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Sample records for brain infarction model

  1. Polyhydroxylated fullerene nanoparticles attenuate brain infarction and oxidative stress in rat model of ischemic stroke

    PubMed Central

    Vani, Javad Rasouli; Mohammadi, Mohammad Taghi; Foroshani, Mahsa Sarami; Jafari, Mahvash

    2016-01-01

    Oxidative stress is the common underlying mechanism of damage in ischemic stroke. Therefore, we aimed to evaluate the possible protective effects of polyhydroxylated fullerene derivatives on brain infarction and oxidative/nitrosative stress in a rat model of ischemic stroke. The experiment was performed by four groups of rats (each; n=12); Sham, Control ischemia, and ischemic treatment groups (Pretreatment and Posttreatment). Brain ischemia was induced by 90 min middle cerebral artery occlusion (MCAO) followed by 24 hours reperfusion. Rats received fullerene nanoparticles at dose of 1 mg/kg 30 min before MCAO and immediately after beginning of reperfusion. Infarct volume, contents of malondialdehyde (MDA), glutathione (GSH) and nitrate as well as superoxide dismutase (SOD) activity were assessed 24 hours after termination of MCAO. Brain infarct volume was 310 ± 21 mm3 in control group. Administration of fullerene nanoparticles before and after MCAO significantly decreased the infarct volume by 53 % (145 ± 45 mm3) and 81 % (59 ± 13 mm3), respectively. Ischemia also enhanced MDA and nitrate contents of ischemic hemispheres by 45 % and 25 % , respectively. Fullerene nanoparticles considerably reduced the MDA and nitrate contents of ischemic hemispheres before MCAO by 58 % and 17 % , respectively, and after MCAO by 38 % and 21 % , respectively. Induction of MCAO significantly decreased GSH content (19 % ) and SOD activity (52 % ) of ischemic hemispheres, whereas fullerene nanoparticles increased the GSH content and SOD activity of ischemic hemispheres by 19 % and 52 % before MCAO, respectively, and 21 % and 55 % after MCAO, respectively. Our findings indicate that fullerene nanoparticles, as a potent scavenger of free radicals, protect the brain cells against ischemia/reperfusion injury and inhibit brain oxidative/nitrosative damage. PMID:27540350

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. Brain protection therapy in acute cerebral infarction.

    PubMed

    Katsura, Ken-ichiro; Suda, Satoshi; Abe, Arata; Kanamaru, Takuya; Toda, Yusuke; Katayama, Yasuo

    2012-01-01

    Many drugs for cerebral infarction that were shown to be effective in animal experiments have shown negative results in human clinical trials. For this reason, a completely new approach is needed to develop brain protection therapies against cerebral infarction. Brain protection therapies can be categorized into 3 types: 1) lengthening the therapeutic time window for thrombolytic therapy, 2) reducing the side effects of thrombolytic therapy, and 3) brain protection drug therapy for patients with contraindications for thrombolytic therapy (including combination therapy). Here, we show our recent results of brain protection therapy. First, combination therapy with 2 effective drugs was tried, and time-lag administration was performed. Combination therapy was effective and lengthened the therapeutic time window. Next, a completely new approach to improve cerebral ischemic damage, namely, H2 gas inhalation therapy, was tried. This therapy was also effective, even in the ischemic core. PMID:22687352

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

    PubMed

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

    2016-04-01

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

  6. Presumed brain infarctions in two dogs with systemic leishmaniasis.

    PubMed

    José-López, R; la Fuente, C De; Añor, S

    2012-09-01

    Clinical signs and magnetic resonance imaging findings of multiple brain infarcts in two dogs infected with Leishmania spp. are reported. Clinical signs of intracranial dysfunction were peracute and there was no further deterioration. Magnetic resonance images of the brain were consistent with multifocal, non-haemorrhagic, ischaemic lesions. Routine serum biochemistry revealed hyperproteinaemia and hyperglobulinaemia. Serum antibody titres were highly positive for Leishmania infantum and Leishmania amastigotes were seen within bone marrow macrophages in both cases. Canine leishmaniasis can cause cerebrovascular alterations, such as vasculitis, that might predispose dogs to brain infarcts. PMID:22882167

  7. Paradoxical brain embolism associated with Kimura disease mimics watershed infarction.

    PubMed

    Tanaka, Yasutaka; Ueno, Yuji; Shimada, Yoshiaki; Yamashiro, Kazuo; Tanaka, Ryota; Urabe, Takao; Hattori, Nobutaka

    2015-02-01

    Kimura disease (KD) is an uncommon chronic inflammatory disease presenting as subcutaneous lymphadenopathy with eosinophilia. To date, only a single case of brain embolism caused by fibroblastic endocarditis associated with KD has been reported. Watershed infarction was seen in patients with episodes of severe hypotension or cardiac surgery. We here report a young case of KD who developed ischemic stroke and showed multiple small infarcts in the border zones between the territories of major cerebral arteries, mimicking watershed infarction. Transesophageal echocardiography revealed patent foramen ovale and atrial septal aneurysm. Concurrently, deep venous thrombus in the femoral vein was found on duplex ultrasonography. Our case supports the notion that paradoxical brain embolism associated with KD can cause multiple small embolisms and mimic watershed infarction. PMID:25447210

  8. Aphasia owing to subcortical brain infarcts in childhood.

    PubMed

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

    2005-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2003-12-01

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

  10. 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

  11. Computational modeling of acute myocardial infarction.

    PubMed

    Sáez, P; Kuhl, E

    2016-01-01

    Myocardial infarction, commonly known as heart attack, is caused by reduced blood supply and damages the heart muscle because of a lack of oxygen. Myocardial infarction initiates a cascade of biochemical and mechanical events. In the early stages, cardiomyocytes death, wall thinning, collagen degradation, and ventricular dilation are the immediate consequences of myocardial infarction. In the later stages, collagenous scar formation in the infarcted zone and hypertrophy of the non-infarcted zone are auto-regulatory mechanisms to partly correct for these events. Here we propose a computational model for the short-term adaptation after myocardial infarction using the continuum theory of multiplicative growth. Our model captures the effects of cell death initiating wall thinning, and collagen degradation initiating ventricular dilation. Our simulations agree well with clinical observations in early myocardial infarction. They represent a first step toward simulating the progression of myocardial infarction with the ultimate goal to predict the propensity toward heart failure as a function of infarct intensity, location, and size. PMID:26583449

  12. Silent brain infarction in the presence of systemic vascular disease

    PubMed Central

    Slark, Julia; Bentley, Paul; Sharma, Pankaj

    2012-01-01

    Objective To determine the prevalence of asymptomatic brain ischaemic in the presence of vascular disease in other arterial territories. Design Studies up to January 2011 were identified through comprehensive search strategies. Arcsine transformation for meta-analysis was used to calculate the standardized mean difference (SMD) and 95% confidence intervals (CI). Setting A systematic review and meta-analysis were performed. Participants For each study, the proportion of patients positive for SBI in the presence of other systemic vascular disease was extracted and analyzed. Main outcome measures Using a random-effects model, a pooled effect estimate interpreted as a percentage prevalence of disease was calculated. Results SBI in the presence of acute ischaemic stroke was found in 23% (SMD 0.99; P < 0.001; 95% CI 0.88–1.10); a 35% prevalence was found in patients with coronary artery disease (SMD 1.26; P < 0.001; 95% CI 0.95–1.58); and a 14% prevalence in patients with peripheral artery disease (SMD 0.48; P < 0.002; 95% CI 0.42–0.54), although the data-set in the latter is smaller. Conclusions Patients with systemic vascular disease are at an increased risk of silent brain infarction. PMID:24175060

  13. Validation of a simple and inexpensive method for the quantitation of infarct in the rat brain.

    PubMed

    Schilichting, C L R; Lima, K C M; Cestari, L A; Sekiyama, J Y; Silva, F M; Milani, H

    2004-04-01

    A gravimetric method was evaluated as a simple, sensitive, reproducible, low-cost alternative to quantify the extent of brain infarct after occlusion of the medial cerebral artery in rats. In ether-anesthetized rats, the left medial cerebral artery was occluded for 1, 1.5 or 2 h by inserting a 4-0 nylon monofilament suture into the internal carotid artery. Twenty-four hours later, the brains were processed for histochemical triphenyltetrazolium chloride (TTC) staining and quantitation of the schemic infarct. In each TTC-stained brain section, the ischemic tissue was dissected with a scalpel and fixed in 10% formalin at 0 masculine C until its total mass could be estimated. The mass (mg) of the ischemic tissue was weighed on an analytical balance and compared to its volume (mm(3)), estimated either by plethysmometry using platinum electrodes or by computer-assisted image analysis. Infarct size as measured by the weighing method (mg), and reported as a percent (%) of the affected (left) hemisphere, correlated closely with volume (mm(3), also reported as %) estimated by computerized image analysis (r = 0.88; P < 0.001; N = 10) or by plethysmography (r = 0.97-0.98; P < 0.0001; N = 41). This degree of correlation was maintained between different experimenters. The method was also sensitive for detecting the effect of different ischemia durations on infarct size (P < 0.005; N = 23), and the effect of drug treatments in reducing the extent of brain damage (P < 0.005; N = 24). The data suggest that, in addition to being simple and low cost, the weighing method is a reliable alternative for quantifying brain infarct in animal models of stroke. PMID:15064814

  14. MAP2 Immunostaining in Thick Sections for Early Ischemic Stroke Infarct Volume in Non-Human Primate Brain

    PubMed Central

    Kharlamov, Alexander; LaVerde, George C.; Nemoto, Edwin M.; Jungreis, Charles A.; Yushmanov, Victor E.; Jones, Stephen C.; Boada, Fernando E.

    2009-01-01

    The delineation of early infarction in large gyrencephalic brain cannot be accomplished with triphenyl-tetrazolium chloride (TTC) due to its limitations in the early phase, nor can it be identified with microtubule-associated protein 2 (MAP2) immunohistochemistry, due to the fragility of large thin sections. We hypothesize that MAP2 immunostaining of thick whole-brain sections can accurately identify early ischemia in the entire monkey brain. Using ischemic brains of one rat and three monkeys, a thick-section MAP2 immunostaining protocol was developed to outline the infarct region over the entire non-human primate brain. Comparison of adjacent thick and thin sections in a rat brain indicated complete correspondence between ischemic regions (100.4 mm3 ± 1.2%, n = 7, p = 0.44). Thick sections in monkey brain possessed the increased structural stability necessary for the extensive MAP2 immunostaining procedure permitting quantification of the ischemic region as a percent of total monkey brain, giving infarct volumes of 11.4, 16.3, and 19.0% of total brain. Stacked 2D images of the intact thick brain tissue sections provided a 3D representation for comparison to MRI images. The infarct volume of 16.1 cm3 from the MAP2 sections registered with MRI images agreed well with the volume calculated directly from the stained sections of 16.6 cm3. Thick brain tissue section MAP2 immunostaining provides a new method for determining infarct volume over the entire brain at early time points in a non-human primate model of ischemic stroke. PMID:19540877

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

    PubMed

    Bai, Xia; Zhuang, Hongming

    2016-04-01

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

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

    PubMed Central

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

    2013-01-01

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

  17. Brain Infarction: Rare Neurological Presentation of African Bee Stings.

    PubMed

    Alvis-Miranda, Hernando Raphael; Duarte-Valdivieso, Nancy Carolina; Alcala-Cerra, Gabriel; Moscote-Salazar, Luis Rafael

    2014-01-01

    Bee stings are commonly encountered worldwide. Various manifestations after bee sting have been described including local reactions which are common, systemic responses such as anaphylaxis, diffuse intravascular coagulation and hemolysis. We report a case of a 74-year-old man who developed neurologic deficit 5 hours after bee stings, which was confirmed to be left frontal infarction on brain CT-scan. The case does not follow the reported  pattern  of hypovolemic or anaphylactic shock, hemolysis and/or  rhabdomyolysis, despite the potentially lethal amount of venom injected. Diverse mechanisms have been proposed to give an explanation to all the clinical manifestation of both toxic and allergic reactions secondary to bee stings. Currently, the most accepted one state that victims can develop severe syndrome characterized by the release of a large amount of cytokines. PMID:27162866

  18. 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

  19. [Brain stem infarction, temporal headache, and elevated inflammatory parameters in a 74-year-old man].

    PubMed

    Gehlen, M; Schwarz-Eywill, M; Schäfer, N; Pfeiffer, A; Bösenberg, H; Maier, A; Hinz, C

    2016-06-01

    We report the case of a 74 year old man with a brain stem infarction, temporal headache and elevated inflammatory parameters. Giant cell arteritis with involvement of the temporal and vertebral arteries was proven by histology, duplex sonography and MRI. Although intensive immunosuppressive therapy was started, the patient developed two brain infarcts within 6 months. Initially, C‑reactive protein and erythrocyte sedimentation rate were significantly elevated, but normalized over time. Involvement of the vertebral artery in giant cell arteritis is thought to be rare; steroid refractory courses are very rare. Brain stem infarction might be the consequence. PMID:27055655

  20. 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

  1. Histologic assessment of the age of recent brain infarcts in man.

    PubMed

    Chuaqui, R; Tapia, J

    1993-09-01

    In order to design a dating system based on the microscopic picture of brain infarcts of recent onset, we performed the histological examination of 31 infarcts covering the first 4 weeks of evolution in 30 autopsy cases. The date of the cerebral vascular accident was clinically established in every case. There were 13 men and 17 women with a mean age of 65 years. Hemorrhagic infarcts were found in 15 cases and anemic infarcts in 16 cases. Based on the histological features four periods were identified: the first period, from day 1 through day 4, was characterized by the predominance of eosinophilic neurons and necrotic oligodendrocytes; the second period, from day 5 through day 7, differed from the first by the appearance of macrophages and of newly formed blood vessels; the third period, from day 8 through day 14, showed neuronal ghosts, macrophages, astrocytic proliferation, gemistocytes, and absence of neutrophils; and in the fourth period, from day 15 through day 27, there were no eosinophilic neurons, and neither necrotic oligodendrocytes nor myelin in the central portion of the infarct were identified. By assessing the histological features and accurately correlating the findings with the corresponding clinical data, we have been able to describe four distinct microscopic patterns of the first month of evolution of brain infarcts. The present findings may be considered useful morphological clues to better characterize the early evolutional phase of brain infarcts in humans. PMID:8360701

  2. Tocilizumab inhibits neuronal cell apoptosis and activates STAT3 in cerebral infarction rat model

    PubMed Central

    Wang, Shaojun; Zhou, Jun; Kang, Weijie; Dong, Zhaoni; Wang, Hezuo

    2016-01-01

    Cerebral infarction is a severe hypoxic ischemic necrosis with accelerated neuronal cell apoptosis in the brain. As a monoclonal antibody against interleukin 6, tocilizumab (TCZ) is widely used in immune diseases, whose function in cerebral infarction has not been studied. This study aims to reveal the role of TCZ in regulating neuronal cell apoptosis in cerebral infarction. The cerebral infarction rat model was constructed by middle cerebral artery occlusion and treated with TCZ. Cell apoptosis in hippocampus and cortex of the brain was examined with TUNEL method. Rat neuronal cells cultured in oxygen-glucose deprivation (OGD) conditions and treated with TCZ were used to compare cell viability and apoptosis. Apoptosis-related factors including B-cell lymphoma extra large (Bcl-xL) and Caspase 3, as well as the phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in brain cortex were analyzed from the protein level. Results indicated that TCZ treatment could significantly prevent the promoted cell apoptosis caused by cerebral infarction or OGD (P < 0.05 or P < 0.01). In brain cortex of the rat model, TCZ up-regulated Bcl-xL and down-regulated Caspase 3, consistent with the inhibited cell apoptosis. It also promoted tyrosine 705 phosphorylation of STAT3, which might be the potential regulatory mechanism of TCZ in neuronal cells. This study provided evidence for the protective role of TCZ against neuronal cell apoptosis in cerebral infarction. Based on these fundamental data, TCZ is a promising option for treating cerebral infarction, but further investigations on related mechanisms are still necessary. PMID:26773188

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

    PubMed Central

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

    2010-01-01

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

  4. 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.…

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  7. 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.

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

    PubMed

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

    2014-07-01

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

  9. 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.

  10. [An automated detection of lacunar infarct regions in brain MR images: preliminary study].

    PubMed

    Yokoyama, Ryujiro; Lee, Yongbum; Hara, Takeshi; Fujita, Hiroshi; Asano, Takahiko; Hoshi, Hiroaki; Iwama, Toru; Sakai, Noboru

    2002-03-01

    The purpose of this study is to develop a technique to detect lacunar infarct regions automatically in brain MR images. Our detection method is based on the definition of lacunar infarcts. After inputted images were binarized, we used feature values such as area, circularities and the center of gravity of candidate regions to extract isolated lacunar infarct regions. We also developed and used a new filter to enhance the signals of lacunar infarcts adjacent to some high intensity regions. 10 cases involving 81 sectional images were applied to our experiment. As a result, the sensitivity was 100% with approximately 1.77 false-positives per image. Our results are promising on the first stage, although it remains to improve on problems that to eliminate false-positives and automatically establish threshold value. PMID:12522348

  11. Mannitol bolus preferentially shrinks non-infarcted brain in patients with ischemic stroke.

    PubMed

    Videen, T O; Zazulia, A R; Manno, E M; Derdeyn, C P; Adams, R E; Diringer, M N; Powers, W J

    2001-12-11

    Changes in brain tissue volume in six patients who had acute complete middle cerebral artery (MCA) infarctions and CT evidence of midline shift were measured using the brain boundary shift integral (BBSI) on sequential T1-weighted MR images acquired before and after a 1.5-g/kg bolus infusion of mannitol. At 50 to 55 minutes after the baseline scan, total brain volume decreased by 8.1 +/- 2.8 mL (0.6%, p < 0.005). Brain in the noninfarcted hemisphere shrank more (0.8 +/- 0.4%) than in the infarcted hemisphere (0.0 +/- 0.5%, p < 0.05). PMID:11739839

  12. Development and Characterization of a Macaque Model of Focal Internal Capsular Infarcts

    PubMed Central

    Murata, Yumi; Higo, Noriyuki

    2016-01-01

    Several studies have used macaque monkeys with lesions induced in the primary motor cortex (M1) to investigate the recovery of motor function after brain damage. However, in human stroke patients, the severity and outcome of motor impairments depend on the degree of damage to the white matter, especially that in the posterior internal capsule, which carries corticospinal tracts. To bridge the gap between results obtained in M1-lesioned macaques and the development of clinical intervention strategies, we established a method of inducing focal infarcts at the posterior internal capsule of macaque monkeys by injecting endothelin-1 (ET-1), a vasoconstrictor peptide. The infarcts expanded between 3 days and 1 week after ET-1 injection. The infarct volume in each macaque was negatively correlated with precision grip performance 3 days and 1 week after injection, suggesting that the degree of infarct expansion may have been a cause of the impairment in hand movements during the early stage. Although the infarct volume decreased and gross movement improved, impairment of dexterous hand movements remained until the end of the behavioral and imaging experiments at 3 months after ET-1 injection. A decrease in the abundance of large neurons in M1, from which the descending motor tracts originate, was associated with this later-stage impairment. The present model is useful not only for studying neurological changes underlying deficits and recovery but also for testing therapeutic interventions after white matter infarcts in primates. PMID:27149111

  13. Intracranial MR angiography: Its role in the integrated approach to brain infarction

    SciTech Connect

    Johnson, B.A.; Heiserman, J.E.; Drayer, B.P.; Keller, P.J.

    1994-05-01

    To determine the contribution of cranial MR angiography (MRA) for the evaluation of patients with acute and subacute brain infarction. MR and MRA studies performed on 78 adult patients with acute and subacute stroke were retrospectively reviewed and correlated with the clinical records. There were 50 acute and 28 subacute infarctions in our series. Five of 78 MRA exams (6%) were nondiagnostic. Sixty examinations (80%) were positive for stenosis or occlusion. The distribution of stenotic or occlusive vascular lesions correlated with the location of infarction in 56 of the 60 positive cases (93%). MRA provided information not obtained from the MR images in 40 cases (55%). One hundred four individual vessels in 8 patients who underwent conventional cerebral angiography were compared with the MRA appearance. The MRA interpretations correlated with the conventional angiographic evaluations for 90 vessels (87%). Vascular lesions demonstrated on intracranial MRA show a high correlation with infarct distribution. MRA provides information adjunctive to conventional MR in a majority of cases. We conclude that MRA is an important component of the complete evaluation of brain infarction. 39 refs., 3 figs., 2 tabs.

  14. Experimental model of myocardial infarction: Histopathology and reperfusion damage revisited.

    PubMed

    Kren, Leos; Meluzin, Jaroslav; Pavlovsky, Zdenek; Mayer, Jiri; Kala, Petr; Groch, Ladislav; Hornacek, Ivan; Rauser, Petr; Vlasin, Michal

    2010-09-15

    The goal of this pilot study was to create an experimental model of myocardial infarction (for subsequent evaluation of the effectiveness of an alternative way of stem cell application - intracoronary cell infusion in the management of acute myocardial infarction). Four experimental animals, female pigs weighing between 30 and 40 kg, were used in the initial phase of this study to create an experimental model of acute myocardial infarction. An experimental myocardial infarction was performed via occlusion of the interventricular arm of the left coronary artery for 90 min. The hearts were examined 1 h, 3 days, 5 days, and 7 days after the procedure. Macroscopically, red infarction characteristic of reperfusion was found. Microscopically, the healing process with granulation tissue production/collagen deposition was remarkably accelerated compared to literature data. Repair processes in reperfused experimental myocardial infarction and/or reperfused autopsy specimens should not be evaluated on the basis of literature data only. Large collections of extracellular calcium were present. This phenomenon is not well described in the literature and probably has the potential for significantly interfering with the repair process. The histopathology of reperfused acute myoardial infarction deserves to be studied in further investigations. PMID:20451332

  15. Nicardipine in models of myocardial infarction

    PubMed Central

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

    1985-01-01

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

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

    PubMed

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

    2012-01-01

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

  17. Multiscale Characterization of Impact of Infarct Size on Myocardial Remodeling in an Ovine Infarct Model

    PubMed Central

    Zhang, Pei; Li, Tielou; Griffith, Bartley P; Wu, Zhongjun J

    2015-01-01

    The surviving myocardium initially compensates the loss of injured myocardium after myocardial infarction (MI) and gradually becomes progressively dysfunctional. There have been limited studies of the influence of infarct size on temporal and spatial alteration of myocardium during progressive myocardial remodeling. MI with three infarct sizes (15%, 25% and 35% of left ventricular wall) was created in an ovine infarction model. The progressive LV remodeling over a 12 week period was studied. Echocardiography, sonomicrometry, histological and molecular analyses were carried out to evaluate cardiac function, regional tissue contractile function and structural remodeling, and regional cardiomycyte hypertrophy and calcium handling proteins. The 15%, 25% and 35% MI groups at 12 weeks after MI had normalized LV end diastole volumes of 1.4±0.2, 1.7±0.3 and 2.0±0.4 mL/Kg, normalized end systole volumes of 1.0±0.1, 1.0±0.2 and 1.3±0.3 mL/Kg and LV ejection fractions of 43%±3%, 42%±6% and 34%±4%, respectively. They all differed from a sham group (p<0.05). All the three MI groups exhibited larger wall areal expansion (remodeling strain), larger cardiomyocyte size and altered expression of calcium handing proteins in the adjacent myocardium compared to the remote counterpart from the infarct. Significant correlation was found between myocardiocyte size and remodeling strain in the adjacent zone. A comparative analysis among the three MI groups showed that a larger infarct size (35% vs. 15% MI) was associated with larger remodeling strain, impairment severity of cellular structure and composition, and regional contractile function at regional tissue level and LV cardiac function at organ level. PMID:26540290

  18. LAD-Ligation: A Murine Model of Myocardial Infarction

    PubMed Central

    Kolk, Mandy V.V.; Meyberg, Danja; Deuse, Tobias; Tang-Quan, Karis R.; Robbins, Robert C.; Reichenspurner, Hermann; Schrepfer, Sonja

    2009-01-01

    Research models of infarction and myocardial ischemia are essential to investigate the acute and chronic pathobiological and pathophysiological processes in myocardial ischemia and to develop and optimize future treatment. Two different methods of creating myocardial ischemia are performed in laboratory rodents. The first method is to create cryo infarction, a fast but inaccurate technique, where a cryo-pen is applied on the surface of the heart (1-3). Using this method the scientist can not guarantee that the cryo-scar leads to ischemia, also a vast myocardial injury is created that shows pathophysiological side effects that are not related to myocardial infarction. The second method is the permanent ligation of the left anterior descending artery (LAD). Here the LAD is ligated with one single stitch, forming an ischemia that can be seen almost immediately. By closing the LAD, no further blood flow is permitted in that area, while the surrounding myocardial tissue is nearly not affected. This surgical procedure imitates the pathobiological and pathophysiological aspects occurring in infarction-related myocardial ischemia. The method introduced in this video demonstrates the surgical procedure of a mouse infarction model by ligating the LAD. This model is convenient for pathobiological and pathophysiological as well as immunobiological studies on cardiac infarction. The shown technique provides high accuracy and correlates well with histological sections. PMID:19829290

  19. Cerebral Venous Infarction: A Potentially Avoidable Complication of Deep Brain Stimulation Surgery

    PubMed Central

    Morishita, Takashi; Okun, Michael S.; Burdick, Adam; Jacobson, Charles E; Foote, Kelly D.

    2013-01-01

    Object Despite numerous reports on the morbidity and mortality of deep brain stimulation (DBS), cerebral venous infarction has rarely been reported. We present four cases of venous infarct secondary to DBS surgery. Methods The diagnosis of venous infarction was based on: 1) delayed onset of new neurologic deficits on post-operative day 1 or 2, and 2) significant edema surrounding the superficial aspect of the implanted lead, with or without subcortical hemorrhage on CT scan. Results Four cases (0.8%/lead, 1.3%/patient) of symptomatic cerebral venous infarction were identified out of 500 DBS lead implantation procedures between July 2002 and August 2009. All four patients had Parkinson’s disease (PD). Their DBS leads were implanted in the subthalamic nucleus (STN) (n=2), and the internal globus pallidus (GPi) (n=2). Retrospective review of the targeting confirmed that the planned trajectory passed within 3mm of a cortical vein in two cases for which contrast-enhanced pre-operative MRI was available. In the other two cases, contrasted targeting images were not obtained preoperatively. Conclusion Cerebral venous infarction is a potentially avoidable, but serious complication. To minimize its incidence, we propose the use of high resolution, contrast-enhanced, T1 weighted MR images to delineate cerebral venous anatomy, along with careful stereotactic planning of the lead trajectory to avoid injury to venous structures. PMID:23738501

  20. Migraine with aura and risk of silent brain infarcts and white matter hyperintensities: an MRI study

    PubMed Central

    Garde, Ellen; Blaabjerg, Morten; Nielsen, Helle H.; Krøigård, Thomas; Østergaard, Kamilla; Møller, Harald S.; Hjelmborg, Jacob; Madsen, Camilla G.; Iversen, Pernille; Kyvik, Kirsten O.; Siebner, Hartwig R.; Ashina, Messoud

    2016-01-01

    A small number of population-based studies reported an association between migraine with aura and risk of silent brain infarcts and white matter hyperintensities in females. We investigated these relations in a population-based sample of female twins. We contacted female twins ages 30–60 years identified through the population-based Danish Twin Registry. Based on questionnaire responses, twins were invited to participate in a telephone-based interview conducted by physicians. Headache diagnoses were established according to the International Headache Society criteria. Cases with migraine with aura, their co-twins, and unrelated migraine-free twins (controls) were invited to a brain magnetic resonance imaging scan performed at a single centre. Brain scans were assessed for the presence of infarcts, and white matter hyperintensities (visual rating scales and volumetric analyses) blinded to headache diagnoses. Comparisons were based on 172 cases, 34 co-twins, and 139 control subjects. Compared with control subjects, cases did not differ with regard to frequency of silent brain infarcts (four cases versus one control), periventricular white matter hyperintensity scores [adjusted mean difference (95% confidence interval): −0.1 (−0.5 to 0.2)] or deep white matter hyperintensity scores [adjusted mean difference (95% confidence interval): 0.1 (−0.8 to 1.1)] assessed by Scheltens’ scale. Cases had a slightly higher total white matter hyperintensity volume compared with controls [adjusted mean difference (95% confidence interval): 0.17 (−0.08 to 0.41) cm3] and a similar difference was present in analyses restricted to twin pairs discordant for migraine with aura [adjusted mean difference 0.21 (−0.20 to 0.63)], but these differences did not reach statistical significance. We found no evidence of an association between silent brain infarcts, white matter hyperintensities, and migraine with aura. PMID:27190013

  1. Migraine with aura and risk of silent brain infarcts and white matter hyperintensities: an MRI study.

    PubMed

    Gaist, David; Garde, Ellen; Blaabjerg, Morten; Nielsen, Helle H; Krøigård, Thomas; Østergaard, Kamilla; Møller, Harald S; Hjelmborg, Jacob; Madsen, Camilla G; Iversen, Pernille; Kyvik, Kirsten O; Siebner, Hartwig R; Ashina, Messoud

    2016-07-01

    A small number of population-based studies reported an association between migraine with aura and risk of silent brain infarcts and white matter hyperintensities in females. We investigated these relations in a population-based sample of female twins. We contacted female twins ages 30-60 years identified through the population-based Danish Twin Registry. Based on questionnaire responses, twins were invited to participate in a telephone-based interview conducted by physicians. Headache diagnoses were established according to the International Headache Society criteria. Cases with migraine with aura, their co-twins, and unrelated migraine-free twins (controls) were invited to a brain magnetic resonance imaging scan performed at a single centre. Brain scans were assessed for the presence of infarcts, and white matter hyperintensities (visual rating scales and volumetric analyses) blinded to headache diagnoses. Comparisons were based on 172 cases, 34 co-twins, and 139 control subjects. Compared with control subjects, cases did not differ with regard to frequency of silent brain infarcts (four cases versus one control), periventricular white matter hyperintensity scores [adjusted mean difference (95% confidence interval): -0.1 (-0.5 to 0.2)] or deep white matter hyperintensity scores [adjusted mean difference (95% confidence interval): 0.1 (-0.8 to 1.1)] assessed by Scheltens' scale. Cases had a slightly higher total white matter hyperintensity volume compared with controls [adjusted mean difference (95% confidence interval): 0.17 (-0.08 to 0.41) cm(3)] and a similar difference was present in analyses restricted to twin pairs discordant for migraine with aura [adjusted mean difference 0.21 (-0.20 to 0.63)], but these differences did not reach statistical significance. We found no evidence of an association between silent brain infarcts, white matter hyperintensities, and migraine with aura. PMID:27190013

  2. Sonolysis in Prevention of Brain Infarction During Cardiac Surgery (SONORESCUE)

    PubMed Central

    Školoudík, David; Hurtíková, Eva; Brát, Radim; Herzig, Roman

    2016-01-01

    Abstract Here, we examined whether intraoperative sonolysis can alter the risk of new ischemic lesions in the insonated brain artery territory during coronary artery bypass grafting (CABG) or valve surgery. Silent brain ischemic lesions could be detected in as many as two-thirds of patients after CABG or valve surgery. Patients indicated for CABG or valve surgery were allocated randomly to sonolysis (60 patients, 37 males; mean age, 65.3 years) of the right middle cerebral artery (MCA) during cardiac surgery and control group (60 patients, 37 males; mean age, 65.3 years). Neurologic examination, cognitive function tests, and brain magnetic resonance imaging (MRI) were conducted before intervention as well as 24 to 72 hours and 30 days after surgery. New ischemic lesions on control diffusion-weighted MRI in the insonated MCA territory ≥0.5 mL were significantly less frequent in the sonolysis group than in the control group (13.3% vs 26.7%, P = 0.109). The sonolysis group exhibited significantly reduced median volume of new brain ischemic lesions (P = 0.026). Stenosis of the internal carotid artery ≥50% and smoking were independent predictors of new brain ischemic lesions ≥0.5 mL (odds ratio = 5.685 [1.272–25.409], P = 0.023 and 4.698 [1.092–20.208], P = 0.038, respectively). Stroke or transient ischemic attack occurred only in 2 control patients (P = 0.496). No significant differences were found in scores for postintervention cognitive tests (P > 0.05). This study provides class-II evidence that sonolysis during CABG or valve surgery reduces the risk of larger, new ischemic lesions in the brain. www.clinicaltrials.gov (NCT01591018). PMID:27196464

  3. Risk of Intraparenchymal Hemorrhage with MRI-Defined Leukoaraiosis and Brain Infarcts

    PubMed Central

    Folsom, Aaron R.; Yatsuya, Hiroshi; Mosley, Thomas H.; Psaty, Bruce M.; Longstreth, W. T.

    2012-01-01

    Objective To determine whether the burden of leukoaraiosis and the number of brain infarcts, defined by MRI, are prospectively and independently associated with intraparenchymal hemorrhage (IPH) incidence in a pooled population-based study. Methods Among 4,872 participants initially free of clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS), we assessed white matter grade (range 0–9), reflecting increasing leukoaraiosis, and brain infarcts using MRI. Over a median of 13 years of follow-up, 71 incident, spontaneous IPH events occurred. Results After adjustment for other IPH risk factors, the hazard ratios (95% confidence intervals) across white matter grades 0–1, 2, 3, and 4–9 were 1.00, 1.68 (0.86–3.30), 3.52 (1.80–6.89), and 3.96 (1.90–8.27) (p for trend <0.0001). These hazard ratios were weakened only modestly (p for trend = 0.0003) with adjustment for MRI-defined brain infarcts. The IPH hazard ratios for 0, 1, 2, or ≥3 MRI-defined brain infarcts were 1.00, 1.97 (1.10–3.54), 2.00 (0.83–4.78), and 3.12 (1.31–7.43) (p for trend = 0.002), but these were substantially attenuated when adjusted for white matter grade (p for trend = 0.049). Interpretation Greater MRI-defined burden of leukoaraiosis is a risk factor for spontaneous IPH. Spontaneous IPH should be added to the growing list of potential poor outcomes in people with leukoaraiosis. PMID:22522444

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

    PubMed

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

    1995-03-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-12-01

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

  7. Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration.

    PubMed

    Blom, Jessica N; Lu, Xiangru; Arnold, Paul; Feng, Qingping

    2016-01-01

    Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and regeneration, and to define new targets for therapeutics. For decades, models of complete heart regeneration existed in amphibians and fish, but a mammalian counterpart was not available. The recent discovery of a postnatal window during which mice possess regenerative capabilities has led to the establishment of a mammalian model of cardiac regeneration. A surgical model of mammalian cardiac regeneration in the neonatal mouse is presented herein. Briefly, postnatal day 1 (P1) mice are anesthetized by isoflurane and placed on an ice pad to induce hypothermia. After the chest is opened, and the left anterior descending coronary artery (LAD) is visualized, a suture is placed around the LAD to inflict myocardial ischemia in the left ventricle. The surgical procedure takes 10-15 min. Visualizing the coronary artery is crucial for accurate suture placement and reproducibility. Myocardial infarction and cardiac dysfunction are confirmed by triphenyl-tetrazolium chloride (TTC) staining and echocardiography, respectively. Complete regeneration 21 days post myocardial infarction is verified by histology. This protocol can be used to as a tool to elucidate mechanisms of mammalian cardiac regeneration after myocardial infarction. PMID:27286473

  8. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  11. Gastroschisis, Destructive Brain Lesions, and Placental Infarction in the Second Trimester Suggest a Vascular Pathogenesis

    PubMed Central

    Folkerth, Rebecca D.; Habbe, Donald M.; Boyd, Theonia K.; McMillan, Kristin; Gromer, Jessica; Sens, Mary Ann; Elliott, Amy J.

    2014-01-01

    The cause and pathogenesis of gastroschisis are uncertain. We report the autopsy and placental pathology of a stillbirth at 20 gestational weeks, in which gastroschisis was accompanied by destructive lesions in the cerebral cortex and brainstem, as well as cardiac calcification, consistent with ischemic injury during the 2nd trimester. An important potential underlying mechanism explaining the fetal abnormalities is the presence of infarcts in the placenta, indicative at this gestational age of maternal vascular underperfusion. The association of gastroschisis with ischemic lesions in the brain, heart, and placenta in this case supports the concept that gastroschisis, at least in some instances, may result from vascular event(s) causing disruption of the fetal abdominal wall and resulting in the extrusion of the abdominal organs, as well as hypoxic–ischemic brain and cardiac injury. PMID:23895144

  12. 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

  13. Laser system refinements to reduce variability in infarct size in the rat photothrombotic stroke model

    PubMed Central

    Alaverdashvili, Mariam; Paterson, Phyllis G.; Bradley, Michael P.

    2015-01-01

    Background The rat photothrombotic stroke model can induce brain infarcts with reasonable biological variability. Nevertheless, we observed unexplained high inter-individual variability despite using a rigorous protocol. Of the three major determinants of infarct volume, photosensitive dye concentration and illumination period were strictly controlled, whereas undetected fluctuation in laser power output was suspected to account for the variability. New method The frequently utilized Diode Pumped Solid State (DPSS) lasers emitting 532 nm (green) light can exhibit fluctuations in output power due to temperature and input power alterations. The polarization properties of the Nd:YAG and Nd:YVO4 crystals commonly used in these lasers are another potential source of fluctuation, since one means of controlling output power uses a polarizer with a variable transmission axis. Thus, the properties of DPSS lasers and the relationship between power output and infarct size were explored. Results DPSS laser beam intensity showed considerable variation. Either a polarizer or a variable neutral density filter allowed adjustment of a polarized laser beam to the desired intensity. When the beam was unpolarized, the experimenter was restricted to using a variable neutral density filter. Comparison with existing method(s) Our refined approach includes continuous monitoring of DPSS laser intensity via beam sampling using a pellicle beamsplitter and photodiode sensor. This guarantees the desired beam intensity at the targeted brain area during stroke induction, with the intensity controlled either through a polarizer or variable neutral density filter. Conclusions Continuous monitoring and control of laser beam intensity is critical for ensuring consistent infarct size. PMID:25840363

  14. Brain-Derived Neurotrophic Factor Regulates TRPC3/6 Channels and Protects Against Myocardial Infarction in Rodents

    PubMed Central

    Hang, Pengzhou; Zhao, Jing; Cai, Benzhi; Tian, Shanshan; Huang, Wei; Guo, Jing; Sun, Chuan; Li, Yue; Du, Zhimin

    2015-01-01

    Background: Brain-derived neurotrophic factor (BDNF) is associated with coronary artery diseases. However, its role and mechanism in myocardial infarction (MI) is not fully understood. Methods: Wistar rat and Kunming mouse model of MI were induced by the ligation of left coronary artery. Blood samples were collected from MI rats and patients. Plasma BDNF level, protein expression of BDNF, tropomyosin-related kinase B (TrkB) and its downstream transient receptor potential canonical (TRPC)3/6 channels were examined by enzyme-linked immunosorbent assay and Western blot. Infarct size, cardiac function and cardiomyocyte apoptosis were measured after intra-myocardium injection with recombinant human BDNF. Protective role of BDNF against cardiomyocyte apoptosis was confirmed by BDNF scavenger TrkB-Fc. The regulation of TRPC3/6 channels by BDNF was validated by pretreating with TRPC blocker (2-Aminoethyl diphenylborinate, 2-APB) and TRPC3/6 siRNAs. Results: Circulating BDNF was significantly enhanced in MI rats and patients. Protein expression of BDNF, TrkB and TRPC3/6 channels were upregulated in MI. 3 days post-MI, BDNF treatment markedly reduced the infarct size and serum lactate dehydrogenase activity. Meanwhile, echocardiography indicated that BDNF significantly improved cardiac function of MI mice. Furthermore, BDNF markedly inhibited cardiomyocyte apoptosis by upregulating Bcl-2 expression and downregulating caspase-3 expression and activity in ischemic myocardium. In neonatal rat ventricular myocytes, cell viability was dramatically increased by BDNF in hypoxia, which was restored by TrkB-Fc. Furthermore, protective role of BDNF against hypoxia-induced apoptosis was reversed by 2-APB and TRPC3/6 siRNAs. Conclusion: BDNF/TrkB alleviated cardiac ischemic injury and inhibited cardiomyocytes apoptosis by regulating TRPC3/6 channels, which provides a novel potential therapeutic candidate for MI. PMID:25892961

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

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

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

  16. 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

  17. Parameters of diffusional kurtosis imaging for the diagnosis of acute cerebral infarction in different brain regions

    PubMed Central

    Guo, Yue-Lin; Li, Su-Juan; Zhang, Zhong-Ping; Shen, Zhi-Wei; Zhang, Gui-Shan; Yan, Gen; Wang, Yan-Ting; Rao, Hai-Bing; Zheng, Wen-Bin; Wu, Ren-Hua

    2016-01-01

    Diffusional kurtosis imaging (DKI) is a new type diffusion-weighted sequence which measures the non-Gaussianity of water diffusion. The present study aimed to investigate whether the parameters of DKI could distinguish between differences in water molecule diffusion in various brain regions under the conditions of acute infarction and to identify the optimal DKI parameter for locating ischemic lesions in each brain region. A total of 28 patients with acute ischemic stroke in different brain regions were recruited for the present study. The relative values of DKI parameters were selected as major assessment indices, and the homogeneity of background image and contrast of adjacent structures were used as minor assessment indices. According to the brain region involved in three DKI parametric maps, including mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Kr), 112 groups of regions of interest were outlined in the following regions: Corpus callosum (n=17); corona radiata (n=26); thalamus (n=21); subcortical white matter (n=24); and cerebral cortex (n=24). For ischemic lesions in the corpus callosum and corona radiata, significant increases in relative Ka were detected, as compared with the other parameters (P<0.05). For ischemic lesions in the thalamus, subcortical white matter and cerebral cortices, an increase in the three parameters was detected, however this difference was not significant. Minor assessment indices demonstrated that Ka lacked tissue contrast and the background of Kr was heterogeneous; thus, MK was the superior assessment parameter for ischemic lesions in these regions. In conclusion, Ka is better suited for the diagnosis of acute ischemic lesions in highly anisotropic brain regions, such as the corpus callosum and corona radiate. MK may be appropriate for the lesions in low anisotropic or isotropic brain regions, such as the thalamus, subcortical white matter and cerebral cortices.

  18. Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    2014-01-01

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

  20. Myocardial infarction and intramyocardial injection models in swine

    PubMed Central

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

    2014-01-01

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

  1. The isolated working heart model in infarcted rat hearts.

    PubMed

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

    2005-04-01

    Congestive heart failure (CHF) is one of the most common causes of death in western countries. The aim of this study was to establish and validate the working heart model in rat hearts with CHF. In the rat model the animals show parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The focus of attention was the evaluation of cardiodynamics (e.g.contractility) in the isolated 'working heart' model. The geometric properties of the left ventricle were measured by planimetry (stereology). Formulae available in the past for determining certain parameters in the working heart model (e.g.external heart work) have to be fitted to the circumstances of the infarcted rat hearts with its different organ properties.CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive rats (SHR/NHsd) by creating a permanent (8 week) occlusion of the left coronary artery, 2 mm distal to the origin from the aorta, by a modified technique (Itter et al. 2004). This resulted in a large infarction of the free left ventricular wall. We were able to establish and adapt a new and predictive working heart model in spontaneously hypertensive rat hearts with myocardial infarction (MI) 8-12 weeks after coronary artery ligation. At this stage the WKY rat did not show any symptoms of CHF. The SHR rat represented characteristic parameters and symptoms that could be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III-IV). Upon inspection, severe clinical symptoms of CHF such as dyspnoea, subcutaneous oedema, palebluish limbs and impaired motion were prominent. On necropsy the SHR showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. In the working heart model the infarcted animals showed reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd than in the Wistar Kyoto rat (WKY/NHsd). The

  2. MTHFR C677T and prothrombin G20210A mutations in a woman from Dalmatia with silent brain infarction. .

    PubMed

    Ivica, Nikolina; Pintarić, Irena; Titlić, Marina

    2014-09-01

    A 55-year-old, previously healthy woman, presented with frequent headaches. She had no neurological disturbances, but had a positive family history; her father died from stroke. Magnetic resonance imaging showed brain infarction; therefore detailed diagnostic evaluation of thrombophilia markers and genetic testing were performed. The patient was found to be homozy- gous for the C677T mutation of the methylenetetrahydrofolate reductase gene and heterozygous for the mutation of the prothrombin G20210A gene. No other cause of cerebral infarction was found in the patient. PMID:25509247

  3. Cancer-related multiple brain infarctions caused by Trousseau syndrome in a patient with metastatic colon cancer: a case report.

    PubMed

    Akiyama, Takahiko; Miyamoto, Yuji; Sakamoto, Yasuo; Tokunaga, Ryuma; Kosumi, Keisuke; Shigaki, Hironobu; Kurashige, Junji; Iwatsuki, Masaaki; Baba, Yoshifumi; Yoshida, Naoya; Baba, Hideo

    2016-12-01

    Thromboembolism that occurs in association with a malignant tumor is known as Trousseau syndrome. We herein present a case of Trousseau syndrome during systemic chemotherapy for metastatic colon cancer. A 65-year-old man with multiple liver metastases underwent primary tumor resection and systemic chemotherapy. Multiple brain infarctions were detected by magnetic resonance imaging immediately after first-line chemotherapy, which was deemed ineffective. There was no evidence of cardioembolic stroke or carotid atherosclerosis. Although the patient was initially asymptomatic, he subsequently developed paralysis. Despite anticoagulant treatment, he developed repeated recurrences of the infarction, and the area of the infarction spread as the liver metastases progressed. The patient's condition showed no response to an alternative treatment regimen for advanced colon carcinoma. He died approximately 11 months after tumor discovery. PMID:27595586

  4. Lysophosphatidic Acid Level and the Incidence of Silent Brain Infarction in Patients with Nonvalvular Atrial Fibrillation

    PubMed Central

    Li, Zhen-Guang; Yu, Zhan-Cai; Yu, Yong-Peng; Ju, Wei-Ping; Wang, Dao-Zhen; Zhan, Xia; Wu, Xi-Juan; Zhou, Li

    2010-01-01

    Lysophosphatidic acid (LPA), which is proposed to play an important role in normal physiological situations such as wound healing, vascular tone, vascular integrity and reproduction, may be involved in the etiology of some diseases such as atherosclerosis, cancer, obesity or myocardial infarction. Abnormal findings, including silent brain infarction (SBI), are frequently observed by magnetic resonance imaging (MRI) in patients with nonvalvular atrial fibrillation (NVAF). However, whether there is a relationship between LPA level and the prevalence of SBI has not been extensively studied. In the present study, the association between them was investigated. 235 patients with NVAF, 116 cases of SBI without NVAF and 120 cases of healthy volunteers (control group), who did not receive any antithrombotic therapy, were enrolled in this study. Plasma LPA levels in the NVAF with SBI group were significantly higher than that in the control group (p < 0.01), NVAF without SBI group (p < 0.01) and SBI without NVAF group (p < 0.01). The LPA levels are lower in the control group than in the NVAF without SBI and SBI without NVAF groups (p < 0.01), however, the latter two groups did not significantly differ from each other for LPA levels (p > 0.05) There were significant differences in the positive rate of platelet activation between each of the groups (p < 0.01). The positive rate of platelet activation was significantly higher in the NVAF with SBI group. We suggest that LPA might be a novel marker for estimation of the status of platelet activation and the risk factor for SBI onset in NVAF patients. We expected that plasma LPA levels could predict the occurrence of SBI in NVAF patients. PMID:21152315

  5. Circumscribed Capsular Infarct Modeling Using a Photothrombotic Technique.

    PubMed

    Song, Hanlim; Park, Ji-Young; Kim, Hyung-Sun; Lee, Min-Cheol; Kim, Young; Kim, Hyoung-Ihl

    2016-01-01

    Recent increase in the prevalence rate of white matter stroke demands specific research in the field. However, the lack of a pertinent animal model for white matter stroke has hampered research investigations. Here, we describe a novel method for creating a circumscribed capsular infarct that minimizes damage to neighboring gray matter structures. We used pre-surgery neural tracing with adeno-associated virus-green fluorescent protein (AAV-GFP) to identify somatotopic organization of the forelimb area within the internal capsule. The adjustment of light intensity based on different optical properties of gray and white matter contributes to selective destruction of white matter with relative preservation of gray matter. Accurate positioning of optical-neural interface enables destruction of entire forelimb area in the internal capsule, which leads to a marked and persistent motor deficit. Thus, this technique produces highly replicable capsular infarct lesions with a persistent motor deficit. The model will be helpful not only to study white matter stroke (WMS) at the behavioral, circuit, and cellular levels, but also to assess its usefulness for development of new therapeutic and rehabilitative interventions. PMID:27284776

  6. 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

  7. Myocardial Infarct Segmentation from Magnetic Resonance Images for Personalized Modeling of Cardiac Electrophysiology

    PubMed Central

    Ukwatta, Eranga; Arevalo, Hermenegild; Li, Kristina; Yuan, Jing; Qiu, Wu; Malamas, Peter; Wu, Katherine C.

    2016-01-01

    Accurate representation of myocardial infarct geometry is crucial to patient-specific computational modeling of the heart in ischemic cardiomyopathy. We have developed a methodology for segmentation of left ventricular (LV) infarct from clinically acquired, two-dimensional (2D), late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) images, for personalized modeling of ventricular electrophysiology. The infarct segmentation was expressed as a continuous min-cut optimization problem, which was solved using its dual formulation, the continuous max-flow (CMF). The optimization objective comprised of a smoothness term, and a data term that quantified the similarity between image intensity histograms of segmented regions and those of a set of training images. A manual segmentation of the LV myocardium was used to initialize and constrain the developed method. The three-dimensional geometry of infarct was reconstructed from its segmentation using an implicit, shape-based interpolation method. The proposed methodology was extensively evaluated using metrics based on geometry, and outcomes of individualized electrophysiological simulations of cardiac dys(function). Several existing LV infarct segmentation approaches were implemented, and compared with the proposed method. Our results demonstrated that the CMF method was more accurate than the existing approaches in reproducing expert manual LV infarct segmentations, and in electrophysiological simulations. The infarct segmentation method we have developed and comprehensively evaluated in this study constitutes an important step in advancing clinical applications of personalized simulations of cardiac electrophysiology. PMID:26731693

  8. Myocardial Infarct Segmentation From Magnetic Resonance Images for Personalized Modeling of Cardiac Electrophysiology.

    PubMed

    Ukwatta, Eranga; Arevalo, Hermenegild; Li, Kristina; Yuan, Jing; Qiu, Wu; Malamas, Peter; Wu, Katherine C; Trayanova, Natalia A; Vadakkumpadan, Fijoy

    2016-06-01

    Accurate representation of myocardial infarct geometry is crucial to patient-specific computational modeling of the heart in ischemic cardiomyopathy. We have developed a methodology for segmentation of left ventricular (LV) infarct from clinically acquired, two-dimensional (2D), late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) images, for personalized modeling of ventricular electrophysiology. The infarct segmentation was expressed as a continuous min-cut optimization problem, which was solved using its dual formulation, the continuous max-flow (CMF). The optimization objective comprised of a smoothness term, and a data term that quantified the similarity between image intensity histograms of segmented regions and those of a set of training images. A manual segmentation of the LV myocardium was used to initialize and constrain the developed method. The three-dimensional geometry of infarct was reconstructed from its segmentation using an implicit, shape-based interpolation method. The proposed methodology was extensively evaluated using metrics based on geometry, and outcomes of individualized electrophysiological simulations of cardiac dys(function). Several existing LV infarct segmentation approaches were implemented, and compared with the proposed method. Our results demonstrated that the CMF method was more accurate than the existing approaches in reproducing expert manual LV infarct segmentations, and in electrophysiological simulations. The infarct segmentation method we have developed and comprehensively evaluated in this study constitutes an important step in advancing clinical applications of personalized simulations of cardiac electrophysiology. PMID:26731693

  9. The use of MRI apparent diffusion coefficient (ADC) in monitoring the development of brain infarction

    PubMed Central

    2011-01-01

    Background To study the rules that apparent diffusion coefficient (ADC) changes with time and space in cerebral infarction, and to provide the evidence in defining the infarction stages. Methods 117 work-ups in 98 patients with cerebral infarction (12 hyperacute, 43 acute, 29 subacute, 10 steady, and 23 chronic infarctions) were imaged with both conventional MRI and diffusion weighted imaging. The average ADC values, the relative ADC (rADC) values, and the ADC values or rADC values from the center to the periphery of the lesion were calculated. Results The average ADC values and the rADC values of hyperacute and acute infarction lesion depressed obviously. rADC values in hyperacute and acute stage was minimized, and increased progressively as time passed and appeared as "pseudonormal" values in approximately 8 to 14 days. Thereafter, rADC values became greater than normal in chronic stage. There was positive correlation between rADC values and time (P < 0.01). The ADC values and the rADC values in hyperacute and acute lesions had gradient signs that these lesions increased from the center to the periphery. The ADC values and the rADC values in subacute lesions had adverse gradient signs that these lesions decreased from the center to the periphery. Conclusion The ADC values of infarction lesions have evolution rules with time and space. The evolution rules with time and those in space can be helpful to decide the clinical stage, and to provide the evidence in guiding the treatment or judging the prognosis in infarction. PMID:21211049

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

    PubMed Central

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

    2015-01-01

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

  11. Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and 18F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia

    PubMed Central

    Cockburn, Neil; Kovacs, Michael

    2016-01-01

    CT Perfusion (CTP) derived cerebral blood flow (CBF) thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to 18F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1) was injected into the brain of Duroc-Cross pigs (n = 11) through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of 18F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155–180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and 18F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min-1·100g-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion. PMID:27347877

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

    PubMed

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

    2016-02-01

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

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

    PubMed

    Rouillard, Andrew D; Holmes, Jeffrey W

    2014-08-01

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

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

    PubMed Central

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

    2011-01-01

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

  15. Brain Stem Infarction Due to Basilar Artery Dissection in a Patient with Moyamoya Disease Four Years after Successful Bilateral Revascularization Surgeries.

    PubMed

    Abe, Takatsugu; Fujimura, Miki; Mugikura, Shunji; Endo, Hidenori; Tominaga, Teiji

    2016-06-01

    Moyamoya disease (MMD) is a rare cerebrovascular disease with an unknown etiology and is characterized by intrinsic fragility in the intracranial vascular walls such as the affected internal elastic lamina and thinning medial layer. The association of MMD with intracranial arterial dissection is extremely rare, whereas that with basilar artery dissection (BAD) has not been reported previously. A 46-year-old woman developed brain stem infarction due to BAD 4 years after successful bilateral superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis for ischemic-onset MMD. She presented with sudden occipitalgia and subsequently developed transient dysarthria and mild hemiparesis. Although a transient ischemic attack was initially suspected, her condition deteriorated in a manner that was consistent with left hemiplegia with severe dysarthria. Magnetic resonance (MR) imaging revealed brain stem infarction, and MR angiography delineated a double-lumen sign in the basilar artery, indicating BAD. She was treated conservatively and brain stem infarction did not expand. One year after the onset of brain stem infarction, her activity of daily living is still dependent (modified Rankin Scale of 4), and there were no morphological changes associated with BAD or recurrent cerebrovascular events during the follow-up period. The association of MMD with BAD is extremely rare. While considering the common underlying pathology such as an affected internal elastic lamina and fragile medial layer, the occurrence of BAD in a patient with MMD in a stable hemodynamic state is apparently unique. PMID:27068774

  16. Partially Silencing Brain Toll-Like Receptor 4 Prevents in Part Left Ventricular Remodeling with Sympathoinhibition in Rats with Myocardial Infarction-Induced Heart Failure

    PubMed Central

    Ogawa, Kiyohiro; Hirooka, Yoshitaka; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji

    2013-01-01

    Background Left ventricular (LV) remodeling and activation of sympathetic nervous system (SNS) are cardinal features of heart failure. We previously demonstrated that enhanced central sympathetic outflow is associated with brain toll-like receptor 4 (TLR4) probably mediated by brain angiotensin II type 1 receptor in mice with myocardial infarction (MI)-induced heart failure. The purpose of the present study was to examine whether silencing brain TLR4 could prevent LV remodeling with sympathoinhibition in MI-induced heart failure. Methodology/Principal Findings MI-induced heart failure model rats were created by ligation of left coronary artery. The expression level of TLR4 in brainstem was significantly higher in MI-induced heart failure treated with intracerebroventricular (ICV) injection of hGAPDH-SiRNA than in sham. TLR4 in brainstem was significantly lower in MI-induced heart failure treated with ICV injection of TLR4-SiRNA than in that treated with ICV injection of hGAPDH-SiRNA. Lung weight, urinary norepinephrine excretion, and LV end-diastolic pressure were significantly lower and LV dimension was significantly smaller in MI-induced heart failure treated with TLR4-SiRNA than in that treated with hGAPDH-SiRNA for 2 weeks. Conclusions Partially silencing brain TLR4 by ICV injection of TLR4-SiRNA for 2 weeks could in part prevent LV remodeling with sympathoinhibition in rats with MI-induced heart failure. Brain TLR4 has a potential to be a target of the treatment for MI-induced heart failure. PMID:23874864

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

    PubMed Central

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

    2015-01-01

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

  18. 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

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

    PubMed

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

    2011-04-01

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

  20. 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.

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

    PubMed Central

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

    2012-01-01

    Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

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

    PubMed Central

    Değirmenci, Hüsnü; Bakırcı, Eftal Murat; Demirtaş, Levent; Duman, Hakan; Hamur, Hikmet; Ceyhun, Gökhan; Topal, Ergün

    2014-01-01

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

  3. 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

  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

  5. 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…

  6. Therapy with Recombinant T-cell Receptor Ligand reduces infarct size and infiltrating inflammatory cells in brain after middle cerebral artery occlusion in mice

    PubMed Central

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

    2011-01-01

    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 4h time window currently in clinical practice for stroke patients. RTL551 was administered subcutaneously 4h after MCAO, with repeated doses every 24h 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 96h reperfusion. RTL551 reduced infarct size in both cortex and striatum at 24h and in cortex at 96h after MCAO and inhibited the accumulation of inflammatory cells in brain at both time points. At 24h 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 4h time window through immune regulation of myelin-reactive inflammatory T-cells. PMID:21472429

  7. Immunocytochemical detection of newly generated neurons in the perilesional area of cortical infarcts after intraventricular application of brain-derived neurotrophic factor.

    PubMed

    Keiner, Silke; Witte, Otto W; Redecker, Christoph

    2009-01-01

    The adult brain responds to focal infarction with proliferation of glial subpopulations. In addition, cells that express the immature neuronal marker doublecortin have been found consistently in the perileisonal zone. We investigated whether application of brain-derived neurotrophic factor (BDNF) would influence this perilesional proliferative response. Photothrombotic infarcts were induced in the sensorimotor forelimb and hindlimb cortex of adult rats. Brain-derived neurotrophic factor or vehicle was continuously infused intraventricularly for 2 weeks after the infarct using osmotic minipumps. Proliferating cells were labeled by daily intraperitoneal injections of bromodeoxyuridine during the first 2 weeks and were quantified at days 14 and 42 using semiautomatic stereology. Triple immunofluorescence with antibodies against immature and mature neuronal and glial markers was used to identify the proliferating cell populations. On day 14 after intraventricular BNDF application, the numbers of doublecortin-positive cells were doubled in the perilesional zone. On day 42, BDNF-treated animals had a small number of mature neurons in these areas, whereas vehicle-treated controls did not. Behavioral analysis with a battery of sensorimotor tests revealed, however, that the alterations in the perilesional cellular response were not associated with an improved functional outcome. PMID:19104443

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

    PubMed Central

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

    2016-01-01

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

  9. Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model

    PubMed Central

    Tanaka, Yuya; Shirasawa, Bungo; Takeuchi, Yuriko; Kawamura, Daichi; Nakamura, Tamami; Samura, Makoto; Nishimoto, Arata; Ueno, Koji; Morikage, Noriyasu; Hosoyama, Tohru; Hamano, Kimikazu

    2016-01-01

    Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts. PMID:27347329

  10. Sulfonylurea receptor 1 expression in human cerebral infarcts.

    PubMed

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

    2013-09-01

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

  11. Sulfonylurea Receptor 1 Expression in Human Cerebral Infarcts

    PubMed Central

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

    2013-01-01

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

  12. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models

    PubMed Central

    Arevalo, Hermenegild J.; Vadakkumpadan, Fijoy; Guallar, Eliseo; Jebb, Alexander; Malamas, Peter; Wu, Katherine C.; Trayanova, Natalia A.

    2016-01-01

    Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients' clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations. PMID:27164184

  13. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models.

    PubMed

    Arevalo, Hermenegild J; Vadakkumpadan, Fijoy; Guallar, Eliseo; Jebb, Alexander; Malamas, Peter; Wu, Katherine C; Trayanova, Natalia A

    2016-01-01

    Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients' clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations. PMID:27164184

  14. Decreased sulfhydryl groups in the reperfused myocardial tissue of a rat model of myocardial infarction.

    PubMed

    Maezawa, H; Manaka, K; Yamakawa, K; Ogawa, K; Iizuka, M

    1997-02-01

    The aim of this study was to determine whether myocardial injury resulting from temporary ischemia followed by reperfusion can be measured by assaying sulfhydryl groups in the affected tissue of a rat model of myocardial infarction. We studied 3 groups: a control group (n = 6), which underwent surgery without left coronary artery (LCA) ligation; group NoR (n = 9), in which the LCA was ligated for 3 h; and group I + R (n = 7), in which 30 min LCA ligation was followed by 3 h reperfusion. The sulfhydryl group content of myocardial tissue was assayed by measuring the fluorescence produced by incubating heart sections with N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM), which binds sulfhydryl groups. The fluorescence intensity (FI) of normal and infarcted myocardium was quantified by our computerized system of microscopic fluorophotometry. Indices such as sulfhydryl group content, the size of the low-FI area [% AREA(lower FI)] and the relative decrease in FI [%FI(decrease)]) in the infarct zone were calculated. Both %AREA(lower FI) and %FI(decrease) were significantly higher in the infarcted zone of animals in NoR and I + R groups than in control animals. Both indices were higher in infarct tissue from animals in the I + R group than in the NoR group. These changes suggest that sulfhydryl group content is significantly reduced in tissue that has been subjected to ischemia-reperfusion. Microscopic fluorophotometry, as defined by DACM staining of myocardial tissue, may help to delineate areas of myocardial reperfusion injury. PMID:9070971

  15. Apolipoprotein A1 regulates coenzyme Q10 absorption, mitochondrial function, and infarct size in a mouse model of myocardial infarction.

    PubMed

    Dadabayev, Alisher R; Yin, Guotian; Latchoumycandane, Calivarathan; McIntyre, Thomas M; Lesnefsky, Edward J; Penn, Marc S

    2014-07-01

    HDL and apolipoprotein A1 (apoA1) concentrations inversely correlate with risk of death from ischemic heart disease; however, the role of apoA1 in the myocardial response to ischemia has not been well defined. To test whether apoA1, the primary HDL apolipoprotein, has an acute anti-inflammatory role in ischemic heart disease, we induced myocardial infarction via direct left anterior descending coronary artery ligation in apoA1 null (apoA1(-/-)) and apoA1 heterozygous (apoA1(+/-)) mice. We observed that apoA1(+/-) and apoA1(-/-) mice had a 52% and 125% increase in infarct size as a percentage of area at risk, respectively, compared with wild-type (WT) C57BL/6 mice. Mitochondrial oxidation contributes to tissue damage in ischemia-reperfusion injury. A substantial defect was present at baseline in the electron transport chain of cardiac myocytes from apoA1(-/-) mice localized to the coenzyme Q (CoQ) pool with impaired electron transfer (67% decrease) from complex II to complex III. Administration of coenzyme Q10 (CoQ10) to apoA1 null mice normalized the cardiac mitochondrial CoQ pool and reduced infarct size to that observed in WT mice. CoQ10 administration did not significantly alter infarct size in WT mice. These data identify CoQ pool content leading to impaired mitochondrial function as major contributors to infarct size in the setting of low HDL/apoA1. These data suggest a previously unappreciated mechanism for myocardial stunning, cardiac dysfunction, and muscle pain associated with low HDL and low apoA1 concentrations that can be corrected by CoQ10 supplementation and suggest populations of patients that may benefit particularly from CoQ10 supplementation. PMID:24759932

  16. 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.

  17. Blood brain barrier breakdown was found in non-infarcted area after 2-h MCAO.

    PubMed

    Wang, Xiaona; Liu, Yushan; Sun, Yanyun; Liu, Wenlan; Jin, Xinchun

    2016-04-15

    The blood brain barrier (BBB) could be damaged within the thrombolytic time window and is considered to be a precursor to hemorrhagic transformation during reperfusion. Although we have recently reported the association between BBB damage and tissue injury within the thrombolytic time window, our knowledge about this early BBB damage is limited. In this study, rats were subjected to 2-h middle cerebral artery occlusion (MCAO) followed by 10 min reperfusion with Evan's blue as a tracer to detect BBB damage. Rat brain was sliced into 10 consecutive sections and with TTC staining, a macro and full view of the spatial distribution of BBB damage and tissue injury could be clearly seen in the same group of animals. After 2-h MCAO, tissue injury started from 2nd slice and the BBB leakage started from the 5th slice, of note, there is no colocalization between BBB damage and tissue injury. Fluoro Jade B was employed to explore the localization of neuronal degeneration, and our results showed that 2-h MCAO produced greater number of positive cells in ischemic cortex and dorsal striatum than other areas. More important, 2-h MCAO induced occludin but not claudin-5 degradation in the ischemic hemisphere and pretreatment with MMP inhibitor GM6001 significantly reduced occludin degradation as well as BBB damage detected by IgG leakage. Taken together, our findings demonstrated a "mismatch" between ischemic tissue injury and BBB leakage and a differential degradation of occludin and claudin-5 by MMP-2 after 2-h MCAO. PMID:27000223

  18. Plasticity of Adult Sensorimotor System in Severe Brain Infarcts: Challenges and Opportunities

    PubMed Central

    Sterr, Annette; Conforto, Adriana Bastos

    2012-01-01

    Functional reorganization forms the critical mechanism for the recovery of function after brain damage. These processes are driven by inherent changes within the central nervous system (CNS) triggered by the insult and further depend on the neural input the recovering system is processing. Therefore these processes interact with not only the interventions a patient receives, but also the activities and behaviors a patient engages in. In recent years, a wide range of research programs has addressed the association between functional reorganization and the spontaneous and treatment-induced recovery. The bulk of this work has focused on upper-limb and hand function, and today there are new treatments available that capitalize on the neuroplasticity of the brain. However, this is only true for patients with mild to moderated impairments; for those with very limited hand function, the basic understanding is much poorer and directly translates into limited treatment opportunities for these patients. The present paper aims to highlight the knowledge gap on severe stroke with a brief summary of the literature followed by a discussion of the challenges involved in the study and treatment of severe stroke and poor long-term outcome. PMID:22548196

  19. Image-based reconstruction of three-dimensional myocardial infarct geometry for patient-specific modeling of cardiac electrophysiology

    PubMed Central

    Ukwatta, Eranga; Arevalo, Hermenegild; Rajchl, Martin; White, James; Pashakhanloo, Farhad; Prakosa, Adityo; Herzka, Daniel A.; McVeigh, Elliot; Lardo, Albert C.; Trayanova, Natalia A.; Vadakkumpadan, Fijoy

    2015-01-01

    Purpose: Accurate three-dimensional (3D) reconstruction of myocardial infarct geometry is crucial to patient-specific modeling of the heart aimed at providing therapeutic guidance in ischemic cardiomyopathy. However, myocardial infarct imaging is clinically performed using two-dimensional (2D) late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) techniques, and a method to build accurate 3D infarct reconstructions from the 2D LGE-CMR images has been lacking. The purpose of this study was to address this need. Methods: The authors developed a novel methodology to reconstruct 3D infarct geometry from segmented low-resolution (Lo-res) clinical LGE-CMR images. Their methodology employed the so-called logarithm of odds (LogOdds) function to implicitly represent the shape of the infarct in segmented image slices as LogOdds maps. These 2D maps were then interpolated into a 3D image, and the result transformed via the inverse of LogOdds to a binary image representing the 3D infarct geometry. To assess the efficacy of this method, the authors utilized 39 high-resolution (Hi-res) LGE-CMR images, including 36 in vivo acquisitions of human subjects with prior myocardial infarction and 3 ex vivo scans of canine hearts following coronary ligation to induce infarction. The infarct was manually segmented by trained experts in each slice of the Hi-res images, and the segmented data were downsampled to typical clinical resolution. The proposed method was then used to reconstruct 3D infarct geometry from the downsampled images, and the resulting reconstructions were compared with the manually segmented data. The method was extensively evaluated using metrics based on geometry as well as results of electrophysiological simulations of cardiac sinus rhythm and ventricular tachycardia in individual hearts. Several alternative reconstruction techniques were also implemented and compared with the proposed method. Results: The accuracy of the LogOdds method in reconstructing 3D

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

    NASA Astrophysics Data System (ADS)

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

    In this study, we performed a cardiac motion analysis by using 1000-frames per second (fps) stereo images to capture the three-dimensional motion of small color markers in a rat heart. This method of recording cardiac motion could quantify the rate of change in the myocardial area, which indicated localized myocardial activity of rhythmic expansion and contraction. We analyzed the three-dimensional motion distributions in a rat model for myocardial infarction, in which the heart rate was 4 times/s or more. In the analysis, we spatiotemporally quantified the characteristic cardiac motion in ischemic heart diseases and found that infarction due to ischemia in the rat heart was spread around the left ventricle.

  1. Effects of Shaoyao-Gancao Decoction on Infarcted Cerebral Cortical Neurons: Suppression of the Inflammatory Response following Cerebral Ischemia-Reperfusion in a Rat Model

    PubMed Central

    Jia, Xinling; Yang, Jian; Li, Qing; Yan, Guofeng; Xu, Zhongju; Wang, Jingye

    2016-01-01

    The mechanisms by which Shaoyao-Gancao decoction (SGD) inhibits the production of inflammatory cytokines in serum and brain tissue after cerebral ischemia-reperfusion (CI-RP) in rats were investigated. A right middle cerebral artery occlusion was used to induce CI-RP after which the rats were divided into model (n = 39), SGD (n = 28), clopidogrel (n = 25) and sham operated (n = 34) groups. The Bederson scale was used to evaluate changes in behavioral indices. The levels of IL-1β, TNF-α, MCP-1, IL-10, RANTES, VEGF, and TGF-β1 in the serum and infarcted brain tissues were measured. Nissl body and immunohistochemical staining methods were used to detect biochemical changes in neurons, microglial cells, and astrocytes. Serum levels of VEGF, TNF-α, MCP-1, IL-1β, and IL-10 increased significantly 24 h after CI-RP. In brain tissue, levels of TNF-α and IL-1β significantly increased 24 h after CI-RP, whereas levels of TGF-β1 and MCP-1 were significantly higher 96 h after CI-RP (P < 0.05). SGD or clopidogrel after CI-RP reduced TNF-α and IL-1β levels in brain tissue and serum levels of MCP-1, IL-1β, and IL-10. SGD increased the number of NeuN-positive cells in infarcted brain tissue and reduced the number of IBA1-positive and GFAP-positive cells. The efficacy of SGD was significantly higher than that of clopidogrel. PMID:27413737

  2. 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 < 0.001). The frequency of 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

  3. 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 < 0.001). The frequency of 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

  4. 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

  5. Fenofibrate plus Metformin Produces Cardioprotection in a Type 2 Diabetes and Acute Myocardial Infarction Model

    PubMed Central

    Oidor-Chan, Víctor Hugo; Hong, Enrique; Pérez-Severiano, Francisca; Montes, Sergio; Torres-Narváez, Juan Carlos; del Valle-Mondragón, Leonardo; Pastelín-Hernández, Gustavo; Sánchez-Mendoza, Alicia

    2016-01-01

    We investigated whether fenofibrate, metformin, and their combination generate cardioprotection in a rat model of type 2 diabetes (T2D) and acute myocardial infarction (AMI). Streptozotocin-induced diabetic- (DB-) rats received 14 days of either vehicle, fenofibrate, metformin, or their combination and immediately after underwent myocardial ischemia/reperfusion (I/R). Fenofibrate plus metformin generated cardioprotection in a DBI/R model, reported as decreased coronary vascular resistance, compared to DBI/R-Vehicle, smaller infarct size, and increased cardiac work. The subchronic treatment with fenofibrate plus metformin increased, compared with DBI/R-Vehicle, total antioxidant capacity, manganese-dependent superoxide dismutase activity (MnSOD), guanosine triphosphate cyclohydrolase I (GTPCH-I) expression, tetrahydrobiopterin : dihydrobiopterin (BH4 : BH2) ratio, endothelial nitric oxide synthase (eNOS) activity, nitric oxide (NO) bioavailability, and decreased inducible NOS (iNOS) activity. These findings suggest that PPARα activation by fenofibrate + metformin, at low doses, generates cardioprotection in a rat model of T2D and AMI and may represent a novel treatment strategy to limit I/R injury in patients with T2D. PMID:27069466

  6. Pediatric Rodent Models of Traumatic Brain Injury.

    PubMed

    Semple, Bridgette D; Carlson, Jaclyn; Noble-Haeusslein, Linda J

    2016-01-01

    Due to a high incidence of traumatic brain injury (TBI) in children and adolescents, age-specific studies are necessary to fully understand the long-term consequences of injuries to the immature brain. Preclinical and translational research can help elucidate the vulnerabilities of the developing brain to insult, and provide model systems to formulate and evaluate potential treatments aimed at minimizing the adverse effects of TBI. Several experimental TBI models have therefore been scaled down from adult rodents for use in juvenile animals. The following chapter discusses these adapted models for pediatric TBI, and the importance of age equivalence across species during model development and interpretation. Many neurodevelopmental processes are ongoing throughout childhood and adolescence, such that neuropathological mechanisms secondary to a brain insult, including oxidative stress, metabolic dysfunction and inflammation, may be influenced by the age at the time of insult. The long-term evaluation of clinically relevant functional outcomes is imperative to better understand the persistence and evolution of behavioral deficits over time after injury to the developing brain. Strategies to modify or protect against the chronic consequences of pediatric TBI, by supporting the trajectory of normal brain development, have the potential to improve quality of life for brain-injured children. PMID:27604726

  7. 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

  8. Splenic infarction

    MedlinePlus

    Splenic infarction is the death of tissue (necrosis) in the spleen due to a blockage in blood flow. ... Common causes of splenic infarction include: Blood clots Blood diseases such as sickle cell anemia Infections such as endocarditis

  9. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine.

    PubMed

    Kircher, David A; Silvis, Mark R; Cho, Joseph H; Holmen, Sheri L

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  10. Multiplex immunoassay characterization and species comparison of inflammation in acute and non-acute ischemic infarcts in human and mouse brain tissue.

    PubMed

    Nguyen, Thuy-Vi V; Frye, Jennifer B; Zbesko, Jacob C; Stepanovic, Kristina; Hayes, Megan; Urzua, Alex; Serrano, Geidy; Beach, Thomas G; Doyle, Kristian P

    2016-01-01

    This study provides a parallel characterization of the cytokine and chemokine response to stroke in the human and mouse brain at different stages of infarct resolution. The study goal was to address the hypothesis that chronic inflammation may contribute to stroke-related dementia. We used C57BL/6 and BALB/c mice to control for strain related differences in the mouse immune response. Our data indicate that in both mouse strains, and humans, there is increased granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-12 p70 (IL-12p70), interferon gamma-induced protein-10 (IP-10), keratinocyte chemoattractant/interleukin-8 (KC/IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1β (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), and Tumor necrosis factor-α (TNF-α) in the infarct core during the acute time period. Nevertheless, correlation and two-way ANOVA analyses reveal that despite this substantial overlap between species, there are still significant differences, particularly in the regulation of granulocyte colony-stimulating factor (G-CSF), which is increased in mice but not in humans. In the weeks after stroke, during the stage of liquefactive necrosis, there is significant resolution of the inflammatory response to stroke within the infarct. However, CD68+ macrophages remain present, and levels of IL-6 and MCP-1 remain chronically elevated in infarcts from both mice and humans. Furthermore, there is a chronic T cell response within the infarct in both species. This response is differentially polarized towards a T helper 1 (Th1) response in C57BL/6 mice, and a T helper 2 (Th2) response in BALB/c mice, suggesting that the chronic inflammatory response to stroke may follow a different trajectory in different patients. To control for the fact that the average age of the patients used in this study was 80 years, they

  11. Modeling of functional brain imaging data

    NASA Astrophysics Data System (ADS)

    Horwitz, Barry

    1999-03-01

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

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

    PubMed Central

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

    2009-01-01

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

  13. Effects of recombinant human brain natriuretic peptide on renal function in patients with acute heart failure following myocardial infarction

    PubMed Central

    Wang, Yanbo; Gu, Xinshun; Fan, Weize; Fan, Yanming; Li, Wei; Fu, Xianghua

    2016-01-01

    Objective: To investigate the effect of recombinant human brain natriuretic peptide (rhBNP) on renal function in patients with acute heart failure (AHF) following acute myocardial infarction (AMI). Methods: Consecutive patients with AHF following AMI were enrolled in this clinical trial. Eligible patients were randomly assigned to receive rhBNP (rhBNP group) or nitroglycerin (NIT group). Patients in the rhBNP group received rhBNP 0.15 μg /kg bolus injection after randomization followed by an adjusted-dose (0.0075-0.020 μg/kg/min) for 72 hours, while patients in NIT received infusion of nitroglycerin with an adjusted-dose (10-100 μg/kg/min) for 72 hours in NIT group. Standard clinical and laboratory data were collected. The levels of serum creatinine (SCr), urea, β-2 microglobulin and cystatin C were measured at baseline and repeated at the end of the 24, 48 and 72 hours after infusion. The primary end point was the incidence of acute renal dysfunction, which was defined as an increase in SCr > 0.5 mg/dl (> 44.2 μmol/L) or 25% above baseline SCr value. The occurrence of major adverse cardiac event (MACE) was followed up for 1 month. Results: Of the 50 patients enrolled, 26 were randomly assigned to rhBNP and 24 to nitroglycerin (NIT). There were no significant differences in baseline characteristics between the two groups (all P > 0.05). The baseline concentrations of SCr, urea, β-2 microglobulin and cystatin C at admission were similar in the two groups. However, the concentrations of SCr and urea were significantly higher in rhBNP group than those in NIT group at hour 24 and 48 after treatments (all P < 0.01). For both groups, the concentrations of SCr, urea, β-2 microglobulin and cystatin C were not significant changed compared with baseline levels. The levels of systolic blood pressure (SBP) and diastolic blood pressures (DBP) at admission were also similar between the two groups. In rhBNP group, levels of SBP and DBP decreased significantly at hour 24

  14. [Bilateral caudate head infarcts].

    PubMed

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

    1997-11-01

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

  15. Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

    PubMed

    Pareja, Jennifer C Munoz; Keeley, Kristen; Duhaime, Ann-Christine; Dodge, Carter P

    2016-01-01

    The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma. PMID:27604727

  16. MicroRNA-208b Alleviates Post-Infarction Myocardial Fibrosis in a Rat Model by Inhibiting GATA4

    PubMed Central

    Zhou, Chaoyuan; Cui, Qintao; Su, Guobao; Guo, Xiaoliang; Liu, Xiaochen; Zhang, Jie

    2016-01-01

    Background Myocardial infarction affects the health of many people. Post-infarction myocardial fibrosis has attracted much attention, but details of the mechanism remain elusive. In this study, the role of microRNA-208b (miR-208b) in modulating post-infarction myocardial fibrosis and the related mechanism were investigated. Material/Methods A rat model of myocardial infarction induced by ligating the left anterior descending artery was used to analyze the expression and roles of miR-208b by overexpression with the lentivirus vector of pre-miR-208b. Myocardial function was assessed and the expression of fibrosis-related factors type I collagen (COL1) and ACTA2 (alias αSMA) was detected. Myocardial fibroblasts isolated from newborn rats were transfected with luciferase reporter vectors containing wild-type or mutant Gata4 3′ UTR to verify the relationship between Gata4 and miR-208b. We then transfected the specific small interference RNA of Gata4 to detect changes in COL1 and ACTA2. Results miR-208b was down-regulated in hearts of model rats (P<0.01). Overexpressing miR-208b improved myocardial functions, such as reducing the infarction area (P<0.05) and promoting LVEF and LVFS (P<0.01), and inhibited COL1 and ACTA2 (P<0.01). Luciferase reporter assay proved Gata4 to be the direct target of miR-208b, with the target sequence in the 3′UTR. Inhibiting GATA4 resulted in the down-regulation of COL1 and ACTA2, suggesting that the role of miR-208b was achieved via regulating GATA4. Conclusions This study demonstrates the protective function of miR-208b via GATA4 in post-infarction myocardial fibrosis, providing a potential therapeutic target for treating myocardial fibrosis. PMID:27236543

  17. Weight Drop Models in Traumatic Brain Injury.

    PubMed

    Kalish, Brian T; Whalen, Michael J

    2016-01-01

    Weight drop models in rodents have been used for several decades to advance our understanding of the pathophysiology of traumatic brain injury. Weight drop models have been used to replicate focal cerebral contusion as well as diffuse brain injury characterized by axonal damage. More recently, closed head injury models with free head rotation have been developed to model sports concussions, which feature functional disturbances in the absence of overt brain damage assessed by conventional imaging techniques. Here, we describe the history of development of closed head injury models in the first part of the chapter. In the second part, we describe the development of our own weight drop closed head injury model that features impact plus rapid downward head rotation, no structural brain injury, and long-term cognitive deficits in the case of multiple injuries. This rodent model was developed to reproduce key aspects of sports concussion so that a mechanistic understanding of how long-term cognitive deficits might develop will eventually follow. Such knowledge is hoped to impact athletes and war fighters and others who suffer concussive head injuries by leading to targeted therapies aimed at preventing cognitive and other neurological sequelae in these high-risk groups. PMID:27604720

  18. Mathematical Model of Evolution of Brain Parcellation.

    PubMed

    Ferrante, Daniel D; Wei, Yi; Koulakov, Alexei A

    2016-01-01

    We study the distribution of brain and cortical area sizes [parcellation units (PUs)] obtained for three species: mouse, macaque, and human. We find that the distribution of PU sizes is close to lognormal. We propose the mathematical model of evolution of brain parcellation based on iterative fragmentation and specialization. In this model, each existing PU has a probability to be split that depends on PU size only. This model suggests that the same evolutionary process may have led to brain parcellation in these three species. Within our model, region-to-region (macro) connectivity is given by the outer product form. We show that most experimental data on non-zero macaque cortex macroscopic-level connections can be explained by the outer product power-law form suggested by our model (62% for area V1). We propose a multiplicative Hebbian learning rule for the macroconnectome that could yield the correct scaling of connection strengths between areas. We thus propose an evolutionary model that may have contributed to both brain parcellation and mesoscopic level connectivity in mammals. PMID:27378859

  19. Mathematical Model of Evolution of Brain Parcellation

    PubMed Central

    Ferrante, Daniel D.; Wei, Yi; Koulakov, Alexei A.

    2016-01-01

    We study the distribution of brain and cortical area sizes [parcellation units (PUs)] obtained for three species: mouse, macaque, and human. We find that the distribution of PU sizes is close to lognormal. We propose the mathematical model of evolution of brain parcellation based on iterative fragmentation and specialization. In this model, each existing PU has a probability to be split that depends on PU size only. This model suggests that the same evolutionary process may have led to brain parcellation in these three species. Within our model, region-to-region (macro) connectivity is given by the outer product form. We show that most experimental data on non-zero macaque cortex macroscopic-level connections can be explained by the outer product power-law form suggested by our model (62% for area V1). We propose a multiplicative Hebbian learning rule for the macroconnectome that could yield the correct scaling of connection strengths between areas. We thus propose an evolutionary model that may have contributed to both brain parcellation and mesoscopic level connectivity in mammals. PMID:27378859

  20. A model for lupus brain disease

    PubMed Central

    Diamond, Betty; Volpe, Bruce T.

    2015-01-01

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

  1. Multimodal, multidimensional models of mouse brain.

    PubMed

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

    2007-01-01

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

  2. 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.

  3. Carnosine pretreatment protects against hypoxia-ischemia brain damage in the neonatal rat model.

    PubMed

    Zhang, Xiangmin; Song, Lili; Cheng, Xiuyong; Yang, Yi; Luan, Bin; Jia, Liting; Xu, Falin; Zhang, Zhan

    2011-09-30

    Perinatal hypoxia-ischemia brain injury is a major cause of mortality and morbidity in neonates and lacks an effective treatment thus far. Carnosine has been demonstrated to play a neuroprotective role in the adult brain injuries. However, there is no information available concerning its neuroprotective role in the immature brains after hypoxia-ischemia insults. Therefore, we investigated whether carnosine could also confer neuroprotective effects in a neonatal rat hypoxia-ischemia model. Hypoxia-ischemia was induced in rats on postnatal day 7 (P7). Carnosine (250 mg/kg) was administered intraperitoneally, 30 min prior to hypoxia-ischemia induction. Morphological brain injury and biochemical markers of apoptosis and oxidative stress were evaluated 24 h after hypoxia-ischemia induction. Cognitive performance was evaluated by the Morris Water Maze test on P28-P33. We found that pretreatment with carnosine significantly reduced the infarct volume and the number of terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hypoxia-ischemia brain. Carnosine also inhibited mRNA expression of apoptosis-inducing factor(AIF) and caspase-3, which was accompanied by an increase in superoxide dismutase(SOD)activity and a decrease in the malondialdehyde(MDA)level in carnosine-treated rats. Furthermore, carnosine also improved the spatial learning and memory abilities of rats declined due to hypoxia-ischemia. These results demonstrate that carnosine can protect rats against hypoxia-ischemia-induced brain damage by antioxidation. PMID:21693116

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

    PubMed Central

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

    2011-01-01

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

  5. Comparison of the effects of EPA and DHA alone or in combination in a murine model of myocardial infarction.

    PubMed

    Madingou, Ness; Gilbert, Kim; Tomaro, Leandro; Prud'homme Touchette, Charles; Trudeau, François; Fortin, Samuel; Rousseau, Guy

    2016-08-01

    The aim of this project was to investigate the impact of two dietary omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alone or in combination, on infarct size. Adult, male Sprague-Dawley rats were fed for 14 days with different omega-3 diets. The animals were subjected to ischemia for 40min followed by reperfusion. Infarct size, Akt (protein kinase B) activation level, caspase-3 activity and mitochondrial permeability transition pore (mPTP) opening were measured. The results indicate that EPA or DHA alone significantly reduced infarct size compared to the other diets. Akt activity was increased in the group fed EPA or DHA alone, whereas no significant activation was observed in the other groups compared to no omega-3 PUFA. DHA alone reduced caspase-3 activity and conferred resistance to mPTP opening. In conclusion, our results demonstrate that EPA and DHA are individually effective in diminishing infarct size in our experimental model while their combination is not. PMID:27499449

  6. The effect of combined treatment with Impella(®) and landiolol in a swine model of acute myocardial infarction.

    PubMed

    Yoshitake, Isamu; Hata, Mitsumasa; Sezai, Akira; Unosawa, Satoshi; Wakui, Shinji; Kimura, Haruka; Nakata, Kin-ichi; Hata, Hiroaki; Shiono, Motomi

    2012-09-01

    Cardiogenic shock is associated with a high mortality rate in patients with acute myocardial infarction (AMI). We developed a new treatment approach named heart rest therapy (HRT) for complete revascularization in the early stage of AMI using an ultra-short-acting β-blocker (landiolol) and an Impella(®) left ventricular assist device and verified the effect of this therapy in a swine model. In 18 male pigs, AMI was induced by left anterior descending coronary artery occlusion at the level of the second diagonal branch for 120 min, followed by 240 min of reperfusion. The animals were divided into three groups: group A had no support, group B was supported with the Impella(®), and group C was treated with HRT from 90 min after ischemia to 240 min after reperfusion. Infarct ratio (percentage of the infarct area relative to the area at infarct risk) was significantly reduced in group C (group A 65.38 ± 6.07, group B 39.66 ± 11.16, group C 21.78 ± 7.29), with a significant difference between groups A and B (P < 0.001), A and C (P < 0.001), and B and C (P = 0.006). Heart rates were significantly lower in group C at 30 min (P = 0.01), 60 min (P = 0.022), and 240 min (P = 0.032) after reperfusion compared with group B, without development of hypotension. HRT at the early stage in AMI stabilized the hemodynamic conditions and reduced infarct size and complications in a swine model. These results suggest that HRT can improve the prognosis of patients with AMI. PMID:22527977

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

    PubMed

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

    1999-01-01

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

  9. 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

  10. Multiscale modeling of brain blow flow

    NASA Astrophysics Data System (ADS)

    Karniadakis, George

    2014-11-01

    Cardiovascular pathologies, such as brain aneurysms, are affected by the global blood circulation as well as by the local microrheology. Hence, developing computational models for such cases requires the coupling of disparate spatial and temporal scales often governed by diverse mathematical descriptions, e.g., by partial differential equations (continuum, 3D or 1D) and ordinary differential equations for discrete particles (atomistic). However, interfacing atomistic-based with continuum-based domain discretizations is a challenging problem that requires both mathematical and computational advances. We will present a physical model of the brain vasculature consisting at the macro level of all major arteries (about 200 down to 0.5 mm), at the mesoscale the fractal arteriolar tree (more than 10 millions down to 20 nm) and at the microscale the capillary bed. Correspondingly, we employ three different methods to model the total brain vasculature by developing proper interface conditions at each level. We will present examples from aneurysms and other hematological diseases, where red blood cell rheology is modeled explicitly.

  11. 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.

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

    PubMed Central

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

    2011-01-01

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

  13. Mouse Genetic Models of Human Brain Disorders.

    PubMed

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases. PMID:27047540

  14. Mouse Genetic Models of Human Brain Disorders

    PubMed Central

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases. PMID:27047540

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

    PubMed

    Roy, Sisir; Llinás, Rodolfo

    2008-01-01

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

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

    PubMed Central

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

    2016-01-01

    BACKGROUND Human ventricular tachycardia (VT) after myocardial infarction usually occurs because of subendocardial reentrant circuits originating in scar tissue that borders surviving myocardial bundles. Several preclinical large animal models have been used to further study postinfarct reentrant VT, but with varied experimental methodologies and limited evaluation of the underlying substrate or induced arrhythmia mechanism. OBJECTIVE We aimed to develop and characterize a swine model of scar-related reentrant VT. METHODS Thirty-five Yorkshire swine underwent 180-minute occlusion of the left anterior descending coronary artery. Thirty-one animals (89%) survived the 6–8-week survival period. These animals underwent cardiac magnetic resonance imaging followed by electrophysiology study, detailed electroanatomic mapping, and histopathological analysis. RESULTS Left ventricular (LV) ejection fraction measured using CMR imaging was 36% ± 6.6% with anteroseptal wall motion abnormality and late gadolinium enhancement across 12.5% ± 4.1% of the LV surface area. Low voltage measured using endocardial electroanatomic mapping encompassed 11.1% ± 3.5% of the LV surface area (bipolar voltage ≤1.5 mV) with anterior, anteroseptal, and anterolateral involvement. Reentrant circuits mapped were largely determined by functional rather than fix anatomical barriers, consistent with “pseudo-block” due to anisotropic conduction. Sustained monomorphic VT was induced in 28 of 31 swine (90%) (67 VTs; 2.4 ± 1.1; range 1–4) and characterized as reentry. VT circuits were subendocardial, with an arrhythmogenic substrate characterized by transmural anterior scar with varying degrees of fibrosis and myocardial fiber disarray on the septal and lateral borders. CONCLUSION This is a well-characterized swine model of scar-related subendocardial reentrant VT. This model can serve as the basis for further investigation in the physiology and therapeutics of humanlike postinfarction

  17. Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis

    PubMed Central

    Wei, You-Dong; Liu, Yi-Yun; Ren, Yi-Fei; Liang, Zi-Hong; Wang, Hai-Yang; Zhao, Li-Bo; Xie, Peng

    2016-01-01

    Background and Purpose Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke. Methods Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger’s test were obtained to detect publication bias. Results We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate. Conclusions This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA. PMID:27387385

  18. Perinatal hypoxic-ischemic brain damage: evolution of an animal model.

    PubMed

    Vannucci, Robert C; Vannucci, Susan J

    2005-01-01

    Early research in the Vannucci laboratory prior to 1981 focused largely on brain energy metabolism in the developing rat. At that time, there was no experimental model to study the effects of perinatal hypoxia-ischemia in the rodent, despite the tremendous need to investigate the pathophysiology of perinatal asphyxial brain damage in infants. Accordingly, we developed such a model in the postnatal day 7 rat, using a modification of the Levine preparation in the adult rat. Rat pups underwent unilateral common carotid artery ligation followed by exposure to systemic hypoxia (8% oxygen) at a constant temperature of 37 degrees C. Brain damage, seen histologically, was generally confined to the cerebral hemisphere ipsilateral to the arterial occlusion, and consisted of selective neuronal death or infarction, depending on the duration of the systemic hypoxia. Tissue injury was observed in the cerebral cortex, hippocampus, striatum, and thalamus. Subcortical and periventricular white matter injury was also observed. This model was originally described in the Annals of Neurology in 1981, and during the more than 20 years since that publication numerous investigations utilizing the model have been conducted in our laboratories as well as laboratories around the world. Cerebral blood flow and metabolic correlates have been fully characterized. Physiologic and pharmacologic manipulations have been applied to the model in search of neuroprotective strategies. More recently, molecular biologic alterations during and following the hypoxic-ischemic stress have been ascertained and the model has been adapted to the immature mouse for specific use in genetically altered animals. As predicted in the original article, the model has proven useful for the study of the short- and long-term effects of hypoxic-ischemic brain damage on motor activity, behavior, seizure incidence, and the process of maturation in the brain and other organ systems. PMID:16046840

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

    PubMed Central

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

    2015-01-01

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

  20. 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

  1. Rehabilitative Training Promotes Rapid Motor Recovery but Delayed Motor Map Reorganization in a Rat Cortical Ischemic Infarct Model

    PubMed Central

    Nishibe, Mariko; Urban, Edward T.R.; Barbay, Scott; Nudo, Randolph J.

    2014-01-01

    Background In preclinical stroke models, improvement in motor performance is associated with reorganization of cortical motor maps. However, the temporal relationship between performance gains and map plasticity is not clear. Objective This study was designed to assess the effects of rehabilitative training on the temporal dynamics of behavioral and neurophysiological endpoints in a rat model of focal cortical infarct. Methods Eight days after an ischemic infarct in primary motor cortex, adult rats received either rehabilitative training or were allowed to recover spontaneously. Motor performance and movement quality of the paretic forelimb was assessed on a skilled reach task. Intracortical microstimulation mapping procedures were conducted to assess the topography of spared forelimb representations either at the end of training (post-lesion day 18) or at the end of a three week follow-up period (post-lesion day 38). Results Rats receiving rehabilitative training demonstrated more rapid improvement in motor performance and movement quality during the training period that persisted through the follow-up period. Motor maps in both groups were unusually small on post-lesion day 18. On post-lesion day 38, forelimb motor maps in the rehabilitative training group were significantly enlarged compared with the no-rehab group, and within the range of normal maps. Conclusions Post-infarct rehabilitative training rapidly improves motor performance and movement quality after an ischemic infarct in motor cortex. However, training-induced motor improvements are not reflected in spared motor maps until substantially later, suggesting that early motor training after stroke can help shape the evolving post-stroke neural network. PMID:25055836

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

    PubMed

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

    2013-01-01

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

  3. Myocardial infarction, ST-elevation and non-ST-elevation myocardial infarction and modelled daily pollution concentrations: a case-crossover analysis of MINAP data

    PubMed Central

    Butland, Barbara K; Atkinson, Richard W; Milojevic, Ai; Heal, Mathew R; Doherty, Ruth M; Armstrong, Ben G; MacKenzie, Ian A; Vieno, Massimo; Lin, Chun; Wilkinson, Paul

    2016-01-01

    Objectives To investigate associations between daily concentrations of air pollution and myocardial infarction (MI), ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI). Methods Modelled daily ground-level gaseous, total and speciated particulate pollutant concentrations and ground-level daily mean temperature, all at 5 km×5 km horizontal resolution, were linked to 202 550 STEMI and 322 198 NSTEMI events recorded on the England and Wales Myocardial Ischaemia National Audit Project (MINAP) database. The study period was 2003–2010. A case-crossover design was used, stratified by year, month and day of the week. Data were analysed using conditional logistic regression, with pollutants modelled as unconstrained distributed lags 0–2 days. Results are presented as percentage change in risk per 10 µg/m3 increase in the pollutant relevant metric, having adjusted for daily mean temperature, public holidays, weekly influenza consultation rates and a sine-cosine annual cycle. Results There was no evidence of an association between MI or STEMI and any of O3, NO2, PM2.5, PM10 or selected PM2.5 components (sulfate and elemental carbon). For NSTEMI, there was a positive association with daily maximum 1-hour NO2 (0.27% (95% CI 0.01% to 0.54%)), which persisted following adjustment for O3 and adjustment for PM2.5. The association appeared to be confined to the midland and southern regions of England and Wales. Conclusions The study found no evidence of an association between the modelled pollutants (including components) investigated and STEMI but did find some evidence of a positive association between NO2 and NSTEMI. Confirmation of this association in other studies is required. PMID:27621827

  4. 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.

  5. Traumatic Brain Injury Models in Animals.

    PubMed

    Rostami, Elham

    2016-01-01

    Traumatic brain injury (TBI) is the leading cause of death in young adults in industrialized nations and in the developing world the WHO considers TBI a silent epidemic caused by an increasing number of traffic accidents. Despite the major improvement of TBI outcome in the acute setting in the past 20 years, the assessment, therapeutic interventions, and prevention of long-term complications remain a challenge. In order to get a deeper insight into the pathology of TBI and advancement of medical understanding and clinical progress experimental animal models are an essential requirement. This chapter provides an overview of most commonly used experimental animal TBI models and the pathobiological findings based on current data. In addition, limitations and advantages of each TBI model are mentioned. This will hopefully give an insight into the possibilities of each model and be of value in choosing one when designing a study. PMID:27604712

  6. Fractional Modeling of Viscoelasticity in Brain Aneurysms

    NASA Astrophysics Data System (ADS)

    Yu, Yue; Karniadakis, George

    2014-11-01

    We develop fundamental new numerical methods for fractional order PDEs, and investigate corresponding models for arterial walls. Specifically, the arterial wall is a heterogeneous soft tissue with complex biomechanical properties, and its constitutive laws are typically derived using integer-order differential equations. However, recent simulations on 1D model have indicated that fractional order models may offer a more powerful alternative for describing arterial wall mechanics, because they are less sensitive to the parameter estimation compared with the integer-calculus-based models. We study the specific fractional PDEs that better model the properties of the 3D arterial walls, and for the first time employ them in simulating flow structure interactions for patient-specific brain aneurysms. A comparison study indicates that for the integer order models, the viscous behavior strongly depends on the relaxation parameters while the fractional order models are less sensitive. This finding is consistent with what is observed in the 1D models for arterial networks (Perdikaris & Karniadakis, 2014), except that when the fractional order is small, the 3D fractional-order models are more sensitive to the fractional order compared to the 1D models.

  7. Association of seizures with cortical spreading depression and peri-infarct depolarisations in the acutely injured human brain

    PubMed Central

    Fabricius, Martin; Fuhr, Susanne; Willumsen, Lisette; Dreier, Jens P; Bhatia, Robin; Boutelle, Martyn G.; Hartings, Jed A; Bullock, Ross; Strong, Anthony J; Lauritzen, Martin

    2008-01-01

    Objective To test the co-occurrence and interrelation of ictal activity and cortical spreading depressions (CSDs) - including the related periinfarct depolarisations in acute brain injury caused by trauma, and spontaneous subarachnoid and/or intracerebral haemorrhage. Methods 63 patients underwent craniotomy and electrocorticographic (ECoG) recordings were taken near foci of damaged cortical tissue for up to 10 days. Results 32 of 63 patients exhibited CSDs (5 to 75 episodes), and 11 had ECoGraphic seizure activity (1-81 episodes). Occurrence of seizures was significantly associated with CSD, as 10 of 11 patients with seizures also had CSD (p=0.007, 2-tailed Fishers exact test). Clinically overt seizures were only observed in one patient. Each patient with CSD and seizures displayed one of four different patterns of interaction between CSD and seizures. In four patients CSD was immediately preceded by prolonged seizure activity. In three patients the two phenomena were separated in time: multiple CSDs were replaced by ictal activity. In one patient seizures appeared to trigger repeated CSDs at the adjacent electrode. In two patients ongoing repeated seizures were interrupted each time CSD occurred. Conclusions Seizure activity occurs in association with CSD in the injured human brain. Significance ECoG recordings in brain injury patients provide insight into pathophysiological mechanisms that is not accessible by scalp EEG recordings. PMID:18621582

  8. Translation of Methodology Used In Human Myocardial Imaging to a Sheep Model of Acute Myocardial Infarction

    PubMed Central

    Bailey, Elizabeth A; Bailey, Dale L; Hunyor, Stephen; Ladd, Leigh; Bautovich, George J

    2013-01-01

    Introduction: Pre-clinical investigation of stem cells for repairing damaged myocardium predominantly uses rodents, however large animals have cardiac circulation closely resembling the human heart. The aim of this study was to evaluate whether SPECT/CT myocardial perfusion imaging (MPI) could be used for assessing sheep myocardium following an acute myocardial infarction (MI) and response to intervention. Methods: Eighteen sheep were enrolled in a pilot study to evaluate [99mTc]-sestamibi MPI at baseline, post-MI and after therapy. Modifications to the standard MPI protocols were developed. All data was reconstructed with OSEM using CT-derived attenuation and scatter correction. Standard analyses were performed and inter-observer agreement was measured using Kappa (κ). Power determined the sample sizes needed to show statistically significant changes due to intervention. Results: Ten sheep completed the full protocol. Data processed was performed with pre-existing hardware and software used in human MPI scanning. No improvement in perfusion was seen in the control group, however improvements of 15%-35% were seen after intra-myocardial stem cell administration. Inter-observer agreement was excellent (К=0.89). Using a target power of 0.9, 28 sheep were required to detect a 10-12% change in perfusion. Conclusion: This study demonstrates the suitability of large animal models for imaging with standard MPI protocols and its feasibility with a manageable number of animals. These protocols could be translated into humans to study the efficacy of stem cell therapy in heart regeneration and repair.

  9. On a Quantum Model of Brain Activities

    NASA Astrophysics Data System (ADS)

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

    2010-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  11. The role of Interleukin Receptor Associated Kinase (IRAK)-M in regulation of myofibroblast phenotype in vitro, and in an experimental model of non-reperfused myocardial infarction.

    PubMed

    Saxena, Amit; Shinde, Arti V; Haque, Zaffar; Wu, Yi-Jin; Chen, Wei; Su, Ya; Frangogiannis, Nikolaos G

    2015-12-01

    In the infarcted myocardium, necrotic cardiomyocytes activate innate immune pathways, stimulating pro-inflammatory signaling cascades. Although inflammation plays an important role in clearance of the infarct from dead cells and matrix debris, repair of the infarcted heart requires timely activation of signals that negatively regulate the innate immune response, limiting inflammatory injury. We have previously demonstrated that Interleukin receptor-associated kinase (IRAK)-M, a member of the IRAK family that suppresses toll-like receptor/interleukin-1 signaling, is upregulated in the infarcted heart in both macrophages and fibroblasts, and restrains pro-inflammatory activation attenuating adverse remodeling. Although IRAK-M is known to suppress inflammatory activation of macrophages, its role in fibroblasts remains unknown. Our current investigation examines the effects of IRAK-M on fibroblast phenotype and function. In vitro, IRAK-M null cardiac fibroblasts have impaired capacity to contract free-floating collagen pads. IRAK-M loss reduces transforming growth factor (TGF)-β-mediated α-smooth muscle actin (α-SMA) expression. IRAK-M deficient cardiac fibroblasts exhibit a modest reduction in TGF-β-stimulated Smad activation and increased expression of the α-SMA repressor, Y-box binding protein (YB)-1. In a model of non-reperfused myocardial infarction, IRAK-M absence does not affect collagen content and myofibroblast density in the infarcted and remodeling myocardium, but increases YB-1 levels and is associated with attenuated α-SMA expression in isolated infarct myofibroblasts. Our findings suggest that, in addition to its role in restraining inflammation following reperfused infarction, IRAK-M may also contribute to myofibroblast conversion. PMID:26542797

  12. Statistical analysis of brain sulci based on active ribbon modeling

    NASA Astrophysics Data System (ADS)

    Barillot, Christian; Le Goualher, Georges; Hellier, Pierre; Gibaud, Bernard

    1999-05-01

    This paper presents a general statistical framework for modeling deformable object. This model is devoted being used in digital brain atlases. We first present a numerical modeling of brain sulci. We present also a method to characterize the high inter-individual variability of basic cortical structures on which the description of the cerebral cortex is based. The aimed applications use numerical modeling of brain sulci to assist non-linear registration of human brains by inter-individual anatomical matching or to better compare neuro-functional recordings performed on a series of individuals. The utilization of these methods is illustrated using a few examples.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. 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.

  16. The Effect of Pulsatility Index on Infarct Volume in Acute Lacunar Stroke

    PubMed Central

    Kim, Yoon; Lee, Hanbin; An, Se-A; Yim, Byeongsoo; Kim, Jonguk; Kim, Ok Joon; Kim, Won Chan; Kim, Hyun Sook; Oh, Seung Hun

    2016-01-01

    Purpose Lacunar stroke, in the context of small vessel disease, is a type of cerebral infarction caused by occlusion of a penetrating artery. Pulsatility index (PI) is an easily measurable parameter in Transcranial Doppler ultrasound (TCD) study. PI reflects distal cerebral vascular resistance and has been interpreted as a surrogate marker of small vessel disease. We hypothesized that an increased PI, a marker of small vessel disease, might be associated with a larger infarct volume in acute lacunar stroke. Materials and Methods This study included 64 patients with acute lacunar stroke who underwent TCD and brain MRI. We evaluated the association between the mean PI value of bilateral middle cerebral arteries and infarct volume on diffusion-weighted MRI using univariate and multivariate linear regression. Results The mean infarct volume and PI were 482.18±406.40 mm3 and 0.86±0.18, respectively. On univariate linear regression, there was a significant positive association between PI and infarct volume (p=0.001). In the multivariate model, a single standard deviation increase of PI (per 0.18) was associated with an increase of 139.05 mm3 in infarct volume (95% confidence interval, 21.25 to 256.85; p=0.022). Conclusion We demonstrated that PI was an independent determinant of infarct volume in acute lacunar stroke. The PI value measured in acute stroke may be a surrogate marker of the extent of ischemic injury. PMID:27189290

  17. The adult Göttingen minipig as a model for chronic heart failure after myocardial infarction: focus on cardiovascular imaging and regenerative therapies.

    PubMed

    Schuleri, Karl H; Boyle, Andrew J; Centola, Marco; Amado, Luciano C; Evers, Robert; Zimmet, Jeffrey M; Evers, Kristine S; Ostbye, Katherine M; Scorpio, Diana G; Hare, Joshua M; Lardo, Albert C

    2008-12-01

    Porcine models have become increasingly popular in cardiovascular research. The standard farm pig rapidly increases in body weight and size, potentially confounding serial measurements of cardiac function and morphology. We developed an adult porcine model that does not show physiologic increases in heart mass during the study period and is suitable for long-term study. We compared adult minipigs with the commonly used adolescent Yorkshire swine. Myocardial infarction was induced in adult Göttingen minipigs and adolescent Yorkshire swine by occlusion of the left anterior descending coronary artery followed by reperfusion. At 8 wk after infarction, the left ventricular ejection fraction was 34.1 +/- 2.3% in minipigs and 30.7 +/- 2.0% in Yorkshire swine. The left ventricular end-diastolic mass in Yorkshire pigs assessed by magnetic resonance imaging increased 17 +/- 5 g, from 42.6 +/- 4.3 g at week 1 after infarction to 52.8 +/- 6.6 g at week 8, whereas it remained unchanged in minipigs. Cardiac anatomy and physiology in adult minipigs were evaluated invasively by angiography and noninvasively by Multidetector Computed Tomography and by Magnetic Resonance Imaging at 1.5 T and 3 T prior to myocardial infarction and during folow-up. This porcine heart failure model is reproducible, mimics the pathophysiology in patients who have experienced myocardial infarction, and is suitable for imaging studies. New heart failure therapies and devices can be tested preclinically in this adult animal model of chronic heart failure. PMID:19149414

  18. Modeling the current distribution across the depth electrode-brain interface in deep brain stimulation.

    PubMed

    Yousif, Nada; Liu, Xuguang

    2007-09-01

    The mismatch between the extensive clinical use of deep brain stimulation (DBS), which is being used to treat an increasing number of neurological disorders, and the lack of understanding of the underlying mechanisms is confounded by the difficulty of measuring the spread of electric current in the brain in vivo. In this article we present a brief review of the recent computational models that simulate the electric current and field distribution in 3D space and, consequently, make estimations of the brain volume being modulated by therapeutic DBS. Such structural modeling work can be categorized into three main approaches: target-specific modeling, models of instrumentation and modeling the electrode-brain interface. Comments are made for each of these approaches with emphasis on our electrode-brain interface modeling, since the stimulating current must travel across the electrode-brain interface in order to reach the surrounding brain tissue and modulate the pathological neural activity. For future modeling work, a combined approach needs to be taken to reveal the underlying mechanisms, and both structural and dynamic models need to be clinically validated to make reliable predictions about the therapeutic effect of DBS in order to assist clinical practice. PMID:17850197

  19. Modeling Brain Resonance Phenomena Using a Neural Mass Model

    PubMed Central

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

    2011-01-01

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

  20. Modeling brain resonance phenomena using a neural mass model.

    PubMed

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

    2011-12-01

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

  1. Intracoronary infusion of autologous mononuclear cells from bone marrow or G-CSF mobilised apheresis product may not improve remodelling, contractile function, perfusion or infarct size in a swine model of large myocardial infarction

    PubMed Central

    de Silva, Ranil; Raval, Amish N.; Hadi, Mohiuddin; Gildea, Karena M.; Bonifacino, Aylin C.; Yu, Zu-Xi; Yau, Yu Ying; Leitman, Susan F.; Bacharach, Stephen L.; Donahue, Robert E.; Read, Elizabeth J.; Lederman, Robert J.

    2008-01-01

    Background In a blinded, placebo controlled study, we investigated whether intracoronary infusion of autologous mononuclear cells from G-CSF mobilised apheresis product or bone marrow (BM) improved sensitive outcome measures in a swine model of large MI. Methods and Results Four days after LAD occlusion and reperfusion, cells from BM or apheresis product of saline (Placebo) or G-CSF injected animals were infused into the LAD. Large infarcts were created: baseline ejection fraction (EF) by MRI of 35.3 ± 8.5%, no difference between the Placebo, G-CSF and BM groups (p=0.16 by ANOVA). At 6 weeks EF fell to a similar degree in the Placebo, G-CSF and BM groups (−7.9±6.0%, −8.5±8.8% and −10.9±7.6%, p=0.78 by ANOVA). Left ventricular volumes and infarct size by MRI deteriorated similarly in all 3 groups. Quantitative PET demonstrated significant decline in FDG uptake rate in the LAD territory at follow-up, with no histological, angiographic or PET perfusion evidence of functional neovascularisation. Immunofluorescence failed to demonstrate transdifferentiation of infused cells. Conclusion Intracoronary infusion of mononuclear cells from either bone marrow or G-CSF mobilised apheresis product may not improve or limit deterioration in systolic function, adverse ventricular remodelling, infarct size or perfusion in a swine model of large MI. PMID:18502738

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

    PubMed

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

    2009-01-01

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

  3. Comparing the effects of MSCs and CD34+ cell therapy in a rat model of myocardial infarction.

    PubMed

    Shalaby, Sally M; El-Shal, Amal S; Zidan, Haidy E; Mazen, Nehad F; Abd El-Haleem, Manal R; Abd El Motteleb, Dalia M

    2016-05-01

    Stem cell therapy is considered as a promising approach in the treatment of myocardial infarction (MI). This study was designed as a comparison of human umbilical cord blood (HUCB)-derived CD34+ and HUCB-derived MSCs for the repair of cardiac tissue by induction of the angiogenesis. Forty-eight male rats were randomized into four groups: sham-operated group, MI group, MSCs-treated group, and CD34+ cells-treated group. After 4 weeks, the rats were sacrificed. All sections from left ventricles of all groups were subjected to hematoxylin & eosin, Masson's trichrome, and immunohistochemical stains (CD133, CD44, and α-smooth muscle actin). RNA was extracted for gene expression of the angiogenic markers. A significant reduction of the infarct size and the amplitude of T-wave in the CD34+ cells-treated group when compared with the MSCs-treated group were determined. Histologically, the MI group showed scar tissue, congested blood capillaries around the infarcted area, some necrotic cells, and inflammatory cells. Administration of either MSCs or CD34+ cells had a therapeutic potential to induce regenerative changes in the myocardium with better results in CD34+cells-treated group. Quantitative RT-PCR analysis revealed a significant increase in the expression of vascular endothelial growth factor (VEGF), VEGFR-2, Ang-1, and Tie-2 and a significant decreased expression of Ang-2 in stem cells transplanted groups when compared with the noncell transplanted hearts. A significant increase of VEGF, VEGFR-2, Ang-1, and Tie-2 expression in the group receiving CD34+ cells than those receiving MSCs was found. Finally, there was an upregulation of both human VEGF and human hypoxia-inducible factor 1α in the infarcted hearts treated by CD34+ cells than that treated by MSCs. We first revealed a superior efficacy of CD34+ cells when compared with MSCs in induction of regenerative changes in the MI model. Both cell therapies may repair the damaged heart tissue primarily by secretion of

  4. Mathematical modelling of blood-brain barrier failure and edema

    NASA Astrophysics Data System (ADS)

    Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

    2015-11-01

    Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

  5. Progenitor Cell Therapy in a Porcine Acute Myocardial Infarction Model Induces Cardiac Hypertrophy, Mediated by Paracrine Secretion of Cardiotrophic Factors Including TGFβ1

    PubMed Central

    Doyle, Brendan; Sorajja, Paul; Hynes, Brian; Kumar, Arun H.S.; Araoz, Phillip A.; Stalboerger, Paul G.; Miller, Dylan; Reed, Cynthia; Schmeckpeper, Jeffrey; Wang, Shaohua; Liu, Chunsheng; Terzic, Andre; Kruger, David; Riederer, Stephen

    2008-01-01

    Administration of endothelial progenitor cells (EPC) is a promising therapy for post-infarction cardiac repair. However, the mechanisms that underlie apparent beneficial effects on myocardial remodeling are unclear. In a porcine model of acute myocardial infarction, we investigated the therapeutic effects of a mixed population of culture modified peripheral blood mononuclear cells (termed hereafter porcine EPC). Porcine EPC were isolated using methods identical to those previously adopted for harvest of EPC in human cell therapy studies. In addition the therapeutic effects of paracrine factors secreted by these cells was evaluated in vitro and in vivo. Intracoronary injection of autologous porcine EPC was associated with increased infarct territory mass and improved regional ventricular systolic function at 2 months compared to control. Treatment with conditioned media derived from autologous EPC was associated with similar improved effects on infarct territory mass and function. Histologic analysis of the infarct territory revealed significantly increased cardiomyocyte size in EPC and conditioned media treated groups, when compared to controls. A paracrine EPC effect was also verified in a pure myocardial preparation in which cardiomyocytes devoid of fibroblast, neuronal and vascular elements directly responded by increasing cell mass when exposed to the same conditioned media. Analysis of conditioned media revealed elevated levels of TGFβ1 (human 267.3±11.8 pg/ml, porcine 57.1±6.1 pg/ml), a recognized mediator of hypertrophic signaling in the heart. Neutralizing antibodies to TGFβ1 attenuated the pro-hypertrophic effect of conditioned media, and use of recombinant TGFβ1 added to fresh media replicated the pro-hypertrophic effects of conditioned media in vitro. These data demonstrate the potential of paracrine factors secreted from endothelial progenitor cells to induce cardiomyocyte hypertrophy contributing to increased infarct territory LV mass, with

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

    NASA Astrophysics Data System (ADS)

    Chao, Tsi-chian; Xu, X. George

    2004-11-01

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

  7. 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.

  8. 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 ...

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

    SciTech Connect

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

    1996-06-01

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

  10. Bone marrow mesenchymal stem cells improve myocardial function in a swine model of acute myocardial infarction.

    PubMed

    Zhao, Jing-Jie; Liu, Xiao-Cheng; Kong, Feng; Qi, Tong-Gang; Cheng, Guang-Hui; Wang, Jue; Sun, Chao; Luan, Yun

    2014-09-01

    The aim of the current study was to confirm the effect and elucidate the mechanism of bone marrow mesenchymal stem cells (BMSCs) in acute myocardial infarction (AMI). AMI was induced in mini‑swine by ligating the left anterior descending coronary artery, and BMSCs (1x107) were injected via a sterile microinjection into the ischemic area. Six months postoperatively, electrocardiograph‑gated single photon emission computed tomography revealed that the myocardial filling defect was reduced and the left ventricular ejection fraction was improved in the BMSC group compared with the control group (P<0.05). Histopathological examination indicated that, in the BMSC treatment group, the percentage of survived myocardial tissue and the vessel density were increased, and the percentage of apoptosis was decreased compared with controls (P<0.05). Reverse transcription‑polymerase chain reaction results indicated that the expression levels of multiple inflammatory factors were significantly upregulated in the BMSC group compared with levels in the control group (P<0.05). In conclusion, the present study demonstrated that BMSC injection significantly improved cardiac function and reduced infarct size in six months, indicating that this method may be valuable for future study in clinical trials. PMID:25060678

  11. 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 ...

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

    PubMed

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

    2014-01-01

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

  13. Tongxinluo Enhances Neurogenesis and Angiogenesis in Peri-Infarct Area and Subventricular Zone and Promotes Functional Recovery after Focal Cerebral Ischemic Infarction in Hypertensive Rats

    PubMed Central

    Chen, Li; Wang, Xiaoting; Zhang, Jian; Dang, Chao; Liu, Gang; Liang, Zhijian; Huang, Gelun; Zhao, Weijia; Zeng, Jinsheng

    2016-01-01

    Background. Tongxinluo is a traditional Chinese medicine compound with the potential to promote the neuronal functional recovery in cerebral ischemic infarction. Objective. This study aimed to disclose whether tongxinluo promotes neurological functional recovery and neurogenesis and angiogenesis in the infarcted area and SVZ after cerebral ischemic infarction in hypertensive rats. Methods. The ischemic model was prepared by distal middle cerebral artery occlusion (MCAO) in hypertensive rats. Tongxinluo was administrated 24 h after MCAO and lasted for 3, 7, or 14 days. Behavioral tests were performed to evaluate the protection of tongxinluo. Immunochemical staining was applied on brain tissue to evaluate the effects of tongxinluo on neurogenesis and vascularization in the MCAO model rats. Results. Postinjury administration of tongxinluo ameliorated the neuronal function deficit in the MCAO model rats. As evidenced by the immunochemical staining, BrdU+/DCX+, BrdU+/nestin+, and BrdU+ vascular endothelial cells were promoted to proliferate in SVZ after tongxinluo administration. The matured neurons stained by NeuN and vascularization by laminin staining were observed after tongxinluo administration in the peri-infarct area. Conclusion. Tongxinluo postischemia administration could ameliorate the neurological function deficit in the model rats. Possible mechanisms are related to neurogenesis and angiogenesis in the peri-infarct area and SVZ. PMID:27069496

  14. The History and Evolution of Experimental Traumatic Brain Injury Models.

    PubMed

    Povlishock, John

    2016-01-01

    This narrative provides a brief history of experimental animal model development for the study of traumatic brain injury. It draws upon a relatively rich history of early animal modeling that employed higher order animals to assess concussive brain injury while exploring the importance of head movement versus stabilization in evaluating the animal's response to injury. These themes are extended to the development of angular/rotational acceleration/deceleration models that also exploited brain movement to generate both the morbidity and pathology typically associated with human traumatic brain injury. Despite the significance of these early model systems, their limitations and overall practicality are discussed. Consideration is given to more contemporary rodent animal models that replicate individual/specific features of human injury, while via various transgenic technologies permitting the evaluation of injury-mediated pathways. The narrative closes on a reconsideration of higher order, porcine animal models of injury and their implication for preclinical/translational research. PMID:27604709

  15. Evaluation of Autophagy Using Mouse Models of Brain Injury

    PubMed Central

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

    2009-01-01

    SUMMARY Autophagy is a homeostatic, carefully regulated, and dynamic process for intracellular recycling of bulk proteins, aging organelles, and lipids. Autophagy occurs in all tissues and cell types, including the brain and neurons. Alteration in the dynamics of autophagy has been observed in many diseases of the central nervous system. Disruption of autophagy for an extended period of time results in accumulation of unwanted proteins and neurodegeneration. However, the role of enhanced autophagy after acute brain injury remains undefined. Established mouse models of brain injury will be valuable in clarifying the role of autophagy after brain injury, and are the topic of discussion in this review. PMID:19879944

  16. Bayesian approach for network modeling of brain structural features

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  17. 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.

  18. Reptiles: a new model for brain evo-devo research.

    PubMed

    Nomura, Tadashi; Kawaguchi, Masahumi; Ono, Katsuhiko; Murakami, Yasunori

    2013-03-01

    Vertebrate brains exhibit vast amounts of anatomical diversity. In particular, the elaborate and complex nervous system of amniotes is correlated with the size of their behavioral repertoire. However, the evolutionary mechanisms underlying species-specific brain morphogenesis remain elusive. In this review we introduce reptiles as a new model organism for understanding brain evolution. These animal groups inherited ancestral traits of brain architectures. We will describe several unique aspects of the reptilian nervous system with a special focus on the telencephalon, and discuss the genetic mechanisms underlying reptile-specific brain morphology. The establishment of experimental evo-devo approaches to studying reptiles will help to shed light on the origin of the amniote brains. PMID:23319423

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

    PubMed

    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

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

    PubMed Central

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

    2011-01-01

    Background and Purpose Osteopontin (OPN) is neuroprotective in ischemic brain injuries in adult experimental models, therefore, we hypothesized that OPN would provide neuroprotection and improve long term neurological function in the immature brain after hypoxic-ischemic (HI) injury. Methods HI was induced by unilateral ligation of the right carotid artery followed by hypoxia (8% O2 for 2h) in postnatal day 7 rats. OPN (0.03 µg or 0.1 µg) was injected intracerebroventricularly at 1h post HI. Temporal expression of endogenous OPN was evaluated in the normal rat brain at the age of day 0, 4, 7, 11, 14, and 21, and in the ipsilateral hemisphere following HI. The effects of OPN were evaluated using TTC staining, apoptotic cell death assay, and cleaved caspase-3 expression. Neurological function was assessed by Morris water maze test. Results Endogenous OPN expression in the brain was the highest at the age of day 0, with continuous reduction till the age of day 21 during development. After HI injury, endogenous OPN expression was increased and peaked at 48h. Exogenous OPN decreased infarct volume and improved neurological outcomes 7 weeks after HI injury. OPN-induced neuroprotection was blocked by an integrin antagonist. Conclusions OPN-induced neuroprotection was associated with cleaved-caspase-3 inhibition and antiapoptotic cell death. OPN treatment improved long-term neurological function against neonatal HI brain injury. PMID:21273567

  1. 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

  2. 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

  3. Differential microRNA Expression and Regulation in the Rat Model of Post-Infarction Heart Failure

    PubMed Central

    Liu, Xueyan; Meng, Heyu; Jiang, Chao; Yang, Sibao; Cui, Fengwen; Yang, Ping

    2016-01-01

    Background Heart failure is a complex end stage of various cardiovascular diseases with a poor prognosis, and the mechanisms for development and progression of heart failure have always been a hot point. However, the molecular mechanisms underlying the post transcriptional regulation of heart failure have not been fully elucidated. Current data suggest that microRNAs (miRNAs) are involved in the pathogenesis of heart failure and could serve as a new biomarker, but the precise regulatory mechanisms are still unclear. Methods The differential miRNA profile in a rat model of post-infarction heart failure was determined using high throughout sequencing and analyzed through bioinformatics approaches. The results were validated using qRT-PCR for 8 selected miRNAs. Then the expression patterns of 4 miRNAs were analyzed in different periods after myocardial infarction. Finally, gain- and loss-of-function experiments of rno-miR-122-5p and rno-miR-184 were analyzed in H2O2 treated H9c2 cells. Results In the heart failure sample, 78 miRNAs were significantly upregulated and 28 were downregulated compared to the controls. GO and KEGG pathway analysis further indicated the likely roles of these miRNAs in heart failure. Time-course analysis revealed different expression patterns of 4 miRNAs: rno-miR-122-5p, rno-miR-199a-5p, rno-miR-184 and rno-miR-208a-3p. Additionally, rno-miR-122-5p and rno-miR-184 were proved to promote apoptosis in vitro. Conclusions Differential profile and expression patterns of miRNAs in the rats model of post-infarction heart failure were found, and the pro-apoptotic roles of rno-miR-122-5p and rno-miR-184 were revealed. These findings may provide a novel way that may assist in heart failure diagnosis and treatment. PMID:27504893

  4. Modeling the brain morphology distribution in the general aging population

    NASA Astrophysics Data System (ADS)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  5. Controlling ferrofluid permeability across the blood–brain barrier model.

    PubMed

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

    2014-02-21

    In the present study, an in vitro 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 FITCDextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this 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). PMID:24457539

  6. Brain microabscesses in a porcine model of Staphylococcus aureus sepsis

    PubMed Central

    2013-01-01

    Background Sepsis caused by Staphylococcus aureus often leads to brain microabscesses in humans. Animal models of haematogenous brain abscesses would be useful to study this condition in detail. Recently, we developed a model of S. aureus sepsis in pigs and here we report that brain microabscesses develop in pigs with such induced S. aureus sepsis. Twelve pigs were divided into three groups. Nine pigs received an intravenous inoculation of S. aureus once at time 0 h (group 1) or twice at time 0 h and 12 h (groups 2 and 3). In each group the fourth pig served as control. The pigs were euthanized at time 12 h (Group 1), 24 h (Group 2) and 48 h (Group 3) after the first inoculation. The brains were collected and examined histopathologically. Results All inoculated pigs developed sepsis and seven out of nine pigs developed brain microabscesses. The microabscesses contained S. aureus and were located in the prosencephalon and mesencephalon. Chorioditis and meningitis occurred from 12 h after inoculation. Conclusions Pigs with experimental S. aureus sepsis often develop brain microabscesses. The porcine brain pathology mirrors the findings in human sepsis patients. We therefore suggest the pig as a useful animal model of the development of brain microabscesses caused by S. aureus sepsis. PMID:24176029

  7. 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).

  8. microRNA-208a in an early stage myocardial infarction rat model and the effect on cAMP-PKA signaling pathway

    PubMed Central

    Feng, Gao; Yan, Zhang; Li, Chuanchuan; Hou, Yuemei

    2016-01-01

    The expression level of microRNA-208a (miR-208a) in a rat model with myocardial infarction and the effect of cAMP-PKA signaling pathway in early stage of myocardial infarction in rats were investigated. The early myocardial infarction model was established in 12 male Sprague-Dawley rats by ligation of the anterior descending coronary artery, and 12 rats were selected as the control group (sham operation group). Reverse-transcription quantitative PCR was conducted to detect the expression levels of miR-208a in the myocardium of and the expression levels of miR-208a in the serum of rats in the two groups. Western blot analysis was used to evaluate the expression levels of cAMP-PKA protein in the rat tissues in the two groups. After stimulating high levels of miR-208a expression in human myocardial cells (HCM), western blot analysis was used to detect the cAMP-PKA protein levels. The expression levels of miR-208a in myocardial tissues in rats with myocardial infarction were significantly higher than those in the control group, and the difference was statistically significant (P<0.05). The expression levels of miR-208a in the early stage of myocardial infarction rats were also significantly higher than those in the control group, and the difference was statistically significant (P<0.05). The level of cAMP-PKA protein in myocardial tissue in rats with chronic myocardial infarction was also significantly higher. Transfection of human myocardial cells with miR-208a analogue significantly increased the cAMP-PKA protein levels in human myocardial cells. In conclusion, the over expression of miR-208a in myocardial infarction tissue and the high levels of this miRNA in the serum, may be involved in the process of myocardial infarction by influencing the cAMP-PKA signaling pathway in myocardial cells. PMID:27314868

  9. Spiral waves and reentry dynamics in an in vitro model of the healed infarct border-zone

    PubMed Central

    Chang, Marvin G.; Zhang, Yibing; Chang, Connie Y.; Xu, Linmiao; Emokpae, Roland; Tung, Leslie; Marbán, Eduardo; Abraham, M. Roselle

    2015-01-01

    Rationale Reentry underlies most ventricular tachycardias (VT) seen post-myocardial infarction (MI). Mapping studies reveal that the majority of VTs late post-MI arise from the infarct border-zone (IBZ). Objective To investigate reentry dynamics and the role of individual ion channels on reentry in in vitro models of the healed IBZ. Methods and Results We designed in vitro models of the healed IBZ by co-culturing skeletal myotubes (SkM) with neonatal rat ventricular myocytes (NRVMs) and performed optical mapping at high temporal and spatial resolution. In culture, NRVMs mature to form striated myocytes and electrically uncoupled SkMs simulate fibrosis seen in the healed IBZ. High resolution mapping revealed that SkMs produced localized slowing of conduction velocity (CV), increased dispersion of CV and directional-dependence of activation delay without affecting myocyte excitability. Reentry was easily induced by rapid pacing in co-cultures; treatment with lidocaine, a Na+ channel blocker, significantly decreased reentry rate and CV, increased reentry pathlength and terminated 30% of reentrant arrhythmias (n=18). In contrast, nitrendipine, an L-type Ca2+ channel (LTCC) blocker terminated 100% of reentry episodes while increasing reentry cycle length and pathlength and decreasing reentry CV (n=16). K+ channel blockers increased reentry APD, but infrequently terminated reentry (n=12). Conclusions Co-cultures reproduce several architectural and EP features of the healed IBZ. Reentry termination by LTCC, but not Na+ channel blockers suggests a greater Ca2+-dependence of propagation. These results may help explain the low efficacy of pure Na+ channel blockers in preventing and terminating clinical VTs late after MI. PMID:19815825

  10. 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

  11. Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse Brain Tumor Model

    PubMed Central

    Wanjiku, Teresia; Rudek, Michelle A; Joshi, Avadhut; Gallia, Gary L.; Riggins, Gregory J.

    2015-01-01

    Purpose Mebendazole (MBZ), first used as an antiparasitic drug, shows preclinical efficacy in models of glioblastoma and medulloblastoma. Three different MBZ polymorphs (A, B and C) exist and a detailed assessment of the brain penetration, pharmacokinetics and anti-tumor properties of each individual MBZ polymorph is necessary to improve mebendazole-based brain cancer therapy. Experimental Design and Results In this study, various marketed and custom-formulated MBZ tablets were analyzed for their polymorph content by IR spectroscopy and subsequently tested in orthotopic GL261 mouse glioma model for efficacy and tolerability. The pharmacokinetics and brain concentration of MBZ polymorphs and two main metabolites were analyzed by LC-MS. We found that polymorph B and C both increased survival in a GL261 glioma model, as B exhibited greater toxicity. Polymorph A showed no benefit. Both, polymorph B and C, reached concentrations in the brain that exceeded the IC50 in GL261 cells 29-fold. In addition, polymorph C demonstrated an AUC0-24h brain-to-plasma (B/P) ratio of 0.82, whereas B showed higher plasma AUC and lower B/P ratio. In contrast, polymorph A presented markedly lower levels in the plasma and brain. Furthermore, the combination with elacridar was able to significantly improve the efficacy of polymorph C in GL261 glioma and D425 medulloblastoma models in mice. Conclusion Among MBZ polymorphs, C reaches therapeutically effective concentrations in the brain tissue and tumor with less side effects and is the better choice for brain cancer therapy. Its efficacy can be further enhanced by combination with elacridar. PMID:25862759

  12. Detrimental role of pericyte Nox4 in the acute phase of brain ischemia.

    PubMed

    Nishimura, Ataru; Ago, Tetsuro; Kuroda, Junya; Arimura, Koichi; Tachibana, Masaki; Nakamura, Kuniyuki; Wakisaka, Yoshinobu; Sadoshima, Junichi; Iihara, Koji; Kitazono, Takanari

    2016-06-01

    Pericytes are mural cells abundantly present in cerebral microvessels and play important roles, including the formation and maintenance of the blood-brain barrier. Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly under pathological conditions. In the present study, we found that the expression of Nox4 was markedly induced in microvascular cells, including pericytes, in peri-infarct areas after middle cerebral artery occlusion stroke models in mice. The upregulation of Nox4 was greater in a permanent middle cerebral artery occlusion model compared with an ischemia/reperfusion transient middle cerebral artery occlusion model. We performed permanent middle cerebral artery occlusion on mice with Nox4 overexpression in pericytes (Tg-Nox4). Infarct volume was significantly greater with enhanced reactive oxygen species production and blood-brain barrier breakdown in peri-infarct areas in Tg-Nox4, compared with littermate controls. In cultured brain pericytes, Nox4 was significantly upregulated by hypoxia and was promptly downregulated by reoxygenation. Phosphorylation of NFκB and production of matrix metalloproteinase 9 were significantly increased in both cultured pericytes overexpressing Nox4 and in peri-infarct areas in Tg-Nox4. Collectively, Nox4 is upregulated in pericytes in peri-infarct areas after acute brain ischemia and may enhance blood-brain barrier breakdown through activation of NFκB and matrix metalloproteinase 9, thereby causing enlargement of infarct volume. PMID:26661159

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

    PubMed Central

    Traudt, Christopher M.; Juul, Sandra E.

    2016-01-01

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

  14. Modelling convection-enhanced delivery in normal and oedematous brain.

    PubMed

    Haar, P J; Chen, Z-J; Fatouros, P P; Gillies, G T; Corwin, F D; Broaddus, W C

    2014-03-01

    Convection-enhanced delivery (CED) could have clinical applications in the delivery of neuroprotective agents in brain injury states, such as ischaemic stroke. For CED to be safe and effective, a physician must have accurate knowledge of how concentration distributions will be affected by catheter location, flow rate and other similar parameters. In most clinical applications of CED, brain microstructures will be altered by pathological injury processes. Ischaemic stroke and other acute brain injury states are complicated by formation of cytotoxic oedema, in which cellular swelling decreases the fractional volume of the extracellular space (ECS). Such changes would be expected to significantly alter the distribution of neuroprotective agents delivered by CED. Quantitative characterization of these changes will help confirm this prediction and assist in efforts to model the distribution of therapeutic agents. Three-dimensional computational models based on a Nodal Point Integration (NPI) scheme were developed to model infusions in normal brain and brain with cytotoxic oedema. These models were compared to experimental data in which CED was studied in normal brain and in a middle cerebral artery (MCA) occlusion model of cytotoxic oedema. The computational models predicted concentration distributions with reasonable accuracy. PMID:24446800

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

    PubMed

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

    2015-01-01

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

  16. 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.

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

    PubMed

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

    2015-05-01

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

  18. 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

  19. Fuzzy object models for newborn brain MR image segmentation

    NASA Astrophysics Data System (ADS)

    Kobashi, Syoji; Udupa, Jayaram K.

    2013-03-01

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

  20. 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

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

    PubMed Central

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

    2014-01-01

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

  2. Comparison of three rheological models of shear flow behavior studied on blood samples from post-infarction patients.

    PubMed

    Marcinkowska-Gapińska, Anna; Gapinski, Jacek; Elikowski, Waldemar; Jaroszyk, Feliks; Kubisz, Leszek

    2007-09-01

    Quantitative analysis of blood viscosity was performed on the basis of mathematical models of non-Newtonian fluid shear flow behavior (Casson, Ree-Eyring and Quemada). A total of 100 blood samples were drawn from clinically stable survivors of myocardial infarction, treated with aspirin or acenocoumarol and controls to these drugs. Whole blood and plasma viscosity were measured at a broad range of shear rates using a rotary-oscillating viscometer Contraves LS40. Numerical analysis of the experimental data was carried out by means of linear (for Casson) and non-linear regression for the remaining models. In the evaluation of the results, both the fit quality and physical interpretation of the models' parameters were considered. The Quemada model fitted most precisely with the experimental findings and, despite the controversies concerning the relationship between in vivo tissue perfusion and in vitro rheological measurements, seemed to be a valuable method enhancing investigation possibilities of cardiovascular patients. Our results suggest that aspirin does not affect blood rheological properties, while acenocoumarol may slightly alter red cell deformability and rouleaux formation. PMID:17674068

  3. 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…

  4. 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

  5. Image guided constitutive modeling of the silicone brain phantom

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  6. 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 with functional conduction block, respectively, at the location of the isthmus entrance boundary and at the lateral isthmus edges. Discussion Reentrant VT onset following premature stimulation can be explained by the presence of critically convex wavefront curvature and unidirectional block at the isthmus entrance boundary when the premature stimulation interval is sufficiently short. The

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

    SciTech Connect

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

    1996-07-01

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

  8. Bone Marrow Mesenchymal Stem Cells (BM-MSCs) Improve Heart Function in Swine Myocardial Infarction Model through Paracrine Effects

    PubMed Central

    Cai, Min; Shen, Rui; Song, Lei; Lu, Minjie; Wang, Jianguang; Zhao, Shihua; Tang, Yue; Meng, Xianmin; Li, Zongjin; He, Zuo-Xiang

    2016-01-01

    Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway. PMID:27321050

  9. Bone Marrow Mesenchymal Stem Cells (BM-MSCs) Improve Heart Function in Swine Myocardial Infarction Model through Paracrine Effects.

    PubMed

    Cai, Min; Shen, Rui; Song, Lei; Lu, Minjie; Wang, Jianguang; Zhao, Shihua; Tang, Yue; Meng, Xianmin; Li, Zongjin; He, Zuo-Xiang

    2016-01-01

    Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway. PMID:27321050

  10. Discrepant Results of Experimental Human Mesenchymal Stromal Cell Therapy after Myocardial Infarction: Are Animal Models Robust Enough?

    PubMed Central

    Pluijmert, Niek J.; Schutte, Cindy I.; Fibbe, Willem E.; Schalij, Martin J.; Roelofs, Helene; Atsma, Douwe E.

    2016-01-01

    Background Human mesenchymal stromal cells (MSCs) have been reported to preserve cardiac function in myocardial infarction (MI) models. Previously, we found a beneficial effect of intramyocardial injection of unstimulated human MSCs (uMSCs) on cardiac function after permanent coronary artery ligation. In the present study we aimed to extend this research by investigating the effect of intramyocardial injection of human MSCs pre-stimulated with the pro-inflammatory cytokine interferon-gamma (iMSCs), since pro-inflammatory priming has shown additional salutary effects in multiple experimental disease models. Methods MI was induced in NOD/Scid mice by permanent ligation of the left anterior descending coronary artery. Animals received intramyocardial injection of uMSCs, iMSCs or PBS. Sham-operated animals were used to determine baseline characteristics. Cardiac performance was assessed after 2 and 14 days using 7-Tesla magnetic resonance imaging and pressure-volume loop measurements. Histology and q-PCR were used to confirm MSC engraftment in the heart. Results Both uMSC and iMSC therapy had no significant beneficial effect on cardiac function or remodelling in contrast to our previous studies. Conclusions Animal models for cardiac MSC therapy appear less robust than initially envisioned. PMID:27050443

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

    PubMed

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

    2012-12-01

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

  12. Mouse Models of Brain Metastasis for Unravelling Tumour Progression.

    PubMed

    Soto, Manuel Sarmiento; Sibson, Nicola R

    2016-01-01

    Secondary tumours in the brain account for 40 % of triple negative breast cancer patients, and the percentage may be higher at the time of autopsy. The use of in vivo models allow us to recapitulate the molecular mechanisms potentially used by circulating breast tumour cells to proliferate within the brain.Metastasis is a multistep process that depends on the success of several stages including cell evasion from the primary tumour, distribution and survival within the blood stream and cerebral microvasculature, penetration of the blood-brain barrier and proliferation within the brain microenvironment. Cellular adhesion molecules are key proteins involved in all of the steps in the metastatic process. Our group has developed two different in vivo models to encompass both seeding and colonisation stages of the metastatic process: (1) haematogenous dissemination of tumour cells by direct injection into the left ventricle of the heart, and (2) direct implantation of the tumour cells into the mouse brain.This chapter describes, in detail, the practical implementation of the intracerebral model, which can be used to analyse tumour proliferation within a specific area of the central nervous system and tumour-host cell interactions. We also describe the use of immunohistochemistry techniques to identify, at the molecular scale, tumour-host cell interactions, which may open new windows for brain metastasis therapy. PMID:27325270

  13. Neural mass model-based tracking of anesthetic brain states.

    PubMed

    Kuhlmann, Levin; Freestone, Dean R; Manton, Jonathan H; Heyse, Bjorn; Vereecke, Hugo E M; Lipping, Tarmo; Struys, Michel M R F; Liley, David T J

    2016-06-01

    Neural mass model-based tracking of brain states from electroencephalographic signals holds the promise of simultaneously tracking brain states while inferring underlying physiological changes in various neuroscientific and clinical applications. Here, neural mass model-based tracking of brain states using the unscented Kalman filter applied to estimate parameters of the Jansen-Rit cortical population model is evaluated through the application of propofol-based anesthetic state monitoring. In particular, 15 subjects underwent propofol anesthesia induction from awake to anesthetised while behavioral responsiveness was monitored and frontal electroencephalographic signals were recorded. The unscented Kalman filter Jansen-Rit model approach applied to frontal electroencephalography achieved reasonable testing performance for classification of the anesthetic brain state (sensitivity: 0.51; chance sensitivity: 0.17; nearest neighbor sensitivity 0.75) when compared to approaches based on linear (autoregressive moving average) modeling (sensitivity 0.58; nearest neighbor sensitivity: 0.91) and a high performing standard depth of anesthesia monitoring measure, Higuchi Fractal Dimension (sensitivity: 0.50; nearest neighbor sensitivity: 0.88). Moreover, it was found that the unscented Kalman filter based parameter estimates of the inhibitory postsynaptic potential amplitude varied in the physiologically expected direction with increases in propofol concentration, while the estimates of the inhibitory postsynaptic potential rate constant did not. These results combined with analysis of monotonicity of parameter estimates, error analysis of parameter estimates, and observability analysis of the Jansen-Rit model, along with considerations of extensions of the Jansen-Rit model, suggests that the Jansen-Rit model combined with unscented Kalman filtering provides a valuable reference point for future real-time brain state tracking studies. This is especially true for studies of

  14. 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.

  15. 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

  16. Model of Reentrant Ventricular Tachycardia based upon Infarct Border Zone Geometry Predicts Reentrant Circuit Features as Determined by Activation Mapping

    PubMed Central

    Ciaccio, Edward J; Ashikaga, Hiroshi; Kaba, Riyaz A; Cervantes, Daniel; Hopenfeld, Bruce; Wit, Andrew L; Peters, Nicholas S; McVeigh, Elliot R; Garan, Hasan; Coromilas, James

    2008-01-01

    Background Infarct border zone (IBZ) geometry likely affects inducibility and characteristics of postinfarction reentrant ventricular tachycardia, but the connection has not been established. Objective To determine characteristics of post infarction ventricular tachycardia in the IBZ. Methods A geometric model describing the relationship between IBZ geometry and wavefront propagation in reentrant circuits was developed. Based on the formulation, slow conduction and block was expected to coincide with areas where IBZ thickness (T) is minimal and the local spatial gradient in thickness (ΔT) is maximal, so that the degree of wavefront curvature ρ ∝ ΔT/T is maximal. Regions of fastest conduction velocity were predicted to coincide with areas of minimum ΔT. In seven arrhythmogenic postinfarction canine heart experiments, tachycardia was induced by programmed stimulation, and activation maps were constructed from multichannel recordings. IBZ thickness was measured in excised hearts from histologic analysis or magnetic resonance imaging. Reentrant circuit properties were predicted from IBZ geometry and compared with ventricular activation maps following tachycardia induction. Results Mean IBZ thickness was 231±140µm at the reentry isthmus and 1440±770µm in the outer pathway (p<0.001). Mean curvature ρ was 1.63±0.45mm−1 at functional block line locations, 0.71±0.18mm−1 at isthmus entrance-exit points, and 0.33±0.13mm−1 in the outer reentrant circuit pathway. The mean conduction velocity about the circuit during reentrant tachycardia was 0.32±0.04mm/ms at entrance-exit points, 0.42±0.13mm/ms for the entire outer pathway, and 0.64±0.16mm/ms at outer pathway regions with minimum ΔT. Model sensitivity and specificity to detect isthmus location was 75.0±5.7% and 97.2±0.7%. Conclusions Reentrant circuit features as determined by activation mapping can be predicted on the basis of IBZ geometrical relationships. PMID:17675078

  17. Electrocardiograms corresponding to the development of myocardial infarction in anesthetized WHHLMI rabbits (Oryctolagus cuniculus), an animal model for familial hypercholesterolemia.

    PubMed

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

    2012-10-01

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

  18. Comparative Analysis of the Cardioprotective Properties of Opioid Receptor Agonists in a Rat Model of Myocardial Infarction

    PubMed Central

    Maslov, Leonid N.; Lishmanov, Yury B.; Oeltgen, Peter R.; Barzakh, Eva I.; Krylatov, Andrey V.; Naryzhnaya, Natalia V.; Pei, Jian-Ming; Brown, Stephen A.

    2010-01-01

    Objectives This study was conducted to test the hypothesis that opioid receptor (OR) mediated cardioprotection is agonist-specific when administered prior to coronary artery occlusion and reperfusion in a rat model. Methods Anesthetized open-chest male Wistar rats were subjected to 45 minutes of left coronary artery occlusion and 2 hours of reperfusion. Opioid agonists were infused 15 minutes prior to coronary artery occlusion. Two control groups and 15 opioid treated groups were studied. Controls were infused with either saline alone (n = 16) or dimethyl sulfoxide (DMSO) plus hydroxypropyl-β-cyclodextrin in saline (n = 19). The μ selective agonist DAMGO was infused at either 150 nmol/kg (n = 15) or 1500 nmol/kg (n = 14), and Dermorphin-H was infused at 150 nmol/kg (n = 14). The δ1 selective agonist D-Pen2,5 Enkephalin (DPDPE) was infused at 150 nmol/kg (n = 16) or 1500 nmol/kg (n = 14). The δ2 selective agonists Deltorphin II (n = 16), Deltorphin-Dvariant (n = 15) and Deltorphin-E (n = 14) were infused at 150 nmol/kg. The selective κ1 opioid agonist U-50488 was infused at 240 nmol/kg (n = 14), 1500 nmol/kg (n = 14), and 2,400 nmol/kg (n = 14). The selective κ2 opioid agonist GR-89696 was infused at 150 nmol/kg (n = 14) and 1500 nmol/kg (n = 15). Orphinan FQ (Nociceptin), also referred to as OR Ligand1 (ORL1), was infused at 220 nmol/kg (n = 15) and 1500 nmol/kg (n = 15). The infarct size/area at risk (IS/AAR) ratio was determined after reperfusion by negative staining with patent blue violet dye. Hemodynamic parameters including heart rate, mean arterial blood pressure (MAP), and rate pressure product (RPP) were determined. Results Pretreatment with the δ2 OR agonist Deltorphin II (150 nmol/kg) significantly reduced the IS/AAR ratio, while Deltorphin-Dvariant and Deltorphin-E did not exhibit an infarct sparing effect at that treatment dose. Activation of δ1 OR by DPDPE, κ1 OR by U-50488, κ2 OR by U-50488, μ OR by DAMGO, Dermophin-H, and Nociceptin had

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

    PubMed Central

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

    2013-01-01

    Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70–75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7–9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×105–5×105 human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow

  20. 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.

  1. 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.

  2. An Adaptive Complex Network Model for Brain Functional Networks

    PubMed Central

    Gomez Portillo, Ignacio J.; Gleiser, Pablo M.

    2009-01-01

    Brain functional networks are graph representations of activity in the brain, where the vertices represent anatomical regions and the edges their functional connectivity. These networks present a robust small world topological structure, characterized by highly integrated modules connected sparsely by long range links. Recent studies showed that other topological properties such as the degree distribution and the presence (or absence) of a hierarchical structure are not robust, and show different intriguing behaviors. In order to understand the basic ingredients necessary for the emergence of these complex network structures we present an adaptive complex network model for human brain functional networks. The microscopic units of the model are dynamical nodes that represent active regions of the brain, whose interaction gives rise to complex network structures. The links between the nodes are chosen following an adaptive algorithm that establishes connections between dynamical elements with similar internal states. We show that the model is able to describe topological characteristics of human brain networks obtained from functional magnetic resonance imaging studies. In particular, when the dynamical rules of the model allow for integrated processing over the entire network scale-free non-hierarchical networks with well defined communities emerge. On the other hand, when the dynamical rules restrict the information to a local neighborhood, communities cluster together into larger ones, giving rise to a hierarchical structure, with a truncated power law degree distribution. PMID:19738902

  3. Midline (Central) Fluid Percussion Model of Traumatic Brain Injury.

    PubMed

    Rowe, Rachel K; Griffiths, Daniel R; Lifshitz, Jonathan

    2016-01-01

    Research models of traumatic brain injury (TBI) hold significant validity towards the human condition, with each model replicating a subset of clinical features and symptoms. After 30 years of characterization and implementation, fluid percussion injury (FPI) is firmly recognized as a clinically relevant model of TBI, encompassing concussion through severe injury. The midline variation of FPI may best represent mild and diffuse clinical brain injury, because of the acute behavioral deficits, the late onset of subtle behavioral morbidities, and the absence of gross histopathology. This chapter outlines the procedures for midline (diffuse) FPI in adult male rats and mice. With these procedures, it becomes possible to generate brain-injured laboratory animals for studies of injury-induced pathophysiology and behavioral deficits, for which rational therapeutic interventions can be implemented. PMID:27604721

  4. An Embodied Brain Model of the Human Foetus

    PubMed Central

    Yamada, Yasunori; Kanazawa, Hoshinori; Iwasaki, Sho; Tsukahara, Yuki; Iwata, Osuke; Yamada, Shigehito; Kuniyoshi, Yasuo

    2016-01-01

    Cortical learning via sensorimotor experiences evoked by bodily movements begins as early as the foetal period. However, the learning mechanisms by which sensorimotor experiences guide cortical learning remain unknown owing to technical and ethical difficulties. To bridge this gap, we present an embodied brain model of a human foetus as a coupled brain-body-environment system by integrating anatomical/physiological data. Using this model, we show how intrauterine sensorimotor experiences related to bodily movements induce specific statistical regularities in somatosensory feedback that facilitate cortical learning of body representations and subsequent visual-somatosensory integration. We also show how extrauterine sensorimotor experiences affect these processes. Our embodied brain model can provide a novel computational approach to the mechanistic understanding of cortical learning based on sensorimotor experiences mediated by complex interactions between the body, environment and nervous system. PMID:27302194

  5. An Embodied Brain Model of the Human Foetus.

    PubMed

    Yamada, Yasunori; Kanazawa, Hoshinori; Iwasaki, Sho; Tsukahara, Yuki; Iwata, Osuke; Yamada, Shigehito; Kuniyoshi, Yasuo

    2016-01-01

    Cortical learning via sensorimotor experiences evoked by bodily movements begins as early as the foetal period. However, the learning mechanisms by which sensorimotor experiences guide cortical learning remain unknown owing to technical and ethical difficulties. To bridge this gap, we present an embodied brain model of a human foetus as a coupled brain-body-environment system by integrating anatomical/physiological data. Using this model, we show how intrauterine sensorimotor experiences related to bodily movements induce specific statistical regularities in somatosensory feedback that facilitate cortical learning of body representations and subsequent visual-somatosensory integration. We also show how extrauterine sensorimotor experiences affect these processes. Our embodied brain model can provide a novel computational approach to the mechanistic understanding of cortical learning based on sensorimotor experiences mediated by complex interactions between the body, environment and nervous system. PMID:27302194

  6. 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

  7. 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

  8. Causation model of autism: Audiovisual brain specialization in infancy competes with social brain networks.

    PubMed

    Heffler, Karen Frankel; Oestreicher, Leonard M

    2016-06-01

    Earliest identifiable findings in autism indicate that the autistic brain develops differently from the typical brain in the first year of life, after a period of typical development. Twin studies suggest that autism has an environmental component contributing to causation. Increased availability of audiovisual (AV) materials and viewing practices of infants parallel the time frame of the rise in prevalence of autism spectrum disorder (ASD). Studies have shown an association between ASD and increased TV/cable screen exposure in infancy, suggesting AV exposure in infancy as a possible contributing cause of ASD. Infants are attracted to the saliency of AV materials, yet do not have the experience to recognize these stimuli as socially relevant. The authors present a developmental model of autism in which exposure to screen-based AV input in genetically susceptible infants stimulates specialization of non-social sensory processing in the brain. Through a process of neuroplasticity, the autistic infant develops the skills that are driven by the AV viewing. The AV developed neuronal pathways compete with preference for social processing, negatively affecting development of social brain pathways and causing global developmental delay. This model explains atypical face and speech processing, as well as preference for AV synchrony over biological motion in ASD. Neural hyper-connectivity, enlarged brain size and special abilities in visual, auditory and motion processing in ASD are also explained by the model. Positive effects of early intervention are predicted by the model. Researchers studying causation of autism have largely overlooked AV exposure in infancy as a potential contributing factor. The authors call for increased public awareness of the association between early screen viewing and ASD, and a concerted research effort to determine the extent of causal relationship. PMID:26146132

  9. 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 μM 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

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

    PubMed

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

    2015-09-01

    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 μM 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

  11. 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

  12. A revised dosimetric model of the head and brain

    SciTech Connect

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

    1995-05-01

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

  13. Inferring brain-computational mechanisms with models of activity measurements.

    PubMed

    Kriegeskorte, Nikolaus; Diedrichsen, Jörn

    2016-10-01

    High-resolution functional imaging is providing increasingly rich measurements of brain activity in animals and humans. A major challenge is to leverage such data to gain insight into the brain's computational mechanisms. The first step is to define candidate brain-computational models (BCMs) that can perform the behavioural task in question. We would then like to infer which of the candidate BCMs best accounts for measured brain-activity data. Here we describe a method that complements each BCM by a measurement model (MM), which simulates the way the brain-activity measurements reflect neuronal activity (e.g. local averaging in functional magnetic resonance imaging (fMRI) voxels or sparse sampling in array recordings). The resulting generative model (BCM-MM) produces simulated measurements. To avoid having to fit the MM to predict each individual measurement channel of the brain-activity data, we compare the measured and predicted data at the level of summary statistics. We describe a novel particular implementation of this approach, called probabilistic representational similarity analysis (pRSA) with MMs, which uses representational dissimilarity matrices (RDMs) as the summary statistics. We validate this method by simulations of fMRI measurements (locally averaging voxels) based on a deep convolutional neural network for visual object recognition. Results indicate that the way the measurements sample the activity patterns strongly affects the apparent representational dissimilarities. However, modelling of the measurement process can account for these effects, and different BCMs remain distinguishable even under substantial noise. The pRSA method enables us to perform Bayesian inference on the set of BCMs and to recognize the data-generating model in each case.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574316

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

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

    PubMed Central

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

    2014-01-01

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

  16. Effects of health belief model-based video training about risk factors on knowledge and attitude of myocardial infarction patients after discharge

    PubMed Central

    Abbaszadeh, Abbas; Borhani, Fariba; Asadi, Neda

    2011-01-01

    BACKGROUND: Ischemic heart diseases are the most common cardiovascular diseases. This study aimed to assess the effects of video training about risk factors based on health belief model on knowledge and attitude of myocardial infarction patients after discharge. METHODS: This was a quasi-experimental study conducted in 2010. Eighty patients were randomly assigned to either intervention or control group. Data was collected by a researcher-made questionnaire. RESULTS: Study results showed that the mean score of knowledge about disease, diet, physical activity and perceived benefit, severity, and susceptibility after video training was increased significantly. CONCLUSIONS: Using videos for educating myocardial infarction patients is a useful method for preventing recurrence of the disease. PMID:22091231

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

    PubMed Central

    Rengifo Valbuena, Carlos Augusto; Ávila Rodríguez, Marco Fidel; Céspedes Rubio, Angel

    2013-01-01

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

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

    PubMed

    Mendizabal, A; Aguinaga, I; Sánchez, E

    2015-05-01

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

  19. 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.

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

    PubMed Central

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

    2012-01-01

    This paper is aimed at exploring the effect of cortical brain atrophy on the currents induced by transcranial magnetic stimulation (TMS). We compared the currents induced by various TMS conditions on several different MRI derived finite element head models of brain atrophy, incorporating both decreasing cortical volume and widened sulci. The current densities induced in the cortex were dependent upon the degree and type of cortical atrophy and were altered in magnitude, location, and orientation when compared to healthy head models. Predictive models of the degree of current density attenuation as a function of the scalp-to-cortex distance were analyzed, concluding that those which ignore the electromagnetic field–tissue interactions lead to inaccurate conclusions. Ultimately, the precise site and population of neural elements stimulated by TMS in an atrophic brain cannot be predicted based on healthy head models which ignore the effects of the altered cortex on the stimulating currents. Clinical applications of TMS should be carefully considered in light of these findings. PMID:18193208

  1. Efficient multilevel brain tumor segmentation with integrated bayesian model classification.

    PubMed

    Corso, J J; Sharon, E; Dube, S; El-Saden, S; Sinha, U; Yuille, A

    2008-05-01

    We present a new method for automatic segmentation of heterogeneous image data that takes a step toward bridging the gap between bottom-up affinity-based segmentation methods and top-down generative model based approaches. The main contribution of the paper is a Bayesian formulation for incorporating soft model assignments into the calculation of affinities, which are conventionally model free. We integrate the resulting model-aware affinities into the multilevel segmentation by weighted aggregation algorithm, and apply the technique to the task of detecting and segmenting brain tumor and edema in multichannel magnetic resonance (MR) volumes. The computationally efficient method runs orders of magnitude faster than current state-of-the-art techniques giving comparable or improved results. Our quantitative results indicate the benefit of incorporating model-aware affinities into the segmentation process for the difficult case of glioblastoma multiforme brain tumor. PMID:18450536

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. 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…

  5. Virtual model of the human brain for neurosurgical simulation.

    PubMed

    De Paolis, Lucio T; De Mauro, Alessandro; Raczkowsky, Joerg; Aloisio, Giovanni

    2009-01-01

    The aim of this work is to develop a realistic virtual model of the human brain that could be used in a neurosurgical simulation for both educational and preoperative planning purposes. The goal of such a system would be to enhance the practice of surgery students, avoiding the use of animals, cadavers and plastic phantoms. A surgeon, before carrying out the real procedure, will, with this system, be able to rehearse by using a surgical simulator based on detailed virtual reality models of the human brain, reconstructed with real patient's medical images. In order to obtain a realistic and useful simulation we focused our research on the physical modelling of the brain as a deformable body and on the interactions with surgical instruments. The developed prototype is based on the mass-spring-damper model and, in order to obtain deformations similar to the real ones, a three tiered structure has been built. In this way, we have obtained local and realistic deformations using an ad-hoc point distribution in the volume where the contact between the brain surface and a surgical instrument takes place. PMID:19745425

  6. 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.

  7. 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 β 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

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

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

    2015-01-01

    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 h2 = 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

  10. 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