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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. Silent brain infarcts: a cause of depression in the elderly?

    PubMed

    Saavedra Perez, Heidi C; Direk, Nese; Hofman, Albert; Vernooij, Meike W; Tiemeier, Henning; Ikram, Mohammad Arfan

    2013-02-28

    The present study included 1047 elderly participants. At baseline, brain magnetic resonance imaging (MRI) was performed to detect infarcts and white matter lesions; further, depressive disorders were assessed. Participants were followed up during 3.6 years to determine incident and recurrent depression. We found an increased risk of recurrent depression associated with silent brain infarcts.

  3. Individualized diffeomorphic mapping of brains with large cortical infarcts.

    PubMed

    Soon, Hock Wei; Qiu, Anqi

    2015-01-01

    Whole brain mapping of stroke patients with large cortical infarcts is not trivial due to the complexity of infarcts' anatomical location and appearance in magnetic resonance image. In this study, we proposed an individualized diffeomorphic mapping framework for solving this problem. This framework is based on our recent work of large deformation diffeomorphic metric mapping (LDDMM) in Du et al. (2011) and incorporates anatomical features, such as sulcal/gyral curves, cortical surfaces, brain intensity image, and masks of infarcted regions, in order to align a normal brain to the brain of stroke patients. We applied this framework to synthetic data and data of stroke patients and validated the mapping accuracy in terms of the alignment of gyral/sulcal curves, sulcal regions, and brain segmentation. Our results revealed that this framework provided comparable mapping results for stroke patients and healthy controls, suggesting the importance of incorporating individualized anatomical features in whole brain mapping of brains with large cortical infarcts.

  4. DJ-1 immunoreactivity in human brain astrocytes is dependent on infarct presence and infarct age.

    PubMed

    Mullett, Steven J; Hamilton, Ronald L; Hinkle, David A

    2009-04-01

    DJ-1 is a protein with anti-oxidative stress and anti-apoptotic properties that is abundantly expressed in reactive CNS astrocytes in chronic neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and Pick's disease. Genetic mutations which eliminate DJ-1 expression in humans are sufficient to produce an early-onset form of familial PD, PARK7, suggesting that DJ-1 is a critical component of the neuroprotective arsenal of the brain. Previous studies in parkinsonism/dementia brain tissues have revealed that reactive astrocytes within and surrounding incidentally identified infarcts were often robustly immunoreactive for DJ-1, especially if the infarcts showed histological features consistent with older age. Given this, we sought to evaluate astrocytic DJ-1 expression in human stroke more extensively, and with a particular emphasis on determining whether immunohistochemical DJ-1 expression in astrocytes correlates with histological infarct age. The studies presented here show that DJ-1 is abundantly expressed in reactive infarct region astrocytes in both gray and white matter, that subacute and chronic infarct region astrocytes are much more robustly DJ-1+ than are acute infarct and non-infarct region astrocytes, and that DJ-1 staining intensity in astrocytes generally correlates with that of the reactive astrocyte marker GFAP. Confocal imaging of DJ-1 and GFAP dual-labelled human brain sections were used to confirm the localization to and expression of DJ-1 in astrocytes. Neuronal DJ-1 staining was minimal under all infarct and non-infarct conditions. Our data support the conclusion that the major cellular DJ-1 response to stroke in the human brain is astrocytic, and that there is a temporal correlation between DJ-1 expression in these cells and advanced infarct age.

  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.

  6. 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.

  7. Computational modeling of acute myocardial infarction

    PubMed Central

    Sáez, P.; Kuhl, E.

    2015-01-01

    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 towards 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

  8. 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.

  9. [Brain abscess following cerebral infarction: a case report].

    PubMed

    Ichimi, K; Ishiguri, H; Kida, Y; Kinomoto, T

    1989-04-01

    The authors report a case of brain abscess following cerebral infarction. A 73-year-old man was admitted to our clinic with symptoms of right hemiparesis and total aphasia. CT scan revealed abnormal low density area in the left fronto-temporo-parietal region. Cerebral angiography demonstrated occlusion of the left middle cerebral artery at the M1 portion. On the 16th hospital day, an episode of generalized seizure with high fever appeared, and intermittent high fever persisted thereafter. Two months after admission, CT scan revealed several cystic lesions with marked ring enhancement at the site of cerebral infarction, suggesting multiple abscesses. Aspirations of left frontal and parietal abscesses were accomplished and the cultures of the pus disclosed Proteus vulgaris. Due to progressive hydrocephalus, a ventriculoperitoneal shunt was constructed one month later. Repeated CT scans showed a gradual diminution of the abscesses. It is considered that the blood-brain barrier is broken and the local immunological system against bacteria may be weakened when the brain is damaged by ischemia. Brain abscess seems to be developed in such circumstances even under the influence of transient bacteremia which originates in other parts of the body. Therefore the possibility of cerebral abscess should be suspected if patients with cerebral infarction suffer from the symptoms such as fever, neck stiffness or disturbance of consciousness.

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

    PubMed Central

    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

  11. Role of Brain Infarcts in Behavioral Variant Frontotemporal Dementia

    PubMed Central

    Torralva, Teresa; Sposato, Luciano A.; Riccio, Patricia M.; Gleichgerrcht, Ezequiel; Roca, María; Toledo, Jon B.; Trojanowski, John Q.; Kukull, Walter A.; Manes, Facundo; Hachinski, Vladimir

    2015-01-01

    Diagnosing behavioral variant frontotemporal dementia (bvFTD) in patients with prior history of stroke or with silent brain infarcts on neuroimaging studies can be challenging. Vascular changes in patients with bvFTD are not unusual, but bvFTD tends to be ruled out in the presence of cerebrovascular disease. We aimed to identify the clinical, cognitive, and risk factor profile of bvFTD with coexistent cerebrovascular disease (V-bvFTD). We compared demographic data, clinical diagnoses, vascular risk factors, functional status, and normalized neuropsychological z-scores between patients with V-bvFTD vs. bvFTD without concomitant cerebrovascular disease (NV-bvFTD) from the National Alzheimer’s Coordinating Centre database. We included 391 neuropathologically diagnosed cases of frontotemporal lobe degeneration (FTLD). We excluded patients that were diagnosed with aphasic variants of frontotemporal dementia before death. Patients with V-bvFTD (n=62) were older at the time of onset of cognitive decline (71.6 vs. 62.5years, p<0.001) and death (78.7 vs. 69.6, p<0.001), more likely to be hypertensive (75.8 vs. 45.7%, p=0.002), and to have a history of stroke (21.2 vs. 6.1%, p=0.007) than those with NV-bvFTD (n=329). V-bvFTD was often underdiagnosed, affected elderly patients, and had a similar cognitive profile as NV-bvFTD despite the presence of brain infarcts. In the whole cohort, we observed enhanced cognitive performance with increasing age quintiles despite larger proportions of cerebrovascular disease pathology, likely meaning that FTLD-related primary neurodegeneration exerts a stronger impact on cognition than cerebrovascular disease. Coexisting cerebrovascular disease should not preclude the diagnosis of bvFTD. PMID:26220367

  12. 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

  13. Prevention of brain infarction by postischemic administration of histidine in rats.

    PubMed

    Adachi, Naoto; Liu, Keyue; Arai, Tatsuru

    2005-03-28

    Focal cerebral ischemia for 2 h by occlusion of the right middle cerebral artery provoked severe brain infarction in the rat brain after 24 h. Intraperitoneal administration of histidine, a precursor of histamine, immediately and 6 h after reperfusion, alleviated brain infarction. The infarct size in the histidine (200 mg/kg, 500 mg/kg, and 1000 mg/kg, each time) groups was 71%, 39%, and 7% of that in the control group, respectively. Although intracerebroventricular administration of mepyramine (3 nmol), an H1 antagonist, did not affect the morphologic outcome in histidine-treated rats, ranitidine (30 nmol), an H2 antagonist, completely abolished the alleviation caused by histidine. These findings indicate that postischemic administration of histidine prevents development of brain infarction by stimulating central histamine H2 receptors.

  14. Allopurinol and dimethylthiourea reduce brain infarction following middle cerebral artery occlusion in rats.

    PubMed

    Martz, D; Rayos, G; Schielke, G P; Betz, A L

    1989-04-01

    Free radicals have been shown to play an important role in ischemia-reperfusion injury in several organ systems; however, the role of free radicals in central nervous system ischemia has been less well studied. Many potential free radical-generating systems exist. The primary products of these reactions, superoxide and hydrogen peroxide, may combine to produce hydroxyl radicals. Of the many potential sources of free radical generation, the enzyme xanthine oxidase has been shown to be important in ischemia in noncerebral tissue. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea and the xanthine oxidase inhibitor allopurinol on infarct volume in a model of continuous partial ischemia. Male Sprague-Dawley rats were treated with dimethylthiourea or allopurinol before middle cerebral artery occlusion. Infarct volume was measured by triphenyltetrazolium chloride staining of brains removed 3 or 24 hours after occlusion. Stroke volume was reduced by 30% after dimethylthiourea treatment and by 32-35% after allopurinol treatment. At 24 hours after stroke, cortical tissue was more effectively protected than caudate tissue with both agents. Pretreatment with dimethylthiourea and allopurinol also significantly reduced cerebral edema formation and improved blood-brain barrier function as measured by fluorescein uptake. Our results imply that hydroxyl radicals are important in tissue injury secondary to partial cerebral ischemia and that xanthine oxidase may be the primary source of these radicals.

  15. 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.…

  16. Clinical and topographic magnetic resonance characteristics of suspected brain infarction in 40 dogs.

    PubMed

    Garosi, L; McConnell, J F; Platt, S R; Barone, G; Baron, J C; de Lahunta, A; Schatzberg, S J

    2006-01-01

    Medical records of 40 dogs presented for evaluation of acute-onset, nonprogressive, intracranial dysfunction by means of magnetic resonance imaging (MRI) diagnosis of brain infarction were reviewed. Location of the brain infarcts was: 11 of 38, telencephalic; 8 of 38, thalamic/midbrain; 18 of 38, cerebellar; and 3 of 38, multifocal. Telencephalic infarcts developed within the territory of the middle cerebral (4/11), rostral cerebral (2/11), and striate (5/11) arteries. Thalamic/midbrain infarcts developed within the territory of perforating arteries of the caudal portion of the thalamus and rostral portion of the brainstem (8/8). All cerebellar infarcts (18/38) were within the territory of the rostral cerebellar artery or one of its branches. All infarcts appeared nonhemorrhagic, with marked contrast enhancement observed in only 3 of 38 dogs, all of which were imaged more than 7 days after the onset of signs of neurologic dysfunction. Diffusion-weighted imaging (DWI) sequences were available from 6 dogs, all imaged within 5 days of the onset of signs of neurologic dysfunction. Suspected infarcts were hyperintense on DWI sequences and were hypointense on the apparent diffusion coefficient map. Telencephalic infarcts caused abnormal mental status, contralateral postural reaction deficit, contralateral nasal hypalgesia, contralateral menace deficit, and ipsilateral circling. Thalamic/midbrain infarcts caused contralateral or ipsilateral postural reaction deficit, contralateral menace deficit, ipsilateral head tilt or turn, nystagmus, ventrolateral strabismus, and anisocoria. Cerebellar infarcts caused ipsilateral asymmetric cerebellar quality ataxia, head tilt, intermittent opisthotonus, nystagmus, and ipsilateral menace deficit with apparent normal vision.

  17. 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.

  18. 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.

  19. Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia.

    PubMed

    Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita

    2017-01-01

    Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison

  20. Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia

    PubMed Central

    Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling

    2017-01-01

    Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8–24 h, whereas the late phase of BBB disruption begins 48–58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in

  1. Visualization of early infarction in rat brain after ischemia using a translocator protein (18 kDa) PET ligand [11C]DAC with ultra-high specific activity.

    PubMed

    Yui, Joji; Hatori, Akiko; Kawamura, Kazunori; Yanamoto, Kazuhiko; Yamasaki, Tomoteru; Ogawa, Masanao; Yoshida, Yuichiro; Kumata, Katsushi; Fujinaga, Masayuki; Nengaki, Nobuki; Fukumura, Toshimitsu; Suzuki, Kazutoshi; Zhang, Ming-Rong

    2011-01-01

    The aim of this study was to visualize early infarction in the rat brain after ischemia using a translocator protein (TSPO) (18 kDa) PET ligand [(11)C]DAC with ultra-high specific activity (SA) of 3670-4450 GBq/μmol. An infarction model of rat brain was prepared by ischemic surgery and evaluated 2 days after ischemia using small-animal PET and in vitro autoradiography. Early infarction with a small increase of TSPO expression in the brain was visualized using PET with high SA [(11)C]DAC (average 4060 GBq/μmol), but was not distinguished clearly with usually reported SA [(11)C]DAC (37 GBq/μmol). Infarction in the rat brain 4 days after ischemia was visualized using high and usually reported SAs [(11)C]DAC. Displacement experiments with unlabeled TSPO-selective AC-5216 or PK11195 diminished the difference in radioactivity between ipsilateral and contralateral sides, confirming that the increased uptake on the infracted brain was specific to TSPO. In vitro autoradiography with high SA [(11)C]DAC showed that the TSPO expression increased on early infarction in the rat brain. High SA [(11)C]DAC is a useful and sensitive biomarker for the visualization of early infarction and the characterization of TSPO expression which was slightly elevated in the infarcted brain using PET.

  2. 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.

  3. Fluid Intake Related to Brain Edema in Acute Middle Cerebral Artery Infarction.

    PubMed

    Dharmasaroja, Pornpatr A

    2016-02-01

    Evidence of the appropriate amount of fluid intake during the first few days after acute stroke was scarce. Concerns were raised in patients with acute malignant middle cerebral infarction, who tended to have malignant brain edema later. The purpose of the study was to evaluate the effect of fluid intake on the occurrence of malignant brain edema in patients with acute middle cerebral artery infarction. Patients with acute middle cerebral artery infarction who had National Institute of Health Stroke Scale (NIHSS) score of at least 15 were included. Baseline characteristics and amount of fluid intake during the first few days were compared in patients with and without malignant brain edema. One hundred ninety-three patients were studied. Mean NIHSS score was 20. Malignant brain edema occurred in 69 patients (36%). Higher amount of fluid intake (>1650 ml or >28 ml/kg/day or >93% of daily maintenance fluid) showed a significant association with malignant brain edema (OR = 13.86, 95% CI 5.11-37.60, p value <0.001). Decompressive surgery was performed in 35 patients (18%). With mean follow-up of 12 months, 49 patients (49/184, 27%) had favorable outcomes (modified Rankin scale (mRS) 0-2) at final follow-up. Seventy-nine patients (79/184, 43%) died. In the subgroup of patients with malignant brain edema, 39 patients (39/65, 60%) died and only 11% (7/65 patients) had favorable outcome. High amount of fluid intake in the first few days of acute middle cerebral infarction was related to the occurrence of malignant brain edema.

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

    PubMed

    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 on the effect of infarct size on temporal and spatial alterations in the myocardium during progressive myocardial remodeling. MI with three infarct sizes, i.e. 15, 25 and 35% of the left ventricular (LV) wall, was created in an ovine infarction model. The progressive LV remodeling over a 12-week period was studied. Echocardiography, sonomicrometry, and histological and molecular analyses were carried out to evaluate cardiac function, regional tissue contractile function, structural remodeling and cardiomyocyte hypertrophy, and calcium handling proteins. Twelve weeks after MI, the 15, 25 and 35% MI groups 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 the 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. A significant correlation was found between cardiomyocyte 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, more serious impairment in the cellular structure and composition, and regional contractile function at regional tissue level and LV function at organ level.

  5. Functional electrical stimulation-facilitated proliferation and regeneration of neural precursor cells in the brains of rats with cerebral infarction

    PubMed Central

    Xiang, Yun; Liu, Huihua; Yan, Tiebin; Zhuang, Zhiqiang; Jin, Dongmei; Peng, Yuan

    2014-01-01

    Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plasticity, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin (a neural precursor cell marker)-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic fibroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was significantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats. PMID:25206808

  6. Total and high molecular weight adiponectin levels in the rat model of post-myocardial infarction heart failure.

    PubMed

    Kalisz, M; Baranowska, B; Wolinska-Witort, E; Maczewski, M; Mackiewicz, U; Tulacz, D; Gora, M; Martynska, L; Bik, W

    2015-10-01

    Adiponectin is a protein secreted primarily by adipose tissue. It has been suggested that adiponectin plays a protective role in the early phase following myocardial infarction. Our primary aim was to investigate the effects of post-myocardial infarction heart failure well-characterized by left ventricular hemodynamic parameters on the total and high molecular weight adiponectin concentrations in plasma, fat and cardiac tissue. Eight weeks after myocardial infarction or sham operation, total and high molecular weight adiponectin concentrations in plasma, fat, and cardiac tissues were assayed in rats. In addition, hemodynamic parameters and expression of the genes encoding atrial natriuretic peptide and brain natriuretic peptide in left ventricle were evaluated. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in left ventricle tissue were higher in rats with myocardial infarction-induced heart failure compared with the controls. Similarly, total adiponectin concentration was increased in left ventricle (but not in right ventricle) in rats with post-myocardial infarction heart failure. In contrast, adiponectin levels in plasma and cardiac adipose tissue in rats with post-myocardial infarction heart failure were lower than in sham-operated animals. Furthermore, there were no significant differences in levels of high molecular weight adiponectin in plasma, cardiac tissue or adipose tissue between these two groups. We conclude that in the rat model of post-myocardial infarction heart failure, adiponectin level is increased in left ventricle tissue. This is accompanied by decreased adiponectin levels in plasma and cardiac adipose tissue.

  7. Ataxia in patients with brain infarcts and hemorrhages.

    PubMed

    Caplan, Louis R

    2012-01-01

    Gait and limb incoordination and ataxia are most often found in patients with brainstem and cerebellar infarcts and hemorrhages. Lesions involving the thalamus and the deep portions of the cerebral hemispheres also may cause ataxia accompanied by weakness and sensory symptoms. Patients who have lesions in the lateral medulla and inferior cerebellum often topple, lean, or veer when attempting to sit, stand, or walk. They list to the side or abruptly veer when walking. The affected limbs are often hypotonic. In pontine lesions, ataxia is accompanied by weakness and pyramidal tract signs as part of an ataxic hemiparesis syndrome. In lesions affecting the superior cerebellum and the brachium conjunctivum, limb dysmetria and overshoot and dysarthria predominate and gait ataxia is absent or slight and transient. Infarcts affecting the thalamus can cause gait instability and astasia with ataxia. Lateral thalamic lesions are characterized by hemisensory symptoms, extrapyramidal limb postures and dysfunction, and gait ataxia. Lesions that affect the posterior limb of the internal capsule and its afferent and efferent projections may also cause an ataxic hemiparesis syndrome, often with accompanying hemisensory abnormalities.

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

    PubMed

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

    1994-01-01

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

  9. 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

  10. Monitoring therapeutic efficacy of decompressive craniotomy in space occupying cerebellar infarcts using brain-stem auditory evoked potentials.

    PubMed

    Krieger, D; Adams, H P; Rieke, K; Hacke, W

    1993-01-01

    Brain-stem auditory evoked potentials (BAEPs) have been used to gauge effects of brain-stem dysfunction in humans and animal models. The purpose of this study was to evaluate the usefulness of BAEP in monitoring patients undergoing decompressive surgery of the posterior fossa for space occupying cerebellar infarcts. We report on serial BAEP recordings in 11 comatose patients with space occupying cerebellar infarcts undergoing decompressive craniotomy. BAEP studies were performed within 12 h after admission, 24 h following surgery and prior to extubation. BAEP signals were analyzed using latency determination and cross-correlation. Following surgery, 9 patients regained consciousness; 2 patients persisted in a comatose state and died subsequently. BAEP interpeak latency (IPL) I-V assessed prior to surgery exceeded normal values in all patients in whom it could be reliably measured (N = 9). Following decompressive surgery BAEP wave I-V IPL normalized in 5 patients, but remained prolonged despite dramatic clinical improvement in 4 patients. We prospectively computed the coefficient of cross-correlation (MCC) of combined ipsilateral BAEP trials after right and left ear stimulation. In all patients increasing MCC was associated with clinical improvement. Unchanging or decreasing MCC indicated poor outcome. We conclude that serial BAEP studies are an appropriate perioperative monitoring modality in patients with space occupying cerebellar infarcts undergoing decompressive surgery of the posterior fossa. Our study suggests advantages of cross-correlation analysis as an objective signal processing strategy; relevant information can be extracted even if BAEP wave discrimination is impossible due to severe brain-stem dysfunction.

  11. [Readaptation to work after myocardial infarction: model considerations].

    PubMed

    Turczyn-Jabłońska, Katarzyna; Waszkowska, Małgorzata

    2005-01-01

    In Poland only 50-60% of persons who have experienced myocardial infarction return to work. Bearing in mind that psychophysical condition changes after such an event, this group of people has to be readapted to work. Factors that determine good work performance among post-infarction workers have been not yet investigated. The aim of our study is to identify those factors and to define their role in the readaptation process. The first stage of our project involved the development of a theoretical model of readaptation to work after myocardial infarction. This model is described in this paper. It comprises the following components: medical evaluation of the workers' health status, his or her subjective assessment of work ability, expectations (optimistic vs. pessimistic attitude), motivation to work, social support, and job characteristics.

  12. 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

  13. Malignant infarction of the middle cerebral artery in a porcine model. A pilot study

    PubMed Central

    Martínez-Valverde, Tamara; Sánchez-Guerrero, Ángela; Campos, Mireia; Esteves, Marielle; Gandara, Dario; Torné, Ramon; Castro, Lidia; Dalmau, Antoni; Tibau, Joan

    2017-01-01

    Background and purpose Interspecies variability and poor clinical translation from rodent studies indicate that large gyrencephalic animal stroke models are urgently needed. We present a proof-of-principle study describing an alternative animal model of malignant infarction of the middle cerebral artery (MCA) in the common pig and illustrate some of its potential applications. We report on metabolic patterns, ionic profile, brain partial pressure of oxygen (PtiO2), expression of sulfonylurea receptor 1 (SUR1), and the transient receptor potential melastatin 4 (TRPM4). Methods A 5-hour ischemic infarct of the MCA territory was performed in 5 2.5-to-3-month-old female hybrid pigs (Large White x Landrace) using a frontotemporal approach. The core and penumbra areas were intraoperatively monitored to determine the metabolic and ionic profiles. To determine the infarct volume, 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry analysis was performed to determine SUR1 and TRPM4 expression. Results PtiO2 monitoring showed an abrupt reduction in values close to 0 mmHg after MCA occlusion in the core area. Hourly cerebral microdialysis showed that the infarcted tissue was characterized by reduced concentrations of glucose (0.03 mM) and pyruvate (0.003 mM) and increases in lactate levels (8.87mM), lactate-pyruvate ratio (4202), glycerol levels (588 μM), and potassium concentration (27.9 mmol/L). Immunohistochemical analysis showed increased expression of SUR1-TRPM4 channels. Conclusions The aim of the present proof-of-principle study was to document the feasibility of a large animal model of malignant MCA infarction by performing transcranial occlusion of the MCA in the common pig, as an alternative to lisencephalic animals. This model may be useful for detailed studies of cerebral ischemia mechanisms and the development of neuroprotective strategies. PMID:28235044

  14. Myocardial infarction and intramyocardial injection models in swine.

    PubMed

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

    2012-07-12

    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.

  15. 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

    2013-12-05

    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.

  16. 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

  17. The effect of butylphthalide on the brain edema, blood-brain barrier of rats after focal cerebral infarction and the expression of Rho A.

    PubMed

    Hu, Jinyang; Wen, Qingping; Wu, Yue; Li, Baozhu; Gao, Peng

    2014-06-01

    The aim of this study was to explore the effect of butylphthalide on the brain edema, blood-brain barrier of rats of rats after focal cerebral infarction and the expression of Rho A. A total of 195 sprague-dawley male rats were randomly divided into control group, model group, and butylphthalide group (40 mg/kg, once a day, by gavage). The model was made by photochemical method. After surgery 3, 12, 24, 72, and 144 h, brain water content was done to see the effect of butylphthalide for the cerebral edema. Evans blue extravasation method was done to see the changes in blood-brain barrier immunohistochemistry, and Western blot was done to see the expression of Rho A around the infarction. Compared with the control group, the brain water content of model group and butylphthalide group rats was increased, the permeability of blood-brain barrier of model group and butylphthalide group rats was increased, and the Rho A protein of model group and butylphthalide group rats was increased. Compared with the model group, the brain water content of butylphthalide group rats was induced (73.67 ± 0.67 vs 74.14 ± 0.46; 74.89 ± 0.57 vs 75.61 ± 0.52; 77.49 ± 0.34 vs 79.33 ± 0.49; 76.31 ± 0.56 vs 78.01 ± 0.48; 72.36 ± 0.44 vs 73.12 ± 0.73; P < 0.05), the permeability of blood-brain barrier of butylphthalide group rats was induced (319.20 ± 8.11 vs 394.60 ± 6.19; 210.40 ± 9.56 vs 266.40 ± 7.99; 188.00 ± 9.22 vs 232.40 ± 7.89; 288.40 ± 7.86 vs 336.00 ± 6.71; 166.60 ± 6.23 vs 213.60 ± 13.79; P < 0.05), and the Rho A protein of butylphthalide group rats was decreased (western blot result: 1.2230 ± 0.0254 vs 1.3970 ± 0.0276; 1.5985 ± 0.0206 vs 2.0368 ± 0.0179; 1.4229 ± 0.0167 vs 1.7930 ± 0.0158;1.3126 ± 0.0236 vs 1.5471 ± 0.0158; P < 0.05). The butylphthalide could reduce the brain edema, protect the blood-brain barrier, and decrease the expression of Rho A around the infarction.

  18. 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

  19. Brain metabolite changes in patients with type 2 diabetes and cerebral infarction using proton magnetic resonance spectroscopy.

    PubMed

    Zhang, Min; Sun, Xinhai; Zhang, Zhengjun; Meng, Qiang; Wang, Yuzhong; Chen, Jing; Ma, Xueqin; Geng, Houfa; Sun, Lin

    2014-01-01

    The aim of this study was to investigate the possible brain metabolic alterations in patients with type 2 diabetes mellitus (T2DM) and cerebral infarction (DMCI) using proton magnetic resonance spectroscopy (MRS). Thirty-four patients with T2DM and DMCI were scanned together with 33 patients with nondiabetic cerebral infarction (NDCI) on a 1.5-T MRI/MRS imager. Voxels were placed in the infarcted area and the contralateral normal area in the basal ganglia. N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and lactate (Lac)/Cr ratios were calculated. Cerebral NAA/Cr ratios in the infarcted area were lower than those in the contralateral normal area of the NDCI group. There was a significant decrease in NAA/Cr in the infarcted area of the DMCI group as compared with the infarcted area of the NDCI group. NAA/Cr ratios in the contralateral normal area of DMCI group were lower than those of the NDCI group. Lac/Cr ratios were increased in the infarcted area of both the DMCI group and NDCI group, and Lac/Cr ratios tended to be higher in the infarcted area of the DMCI group than those of the NDCI group. Glycosylated hemoglobin (HbA1c) levels were negatively correlated with NAA/Cr ratios. The study suggested that the metabolite changes were different between DMCI patients and NDCI patients, which may provide important information in the treatment of DMCI.

  20. How well does the Oxfordshire Community Stroke Project classification predict the site and size of the infarct on brain imaging?

    PubMed Central

    Mead, G; Lewis, S; Wardlaw, J; Dennis, M; Warlow, C

    2000-01-01

    OBJECTIVES—The Oxfordshire Community Stroke Project (OCSP) classification is a simple clinical scheme for subdividing first ever acute stroke. Several small studies have shown that when an infarct is visible on CT or MRI, the classification predicts its site in about three quarters of patients. The aim was to further investigate this relation in a much larger cohort of patients in hospital with ischaemic stroke.
METHODS—Between 1994 and 1997, inpatients and outpatients with ischaemic stroke were assessed by one of several stroke physicians who noted the OCSP classification. A neuroradiologist classified the site and extent of recent infarction on CT or MRI.
RESULTS—Of 1012 patients with ischaemic stroke, 655 (65%) had recent visible infarcts. These radiological lesions were appropriate to the clinical classification in 69/87 (79%) patients with a total anterior circulation syndrome, 213/298 (71%) with a partial anterior circulation syndrome, 105/144 (73%) with a lacunar syndrome, and 105/126 (83%) with a posterior circulation syndrome. Overall, 75% of patients with visible infarcts were correctly classified clinically. If patients without a visible infarct did have an appropriate lesion in the brain (best case), the classification would have correctly predicted its site and size in 849/1012 (84%) patients, compared with only 492/1012 (49%) in the worst case scenario.
CONCLUSION—The OCSP classification predicted the site of infarct in three quarters of patients. When an infarct is visible on brain imaging, the site of the infarct should guide the use of further investigations, but if an infarct is not seen, the OCSP classification could be used to predict its likely size and site.

 PMID:10766882

  1. Changes in neuropeptide Y protein expression following photothrombotic brain infarction and epileptogenesis.

    PubMed

    Kharlamov, Elena A; Kharlamov, Alexander; Kelly, Kevin M

    2007-01-05

    This study characterized morphological changes in the cortex and hippocampus of Sprague-Dawley rats following photothrombotic infarction and epileptogenesis with emphasis on the distribution of neuropeptide Y (NPY) expression. Animals were lesioned in the left sensorimotor cortex and compared with age-matched naive and sham-operated controls by immunohistochemical techniques at 1, 3, 7, and 180 days post-lesioning (DPL). NPY immunostaining was assessed by light microscopy and quantified by the optical fractionator technique using unbiased stereological methods. At 1, 3, and 7 DPL, the number of NPY-positive somata in the lesioned cortex was increased significantly compared to controls and the contralateral cortex. At 180 DPL, lesioned epileptic animals with frequent seizure activity demonstrated significant increases of NPY expression in the cortex, CA1, CA3, hilar interneurons, and granule cells of the dentate gyrus. In addition to NPY immunostaining, neuronal degeneration, cell death/cell loss, and astroglial response were assessed with cell-specific markers. Nissl and NeuN staining showed reproducible infarctions at each investigated time point. FJB-positive somata were most abundant in the infarct core at 1 DPL, decreased markedly at 3 DPL, and virtually absent by 7 DPL. Activated astroglia were detected in the cortex and hippocampus following lesioning and the development of seizure activity. In summary, NPY protein expression and morphological changes following cortical photothrombosis were time-, region-, and pathologic state-dependent. Alterations in NPY expression may reflect reactive or compensatory responses of the rat brain to acute infarction and to the development and expression of epileptic seizures.

  2. Changes in neuropeptide Y protein expression following photothrombotic brain infarction and epileptogenesis.

    PubMed Central

    Kharlamov, Elena A.; Kharlamov, Alexander; Kelly, Kevin M.

    2007-01-01

    This study characterized morphological changes in the cortex and hippocampus of Sprague-Dawley rats following photothrombotic infarction and epileptogenesis with emphasis on the distribution of neuropeptide Y (NPY) expression. Animals were lesioned in the left sensorimotor cortex and compared with age-matched naïve and sham-operated controls by immunohistochemical techniques at 1, 3, 7, and 180 days post-lesioning (DPL). NPY immunostaining was assessed by light microscopy and quantified by the optical fractionator technique using unbiased stereological methods. At 1, 3, and 7 DPL, the number of NPY-positive somata in the lesioned cortex was increased significantly compared to controls and the contralateral cortex. At 180 DPL, lesioned epileptic animals with frequent seizure activity demonstrated significant increases of NPY expression in the cortex, CA1, CA3, hilar interneurons, and granule cells of the dentate gyrus. In addition to NPY immunostaining, neuronal degeneration, cell death/cell loss, and astroglial response were assessed with cell-specific markers. Nissl and NeuN staining showed reproducible infarctions at each investigated time point. FJB-positive somata were most abundant in the infarct core at 1 DPL, decreased markedly at 3 DPL, and virtually absent by 7 DPL. Activated astroglia were detected in the cortex and hippocampus following lesioning and the development of seizure activity. In summary, NPY protein expression and morphological changes following cortical photothrombosis were time-, region- and pathologic state-dependent. Alterations in NPY expression may reflect reactive or compensatory responses of the rat brain to acute infarction and to the development and expression of epileptic seizures. PMID:17123484

  3. 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

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

    PubMed

    Colliez, Florence; Safronova, Marta M; Magat, Julie; Joudiou, Nicolas; Peeters, André P; Jordan, Bénédicte F; Gallez, Bernard; Duprez, Thierry

    2015-01-01

    The clinical applicability of brain oxygenation mapping using the MOBILE (Mapping of Oxygen By Imaging Lipids relaxation Enhancement) magnetic resonance (MR) technique was assessed in the clinical setting of normal brain and of acute cerebral ischemia as a founding proof-of-concept translational study. Changes in the oxygenation level within healthy brain tissue can be detected by analyzing the spin-lattice proton relaxation ('Global T1' combining water and lipid protons) because of the paramagnetic properties of molecular oxygen. It was hypothesized that selective measurement of the relaxation of the lipid protons ('Lipids T1') would result in enhanced sensitivity of pO2 mapping because of higher solubility of oxygen in lipids than in water, and this was demonstrated in pre-clinical models using the MOBILE technique. In the present study, 12 healthy volunteers and eight patients with acute (48-72 hours) brain infarction were examined with the same clinical 3T MR system. Both Lipids R1 (R1 = 1/T1) and Global R1 were significantly different in the infarcted area and the contralateral unaffected brain tissue, with a higher statistical significance for Lipids R1 (median difference: 0.408 s-1; p<0.0001) than for Global R1 (median difference: 0.154 s-1; p = 0.027). Both Lipids R1 and Global R1 values in the unaffected contralateral brain tissue of stroke patients were not significantly different from the R1 values calculated in the brain tissue of healthy volunteers. The main limitations of the present prototypic version of the MOBILE sequence are the long acquisition time (4 min), hampering robustness of data in uncooperative patients, and a 2 mm slice thickness precluding accurate measurements in small infarcts because of partial volume averaging effects.

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

    PubMed

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

    2015-03-01

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

  6. Regulatory T cells modulate inflammation and reduce infarct volume in experimental brain ischaemia

    PubMed Central

    Brea, David; Agulla, Jesús; Rodríguez-Yáñez, Manuel; Barral, David; Ramos-Cabrer, Pedro; Campos, Francisco; Almeida, Angeles; Dávalos, Antoni; Castillo, José

    2014-01-01

    Brain ischaemia (stroke) triggers an intense inflammatory response predominately mediated by the accumulation of inflammatory cells and mediators in the ischaemic brain. In this context, regulatory T (Treg) cells, a subpopulation of CD4+ T cells with immunosuppressive and anti-inflammatory properties, are activated in the late stages of the disease. To date, the potential therapeutic usefulness of Treg cells has not been tested. In this study, we aimed to investigate whether Treg cells exert protection/repair following stroke. Both the adoptive transfer of Treg cells into ischaemic rats and the stimulation of endogenous T-cell proliferation using a CD28 superagonist reduced the infarct size at 3–28 days following the ischaemic insult. Moreover, T cell-treated animals had higher levels of FoxP3 and lower levels of IL-1β, CD11b+ and CD68+ cells in the infarcted hemisphere when compared with control animals. However, T-cell treatment did not alter the rate of proliferation of NeuN-, NCAM- or CD31-positive cells, thereby ruling out neurogenesis and angiogenesis in protection. These results suggest that adoptive transfer of T cells is a promising therapeutic strategy against the neurological consequences of stroke. PMID:24889329

  7. A simple prediction score system for malignant brain edema progression in large hemispheric infarction

    PubMed Central

    Jo, KwangWook; Bajgur, Suhas S.; Kim, Hoon; Choi, Huimahn A.; Huh, Pil-Woo; Lee, Kiwon

    2017-01-01

    Malignant brain edema (MBE) due to hemispheric infarction can result in brain herniation, poor outcomes, and death; outcome may be improved if certain interventions, such as decompressive craniectomy, are performed early. We sought to generate a prediction score to easily identify those patients at high risk for MBE. 121 patients with large hemispheric infarction (LHI) (2011 to 2014) were included. Patients were divided into two groups: those who developed MBE and those who did not. Independent predictors of MBE were identified by logistic regression and a score was developed. Four factors were independently associated with MBE: baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.048), Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (p = 0.007), collateral score (CS) (p<0.001) and revascularization failure (p = 0.013). Points were assigned for each factor as follows: NIHSS ≤ 8 (= 0), 9–17 (= 1), ≥ 18 (= 2); ASPECTS≤ 7 (= 1), >8 (= 0); CS<2 (= 1), ≥2 (= 0); revascularization failure (= 1),success (= 0). The MBE Score (MBES) represents the sum of these individual points. Of 26 patients with a MBES of 0 to 1, none developed MBE. All patients with a MBES of 6 developed MBE. Both MBE development and functional outcomes were strongly associated with the MBES (p = 0.007 and 0.002, respectively). The MBE score is a simple reliable tool for the prediction of MBE. PMID:28178299

  8. Overproduction of nitric oxide intensifies brain infarction and cerebrovascular damage through reduction of claudin-5 and ZO-1 expression in striatum of ischemic brain.

    PubMed

    Mohammadi, Mohammad Taghi

    2016-11-01

    Nitric oxide (NO) overproduction has been demonstrated from different NO-synthase overexpression or hyperactivity after brain ischemia. Here, we examined the effects of inhibition of NO overproduction on brain infarction, cerebrovascular damage and expression of claudin-5 and zonula occludens-1 (ZO-1) in striatum of ischemic brain. The experiment was performed in three groups of rats; sham, control ischemia and ischemic treatment. Brain ischemia was induced by 60min of middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. Treated rats received L-NAME 30min before induction of ischemia (1mg/kg, i.p.). Infarct volume and histopathological changes of ischemic striatum were assessed by TTC and LFB staining methods, respectively. Ultimately, quantitative RT-PCR was used for assessment of claudins-5 and ZO-1 expression. MCAO in the control group induced infarction (135±25mm(3)) at large areas of striatum in accompany with neuronal damages, whereas L-NAME significantly reduced infarction (87±16mm(3)) and neuronal injuries. The mRNA of ZO-1 and claudin-5 decreased in ischemic striatum, whereas inhibition of NO overproduction by L-NAME attenuated this reduction for these genes. Our findings indicated that NO overproduction after brain ischemia plays a crucial role in neuronal damage especially at striatal regions. Hence, inhibition of excessive NO production may save striatal cerebrovascular integrity of ischemic brain.

  9. 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

  10. 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

  11. Myocardial infarction and intramyocardial injection models in swine

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    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

    2016-08-01

    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.

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

    PubMed

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

    2015-01-01

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

  14. 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.

  15. Silent Brain Infarction and Risk of Future Stroke: A Systematic Review and Meta-Analysis

    PubMed Central

    Gupta, Ajay; Giambrone, Ashley E.; Gialdini, Gino; Finn, Caitlin; Delgado, Diana; Gutierrez, Jose; Wright, Clinton; Beiser, Alexa S.; Seshadri, Sudha; Pandya, Ankur; Kamel, Hooman

    2016-01-01

    Background and Purpose Silent brain infarction (SBI) on magnetic resonance imaging (MRI) has been proposed as a subclinical risk marker for future symptomatic stroke. We performed a systematic review and meta-analysis to summarize the association between MRI-defined SBI and future stroke risk. Methods We searched the medical literature to identify cohort studies involving adults with MRI detection of SBI who were subsequently followed for incident clinically-defined stroke. Study data and quality assessment were recorded in duplicate with disagreements in data extraction resolved by a third reader. Strength association between MRI detected SBI and future symptomatic stroke measured by a hazard ratio (HR). Results The meta-analysis included 13 studies (14,764 subjects) with a mean follow-up ranging from 25.7 to 174 months. SBI predicted the occurrence of stroke with a random effects crude relative risk of 2.94 (95% CI 2.24–3.86, P<0.001; Q=39.65, P<0.001). In the eight studies of 10,427 subjects providing HR adjusted for cardiovascular risk factors, SBI was an independent predictor of incident stroke (HR 2.08 [95% CI 1.69–2.56, P<0.001]; Q=8.99, P=0.25). In a subgroup analysis pooling 9,483 stroke-free individuals from large population-based studies, SBI was present in ~18% of participants and remained a strong predictor of future stroke (HR 2.06 [95% CI 1.64–2.59], p<0.01). Conclusions SBI is present in approximately one in five stroke-free older adults and is associated with a 2-fold increased risk of future stroke. Future studies of in-depth stroke risk evaluations and intensive prevention measures are warranted in patients with clinically unrecognized radiologically evident brain infarctions. PMID:26888534

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

    PubMed Central

    Liao, Yiliu; Gu, Ning; Rundén-Pran, Elise; Ruth, Peter; Sausbier, Matthias; Storm, Johan F.

    2010-01-01

    Neuronal calcium-activated potassium channels of the BK type are activated by membrane depolarization and intracellular Ca2+ ions. It has been suggested that these channels may play a key neuroprotective role during and after brain ischemia, but this hypothesis has so far not been tested by selective BK-channel manipulations in vivo. To elucidate the in vivo contribution of neuronal BK channels in acute focal cerebral ischemia, we performed middle cerebral artery occlusion (MCAO) in mice lacking BK channels (homozygous mice lacking the BK channel alpha subunit, BK−/−). MCAO was performed in BK−/− and WT mice for 90 minutes followed by a 7-hour-reperfusion period. Coronal 1 mm thick sections were stained with 2,3,5-triphenyltetrazolium chloride to reveal the infarction area. We found that transient focal cerebral ischemia by MCAO produced larger infarct volume, more severe neurological deficits, and higher post-ischemic mortality in BK−/− mice compared to WT littermates. However, the regional cerebral blood flow was not significantly different between genotypes as measured by Laser Doppler (LD) flowmetry pre-ischemically, intra-ischemically, and post-ischemically, suggesting that the different impact of MCAO in BK−/− vs. WT was not due to vascular BK channels. Furthermore, when NMDA was injected intracerebrally in non-ischemic mice, NMDA-induced neurotoxicity was found to be larger in BK−/− mice compared to WT. Whole-cell patch clamp recordings from CA1 pyramidal cells in organotypic hippocampal slice cultures revealed that BK channels contribute to rapid action potential repolarization, as previously found in acute slices. When these cultures were exposed to ischemia-like conditions this induced significantly more neuronal death in BK−/− than in WT cultures. These results indicate that neuronal BK channels are important for protection against ischemic brain damage. PMID:21209897

  17. Application of cell sheet technology to bone marrow stromal cell transplantation for rat brain infarct.

    PubMed

    Ito, Masaki; Shichinohe, Hideo; Houkin, Kiyohiro; Kuroda, Satoshi

    2017-02-01

    Bone marrow stromal cells (BMSC) transplantation enhances functional recovery after cerebral infarct, but the optimal delivery route is undetermined. This study was aimed to assess whether a novel cell-sheet technology non-invasively serves therapeutic benefits to ischemic stroke. First, the monolayered cell sheet was engineered by culturing rat BMSCs on a temperature-responsive dish. The cell sheet was analysed histologically and then transplanted onto the ipsilateral neocortex of rats subjected to permanent middle cerebral artery occlusion at 7 days after the insult. Their behaviours and histology were compared with those in the animals treated with direct injection of BMSCs or vehicle over 4 weeks post-transplantation. The cell sheet was 27.9 ± 8.0 μm thick and was composed of 9.8 ± 2.4 × 10(5) cells. Cell sheet transplantation significantly improved motor function when compared with the vehicle-injected animals. Histological analysis revealed that the BMSCs were densely distributed to the neocortex adjacent to the cerebral infarct and expressed neuronal phenotype in the cell sheet-transplanted animals. These findings were almost equal to those for the animals treated with direct BMSC injection. The attachment of the BMSC sheet to the brain surface did not induce reactive astrocytes in the adjacent neocortex, although direct injection of BMSCs profoundly induced reactive astrocytes around the injection site. These findings suggest that the BMSCs in cell sheets preserve their biological capacity of migration and neural differentiation. Cell-sheet technology may enhance functional recovery after ischaemic stroke, using a less invasive method. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Brain Functioning Models for Learning.

    ERIC Educational Resources Information Center

    Tipps, Steve; And Others

    This paper describes three models of brain function, each of which contributes to an integrated understanding of human learning. The first model, the up-and-down model, emphasizes the interconnection between brain structures and functions, and argues that since physiological, emotional, and cognitive responses are inseparable, the learning context…

  19. Natural IgM Blockade Limits Infarct Expansion and Left Ventricular Dysfunction in a Swine Myocardial Infarct Model

    PubMed Central

    Sihag, Smita; Haas, Michael S.; Kim, Karen M.; Guerrero, J. Luis; Beaudoin, Jonathan; Alicot, Elisabeth M.; Schuerpf, Franziska; Gottschall, James D.; Puro, Robyn J.; Madsen, Joren C.; Sachs, David H.; Newman, Walter; Carroll, Michael C.; Allan, James S.

    2015-01-01

    Background Acute coronary syndrome is the leading cause of mortality worldwide. However, treatment of acute coronary occlusion inevitably results in ischemia-reperfusion (I/R) injury. Circulating natural IgM has been shown to play a significant role in mouse models of I/R injury. A highly conserved self-antigen, non-muscle myosin heavy chain II (NMHC-II), has been identified as a target of pathogenic IgM. We hypothesized that a monoclonal antibody (m21G6) directed against NMHC-II may inhibit IgM binding and reduce injury in a pre-clinical model of myocardial infarction (MI). Thus, our objective was to evaluate the efficacy of intravenous m21G6 treatment in limiting infarct expansion, troponin release, and left ventricular dysfunction in a swine MI model. Methods and Results MGH miniature swine underwent occlusion of the mid left anterior descending coronary artery for 60min, followed by 1h, 5d, or 21d reperfusion. Specificity and localization of m21G6 to injured myocardium were confirmed using fluorescently labeled m21G6. Treatment with m21G6 prior to reperfusion resulted in a 49% reduction in infarct size (p<0.005) and a 61% reduction in troponin-T levels (p<0.05) in comparison to saline controls at 5d reperfusion. Furthermore, m21G6 treated animals recovered 85.4% of their baseline left ventricular function as measured by two-dimensional transthoracic echocardiography (2D TTE) in contrast to 67.1% in controls at 21d reperfusion (p<0.05). Conclusions Treatment with m21G6 significantly reduced infarct size and troponin-T release, and led to marked preservation of cardiac function in our study. Overall, these findings suggest that pathogenic IgM blockade represents a valid therapeutic strategy in mitigating myocardial I/R injury. PMID:26671971

  20. Evidence synthesis through a degradation model applied to myocardial infarction

    PubMed Central

    Commenges, Daniel; Hejblum, Boris P.

    2013-01-01

    We propose an evidence synthesis approach through a degradation model to estimate causal influences of physiological factors on myocardial infarction (MI) and coronary heart disease (CHD). For instance several studies give incidences of MI and CHD for different age strata, other studies give relative or absolute risks for strata of main risk factors of MI or CHD. Evidence synthesis of several studies allows incorporating these disparate pieces of information into a single model. For doing this we need to develop a sufficiently general dynamical model; we also need to estimate the distribution of explanatory factors in the population. We develop a degradation model for both MI and CHD using a Brownian motion with drift, and the drift is modeled as a function of indicators of obesity, lipid profile, inflammation and blood pressure. Conditionally on these factors the times to MI or CHD have inverse Gaussian ( ) distributions. The results we want to fit are generally not conditional on all the factors and thus we need marginal distributions of the time of occurrence of MI and CHD; this leads us to manipulate the inverse Gaussian normal distribution ( ) (an whose drift parameter has a normal distribution). Another possible model arises if a factor modifies the threshold. This led us to define an extension of obtained when both drift and threshold parameters have normal distributions. We applied the model to results published in five important studies of MI and CHD and their risk factors. The fit of the model using the evidence synthesis approach was satisfactory and the effects of the four risk factors were highly significant. PMID:22918702

  1. Evaluation and simplified measurement of infarct size by myocardial contrast echocardiography in a rat model of myocardial infarction.

    PubMed

    Chen, Xianghui; Cui, Kai; Xiu, Jiancheng; Lin, Huanbing; Lao, Yi; Zhou, Biying; Liang, Feixue; Zha, Daogang; Bin, Jianping; Liu, Yili

    2009-10-01

    To test the feasibility and accuracy of myocardial contrast echocardiography (MCE) for predicting infarct size (IS) in a rat model of myocardial infarction (MI) and to compare a simplified single plane-based measurement of IS with the conventional three plane-based approach. Fifty male SD rats underwent left anterior descending artery ligation and were evaluated by MCE 8 h post MI. IS was calculated by the single and three plane-based approaches, compared to that determined by triphenyltetrazolium chloride (TTC) staining method. Simplified single plane-based MCE approach and TTC method showed similar IS values (38.48 +/- 16.80% vs. 35.72 +/- 15.33%, P > 0.05) and presented a favorable positive correlation (r = 0.851, P < 0.001). IS values derived from simplified single plane-based approach was also highly significantly correlated with that by the conventional MCE method (r = 0.973, P < 0.001). Bland-Altman plots also displayed satisfactory agreement between them. MCE was validated as a novel technique to quantify infarct area in rats with MI. A single measurement at the mid-papillary muscle level may become a simple, efficient and reliable approach for in vivo IS assessment.

  2. A multicenter, randomized trial on neuroprotection with remote ischemic per-conditioning during acute ischemic stroke: the REmote iSchemic Conditioning in acUtE BRAin INfarction study protocol.

    PubMed

    Pico, Fernando; Rosso, Charlotte; Meseguer, Elena; Chadenat, Marie-Laure; Cattenoy, Amina; Aegerter, Philippe; Deltour, Sandrine; Yeung, Jennifer; Hosseini, Hassan; Lambert, Yves; Smadja, Didier; Samson, Yves; Amarenco, Pierre

    2016-10-01

    Rationale Remote ischemic per-conditioning-causing transient limb ischemia to induce ischemic tolerance in other organs-reduces final infarct size in animal stroke models. Aim To evaluate whether remote ischemic per-conditioning during acute ischemic stroke (<6 h) reduces brain infarct size at 24 h. Methods and design This study is being performed in five French hospitals using a prospective randomized open blinded end-point design. Adults with magnetic resonance imaging confirmed ischemic stroke within 6 h of symptom onset and clinical deficit of 5-25 according to National Institutes of Health Stroke Scale will be randomized 1:1 to remote ischemic per-conditioning or control (stratified by center and intravenous fibrinolysis use). Remote ischemic per-conditioning will consist of four cycles of electronic tourniquet inflation (5 min) and deflation (5 min) to a thigh within 6 h of symptom onset. Magnetic resonance imaging is repeated 24 h after stroke onset. Sample size estimates For a difference of 15 cm(3) in brain infarct growth between groups, 200 patients will be included for 5% significance and 80% power. Study outcomes The primary outcome will be the difference in brain infarct growth from baseline to 24 h in the intervention versus control groups (by diffusion-weighted image magnetic resonance imaging). Secondary outcomes include: National Institutes of Health Stroke Scale score absolute difference between baseline and 24 h, three-month modified Rankin score and daily living activities, mortality, and tolerance and side effects of remote ischemic per-conditioning. Discussion The only remote ischemic per-conditioning trial in humans with stroke did not show remote ischemic per-conditioning to be effective. REmote iSchemic Conditioning in acUtE BRAin INfarction, which has important design differences, should provide more information on the use of this intervention in patients with acute ischemic stroke.

  3. Risk prediction for myocardial infarction via generalized functional regression models.

    PubMed

    Ieva, Francesca; Paganoni, Anna M

    2016-08-01

    In this paper, we propose a generalized functional linear regression model for a binary outcome indicating the presence/absence of a cardiac disease with multivariate functional data among the relevant predictors. In particular, the motivating aim is the analysis of electrocardiographic traces of patients whose pre-hospital electrocardiogram (ECG) has been sent to 118 Dispatch Center of Milan (the Italian free-toll number for emergencies) by life support personnel of the basic rescue units. The statistical analysis starts with a preprocessing of ECGs treated as multivariate functional data. The signals are reconstructed from noisy observations. The biological variability is then removed by a nonlinear registration procedure based on landmarks. Thus, in order to perform a data-driven dimensional reduction, a multivariate functional principal component analysis is carried out on the variance-covariance matrix of the reconstructed and registered ECGs and their first derivatives. We use the scores of the Principal Components decomposition as covariates in a generalized linear model to predict the presence of the disease in a new patient. Hence, a new semi-automatic diagnostic procedure is proposed to estimate the risk of infarction (in the case of interest, the probability of being affected by Left Bundle Brunch Block). The performance of this classification method is evaluated and compared with other methods proposed in literature. Finally, the robustness of the procedure is checked via leave-j-out techniques.

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

    ERIC Educational Resources Information Center

    Bowlen, Clark

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

  7. 'Iatrogenic' brain stem infarction. A complication of x-ray examination of the cervical spine and following posterior tamponation of the nose.

    PubMed

    Fogelholm, R; Karli, P

    1975-01-01

    Two patients sustained an ischemic brain stem infarction during medical examination and treatment. The first patient lost consciousness and the spontaneous respiration ceased during X-ray examination of the cervical spine when the neck was hyperextended. After some minutes he regained conciousness but was found to be tetraplegic, and the patient deceased 4 months later. The angiogram revealed thrombosis of the basilar artery. The other patient had profuse nosebleed and was treated with posterior tamponation during which she sat for about 10 min with the neck hyperextended. Some hours after this procedure symptoms and signs of lateral caudal brain stem infarction emerged.

  8. Brain CT-scan in acute stroke patients: silent infarcts and relation to outcome.

    PubMed

    Corea, Francesco; Tambasco, Nicola; Luccioli, Roberto; Ciorba, Ettore; Parnetti, Lucilla; Gallai, Virgilio

    2002-01-01

    Silent infarcts (SIs) are common findings in stroke patients, but their clinical significance remains controversial. Aim of this study was to evaluate the prevalence of SI in consecutive stroke patients, characteristics, associated factors, and influence on in-hospital mortality. The population consisted of 191 patients, consecutively admitted for an acute stroke. Of 191 patients, 74 had SI on CT-scan. Silent infarcts were often multiple, right sided, lacunar. We found SI more frequently in older patients, smokers, with an ischemic stroke having small vessel disease as presumed cause. In our study SI were associated with ageing, smoke habit and lacunar stroke. Silent infarcts size influenced the rate of in-hospital mortality.

  9. Tachycardia in post-infarction hearts: insights from 3D image-based ventricular models.

    PubMed

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

    2013-01-01

    Ventricular tachycardia, a life-threatening regular and repetitive fast heart rhythm, frequently occurs in the setting of myocardial infarction. Recently, the peri-infarct zones surrounding the necrotic scar (termed gray zones) have been shown to correlate with ventricular tachycardia inducibility. However, it remains unknown how the latter is determined by gray zone distribution and size. The goal of this study is to examine how tachycardia circuits are maintained in the infarcted heart and to explore the relationship between the tachycardia organizing centers and the infarct gray zone size and degree of heterogeneity. To achieve the goals of the study, we employ a sophisticated high-resolution electrophysiological model of the infarcted canine ventricles reconstructed from imaging data, representing both scar and gray zone. The baseline canine ventricular model was also used to generate additional ventricular models with different gray zone sizes, as well as models in which the gray zone was represented as different heterogeneous combinations of viable tissue and necrotic scar. The results of the tachycardia induction simulations with a number of high-resolution canine ventricular models (22 altogether) demonstrated that the gray zone was the critical factor resulting in arrhythmia induction and maintenance. In all models with inducible arrhythmia, the scroll-wave filaments were contained entirely within the gray zone, regardless of its size or the level of heterogeneity of its composition. The gray zone was thus found to be the arrhythmogenic substrate that promoted wavebreak and reentry formation. We found that the scroll-wave filament locations were insensitive to the structural composition of the gray zone and were determined predominantly by the gray zone morphology and size. The findings of this study have important implications for the advancement of improved criteria for stratifying arrhythmia risk in post-infarction patients and for the development of

  10. Development and evaluation of models to predict death and myocardial infarction following coronary angioplasty and stenting.

    PubMed

    Resnic, F S; Popma, J J; Ohno-Machado, L

    2000-01-01

    Prior estimates of the risk death and myocardial infarction following percutaneous coronary intervention (PCI) may not be uniformly applicable due to recent significant changes in clinical practice. Accordingly, we studied 2,804 cases from January 1997 through February 1999, in order to develop risk models to predict death, and post-procedural myocardial infarction following PCI. Risk models were constructed using multivariate logistic regression, artificial neural networks and prognostic risk scoring systems. Composite logistic regression models and artificial neural networks performed similarly in predicting the risk of major acute complications (c-index for predicting death of 0.812 and 0.807, respectively). Risk scoring models, based on the composite logistic regression beta coefficients, performed only slightly worse (c-index death = 0.794). Risk score models appear to provide reasonable discrimination while offering the potential for simple clinical implementation in the estimation of the risk of death and myocardial infarction in interventional cardiology.

  11. Development and evaluation of models to predict death and myocardial infarction following coronary angioplasty and stenting.

    PubMed Central

    Resnic, F. S.; Popma, J. J.; Ohno-Machado, L.

    2000-01-01

    Prior estimates of the risk death and myocardial infarction following percutaneous coronary intervention (PCI) may not be uniformly applicable due to recent significant changes in clinical practice. Accordingly, we studied 2,804 cases from January 1997 through February 1999, in order to develop risk models to predict death, and post-procedural myocardial infarction following PCI. Risk models were constructed using multivariate logistic regression, artificial neural networks and prognostic risk scoring systems. Composite logistic regression models and artificial neural networks performed similarly in predicting the risk of major acute complications (c-index for predicting death of 0.812 and 0.807, respectively). Risk scoring models, based on the composite logistic regression beta coefficients, performed only slightly worse (c-index death = 0.794). Risk score models appear to provide reasonable discrimination while offering the potential for simple clinical implementation in the estimation of the risk of death and myocardial infarction in interventional cardiology. PMID:11079972

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

    PubMed

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

    2013-01-01

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

  13. Human heart valve-derived scaffold improves cardiac repair in a murine model of myocardial infarction

    PubMed Central

    Wan, Long; Chen, Yao; Wang, Zhenhua; Wang, Weijun; Schmull, Sebastian; Dong, Jun; Xue, Song; Imboden, Hans; Li, Jun

    2017-01-01

    Cardiac tissue engineering using biomaterials with or without combination of stem cell therapy offers a new option for repairing infarcted heart. However, the bioactivity of biomaterials remains to be optimized because currently available biomaterials do not mimic the biochemical components as well as the structural properties of native myocardial extracellular matrix. Here we hypothesized that human heart valve-derived scaffold (hHVS), as a clinically relevant novel biomaterial, may provide the proper microenvironment of native myocardial extracellular matrix for cardiac repair. In this study, human heart valve tissue was sliced into 100 μm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function and reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first clinically relevant evidence for translating the hHVS-based biomaterials into clinical strategies to treat myocardial infarction. PMID:28051180

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

    PubMed Central

    Lo, Eng H.

    2015-01-01

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

  15. 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

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

    PubMed Central

    Correa, Edgar; Martinez, Braulio

    2014-01-01

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

  17. 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.

  18. Comparison of two preclinical myocardial infarct models: coronary coil deployment versus surgical ligation

    PubMed Central

    2014-01-01

    Background Despite recent advances, myocardial infarction (MI) remains the leading cause of death worldwide. Pre-clinical animal models that closely mimic human MI are pivotal for a quick translation of research and swine have similarities in anatomy and physiology. Here, we compared coronary surgical ligation versus coil embolization MI models in swine. Methods Fifteen animals were randomly distributed to undergo surgical ligation (n = 7) or coil embolization (n = 8). We evaluated infarct size, scar fibrosis, inflammation, myocardial vascularization, and cardiac function by magnetic resonance imaging (MRI). Results Thirty-five days after MI, there were no differences between the models in infarct size (P = 0.53), left ventricular (LV) ejection fraction (P = 0.19), LV end systolic volume (P = 0.22), LV end diastolic volume (P = 0.84), and cardiac output (P = 0.89). Histologically, cardiac scars did not differ and the collagen content, collagen type I (I), collagen type III (III), and the I/III ratio were similar in both groups. Inflammation was assessed using specific anti-CD3 and anti-CD25 antibodies. There was similar activation of inflammation throughout the heart after coil embolization (P = 0.78); while, there were more activated lymphocytes in the infarcted myocardium in the surgical occlusion model (P = 0.02). Less myocardial vascularization in the infarction areas compared with the border and remote zones only in coil embolization animals was observed (P = 0.004 and P = 0.014, respectively). Conclusions Our results support that surgical occlusion and coil embolization MI models generate similar infarct size, cardiac function impairment, and myocardial fibrosis; although, inflammation and myocardial vascularization levels were closer to those found in humans when coil embolization was performed. PMID:24885652

  19. Sonographic parenchymal and brain perfusion imaging: preliminary results in four patients following decompressive surgery for malignant middle cerebral artery infarct.

    PubMed

    Schlachetzki, F; Hoelscher, T; Dorenbeck, U; Greiffenberg, B; Marienhagen, J; Ullrich, O W; Bogdahn, U

    2001-01-01

    To investigate new methods of diagnostic transcranial sonography for brain parenchymal, vascular and perfusion imaging, we performed 3-D native tissue harmonic transcranial sonography (3D-nthTCS), 3-D transcranial color-coded duplex sonography (3D-TCCS), and "loss-of-correlation" imaging (LOC-TCCS) in four patients following early hemicraniectomy due to space-occupying "malignant" middle cerebral artery infarction (MMCAI). Three-dimensional datasets, utilizing 3D-nthTCS and 3D-TCCS, were created and up to 10 axial 2-D B-mode image planes, similar to CCT, reconstructed in each patient. Three-dimensional reconstructions of the circle of Willis documented one persistent carotid-T occlusion and three recanalizations of the MCA. LOC-TCCS, based on stimulated acoustic emission from an ultrasound (US) contrast agent, demonstrated a perfusion deficit in 2 of 3 patients, with regard to their infarcts. Concluding, 3D-nthTCS, 3D-TCCS and LOC-TCCS are promising tools for bedside monitoring, early prognosis and treatment evaluation for MMCAI in the postoperative period. Further studies should be performed to standardize these new methods and evaluate their applications through the intact calvarina.

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

    PubMed

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

    2012-11-01

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

  1. 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.

  2. Animal models of focal brain ischemia

    PubMed Central

    2009-01-01

    Stroke is a leading cause of disability and death in many countries. Understanding the pathophysiology of ischemic injury and developing therapies is an important endeavor that requires much additional research. Animal stroke models provide an important mechanism for these activities. A large number of stroke models have been developed and are currently used in laboratories around the world. These models are overviewed as are approaches for measuring infarct size and functional outcome. PMID:20150985

  3. Hierarchical Models in the Brain

    PubMed Central

    Friston, Karl

    2008-01-01

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

  4. Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE)

    PubMed Central

    Harding, Benjamin; Conception, Katherine; Li, Yong; Zhang, Lubo

    2016-01-01

    Hypoxic-ischemic encephalopathy (HIE) resulting from asphyxia in the peripartum period is the most common cause of neonatal brain damage and can result in significant neurologic sequelae, including cerebral palsy. Currently therapeutic hypothermia is the only accepted treatment in addition to supportive care for infants with HIE, however, many additional neuroprotective therapies have been investigated. Of these, glucocorticoids have previously been shown to have neuroprotective effects. HIE is also frequently compounded by infectious inflammatory processes (sepsis) and as such, the infants may be more amenable to treatment with an anti-inflammatory agent. Thus, the present study investigated dexamethasone and hydrocortisone treatment given after hypoxic-ischemic (HI) insult in neonatal rats via intracerebroventricular (ICV) injection and intranasal administration. In addition, we examined the effects of hydrocortisone treatment in HIE after lipopolysaccharide (LPS) sensitization in a model of HIE and sepsis. We found that dexamethasone significantly reduced rat brain infarction size when given after HI treatment via ICV injection; however it did not demonstrate any neuroprotective effects when given intranasally. Hydrocortisone after HI insult also significantly reduced brain infarction size when given via ICV injection; and the intranasal administration showed to be protective of brain injury in male rats at a dose of 300 µg. LPS sensitization did significantly increase the brain infarction size compared to controls, and hydrocortisone treatment after LPS sensitization showed a significant decrease in brain infarction size when given via ICV injection, as well as intranasal administration in both genders at a dose of 300 µg. To conclude, these results show that glucocorticoids have significant neuroprotective effects when given after HI injury and that these effects may be even more pronounced when given in circumstances of additional inflammatory injury, such

  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. Plasmodium vivax Malaria Presenting with Multifocal Hemorrhagic Brain Infarcts in a School-going Child.

    PubMed

    Rathia, Santosh Kumar; Sankar, Jhuma; Kandasamy, Devasenathipathy; Lodha, Rakesh

    2016-08-01

    Cerebral malaria is a well-known complication of Plasmodium falciparum malaria. Over recent years, however, Plasmodium vivax also has been reported to cause cerebral malaria with or without co-infection with P. falciparum Here, we report a boy aged 10 years presenting with acute febrile encephalopathy with raised intracranial pressure to the emergency, who was later diagnosed to have P. vivax malaria. His neurological status improved gradually during 6 weeks of pediatric intensive care unit stay. We report this case to highlight the unusual radiologic findings in the patient, such as multifocal hemorrhagic infarcts in the brainstem, bilateral thalami, frontal cortex and basal ganglia, which have not been reported with P. vivax malaria.

  7. 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

  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. Subacute Subclinical Brain Infarctions after Transcatheter Aortic Valve Implantation Negatively Impact Cognitive Function in Long-Term Follow-Up

    PubMed Central

    Schulze-Hagen, Leonie; Müller, Andreas; Wilsing, Marius; Sinning, Jan-Malte; Lütkens, Julian; Frerker, Christian; Kuck, Karl-Heinz; Gräff, Ingo; Schild, Hans; Werner, Nikos; Grube, Eberhard; Nickenig, Georg

    2017-01-01

    Aims To date every post-procedural cerebrovascular embolic event (CVE) is dreaded for its potential to accelerate cognitive decline after transcatheter aortic valve implantation (TAVI). This study differentiates the impact of acute (procedural) and post-acute cerebrovascular embolic events (CVEs) on cognitive performance. Methods Magnetic resonance imaging (MRI) before, early and late after TAVI was performed to quantify embolic burden. Quantification of diffusion- and T1-weighted lesions, as well as white-matter and total brain volumes, as well as cognitive function testing (MMSE) were assessed in 28 patients with a medium follow-up period of 34 months. Results Procedural diffusion-weighted lesions were observed in 17 patients (61%), but demonstrated locoregional remnants only in a minority of patients in long-term follow-up (6.5%). Acute CVEs did not impact the trajectory of late silent brain infarctions (SBI), white-matter hyperintensities, and cerebral atrophy. Functionally, early CVEs did not affect cognitive function. In contrast, patients with “new” SBIs after TAVI had a trend to cognitive deterioration in long-term follow-up (“new”SBI: MMSE -1.4 / no “new”SBI: MMSE +1.5, p = 0.067). Interestingly, only a fraction of these “new” SBIs evolved from procedural CVEs (22.2%). Conclusions Aquired SBIs after TAVI, but not DW-CVE per se are associated with functional impairment long-term after TAVI. In the context of subacute thrombosis seen in TAVI prostheses, these findings set the stage for tailored stroke prevention and comprehensive surrogate endpoint definitions in neuroprotective trials. PMID:28056466

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

    PubMed Central

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

    2015-01-01

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

  11. 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.

  12. Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats.

    PubMed

    Schwab, M; Antonow-Schlorke, I; Zwiener, U; Bauer, R

    1998-01-01

    The effects of brain-derived peptides (BDP; Cerebrolysin) upon the amount of brain injury due to focal brain ischemia were assessed. Male Thomae rats were divided randomly into a sham-operated group (n = 5), an ischemic control (untreated) group (n = 7) and an ischemic BDP-treated group (n = 6) and subjected to reversible middle cerebral artery occlusion (MCAO) for 2h followed by 90min of reperfusion. Local cortical blood flow (LCBF) was monitored by Laser-Doppler flowmetry to assess the MCAO and to measure the blood flow in regions peripheral to the infarction. Infarcted areas of the hippocampus and subcortical structures were quantified in hematoxylin and eosin (H&E) stainings. Functional disturbances of the neurons were detected by immunohistochemical staining of the microtubule associated protein MAP2. Moreover, brain edema was estimated morphometrically. LCBF was estimated from the periphery of infarcted areas and was reduced to 55 to 65% of baseline values (p < 0.05). Reperfusion led to LCBF being increased again to baseline values. No differences in LCBF between the control and the BDP-treated animals were found. In the hippocampus, BDP-treated animals showed a significant reduction of loss of MAP2 immunoreactivity in the subiculum and CA1 region by 59% and 64%, respectively, in comparison to control animals (p < 0.05). The amount of irreversibly damaged neurons in these regions was decreased in tendency. However, the inner blade of the dentate gyrus in BDP-treated animals showed a significant reduction of neuronal injury by 98% (p < 0.05). Likewise, BDP treatment reduced the size of the areas showing a loss of MAP2 immunoreactivity in the thalamic and hypothalamic structures by 51% and in the mesencephalon by 81% (p < 0.05). The size of the infarcted areas in these regions (H&E) was reduced in tendency. In the caudate putamen, no protective effect of BDP-treatment could be proven. Cerebral infarction was accompanied by an increase in the volume of the

  13. 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.

  14. High dose intracoronary N-acetylcysteine in a porcine model of ST-elevation myocardial infarction.

    PubMed

    Meyer, Markus; Bell, Stephen P; Chen, Zengyi; Nyotowidjojo, Iwan; Lachapelle, Richard R; Christian, Timothy F; Gibson, Pamela C; Keating, Friederike F; Dauerman, Harold L; LeWinter, Martin M

    2013-11-01

    We sought to evaluate the safety and efficacy of N-acetylcysteine (NAC) on ischemia and reperfusion in a pig model focusing on cardio-renal protection. High doses of NAC may provide protection from contrast induced nephropathy (CIN). NAC has also been demonstrated to reduce myocardial infarction size and improve left ventricular function after ischemia in both humans and animals studies. In this study we tested the safety and cardiorenal protective efficacy of intracoronary NAC delivered in the radiographic contrast agent in a pig model that simulates the catheter based reperfusion therapy of ST elevation myocardial infarctions. 27 pigs underwent 45 min of ischemia after surgical ligation of distal left descending coronary artery. With coronary reperfusion the animals received at total of 200 mL of the contrast agent Iopamidol with and without NAC to mimic radiographic contrast use during invasive reperfusion therapy. At 24 h the following endpoints were compared: LV function (MRI, echocardiography), myocardial injury (infarct size, area-at-risk, troponin, creatinine kinase) and CIN (creatinine, BUN and renal histology). The effects of NAC on platelet reactivity were also evaluated. Intracoronary administration of NAC administered in the contrast agent is safe. NAC reduces platelet reactivity and there was a trend towards a better cardiac function at 24 h. There was no significant difference in the size of the myocardial infarction. In this model of ischemia-reperfusion high dose NAC did not protect from CIN. High dose intracoronary NAC administered with the radiographic contrast is safe but does not provide significant cardio-renal protection.

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

    SciTech Connect

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

    2015-08-15

    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

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

    PubMed Central

    Muñetón-Gómez, Vilma C.; Doncel-Pérez, Ernesto; Fernandez, Ana P.; Serrano, Julia; Pozo-Rodrigálvarez, Andrea; Vellosillo-Huerta, Lara; Taylor, Julian S.; Cardona-Gómez, Gloria P.; Nieto-Sampedro, Manuel; Martínez-Murillo, Ricardo

    2012-01-01

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

  17. 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.

  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. Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction.

    PubMed

    Wang, Fengyue; Yang, Jing; Sun, Junfeng; Dong, Yanli; Zhao, Hong; Shi, Hui; Fu, Lu

    2015-05-01

    Testosterone can affect cardiovascular disease, but its effects on mitochondrial dynamics in the post-infarct myocardium remain unclear. To observe the effects of testosterone replacement, a rat model of castration-myocardial infarction (MI) was established by ligating the left anterior descending coronary artery 2 weeks after castration with or without testosterone treatment. Expression of mitochondrial fission and fusion proteins was detected by western blot and immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure, and ATP levels were also assessed. Compared with MI rats, castrated rats showed aggravated mitochondrial and myocardial insults, including mitochondrial swelling and disordered arrangement; loss of cristae, reduced mitochondrial length; decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function. Results of western blotting analyses indicated that castration downregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and mitofusin 2, but upregulated dynamin-related protein 1. The results were also supported by results obtained using immunofluorescence. However, these detrimental effects were reversed by testosterone supplementation, which also elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A. Thus, testosterone can protect mitochondria in the post-infarct myocardium, partly via the AMPK-PGC1A pathway, thereby decreasing mitochondrial dysfunction and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the results of ELISA analyses.

  20. Effects of xenon and isoflurane on apoptosis and inflammation in a porcine myocardial infarction model.

    PubMed

    Sopka, Sasa; Mertens, Christine; Roehl, Anna Bettina; Schiffl, Katharina; Rossaint, Rolf; Classen-Linke, Irmgard

    2013-03-01

    Volatile anaesthetics can reduce the infarction size in myocardial tissue when administered before and during experimentally induced ischaemia. The aim of this study was to investigate whether xenon is beneficial compared to isoflurane in limiting myocardial tissue apoptosis and inflammation induced by experimental ischaemia-reperfusion injury in a porcine right ventricular infarction model. Twenty-one animals used for this study randomly received isoflurane, xenon or thiopental, (n=6-8 per group). Myocardial infarction was induced for 90min, followed by reperfusion for 120min. Tissues from the left and right ventricles were removed from the sites of infarction, reperfusion and remote areas, and processed for immunohistochemistry. Apoptosis (caspase-3 staining) and neutrophilic infiltration (naphthol AS-D chloroacetate-specific esterase) were assessed and evaluated. Statistical analysis was performed using an ANOVA of repeated measures. Density of apoptotic cells were higher in tissues from animals that were anesthetized with xenon. This effect was significant in comparison to isoflurane (p=0.0177). Neutrophilic infiltration was significantly higher in the right compared to the left ventricle (p<0.001), whereas no significant differences in the number of granulocytes based on the anaesthetic regime or the different tissue areas were found. We conclude that xenon, in the early phase of ischaemia and reperfusion, induces a significant increase in apoptosis compared to isoflurane. Therefore, clinical use of this anaesthetic in cardiocompromised patients should be taken with care until more long-term studies have been carried out. The increased neutrophilic infiltration in the right vs. the left ventricle indicates the right ventricle being more susceptible to ischaemia-reperfusion injury.

  1. Acute Multi-modal Neuroimaging in a Porcine Model of Endothelin-1-Induced Cerebral Ischemia: Defining the Acute Infarct Core.

    PubMed

    d'Esterre, Christopher D; Aviv, Richard I; Morrison, Laura; Fainardi, Enrico; Lee, Ting Yim

    2015-06-01

    In a porcine ischemic stroke model, we sought to compare the acute predicted infarct core volume (PIV) defined by CT perfusion (CTP)-hemodynamic parameters and MR-diffusion-weighted imaging (MR-DWI)/apparent diffusion coefficient (ADC), with the true infarct core volume (TIV) as defined by histology. Ten Duroc-cross pigs had a CTP scan prior to injection of endothelin-1 (ET-1) into the left striatum. CTP scans were used to monitor ischemic progression. A second dose of ET-1 was injected 2 h from the first injection. The animal was moved to a 3-T MRI scanner where DWI was performed. CTP imaging was acquired immediately after the MR imaging. Next, the brain was removed and stained with tetrazolium chloride (TTC). Linear regression and Bland-Altman plots were used to correlate the PIV measured by each imaging modality to that of the TIV from the histological gold standard. The CTP-cerebral blood flow (CBF) parameter had the highest R (2) value and slope closest to unity, while the CTP-cerebral blood volume (CBV) had the lowest R(2) value and slope furthest away from unity. The CTP-CBF • CBV product parameter had a higher R(2) value but lower slope than both MR parameers. The best Bland-Altman agreement was observed with the CTP-CBF parameter. PIV from MR-DWI, ADC, and CTP-CBF overestimated the TIV defined with histology. We show that the PIV defined with absolute gray and white matter CT-CBF thresholds correlates best with the TIV and is similar to both MR-DWI and ADC-defined PIVs. Further, the acute CBF • CBV mismatch may not indicate penumbral tissue in the acute stroke setting.

  2. A model for brain life history evolution.

    PubMed

    González-Forero, Mauricio; Faulwasser, Timm; Lehmann, Laurent

    2017-03-01

    Complex cognition and relatively large brains are distributed across various taxa, and many primarily verbal hypotheses exist to explain such diversity. Yet, mathematical approaches formalizing verbal hypotheses would help deepen the understanding of brain and cognition evolution. With this aim, we combine elements of life history and metabolic theories to formulate a metabolically explicit mathematical model for brain life history evolution. We assume that some of the brain's energetic expense is due to production (learning) and maintenance (memory) of energy-extraction skills (or cognitive abilities, knowledge, information, etc.). We also assume that individuals use such skills to extract energy from the environment, and can allocate this energy to grow and maintain the body, including brain and reproductive tissues. The model can be used to ask what fraction of growth energy should be allocated at each age, given natural selection, to growing brain and other tissues under various biological settings. We apply the model to find uninvadable allocation strategies under a baseline setting ("me vs nature"), namely when energy-extraction challenges are environmentally determined and are overcome individually but possibly with maternal help, and use modern-human data to estimate model's parameter values. The resulting uninvadable strategies yield predictions for brain and body mass throughout ontogeny and for the ages at maturity, adulthood, and brain growth arrest. We find that: (1) a me-vs-nature setting is enough to generate adult brain and body mass of ancient human scale and a sequence of childhood, adolescence, and adulthood stages; (2) large brains are favored by intermediately challenging environments, moderately effective skills, and metabolically expensive memory; and (3) adult skill is proportional to brain mass when metabolic costs of memory saturate the brain metabolic rate allocated to skills.

  3. 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.

  4. 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

  5. Rotating Frame Spin Lattice Relaxation in a Swine Model of Chronic, Left Ventricular Myocardial Infarction

    PubMed Central

    Witschey, Walter RT; Pilla, James J; Ferrari, Giovanni; Koomalsingh, Kevin; Haris, Mohammed; Hinmon, Robin; Zsido, Gerald; Gorman, Joseph H; Gorman, Robert C; Reddy, Ravinder

    2010-01-01

    T1ρ relaxation times were quantified in a swine model of chronic, left ventricular myocardial infarction. It was found that there were low frequency relaxation mechanisms that suppress endogenous contrast at low spin lock amplitudes and in T2-weighted images. A moderate amplitude spin locking pulse could overcome these relaxation mechanisms. Relaxation dispersion data was measured over a range of RF field amplitudes and a model was formulated to include dipole-dipole relaxation modulated by molecular rotation and an apparent exchange mechanism. These techniques may find some use in the clinic for the observation of chronic, left ventricular cardiac remodeling. PMID:20677236

  6. Personalised computational cardiology: Patient-specific modelling in cardiac mechanics and biomaterial injection therapies for myocardial infarction.

    PubMed

    Sack, Kevin L; Davies, Neil H; Guccione, Julius M; Franz, Thomas

    2016-11-01

    Predictive computational modelling in biomedical research offers the potential to integrate diverse data, uncover biological mechanisms that are not easily accessible through experimental methods and expose gaps in knowledge requiring further research. Recent developments in computing and diagnostic technologies have initiated the advancement of computational models in terms of complexity and specificity. Consequently, computational modelling can increasingly be utilised as enabling and complementing modality in the clinic-with medical decisions and interventions being personalised. Myocardial infarction and heart failure are amongst the leading causes of death globally despite optimal modern treatment. The development of novel MI therapies is challenging and may be greatly facilitated through predictive modelling. Here, we review the advances in patient-specific modelling of cardiac mechanics, distinguishing specificity in cardiac geometry, myofibre architecture and mechanical tissue properties. Thereafter, the focus narrows to the mechanics of the infarcted heart and treatment of myocardial infarction with particular attention on intramyocardial biomaterial delivery.

  7. A model for brain life history evolution

    PubMed Central

    Lehmann, Laurent

    2017-01-01

    Complex cognition and relatively large brains are distributed across various taxa, and many primarily verbal hypotheses exist to explain such diversity. Yet, mathematical approaches formalizing verbal hypotheses would help deepen the understanding of brain and cognition evolution. With this aim, we combine elements of life history and metabolic theories to formulate a metabolically explicit mathematical model for brain life history evolution. We assume that some of the brain’s energetic expense is due to production (learning) and maintenance (memory) of energy-extraction skills (or cognitive abilities, knowledge, information, etc.). We also assume that individuals use such skills to extract energy from the environment, and can allocate this energy to grow and maintain the body, including brain and reproductive tissues. The model can be used to ask what fraction of growth energy should be allocated at each age, given natural selection, to growing brain and other tissues under various biological settings. We apply the model to find uninvadable allocation strategies under a baseline setting (“me vs nature”), namely when energy-extraction challenges are environmentally determined and are overcome individually but possibly with maternal help, and use modern-human data to estimate model’s parameter values. The resulting uninvadable strategies yield predictions for brain and body mass throughout ontogeny and for the ages at maturity, adulthood, and brain growth arrest. We find that: (1) a me-vs-nature setting is enough to generate adult brain and body mass of ancient human scale and a sequence of childhood, adolescence, and adulthood stages; (2) large brains are favored by intermediately challenging environments, moderately effective skills, and metabolically expensive memory; and (3) adult skill is proportional to brain mass when metabolic costs of memory saturate the brain metabolic rate allocated to skills. PMID:28278153

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

    PubMed Central

    Pokreisz, Peter; Schnitzer, Jan E.

    2013-01-01

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

  9. Cerebral infarction in childhood bacterial meningitis.

    PubMed

    Snyder, R D; Stovring, J; Cushing, A H; Davis, L E; Hardy, T L

    1981-07-01

    Forty-nine children with complicated bacterial meningitis were studied. Thirteen had abnormalities on computed tomography compatible with the diagnosis of brain infarction; one had a brain biopsy with the histological appearance of infarction. Factors exist in childhood bacterial meningitis which are associated with the development of brain infraction.

  10. 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.

  11. 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

  12. Post-infarct sleep disruption and its relation to cardiac remodeling in a rat model of myocardial infarction.

    PubMed

    Aghajani, Marjan; Faghihi, Mahdieh; Imani, Alireza; Vaez Mahdavi, Mohammad Reza; Shakoori, Abbas; Rastegar, Tayebeh; Parsa, Hoda; Mehrabi, Saman; Moradi, Fatemeh; Kazemi Moghaddam, Ehsan

    2017-02-03

    Sleep disruption after myocardial infarction (MI) by affecting ubiquitin-proteasome system (UPS) is thought to contribute to myocardial remodeling and progressive worsening of cardiac function. The aim of current study was to test the hypothesis about the increased risk of developing heart failure due to experience of sleep restriction (SR) after MI. Male Wistar rats (n = 40) were randomly assigned to four experimental groups: (1) Sham, (2) MI, (3) MI and SR (MI + SR) (4) Sham and SR (Sham + SR). MI was induced by permanent ligation of left anterior descending coronary artery. Twenty-four hours after surgery, animals were subjected to chronic SR paradigm. Blood sampling was performed at days 1, 8 and 21 after MI for determination of serum levels of creatine kinase-MB (CK-MB), corticosterone, malondialdehyde (MDA) and nitric oxide (NO). Finally, at 21 days after MI, echocardiographic parameters and expression of MuRF1, MaFBx, A20, eNOS, iNOS and NF-kB in the heart were evaluated. We used H&E staining to detect myocardial hypertrophy. We found out that post infarct SR increased corticosterone levels. Our results highlighted deteriorating effects of post-MI SR on NO production, oxidative stress, and echocardiographic indexes (p < 0.05). Moreover, its detrimental effects on myocardial damage were confirmed by overexpression of MuRF1, MaFBx, iNOS and NF-kB (p < 0.001) in left ventricle and downregulation of A20 and eNOS (p < 0.05). Furthermore, histological examination revealed that experience of SR after MI increased myocardial diameter as compared to Sham subjects (p < 0.05). Our data suggest that SR after MI leads to an enlargement of the heart within 21 days, marked by an increase in oxidative stress and NO production as well as an imbalance in UPS that ultimately results in cardiac dysfunction and heart failure.

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

    PubMed

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

    2016-09-02

    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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

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

  16. 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

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

    NASA Astrophysics Data System (ADS)

    Liu, Feng; Xia, Ling; Zhang, Xin

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

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

    PubMed Central

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

    2013-01-01

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

  19. 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

    2016-09-06

    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

  20. Human recombinant relaxin reduces heart injury and improves ventricular performance in a swine model of acute myocardial infarction.

    PubMed

    Perna, Avio-Maria; Masini, Emanuela; Nistri, Silvia; Bani Sacchi, Tatiana; Bigazzi, Mario; Bani, Daniele

    2005-05-01

    This study shows that relaxin can be effective in the treatment of acute myocardial infarction. In a swine model of heart ischemia-reperfusion currently used to test cardiotropic drugs because of its similarities with human myocardial infarction, human recombinant relaxin (2.5 and 5 microg/kg body weight), given at reperfusion after a 30-min ischemia, markedly reduced the main serum markers of myocardial damage (myoglobin, CK-MB, and troponin T) and the metabolic and histopathologic parameters of myocardial inflammation and cardiomyocyte injury, resulting in overall improvement of ventricular performance (increased cardiac index) compared to the controls. These results provide a background for future clinical trials with human relaxin as adjunctive therapy to catheter-based coronary angioplasty in patients with acute myocardial infarction.

  1. Sector-Based Assessment of Infarct Size on Late-Gadolinium-Enhancement MRI in a Mouse Model of Acute Myocardial Infarction.

    PubMed

    Park, Cheongsoo; Park, Eun-Hye; Chang, Kiyuk; Hong, Kwan Soo

    2016-12-02

    Scoring of myocardial infarction (MI) disease extent in cardiac magnetic resonance (CMR) images has been generally presented in terms of area-based infarct size. However, gradual thinning of the infarcted wall and compensatory hypertrophy of the noninfarcted remote wall during left ventricular (LV) remodeling after MI complicate the accuracy of infarct size measurement. In this study, we measured and compared infarct sizes in mice on late gadolinium enhancement (LGE) images using area-, length-, and radial sector-based methods.MI was induced by permanent ligation of the left coronary artery (n = 6). LGE images were acquired 30 minutes after intravenous injection of Gd-DTPA-BMA. Percentages of infarct size (%Area, %Length, and %Sector) on the LGE images were calculated and compared with histological findings.Infarct sizes obtained by an area-based approach were smaller than those obtained by other measurements. The area-based approach underestimated infarct size compared with the length-based approach. Most infarct sizes measured by each method demonstrated a similar trend, with maximum values determined by sector-based measurements using a mean + SD threshold. Spearman's rank correlation coefficients indicated that the 3 measurements were strongly correlated (P < 0.05) to each other. Significant differences and trends were observed between sector-based infarct sizes with different thresholds when 16 or more sectors were used.In conclusion, our study demonstrated that methods used for the histological calculation of infarct size could be applied to CMR analysis. Moreover, our results showed a similar trend to histological assessment. Sector-based CMR approaches can be useful for infarct size measurement.

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

    PubMed Central

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

    2013-01-01

    Objectives Endothelial progenitor cells (EPCs) can be used to repair tissues after myocardial infarction (MI) but EPC activators have adverse reactions. Rehmannia glutinosa is a herb used in traditional Chinese medicine, which can promote bone-marrow proliferation and protect the ischemic myocardium. We investigated the effects of Rehmannia glutinosa extract (RGE) on EPCs in a rat model of MI. Methods A total of 120 male Wistar rats were randomized to 2 groups (n = 60 each) for treatment: high-dose RGE (1.5 g·kg−1·day−1 orally) for 8 weeks, then left anterior descending coronary artery ligation, mock surgery or no treatment, then RGE orally for 4 weeks; or normal saline (NS) as the above protocol. The infarct region of the left ventricle was assessed by serial sectioning and morphology. EPCs were evaluated by number and function. Protein and mRNA levels of CD133, vascular endothelial growth factor receptor 2 (VEGFR2), chemokine C-X-C motif receptor 4 (CXCR4), stromal cell–derived factor-1α (SDF-1α) were measured by immunohistochemistry, Western blot and quantitative PCR analysis. Results RGE significantly improved left ventricular function, decreased the ischemic area and the apoptotic index in the infarct myocardium, also decreased the concentration of serum cardiac troponin T and brain natriuretic peptide at the chronic stage after MI (from week 2 to week 4). RGE increased EPC number, proliferation, migration and tube-formation capacity. It was able to up-regulate the expression of angiogenesis-associated ligand/receptor, including CD133, VEGFR2 and SDF-1α/CXCR4. In vitro, the effect of RGE on SDF-1α/CXCR4 cascade was reversed by the CXCR4 specific antagonist AMD3100. Conclusion RGE may enhance the mobilization, migration and therapeutic angiogenesis of EPCs after MI by activating the SDF-1α/CXCR4 cascade. PMID:23349848

  3. Cardiac repair in a mouse model of acute myocardial infarction with trophoblast stem cells

    PubMed Central

    Li, Guannan; Chen, Jianzhou; Zhang, Xinlin; He, Guixin; Tan, Wei; Wu, Han; Li, Ran; Chen, Yuhan; Gu, Rong; Xie, Jun; Xu, Biao

    2017-01-01

    Various stem cells have been explored for the purpose of cardiac repair. However, any individual stem cell population has not been considered as the ideal source. Recently, trophoblast stem cells (TSCs), a newly described stem cell type, have demonstrated extensive plasticity. The present study evaluated the therapeutic effect of TSCs transplantation for heart regeneration in a mouse model of myocardial infarction (MI) and made a direct comparison with the most commonly used mesenchymal stem cells (MSCs). Transplantation of TSCs and MSCs led to a remarkably improved cardiac function in contrast with the PBS control, but only the TSCs exhibited the potential of differentiation into cardiomyocytes in vivo. In addition, a significantly high proliferation level of both transplanted stem cells and resident cardiomyocytes was observed in the TSCs group. These findings primary revealed the therapeutic potential of TSCs in transplantation therapy for MI. PMID:28295048

  4. Modelling Brain Temperature and Cerebral Cooling Methods

    NASA Astrophysics Data System (ADS)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2014-11-01

    Direct measurement of cerebral temperature is invasive and impractical meaning treatments for reduction of core brain temperature rely on predictive mathematical models. Current models rely on continuum equations which heavily simplify thermal interactions between blood and tissue. A novel two-phase 3D porous-fluid model is developed to address these limitations. The model solves porous flow equations in 3D along with energy transport equation in both the blood and tissue phases including metabolic generation. By incorporating geometry data extracted from MRI scans, 3D vasculature can be inserted into a porous brain structure to realistically represent blood distribution within the brain. Therefore, thermal transport and convective heat transfer of blood are solved by means of direct numerical simulations. In application, results show that external scalp cooling has a higher impact on both maximum and average core brain temperatures than previously predicted. Additionally, the extent of alternative treatment methods such as pharyngeal cooling and carotid infusion can be investigated using this model. Acknowledgement: EPSRC DTA.

  5. 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.

  6. Empirical Movement Models for Brain Computer Interfaces.

    PubMed

    Matlack, Charles; Chizeck, Howard; Moritz, Chet T

    2016-06-30

    For brain-computer interfaces (BCIs) which provide the user continuous position control, there is little standardization of performance metrics or evaluative tasks. One candidate metric is Fitts's law, which has been used to describe aimed movements across a range of computer interfaces, and has recently been applied to BCI tasks. Reviewing selected studies, we identify two basic problems with Fitts's law: its predictive performance is fragile, and the estimation of 'information transfer rate' from the model is unsupported. Our main contribution is the adaptation and validation of an alternative model to Fitts's law in the BCI context. We show that the Shannon-Welford model outperforms Fitts's law, showing robust predictive power when target distance and width have disproportionate effects on difficulty. Building on a prior study of the Shannon-Welford model, we show that identified model parameters offer a novel approach to quantitatively assess the role of controldisplay gain in speed/accuracy performance tradeoffs during brain control.

  7. Modeling brain disease in a dish: really?

    PubMed

    Marchetto, Maria C; Gage, Fred H

    2012-06-14

    Cellular programming and reprogramming technology (CPART) presents a novel approach for understanding disease progression and mechanism. In addition, CPART provides an innovative opportunity for developing diagnostic tools and novel drug candidates for therapy. In this Forum, we will discuss obstacles and solutions for modeling brain disease using CPART.

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

    PubMed Central

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

    2008-01-01

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

  9. 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.

  10. 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.

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

    PubMed

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

    2005-01-01

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

  12. Safety Evaluation of Sevoflurane as Anesthetic Agent in Mouse Model of Myocardial Ischemic Infarction.

    PubMed

    Cheng, Xiang; Hou, Jianglong; Liu, Jiaming; Sun, Xiaorong; Sheng, Qin; Han, Pengfei; Kang, Y James

    2017-04-01

    The selection of anesthetics for patients with myocardial infarction is critically challenging. Sevoflurane is a volatile anesthetic gradually used in recent years. The intraoperative hemodynamic stability of sevoflurane was supported by several studies with some suggestions for its use for patients with cardiac events. The present study was undertaken to investigate the effect of sevoflurane on mice with myocardial infarction to evaluate the safety issue of this agent for possible application in patients with myocardial infarction. Mice of 7-12 weeks old were subjected to left anterior descending artery ligation to introduce acute myocardial infarction. The effect of sevoflurane on the hemodynamics was examined in comparison with that of currently available agent etomidate at low and moderate doses. The results showed that sevoflurane caused unstable hemodynamic changes in mice with myocardial infarction at both low and moderate inhaled concentrations relative to low and moderate doses of etomidate. In addition, the relative safety margin estimated from therapeutic index was decreased by 50 % when sevoflurane was used for mice with myocardial infarction relative to control mice, but only decreased by 20 % for etomidate. These analyses indicate that in comparison with currently available agent etomidate, sevoflurane should not be applied to patients with myocardial infarction or other cardiac events.

  13. 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.

  14. 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

  15. The detection of surfactant proteins A, B, C and D in the human brain and their regulation in cerebral infarction, autoimmune conditions and infections of the CNS.

    PubMed

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

    2013-01-01

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

  16. Neurometric Modeling: Computational Modeling of Individual Brains

    DTIC Science & Technology

    2011-05-16

    Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 15. SUBJECT TERMS Neural networks, computational neuroscience, fMRI ...obtained using functional MRI. Algorithmic processing of these measurements can exploit a variety of statistical machine learning methods to... statistical machine learning methods to synthesize a new kind of neuro-cognitive model, which we call neurometric models. These executable models could be

  17. 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

  18. Development of a new model for acute myocardial infarction in rabbits

    PubMed Central

    TAN, Mei-Yun; XIA, Bo; XIAO, Zhun; FAN, Zhong-Wei; ZHOU, Hong; GUO, Xing; HUANG, Yong-Can

    2017-01-01

    The rabbit left anterior descending coronary artery is not macroscopically apparent; this often leads to failure in creation of an acute myocardial infarction (AMI) model. In order to devise a simple method with good reproducibility and high success rate for use as a rabbit AMI model, a new surgical technique was developed, in which the obtuse marginal (OM) branch of the left circumflex coronary artery was coagulated with an electric knife using a left parasternal approach. Four weeks after OM branch coagulation, an electrocardiogram (ECG), blood biochemistry analysis, echocardiographic measurements and pathologic analysis were performed. The left parasternal approach provided the surgeon clear visualization of the targeted blood vessel to accurately identify the proper site to occlude. The successful development of AMI was confirmed by ST segment elevation on the ECG, by high levels of AMI-related markers in blood samples, by cardiac functional damage reflected on echocardiographic images and by changes in pathological sections. Furthermore, an acceptable success rate and low mortality were achieved. Hence, this surgical technique was suggested to be a highly reliable and reproducible method to induce AMI in rabbits for the assessment of new therapeutic interventions or regenerative approaches. PMID:28111375

  19. 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.

  20. 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

  1. Comparison of the usefulness of Doppler-derived deceleration time versus plasma brain natriuretic peptide to predict left ventricular remodeling after mechanical revascularization in patients with ST-elevation acute myocardial infarction and left ventricular systolic dysfunction.

    PubMed

    Cerisano, Giampaolo; Pucci, Paolo Domenico; Valenti, Renato; Boddi, Vieri; Migliorini, Angela; Tommasi, Maria Silvia; Raspanti, Silvia; Parodi, Guido; Antoniucci, David

    2005-04-15

    The correlation between Doppler deceleration time (DT) and brain natriuretic peptide (BNP) and their predictive value for detecting left ventricular (LV) remodeling in patients who are treated with primary percutaneous intervention for infarction and LV dysfunction are unknown. Fifty-six patients (64 +/- 12 years of age; 11 women) who had a first ST-segment elevation myocardial infarction and systolic dysfunction that was successfully treated with direct primary coronary intervention underwent 2-dimensional Doppler echocardiographic and plasma BNP evaluation at days 1 and 3 and 1 and 6 months after the index infarction. Repeat coronary angiograms were obtained at 1 and 6 months. Because of previous consistent evidence, 3 days after the index infarction was the time point of comparison between BNP and DT values. Echocardiographic LV remodeling was defined as an increase in end-diastolic volume index above baseline values of 2 x SD. Ventricular remodeling occurred in 20 patients (36%). Multivariate analyses that included BNP level, Doppler DT, echocardiographic measurements of systolic function, peak creatine kinase, and anterior infarct location showed Doppler DT to be the only predictor of LV remodeling (odds ratio 0.963, 95% confidence interval 0.936 to 0.990, p = 0.008). The optimal cutoff for DT in the prediction of 6-month LV remodeling was <136 ms (sensitivity 75%, specificity 97%, accuracy 81%, area under receiver-operating characteristic curve 0.90). Thus, in patients who have a first ST-segment elevation myocardial infarction and LV systolic dysfunction that is successfully treated with primary percutaneous coronary intervention, Doppler-derived DT 3 days after index infarction is more effective than BNP level in detecting patients who are at higher risk for 6-month LV remodeling.

  2. 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

  3. Neurons containing Alz-50-immunoreactive granules around the cerebral infarction: evidence for the lysosomal degradation of altered tau in human brain?

    PubMed

    Ikeda, K; Akiyama, H; Arai, T; Kondo, H; Haga, C; Tsuchiya, K; Yamada, S; Murayama, S; Hori, A

    2000-04-28

    Little is known about the metabolic process of tau and tau-derived substances. Alz-50- and tau 2-immunoreactivities in intracellular granules of neurons were observed in regions surrounding infarcted foci in the human cerebral cortex. Ultrastructurally, these granules in the fresh infarcted region exhibited primary lysosome-like structures, while those in old infarctions were lipofuscin. These findings indicate that tau is metabolized within lysosomes in neurons damaged by ischemic injury in human cortical penumbra. Alz-50-positive granules were more prominent in fresh infarction than in old infarction. After undergoing degradation and modification, altered tau might remain, at least partially, in secondary lysosomes.

  4. Random Walks in Model Brain Tissue

    NASA Astrophysics Data System (ADS)

    Grinberg, Farida; Farrher, Ezequiel; Oros-Peusquens, Ana-Maria; Shah, N. Jon

    2011-03-01

    The propagation of water molecules in the brain and the corresponding NMR response are affected by many factors such as compartmentalization, restrictions and anisotropy imposed by the cellular microstructure. Interfacial interactions with cell membranes and exchange additionally come into play. Due to the complexity of the underlying factors, a differentiation between the various contributions to the average NMR signal in in vivo studies represents a difficult task. In this work we perform random-walk Monte Carlo simulations in well-defined model systems aiming at establishing quantitative relations between dynamics and microstructure. The results are compared with experimental data obtained for artificial anisotropic model systems.

  5. Statistical shape modeling of the left ventricle: myocardial infarct classification challenge.

    PubMed

    Suinesiaputra, Avan; Ablin, Pierre; Alba, Xenia; Alessandrini, Martino; Allen, Jack; Bai, W; Cimen, Serkan; Claes, Peter; Cowan, Brett R; D'hooge, Jan; Duchateau, Nicolas; Ehrhardt, Jan; Frangi, Alejandro F; Gooya, Ali; Grau, Vicente; Lekadir, Karim; Lu, Allen; Mukhopadhyay, Anirban; Oksuz, Ilkay; Pennec, Xavier; Pereanez, Marco; Pinto, Catarina; Piras, Paolo; Rohe, Marc-Michel; Rueckert, Daniel; Sermesant, Maxime; Siddiqi, Kaleem; Tabassian, Mahdi; Teresi, Luciano; Tsaftaris, Sotirios A; Wilms, Matthias; Young, Alistair A; Zhang, Xingyu; Medrano-Gracia, Pau

    2017-01-17

    Statistical shape modeling is a powerful tool for visualizing and quantifying geometric and functional patterns of the heart. After myocardial infarction (MI), the left ventricle typically remodels in response to physiological challenges. Several methods have been proposed in the literature to describe statistical shape changes. Which method best characterizes left ventricular remodeling after MI is an open research question. A better descriptor of remodeling is expected to provide a more accurate evaluation of disease status in MI patients. We therefore designed a challenge to test shape characterization in MI given a set of three-dimensional left ventricular surface points. The training set comprised 100 MI patients, and 100 asymptomatic volunteers (AV). The challenge was initiated in 2015 at the Statistical Atlases and Computational Models of the Heart workshop, in conjunction with the MICCAI conference. The training set with labels was provided to participants, who were asked to submit the likelihood of MI from a different (validation) set of 200 cases (100 AV and 100 MI). Sensitivity, specificity, accuracy and area under the receiver operating characteristic curve were used as the outcome measures. The goals of this challenge were to (1) establish a common dataset for evaluating statistical shape modeling algorithms in MI, and (2) test whether statistical shape modeling provides additional information characterizing MI patients over standard clinical measures. Eleven groups with a wide variety of classification and feature extraction approaches participated in this challenge. All methods achieved excellent classification results with accuracy ranges from 0.83 to 0.98. The areas under the receiver operating characteristic curves were all above 0.90. Four methods showed significantly higher performance than standard clinical measures. The dataset and software for evaluation are available from the Cardiac Atlas Project website1.

  6. Endothelial Progenitor Cells Physiology and Metabolic Plasticity in Brain Angiogenesis and Blood-Brain Barrier Modeling

    PubMed Central

    Malinovskaya, Natalia A.; Komleva, Yulia K.; Salmin, Vladimir V.; Morgun, Andrey V.; Shuvaev, Anton N.; Panina, Yulia A.; Boitsova, Elizaveta B.; Salmina, Alla B.

    2016-01-01

    Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB) development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons). Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis. Deciphering endothelial progenitor cells physiology would provide novel engineering approaches to establish adequate microfluidically-supported BBB models and brain microphysiological systems for translational studies. PMID:27990124

  7. 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

  8. 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.

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

    PubMed Central

    2012-01-01

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

  10. 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.

  11. 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

  12. Modeling the brain with laser diodes

    NASA Astrophysics Data System (ADS)

    McAulay, Alastair D.

    2007-09-01

    The Wilson-Cowan mathematical model is popular for representing a neuron in the brain and may be viewed as two cross-coupled dynamical nonlinear neural networks, one excitatory and one inhibitory. This gives rise to two coupled first order equations. Varying an input parameter, the sum of input intensities from all other incoming neurons, causes the Wilson-Cowan neural oscillator to move through a supercritical Hopf bifurcation so as to switch its output from a stable-off when the input is below a firing threshold to a stable-oscillation (limit cycle) for signals above the threshold; the frequency of which depends on the level of input stimulation. The use of frequency to represent pulse rate makes the brain robust against electromagnetic interference and drift. We show that the laser diode rate equations for a single optically injected laser diode can also be modeled by two coupled first order equations that give rise to supercritical Hopf bifurcations. But the laser rate equations have a complex variable where that for the Wilson-Cowan model equations is real. By using the real part of the complex variable (a projection onto the real plane), the optically injected laser diode can exactly simulate the movement through supercritical Hopf bifurcation of the Wilson-Cowan equations by varying the amplitude and frequency of the optical injection.

  13. 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.

  14. Animal models of traumatic brain injury

    PubMed Central

    Xiong, Ye; Mahmood, Asim; Chopp, Michael

    2014-01-01

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

  15. 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.

  16. Causal linear parametric model for baroreflex gain assessment in patients with recent myocardial infarction.

    PubMed

    Nollo, G; Porta, A; Faes, L; Del Greco, M; Disertori, M; Ravelli, F

    2001-04-01

    Spectral and cross-spectral analysis of R-R interval and systolic arterial pressure (SAP) spontaneous fluctuations have been proposed for noninvasive evaluation of baroreflex sensitivity (BRS). However, results are not in good agreement with clinical measurements. In this study, a bivariate parametric autoregressive model with exogenous input (ARXAR model), able to divide the R-R variability into SAP-related and -unrelated parts, was used to quantify the gain (alpha(ARXAR)) of the baroreflex regulatory mechanism. For performance assessing, two traditional noninvasive methods based on frequency domain analysis [spectral, baroreflex gain by autogressive model (alpha(AR)); cross-spectral, baroreflex gain by bivariate autoregressive model (alpha(2AR))] and one based on the time domain [baroreflex gain by sequence analysis (alpha(SEQ))] were considered and compared with the baroreflex gain by phenylephrine test (alpha(PHE)). The BRS evaluation was performed on 30 patients (61 +/- 10 yr) with recent (10 +/- 3 days) myocardial infarction. The ARXAR model allowed dividing the R-R variability (950 +/- 1,099 ms(2)) into SAP-related (256 +/- 418 ms(2)) and SAP-unrelated (694 +/- 728 ms(2)) parts. alpha(AR) (12.2 +/- 6.1 ms/mmHg) and alpha(2AR) (8.9 +/- 5.6 ms/mmHg) as well as alpha(SEQ) (12.6 +/- 7.1 ms/mmHg) overestimated BRS assessed by alpha(PHE) (6.4 +/- 4.7 ms/mmHg), whereas the ARXAR index gave a comparable value (alpha(ARXAR) = 5.4 +/- 3.3 ms/mmHg). All noninvasive methods were significantly correlated to alpha(PHE) (alpha(ARXAR) and alpha(SEQ) were more correlated than the other indexes). Thus the baroreflex gain obtained describing the causal dependence of R-R interval on SAP showed a good agreement with alpha(PHE) and may provide additional information regarding the gain estimation in the frequency domain.

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

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

  18. 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

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

    PubMed Central

    He, Zhan-ping; Lu, Hong

    2015-01-01

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

  20. Adenosine receptor expression in an experimental animal model of myocardial infarction with preserved left ventricular ejection fraction.

    PubMed

    Cabiati, Manuela; Martino, Alessandro; Mattii, Letizia; Caselli, Chiara; Prescimone, Tommaso; Lionetti, Vincenzo; Morales, Maria-Aurora; Del Ry, Silvia

    2014-07-01

    Adenosine, a purine nucleoside and a "retaliatory metabolite" in ischemia, is ubiquitous in the body and increases 100-fold during ischemia. Its biological actions are mediated by four adenosine receptors (ARs): A(1), A(2A), A(2B) and A(3). The aim of this study was to determine possible myocardial alterations in AR expression in an experimental animal model of myocardial infarction (MI) with a preserved left ventricular (LV) ejection fraction. LV tissue was collected from sexually mature male farm pigs with MI (n = 6) induced by permanent surgical ligation of the left anterior descending coronary artery and from five healthy pigs (C). mRNA expression of A(1)R, A(2A)R, A(2B)R, A(3)R and TNF-α was determined by real-time PCR in tissue collected from border (BZ) and remote zones (RZ) of the infarcted area and from LV of C. BZ, RZ and samples of C were stained immunohistochemically to investigate A(3)R immunoreaction. After 4 weeks a different regulation of ARs was observed. A(1)R mRNA expression was significantly lower in the infarct regions than in controls (C = 0.75 ± 0.2, BZ = 0.05 ± 0.2, RZ = 0.07 ± 0.02 p = 0.0025, p = 0.0016, C vs. BZ and RZ, respectively). Conversely A(3)R was higher in infarct areas (C = 0.94 ± 0.2, BZ = 2.85 ± 0.5, RZ = 3.48 ± 1.0, p = 0.048 C vs. RZ). No significant differences were observed for A(2A)R (C = 1.58 ± 0.6, BZ = 0.42 ± 0.1, RZ = 1.37 ± 0.6) and A(2B)R (C = 1.66 ± 0.2, BZ = 1.54 ± 0.5, RZ = 1.25 ± 0.4). A(3)R expression was confirmed by immunohistochemical analysis and was principally localized in cardiomyocytes. TNF-α mRNA results were: C 0.41 ± 0.25; BZ 1.60 ± 0.19; RZ 0.17 ± 0.04. The balance between A(1)R and A(3)R as well as between A(2A)R and A(2B)R was consistent with adaptative retaliatory anti-ischemic adenosinergic changes in the infarcted heart with preserved LV function.

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

    PubMed

    Han, Shihui; Ma, Yina

    2015-11-01

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

  2. 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.

  3. In-vivo MRI and in-vivo electro-anatomical voltage map characteristics of infarct heterogeneity in a swine model.

    PubMed

    Shokrollahi, E; Pop, M; Safri, M; Yang, Y; Radau, P E; Barry, J; Detsky, J; Griffin, G H; Crystal, E; Wright, G A

    2011-01-01

    The arrhythmogenic substrate in patients with prior myocardial infarct (MI) is located at the border zone, BZ. In this study we correlated the BZ identified by two methods: electro-anatomical voltage mapping (EAVM) and a novel MRI method, multi-contrast late enhancement (MCLE). A pre-clinical porcine model with chronic MI was used to characterize BZ via MRI and EAVM. Results focus on the comparison between scar percentage and BZ percentage identified by each method. The correlation coefficient for BZ percentage between the two methods was 0.74 with a p-value of less the 0.0001. Bland-Altman plots were also used to compare between the two methods (slope of 0.83 ± 0.045). For a case of subtle infarct, there was only 1.3% infarct identified on EAVM compared to 22.2% on the corresponding slice on MCLE. The percentage of infarct on MCLE in subtle infarct does not relate to percentage of infarct in EAVM. Future registration between T(1) maps and EAVM will permit a quantitative comparison of MRI and EAVM measures.

  4. Caudate infarcts.

    PubMed

    Caplan, L R; Schmahmann, J D; Kase, C S; Feldmann, E; Baquis, G; Greenberg, J P; Gorelick, P B; Helgason, C; Hier, D B

    1990-02-01

    Eighteen patients had caudate nucleus infarcts (10 left-sided; 8 right-sided). Infarcts extended into the anterior limb of the internal capsule in 9 patients, and also the anterior putamen in 5 patients. Thirteen patients had motor signs, most often a slight transient hemiparesis. Dysarthria was common (11 patients). Cognitive and behavioral abnormalities were frequent, and included abulia (10 patients), agitation and hyperactivity (7 patients), contralateral neglect (3 patients, all right caudate), and language abnormalities (2 patients, both left caudate). The majority of patients had risk factors for penetrating artery disease. Branch occlusion of Heubner's artery, or perforators from the proximal anterior or middle cerebral arteries were the posited mechanism of infarction.

  5. The site of embolization related to infarct size, oedema and clinical outcome in a rat stroke model - further translational stroke research

    PubMed Central

    2010-01-01

    Background and purpose Reliable models are essential for translational stroke research to study the pathophysiology of ischaemic stroke in an effort to find therapies that may ultimately reduce oedema, infarction and mortality in the clinic. The purpose of this study was to investigate the relation between the site of arterial embolization and the subsequent oedema, infarction and clinical outcome in a rat embolic stroke model. Methods Thirty-six male Sprague-Dawley rats were thromboembolized into the internal carotid artery. The site of occlusion was demonstrated by arteriography. Following histological preparation and evaluation, the size of the hemispheres and the infarcts were measured by quantitative histology and planimetry. Another parallel stroke model study was subsequently examined to investigate if the conclusions from the first study could be applied to the second study. Results The median size of the infarct was 40% of the ipsilateral hemisphere in both the 19 animals with occlusion localised to the intracranial part of the internal carotid artery and in the 11 animals where the main trunk of the middle cerebral artery was occluded. In 5 animals, occlusion of the extracranial part of the internal carotid artery resulted in significantly smaller infarcts compared to other groups (p < 0.01). Another independent study re-confirmed these results. Furthermore, significant correlations (R > 0.76, p < 0.0001) were found between 1) cortical, subcortical, and total infarct volumes, 2) oedema in percent of the left hemisphere, 3) clinical score before termination and 4) postoperative weight loss. Conclusions Distal occlusions of the intracranial part of the internal carotid or middle cerebral arteries resulted in comparable large sized infarctions and oedema. This indicates that investigators do not need a similar number of such occlusions in each experimental group. Contrary to observations in the clinic, distal internal carotid artery occlusions did not result

  6. 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

  7. 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

    2016-02-11

    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.

  8. Pretreatment with Ginseng Fruit Saponins Affects Serotonin Expression in an Experimental Comorbidity Model of Myocardial Infarction and Depression

    PubMed Central

    Liu, Mei-Yan; Ren, Yan-Ping; Zhang, Li-Jun; Ding, Jamie Y.

    2016-01-01

    We previously demonstrated that serotonin (5-HT) and 5-HT2A receptor (5-HT2AR) levels in platelets were up- or down-regulated after myocardial infarction (MI) associated with depression. In this study, we further evaluated the effects of pretreatment with ginseng fruit saponins (GFS) on the expression of 5-HT and 5-HT2AR in MI with or without depression. Eighty Sprague-Dawley (SD) rats were treated with saline and GFS (n=40 per group). The animals were then randomly divided into four subgroups: sham, MI, depression, and MI + depression (n=10 per subgroup). Protein levels of 5-HT and 5-HT2AR in the serum, platelets and brain tissues were determined with ELISA. The results demonstrated that serum 5-HT levels was significantly increased by GFS pretreatment in all subgroups (except the sham subgroup) when compared with saline-treated counterparts (p<0.01). In platelets, GFS pretreatment significantly increased 5-HT levels in all subgroups when compared with their respective saline-treated counterparts (p<0.01). Brain 5-HT levels also declined with GFS pretreatment in the MI-only and depression-only subgroups (p<0.05 vs. saline pretreatment). With respect to 5-HT2AR levels, platelet 5-HT2AR was decreased in GFS pretreated MI, depression and MI + depression subgroups (p<0.01 vs. saline pretreatment). Similarly, brain 5-HT2AR levels decreased in all four subgroups pretreated with GFS (p<0.01 vs. saline pretreatment). We conclude that GFS plays a clear role in modulating 5-HT and 5-HT2AR expressions after MI and depression. Although the effects of GFS on brain 5-HT remain to be elucidated, its therapeutic potential for comorbidities of acute cardiovascular events and depression appears to hold much promise. PMID:28053817

  9. 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

  10. [Ventricular "remodeling" after myocardial infarction].

    PubMed

    Cohen-Solal, A; Himbert, D; Guéret, P; Gourgon, R

    1991-06-01

    Cardiac failure is the principal medium-term complication of myocardial infarction. Changes in left ventricular geometry are observed after infarction, called ventricular remodeling, which, though compensatory initially, cause ventricular failure in the long-term. Experimental and clinical studies suggest that early treatment by coronary recanalisation, trinitrin and angiotensin converting enzyme inhibitors may prevent or limit the expansion and left ventricular dilatation after infarction, so improving ventricular function, and, at least in the animal, reduce mortality. Large scale trials with converting enzyme inhibitors are currently under way to determine the effects of this new therapeutic option. It would seem possible at present, independently of any reduction in the size of the infarction, to reduce or delay left ventricular dysfunction by interfering with the natural process of dilatation and ventricular modeling after infarction.

  11. Mathematical modeling of human brain physiological data

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  12. 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.

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

    PubMed

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

    2016-01-01

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

  14. Correlation of Scar in Cardiac MRI and High‐Resolution Contact Mapping of Left Ventricle in a Chronic Infarct Model

    PubMed Central

    THAJUDEEN, ANEES; STEWART, BRIAN; COKIC, IVAN; NAKAGAWA, HIROSHI; SHEHATA, MICHAEL; AMORN, ALLEN M.; KALI, AVINASH; LIU, EZH; HARLEV, DORON; BENNETT, NATHAN; DHARMAKUMAR, ROHAN; CHUGH, SUMEET S.; WANG, XUNZHANG

    2015-01-01

    Background Endocardial mapping for scars and abnormal electrograms forms the most essential component of ventricular tachycardia ablation. The utility of ultra‐high resolution mapping of ventricular scar was assessed using a multielectrode contact mapping system in a chronic canine infarct model. Methods Chronic infarcts were created in five anesthetized dogs by ligating the left anterior descending coronary artery. Late gadolinium‐enhanced magnetic resonance imaging (LGE MRI) was obtained 4.9 ± 0.9 months after infarction, with three‐dimensional (3D) gadolinium enhancement signal intensity maps at 1‐mm and 5‐mm depths from the endocardium. Ultra‐high resolution electroanatomical maps were created using a novel mapping system (Rhythmia Mapping System, Rhythmia Medical/Boston Scientific, Marlborough, MA, USA) Rhythmia Medical, Boston Scientific, Marlborough, MA, USA with an 8.5F catheter with mini‐basket electrode array (64 tiny electrodes, 2.5‐mm spacing, center‐to‐center). Results The maps contained 7,754 ± 1,960 electrograms per animal with a mean resolution of 2.8 ± 0.6 mm. Low bipolar voltage (<2 mV) correlated closely with scar on the LGE MRI and the 3D signal intensity map (1‐mm depth). The scar areas between the MRI signal intensity map and electroanatomic map matched at 87.7% of sites. Bipolar and unipolar voltages, compared in 592 electrograms from four MRI‐defined scar types (endocardial scar, epicardial scar, mottled transmural scar, and dense transmural scar) as well as normal tissue, were significantly different. A unipolar voltage of <13 mV correlated with transmural extension of scar in MRI. Electrograms exhibiting isolated late potentials (ILPs) were manually annotated and ILP maps were created showing ILP location and timing. ILPs were identified in 203 ± 159 electrograms per dog (within low‐voltage areas) and ILP maps showed gradation in timing of ILPs at different locations in the scar. Conclusions Ultra

  15. Infarct density distribution by MRI in the porcine model of acute and chronic myocardial infarction as a potential method transferable to the clinic.

    PubMed

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

    2014-06-01

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

  16. Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

    PubMed

    Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

    2009-01-01

    This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

  17. Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model

    PubMed Central

    Das, Hiranmoy; George, Jon C.; Joseph, Matthew; Das, Manjusri; Abdulhameed, Nasreen; Blitz, Anna; Khan, Mahmood; Sakthivel, Ramasamy; Mao, Hai-Quan; Hoit, Brian D.; Kuppusamy, Periannan; Pompili, Vincent J.

    2009-01-01

    Background Therapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+/CD34+) genetically modified with VEGF plus PDGF genes (VIP). Methods and Findings Myocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue velocity, wall motion score index, strain and strain rate in animals treated with VEGF plus PDGF overexpressed stem cells (VIP) compared to nanofiber expanded cells (Exp), freshly isolated cells (FCB) or media control (Media). Improvement observed was as follows: VIP>Exp> FCB>media. Similar trend was noticed in the exercise capacity of rats on a treadmill. These findings correlated with significantly increased neovascularization in ischemic tissue and markedly reduced infarct area in animals in the VIP group. Stem cells in addition to their usual homing sites such as lung, spleen, bone marrow and liver, also migrated to sites of myocardial ischemia. The improvement of cardiac function correlated with expression of heart tissue connexin 43, a gap junctional protein, and heart tissue angiogenesis related protein molecules like VEGF, pNOS3, NOS2 and GSK3. There was no evidence of upregulation in the molecules of oncogenic potential in genetically modified or other stem cell therapy groups. Conclusion Regenerative therapy using nanofiber-expanded hematopoietic stem cells with overexpression of VEGF and PDGF has a favorable impact on the improvement of rat myocardial function accompanied by upregulation of tissue connexin 43 and pro-angiogenic molecules after infarction. PMID:19809493

  18. Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

    PubMed Central

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

    2014-01-01

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

  19. Effects of the TLR4 signaling pathway on apoptosis of neuronal cells in diabetes mellitus complicated with cerebral infarction in a rat model

    PubMed Central

    Li, Chao; Che, Li-He; Ji, Tie-Feng; Shi, Lei; Yu, Jin-Lu

    2017-01-01

    This study aims to explore the effects of the TLR4 signaling pathway on the apoptosis of neuronal cells in rats with diabetes mellitus complicated with cerebral infarction (DMCI). A DMCI model was established with 40 Sprague Dawley rats, which were assigned into blank, sham, DM + middle cerebral artery occlusion (MCAO) and DM + MCAO + TAK242 groups. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured. A TUNEL assay was applied for detecting cell apoptosis, and Western blotting was used for detecting the expression of TLR4, TNF-α, IL-1β and apoptosis-related proteins. Compared with the blank and sham groups, there was an increase in cell apoptosis, expression of Bcl-2, Bax, cleaved caspase-3, TNF-α, IL-1β and TLR4 proteins and MDA content and a decrease in SOD activity in the DM + MCAO and DM + MCAO + TAK242 groups. Compared with those in the DM + MCAO group, rats in the DM + MCAO + TAK242 group exhibited an increase in SOD activity and a decrease in cell apoptosis, expression of Bcl-2, Bax, cleaved caspase-3, TNF-α, IL-1β and TLR4 proteins and MDA content. Inhibition of the TLR4 signaling pathway reduces neuronal cell apoptosis and nerve injury to protect the brain. PMID:28272417

  20. 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.

  1. Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction.

    PubMed

    Park, Jae-Hyeong; Yoon, Jung Yeon; Ko, Seon Mi; Jin, Seon Ah; Kim, Jun Hyung; Cho, Chung-Hyun; Kim, Jin-Man; Lee, Jae-Hwan; Choi, Si Wan; Seong, In-Whan; Jeong, Jin Ok

    2011-08-31

    Cardiac lymphatic system in the remodeling after acute myocardial infarction (AMI) has been overlooked. We wanted to investigate the role of bone marrow-derived endothelial progenitor cells (EPCs) and their contribution to lymphatic distribution in myocardial remodeling after AMI. Mouse (C57bl/6J) MI models were created by ligation of the left anterior descending coronary artery and were treated with phosphate buffered saline (PBS) or EPCs. Real-time RT-PCR with 2- to 4-week myocardial tissue samples revealed that lymphangiogenetic factors such as vascular endothelial growth factor (VEGF)-C (8.5 fold, P < 0.05), VEGF-D (6.1 fold, P < 0.05), Lyve-1 (15 fold, P < 0.05), and Prox-1 (11 fold, P < 0.05) were expressed at significantly higher levels in the PBS group than the EPC group. The PBS group also showed a significantly higher density of lymphatic vessels in the peri-infarction area. Echocardiography showed that from 2 weeks after the treatment, left ventricle (LV) dimensions at both systole and diastole were significantly smaller in the EPC group than in the PBS group (P < 0.01) and LV fractional shortening was higher in the EPC group accordingly (P < 0.01). Lymphangiogenic markers increased in a mouse MI model. EPC transplantation decreased lymphangiogenesis and adverse ventricular remodeling after AMI. These novel findings suggest that new lymphatic vessels may be formed in severely damaged myocardium, and may be involved in adverse myocardial remodeling after AMI.

  2. 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.

  3. 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.

  4. Modeling Blast-Related Brain Injury

    DTIC Science & Technology

    2008-12-01

    02139 D. Moore Defense and Veterans Brain Injury Center (WRAMC) 6900 Georgia Ave. NW, Washington, DC 20307 L. Noels University of Liege Chemin des...chevreuils 1, B4000 Liege , Belgium ABSTRACT Recent military conflicts in Iraq and Afghanistan have highlighted the wartime effect of traumatic brain in

  5. Cilostazol protects the heart against ischaemia reperfusion injury in a rabbit model of myocardial infarction: focus on adenosine, nitric oxide and mitochondrial ATP-sensitive potassium channels.

    PubMed

    Bai, Yushan; Muqier; Murakami, Hiroya; Iwasa, Masamitsu; Sumi, Shohei; Yamada, Yoshihisa; Ushikoshi, Hiroaki; Aoyama, Takuma; Nishigaki, Kazuhiko; Takemura, Genzou; Uno, Bunji; Minatoguchi, Shinya

    2011-10-01

    1. The present study examined whether or not cilostazol reduces the myocardial infarct size, and investigated its mechanism in a rabbit model of myocardial infarction. 2. Japanese white rabbits underwent 30 min of coronary occlusion, followed by 48 h of reperfusion. Cilostazol (1 and 5 mg/kg) or vehicle was given intravenously 5 min before ischaemia. 8-p-sulfophenyl theophylline (8SPT; an adenosine receptor blocker, 7.5 mg/kg), Nω-nitro-L-arginine methylester (l-NAME; an NOS inhibitor, 10 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD; a mitochondrial ATP-sensitive potassium (KATP) channel blocker, 5 mg/kg) was given intravenously 5 min before cilostazol injection. Infarct size was determined as a percentage of the risk area. 3. The myocardial interstitial levels of adenosine and nitrogen oxide (NOx) during ischaemia and reperfusion, and the intensity of myocardial dihydroethidium staining were determined. 4. Infarct size was significantly reduced in the cilostazol 1 mg/kg (38.4% (2.9%)) and cilostazol 5 mg/kg (30.7% (4.7%)) groups compared with that in the control group (46.5% (4.2%)). The infarct size-reducing effect of cilostazol was completely abolished by 8SPT (46.6% (3.5%)), L-NAME (49.0% (5.5%)), or 5HD (48.5% (5.1%)). 8SPT, L-NAME or 5HD alone did not affect the infarct size. Cilostazol treatment significantly increased myocardial levels of adenosine and NOx during ischaemia, and attenuated the intensity of dihydroethidium staining during reperfusion. 5. These findings show that cilostazol reduces the myocardial infarct size by increasing adenosine and NOx levels, attenuating superoxide production and opening the mitochondrial KATP channels. Cilostazol might provide a new strategy for the treatment of coronary heart disease.

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

    PubMed Central

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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).

  16. 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).

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-08-01

    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.

  19. A Novel Three-Phase Model of Brain Tissue Microstructure

    PubMed Central

    Gevertz, Jana L.; Torquato, Salvatore

    2008-01-01

    We propose a novel biologically constrained three-phase model of the brain microstructure. Designing a realistic model is tantamount to a packing problem, and for this reason, a number of techniques from the theory of random heterogeneous materials can be brought to bear on this problem. Our analysis strongly suggests that previously developed two-phase models in which cells are packed in the extracellular space are insufficient representations of the brain microstructure. These models either do not preserve realistic geometric and topological features of brain tissue or preserve these properties while overestimating the brain's effective diffusivity, an average measure of the underlying microstructure. In light of the highly connected nature of three-dimensional space, which limits the minimum diffusivity of biologically constrained two-phase models, we explore the previously proposed hypothesis that the extracellular matrix is an important factor that contributes to the diffusivity of brain tissue. Using accurate first-passage-time techniques, we support this hypothesis by showing that the incorporation of the extracellular matrix as the third phase of a biologically constrained model gives the reduction in the diffusion coefficient necessary for the three-phase model to be a valid representation of the brain microstructure. PMID:18704170

  20. 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

  1. 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

  2. Development of a model for whole brain learning of physiology.

    PubMed

    Eagleton, Saramarie; Muller, Anton

    2011-12-01

    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 elaborates on these layers by relating the personality traits central to learning to the different quadrants of brain preference, as described by Neethling's brain profile, as the inner layer of the onion. This layer is encircled by the learning styles that describe different information-processing preferences for each brain quadrant. For the middle layer, the different stages of Kolb's learning cycle are classified into the four brain quadrants associated with the different brain processing strategies within the information processing circle. Each of the stages of Kolb's learning cycle is also associated with a specific cognitive learning strategy. These two inner circles are enclosed by the circle representing the role of the environment and instruction on learning. It relates environmental factors that affect learning and distinguishes between face-to-face and technology-assisted learning. This model informs on the design of instructional interventions for physiology to encourage whole brain learning.

  3. Clinical features of acute corpus callosum infarction patients

    PubMed Central

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

    2014-01-01

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

  4. 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.

  5. Anti-inflammatory and anti-thrombotic effects of zingerone in a rat model of myocardial infarction.

    PubMed

    Hemalatha, K L; Stanely Mainzen Prince, P

    2016-11-15

    Myocardial infarction continues to be a major public health problem. Reduction in mortality rate and prevention of myocardial infarction are of utmost importance. Inflammation and thrombosis play an important role in the pathogenesis of myocardial infarction. The anti-inflammatory and anti-thrombotic effects of zingerone were evaluated in isoproterenol induced myocardial infarcted rats. Rats were pretreated with zingerone (6mg/kg body weight) daily for 14 days and were then induced myocardial infarction with isoproterenol (100mg/kg body weight) on 15th and 16th day. Isoproterenol induced myocardial infarcted rats showed significant (P<0.05) increase in the levels/ activities of cardiac troponin-I (cTnI), high sensitive C-reactive protein (Hs CRP), lysosomal hydrolases in the serum and concentration of heart lysosomal lipid peroxidation (LPO) products. RT-PCR study revealed over expression of myocardial tumour necrosis factor - alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) genes in the myocardial infarcted rats. Histopathology of heart and coronary artery revealed marked inflammation and coronary thrombosis. Zingerone pretreatment significantly (P<0.05) decreased serum cTnI, Hs CRP, lysosomal hydrolases and heart lysosomal LPO and down regulated myocardial TNF-α, IL-1β and IL-6 genes and prevented coronary thrombosis in isoproterenol induced myocardial infarcted rats. The observed effects of zingerone could be attributed to its anti-inflammatory and anti-thrombotic properties.

  6. The Adult Göttingen Minipig as a Model for Chronic Heart Failure After Myocardial Infarction: Focus on Cardiovascular Imaging and Regenerative Therapies

    PubMed Central

    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

    2008-01-01

    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

  7. Cerebral organoids model human brain development and microcephaly.

    PubMed

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

    2013-09-19

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

  8. 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

  9. 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…

  10. 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.

  11. 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

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

    PubMed Central

    Barrett, H. Clark

    2012-01-01

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

  13. Neurodynamic models of brain in psychiatry.

    PubMed

    Freeman, Walter J

    2003-07-01

    The history of brain theory is described in terms of three kinds of theory of perception. The most widely used kind sees perception as dependent on passive inflow from the environment of information that is used to make and process representations of objects and events. A second kind views perception as an active search for information that is inherent in the environment and is extracted by tuned resonances in brain circuits. A third kind holds that perception works by the creation of information through chaotic dynamics by forming hypotheses about the environment, through which learning takes place. Experimental evidence for creative dynamics in brains is briefly sketched. The explanation is offered that brains, being finite systems, work this way in order to cope with the infinite complexity of the world. All that brains can know is the hypotheses they construct and the results of testing them by acting into the environment, and learning by assimilation from the sensory consequences of their actions. The process is described as intentionality. It works through the action-perception-assimilation cycle. The cost of this solution to the problem of infinite complexity by hypothesis testing is the progressive isolation of individuals, as they accumulate their unique experiences through which their personalities form. Socialization and the acquisition of shared knowledge requires the emergence of new personality structure by self-organization through chaotic dissolution of existing the structure, as a prelude to the creation of new traits, habits, and values. Dissolution works in a crisis situation by regression to earlier stages of development, from which a fresh start can be made. A state of malleability emerges in the depth of crisis, in which compassionate companions through loving care can invite cooperative actions. Joint actions support the growth of a new lifestyle based on trust. Socialization requires neurochemical mechanisms of affiliation and bonding that

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

    PubMed

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

    2013-03-01

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

  15. [Animal models of injury and repair in developing brain].

    PubMed

    Cuestas, Eduardo; Caceres, Alfredo; Palacio, Santiago

    2007-01-01

    Animal models of injury and repair in developing brain. Brain injury is a major contributor to neonatal morbidity and mortality, a considerable group of these children will develop long term neurological sequels. Despite the great clinical and social significance and the advances in neonatal medicine, no therapy yet does exist that prevent or decrease detrimental effects in cases of neonatal brain injury. Our objective was to review recent research in relation to the hypothesis for repair mechanism in the developing brain, based in animal models that show developmental compensatory mechanisms that promote neural and functional plasticity. A better understanding of these adaptive mechanisms will help clinicians to apply knowledge derived from animals to human clinical situations.

  16. Canine brain tumours: a model for the human disease?

    PubMed

    Hicks, J; Platt, S; Kent, M; Haley, A

    2017-03-01

    Canine brain tumours are becoming established as naturally occurring models of disease to advance diagnostic and therapeutic understanding successfully. The size and structure of the dog's brain, histopathology and molecular characteristics of canine brain tumours, as well as the presence of an intact immune system, all support the potential success of this model. The limited success of current therapeutic regimens such as surgery and radiation for dogs with intracranial tumours means that there can be tremendous mutual benefit from collaboration with our human counterparts resulting in the development of new treatments. The similarities and differences between the canine and human diseases are described in this article, emphasizing both the importance and limitations of canines in brain tumour research. Recent clinical veterinary therapeutic trials are also described to demonstrate the areas of research in which canines have already been utilized and to highlight the important potential benefits of translational research to companion dogs.

  17. Biothermal Model of Patient and Automatic Control System of Brain Temperature for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Wakamatsu, Hidetoshi; Gaohua, Lu

    Various surface-cooling apparatus such as the cooling cap, muffler and blankets have been commonly used for the cooling of the brain to provide hypothermic neuro-protection for patients of hypoxic-ischemic encephalopathy. The present paper is aimed at the brain temperature regulation from the viewpoint of automatic system control, in order to help clinicians decide an optimal temperature of the cooling fluid provided for these three types of apparatus. At first, a biothermal model characterized by dynamic ambient temperatures is constructed for adult patient, especially on account of the clinical practice of hypothermia and anesthesia in the brain hypothermia treatment. Secondly, the model is represented by the state equation as a lumped parameter linear dynamic system. The biothermal model is justified from their various responses corresponding to clinical phenomena and treatment. Finally, the optimal regulator is tentatively designed to give clinicians some suggestions on the optimal temperature regulation of the patient’s brain. It suggests the patient’s brain temperature could be optimally controlled to follow-up the temperature process prescribed by the clinicians. This study benefits us a great clinical possibility for the automatic hypothermia treatment.

  18. Intramyocardial Injection of Recombinant Adeno-Associated Viral Vector Coexpressing PR39/Adrenomedullin Enhances Angiogenesis and Reduces Apoptosis in a Rat Myocardial Infarction Model

    PubMed Central

    An, Rui; Xi, Cong; Xu, Jian; Liu, Ying; Zhang, Shumiao; Wang, Yuemin

    2017-01-01

    Cotransfer of angiogenic and antiapoptotic genes could be the basis of new gene therapy strategies for myocardial infarction. In this study, rAAV-PR39-ADM, coexpressing antimicrobial peptide (PR39) and adrenomedullin (ADM), was designed with the mediation of recombinant adeno-associated virus. In vitro, CRL-1730 cells were divided into four groups, namely, the sham group, the AAV-null group, the NS (normal saline) group, and the PR39-ADM group. Immunocytochemistry analysis, CCK-8 assays, Matrigel assays, and apoptotic analysis were performed; in vivo, myocardial infarction model was established through ligation of the left coronary artery on rats, and treatment groups corresponded to those used in vitro. Myocardial injury, cardiac performance, and the extent of myocardial apoptosis were assessed. Results suggested that rAAV-PR39-ADM administration after myocardial infarction improved cell viability and cardiac function, attenuated apoptosis and myocardial injury, and promoted angiogenesis. Subsequently, levels of 6×His, HIF-1α, VEGF, p-Akt, Akt, ADM, Bcl-2, and Bax were measured by western blot. rAAV-PR39-ADM increased p-Akt, HIF-1α, and VEGF levels and induced higher Bcl-2 expression and lower Bax expression. In conclusion, our results demonstrate that rAAV-PR39-ADM mitigates myocardial injury by promoting angiogenesis and reducing apoptosis. This study suggests a potential novel gene therapy-based method that could be used clinically for myocardial infarction. PMID:28348718

  19. Efficacy of cabazitaxel in mouse models of pediatric brain tumors

    PubMed Central

    Girard, Emily; Ditzler, Sally; Lee, Donghoon; Richards, Andrew; Yagle, Kevin; Park, Joshua; Eslamy, Hedieh; Bobilev, Dmitri; Vrignaud, Patricia; Olson, James

    2015-01-01

    Background There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors. Methods The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS-PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model. Results This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel. Conclusion These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors. PMID:25140037

  20. 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

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

    PubMed

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

    2006-11-01

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

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

    NASA Astrophysics Data System (ADS)

    Wang, Zhihui; Deisboeck, Thomas S.

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

  3. Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer-like brain amyloidosis

    PubMed Central

    Yao, Yuemang; Chinnici, Cinzia; Tang, Hanguan; Trojanowski, John Q; Lee, Virginia MY; Praticò, Domenico

    2004-01-01

    Background An increasing body of evidence implicates both brain inflammation and oxidative stress in the pathogenesis of Alzheimer's disease (AD). The relevance of their interaction in vivo, however, is unknown. Previously, we have shown that separate pharmacological targeting of these two components results in amelioration of the amyloidogenic phenotype of a transgenic mouse model of AD-like brain amyloidosis (Tg2576). Methods In the present study, we investigated the therapeutic effects of a combination of an anti-inflammatory agent, indomethacin, and a natural anti-oxidant, vitamin E, in the Tg2576 mice. For this reason, animals were treated continuously from 8 (prior to Aβ deposition) through 15 (when Aβ deposits are abundant) months of age. Results At the end of the study, these therapeutic interventions suppressed brain inflammatory and oxidative stress responses in the mice. This effect was accompanied by significant reductions of soluble and insoluble Aβ1-40 and Aβ1-42 in neocortex and hippocampus, wherein the burden of Aβ deposits also was significantly decreased. Conclusions The results of the present study support the concept that brain oxidative stress and inflammation coexist in this animal model of AD-like brain amyloidosis, but they represent two distinct therapeutic targets in the disease pathogenesis. We propose that a combination of anti-inflammatory and anti-oxidant drugs may be a useful strategy for treating AD. PMID:15500684

  4. Thermal imaging of brain tumors in a rat glioma model

    NASA Astrophysics Data System (ADS)

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

    2002-05-01

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

  5. Cognitive Models as Bridge between Brain and Behavior.

    PubMed

    Love, Bradley C

    2016-04-01

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

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

    PubMed

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

    2015-05-01

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

  7. Modeled estimates of myocardial infarction and venous thromboembolic disease in users of second and third generation oral contraceptives.

    PubMed

    Schwingl, P J; Shelton, J

    1997-03-01

    Consistent reports from several recent studies suggest that users of third generation oral contraceptives (OCs) containing gestodene and desogestrel may be at increased risk of venous thromboembolic disease (VTE). Paradoxically, other reports indicate that these users may be at decreased risk of acute myocardial infarction (MI) compared with users of second generation OCs. To determine whether the potentially increased risk of VTE would outweigh the potentially reduced risk of MI in users of third generation OCs, we conducted an analysis to quantify the trade-offs providers and users may be faced to make between these formulations. The baseline rates of VTE and MI among non-users were calculated using US data on incidence and mortality of these conditions and estimates of the proportion of women exposed to these formulations in the US. These were multiplied by relative risks published in recent studies on third generation progestins to produce age- and formulation-specific risks. Results indicate that there would be small differences in disease burden between users of second and third generation OCs under the model assumptions at younger ages. However, among women 35-44 years of age, modeling results indicate that the potentially decreased incidence of MI among users of third generation OCs more than offsets the potentially increased risk of VTE at this age.

  8. 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.

  9. 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

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

    PubMed

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

    2008-01-01

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

  11. Astrocyte Proliferation Following Stroke in the Mouse Depends on Distance from the Infarct

    PubMed Central

    Barreto, George E.; Sun, Xiaoyun; Xu, Lijun; Giffard, Rona G.

    2011-01-01

    Reactive gliosis is a hallmark of brain pathology and the injury response, yet the extent to which astrocytes proliferate, and whether this is central to astrogliosis is still controversial. We determined the fraction of mature astrocytes that proliferate in a mouse stroke model using unbiased stereology as a function of distance from the infarct edge. Cumulatively 11.1±1.2% of Aldh1l1+ astrocytes within 400 µm in the cortical penumbra incorporate BrdU in the first week following stroke, while the overall number of astrocytes does not change. The number of astrocytes proliferating fell sharply with distance with more than half of all proliferating astrocytes found within 100 µm of the edge of the infarct. Despite extensive cell proliferation primarily of microglia and neutrophils/monocytes in the week following stroke, few mature astrocytes re-enter cell cycle, and these are concentrated close to the infarct boundary. PMID:22132159

  12. Astrocyte proliferation following stroke in the mouse depends on distance from the infarct.

    PubMed

    Barreto, George E; Sun, Xiaoyun; Xu, Lijun; Giffard, Rona G

    2011-01-01

    Reactive gliosis is a hallmark of brain pathology and the injury response, yet the extent to which astrocytes proliferate, and whether this is central to astrogliosis is still controversial. We determined the fraction of mature astrocytes that proliferate in a mouse stroke model using unbiased stereology as a function of distance from the infarct edge. Cumulatively 11.1±1.2% of Aldh1l1(+) astrocytes within 400 µm in the cortical penumbra incorporate BrdU in the first week following stroke, while the overall number of astrocytes does not change. The number of astrocytes proliferating fell sharply with distance with more than half of all proliferating astrocytes found within 100 µm of the edge of the infarct. Despite extensive cell proliferation primarily of microglia and neutrophils/monocytes in the week following stroke, few mature astrocytes re-enter cell cycle, and these are concentrated close to the infarct boundary.

  13. 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

  14. Models for predicting blood-brain barrier permeation.

    PubMed

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

    2011-06-01

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

  15. 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

    Emmert, Maximilian Y; Weber, Benedikt; 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 1×10(5)-5×10(5) 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

  16. Cellular-based modeling of oscillatory dynamics in brain networks.

    PubMed

    Skinner, Frances K

    2012-08-01

    Oscillatory, population activities have long been known to occur in our brains during different behavioral states. We know that many different cell types exist and that they contribute in distinct ways to the generation of these activities. I review recent papers that involve cellular-based models of brain networks, most of which include theta, gamma and sharp wave-ripple activities. To help organize the modeling work, I present it from a perspective of three different types of cellular-based modeling: 'Generic', 'Biophysical' and 'Linking'. Cellular-based modeling is taken to encompass the four features of experiment, model development, theory/analyses, and model usage/computation. The three modeling types are shown to include these features and interactions in different ways.

  17. Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction.

    PubMed

    Lassen, Thomas Ravn; Nielsen, Jan Møller; Johnsen, Jacob; Ringgaard, Steffen; Bøtker, Hans Erik; Kristiansen, Steen Buus

    2017-05-01

    Left ventricular (LV) remodeling following a myocardial infarction (MI) involves formation of reactive oxygen species (ROS). Paroxetine, a selective serotonin reuptake inhibitor, has an antioxidant effect in the vascular wall. We investigated whether paroxetine reduces myocardial ROS formation and LV remodeling following a MI. In a total of 32 Wistar rats, MI was induced by a 30-min ligation of the left anterior descending artery followed by 7- or 28-day reperfusion. During the 28 days of reperfusion, LV remodeling was evaluated by magnetic resonance imaging (MRI) and echocardiography (n = 20). After 28 days of reperfusion, the susceptibility to ventricular tachycardia was evaluated prior to sacrifice and histological assessment of myocyte cross-sectional area, fibrosis, and presence of myofibroblasts. Myocardial ROS formation was measured with dihydroethidium after 7 days of reperfusion in separate groups (n = 12). Diastolic LV volume, evaluated by MRI (417 ± 60 vs. 511 ± 64 µL, p < 0.05), and echocardiography (515 ± 80 vs. 596 ± 83 µL, p < 0.05) as well as diastolic LV internal diameter evaluated with echocardiography (7.2 ± 0.6 vs. 8.1 ± 0.7 mm, p < 0.05) were lower in the paroxetine group than in controls. Furthermore, myocyte cross-sectional area was reduced in the paroxetine group compared with controls (277 ± 26 vs. 354 ± 23 mm(3), p < 0.05) and ROS formation was reduced in the remote myocardium (0.415 ± 0.19 normalized to controls, p < 0.05). However, no differences in the presence of fibrosis or myofibroblasts were observed. Finally, paroxetine reduced the susceptibility to ventricular tachycardia (induced in 2/11 vs. 6/8 rats, p < 0.05). Paroxetine treatment following MI decreases LV remodeling and susceptibility to arrhythmias, probably by reducing ROS formation.

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

    PubMed Central

    2013-01-01

    Cerebral small vessel disease (CSVD, cerebral microangiopathy) leads to dementia and stroke-like symptoms. Lacunes, white matter lesions (WML) and microbleeds are the main pathological correlates depicted in in-vivo imaging diagnostics. Early studies described segmental arterial wall disorganizations of small penetrating cerebral arteries as the most pronounced underlying histopathology of lacunes. Luminal narrowing caused by arteriolosclerosis was supposed to result in hypoperfusion with WML and infarcts. We have used the model of spontaneously hypertensive stroke-prone rats (SHRSP) for a longitudinal study to elucidate early histological changes in small cerebral vessels. We suggest that endothelial injuries lead to multiple sites with blood brain barrier (BBB) leakage which cause an ongoing damage of the vessel wall and finally resulting in vessel ruptures and microbleeds. These microbleeds together with reactive small vessel occlusions induce overt cystic infarcts of the surrounding parenchyma. Thus, multiple endothelial leakage sites seem to be the starting point of cerebral microangiopathy. The vascular system reacts with an activated coagulatory state to these early endothelial injuries and by this induces the formation of stases, accumulations of erythrocytes, which represent the earliest detectable histological peculiarity of small vessel disease in SHRSP. In this review we focus on the meaning of the BBB breakdown in CSVD and finally discuss possible consequences for clinicians. PMID:23497521

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

    PubMed Central

    Diedrichsen, Jörn

    2016-01-01

    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

  20. 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

  1. Transcranial current brain stimulation (tCS): models and technologies.

    PubMed

    Ruffini, Giulio; Wendling, Fabrice; Merlet, Isabelle; Molaee-Ardekani, Behnam; Mekonnen, Abeye; Salvador, Ricardo; Soria-Frisch, Aureli; Grau, Carles; Dunne, Stephen; Miranda, Pedro C

    2013-05-01

    In this paper, we provide a broad overview of models and technologies pertaining to transcranial current brain stimulation (tCS), a family of related noninvasive techniques including direct current (tDCS), alternating current (tACS), and random noise current stimulation (tRNS). These techniques are based on the delivery of weak currents through the scalp (with electrode current intensity to area ratios of about 0.3-5 A/m2) at low frequencies (typically < 1 kHz) resulting in weak electric fields in the brain (with amplitudes of about 0.2-2 V/m). Here we review the biophysics and simulation of noninvasive, current-controlled generation of electric fields in the human brain and the models for the interaction of these electric fields with neurons, including a survey of in vitro and in vivo related studies. Finally, we outline directions for future fundamental and technological research.

  2. 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.

  3. 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.

  4. The Specific Protein Kinase R (PKR) Inhibitor C16 Protects Neonatal Hypoxia-Ischemia Brain Damages by Inhibiting Neuroinflammation in a Neonatal Rat Model

    PubMed Central

    Xiao, Jinglei; Tan, Yongchang; Li, Yinjiao; Luo, Yan

    2016-01-01

    Background Brain injuries induced by hypoxia-ischemia in neonates contribute to increased mortality and lifelong neurological dysfunction. The specific PKR inhibitor C16 has been previously demonstrated to exert a neuroprotective role in adult brain injuries. However, there is no recent study available concerning its protective role in hypoxia-ischemia-induced immature brain damage. Therefore, we investigated whether C16 protects against neonatal hypoxia-ischemia injuries in a neonatal rat model. Material/Methods Postnatal day 7 (P7) rats were used to establish classical hypoxia-ischemia animal models, and C16 postconditioning with 100 ug/kg was performed immediately after hypoxia. Western blot analysis was performed to quantify the phosphorylation of the PKR at 0 h, 3 h, 6 h, 12 h, 24 h, and phosphorylation of NF-κB 24h after hypoxia exposure. The TTC stain for infarction area and TUNEL stain for apoptotic cells were assayed 24 h after the brain hypoxia. Gene expression of IL-1β, IL-6, and TNF-α was performed at 3 h, 6 h, 12 h, and 24 h. Results The level of PKR autophosphorylation was increased dramatically, especially at 3 h (C16 group vs. HI group, P<0.01). Intraperitoneal C16 administration reduced the infarct volume and apoptosis ratio after this insult (C16 group vs. HI group<0.01), and C16 reduced proinflammatory cytokines mRNA expression, partly through inhibiting NF-κB activation (C16 group vs. HI group<0.05). Conclusions C16 can protect immature rats against hypoxia-ischemia-induced brain damage by modulating neuroinflammation. PMID:28008894

  5. A mathematical model of blood, cerebrospinal fluid and brain dynamics.

    PubMed

    Linninger, Andreas A; Xenos, Michalis; Sweetman, Brian; Ponkshe, Sukruti; Guo, Xiaodong; Penn, Richard

    2009-12-01

    Using first principles of fluid and solid mechanics a comprehensive model of human intracranial dynamics is proposed. Blood, cerebrospinal fluid (CSF) and brain parenchyma as well as the spinal canal are included. The compartmental model predicts intracranial pressure gradients, blood and CSF flows and displacements in normal and pathological conditions like communicating hydrocephalus. The system of differential equations of first principles conservation balances is discretized and solved numerically. Fluid-solid interactions of the brain parenchyma with cerebral blood and CSF are calculated. The model provides the transitions from normal dynamics to the diseased state during the onset of communicating hydrocephalus. Predicted results were compared with physiological data from Cine phase-contrast magnetic resonance imaging to verify the dynamic model. Bolus injections into the CSF are simulated in the model and found to agree with clinical measurements.

  6. 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.

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

    PubMed

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

    2007-01-01

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

  8. 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…

  9. Cardioprotective activity of placental growth factor combined with oral supplementation of l-arginine in a rat model of acute myocardial infarction

    PubMed Central

    Luo, Liyun; Chen, Bairong; Huang, Yin; Liang, Zibin; Li, Songbiao; Yin, Yuelan; Chen, Jian; Wu, Wei

    2016-01-01

    Objective Exogenous administration of placental growth factor (PlGF) stimulates angiogenesis and improves ventricular remodeling after acute myocardial infarction (AMI), and supplementation with l-arginine ameliorates endothelial function. The objective of the present study was to compare the cardioprotective effects of combination therapy of PlGF and l-arginine with those of direct administration of PlGF alone in a rat model of AMI. Materials and methods Fifty male Sprague Dawley rats were randomly divided into five groups: sham group, normal saline group, l-arginine group, PlGF group, and combination group (PlGF + l-arginine). An AMI rat model was established by ligation of the left anterior descending of coronary arteries. After 4 weeks of postligation treatment, cardiac function, scar area, angiogenesis and arteriogenesis, myocardial endothelial nitric oxide synthase (eNOS) and collagen I protein content, and plasma concentration of brain natriuretic peptide (BNP) were studied. Echocardiography, Masson’s staining, immunohistochemical analyses, Western blot, and enzyme-linked immunosorbent assay were performed. Results Left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and capillary and arteriole densities were higher in the PlGF group than in the normal saline group (P<0.01). Scar area, collagen I protein content, and plasma concentration of BNP were decreased in the PlGF group (P<0.01). Myocardial eNOS protein level was elevated in the l-arginine group and PlGF + l-arginine group (P<0.01). Compared with the PlGF group, LVEF, LVFS, myocardial eNOS, and capillary and arteriole densities were higher in the combination group (P<0.01). Scar area, content of collagen I protein, and plasma concentration of BNP were reduced in the combination group (P<0.01). Conclusion Exogenous administration of PlGF stimulates angiogenesis and improves cardiac function. l-arginine increases the expression of the eNOS protein. PlGF and l

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

    PubMed

    Yi, Sun Shin

    2015-05-15

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

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

    PubMed Central

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

    2015-01-01

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

  12. 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

    2015-09-24

    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.

  13. A Simple Risk Stratification Model for ST-Elevation Myocardial Infarction (STEMI) from the Combination of Blood Examination Variables: Acute Myocardial Infarction-Kyoto Multi-Center Risk Study Group

    PubMed Central

    Nakamura, Takeshi; Yokota, Isao; Zen, Kan; Yamano, Tetsuhiro; Shiraishi, Hirokazu; Shiraishi, Jun; Sawada, Takahisa; Kohno, Yoshio; Kitamura, Makoto; Furukawa, Keizo; Matoba, Satoaki

    2016-01-01

    Background Many mortality risk scoring tools exist among patients with ST-elevation Myocardial Infarction (STEMI). A risk stratification model that evaluates STEMI prognosis more simply and rapidly is preferred in clinical practice. Methods and Findings We developed a simple stratification model for blood examination by using the STEMI data of AMI-Kyoto registry in the derivation set (n = 1,060) and assessed its utility for mortality prediction in the validation set (n = 521). We selected five variables that significantly worsen in-hospital mortality: white blood cell count, hemoglobin, C-reactive protein, creatinine, and blood sugar levels at >10,000/μL, <10 g/dL, >1.0 mg/dL, >1.0 mg/dL, and >200 mg/dL, respectively. In the derivation set, each of the five variables significantly worsened in-hospital mortality (p < 0.01). We developed the risk stratification model by combining laboratory variables that were scored based on each beta coefficient obtained using multivariate analysis and divided three laboratory groups. We also found a significant trend in the in-hospital mortality rate for three laboratory groups. Therefore, we assessed the utility of this model in the validation set. The prognostic discriminatory capacity of our laboratory stratification model was comparable to that of the full multivariable model (c-statistic: derivation set vs validation set, 0.81 vs 0.74). In addition, we divided all cases (n = 1,581) into three thrombolysis in myocardial infarction (TIMI) risk index groups based on an In TIME II substudy; the cases were further subdivided based on this laboratory model. The high laboratory group had significantly high in-hospital mortality rate in each TIMI risk index group (trend of in-hospital mortality; p < 0.01). Conclusions This laboratory stratification model can predict in-hospital mortality of STEMI simply and rapidly and might be useful for predicting in-hospital mortality of STEMI by further subdividing the TIMI risk index. PMID

  14. Blast and the Consequences on Traumatic Brain Injury-Multiscale Mechanical Modeling of Brain

    DTIC Science & Technology

    2011-02-17

    exposed to the Nahum head test scenarios. 4. Simulations under Blast Shock Waves Publication #s: [9], [10], [11], [41], [43] At many blast...the head model for three explosive scenarios[43]. Figure 8. Relative displacement-time histories for two clusters of a particular test with...Blasts, Brain Injury Professional, 2007;4(1), 10-15. [2] Naik , N. Abolfathi, G. Karami and M. Ziejewski, Micromechanical Viscoelastic

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

    PubMed Central

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

    2016-01-01

    Recent reports indicate that elevating DNA glycosylase/AP lyase repair enzyme activity offers marked cytoprotection in cultured cells and a variety of injury models. In this study, we measured the effect of EndoIII, a fusion protein construct that traffics Endonuclease III, a DNA glycosylase/AP lyase, to the mitochondria, on infarct size in a rat model of myocardial ischemia/reperfusion. Open-chest, anesthetized rats were subjected to 30 min of occlusion of a coronary artery followed by 2 h of reperfusion. An intravenous bolus of EndoIII, 8 mg/kg, just prior to reperfusion reduced infarct size from 43.8 ± 1.4 % of the risk zone in control animals to 24.0 ± 1.3 % with no detectable hemodynamic effect. Neither EndoIII’s vehicle nor an enzymatically inactive EndoIII mutant (K120Q) offered any protection. The magnitude of EndoIII’s protection was comparable to that seen with the platelet aggregation inhibitor cangrelor (25.0 ± 1.8 % infarction of risk zone). Because loading with a P2Y12 receptor blocker to inhibit platelets is currently the standard of care for treatment of acute myocardial infarction, we tested whether EndoIII could further reduce infarct size in rats treated with a maximally protective dose of cangrelor. The combination reduced infarct size to 15.1 ± 0.9 % which was significantly smaller than that seen with either cangrelor or EndoIII alone. Protection from cangrelor but not EndoIII was abrogated by pharmacologic blockade of phosphatidylinositol-3 kinase or adenosine receptors indicating differing cellular mechanisms. We hypothesized that EndoIII protected the heart from spreading necrosis by preventing the release of proinflammatory fragments of mitochondrial DNA (mtDNA) into the heart tissue. In support of this hypothesis, an intravenous bolus at reperfusion of deoxyribonuclease I (DNase I) which should degrade any DNA fragments escaping into the extracellular space was as protective as EndoIII. Furthermore, the combination of EndoIII and

  16. Modelling Brain Temperature and Perfusion for Cerebral Cooling

    NASA Astrophysics Data System (ADS)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2015-11-01

    Brain temperature relies heavily on two aspects: i) blood perfusion and porous heat transport through tissue and ii) blood flow and heat transfer through embedded arterial and venous vasculature. Moreover brain temperature cannot be measured directly unless highly invasive surgical procedures are used. A 3D two-phase fluid-porous model for mapping flow and temperature in brain is presented with arterial and venous vessels extracted from MRI scans. Heat generation through metabolism is also included. The model is robust and reveals flow and temperature maps in unprecedented 3D detail. However, the Karmen-Kozeny parameters of the porous (tissue) phase need to be optimised for expected perfusion profiles. In order to optimise the K-K parameters a reduced order two-phase model is developed where 1D vessels are created with a tree generation algorithm embedded inside a 3D porous domain. Results reveal that blood perfusion is a strong function of the porosity distribution in the tissue. We present a qualitative comparison between the simulated perfusion maps and those obtained clinically. We also present results studying the effect of scalp cooling on core brain temperature and preliminary results agree with those observed clinically.

  17. Models to Tailor Brain Stimulation Therapies in Stroke.

    PubMed

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

    2016-01-01

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

  18. Fuzzy local Gaussian mixture model for brain MR image segmentation.

    PubMed

    Ji, Zexuan; Xia, Yong; Sun, Quansen; Chen, Qiang; Xia, Deshen; Feng, David Dagan

    2012-05-01

    Accurate brain tissue segmentation from magnetic resonance (MR) images is an essential step in quantitative brain image analysis. However, due to the existence of noise and intensity inhomogeneity in brain MR images, many segmentation algorithms suffer from limited accuracy. In this paper, we assume that the local image data within each voxel's neighborhood satisfy the Gaussian mixture model (GMM), and thus propose the fuzzy local GMM (FLGMM) algorithm for automated brain MR image segmentation. This algorithm estimates the segmentation result that maximizes the posterior probability by minimizing an objective energy function, in which a truncated Gaussian kernel function is used to impose the spatial constraint and fuzzy memberships are employed to balance the contribution of each GMM. We compared our algorithm to state-of-the-art segmentation approaches in both synthetic and clinical data. Our results show that the proposed algorithm can largely overcome the difficulties raised by noise, low contrast, and bias field, and substantially improve the accuracy of brain MR image segmentation.

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

    PubMed

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

    2010-07-01

    Compared to other neurological diseases, the research surrounding traumatic brain injury (TBI) has a more recent history. The establishment and use of animal models of TBI remains vital to understand the pathophysiology of this highly complex disease. Such models share the ultimate goals of reproducing patterns of tissue damage observed in humans (thus rendering them clinically relevant), reproducible and highly standardised to allow for the manipulation of individual variables, and to finally explore novel therapeutics for clinical translation. There is no doubt that the similarity of cellular and molecular events observed in human and rodent TBI has reinforced the use of small animals for research. When confronted with the choice of the experimental model it becomes clear that the ideal animal model does not exist. This limitation derives from the fact that most models mimic either focal or diffuse brain injury, whereas the clinical reality suggests that each patient has an individual form of TBI characterised by various combinations of focal and diffuse patterns of tissue damage. This is additionally complicated by the occurrence of secondary insults such as hypotension, hypoxia, ischaemia, extracranial injuries, modalities of traumatic events, age, gender and heterogeneity of medical treatments and pre-existing conditions. This brief review will describe the variety of TBI models available for laboratory research beginning from the most widely used rodent models of focal brain trauma, to complex large species such as the pig. In addition, the models mimicking diffuse brain damage will be discussed in relation to the early primate studies until the use of most common rodent models to elucidate the intriguing and less understood pathology of axonal dysfunction. The most recent establishment of in vitro paradigms has complemented the in vivo modelling studies offering a further cellular and molecular insight of this pathology.

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

    PubMed Central

    Travis, Frederick T.; Wallace, Robert Keith

    2015-01-01

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

  1. Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke

    PubMed Central

    Wallace, Christopher Glenn; Yuen, Chun-Man; Kao, Gour-Shenq; Chen, Yi-Ling; Shao, Pei-Lin; Chen, Yung-Lung; Chai, Han-Tan; Lin, Kun-Chen; Liu, Chu-Feng; Chang, Hsueh-Wen; Lee, Mel S.; Yip, Hon-Kan

    2016-01-01

    We tested the hypothesis that combined xenogenic (from mini-pig) adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy could reduce brain-infarct zone (BIZ) and enhance neurological recovery in rat after acute ischemic stroke (AIS) induced by 50-min left middle cerebral artery occlusion. Adult-male Sprague-Dawley rats (n = 60) were divided equally into group 1 (sham-control), group 2 (AIS), group 3 [AIS-ADMSC (1.2×106 cells)], group 4 [AIS-exosome (100μg)], and group 5 (AIS-exosome-ADMSC). All therapies were provided intravenously at 3h after AIS procedure. BIZ determined by histopathology (by day-60) and brain MRI (by day-28) were highest in group 2, lowest in group 1, higher in groups 3 and 4 than in group 5, but they showed no difference between groups 3 and 4 (all p < 0.0001). By day-28, sensorimotor functional results exhibited an opposite pattern to BIZ among the five groups (p < 0.005). Protein expressions of inflammatory (inducible nitric oxide synthase/tumor necrosis factor-α/nuclear factor-κB/interleukin-1β/matrix metalloproteinase-9/plasminogen activator inhibitor-1/RANTES), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (caspase-3/ Poly-ADP-ribose polymerase), and fibrotic (Smad3/transforming growth factor-β) biomarkers, and cellular expressions of brain-damaged (γ-H2AX+/ XRCC1-CD90+/p53BP1-CD90+), inflammatory (CD11+/CD68+/glial fibrillary acid protein+) and brain-edema (aquaporin-4+) markers showed a similar pattern of BIZ among the groups (all n < 0.0001). In conclusion, xenogenic ADMSC/ADMSC-derived exosome therapy was safe and offered the additional benefit of reducing BIZ and improving neurological function in rat AIS. PMID:27793019

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

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

    PubMed Central

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

    2015-01-01

    The aim of the present study was to examine the role of eIF2α in cardiomyocyte apoptosis and evaluate the cardioprotective role of salubrinal in a rat myocardial infarction (MI) model. Rat left anterior descending coronary arteries were ligated and the classical proteins involved in the endoplasmic reticulum stress (ERS)-induced apoptotic pathway were analyzed using quantitative polymerase chain reaction and western blot analysis. Salubrinal was administered to the rats and cardiomyocyte apoptosis and infarct size were evaluated by a specific staining method. Compared with the sham surgery group, the rate of cardiomyocyte apoptosis in the MI group was increased with the development of the disease. It was also demonstrated that the mRNA and protein levels of GRP78, caspase-12, CHOP and the protein expression of p-eIF2α were increased in the MI group. Furthermore, the results showed that treatment with salubrinal can decrease cardiomyocyte apoptosis and infarct size by increasing eIF2α phosphorylation and decreasing the expression of caspase-12 and CHOP. The present study suggests that salubrinal protects against ER stress-induced rat cadiomyocyte apoptosis via suppressing the dephosphorylation of eIF2α in the ERS-associated pathway. PMID:25816071

  4. Lavandula Reduces Heart Injury via Attenuating Tumor Necrosis Factor-Alpha and Oxidative Stress in A Rat Model of Infarct-Like Myocardial Injury

    PubMed Central

    Vakili, Abedin; Sameni, Hamid Reza; Zahedi khorasani, Mahdi; Darabian, Mohsen

    2017-01-01

    Objective Lavender is used in herbal medicine for different therapeutic purposes. Nonetheless, potential therapeutic effects of this plant in ischemic heart disease and its possible mechanisms remain to be investigated. Materials and Methods In this experimental study, lavender oil at doses of 200, 400 or 800 mg/kg was administered through gastric gavage for 14 days before infarct-like myocardial injury (MI). The carotid artery and left ventricle were cannulated to record arterial blood pressure (BP) and cardiac function. At the end of experiment, the heart was removed and histopathological alteration, oxidative stress biomarkers as well as tumor necrosis factor-alpha (TNF-α) level were evaluated. Results Induction of M.I caused cardiac dysfunction, increased levels of lipid peroxidation, TNF-α and troponin I in heart tissue (P<0.001). Pretreatment with lavender oil at doses of 200 and 400 mg/kg significantly reduced myocardial injury, troponin I and TNF-α. In addition, it improved cardiac function and antioxidant enzyme activity (P<0.01). Conclusion Our finding showed that lavender oil has cardioprotective effect through inhibiting oxidative stress and inflammatory pathway in the rat model with infarct-like MI. We suggest that lavender oil may be helpful in prevention or attenuation of heart injury in patients with high risk of myocardial infarction and/or ischemic heart disease. PMID:28367419

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

    SciTech Connect

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

    2007-04-15

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

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

    PubMed

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

    2013-09-01

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

  8. Multiscale modeling for image analysis of brain tumor studies.

    PubMed

    Bauer, Stefan; May, Christian; Dionysiou, Dimitra; Stamatakos, Georgios; Büchler, Philippe; Reyes, Mauricio

    2012-01-01

    Image-based modeling of tumor growth combines methods from cancer simulation and medical imaging. In this context, we present a novel approach to adapt a healthy brain atlas to MR images of tumor patients. In order to establish correspondence between a healthy atlas and a pathologic patient image, tumor growth modeling in combination with registration algorithms is employed. In a first step, the tumor is grown in the atlas based on a new multiscale, multiphysics model including growth simulation from the cellular level up to the biomechanical level, accounting for cell proliferation and tissue deformations. Large-scale deformations are handled with an Eulerian approach for finite element computations, which can operate directly on the image voxel mesh. Subsequently, dense correspondence between the modified atlas and patient image is established using nonrigid registration. The method offers opportunities in atlas-based segmentation of tumor-bearing brain images as well as for improved patient-specific simulation and prognosis of tumor progression.

  9. Self-organized criticality model for brain plasticity.

    PubMed

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

    2006-01-20

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

  10. Neuroinflammation in animal models of traumatic brain injury

    PubMed Central

    Chiu, Chong-Chi; Liao, Yi-En; Yang, Ling-Yu; Wang, Jing-Ya; Tweedie, David; Karnati, Hanuma K.; Greig, Nigel H.; Wang, Jia-Yi

    2016-01-01

    Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Neuroinflammation is prominent in the short and long-term consequences of neuronal injuries that occur after TBI. Neuroinflammation involves the activation of glia, including microglia and astrocytes, to release inflammatory mediators within the brain, and the subsequent recruitment of peripheral immune cells. Various animal models of TBI have been developed that have proved valuable to elucidate the pathophysiology of the disorder and to assess the safety and efficacy of novel therapies prior to clinical trials. These models provide an excellent platform to delineate key injury mechanisms that associate with types of injury (concussion, contusion, and penetration injuries) that occur clinically for the investigation of mild, moderate, and severe forms of TBI. Additionally, TBI modeling in genetically engineered mice, in particular, has aided the identification of key molecules and pathways for putative injury mechanisms, as targets for development of novel therapies for human TBI. This Review details the evidence showing that neuroinflammation, characterized by the activation of microglia and astrocytes and elevated production of inflammatory mediators, is a critical process occurring in various TBI animal models, provides a broad overview of commonly used animal models of TBI, and overviews representative techniques to quantify markers of the brain inflammatory process. A better understanding of neuroinflammation could open therapeutic avenues for abrogation of secondary cell death and behavioral symptoms that may mediate the progression of TBI. PMID:27382003

  11. Constitutive modelling of brain tissue: experiment and theory.

    PubMed

    Miller, K; Chinzei, K

    1997-01-01

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

  12. MR Vascular Fingerprinting in Stroke and Brain Tumors Models

    NASA Astrophysics Data System (ADS)

    Lemasson, B.; Pannetier, N.; Coquery, N.; Boisserand, Ligia S. B.; Collomb, Nora; Schuff, N.; Moseley, M.; Zaharchuk, G.; Barbier, E. L.; Christen, T.

    2016-11-01

    In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

  13. MR Vascular Fingerprinting in Stroke and Brain Tumors Models

    PubMed Central

    Lemasson, B.; Pannetier, N.; Coquery, N.; Boisserand, Ligia S. B.; Collomb, Nora; Schuff, N.; Moseley, M.; Zaharchuk, G.; Barbier, E. L.; Christen, T.

    2016-01-01

    In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases. PMID:27883015

  14. MR Vascular Fingerprinting in Stroke and Brain Tumors Models.

    PubMed

    Lemasson, B; Pannetier, N; Coquery, N; Boisserand, Ligia S B; Collomb, Nora; Schuff, N; Moseley, M; Zaharchuk, G; Barbier, E L; Christen, T

    2016-11-24

    In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

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

    PubMed Central

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

    2015-01-01

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

  16. Omics analysis of mouse brain models of human diseases.

    PubMed

    Paban, Véronique; Loriod, Béatrice; Villard, Claude; Buee, Luc; Blum, David; Pietropaolo, Susanna; Cho, Yoon H; Gory-Faure, Sylvie; Mansour, Elodie; Gharbi, Ali; Alescio-Lautier, Béatrice

    2017-02-05

    The identification of common gene/protein profiles related to brain alterations, if they exist, may indicate the convergence of the pathogenic mechanisms driving brain disorders. Six genetically engineered mouse lines modelling neurodegenerative diseases and neuropsychiatric disorders were considered. Omics approaches, including transcriptomic and proteomic methods, were used. The gene/protein lists were used for inter-disease comparisons and further functional and network investigations. When the inter-disease comparison was performed using the gene symbol identifiers, the number of genes/proteins involved in multiple diseases decreased rapidly. Thus, no genes/proteins were shared by all 6 mouse models. Only one gene/protein (Gfap) was shared among 4 disorders, providing strong evidence that a common molecular signature does not exist among brain diseases. The inter-disease comparison of functional processes showed the involvement of a few major biological processes indicating that brain diseases of diverse aetiologies might utilize common biological pathways in the nervous system, without necessarily involving similar molecules.

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

    PubMed Central

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

    2011-01-01

    Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2. Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4. The resulting hematomas and lacerations cause a vascular response 3,5, and the morphological and functional damage of the white matter leads to diffuse axonal injury 6-8. Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure 9. Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals 10-12, which ultimately result in long-term neurological disabilities 13,14. Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1. The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15. Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17. The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed

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

    PubMed

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

    2011-08-22

    Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific

  19. Normal brain ageing: models and mechanisms

    PubMed Central

    Toescu, Emil C

    2005-01-01

    Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria–reactive oxygen species (ROS)–intracellular Ca2+. The perturbation in the relationship between the members of this metabolic triad generate a state of decreased homeostatic reserve, in which the aged neurons could maintain adequate function during normal activity, as demonstrated by the fact that normal ageing is not associated with widespread neuronal loss, but become increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischaemia or neurodegenerative processes. This review will concentrate on some of the evidence showing altered mitochondrial function with ageing and also discuss some of the functional consequences that would result from such events, such as alterations in mitochondrial Ca2+ homeostasis, ATP production and generation of ROS. PMID:16321805

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

    PubMed Central

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

    2012-01-01

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

  1. Data-driven forward model inference for EEG brain imaging.

    PubMed

    Hansen, Sofie Therese; Hauberg, Søren; Hansen, Lars Kai

    2016-06-13

    Electroencephalography (EEG) is a flexible and accessible tool with excellent temporal resolution but with a spatial resolution hampered by volume conduction. Reconstruction of the cortical sources of measured EEG activity partly alleviates this problem and effectively turns EEG into a brain imaging device. The quality of the source reconstruction depends on the forward model which details head geometry and conductivities of different head compartments. These person-specific factors are complex to determine, requiring detailed knowledge of the subject's anatomy and physiology. In this proof-of-concept study, we show that, even when anatomical knowledge is unavailable, a suitable forward model can be estimated directly from the EEG. We propose a data-driven approach that provides a low-dimensional parametrization of head geometry and compartment conductivities, built using a corpus of forward models. Combined with only a recorded EEG signal, we are able to estimate both the brain sources and a person-specific forward model by optimizing this parametrization. We thus not only solve an inverse problem, but also optimize over its specification. Our work demonstrates that personalized EEG brain imaging is possible, even when the head geometry and conductivities are unknown.

  2. A Novel Mouse Model of Penetrating Brain Injury

    PubMed Central

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

    2014-01-01

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

  3. Dietary Soy May Not Confound Acute Experimental Stroke Infarct Volume Outcomes In Ovariectomized Female Rats

    PubMed Central

    Prongay, Kamm D.; Lewis, Anne D.; Hurn, Patricia D.; Murphy, Stephanie J.

    2009-01-01

    Estrogen administration can alter experimental stroke outcomes. Soy as a source of phytoestrogens may therefore modulate responses in “estrogen-sensitive” stroke models, thus potentially confounding results. We evaluated the effects of dietary soy on acute infarct volumes in a pilot study using a rat focal stroke model. We hypothesized that ovariectomized (OVX) rats fed a soy-rich diet would have smaller acute infarct volumes than rats fed a soy-free diet. OVX rats were randomly assigned to a soy-free (n=6) or a soy-rich (n=6) diet for 4 weeks and weighed weekly. Following the dietary trial, rats underwent 2 hours of middle cerebral artery occlusion (MCAO). Mean arterial blood pressure, rectal and temporalis muscle temperatures, arterial blood gases, and blood glucose were recorded peri-ischemia. Rats were euthanized 22 hours following 2 hours of MCAO. Brains were stained with 2,3,5-triphenyl tetrazolium chloride for acute infarct volume analysis. Uterine weight and histology were also evaluated as additional internal estrogen-sensitive controls. Rats on the soy-free diet had greater gains in body weight (259±6% baseline body weight) than rats on the soy-rich diet (238±4% baseline body weight). No differences were seen in uterine weight and histology, peri-ischemic physiological parameters, and infarct volumes between the treatment groups. Results of this pilot study suggest that the dietary soy level tested may not alter acute infarct volumes in ischemic female rat brain. More studies addressing the potential confounding effects of dietary soy in “estrogen-sensitive” stroke models are needed if investigators are to make informed choices regarding diets used in experimental stroke research. PMID:20147341

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

    SciTech Connect

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

    1984-07-01

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

  5. Genetic mouse models of brain ageing and Alzheimer's disease.

    PubMed

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed.

  6. Self-organization in a simple brain model

    SciTech Connect

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

    1994-03-10

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

  7. 77 FR 13578 - Disability and Rehabilitation Research Project; Traumatic Brain Injury Model Systems Centers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-07

    ... Disability and Rehabilitation Research Project; Traumatic Brain Injury Model Systems Centers AGENCY: Office... Brain Injury Model Systems Centers. CFDA Number: 84.133A-5. SUMMARY: The Assistant Secretary for Special... Projects (DRRPs) to serve as Traumatic Brain Injury Model Systems (TBIMS) Centers. The Assistant...

  8. Opioid Abuse after Traumatic Brain Injury: Evaluation Using Rodent Models

    DTIC Science & Technology

    2015-09-01

    neurological changes that increase vulnerability for drug abuse and addiction. Consequently, we have been evaluating the effects of TBI on both the...rewarding effects of opioid drugs as well as the development of tolerance and physical dependence in well-established rat models of abuse-related drug ...brain injured rats have a greater sensitivity to the rewarding effects of oxycodone and will self-administer greater total doses of drug compared to

  9. A hierarchical coherent-gene-group model for brain development.

    PubMed

    Tsigelny, I F; Kouznetsova, V L; Baitaluk, M; Changeux, J-P

    2013-03-01

    We have described a strategy to analyze the data available on brain genes expression, using the concept of coherent-gene groups controlled by transcription factors (TFs). A hierarchical model of gene-expression patterns during brain development was established that identified the genes assumed to behave as functionally coding. Analysis of the concerned signaling pathways and processes showed distinct temporal gene-expression patterns in relation with neurogenesis/synaptogenesis. We identified the hierarchical tree of TF networks that determined the patterns of genes expressed during brain development. Some 'master TFs' at the top level of the hierarchy regulated the expression of gene groups. Enhanced/decreased activity of a few master TFs may explain paradoxes raised by the genetic determination of autism-spectrum disorders and schizophrenia. Our analysis showed gene-TF networks, common or related, to these disorders that exhibited two maxima of expression, one in the prenatal and the other at early postnatal period of development, consistent with the view that these disorders originate in the prenatal period, develop in the postnatal period, and reach the ultimate neural and behavioral phenotype with different sets of genes regulating each of these periods. We proposed a strategy for drug design based upon the temporal patterns of expression of the concerned TFs. Ligands targeting specific TFs can be designed to specifically affect the pathological evolution of the mutated gene(s) in genetically predisposed patients when administered at relevant stages of brain development.

  10. A model for genomic imprinting in the social brain: juveniles.

    PubMed

    Ubeda, Francisco; Gardner, Andy

    2010-09-01

    What are imprinted genes doing in the adult brain? Genomic imprinting is when a gene's expression depends upon parent of origin. According to the prevailing view, the "kinship theory" of genomic imprinting, this effect is driven by evolutionary conflicts between genes inherited via sperm versus egg. This theory emphasizes conflicts over the allocation of maternal resources, and focuses upon genes that are expressed in the placenta and infant brain. However, there is growing evidence that imprinted genes are also expressed in the juvenile and adult brain, after cessation of parental care. These genes have recently been suggested to underpin neurological disorders of the social brain such as psychosis and autism. Here we advance the kinship theory by developing an evolutionary model of genomic imprinting for social behavior beyond the nuclear family. We consider the role of demography and mating system, emphasizing the importance of sex differences in dispersal and variance in reproductive success. We predict that, in hominids and birds, altruism will be promoted by paternally inherited genes and egoism will be promoted by maternally inherited genes. In nonhominid mammals we predict more diversity, with some mammals showing the same pattern and other showing the reverse. We discuss the implications for the evolution of psychotic and autistic spectrum disorders in human populations with different social structures.

  11. Performance bounds for dynamic causal modeling of brain connectivity.

    PubMed

    Wu, Shun Chi; Swindlehurst, A Lee

    2012-01-01

    The use of complex dynamical models have been proposed for describing the connections and causal interactions between different regions of the brain. The goal of these models is to accurately mimic the event-related potentials observed by EEG/MEG measurement systems, and are useful in understanding overall brain functionality. In this paper, we focus on a class of nonlinear dynamic causal models (DCM) that are described by a set of connectivity parameters. In practice, the DCM parameters are inferred using data obtained by an EEG or MEG sensor array in response to a certain event or stimulus, and the resulting estimates are used to analyze the strength and direction of the causal interactions between different brain regions. The usefulness of the parameter estimates will depend on how accurately they can be estimated, which in turn will depend on noise, the sampling rate, number of data samples collected, the accuracy of the source localization and reconstruction steps, etc. The goal of this paper is to derive Cramér-Rao performance bounds for DCM estimates, and examine the behavior of the bounds under different operating conditions.

  12. Fluid-percussion–induced traumatic brain injury model in rats

    PubMed Central

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

    2013-01-01

    Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Various attempts have been made to replicate clinical TBI using animal models. The fluid-percussion model (FP) is one of the oldest and most commonly used models of experimentally induced TBI. Both central (CFP) and lateral (LFP) variations of the model have been used. Developed initially for use in larger species, the standard FP device was adapted more than 20 years ago to induce consistent degrees of brain injury in rodents. Recently, we developed a microprocessor-controlled, pneumatically driven instrument, micro-FP (MFP), to address operational concerns associated with the use of the standard FP device in rodents. We have characterized the MFP model with regard to injury severity according to behavioral and histological outcomes. In this protocol, we review the FP models and detail surgical procedures for LFP. The surgery involves tracheal intubation, craniotomy and fixation of Luer fittings, and induction of injury. The surgical procedure can be performed within 45–50 min. PMID:20725070

  13. Regulatory T cells exhibit neuroprotective effect in a mouse model of traumatic brain injury

    PubMed Central

    Yu, Yunhu; Cao, Fang; Ran, Qishan; Sun, Xiaochuan

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socioeconomic problem as it is associated with high rates of mortality and morbidity worldwide. Regulatory T cells (Tregs) have been reported to reduce inflammatory response in several diseases, including myasthenia gravis, viral myocarditis and cerebral infarction. The present study investigated the role of Tregs in mediating neuro-protective effects in a mouse model of TBI. Initially, Treg levels were determined, and compared between the controlled cortical impact (CCI) model for moderate TBI and the sham group, by using flow cytometry and ELISA. Afterwards, the number of Tregs was upregulated (by injection) and downregulated (by depletion), respectively, to elucidate the effect of Tregs in the presence of an inflammatory reaction and a deficient neurological function and consequently, in the prognosis of TBI in the mouse. The expression of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6)] and anti-inflammatory cytokines [IL-10, transforming growth factor (TGF)-β] in blood and brain tissues was also measured in the five groups: Μice receiving a saline injection, mice experiencing Treg depletion, small-dose (SD Tregs, 1.25×105), and mice receiving different doses of Tregs: Moderate-dose (MD Tregs, 2.5×105) and large-dose (LD Tregs, 5×105), using ELISA and PCR. Co-cultures of Tregs and microglia were performed to evaluate the expression of pro-inflammatory cytokines and observe the interaction between the two types of cells. The regulation patterns in JNK-NF-κB pathway by Tregs were also evaluated by western blot analysis. Treg levels were significantly reduced in TBI mouse group on the 3rd day after TBI (P<0.05). In the mouse model of TBI, the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) was enhanced, while the expression of anti-inflammatory cytokines (IL-10, TGF-β) was reduced (P<0.05). Tregs exhibited a suppressive effect on inflammatory reactions

  14. Regulatory T cells exhibit neuroprotective effect in a mouse model of traumatic brain injury.

    PubMed

    Yu, Yunhu; Cao, Fang; Ran, Qishan; Sun, Xiaochuan

    2016-12-01

    Traumatic brain injury (TBI) is a major health and socioeconomic problem as it is associated with high rates of mortality and morbidity worldwide. Regulatory T cells (Tregs) have been reported to reduce inflammatory response in several diseases, including myasthenia gravis, viral myocarditis and cerebral infarction. The present study investigated the role of Tregs in mediating neuro‑protective effects in a mouse model of TBI. Initially, Treg levels were determined, and compared between the controlled cortical impact (CCI) model for moderate TBI and the sham group, by using flow cytometry and ELISA. Afterwards, the number of Tregs was upregulated (by injection) and downregulated (by depletion), respectively, to elucidate the effect of Tregs in the presence of an inflammatory reaction and a deficient neurological function and consequently, in the prognosis of TBI in the mouse. The expression of pro‑inflammatory cytokines [tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6)] and anti‑inflammatory cytokines [IL‑10, transforming growth factor (TGF)‑β] in blood and brain tissues was also measured in the five groups: Μice receiving a saline injection, mice experiencing Treg depletion, small‑dose (SD Tregs, 1.25x105), and mice receiving different doses of Tregs: Moderate‑dose (MD Tregs, 2.5x105) and large‑dose (LD Tregs, 5x105), using ELISA and PCR. Co‑cultures of Tregs and microglia were performed to evaluate the expression of pro‑inflammatory cytokines and observe the interaction between the two types of cells. The regulation patterns in JNK‑NF‑κB pathway by Tregs were also evaluated by western blot analysis. Treg levels were significantly reduced in TBI mouse group on the 3rd day after TBI (P<0.05). In the mouse model of TBI, the expression of pro‑inflammatory cytokines (TNF‑α, IL‑1β, IL‑6) was enhanced, while the expression of anti‑inflammatory cytokines (IL‑10, TGF‑β) was reduced (P<0.05). Tregs exhibited a

  15. In vitro bioengineered model of cortical brain tissue

    PubMed Central

    Chwalek, Karolina; Tang-Schomer, Min D.; Omenetto, Fiorenzo G.; Kaplan, David L.

    2016-01-01

    A bioengineered model of three-dimensional (3D) brain-like tissue was developed using silk-collagen protein scaffolds seeded with primary cortical neurons. The scaffold design provides compartmentalized control for spatial separation of neuronal cell bodies and neural projections, resembling the layered structure of the brain (cerebral cortex). Neurons seeded in a donut-shaped porous silk sponge grow robust neuronal projections within a collagen-filled central region, generating 3D neural networks with structural and functional connectivity. The silk scaffold preserves the mechanical stability of the engineered tissues, allowing for ease of handling, long-term culture in vitro, anchoring of the central collagen gel to avoid shrinkage, and neural network maturation. This protocol describes the preparation and manipulation of silk-collagen constructs, including the isolation and seeding of primary rat cortical neurons. This 3D technique is useful for mechanical injury studies, as a drug screening tool and could serve as a foundation for brain-related disease models. The protocol of construct assembly takes 2 days and the resulting tissues can be maintained in culture for several weeks. PMID:26270395

  16. SyM-BBB: A Microfluidic Blood Brain Barrier Model

    PubMed Central

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

    2013-01-01

    Current techniques for mimicking the Blood-Brain Barrier (BBB) largely use incubation chambers (Transwell) separated with a filter and matrix coating to represent and to study barrier permeability. These devices have several critical shortcomings; (a) they do not reproduce critical microenvironmental parameters, primarily anatomical size or hemodynamic shear stress, (b) they often do not provide real-time visualization capability, and (c) they require a large amount of consumables. To overcome these limitations, we have developed a microfluidics based Synthetic Microvasculature model of the Blood-Brain Barrier (SyM-BBB). The SyM-BBB platform is comprised of a plastic, disposable and optically clear microfluidic chip with a microcirculation sized two-compartment chamber. The chamber is designed in such a way as to permit the realization of side-by-side apical and basolateral compartments, thereby simplifying fabrication and facilitating integration with standard instrumentation. The individually addressable apical side is seeded with endothelial cells and the basolateral side can support neuronal cells or conditioned media. In the present study, an immortalized Rat Brain Endothelial cell line (RBE4) was cultured in SyM-BBB with a perfusate of Astrocyte Conditioned Media (ACM). Biochemical analysis showed upregulation of tight junction molecules while permeation studies showed an intact BBB. Finally, transporter assay was successfully demonstrated in SyM-BBB indicating a functional model. PMID:23344641

  17. Building better biomarkers: brain models in translational neuroimaging.

    PubMed

    Woo, Choong-Wan; Chang, Luke J; Lindquist, Martin A; Wager, Tor D

    2017-02-23

    Despite its great promise, neuroimaging has yet to substantially impact clinical practice and public health. However, a developing synergy between emerging analysis techniques and data-sharing initiatives has the potential to transform the role of neuroimaging in clinical applications. We review the state of translational neuroimaging and outline an approach to developing brain signatures that can be shared, tested in multiple contexts and applied in clinical settings. The approach rests on three pillars: (i) the use of multivariate pattern-recognition techniques to develop brain signatures for clinical outcomes and relevant mental processes; (ii) assessment and optimization of their diagnostic value; and (iii) a program of broad exploration followed by increasingly rigorous assessment of generalizability across samples, research contexts and populations. Increasingly sophisticated models based on these principles will help to overcome some of the obstacles on the road from basic neuroscience to better health and will ultimately serve both basic and applied goals.

  18. Quantitative myocardial perfusion measurement using CT perfusion: a validation study in a porcine model of reperfused acute myocardial infarction.

    PubMed

    So, Aaron; Hsieh, Jiang; Li, Jian-Ying; Hadway, Jennifer; Kong, Hua-Fu; Lee, Ting-Yim

    2012-06-01

    We validated a CT perfusion technique with beam hardening (BH) correction for quantitative measurement of myocardial blood flow (MBF). Acute myocardial infarction (AMI) was created in four pigs by occluding the distal LAD for 1 h followed by reperfusion. MBF was measured from dynamic contrast enhanced CT (DCE-CT) scanning of the heart, with correction of cardiac motion and BH, before ischemic insult and on day 7, 10 and 14 post. On day 14 post, radiolabeled microspheres were injected to measure MBF and the results were compared with those measured by CT perfusion. Excised hearts were stained with 2,3,5-triphenyltetrazolium chloride (TTC) to determine the relationship between MBF measured by CT Perfusion and myocardial viability. MBF measured by CT perfusion was strongly correlated with that by microspheres over a wide range of MBF values (R = 0.81, from 25 to 225 ml min(-1) 100 g(-1)). While MBF in the LAD territory decreased significantly from 98.4 ± 2.5 ml min(-1) 100 g(-1) at baseline to 32.2 ± 9.1 ml min(-1) 100 g(-1), P < 0.05 at day 7 and to 49.4 ± 9.3 ml min(-1) 100 g(-1), P < 0.05 at day 14, the decrease in remote myocardium (LCx territory) from baseline (103.9 ± 1.9 ml min(-1) 100 g(-1)) was minimal throughout the study (90.6 ± 5.1 ml min(-1) 100 g(-1) on day 14 post, P > 0.05). TTC staining confirmed incomplete infarction in the LAD territory and no infarction in the LCx territory. Microvascular obstruction in infarcted tissue resulted in no-reflow and hence persistently low MBF in the reperfused LAD territory which contained a mixture of viable and non-viable tissue. CT perfusion measurement of MBF was accurate and correlated well with histology and microspheres measurements.

  19. Artery of Percheron Infarction

    PubMed Central

    Vinod, K.V.; Kaaviya, R.; Arpita, Bhaumik

    2016-01-01

    Artery of Percheron (AOP) occlusion is a rare cause of ischemic stroke characterized by bilateral paramedian thalamic infarcts, with or without mesencephalic infarction. Clinically it presents with mental state disturbances, hypersomnolence, aphasia/dysarthria, amnesia and ocular movement disorders, including vertical gaze palsy. Here, we report a case of cardioembolic AOP infarction in a 37-year-old woman with rheumatic mitral valvular stenosis. This case is being reported to highlight the interesting clinical and neuroimaging features of this rare condition, and the differential diagnosis of AOP infarction on imaging have been discussed. PMID:27647964

  20. Biothermal Model of Patient for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Wakamatsu, Hidetoshi; Gaohua, Lu

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

  1. Cognitive Function and Emotional Status of Middle-aged Chinese Hypertensive Patients Without Detectable White Matter Brain Lesions or Lacunar Infarctions

    DTIC Science & Technology

    2006-08-30

    with extremes of systolic blood pressure in older Caucasians appears to be muted in elderly African Americans (Bohannon, Fillenbaum, Pieper, Hanlon...145-151. DeCarli, C., Miller, B. L., Swan , G. E., Reed, T., Wolf, P. A., Garner, J., et al. (1999). Predictors of brain morphology for the men of

  2. Cognitive Function and Emotional Status of Middle-aged Chinese Hypertensive Patients Without Detectable White Matter Brain Lesions or Lacunar Infarctions

    DTIC Science & Technology

    2006-01-01

    extremes of systolic blood pressure in older Caucasians appears to be muted in elderly African Americans (Bohannon, Fillenbaum, Pieper, Hanlon, & Blazer...DeCarli, C., Miller, B. L., Swan , G. E., Reed, T., Wolf, P. A., Garner, J., et al. (1999). Predictors of brain morphology for the men of the NHLBI

  3. [Stem cell perspectives in myocardial infarctions].

    PubMed

    Aceves, José Luis; Archundia, Abel; Díaz, Guillermo; Páez, Araceli; Masso, Felipe; Alvarado, Martha; López, Manuel; Aceves, Rocío; Ixcamparij, Carlos; Puente, Adriana; Vilchis, Rafael; Montaño, Luis Felipe

    2005-01-01

    Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, different cellular lines such as cardiomyocites, skeletal myoblasts, embryonic stem cells and adult mesenchymal stem cells have been used, resulting in an improvement in ventricular function and decrease in amount of infarcted tissue. The first three cells lines have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, after stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation methods in infarcted myocardial tissue.

  4. [Disappearance of essential tremor after thalamic infarction].

    PubMed

    Nakamura, Y; Miura, K; Yamada, I; Takada, K

    1999-01-01

    Stereotactic thalamotomy has been used with some benefit in the treatment of essential tremor. We report a 73-year-old woman whose essential tremor of the right hand spontaneously disappeared after thalamic infarction. She had suffered hand tremor of the right hand for seven years. One morning, she noticed mild muscular weakness in her right upper and lower extremities, numbness around her mouth and paresthesia in her right arm. Simultaneously, she noticed disappearance of the tremor of her right hand. Several days later, right hemiplegia and paresthesia completely resolved. Neurological examination revealed no postural tremor or resting tremor. T 2-weighted brain MR imaging showed a high-intensity signal in the left thalamus that involved the ventralis intermedius nucleus. Clinical recovery from the effect of the infarct on essential tremor was complete. Therefore, it seems that thalamic infarction in this patient had an effect on essential tremor similar to that achieved with thalamotomy.

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

    PubMed Central

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

    2013-01-01

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

  6. Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents.

    PubMed

    Backhauss, C; Krieglstein, J

    1992-05-14

    The purpose of the present study was to test whether kava extract and its constituents kawain, dihydrokawain, methysticin, dihydromethysticin and yangonin provide protection against ischemic brain damage. To this end, we used a model of focal cerebral ischemia in mice and rats. Ischemia was induced by microbipolar coagulation of the left middle cerebral artery (MCA). To quantify the size of the lesion in mice, the area of the infarct on the brain surface was assessed planimetrically 48 h after MCA occlusion by transcardial perfusion of carbon black. In the rat model infarct volume was determined 48 h after MCA occlusion by planimetric analysis and subsequent integration of the infarct areas on serial coronal slices. Compounds were administered i.p., except the kava extract, which was administered orally. The effects of the kava extract and its constituents were compared with those produced by the typical anticonvulsant, memantine. The kava extract, methysticin and dihydromethysticin produced effects similar to those of the reference substance memantine. The kava extract (150 mg/kg, 1 h before ischemia) diminished the infarct area (P less than 0.05) in mouse brains and the infarct volume (P less than 0.05) in rat brains. Methysticin, dihydromethysticin (both 10 and 30 mg/kg, 15 min before ischemia) and memantine (20 mg/kg, 30 min before ischemia) significantly reduced the infarct area in mouse brains. All other compounds failed to produce a beneficial effect on the infarct area in mouse brains. In conclusion, the kava extract exhibited neuroprotective activity, which was probably mediated by its constituents methysticin and dihydromethysticin.

  7. Multiscale modeling and simulation of brain blood flow

    SciTech Connect

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

    2016-02-15

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

  8. Multiscale modeling and simulation of brain blood flow

    PubMed Central

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

    2016-01-01

    The aim of this work is to present an overview of recent advances in multi-scale modeling of brain blood flow. In particular, we present some approaches that enable the in silico study of multi-scale and multi-physics phenomena in the cerebral vasculature. We discuss the formulation of continuum and atomistic modeling approaches, present a consistent framework for their concurrent coupling, and list some of the challenges that one needs to overcome in achieving a seamless and scalable integration of heterogeneous numerical solvers. The effectiveness of the proposed framework is demonstrated in a realistic case involving modeling the thrombus formation process taking place on the wall of a patient-specific cerebral aneurysm. This highlights the ability of multi-scale algorithms to resolve important biophysical processes that span several spatial and temporal scales, potentially yielding new insight into the key aspects of brain blood flow in health and disease. Finally, we discuss open questions in multi-scale modeling and emerging topics of future research. PMID:26909005

  9. Multiscale modeling and simulation of brain blood flow.

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2015-04-01

    The transplantation of adipose tissue-derived stem cells (ADSCs) improves cardiac contractility after myocardial infarction (MI); however, little is known about the electrophysiological consequences of transplantation. The purpose of this study was to clarify whether the transplantation of ADSCs increases or decreases the incidence of ventricular tachyarrhythmias (VT) in a rat model of MI. MI was induced experimentally by permanent occlusion of the left anterior descending artery of Lewis rats. ADSCs were harvested from GFP-transgenic rats, and were cultured until passage four. ADSCs (10×10(6)) resuspended in 100μL saline or pro-survival cocktail (PSC), which enhances cardiac graft survival, were injected directly into syngeneic rat hearts 1week after MI. The recipients of ADSCs suspended in PSC had a larger graft area compared with those receiving ASDCs suspended in saline at 1week post-transplantation (number of graft cells/section: 148.7±10.6 vs. 22.4±3.4, p<0.05, n=5/group). Thereafter, all ADSC recipients were transplanted with ASDCs in PSC. ADSCs were transplanted into infarcted hearts, and the mechanical and electrophysiological functions were assessed. Echocardiography revealed that ADSC recipients had improved contractile function compared with those receiving PSC vehicle (fractional shortening: 21.1±0.9 vs. 14.1±1.2, p<0.05, n≥12/group). Four weeks post-transplantation, VT was induced via in vivo programmed electrical stimulation. The recipients of ADSCs showed a significantly lower incidence of induced VT compared with the control (31.3% vs. 83.3%, p<0.05, n≥12/group). To understand the electrical activity following transplantation, we performed ex vivo optical mapping using a voltage sensitive dye, and found that ADSC transplantation decreased conduction velocity and its dispersion in the peri-infarct area. These results suggest that ADSC transplantation improved cardiac mechanical and electrophysiological functions in subacute MI.

  11. [The Granger causality models and their applications in brain effective connectivity networks].

    PubMed

    Zhao, Tiezhu; Zheng, Gang; Pan, Zhiying; Li, Qiang; Wang, Li; Lu, Guangming

    2013-12-01

    Granger causality model is an analysis method that requires no priori knowledge and emphasizes time sequence. Such model applied to brain effective connectivity network can reflect the directional connectivity among brain regions or neurons. This paper reviews the principle of Granger causality model, basic test steps and improved models, analyzes and discusses applications and existing problems of Granger causality model in brain effective connectivity network.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

    Feng, Yuanbo; Bogaert, Jan; Oyen, Raymond

    2014-01-01

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

  15. Regional mechanics determine collagen fiber structure in healing myocardial infarcts.

    PubMed

    Fomovsky, Gregory M; Rouillard, Andrew D; Holmes, Jeffrey W

    2012-05-01

    Following myocardial infarction, the mechanical properties of the healing infarct are an important determinant of heart function and the risk of progression to heart failure. In particular, mechanical anisotropy (having different mechanical properties in different directions) in the healing infarct can preserve pump function of the heart. Based on reports of different collagen structures and mechanical properties in various animal models, we hypothesized that differences in infarct size, shape, and/or location produce different patterns of mechanical stretch that guide evolving collagen fiber structure. We tested the effects of infarct shape and location using a combined experimental and computational approach. We studied mechanics and collagen fiber structure in cryoinfarcts in 53 Sprague-Dawley rats and found that regardless of shape or orientation, cryoinfarcts near the equator of the left ventricle stretched primarily in the circumferential direction and developed circumferentially aligned collagen, while infarcts at the apex stretched similarly in the circumferential and longitudinal directions and developed randomly oriented collagen. In a computational model of infarct healing, an effect of mechanical stretch on fibroblast and collagen alignment was required to reproduce the experimental results. We conclude that mechanical environment determines collagen fiber structure in healing myocardial infarcts. Our results suggest that emerging post-infarction therapies that alter regional mechanics will also alter infarct collagen structure, offering both potential risks and novel therapeutic opportunities.

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  17. Experimental models of perinatal hypoxic-ischemic brain damage.

    PubMed

    Vannucci, R C

    1993-01-01

    Animal research has provided important information on the pathogenesis of and neuropathologic responses to perinatal cerebral hypoxia-ischemia. In experimental animals, structural brain damage from hypoxia-ischemia has been produced in immature rats, rabbits, guinea pigs, sheep and monkeys (18, 20, 24, 25, 38). Of the several available animal models, the fetal and newborn rhesus monkey and immature rat have been studied most extensively because of their similarities to humans in respect to the physiology of reproduction and their neuroanatomy at or shortly following birth. Given the frequency of occurrence of human perinatal hypoxic-ischemic brain damage and the multiple, often severe neurologic handicaps which ensue in infants and children, it is not surprising that the above described animal models have been developed. These models have provided the basis for investigations to clarify not only physiologic and biochemical mechanisms of tissue injury but also the efficacy of specific management strategies. Hopefully, such animal research will continue to provide important information regarding how best to prevent or minimize the devastating consequences of perinatal cerebral hypoxia-ischemia.

  18. Melanoma Cells Homing to the Brain: An In Vitro Model

    PubMed Central

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

    2015-01-01

    We developed an in vitro contact through-feet blood brain barrier (BBB) model built using type IV collagen, rat astrocytes, and human umbilical vein endothelial cells (HUVECs) cocultured through Transwell porous polycarbonate membrane. The contact between astrocytes and HUVECs was demonstrated by electron microscopy: astrocytes endfeet pass through the 8.0 μm pores inducing HUVECs to assume a cerebral phenotype. Using this model we evaluated transmigration of melanoma cells from two different patients (M1 and M2) selected among seven melanoma primary cultures. M2 cells showed a statistically significant higher capability to pass across the in vitro BBB model, compared to M1. Expression of adhesion molecules was evaluated by flow cytometry: a statistically significant increased expression of MCAM, αvβ3, and CD49b was detected in M1. PCR array data showed that M2 had a higher expression of several matrix metalloproteinase proteins (MMPs) compared to M1. Specifically, data suggest that MMP2 and MMP9 could be directly involved in BBB permeability and that brain invasion by melanoma cells could be related to the overexpression of many MMPs. Future studies will be necessary to deepen the mechanisms of central nervous system invasion. PMID:25692137

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

    PubMed Central

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

    2013-01-01

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

  20. [Value of MRI in the etiologic diagnosis of cerebral infarction].

    PubMed

    Gauvrit, J Y; Leclerc, X; Pernodet, M; Oppenheim, C; Leys, D; Pruvo, J P

    2005-09-01

    The causes of ischaemic brain damage are numerous. Four main groups are described: atherosclerotic disease of the cervical and intracranial arteries represents 50% of the causes, small vessel disease with lacunar infarcts 25%, cardio-embolic disease 20% and non-atheromatous arterial disease and blood dyscrasias 10%. In 10% of cases, no etiology is identified. MRI has a dominating place in the etiologic assessment of cerebral infarction, by distinguishing the various types of infarction, detecting associated abnormalities like leukoencephalopathy and haemorrhage and by analyzing the lumen and wall of vessels.

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

    NASA Astrophysics Data System (ADS)

    Medich, David Christopher

    1997-09-01

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

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

    PubMed

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

    2015-08-01

    Methods to quantify ventricle material properties noninvasively using in vivo data are of great important in clinical applications. An ultrasound echo-based computational modeling approach was proposed to quantify left ventricle (LV) material properties, curvature, and stress/strain conditions and find differences between normal LV and LV with infarct. Echo image data were acquired from five patients with myocardial infarction (I-Group) and five healthy volunteers as control (H-Group). Finite element models were constructed to obtain ventricle stress and strain conditions. Material stiffening and softening were used to model ventricle active contraction and relaxation. Systolic and diastolic material parameter values were obtained by adjusting the models to match echo volume data. Young's modulus (YM) value was obtained for each material stress-strain curve for easy comparison. LV wall thickness, circumferential and longitudinal curvatures (C- and L-curvature), material parameter values, and stress/strain values were recorded for analysis. Using the mean value of H-Group as the base value, at end-diastole, I-Group mean YM value for the fiber direction stress-strain curve was 54% stiffer than that of H-Group (136.24 kPa versus 88.68 kPa). At end-systole, the mean YM values from the two groups were similar (175.84 kPa versus 200.2 kPa). More interestingly, H-Group end-systole mean YM was 126% higher that its end-diastole value, while I-Group end-systole mean YM was only 29% higher that its end-diastole value. This indicated that H-Group had much greater systole-diastole material stiffness variations. At beginning-of-ejection (BE), LV ejection fraction (LVEF) showed positive correlation with C-curvature, stress, and strain, and negative correlation with LV volume, respectively. At beginning-of-filling (BF), LVEF showed positive correlation with C-curvature and strain, but negative correlation with stress and LV volume, respectively. Using averaged values of two groups

  3. Homing of neural stem cells from the venous compartment into a brain infarct does not involve conventional interactions with vascular endothelium.

    PubMed

    Goncharova, Valentina; Das, Shreyasi; Niles, Walter; Schraufstatter, Ingrid; Wong, Aaron K; Povaly, Tatiana; Wakeman, Dustin; Miller, Leonard; Snyder, Evan Y; Khaldoyanidi, Sophia K

    2014-02-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2012-01-15

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

  6. Performance modeling of a wearable brain PET (BET) camera

    NASA Astrophysics Data System (ADS)

    Schmidtlein, C. R.; Turner, J. N.; Thompson, M. O.; Mandal, K. C.; Häggström, I.; Zhang, J.; Humm, J. L.; Feiglin, D. H.; Krol, A.

    2016-03-01

    Purpose: To explore, by means of analytical and Monte Carlo modeling, performance of a novel lightweight and low-cost wearable helmet-shaped Brain PET (BET) camera based on thin-film digital Geiger Avalanche Photo Diode (dGAPD) with LSO and LaBr3 scintillators for imaging in vivo human brain processes for freely moving and acting subjects responding to various stimuli in any environment. Methods: We performed analytical and Monte Carlo modeling PET performance of a spherical cap BET device and cylindrical brain PET (CYL) device, both with 25 cm diameter and the same total mass of LSO scintillator. Total mass of LSO in both the BET and CYL systems is about 32 kg for a 25 mm thick scintillator, and 13 kg for 10 mm thick scintillator (assuming an LSO density of 7.3 g/ml). We also investigated a similar system using an LaBr3 scintillator corresponding to 22 kg and 9 kg for the 25 mm and 10 mm thick systems (assuming an LaBr3 density of 5.08 g/ml). In addition, we considered a clinical whole body (WB) LSO PET/CT scanner with 82 cm ring diameter and 15.8 cm axial length to represent a reference system. BET consisted of distributed Autonomous Detector Arrays (ADAs) integrated into Intelligent Autonomous Detector Blocks (IADBs). The ADA comprised of an array of small LYSO scintillator volumes (voxels with base a×a: 1.0 <= a <= 2.0 mm and length c: 3.0 <= c <= 6.0 mm) with 5-65 μm thick reflective layers on its five sides and sixth side optically coupled to the matching array of dGAPDs and processing electronics with total thickness of 50 μm. Simulated energy resolution was 10.8% and 3.3% for LSO and LaBr3 respectively and the coincidence window was set at 2 ns. The brain was simulated as a sphere of uniform F-18 activity with diameter of 10 cm embedded in a center of water sphere with diameter of 10 cm. Results: Analytical and Monte Carlo models showed similar results for lower energy window values (458 keV versus 445 keV for LSO, and 492 keV versus 485 keV for LaBr3

  7. Bayesian network models in brain functional connectivity analysis

    PubMed Central

    Zhang, Sheng; Li, Chiang-shan R.

    2013-01-01

    Much effort has been made to better understand the complex integration of distinct parts of the human brain using functional magnetic resonance imaging (fMRI). Altered functional connectivity between brain regions is associated with many neurological and mental illnesses, such as Alzheimer and Parkinson diseases, addiction, and depression. In computational science, Bayesian networks (BN) have been used in a broad range of studies to model complex data set in the presence of uncertainty and when expert prior knowledge is needed. However, little is done to explore the use of BN in connectivity analysis of fMRI data. In this paper, we present an up-to-date literature review and methodological details of connectivity analyses using BN, while highlighting caveats in a real-world application. We present a BN model of fMRI dataset obtained from sixty healthy subjects performing the stop-signal task (SST), a paradigm widely used to investigate response inhibition. Connectivity results are validated with the extant literature including our previous studies. By exploring the link strength of the learned BN’s and correlating them to behavioral performance measures, this novel use of BN in connectivity analysis provides new insights to the functional neural pathways underlying response inhibition. PMID:24319317

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

    SciTech Connect

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

    2006-08-24

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

  9. Fast correspondences for statistical shape models of brain structures

    NASA Astrophysics Data System (ADS)

    Bernard, Florian; Vlassis, Nikos; Gemmar, Peter; Husch, Andreas; Thunberg, Johan; Goncalves, Jorge; Hertel, Frank

    2016-03-01

    Statistical shape models based on point distribution models are powerful tools for image segmentation or shape analysis. The most challenging part in the generation of point distribution models is the identification of corresponding landmarks among all training shapes. Since in general the true correspondences are unknown, correspondences are frequently established under the hypothesis that correct correspondences lead to a compact model, which is mostly tackled by continuous optimisation methods. In favour of the prospect of an efficient optimisation, we present a simplified view of the correspondence problem for statistical shape models that is based on point-set registration, the linear assignment problem and mesh fairing. At first, regularised deformable point-set registration is performed and combined with solving the linear assignment problem to obtain correspondences between shapes on a global scale. With that, rough correspondences are established that may not yet be accurate on a local scale. Then, by using a mesh fairing procedure, consensus of the correspondences on a global and local scale among the entire set of shapes is achieved. We demonstrate that for the generation of statistical shape models of deep brain structures, the proposed approach is preferable over existing population-based methods both in terms of a significantly shorter runtime and in terms of an improved quality of the resulting shape model.

  10. Predicting individual brain functional connectivity using a Bayesian hierarchical model.

    PubMed

    Dai, Tian; Guo, Ying

    2017-02-15

    Network-oriented analysis of functional magnetic resonance imaging (fMRI), especially resting-state fMRI, has revealed important association between abnormal connectivity and brain disorders such as schizophrenia, major depression and Alzheimer's disease. Imaging-based brain connectivity measures have become a useful tool for investigating the pathophysiology, progression and treatment response of psychiatric disorders and neurodegenerative diseases. Recent studies have started to explore the possibility of using functional neuroimaging to help predict disease progression and guide treatment selection for individual patients. These studies provide the impetus to develop statistical methodology that would help provide predictive information on disease progression-related or treatment-related changes in neural connectivity. To this end, we propose a prediction method based on Bayesian hierarchical model that uses individual's baseline fMRI scans, coupled with relevant subject characteristics, to predict the individual's future functional connectivity. A key advantage of the proposed method is that it can improve the accuracy of individualized prediction of connectivity by combining information from both group-level connectivity patterns that are common to subjects with similar characteristics as well as individual-level connectivity features that are particular to the specific subject. Furthermore, our method also offers statistical inference tools such as predictive intervals that help quantify the uncertainty or variability of the predicted outcomes. The proposed prediction method could be a useful approach to predict the changes in individual patient's brain connectivity with the progression of a disease. It can also be used to predict a patient's post-treatment brain connectivity after a specified treatment regimen. Another utility of the proposed method is that it can be applied to test-retest imaging data to develop a more reliable estimator for individual

  11. N-acetylcysteine prevents low T3 syndrome and attenuates cardiac dysfunction in a male rat model of myocardial infarction.

    PubMed

    Lehnen, Tatiana Ederich; Santos, Marcus Vinicius; Lima, Adrio; Maia, Ana Luiza; Wajner, Simone Magagnin

    2017-02-17

    Nonthyroidal illness syndrome (NTIS) affects patients with myocardial infarction (MI). Oxidative stress has been implicated as a causative factor of NTIS, and reversed via N-acetylcysteine (NAC). Male Wistar rats submitted to left anterior coronary artery occlusion received NAC or placebo. Decreases in T3 levels were noted in MI-placebo at 10 and 28 days post-MI, but not in MI-NAC. Groups exhibited similar infarct areas whereas MI-NAC exhibited higher ejection fraction (EF) than MI-placebo. Left ventricular systolic (LVSd) and diastolic (LVDd) diameters were also preserved in MI-NAC, but not in MI-placebo. EF was positively correlated with T3 levels. Oxidative balance was deranged only in MI-placebo animals. Increased D3 expression was detected in the cardiomyocytes of MI-placebo compared with normal heart tissue. NAC was shown to diminish D3 expression and activity in MI-NAC. These results show that restoring redox balance by NAC treatment prevents NTIS- related thyroid hormone derangement and preserve heart function in rats subjected to MI.

  12. Planarian brain regeneration as a model system for developmental neurotoxicology

    PubMed Central

    Hagstrom, Danielle; Cochet‐Escartin, Olivier

    2016-01-01

    Abstract Freshwater planarians, famous for their regenerative prowess, have long been recognized as a valuable in vivo animal model to study the effects of chemical exposure. In this review, we summarize the current techniques and tools used in the literature to assess toxicity in the planarian system. We focus on the planarian's particular amenability for neurotoxicology and neuroregeneration studies, owing to the planarian's unique ability to regenerate a centralized nervous system. Zooming in from the organismal to the molecular level, we show that planarians offer a repertoire of morphological and behavioral readouts while also being amenable to mechanistic studies of compound toxicity. Finally, we discuss the open challenges and opportunities for planarian brain regeneration to become an important model system for modern toxicology. PMID:27499880

  13. Computational modeling of brain pathologies: the case of multiple sclerosis.

    PubMed

    Pappalardo, Francesco; Rajput, Abdul-Mateen; Motta, Santo

    2016-12-22

    The central nervous system is the most complex network of the human body. The existence and functionality of a large number of molecular species in human brain are still ambiguous and mostly unknown, thus posing a challenge to Science and Medicine. Neurological diseases inherit the same level of complexity, making effective treatments difficult to be found. Multiple sclerosis (MS) is a major neurological disease that causes severe inabilities and also a significant social burden on health care system: between 2 and 2.5 million people are affected by it, and the cost associated with it is significantly higher as compared with other neurological diseases because of the chronic nature of the disease and to the partial efficacy of current therapies. Despite difficulties in understanding and treating MS, many computational models have been developed to help neurologists. In the present work, we briefly review the main characteristics of MS and present a selection criteria of modeling approaches.

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

    PubMed Central

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

    2014-01-01

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

  15. A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

    PubMed Central

    Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

    2016-01-01

    The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes–permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research. PMID:27830712

  16. A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

    NASA Astrophysics Data System (ADS)

    Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

    2016-11-01

    The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes–permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

  17. Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

    PubMed

    Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

    2014-03-25

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

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

    SciTech Connect

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

    2009-09-15

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

  19. Computational modeling of pedunculopontine nucleus deep brain stimulation

    PubMed Central

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

    2013-01-01

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

  20. Computational modeling of pedunculopontine nucleus deep brain stimulation

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  1. PRIORITIZING THE DEVELOPMENT OF MOUSE MODELS FOR CHILDHOOD BRAIN DISORDERS

    PubMed Central

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

    2015-01-01

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

  2. Customizing Deep Brain Stimulation to the Patient Using Computational Models

    PubMed Central

    McIntyre, Cameron C.; Frankenmolle, Anneke; Wu, Jennifer; Noecker, Angela M.; Alberts, Jay L.

    2011-01-01

    Bilateral subthalamic (STN) deep brain stimulation (DBS) is effective in improving the cardinal motor signs of advanced Parkinson's disease (PD); however declines in cognitive function have been associated with this procedure. The aim of this study was to assess cognitive-motor performance of 10 PD patients implanted with STN DBS systems during either clinically determined stimulation settings or settings derived from a computational model. Cicerone DBS software was used to define the model parameters such that current spread to non-motor areas of the STN was minimized. Clinically determined and model defined parameters were equally effective in improving motor scores on the traditional clinical rating scale (UPDRS-III). Under modest dual-task conditions, cognitive-motor performance was worse with clinically determined compared to model derived parameters. In addition, the model parameters provided a 33% reduction in power consumption. These results indicate that the cognitivemotor declines associated with bilateral STN can be mitigated, without compromising motor benefits, utilizing stimulation parameters that minimize current spread into non-motor regions of the STN. PMID:19965023

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  4. Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats

    PubMed Central

    Liu, Chunyan; Wang, Yangang

    2017-01-01

    In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive

  5. Modeling brain circuitry over a wide range of scales

    PubMed Central

    Fua, Pascal; Knott, Graham W.

    2015-01-01

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

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

    PubMed

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

    2014-08-01

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

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

    PubMed Central

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

    2014-01-01

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

  8. A model for genomic imprinting in the social brain: adults.

    PubMed

    Ubeda, Francisco; Gardner, Andy

    2011-02-01

    Genomic imprinting refers to genes that are silenced when inherited via sperm or via egg. The silencing of genes conditional upon their parental origin requires an evolutionary explanation. The most widely accepted theory for the evolution of genomic imprinting-the kinship theory-argues that conflict between maternally inherited and paternally inherited genes over phenotypes with asymmetric effects on matrilineal and patrilineal kin results in self-imposed silencing of one of the copies. This theory has been applied to imprinting of genes expressed in the placenta, and infant brain determining the allocation of parental resources being the source of conflict parental promiscuity. However, there is growing evidence that imprinted genes are expressed in the postinfant brain where parental promiscuity per se is no longer a source of conflict. Here, we advance the kinship theory by developing an evolutionary model of genomic imprinting in adults, driven by intragenomic conflict over allocation to parental versus communal care. We consider the role of sex differences in dispersal and variance in reproductive success as sources of conflict. We predict that, in hominids and birds, parental care will be expressed by maternally inherited genes. In nonhominid mammals, we predict more diversity, with some mammals showing the same pattern and other showing the reverse. We use the model to interpret experimental data on imprinted genes in the house mouse: specifically, paternally expressed Peg1 and Peg3 genes, underlying maternal care, and maternally expressed Gnas and paternally expressed Gnasxl genes, underlying communal care. We also use the model to relate ancestral demography to contemporary imprinting disorders of adults, in humans and other taxa.

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

    PubMed Central

    Arbib, Michael; Ganesh, Varsha; Gasser, Brad

    2014-01-01

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

  10. Mesenchymal Stem Cell Transplantation Enhancement in Myocardial Infarction Rat Model under Ultrasound Combined with Nitric Oxide Microbubbles

    PubMed Central

    Tong, Jiayi; Ding, Jiandong; Shen, Xiangbo; Chen, Long; Bian, Yeping; Ma, Genshan; Yao, Yuyu; Yang, Fang

    2013-01-01

    Objective This study evaluated the effects of ultrasound combined with the homemade nitric oxide (NO) micro-bubble destruction on the in vitro proliferation, apoptosis, and migration of mesenchymal stem cells (MSCs). Furthermore, we studied whether or not irradiation of the NO micro-bubble combined with bone-marrow derived MSC infusion had a better effect on treating myocardial infarction. The possible mechanism of MSC delivery into the infarcted myocardium was also investigated. Methods The murine bone marrow-derived MSCs were isolated, cultured, irradiated, and combined with different concentrations of NO microbubbles. MTT proliferation assay, annexin V-FITC apoptosis detection, migration assay, and RT-PCR were performed 24 h after the irradiation. The NO micro-bubbles was a intravenously injected, followed by the infusion of MSCs, which were labeled by CM-Dil. Myocardium was harvested 48 h later and the distribution of MSCs was observed by laser scanning confocal microscope after frozen sectioning. Echocardiography, histological examination, RT-PCR, and western blotting were performed four weeks after the cell transplantation. Results Ultrasound combined with 1:70 NO micro-bubbles had no significant impact on the proliferation or apoptosis of MSCs. Transwell chamber findings demonstrated that MSCs migrated more efficiently in group that underwent ultrasound combined with 1:70 NO micro-bubbles. The Real-time PCR results indicated that the expression of CXCR4 was much higher in the group undergoing ultrasound combined with 1:70 NO micro-bubbles. The normalized fluorescence intensity greatly increased in the group of US+NO micro-bubbles and the cardiac function was also markedly improved. Immunohistochemical staining showed that the capillary density was much greater in the group of US+NO micro-bubbles as compared to that of the other groups. RT-PCR and western blotting also revealed a higher SDF-1 and VEGF expression in the group of US+NO micro

  11. Opioid Abuse After Traumatic Brain Injury: Evaluation Using Rodet Models

    DTIC Science & Technology

    2014-07-01

    dependence development using both precipitated and spontaneous withdrawal. Key findings to date: • There was no difference in baseline nociception ( pain ...analgesia studies demonstrate that moderate brain injury does not result in an altered pain state or diminished response to oxycodone analgesia, the... pain medications. There is significant overlap in anatomical brain regions involved in reward pathways associated with addiction and the brain regions

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

    PubMed

    Wittek, Adam; Hawkins, Trent; Miller, Karol

    2009-02-01

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

  13. Vitamin E isoforms alpha-tocotrienol and gamma-tocopherol prevent cerebral infarction in mice.

    PubMed

    Mishima, Kenichi; Tanaka, Takamitsu; Pu, Fengling; Egashira, Nobuaki; Iwasaki, Katsunori; Hidaka, Ryoji; Matsunaga, Kazuhisa; Takata, Jiro; Karube, Yoshiharu; Fujiwara, Michihiro

    2003-01-30

    Alpha-tocopherol and its derivatives have been shown to be effective in reducing cerebral ischemia-induced brain damage. However, the effects of other vitamin E isoforms have not been characterized. In the present study, we investigated the effects of six different isoforms of vitamin E on the ischemic brain damage in the mice middle cerebral artery (MCA) occlusion model. All vitamin E isoforms were injected i.v., twice, immediately before and 3 h after the occlusion. Alpha-tocopherol (2 mM), alpha-tocotrienol (0.2 and 2 mM) and gamma-tocopherol (0.2 and 2 mM) significantly decreased the size of the cerebral infarcts 1 day after the MCA occlusion, while gamma-tocotrienol, delta-tocopherol and delta-tocotrienol showed no effect on the cerebral infarcts. These results suggest that alpha-tocotrienol and gamma-tocopherol are potent and effective agents for preventing cerebral infarction induced by MCA occlusion.

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

    PubMed Central

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

    2007-01-01

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

  15. The role of infarct transmural extent in infarct extension: A computational study.

    PubMed

    Leong, Chin-Neng; Lim, Einly; Andriyana, Andri; Al Abed, Amr; Lovell, Nigel Hamilton; Hayward, Christopher; Hamilton-Craig, Christian; Dokos, Socrates

    2017-02-01

    Infarct extension, a process involving progressive extension of the infarct zone (IZ) into the normally perfused border zone (BZ), leads to continuous degradation of the myocardial function and adverse remodelling. Despite carrying a high risk of mortality, detailed understanding of the mechanisms leading to BZ hypoxia and infarct extension remains unexplored. In the present study, we developed a 3D truncated ellipsoidal left ventricular model incorporating realistic electromechanical properties and fibre orientation to examine the mechanical interaction among the remote, infarct and BZs in the presence of varying infarct transmural extent (TME). Localized highly abnormal systolic fibre stress was observed at the BZ, owing to the simultaneous presence of moderately increased stiffness and fibre strain at this region, caused by the mechanical tethering effect imposed by the overstretched IZ. Our simulations also demonstrated the greatest tethering effect and stress in BZ regions with fibre direction tangential to the BZ-remote zone boundary. This can be explained by the lower stiffness in the cross-fibre direction, which gave rise to a greater stretching of the IZ in this direction. The average fibre strain of the IZ, as well as the maximum stress in the sub-endocardial layer, increased steeply from 10% to 50% infarct TME, and slower thereafter. Based on our stress-strain loop analysis, we found impairment in the myocardial energy efficiency and elevated energy expenditure with increasing infarct TME, which we believe to place the BZ at further risk of hypoxia. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Ischemic brain injury decreases dynamin-like protein 1 expression in a middle cerebral artery occlusion animal model and glutamate-exposed HT22 cells

    PubMed Central

    Jang, Ah-Ram

    2016-01-01

    Dynamin-like protein I (DLP-1) is an important mitochondrial fission and fusion protein that is associated with apoptotic cell death in neurodegenerative diseases. In this study, we investigated DLP-1 expression in a focal cerebral ischemia animal model and glutamate-exposed hippocampal-derived cell line. Middle cerebral artery occlusion (MCAO) was surgically induced in adult male rats to induce focal cerebral ischemic injury. Brain tissues were collected 24 hours after the onset of MCAO. MCAO induces an increase in infarct volume and histopathological changes in the cerebral cortex. We identified a decrease in DLP-1 in the cerebral cortices of MCAO-injured animals using a proteomic approach and Western blot analysis. Moreover, glutamate treatment significantly decreased DLP-1 expression in a hippocampal-derived cell line. The decrease in DLP-1 indicates mitochondrial dysfunction. Thus, these results suggest that neuronal cell injury induces a decrease in DLP-1 levels and consequently leads to neuronal cell death. PMID:28053612

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

    ERIC Educational Resources Information Center

    Bump, Jerome

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. Informing pedagogy through the brain-targeted teaching model.

    PubMed

    Hardiman, Mariale

    2012-01-01

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

  1. Informing Pedagogy Through the Brain-Targeted Teaching Model

    PubMed Central

    Hardiman, Mariale

    2012-01-01

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

  2. Mapping Metabolic Brain Activity in Three Models of Hepatic Encephalopathy

    PubMed Central

    Méndez, Marta; Fidalgo, Camino; Aller, María Ángeles; Arias, Jaime; Arias, Jorge L.

    2013-01-01

    Cirrhosis is a common disease in Western countries. Liver failure, hyperammonemia, and portal hypertension are the main factors that contribute to human cirrhosis that frequently leads to a neuropsychiatric disorder known as hepatic encephalopathy (HE). In this study, we examined the differential contribution of these leading factors to the oxidative metabolism of diverse brain limbic system regions frequently involved in memory process by histochemical labelling of cytochrome oxidase (COx). We have analyzed cortical structures such as the infralimbic and prelimbic cotices, subcortical structures such as hippocampus and ventral striatum, at thalamic level like the anterodorsal, anteroventral, and mediodorsal thalamus, and, finally, the hypothalamus, where the mammillary nuclei (medial and lateral) were measured. The severest alteration is found in the model that mimics intoxication by ammonia, followed by the thioacetamide-treated group and the portal hypertension group. No changes were found at the mammillary bodies for any of the experimental groups. PMID:23573412

  3. A propositional representation model of anatomical and functional brain data.

    PubMed

    Maturana, Pablo; Batrancourt, Bénédicte

    2011-01-01

    Networks can represent a large number of systems. Recent advances in the domain of networks have been transferred to the field of neuroscience. For example, the graph model has been used in neuroscience research as a methodological tool to examine brain networks organization, topology and complex dynamics, as well as a framework to test the structure-function hypothesis using neuroimaging data. In the current work we propose a graph-theoretical framework to represent anatomical, functional and neuropsychological assessment instruments information. On the one hand, interrelationships between anatomic elements constitute an anatomical graph. On the other hand, a functional graph contains several cognitive functions and their more elementary cognitive processes. Finally, the neuropsychological assessment instruments graph includes several neuropsychological tests and scales linked with their different sub-tests and variables. The two last graphs are connected by relations of type "explore" linking a particular instrument with the cognitive function it explores. We applied this framework to a sample of patients with focal brain damage. Each patient was related to: (i) the cerebral entities injured (assessed with structural neuroimaging data) and (ii) the neusopsychological assessment tests carried out (weight by performance). Our model offers a suitable platform to visualize patients' relevant information, facilitating the representation, standardization and sharing of clinical data. At the same time, the integration of a large number of patients in this framework will make possible to explore relations between anatomy (injured entities) and function (performance in different tests assessing different cognitive functions) and the use of neurocomputational tools for graph analysis may help diagnostic and contribute to the comprehension of neural bases of cognitive functions.

  4. Effects of recombinant human brain natriuretic peptide on the prognosis of patients with acute anterior myocardial infarction undergoing primary percutaneous coronary intervention: a prospective, multi-center, randomized clinical trial

    PubMed Central

    Hou, Ai-Jie; Zang, Hong-Yun; Huang, Ru-Gang; Zheng, Xiao-Qun; Lin, Hai-Long; Wang, Wei; Hou, Ping; Xia, Fei; Li, Zhan-Quan

    2017-01-01

    Background This study aims to investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on serum enzyme data, cardiac function parameters and cardiovascular events in patients with acute anterior myocardial infarction (MI). Methods A total of 421 patients with acute anterior or extensive anterior MI were collected from 20 hospitals. These patients were randomly divided into two groups: rhBNP and control groups. Both groups of patients received primary percutaneous coronary intervention (PCI) within the effective time window. In the rhBNP group, rhBNP administration (0.01 µg/kg/min, 48–72 successive hours) was performed as early as possible after hospital admission. Prior to and one or seven days after PCI, serum concentrations of cardiac troponin (cTnT), creatine kinase-MB (CK-MB) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. At seven days and 6 months after PCI, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd) and stroke volume (SV) were measured using 2D Doppler echocardiography. MACEs that occurred during hospitalization and within 6 months after PCI were recorded. Results At postoperative days one and seven, serum concentrations of cTnT were significantly lower in the rhBNP group than in the control group. At postoperative day one, serum concentrations of CK-MB were significantly lower in the rhBNP group than in the control group. At postoperative day seven, serum concentrations of NT-proBNP were significantly lower in the rhBNP group than in the control group, and LVEF was significantly greater in the rhBNP group than in the control group. At postoperative 6 months, LVEDd was significantly lower in the rhBNP group compared with the control group. In addition, SV and LVEF were significantly greater in the rhBNP group than in the control group. By postoperative month 6, the incidence of composite cardiovascular events (16.0% vs. 26.0%, P=0.012), cardiac death (7.0% vs.13

  5. Mapping the dynamics of brain perfusion using functional ultrasound in a rat model of transient middle cerebral artery occlusion.

    PubMed

    Brunner, Clément; Isabel, Clothilde; Martin, Abraham; Dussaux, Clara; Savoye, Anne; Emmrich, Julius; Montaldo, Gabriel; Mas, Jean-Louis; Baron, Jean-Claude; Urban, Alan

    2017-01-01

    Following middle cerebral artery occlusion, tissue outcome ranges from normal to infarcted depending on depth and duration of hypoperfusion as well as occurrence and efficiency of reperfusion. However, the precise time course of these changes in relation to tissue and behavioral outcome remains unsettled. To address these issues, a three-dimensional wide field-of-view and real-time quantitative functional imaging technique able to map perfusion in the rodent brain would be desirable. Here, we applied functional ultrasound imaging, a novel approach to map relative cerebral blood volume without contrast agent, in a rat model of brief proximal transient middle cerebral artery occlusion to assess perfusion in penetrating arterioles and venules acutely and over six days thanks to a thinned-skull preparation. Functional ultrasound imaging efficiently mapped the acute changes in relative cerebral blood volume during occlusion and following reperfusion with high spatial resolution (100 µm), notably documenting marked focal decreases during occlusion, and was able to chart the fine dynamics of tissue reperfusion (rate: one frame/5 s) in the individual rat. No behavioral and only mild post-mortem immunofluorescence changes were observed. Our study suggests functional ultrasound is a particularly well-adapted imaging technique to study cerebral perfusion in acute experimental stroke longitudinally from the hyper-acute up to the chronic stage in the same subject.

  6. Traumatic Brain Injury – Modeling Neuropsychiatric Symptoms in Rodents

    PubMed Central

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

    2013-01-01

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

  7. Using chaotic artificial neural networks to model memory in the brain

    NASA Astrophysics Data System (ADS)

    Aram, Zainab; Jafari, Sajad; Ma, Jun; Sprott, Julien C.; Zendehrouh, Sareh; Pham, Viet-Thanh

    2017-03-01

    In the current study, a novel model for human memory is proposed based on the chaotic dynamics of artificial neural networks. This new model explains a biological fact about memory which is not yet explained by any other model: There are theories that the brain normally works in a chaotic mode, while during attention it shows ordered behavior. This model uses the periodic windows observed in a previously proposed model for the brain to store and then recollect the information.

  8. Lipid mapping of the rat brain for models of disease.

    PubMed

    Martínez-Gardeazabal, J; González de San Román, E; Moreno-Rodríguez, M; Llorente-Ovejero, A; Manuel, I; Rodríguez-Puertas, R

    2017-02-21

    Lipids not only constitute the primary component of cellular membranes and contribute to metabolism but also serve as intracellular signaling molecules and bind to specific membrane receptors to control cell proliferation, growth and convey neuroprotection. Over the last several decades, the development of new analytical techniques, such as imaging mass spectrometry (IMS), has contributed to our understanding of their involvement in physiological and pathological conditions. IMS allows researchers to obtain a wide range of information about the spatial distribution and abundance of the different lipid molecules that is crucial to understand brain functions. The primary aim of this study was to map the spatial distribution of different lipid species in the rat central nervous system (CNS) using IMS to find a possible relationship between anatomical localization and physiology. The data obtained were subsequently applied to a model of neurological disease, the 192IgG-saporin lesion model of memory impairment. The results were obtained using a LTQ-Orbitrap XL mass spectrometer in positive and negative ionization modes and analyzed by ImageQuest and MSIReader software. A total of 176 different molecules were recorded based on the specific localization of their intensities. However, only 34 lipid species in negative mode and 51 in positive were assigned to known molecules with an error of 5ppm. These molecules were grouped by different lipid families, resulting in: Phosphatidylcholines (PC): PC (34: 1)+K(+) and PC (32: 0)+K(+) distributed primarily in gray matter, and PC (36: 1)+K(+) and PC (38: 1)+Na(+) distributed in white matter. Phosphatidic acid (PA): PA (38: 3)+K(+) in white matter, and PA (38: 5)+K(+) in gray matter and brain ventricles. Phosphoinositol (PI): PI (18: 0/20: 4)-H(+) in gray matter, and PI (O-30: 1) or PI (P-30: 0)-H(+) in white matter. Phosphatidylserines (PS): PS (34: 1)-H(+) in gray matter, and PS (38: 1)-H(+) in white matter. Sphingomyelin (SM

  9. An in vitro model for the assessment of stem cell fate following implantation within the infarct microenvironment identifies ISL-1 expression as the strongest predictor of c-Kit(+) cardiac progenitor cells' therapeutic potential.

    PubMed

    Sullivan, Kelly E; Burns, Laura J; Black, Lauren D

    2015-11-01

    Cell therapy has the potential to drastically improve clinical outcomes for the 1.45 million patients suffering from a myocardial infarction (MI) each year in the U.S. However, the limitations associated with this treatment - including poor engraftment, significant cell death and poor differentiation potential - have prevented its widespread application clinically. To optimize functional improvements provided by transplanted cells, there is a need to develop methods that increase cellular retention and viability, while supporting differentiation and promoting paracrine signaling. Current in vivo models are expensive, difficult to access and manipulate and are time consuming. We have developed an in vitro model of MI which allows for a straightforward, consistent and relatively accurate prediction of cell fate following injection in vivo. The model demonstrated how the infarct environment impairs cellular engraftment and differentiation, but identified an implantation strategy which enhanced cell fate in vitro. Multivariate linear regression identified variables within the model that regulated vascular differentiation potential including oxygen tension, stiffness and cytokine presence, while cardiac differentiation was more accurately predicted by Isl-1 expression in the original cell isolate than any other variable present within the model system. The model highlighted how the cells' sensitivity to the infarct variables varied from line to line, which emphasizes the importance of the model system for the prediction of cell fate on a patient specific basis. Further development of this model system could help predict the clinical efficacy of cardiac progenitor cell therapy at the patient level as well as identify the optimal strategy for cell delivery.

  10. A Drosophila model of closed head traumatic brain injury.

    PubMed

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

    2013-10-29

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

  11. Local Model of Arteriovenous Malformation of the Human Brain

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  12. A New Rabbit Model of Pediatric Traumatic Brain Injury

    PubMed Central

    Zhang, Zhi; Saraswati, Manda; Koehler, Raymond C.; Robertson, Courtney

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a common cause of disability in childhood, resulting in numerous physical, behavioral, and cognitive sequelae, which can influence development through the lifespan. The mechanisms by which TBI influences normal development and maturation remain largely unknown. Pediatric rodent models of TBI often do not demonstrate the spectrum of motor and cognitive deficits seen in patients. To address this problem, we developed a New Zealand white rabbit model of pediatric TBI that better mimics the neurological injury seen after TBI in children. On postnatal Day 5-7 (P5-7), rabbits were injured by a controlled cortical impact (6-mm impactor tip; 5.5 m/sec, 2-mm depth, 50-msec duration). Rabbits from the same litter served as naïve (no injury) and sham (craniotomy alone) controls. Functional abilities and activity levels were measured 1 and 5 d after injury. Maturation level was monitored daily. We performed cognitive tests during P14-24 and sacrificed the animals at 1, 3, 7, and 21 d after injury to evaluate lesion volume and microglia. TBI kits exhibited delayed achievement of normal developmental milestones. They also demonstrated significant cognitive deficits, with lower percentage of correct alternation rate in the T-maze (n=9-15/group; p<0.001) and less discrimination between novel and old objects (p<0.001). Lesion volume increased from 16% at Day 3 to 30% at Day 7 after injury, indicating ongoing secondary injury. Activated microglia were noted at the injury site and also in white matter regions of the ipsilateral and contralateral hemispheres. The neurologic and histologic changes in this model are comparable to those reported clinically. Thus, this rabbit model provides a novel platform for evaluating neuroprotective therapies in pediatric TBI. PMID:25758339

  13. Multistability in Large Scale Models of Brain Activity

    PubMed Central

    Golos, Mathieu; Jirsa, Viktor; Daucé, Emmanuel

    2015-01-01

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

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

    PubMed

    Namazi, Hamidreza; Kulish, Vladimir V

    2015-01-01

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

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

    PubMed Central

    Kulish, Vladimir V.

    2015-01-01

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

  16. Brain mechanisms of Change in Addictions Treatment: Models, Methods, and Emerging Findings.

    PubMed

    Chung, Tammy; Noronha, Antonio; Carroll, Kathleen M; Potenza, Marc N; Hutchison, Kent; Calhoun, Vince D; Gabrieli, John D E; Morgenstern, Jon; Nixon, Sara Jo; Wexler, Bruce E; Brewer, Judson; Ray, Lara; Filbey, Francesca; Strauman, Timothy J; Kober, Hedy; Feldstein Ewing, Sarah W

    2016-09-01

    Increased understanding of "how" and "for whom" treatment works at the level of the brain has potential to transform addictions treatment through the development of innovative neuroscience-informed interventions. The 2015 Science of Change meeting bridged the fields of neuroscience and psychotherapy research to identify brain mechanisms of behavior change that are "common" across therapies, and "specific" to distinct behavioral interventions. Conceptual models of brain mechanisms underlying effects of Cognitive Behavioral Therapy, mindfulness interventions, and Motivational Interviewing were discussed. Presentations covered methods for integrating neuroimaging into psychotherapy research, and novel analytic approaches. Effects of heavy substance use on the brain, and recovery of brain functioning with sustained abstinence, which may be facilitated by cognitive training, were reviewed. Neuroimaging provides powerful tools for determining brain mechanisms underlying psychotherapy and medication effects, predicting and monitoring outcomes, developing novel interventions that target specific brain circuits, and identifying for whom an intervention will be effective.

  17. A comparative study of theoretical graph models for characterizing structural networks of human brain.

    PubMed

    Li, Xiaojin; Hu, Xintao; Jin, Changfeng; Han, Junwei; Liu, Tianming; Guo, Lei; Hao, Wei; Li, Lingjiang

    2013-01-01

    Previous studies have investigated both structural and functional brain networks via graph-theoretical methods. However, there is an important issue that has not been adequately discussed before: what is the optimal theoretical graph model for describing the structural networks of human brain? In this paper, we perform a comparative study to address this problem. Firstly, large-scale cortical regions of interest (ROIs) are localized by recently developed and validated brain reference system named Dense Individualized Common Connectivity-based Cortical Landmarks (DICCCOL) to address the limitations in the identification of the brain network ROIs in previous studies. Then, we construct structural brain networks based on diffusion tensor imaging (DTI) data. Afterwards, the global and local graph properties of the constructed structural brain networks are measured using the state-of-the-art graph analysis algorithms and tools and are further compared with seven popular theoretical graph models. In addition, we compare the topological properties between two graph models, namely, stickiness-index-based model (STICKY) and scale-free gene duplication model (SF-GD), that have higher similarity with the real structural brain networks in terms of global and local graph properties. Our experimental results suggest that among the seven theoretical graph models compared in this study, STICKY and SF-GD models have better performances in characterizing the structural human brain network.

  18. Development of multifunctional optical coherence tomography and application to mouse myocardial infarction model in vivo (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jang, Sun-Joo; Park, Taejin; Shin, Inho; Park, Hyun Sang; Shin, Paul; Oh, Wang-Yuhl

    2016-02-01

    Optical coherence tomography (OCT) is a useful imaging method for in vivo tissue imaging with deep penetration and high spatial resolution. However, imaging of the beating mouse heart is still challenging due to limited temporal resolution or penetration depth. Here, we demonstrate a multifunctional OCT system for a beating mouse heart, providing various types of visual information about heart pathophysiology with high spatiotemporal resolution and deep tissue imaging. Angiographic imaging and polarization-sensitive (PS) imaging were implemented with the electrocardiogram (ECG)-triggered beam scanning scheme on the high-speed OCT platform (A-line rate: 240 kHz). Depth-resolved local birefringence and the local orientation of the mouse myocardial fiber were visualized from the PS-OCT. ECG-triggered angiographic OCT (AOCT) with the custom-built motion stabilization imaging window provided myocardial vasculature of a beating mouse heart. Mice underwent coronary artery ligation to derive myocardial infarction (MI) and were imaged with the multifunctional OCT system at multiple time points. AOCT and PS-OCT visualize change of functionality of coronary vessels and myocardium respectively at different phases (acute and chronic) of MI in an ischemic mouse heart. Taken together, the integrated imaging of PS-OCT and AOCT would play an important role in study of MI providing multi-dimensional information of the ischemic mouse heart in vivo.

  19. Synchronization Tomography: Modeling and Exploring Complex Brain Dynamics

    NASA Astrophysics Data System (ADS)

    Fieseler, Thomas

    2002-03-01

    Phase synchronization (PS) plays an important role both under physiological and pathological conditions. With standard averaging techniques of MEG data, it is difficult to reliably detect cortico-cortical and cortico-muscular PS processes that are not time-locked to an external stimulus. For this reason, novel synchronization analysis techniques were developed and directly applied to MEG signals. Of course, due to the lack of an inverse modeling (i.e. source localization), the spatial resolution of this approach was limited. To detect and localize cerebral PS, we here present the synchronization tomography (ST): For this, we first estimate the cerebral current source density by means of the magnetic field tomography (MFT). We then apply the single-run PS analysis to the current source density in each voxel of the reconstruction space. In this way we study simulated PS, voxel by voxel in order to determine the spatio-temporal resolution of the ST. To this end different generators of ongoing rhythmic cerebral activity are simulated by current dipoles at different locations and directions, which are modeled by slightly detuned chaotic oscillators. MEG signals for these generators are simulated for a spherical head model and a whole-head MEG system. MFT current density solutions are calculated from these simulated signals within a hemispherical source space. We compare the spatial resolution of the ST with that of the MFT. Our results show that adjacent sources which are indistinguishable for the MFT, can nevertheless be separated with the ST, provided they are not strongly phase synchronized. This clearly demonstrates the potential of combining spatial information (i.e. source localization) with temporal information for the anatomical localization of phase synchronization in the human brain.

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

    NASA Astrophysics Data System (ADS)

    Moualhi, Wafa; Ezzeddine, Zagrouba

    2015-02-01

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

  1. Probabilistic multiobject deformable model for MR/SPECT brain image registration and segmentation

    NASA Astrophysics Data System (ADS)

    Nikou, Christophoros; Heitz, Fabrice; Armspach, Jean-Paul

    1999-05-01

    A probabilistic deformable model for the representation of brain structures is described. The statistically learned deformable model represents the relative location of head (skull and scalp) and brain surfaces in MR/SPECT images pairs and accommodates the significant variability of these anatomical structures across different individuals. To provide a training set, a representative collection of 3D MRI volumes of different patients have first been registered to a reference image. The head and brain surfaces of each volume are parameterized by the amplitudes of the vibration modes of a deformable spherical mesh. For a given MR image in the training set, a vector containing the largest vibration modes describing the head and the brain is created. This random vector is statistically constrained by retaining the most significant variations modes of its Karhunen-Loeve expansion on the training population. By these means, both head and brain surfaces are deformed according to the anatomical variability observed in the training set. Two applications of the probabilistic deformable model are presented: the deformable model-based registration of 3D multimodal (MR/SPECT) brain images and the segmentation of the brain from MRI using the probabilistic constraints embedded in the deformable model. The multi-object deformable model may be considered as a first step towards the development of a general purpose probabilistic anatomical atlas of the brain.

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

    PubMed Central

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

    2015-01-01

    Background When the infarct border zone is stimulated prematurely, a unidirectional block line (UBL) can form and lead to double-loop (figure-of-eight) reentrant ventricular tachycardia (VT) with a central isthmus. The isthmus is composed of an entrance, center, and exit. It was hypothesized that for certain stimulus site locations and coupling intervals, the UBL would coincide with the isthmus entrance boundary, where infarct border zone thickness changes from thin-to-thick in the travel direction of the premature stimulus wavefront. Method A quantitative model was developed to describe how thin-to-thick changes in the border zone result in critically convex wavefront curvature leading to conduction block, which is dependent upon coupling interval. The model was tested in 12 retrospectively analyzed postinfarction canine experiments. Electrical activation was mapped for premature stimulation and for the first reentrant VT cycle. The relationship of functional conduction block forming during premature stimulation to functional block during reentrant VT was quantified. Results For an appropriately placed stimulus, in accord with model predictions: 1. The UBL and reentrant VT isthmus lateral boundaries overlapped (error: 4.8±5.7 mm). 2. The UBL leading edge coincided with the distal isthmus where the center-entrance boundary would be expected to occur. 3. The mean coupling interval was 164.6±11.0 ms during premature stimulation and 190.7±20.4 ms during the first reentrant VT cycle, in accord with model calculations, which resulted in critically convex wavefront curvature and functional conduction block, respectively, at the location of the isthmus entrance boundary and at the lateral isthmus edges. Discussion Reentrant VT onset following premature stimulation can be explained by the presence of critically convex wavefront curvature and unidirectional block at the isthmus entrance boundary when the premature stimulation interval is sufficiently short. The double

  3. Ex vivo Evans blue assessment of the blood brain barrier in three breast cancer brain metastasis models.

    PubMed

    Do, John; Foster, Deshka; Renier, Corinne; Vogel, Hannes; Rosenblum, Sahar; Doyle, Timothy C; Tse, Victor; Wapnir, Irene

    2014-02-01

    The limited entry of anticancer drugs into the central nervous system represents a special therapeutic challenge for patients with brain metastases and is primarily due to the blood brain barrier (BBB). Albumin-bound Evans blue (EB) dye is too large to cross the BBB but can grossly stain tissue blue when the BBB is disrupted. The course of tumor development and the integrity of the BBB were studied in three preclinical breast cancer brain metastasis (BCBM) models. A luciferase-transduced braintropic clone of MDA-231 cell line was used. Nude mice were subjected to stereotactic intracerebral inoculation, mammary fat pad-derived tumor fragment implantation, or carotid artery injections. EB was injected 30 min prior to euthanasia at various timepoints for each of the BCBM model animals. Serial bioluminescent imaging demonstrated exponential tumor growth in all models. Carotid BCBM appeared as diffuse multifocal cell clusters. EB aided the localization of metastases ex vivo. Tumor implants stained blue at 7 days whereas gross staining was not evident until day 14 in the stereotactic model and day 28 for the carotid model. EB assessment of the integrity of the BBB provides useful information relevant to drug testing in preclinical BCBM models.

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

    PubMed

    Weston, Eleanor M; Lister, Adrian M

    2009-05-07

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

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

    PubMed Central

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

    2015-01-01

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

  6. Plant-based foods containing cell wall polysaccharides rich in specific active monosaccharides protect against myocardial injury in rat myocardial infarction models

    PubMed Central

    Lim, Sun Ha; Kim, Yaesil; Yun, Ki Na; Kim, Jin Young; Jang, Jung-Hee; Han, Mee-Jung; Lee, Jongwon

    2016-01-01

    Many cohort studies have shown that consumption of diets containing a higher composition of foods derived from plants reduces mortality from coronary heart disease (CHD). Here, we examined the active components of a plant-based diet and the underlying mechanisms that reduce the risk of CHD using three rat models and a quantitative proteomics approach. In a short-term myocardial infarction (MI) model, intake of wheat extract (WE), the representative cardioprotectant identified by screening approximately 4,000 samples, reduced myocardial injury by inhibiting apoptosis, enhancing ATP production, and maintaining protein homeostasis. In long-term post-MI models, this myocardial protection resulted in ameliorating adverse left-ventricular remodelling, which is a predictor of heart failure. Among the wheat components, arabinose and xylose were identified as active components responsible for the observed efficacy of WE, which was administered via ingestion and tail-vein injections. Finally, the food components of plant-based diets that contained cell wall polysaccharides rich in arabinose, xylose, and possibly fucose were found to confer protection against myocardial injury. These results show for the first time that specific monosaccharides found in the cell wall polysaccharides in plant-based diets can act as active ingredients that reduce CHD by inhibiting postocclusion steps, including MI and heart failure. PMID:27929093

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

    PubMed Central

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

    2014-01-01

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

  8. Agraphia caused by acute right parietal infarction.

    PubMed

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

    2015-04-01

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

  9. Disordered cholinergic neurotransmission and dysautoregulation after acute cerebral infarction.

    PubMed

    Ott, E O; Abraham, J; Meyer, J S; Achari, A N; Chee, A N; Mathew, N T

    1975-01-01

    The possible role of displaced neurotransmitter acetylcholine (ACHh) in dysautoregulation was examined after experimental regional cerebral infarction was produced by occluding the middle cerebral artery (MCA) in babons. Regional cerebral blood flow (rCBF) was measured after intracarotid injection of 133Xenon using the gamma camera. Autoregulation was tested with metaraminol or angiotensin infusion and the autoregulation index (A.I.) was calculated. Acetylcholinesterase (ACHhE) was measured in brain tissue of noninfarcted and infarcted hemispheres. Cerebral arteriovenous (A-V) differences for cholinesterase (ChE) were also measured. Regional dysautoregulation was found in infarcted gray matter and correlated with increased AChE levels in the same zones of cortex and basal ganglia. The time course of onset of dysautoregulation correlated with increased ChE uptake by the brain. Intravenous infusion of the cholinergic neurotransmitter blocker, scopolamine, restored autoregulation to the ischemic zones. Autoregulation appears to be a myogenic reflex, influenced by neurogenic and metabolic mechanisms.

  10. Confusional state and cerebral infarcts.

    PubMed Central

    García-Albea, E.

    1989-01-01

    Thirteen patients with confusional state and cerebral infarction were studied. Seven patients had optic pathway alterations. On computed tomographic scan, 2 patients had multiple infarctions and 10 had single infarctions, predominantly located in the temporo-occipital associative cortex. One patient had a normal scan. Reduction of 'selective attention', 'release' hallucinations, amnesic syndrome and secondary individual adjustment could explain the confusional state. PMID:2608563

  11. Modeling of in hospital mortality determinants in myocardial infarction patients, with and without stroke: A national study in Iran

    PubMed Central

    Ahmadi, Ali; Khaledifar, Arsalan; Etemad, Koorosh

    2016-01-01

    Background: The data and determinants of mortality due to stroke in myocardial infarction (MI) patients are unknown. This study was conducted to evaluate the differences in risk factors for hospital mortality among MI patients with and without stroke history. Materials and Methods: This study was a retrospective, cohort study; 20,750 new patients with MI from April, 2012 to March, 2013 were followed up and their data were analyzed according to having or not having the stroke history. Stroke and MI were defined based on the World Health Organization's definition. The data were analyzed by logistic regression in STATA software. Results: Of the 20,750 studied patients, 4293 had stroke history. The prevalence of stroke in the studied population was derived 20.96% (confidence interval [CI] 95%: 20.13–21.24). Of the patients, 2537 (59.1%) had ST-elevation MI (STEMI). Mortality ratio in patients with and without stroke was obtained 18.8% and 10.3%, respectively. The prevalence of risk factors in MI patients with and without a stroke is various. The adjusted odds ratio of mortality in patients with stroke history was derived 7.02 (95% CI: 5.42–9) for chest pain resistant to treatment, 2.39 (95% CI: 1.97–2.9) for STEMI, 3.02 (95% CI: 2.5–3.64) for lack of thrombolytic therapy, 2.2 (95% CI: 1.66–2.91) for heart failure, and 2.17 (95% CI: 1.6–2.9) for ventricular tachycardia. Conclusion: With regards to the factors associated with mortality in this study, it is particularly necessary to control the mortality in MI patients with stroke history. More emphasis should be placed on the MI patients with the previous stroke over those without in the interventions developed for prevention and treatment, and for the prevention of avoidable mortalities. PMID:27904619

  12. Assessing the Associations Between Awareness of Myocardial Infarction Symptoms, Socioeconomic Factors, and Cardiovascular Disease Risk Factors Through Regression Models.

    PubMed

    Tran, Phoebe; Mittleman, Murray A

    2016-11-18

    There are few studies that consider the association between awareness of symptoms of acute myocardial infarction (MI), socioeconomic factors (household income, sex, race/ethnicity, and educational attainment), and cardiovascular (CVD) risk factors. It is important to understand these associations because there is evidence that suggests that disparities in the awareness of MI symptoms lead to disparities in delays in receiving treatment and outcomes of patients with MI. The study was to determine if there are disparities in the awareness of different MI symptoms among different groups with respect to self-reported race, ethnicity, education, age, and income (i.e., various SES factors) in the presence/absence of modifiable cardiovascular disease risk factors. We utilized the 2003-2009 Behavioral Risk Factor Surveillance Survey, a nationally representative telephone-based survey, to evaluate the relationships between five common symptoms of MI, socioeconomic factors, and four major modifiable CVD risk factors. We found that being college-educated, a higher household income, making $75,000 a year or more, being female, being non-Hispanic White, having hypertension, and exercising regularly were generally associated with a higher probability of being aware of the MI symptoms evaluated in this study. Additionally, awareness that jaw/back/neck pain and feeling weak/light-headed/faint are symptoms of MI were found to be consistently lower compared to that of other MI symptoms, ranging from 50 to 75%, across all SES factors and CVD risk factors. The findings from this study can serve as a useful guide to facilitating targeted educational efforts aimed at improving awareness of MI symptoms that may ultimately reduce disparities in the outcomes of patients at risk for MI.

  13. Arterial hypertension and brain damage--evidence from animal models (review).

    PubMed

    Amenta, Francesco; Di Tullio, Maria Antonietta; Tomassoni, Daniele

    2003-08-01

    Hypertension is an important risk factor for cerebrovascular disease including stroke and has also a role in the development of vascular cognitive impairment (VCI) and vascular dementia (VaD). Research on pathophysiology and treatment of hypertensive brain damage may benefit from the availability of animal models. This paper has reviewed the main animal models of hypertension in which brain damage is documented. Spontaneously hypertensive rats (SHR) represent the animal model more largely used. In these rats cerebrovascular changes, brain atrophy, loss of nerve cells in cerebrocortical areas, and glial reaction were documented. Several changes observed in SHR are similar to those found by in vivo imaging studies in essential hypertensives. It is documented that brain gets benefit from lowering abnormally elevated blood pressure and that reduction of hypertension protects brain from stroke and probably reduces the incidence of VaD. The influence of anti-hypertensive treatment on brain structure and function in animal models of hypertension is reviewed. Among classes of drugs investigated, dihydropyridine-type Ca2+ antagonists were those with a most documented protective effect on hypertensive brain damage. Limits and perspectives in the use of animal models for assessing brain damage caused by hypertension and protection from it are discussed.

  14. Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling.

    PubMed

    Ponce-Alvarez, Adrián; He, Biyu J; Hagmann, Patric; Deco, Gustavo

    2015-08-01

    How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI) signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model's prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information.

  15. Immortalized endothelial cell lines for in vitro blood-brain barrier models: A systematic review.

    PubMed

    Rahman, Nurul Adhwa; Rasil, Alifah Nur'ain Haji Mat; Meyding-Lamade, Uta; Craemer, Eva Maria; Diah, Suwarni; Tuah, Ani Afiqah; Muharram, Siti Hanna

    2016-07-01

    Endothelial cells play the most important role in construction of the blood-brain barrier. Many studies have opted to use commercially available, easily transfected or immortalized endothelial cell lines as in vitro blood-brain barrier models. Numerous endothelial cell lines are available, but we do not currently have strong evidence for which cell lines are optimal for establishment of such models. This review aimed to investigate the application of immortalized endothelial cell lines as in vitro blood-brain barrier models. The databases used for this review were PubMed, OVID MEDLINE, ProQuest, ScienceDirect, and SpringerLink. A narrative systematic review was conducted and identified 155 studies. As a result, 36 immortalized endothelial cell lines of human, mouse, rat, porcine and bovine origins were found for the establishment of in vitro blood-brain barrier and brain endothelium models. This review provides a summary of immortalized endothelial cell lines as a guideline for future studies and improvements in the establishment of in vitro blood-brain barrier models. It is important to establish a good and reproducible model that has the potential for multiple applications, in particular a model of such a complex compartment such as the blood-brain barrier.

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

    PubMed Central

    Chaudhuri, Swapna

    2015-01-01

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

  17. Opioid Abuse after Traumatic Brain Injury: Evaluation Using Rodent Models

    DTIC Science & Technology

    2013-07-01

    rats induces structural changes in brain regions associated with reward/risk circuitry including the nucleus accumbens, amygdala, hippocampus , and...to injury, animals underwent surgical implantation of a chronic indwelling venous catheter under isoflurane anesthesia with morphine pretreatment. A

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

    PubMed

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

    2015-08-01

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

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

    ERIC Educational Resources Information Center

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

    2014-01-01

    The present study assessed the impact of sample size on the power and fit of structural equation modeling applied to functional brain connectivity hypotheses. The data consisted of time-constrained minimum norm estimates of regional brain activity during performance of a reading task obtained with magnetoencephalography. Power analysis was first…

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    SciTech Connect

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

    1989-12-01

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

  2. Modeling the Dynamics of Human Brain Activity with Recurrent Neural Networks

    PubMed Central

    Güçlü, Umut; van Gerven, Marcel A. J.

    2017-01-01

    Encoding models are used for predicting brain activity in response to sensory stimuli with the objective of elucidating how sensory information is represented in the brain. Encoding models typically comprise a nonlinear transformation of stimuli to features (feature model) and a linear convolution of features to responses (response model). While there has been extensive work on developing better feature models, the work on developing better response models has been rather limited. Here, we investigate the extent to which recurrent neural network models can use their internal memories for nonlinear processing of arbitrary feature sequences to predict feature-evoked response sequences as measured by functional magnetic resonance imaging. We show that the proposed recurrent neural network models can significantly outperform established response models by accurately estimating long-term dependencies that drive hemodynamic responses. The results open a new window into modeling the dynamics of brain activity in response to sensory stimuli. PMID:28232797

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

    SciTech Connect

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

    2015-01-02

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  5. Parallel optimization of tumor model parameters for fast registration of brain tumor images

    NASA Astrophysics Data System (ADS)

    Zacharaki, Evangelia I.; Hogea, Cosmina S.; Shen, Dinggang; Biros, George; Davatzikos, Christos

    2008-03-01

    The motivation of this work is to register MR brain tumor images with a brain atlas. Such a registration method can make possible the pooling of data from different brain tumor patients into a common stereotaxic space, thereby enabling the construction of statistical brain tumor atlases. Moreover, it allows the mapping of neuroanatomical brain atlases into the patient's space, for segmenting brains and thus facilitating surgical or radiotherapy treatment planning. However, the methods developed for registration of normal brain images are not directly applicable to the registration of a normal atlas with a tumor-bearing image, due to substantial dissimilarity and lack of equivalent image content between the two images, as well as severe deformation or shift of anatomical structures around the tumor. Accordingly, a model that can simulate brain tissue death and deformation induced by the tumor is considered to facilitate the registration. Such tumor growth simulation models are usually initialized by placing a small seed in the normal atlas. The shape, size and location of the initial seed are critical for achieving topological equivalence between the atlas and patient's images. In this study, we focus on the automatic estimation of these parameters, pertaining to tumor simulation. In particular, we propose an objective function reflecting feature-based similarity and elastic stretching energy and optimize it with APPSPACK (Asynchronous Parallel Pattern Search), for achieving significant reduction of the computational cost. The results indicate that the registration accuracy is high in areas around the tumor, as well as in the healthy portion of the brain.

  6. Brain and Plasma Molecular Characterization of the Pathogenic TBI-AD Interrelationship in Mouse Models

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-13-1-0253 TITLE: Brain and Plasma Molecular Characterization of the Pathogenic TBI-AD Interrelationship in Mouse Models ... brain and plasma responses in mouse models of TBI, AD and other neurodegenerative conditions (Abdullah et al., 2014; Abdullah et al., 2013; Crawford...identify age/time-dependent expression of brain proteins and lipids in mouse models of AD (PSAPP and hTau) and of mTBI (single and repetitive mTBI in hTau

  7. Assessment of brain compliance using ICP waveform analysis in water intoxication rat model.

    PubMed

    Oshio, Kotaro; Onodera, Hidetaka; Uchida, Masashi; Tanaka, Yuichiro; Hashimoto, Takuo

    2013-01-01

    Intracranial pressure (ICP) monitoring has been used widely for patients with intracranial hypertension. However, the data of mean ICP do not reflect various brain conditions correctly. Therefore, we performed ICP -waveform analysis to assess brain compliance. Data for ICP -waveform analysis were obtained by stereotactic intraventricle puncture. ICP waveform is expressed as a three-phase wave. Analyzed differential waveforms in a water intoxication model and continuous infusion models were evaluated respectively. In the water intoxication models, the second wave (P2) known to reflect compliance is elevated. ICP waveform analysis will be valuable for the assessment of the pathological condition of the brain.

  8. Genetic deletion of neuronal pentraxin 1 expression prevents brain injury in a neonatal mouse model of cerebral hypoxia-ischemia.

    PubMed

    Thatipamula, Shabarish; Al Rahim, Md; Zhang, Jiangyang; Hossain, Mir Ahamed

    2015-03-01

    Neonatal hypoxic-ischemic (HI) brain injury is a leading cause of mortality and morbidity in infants and children for which there is no promising therapy at present. Previously, we reported induction of neuronal pentraxin 1 (NP1), a novel neuronal protein of the long-pentraxin family, following HI injury in neonatal brain. Here, we report that genetic deletion of NP1 expression prevents HI injury in neonatal brain. Elevated expression of NP1 was observed in neurons, not in astrocytes, of the ipsilateral cortical layers (I-IV) and in the hippocampal CA1 and CA3 areas of WT brains following hypoxia-ischemia; brain areas that developed infarcts (at 24-48 h), showed significantly increased numbers of TUNEL-(+) cells and tissue loss (at 7 days). In contrast, NP1-KO mice showed no evidence of brain infarction and tissue loss after HI. The immunofluorescence staining of brain sections with mitochondrial protein COX IV and subcellular fractionation analysis showed increased accumulation of NP1 in mitochondria, pro-death protein Bax activation and NP1 co-localization with activated caspase-3 in WT, but not in the NP1-KO brains; corroborating NP1 interactions with the mitochondria-derived pro-death pathways. Disruption of NP1 translocation to mitochondria by NP1-siRNA in primary cortical cultures significantly reduced ischemic neuronal death. NP1 was immunoprecipitated with activated Bax [6A7] proteins; HI caused increased interactions of NP1 with Bax, thereby, facilitating Bax translocation to mitochondrial and neuronal death. To further delineate the specificity of NPs, we found that NP1 but not the NP2 induction is specifically involved in brain injury mechanisms and that knockdown of NP1 only results in neuroprotection. Furthermore, live in vivo T2-weighted magnetic resonance imaging (MRI) including fractional anisotropy (FA) mapping showed no sign of delayed brain injury or tissue loss in the NP1-KO mice as compared to the WT at different post-HI periods (4-24 weeks

  9. Genetic deletion of neuronal pentraxin 1 expression prevents brain injury in a neonatal mouse model of cerebral hypoxia-ischemia

    PubMed Central

    Thatipamula, Shabarish; Rahim, Md Al; Zhang, Jiangyang; Hossain, Mir Ahamed

    2015-01-01

    Neonatal hypoxic-ischemic (HI) brain injury is a leading cause of mortality and morbidity in infants and children for which there is no promising therapy at present. Previously, we reported induction of neuronal pentraxin 1 (NP1), a novel neuronal protein of the long-pentraxin family, following HI injury in neonatal brain. Here, we report that genetic deletion of NP1 expression prevents HI injury in neonatal brain. Elevated expression of NP1 was observed in neurons, not in astrocytes, of the ipsilateral cortical layers (I–IV) and in the hippocampal CA1 and CA3 areas of WT brains following hypoxia-ischemia; brain areas that developed infarcts (at 24–48 h), showed significantly increased numbers of TUNEL-(+) cells and tissue loss (at 7 d). In contrast, NP1-KO mice showed no evidence of brain infarction and tissue loss after HI. The immunofluorescence staining of brain sections with mitochondrial protein COX IV and subcellular fractionation analysis showed increased accumulation of NP1 in mitochondria, pro-death protein Bax activation and NP1 co-localization with activated caspase-3 in WT, but not in the NP1-KO brains; corroborating NP1 interactions with the mitochondria-derived pro-death pathways. Disruption of NP1 translocation to mitochondria by NP1-siRNA in primary cortical cultures significantly reduced ischemic neuronal death. NP1 was immunoprecipitated with activated Bax[6A7] proteins; HI caused increased interactions of NP1 with Bax, thereby, facilitating Bax translocation to mitochondrial and neuronal death. To further delineate the specificity of NPs, we found that NP1 but not the NP2 induction is specifically involved in brain injury mechanisms and that knockdown of NP1 only results in neuroprotection. Furthermore, live in vivo T2-weighted magnetic resonance imaging (MRI) including fractional anisotropy (FA) mapping showed no sign of delayed brain injury or tissue loss in the NP1-KO mice as compared to the WT at different post-HI periods (4–24 weeks

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

    PubMed

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

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

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

    SciTech Connect

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

    2009-03-10

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

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

    PubMed

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

    2013-02-01

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

  14. [Segmental testicular infarction].

    PubMed

    Ripa Saldías, L; Guarch Troyas, R; Hualde Alfaro, A; de Pablo Cárdenas, A; Ruiz Ramo, M; Pinós Paul, M

    2006-02-01

    We report the case of a 47 years old man previously diagnosed of left hidrocele. After having a recent mild left testicular pain, an ultrasonografic study revealed a solid hipoecoic testicular lesion rounded by a big hidrocele, suggesting a testicular neoplasm. Radical inguinal orchiectomy was made and pathologic study showed segmental testicular infarction. No malignancy was found. We review the literature of the topic.

  15. From animal model to human brain networking: dynamic causal modeling of motivational systems.

    PubMed

    Gonen, Tal; Admon, Roee; Podlipsky, Ilana; Hendler, Talma

    2012-05-23

    An organism's behavior is sensitive to different reinforcements in the environment. Based on extensive animal literature, the reinforcement sensitivity theory (RST) proposes three separate neurobehavioral systems to account for such context-sensitive behavior, affecting the tendency to react to punishment, reward, or goal-conflict stimuli. The translation of animal findings to complex human behavior, however, is far from obvious. To examine whether the neural networks underlying humans' motivational processes are similar to those proposed by the RST model, we conducted a functional MRI study, in which 24 healthy subjects performed an interactive game that engaged the different motivational systems using distinct time periods (states) of punishment, reward, and conflict. Crucially, we found that the different motivational states elicited activations in brain regions that corresponded exactly to the brain systems underlying RST. Moreover, dynamic causal modeling of each motivational system confirmed that the coupling strengths between the key brain regions of each system were enabled selectively by the appropriate motivational state. These results may shed light on the impairments that underlie psychopathologies associated with dysfunctional motivational processes and provide a translational validity for the RST.

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

    NASA Astrophysics Data System (ADS)

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

    2002-06-01

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

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

    PubMed Central

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

    2007-01-01

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

  18. Pure right ventricular infarction.

    PubMed

    Inoue, Katsuji; Matsuoka, Hiroshi; Kawakami, Hideo; Koyama, Yasushi; Nishimura, Kazuhisa; Ito, Taketoshi

    2002-02-01

    A 76-year-old man with chest pain was admitted to hospital where electrocardiography (ECG) showed ST-segment elevation in leads V1-4, indicative of acute anterior myocardial infarction. ST-segment elevation was also present in the right precordial leads V4R-6R. Emergency coronary angiography revealed that the left coronary artery was dominant and did not have significant stenosis. Aortography showed ostial occlusion of the right coronary artery (RCA). Left ventriculography showed normal function and right ventriculography showed a dilated right ventricle and severe hypokinesis of the right ventricular free wall. Conservative treatment was selected because the patient's symptoms soon ameliorated and his hemodynamics was stable. 99mTc-pyrophosphate and 201Tl dual single-photon emission computed tomography showed uptake of 99mTc-pyrophosphate in only the right ventricular free wall, but no uptake of 99mTc-pyrophosphate and no perfusion defect of 201Tl in the left ventricle. The peak creatine kinase (CK) and CK-MB were 1,381 IU/L and 127 IU/L, respectively. His natural course was favorable and the chest pain disappeared under medication. Two months after the onset, the ECG showed poor R progression in leads V1-4 indicating an old anterior infarction. Coronary angiography confirmed the ostial stenosis of the hypoplastic RCA. This was a case of pure right ventricular free wall infarction because of the occlusion of the ostium of the hypoplastic RCA, but not of the right ventricular branch. Because the electrocardiographic findings resemble those of an acute anterior infarction, it is important to consider pure right ventricular infarction in the differential diagnosis.

  19. Brain cooling maintenance with cooling cap following induction with intracarotid cold saline infusion: a quantitative model.

    PubMed

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

    2008-07-21

    Intracarotid cold saline infusion (ICSI) is potentially much faster than whole-body cooling and more effective than cooling caps in inducing therapeutic brain cooling. One drawback of ICSI is hemodilution and volume loading. We hypothesized that cooling caps could enhance brain cooling with ICSI and minimize hemodilution and volume loading. Six-hour-long simulations were performed in a 3D mathematical brain model. The Pennes bioheat equation was used to propagate brain temperature. Convective heat transfer through jugular venous return and the circle of Willis was simulated. Hemodilution and volume loading were modeled using a two-compartment saline infusion model. A feedback method of local brain temperature control was developed where ICSI flow rate was varied based on the rate of temperature change and the deviation of temperature to a target (32 degrees C) within a voxel in the treated region of brain. The simulations confirmed the inability of cooling caps alone to induce hypothermia. In the ICSI and the combination models (ICSI and cap), the control algorithm guided ICSI to quickly achieve and maintain the target temperature. The combination model had lower ICSI flow rates than the ICSI model resulting in a 55% reduction of infusion volume over a 6h period and higher hematocrit values compared to the ICSI model. Moreover, in the combination model, the ICSI flow rate decreased to zero after 4h, and hypothermia was subsequently maintained solely by the cooling cap. This is the first study supporting a role of cooling caps in therapeutic hypothermia in adults.

  20. Relationships between high oxygen extraction fraction in the acute stage and final infarction in reversible middle cerebral artery occlusion: an investigation in anesthetized baboons with positron emission tomography.

    PubMed

    Young, A R; Sette, G; Touzani, O; Rioux, P; Derlon, J M; MacKenzie, E T; Baron, J C

    1996-11-01

    Studies in humans suggest that regions that show maximal increases in brain oxygen extraction fraction (OEF) in the hours following an ischemic episode are those most vulnerable for infarction and are often, although not always, associated with the final site of infarction. To clarify this issue, we followed the hemodynamic and metabolic characteristics of regions with an initially maximally increased OEF and compared them with the ultimately infarcted region in an experimental stroke model. Positron emission tomography (PET) was used to obtain functional images of the brain prior to and following reversible unilateral middle cerebral artery occlusion (MCAO) in 11 anesthetized baboons. To model early reperfusion, the clips were removed 6 h after occlusion. Successive measurements of regional CBF (rCBF), regional CMRO2 (rCMRO2), regional cerebral blood volume, and regional OEF (rOEF) were performed during the acute (up to 2 days) and chronic (> 15 days) stage. Late magnetic resonance imaging (MRI) scans (co-registered with PET) were obtained to identify infarction. Reversible MCAO produced an MRI-measurable infarction in 6 of 11 baboons; the others had no evidence of ischemic damage. Histological analysis confirmed the results of the MRI investigation but failed to show any evidence of cortical ischemic damage. The lesion was restricted to the head of the caudate nucleus, internal capsule, and putamen. The infarct volume obtained was 0.58 +/- 0.31 cm3. The infarcts were situated in the deep MCA territory, while the area of initially maximally increased OEF was within the cortical mantle. The mean absolute rCBF value in the infarct region of interest (ROI) was not significantly lower than in the highest-OEF ROI until 1-2 days post-MCAO. Cerebral metabolism in the deep MCA territory was always significantly lower than that of the cortical mantle; decreases in CMRO2 in the former region were evident as early as 1 h post-MCAO. In the cortical mantle, the rOEF was

  1. Quantitative Imaging Methods for the Development and Validation of Brain Biomechanics Models

    PubMed Central

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

    2013-01-01

    Rapid deformation of brain tissue in response to head impact or acceleration can lead to numerous pathological changes, both immediate and delayed. Modeling and simulation hold promise for illuminating the mechanisms of traumatic brain injury (TBI) and for developing preventive devices and strategies. However, mathematical models have predictive value only if they satisfy two conditions. First, they must capture the biomechanics of the brain as both a material and a structure, including the mechanics of brain tissue and its interactions with the skull. Second, they must be validated by direct comparison with experimental data. Emerging imaging technologies and recent imaging studies provide important data for these purposes. This review describes these techniques and data, with an emphasis on magnetic resonance imaging approaches. In combination, these imaging tools promise to extend our understanding of brain biomechanics and improve our ability to study TBI in silico. PMID:22655600

  2. System Dynamics Modeling in the Evaluation of Delays of Care in ST-Segment Elevation Myocardial Infarction Patients within a Tiered Health System

    PubMed Central

    de Andrade, Luciano; Lynch, Catherine; Carvalho, Elias; Rodrigues, Clarissa Garcia; Vissoci, João Ricardo Nickenig; Passos, Guttenberg Ferreira; Pietrobon, Ricardo; Nihei, Oscar Kenji; de Barros Carvalho, Maria Dalva

    2014-01-01

    Background Mortality rates amongst ST segment elevation myocardial infarction (STEMI) patients remain high, especially in developing countries. The aim of this study was to evaluate the factors related with delays in the treatment of STEMI patients to support a strategic plan toward structural and personnel modifications in a primary hospital aligning its process with international guidelines. Methods and Findings The study was conducted in a primary hospital localized in Foz do Iguaçu, Brazil. We utilized a qualitative and quantitative integrated analysis including on-site observations, interviews, medical records analysis, Qualitative Comparative Analysis (QCA) and System Dynamics Modeling (SD). Main cause of delays were categorized into three themes: a) professional, b) equipment and c) transportation logistics. QCA analysis confirmed four main stages of delay to STEMI patient’s care in relation to the ‘Door-in-Door-out’ time at the primary hospital. These stages and their average delays in minutes were: a) First Medical Contact (From Door-In to the first contact with the nurse and/or physician): 7 minutes; b) Electrocardiogram acquisition and review by a physician: 28 minutes; c) ECG transmission and Percutaneous Coronary Intervention Center team feedback time: 76 minutes; and d) Patient’s Transfer Waiting Time: 78 minutes. SD baseline model confirmed the system’s behavior with all occurring delays and the need of improvements. Moreover, after model validation and sensitivity analysis, results suggested that an overall improvement of 40% to 50% in each of these identified stages would reduce the delay. Conclusions This evaluation suggests that investment in health personnel training, diminution of bureaucracy, and management of guidelines might lead to important improvements decreasing the delay of STEMI patients’ care. In addition, this work provides evidence that SD modeling may highlight areas where health system managers can implement and

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

    PubMed

    Kybartaite, Asta

    2012-11-01

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

  4. Adolescent Emotional Maturation through Divergent Models of Brain Organization.

    PubMed

    Oron Semper, Jose V; Murillo, Jose I; Bernacer, Javier

    2016-01-01

    In this article we introduce the hypothesis that neuropsychological adolescent maturation, and in particular emotional management, may have opposing explanations depending on the interpretation of the assumed brain architecture, that is, whether a componential computational account (CCA) or a dynamic systems perspective (DSP) is used. According to CCA, cognitive functions are associated with the action of restricted brain regions, and this association is temporally stable; by contrast, DSP argues that cognitive functions are better explained by interactions between several brain areas, whose engagement in specific functions is temporal and context-dependent and based on neural reuse. We outline the main neurobiological facts about adolescent maturation, focusing on the neuroanatomical and neurofunctional processes associated with adolescence. We then explain the importance of emotional management in adolescent maturation. We explain the interplay between emotion and cognition under the scope of CCA and DSP, both at neural and behavioral levels. Finally, we justify why, according to CCA, emotional management is understood as regulation, specifically because the cognitive aspects of the brain are in charge of regulating emotion-related modules. However, the key word in DSP is integration, since neural information from different brain areas is integrated from the beginning of the process. Consequently, although the terms should not be conceptually confused, there is no cognition without emotion, and vice versa. Thus, emotional integration is not an independent process that just happens to the subject, but a crucial part of personal growth. Considering the importance of neuropsychological research in the development of educational and legal policies concerning adolescents, we intend to expose that the holistic view of adolescents is dependent on whether one holds the implicit or explicit interpretation of brain functioning.

  5. Adolescent Emotional Maturation through Divergent Models of Brain Organization

    PubMed Central

    Oron Semper, Jose V.; Murillo, Jose I.; Bernacer, Javier

    2016-01-01

    In this article we introduce the hypothesis that neuropsychological adolescent maturation, and in particular emotional management, may have opposing explanations depending on the interpretation of the assumed brain architecture, that is, whether a componential computational account (CCA) or a dynamic systems perspective (DSP) is used. According to CCA, cognitive functions are associated with the action of restricted brain regions, and this association is temporally stable; by contrast, DSP argues that cognitive functions are better explained by interactions between several brain areas, whose engagement in specific functions is temporal and context-dependent and based on neural reuse. We outline the main neurobiological facts about adolescent maturation, focusing on the neuroanatomical and neurofunctional processes associated with adolescence. We then explain the importance of emotional management in adolescent maturation. We explain the interplay between emotion and cognition under the scope of CCA and DSP, both at neural and behavioral levels. Finally, we justify why, according to CCA, emotional management is understood as regulation, specifically because the cognitive aspects of the brain are in charge of regulating emotion-related modules. However, the key word in DSP is integration, since neural information from different brain areas is integrated from the beginning of the process. Consequently, although the terms should not be conceptually confused, there is no cognition without emotion, and vice versa. Thus, emotional integration is not an independent process that just happens to the subject, but a crucial part of personal growth. Considering the importance of neuropsychological research in the development of educational and legal policies concerning adolescents, we intend to expose that the holistic view of adolescents is dependent on whether one holds the implicit or explicit interpretation of brain functioning. PMID:27602012

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  7. A Simulation Model of Periarterial Clearance of Amyloid-β from the Brain

    PubMed Central

    Diem, Alexandra K.; Tan, Mingyi; Bressloff, Neil W.; Hawkes, Cheryl; Morris, Alan W. J.; Weller, Roy O.; Carare, Roxana O.

    2016-01-01

    The accumulation of soluble and insoluble amyloid-β (Aβ) in the brain indicates failure of elimination of Aβ from the brain with age and Alzheimer's disease (AD). There is a variety of mechanisms for elimination of Aβ from the brain. They include the action of microglia and enzymes together with receptor-mediated absorption of Aβ into the blood and periarterial lymphatic drainage of Aβ. Although the brain possesses no conventional lymphatics, experimental studies have shown that fluid and solutes, such as Aβ, are eliminated from the brain along 100 nm wide basement membranes in the walls of cerebral capillaries and arteries. This lymphatic drainage pathway is reflected in the deposition of Aβ in the walls of human arteries with age and AD as cerebral amyloid angiopathy (CAA). Initially, Aβ diffuses through the extracellular spaces of gray matter in the brain and then enters basement membranes in capillaries and arteries to flow out of the brain. Although diffusion through the extracellular spaces of the brain has been well characterized, the exact mechanism whereby perivascular elimination of Aβ occurs has not been resolved. Here we use a computational model to describe the process of periarterial drainage in the context of diffusion in the brain, demonstrating that periarterial drainage along basement membranes is very rapid compared with diffusion. Our results are a validation of experimental data and are significant in the context of failure of periarterial drainage as a mechanism underlying the pathogenesis of AD as well as complications associated with its immunotherapy. PMID:26903861

  8. A Simulation Model of Periarterial Clearance of Amyloid-β from the Brain.

    PubMed

    Diem, Alexandra K; Tan, Mingyi; Bressloff, Neil W; Hawkes, Cheryl; Morris, Alan W J; Weller, Roy O; Carare, Roxana O

    2016-01-01

    The accumulation of soluble and insoluble amyloid-β (Aβ) in the brain indicates failure of elimination of Aβ from the brain with age and Alzheimer's disease (AD). There is a variety of mechanisms for elimination of Aβ from the brain. They include the action of microglia and enzymes together with receptor-mediated absorption of Aβ into the blood and periarterial lymphatic drainage of Aβ. Although the brain possesses no conventional lymphatics, experimental studies have shown that fluid and solutes, such as Aβ, are eliminated from the brain along 100 nm wide basement membranes in the walls of cerebral capillaries and arteries. This lymphatic drainage pathway is reflected in the deposition of Aβ in the walls of human arteries with age and AD as cerebral amyloid angiopathy (CAA). Initially, Aβ diffuses through the extracellular spaces of gray matter in the brain and then enters basement membranes in capillaries and arteries to flow out of the brain. Although diffusion through the extracellular spaces of the brain has been well characterized, the exact mechanism whereby perivascular elimination of Aβ occurs has not been resolved. Here we use a computational model to describe the process of periarterial drainage in the context of diffusion in the brain, demonstrating that periarterial drainage along basement membranes is very rapid compared with diffusion. Our results are a validation of experimental data and are significant in the context of failure of periarterial drainage as a mechanism underlying the pathogenesis of AD as well as complications associated with its immunotherapy.

  9. Material and physical model for evaluation of deep brain activity contribution to EEG recordings

    NASA Astrophysics Data System (ADS)

    Ye, Yan; Li, Xiaoping; Wu, Tiecheng; Li, Zhe; Xie, Wenwen

    2015-12-01

    Deep brain activity is conventionally recorded with surgical implantation of electrodes. During the neurosurgery, brain tissue damage and the consequent side effects to patients are inevitably incurred. In order to eliminate undesired risks, we propose that deep brain activity should be measured using the noninvasive scalp electroencephalography (EEG) technique. However, the deeper the neuronal activity is located, the noisier the corresponding scalp EEG signals are. Thus, the present study aims to evaluate whether deep brain activity could be observed from EEG recordings. In the experiment, a three-layer cylindrical head model was constructed to mimic a human head. A single dipole source (sine wave, 10 Hz, altering amplitudes) was embedded inside the model to simulate neuronal activity. When the dipole source was activated, surface potential was measured via electrodes attached on the top surface of the model and raw data were recorded for signal analysis. Results show that the dipole source activity positioned at 66 mm depth in the model, equivalent to the depth of deep brain structures, is clearly observed from surface potential recordings. Therefore, it is highly possible that deep brain activity could be observed from EEG recordings and deep brain activity could be measured using the noninvasive scalp EEG technique.

  10. Pharmacokinetic modeling of subcutaneous heroin and its metabolites in blood and brain of mice.

    PubMed

    Boix, Fernando; Andersen, Jannike M; Mørland, Jørg

    2013-01-01

    High blood-brain permeability and effective delivery of morphine to the brain have been considered as explanations for the high potency of heroin. Results from Andersen et al. indicate that 6-monoacetylmorphine (6-MAM), and not morphine, is the active metabolite responsible for the acute effects observed for heroin. Here, we use pharmacokinetic modeling on data from the aforementioned study to calculate parameters of the distribution of heroin, 6-MAM and morphine in blood and brain tissue after subcutaneous heroin administration in mice. The estimated pharmacokinetic parameters imply that the very low heroin and the high 6-MAM levels observed both in blood and brain in the original experiment are likely to be caused by a very high metabolic rate of heroin in blood. The estimated metabolic rate of heroin in brain was much lower and cannot account for the low heroin and high 6-MAM levels in the brain, which would primarily reflect the concentrations of these compounds in blood. The very different metabolic rates for heroin in blood and brain calculated by the model were confirmed by in vitro experiments. These results show that heroin's fast metabolism in blood renders high concentrations of 6-MAM which, due to its relatively good blood-brain permeability, results in high levels of this metabolite in the brain. Thus, it is the high blood metabolism rate of heroin and the blood-brain permeability to 6-MAM, and not to heroin, which could account for the highly efficient delivery of active metabolites to the brain after heroin administration.

  11. Spatial disorientation in right-hemisphere infarction.

    PubMed Central

    Meerwaldt, J D; van Harskamp, F

    1982-01-01

    Spatial orientation was tested with the rod orientation test. The subjects were 40 normal controls and 68 brain-damaged patients with cerebral infarcts. Patients in whom the lesion included the post-rolandic region of the right hemisphere performed worse than controls or patients with lesions at other sites. Patients with an exclusively postrolandic (usually occipital) lesion showed higher error rates than patients with a combined prerolandic and postrolandic lesion, but only for the visual part of the test. These patients were re-examined one year after the stroke. Most of them showed an incomplete recovery of spatial function. PMID:7119828

  12. TU-G-204-06: Correlation Between Texture Analysis-Based Model Observer and Human Observer in Diagnosis of Ischemic Infarct in Non-Contrast Head CT of Adults

    SciTech Connect

    Li, B; Fujita, A; Buch, K; Sakai, O

    2015-06-15

    Purpose: To investigate the correlation between texture analysis-based model observer and human observer in the task of diagnosis of ischemic infarct in non-contrast head CT of adults. Methods: Non-contrast head CTs of five patients (2 M, 3 F; 58–83 y) with ischemic infarcts were retro-reconstructed using FBP and Adaptive Statistical Iterative Reconstruction (ASIR) of various levels (10–100%). Six neuro -radiologists reviewed each image and scored image quality for diagnosing acute infarcts by a 9-point Likert scale in a blinded test. These scores were averaged across the observers to produce the average human observer responses. The chief neuro-radiologist placed multiple ROIs over the infarcts. These ROIs were entered into a texture analysis software package. Forty-two features per image, including 11 GLRL, 5 GLCM, 4 GLGM, 9 Laws, and 13 2-D features, were computed and averaged over the images per dataset. The Fisher-coefficient (ratio of between-class variance to in-class variance) was calculated for each feature to identify the most discriminating features from each matrix that separate the different confidence scores most efficiently. The 15 features with the highest Fisher -coefficient were entered into linear multivariate regression for iterative modeling. Results: Multivariate regression analysis resulted in the best prediction model of the confidence scores after three iterations (df=11, F=11.7, p-value<0.0001). The model predicted scores and human observers were highly correlated (R=0.88, R-sq=0.77). The root-mean-square and maximal residual were 0.21 and 0.44, respectively. The residual scatter plot appeared random, symmetric, and unbiased. Conclusion: For diagnosis of ischemic infarct in non-contrast head CT in adults, the predicted image quality scores from texture analysis-based model observer was highly correlated with that of human observers for various noise levels. Texture-based model observer can characterize image quality of low contrast

  13. Single or multiple frequency generators in on-going brain activity: A mechanistic whole-brain model of empirical MEG data.

    PubMed

    Deco, Gustavo; Cabral, Joana; Woolrich, Mark W; Stevner, Angus B A; van Hartevelt, Tim J; Kringelbach, Morten L

    2017-03-15

    During rest, envelopes of band-limited on-going MEG signals co-vary across the brain in consistent patterns, which have been related to resting-state networks measured with fMRI. To investigate the genesis of such envelope correlations, we consider a whole-brain network model assuming two distinct fundamental scenarios: one where each brain area generates oscillations in a single frequency, and a novel one where each brain area can generate oscillations in multiple frequency bands. The models share, as a common generator of damped oscillations, the normal form of a supercritical Hopf bifurcation operating at the critical border between the steady state and the oscillatory regime. The envelopes of the simulated signals are compared with empirical MEG data using new methods to analyse the envelope dynamics in terms of their phase coherence and stability across the spectrum of carrier frequencies. Considering the whole-brain model with a single frequency generator in each brain area, we obtain the best fit with the empirical MEG data when the fundamental frequency is tuned at 12Hz. However, when multiple frequency generators are placed at each local brain area, we obtain an improved fit of the spatio-temporal structure of on-going MEG data across all frequency bands. Our results indicate that the brain is likely to operate on multiple frequency channels during rest, introducing a novel dimension for future models of large-scale brain activity.

  14. A simple rat model of mild traumatic brain injury: a device to reproduce anatomical and neurological changes of mild traumatic brain injury

    PubMed Central

    Kim, Ho Jeong

    2017-01-01

    Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used water pressure or rotational injury for designing the device to make a rat a mild traumatic brain injury model. The objective of this study was to make a simple model of causing mild traumatic brain injury in rats. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175 g) was freely dropped 30 cm to rat’s skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague-Dawley rats, we performed magnetic resonance imaging (MRI) of the brain within 24 h after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. The absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain injury. However, the difference of the ratio was a less than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rats. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury. PMID:28070456

  15. Perceived Neighborhood Social Cohesion and Myocardial Infarction

    PubMed Central

    Kim, Eric S.; Hawes, Armani M.; Smith, Jacqui

    2015-01-01

    Background The main strategy for alleviating heart disease has been to target individuals and encourage them to change their health behaviors. Though important, emphasis on individuals has diverted focus and responsibility away from neighborhood characteristics, which also strongly influence people’s behaviors. Although a growing body of research has repeatedly demonstrated strong associations between neighborhood characteristics and cardiovascular health, it has typically focused on negative neighborhood characteristics. Only a few studies have examined the potential health enhancing effects of positive neighborhood characteristics, such as perceived neighborhood social cohesion. Methods Using multiple logistic regression models, we tested whether higher perceived neighborhood social cohesion was associated with lower incidence of myocardial