; Kim, Hahn-Young; Kim, Yoon-Seong; Choi, Wahn Soo; Lee, Jongmin

    2015-01-01

    The molecular mechanism underlying the selective vulnerability of neurons to oxidative damage caused by ischemia—reperfusion (I/R) injury remains unknown. We sought to determine the role of NADPH oxidase 1 (Nox1) in cerebral I/R-induced brain injury and survival of newborn cells in the ischemic injured region. Male Wistar rats were subjected to 90 min middle cerebral artery occlusion (MCAO) followed by reperfusion. After reperfusion, infarction size, level of superoxide and 8-hydroxy-2?-deoxyguanosine (8-oxo-2dG), and Nox1 immunoreactivity were determined. RNAi-mediated knockdown of Nox1 was used to investigate the role of Nox1 in I/R-induced oxidative damage, neuronal death, motor function recovery, and ischemic neurogenesis. After I/R, Nox1 expression and 8-oxo-2dG immunoreactivity was increased in cortical neurons of the peri-infarct regions. Both infarction size and neuronal death in I/R injury were significantly reduced by adeno-associated virus (AAV)-mediated transduction of Nox1 short hairpin RNA (shRNA). AAV-mediated Nox1 knockdown enhanced functional recovery after MCAO. The level of survival and differentiation of newborn cells in the peri-infarct regions were increased by Nox1 inhibition. Our data suggest that Nox-1 may be responsible for oxidative damage to DNA, subsequent cortical neuronal degeneration, functional recovery, and regulation of ischemic neurogenesis in the peri-infarct regions after stroke. PMID:25617620

  1. PET/MRI in the infarcted mouse heart with the Cambridge split magnet

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

    Chronic heart failure, as a result of acute myocardial infarction, is a leading cause of death worldwide. Combining diagnostic imaging modalities may aid the direct assessment of experimental treatments targeting heart failure in vivo. Here we present preliminary data using the Cambridge combined PET/MRI imaging system in a mouse model of acute myocardial infarction. The split-magnet design can deliver uncompromised MRI and PET performance, for better assessment of disease and treatment in a preclinical environment.

  2. A Finite Element Study of the Dynamic Response of Brain Based on Two Parasagittal Slice Models

    PubMed Central

    Song, Xuewei; Wang, Cong; Hu, Hao; Huang, Tianlun; Jin, Jingxu

    2015-01-01

    The objective of this study is to investigate the influence of gyri and sulci on the response of human head under transient loading. To this end, two detailed parasagittal slice models with and without gyri and sulci have been developed. The models comprised not only cerebrum and skull but also cerebellum, brain stem, CSF, and corpus callosum. In addition, white and gray matters were separated. The material properties were adopted from the literature and assigned to different parts of the models. Nahum's and Trosseille's experiments reported in relevant literature were simulated and the simulation results were compared with the test data. The results show that there is no evident difference in terms of intracranial pressure between the models with and without gyri and sulci under simulated conditions. The equivalent stress below gyri and sulci in the model with gyri and sulci is slightly higher than that in the counterpart model without gyri and sulci. The maximum principle strain in brain tissue is lower in the model with gyri and sulci. The stress and strain distributions are changed due to the existence of gyri and sulci. These findings highlight the necessity to include gyri and sulci in the finite element head modeling. PMID:26495034

  3. A brain network model explaining tremor in Parkinson's disease.

    PubMed

    Duval, Christian; Daneault, Jean-Francois; Hutchison, William D; Sadikot, Abbas F

    2016-01-01

    This paper presents a novel model of tremor in Parkinson's disease (PD) based on extensive literature review as well as novel results stemming from functional stereotactic neurosurgery for the alleviation of tremor in PD. Specifically, evidence that suggests the basal ganglia induces PD tremor via excessive inhibitory output to the thalamus and altered firing patterns which in turn generate rhythmic bursting activity of thalamic cells is presented. Then, evidence that the thalamus generates PD tremor by facilitating the generation and consolidation of rhythmic bursting activity of neurons within its nuclei is also offered. Finally, evidence that the cerebellum may modulate characteristics of PD tremor by treating it as if it was a voluntary motor behavior is presented. Accordingly, the current paper proposes that PD tremor is induced by abnormal basal ganglia activity; it is generated by the thalamus, and modulated or reinforced by the cerebellum. PMID:26459110

  4. Brain monoamine receptors in a chronic unpredictable stress model in rats.

    PubMed

    Ossowska, G; Nowa, G; Kata, R; Klenk-Majewska, B; Danilczuk, Z; Zebrowska-Lupina, I

    2001-01-01

    Antidepressant drugs are devoid of mood-elevating effects in normal (non-depressed) human subjects, thus, it is necessary to evaluate the antidepressant property of compounds (drugs) in animal models of depression. Several animal models of depression have been introduced, however, only a few have been extensively validated. In the present study we report the results of investigations into monoaminergic receptors in the brain of rats subjected to chronic unpredictable stress (CUS) procedure (one of the well validated animal models of depression). We have examined the dopaminergic (D-1, D-2), adrenergic (alpha-1, beta-1) and serotonergic (5HT-1A, 5HT-2A) receptors in different brain regions by a saturation radioligand binding method in rats subjected to CUS paradigm and control animals. CUS procedure resulted in a significant 29% increase in the D-1 receptor density in the limbic system and 52% increase of the density of 5HT-2A receptors in the cerebral cortex. The present data indicate that the increase of the density of brain D-1 and 5HT-2A receptors of rats subjected to CUS might be involved in the pathophysiology of "animal depression" (since chronic antidepressant treatment produced opposite changes i.e. decrease in the density of these receptors) and thus in pathophysiology of human depression. PMID:11341483

  5. Firing patterns in a random network cellular automata model of the brain

    NASA Astrophysics Data System (ADS)

    Acedo, L.; Lamprianidou, E.; Moraño, J.-A.; Villanueva-Oller, J.; Villanueva, R.-J.

    2015-10-01

    One of the main challenges in the simulation of even reduced areas of the brain is the presence of a large number of neurons and a large number of connections among them. Even from a theoretical point of view, the behaviour of dynamical models of complex networks with high connectivity is unknown, precisely because the cost of computation is still unaffordable and it will likely be in the near future. In this paper we discuss the simulation of a cellular automata network model of the brain including up to one million sites with a maximum average of three hundred connections per neuron. This level of connectivity was achieved thanks to a distributed computing environment based on the BOINC (Berkeley Open Infrastructure for Network Computing) platform. Moreover, in this work we consider the interplay among excitatory neurons (which induce the excitation of their neighbours) and inhibitory neurons (which prevent resting neurons from firing and induce firing neurons to pass to the refractory state). Our objective is to classify the normal (noisy but asymptotically constant patterns) and the abnormal (high oscillations with spindle-like behaviour) patterns of activity in the model brain and their stability and parameter ranges in order to determine the role of excitatory and inhibitory compensatory effects in healthy and diseased individuals.

  6. Microfluidic modeling of the effects of nanoparticles on the blood-brain barrier in flow

    NASA Astrophysics Data System (ADS)

    Schwait, Craig; Hartman, Ryan; Bao, Yuping; Xu, Yaolin

    2011-11-01

    The difficulty of diffusing drugs across the blood-brain barrier (BBB) has caused an impasse for many brain treatments. Nanoparticles (NPs), to which drugs can adsorb, attach, or be entrapped, have the potential to deliver drugs past the BBB. Before nanoparticles can be used, their effects on the BBB and brain must be ascertained. Previous steady-state studies fall short for closely modeling in vivo conditions . Convection of nanoparticles is ignored, and endothelial cells' (ECs) morphology differs based on loading conditions; in vitro loading with continuous flow exhibit ECs indicating a more similar in vivo phenotype. NPs interact with monocytes prior to the BBB, and their toxicity effects were measured in flow conditions using both Trypan Blue cell counting and cell proliferation assays. The microfluidic device designed to model the BBB contained a concentric PES hollow fiber porous membrane in PFA tubing. Full use of the device will include ECs adhered on the inner surface and astrocytes adhered to the outer surface of the PES membrane to model cerebrovascular capillaries. Funded by NSF REU Site 1062611.

  7. Task decomposition: a framework for comparing diverse training models in human brain plasticity studies.

    PubMed

    Coffey, Emily B J; Herholz, Sibylle C

    2013-01-01

    Training studies, in which the structural or functional neurophysiology is compared before and after expertise is acquired, are increasingly being used as models for understanding the human brain's potential for reorganization. It is proving difficult to use these results to answer basic and important questions like how task training leads to both specific and general changes in behavior and how these changes correspond with modifications in the brain. The main culprit is the diversity of paradigms used as complex task models. An assortment of activities ranging from juggling to deciphering Morse code has been reported. Even when working in the same general domain, few researchers use similar training models. New ways to meaningfully compare complex tasks are needed. We propose a method for characterizing and deconstructing the task requirements of complex training paradigms, which is suitable for application to both structural and functional neuroimaging studies. We believe this approach will aid brain plasticity research by making it easier to compare training paradigms, identify "missing puzzle pieces," and encourage researchers to design training protocols to bridge these gaps. PMID:24115927

  8. Rodent models of cerebral ischemia

    SciTech Connect

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

    1989-12-01

    The use of physiologically regulated, reproducible animal models is crucial to the study of ischemic brain injury--both the mechanisms governing its occurrence and potential therapeutic strategies. Several laboratory rodent species (notably rats and gerbils), which are readily available at relatively low cost, are highly suitable for the investigation of cerebral ischemia and have been widely employed for this purpose. We critically examine and summarize several rodent models of transient global ischemia, resulting in selective neuronal injury within vulnerable brain regions, and focal ischemia, typically giving rise to localized brain infarction. We explore the utility of individual models and emphasize the necessity for meticulous experimental control of those variables that modulate the severity of ischemic brain injury.169 references.

  9. Toward a 3D model of human brain development for studying gene/environment interactions

    PubMed Central

    2013-01-01

    This project aims to establish and characterize an in vitro model of the developing human brain for the purpose of testing drugs and chemicals. To accurately assess risk, a model needs to recapitulate the complex interactions between different types of glial cells and neurons in a three-dimensional platform. Moreover, human cells are preferred over cells from rodents to eliminate cross-species differences in sensitivity to chemicals. Previously, we established conditions to culture rat primary cells as three-dimensional aggregates, which will be humanized and evaluated here with induced pluripotent stem cells (iPSCs). The use of iPSCs allows us to address gene/environment interactions as well as the potential of chemicals to interfere with epigenetic mechanisms. Additionally, iPSCs afford us the opportunity to study the effect of chemicals during very early stages of brain development. It is well recognized that assays for testing toxicity in the developing brain must consider differences in sensitivity and susceptibility that arise depending on the time of exposure. This model will reflect critical developmental processes such as proliferation, differentiation, lineage specification, migration, axonal growth, dendritic arborization and synaptogenesis, which will probably display differences in sensitivity