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  1. Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia

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    Wang, Wenqing; Wang, Aihui; Yu, Limin; Han, Xuesong; Jiang, Guiyun; Weng, Changshui; Zhang, Hongwei; Zhou, Zhiqiang

    2012-01-01

    Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia. PMID:25337108

  2. Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

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    Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

    2017-07-01

    Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic

  3. Brain Basics: Preventing Stroke

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    ... NINDS) are committed to reducing that burden through biomedical research. What is a Stroke? A stroke, or "brain ... Testimony Legislative Updates Impact NINDS Contributions to Approved Therapies ... Director, Division of Intramural Research

  4. Stimulation of the sphenopalatine ganglion induces reperfusion and blood-brain barrier protection in the photothrombotic stroke model.

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    Haviv Levi

    Full Text Available The treatment of stroke remains a challenge. Animal studies showing that electrical stimulation of the sphenopalatine ganglion (SPG exerts beneficial effects in the treatment of stroke have led to the initiation of clinical studies. However, the detailed effects of SPG stimulation on the injured brain are not known.The effect of acute SPG stimulation was studied by direct vascular imaging, fluorescent angiography and laser Doppler flowmetry in the sensory motor cortex of the anaesthetized rat. Focal cerebral ischemia was induced by the rose bengal (RB photothrombosis method. In chronic experiments, SPG stimulation, starting 15 min or 24 h after photothrombosis, was given for 3 h per day on four consecutive days. Structural damage was assessed using histological and immunohistochemical methods. Cortical functions were assessed by quantitative analysis of epidural electro-corticographic (ECoG activity continuously recorded in behaving animals.Stimulation induced intensity- and duration-dependent vasodilation and increased cerebral blood flow in both healthy and photothrombotic brains. In SPG-stimulated rats both blood brain-barrier (BBB opening, pathological brain activity and lesion volume were attenuated compared to untreated stroke animals, with no apparent difference in the glial response surrounding the necrotic lesion.SPG-stimulation in rats induces vasodilation of cortical arterioles, partial reperfusion of the ischemic lesion, and normalization of brain functions with reduced BBB dysfunction and stroke volume. These findings support the potential therapeutic effect of SPG stimulation in focal cerebral ischemia even when applied 24 h after stroke onset and thus may extend the therapeutic window of currently administered stroke medications.

  5. Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

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    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

    2015-10-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

  6. Novel Regenerative Therapies Based on Regionally Induced Multipotent Stem Cells in Post-Stroke Brains: Their Origin, Characterization, and Perspective.

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    Takagi, Toshinori; Yoshimura, Shinichi; Sakuma, Rika; Nakano-Doi, Akiko; Matsuyama, Tomohiro; Nakagomi, Takayuki

    2017-12-01

    Brain injuries such as ischemic stroke cause severe neural loss. Until recently, it was believed that post-ischemic areas mainly contain necrotic tissue and inflammatory cells. However, using a mouse model of cerebral infarction, we demonstrated that stem cells develop within ischemic areas. Ischemia-induced stem cells can function as neural progenitors; thus, we initially named them injury/ischemia-induced neural stem/progenitor cells (iNSPCs). However, because they differentiate into more than neural lineages, we now refer to them as ischemia-induced multipotent stem cells (iSCs). Very recently, we showed that putative iNSPCs/iSCs are present within post-stroke areas in human brains. Because iNSPCs/iSCs isolated from mouse and human ischemic tissues can differentiate into neuronal lineages in vitro, it is possible that a clearer understanding of iNSPC/iSC profiles and the molecules that regulate iNSPC/iSC fate (e.g., proliferation, differentiation, and survival) would make it possible to perform neural regeneration/repair in patients following stroke. In this article, we introduce the origin and traits of iNSPCs/iSCs based on our reports and recent viewpoints. We also discuss their possible contribution to neurogenesis through endogenous and exogenous iNSPC/iSC therapies following ischemic stroke.

  7. Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

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    Valérie Wolff

    2015-01-01

    Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

  8. Brain-Heart Interaction: Cardiac Complications After Stroke.

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    Chen, Zhili; Venkat, Poornima; Seyfried, Don; Chopp, Michael; Yan, Tao; Chen, Jieli

    2017-08-04

    Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, that is, the effects of cardiac injury on the brain and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage. The majority of post-stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post-stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke-induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart failure), or to mild and recoverable damage such as neurogenic stress cardiomyopathy and Takotsubo cardiomyopathy. The role of location and lateralization of brain lesions after stroke in brain-heart interaction; clinical biomarkers and manifestations of cardiac complications; and underlying mechanisms of brain-heart interaction after stroke, such as the hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic and parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, and systemic inflammation, are discussed. © 2017 American Heart Association, Inc.

  9. Acupuncture Induces Time-Dependent Remodelling Brain Network on the Stable Somatosensory First-Ever Stroke Patients: Combining Diffusion Tensor and Functional MR Imaging

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    Lijun Bai

    2014-01-01

    Full Text Available Different treatment interventions induce distinct remodelling of network architecture of entire motor system. Acupuncture has been proved to be of a promising efficacy in motor recovery. However, it is still unclear whether the reorganization of motor-related brain network underlying acupuncture is related with time since stroke and severity of deficit at baseline. The aim of study was to characterize the relation between motor-related brain organization following acupuncture and white matter microstructural changes at an interval of two weeks. We demonstrated that acupuncture induced differential reorganization of motor-related network for stroke patients as time-lapse since stroke. At the baseline, acupuncture can induce the increased functional connectivity between the left primary motor cortex (M1 and the right M1, premotor cortex, supplementary motor area (SMA, thalamus, and cerebellum. After two-week recovery, the increased functional connectivity of the left M1 was more widely distributed and primarily located in the insula, cerebellum, basal ganglia, and SMA. Furthermore, a significant negative relation existed between the FA value in the left M1 at the baseline scanning and node centrality of this region following acupuncture for both baseline and two-week recovery. Our findings may shed a new insight on understanding the reorganization of motor-related theory underlying motor impairments after brain lesions in stroke patients.

  10. Task-induced brain activity in aphasic stroke patients: what is driving recovery?

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    Brownsett, Sonia L. E.; Wise, Richard J. S.

    2014-01-01

    The estimated prevalence of aphasia in the UK and the USA is 250 000 and 1 000 000, respectively. The commonest aetiology is stroke. The impairment may improve with behavioural therapy, and trials using cortical stimulation or pharmacotherapy are undergoing proof-of-principle investigation, but with mixed results. Aphasia is a heterogeneous syndrome, and the simple classifications according to the Broca-Wernicke-Lichtheim model inadequately describe the diverse communication difficulties with which patients may present. Greater knowledge of how intact neural networks promote recovery after aphasic stroke, either spontaneously or in response to interventions, will result in clearer hypotheses about how to improve the treatment of aphasia. Twenty-five years ago, a pioneering study on healthy participants heralded the introduction of functional neuroimaging to the study of mechanisms of recovery from aphasia. Over the ensuing decades, such studies have been interpreted as supporting one of three hypotheses, which are not mutually exclusive. The first two predate the introduction of functional neuroimaging: that recovery is the consequence of the reconstitution of domain-specific language systems in tissue around the lesion (the ‘perilesional’ hypothesis), or by homotopic cortex in the contralateral hemisphere (the ‘laterality-shift’ hypothesis). The third is that loss of transcallosal inhibition to contralateral homotopic cortex hinders recovery (the ‘disinhibition’ hypothesis). These different hypotheses at times give conflicting views about rehabilitative intervention; for example, should one attempt to activate or inhibit a contralateral homotopic region with cortical stimulation techniques to promote recovery? This review proposes that although the functional imaging data are statistically valid in most cases, their interpretation has often favoured one explanation while ignoring plausible alternatives. In our view, this is particularly evident when

  11. Training the brain to survive stroke.

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    Jeff F Dunn

    Full Text Available Presently, little can be done to repair brain tissue after stroke damage. We hypothesized that the mammalian brain has an intrinsic capacity to adapt to low oxygen which would improve outcome from a reversible hypoxic/ischemic episode. Acclimation to chronic hypoxia causes increased capillarity and tissue oxygen levels which may improve the capacity to survive ischemia. Identification of these adaptations will lead to protocols which high risk groups could use to improve recovery and reduce costs.Rats were exposed to hypoxia (3 weeks living at ½ an atmosphere. After acclimation, capillary density was measured morphometrically and was increased by 30% in the cortex. Novel implantable oxygen sensors showed that partial pressure of oxygen in the brain was increased by 40% in the normal cortex. Infarcts were induced in brain with 1 h reversible middle cerebral artery occlusions. After ischemia (48 h behavioural scores were improved and T2 weighted MRI lesion volumes were reduced by 52% in acclimated groups. There was a reduction in inflammation indicated by reduced lymphocytes (by 27-33%, and ED1 positive cells (by 35-45%.It is possible to stimulate a natural adaptive mechanism in the brain which will reduce damage and improve outcome for a given ischemic event. Since these adaptations occur after factors such as HIF-1α have returned to baseline, protection is likely related more to morphological changes such as angiogenesis. Such pre-conditioning, perhaps with exercise or pharmaceuticals, would not necessarily reduce the incidence of stroke, but the severity of damage could be reduced by 50%.

  12. Structural Changes Induced by Daily Music Listening in the Recovering Brain after Middle Cerebral Artery Stroke: A Voxel-Based Morphometry Study

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    Särkämö, Teppo; Ripollés, Pablo; Vepsäläinen, Henna; Autti, Taina; Silvennoinen, Heli M.; Salli, Eero; Laitinen, Sari; Forsblom, Anita; Soinila, Seppo; Rodríguez-Fornells, Antoni

    2014-01-01

    Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM) analysis utilizing cost function masking was performed on the acute and 6-month post-stroke stage structural magnetic resonance imaging data of the patients (n = 49) who either listened to their favorite music [music group (MG), n = 16] or verbal material [audio book group (ABG), n = 18] or did not receive any listening material [control group (CG), n = 15] during the 6-month recovery period. Although all groups showed significant gray matter volume (GMV) increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral striatum (VS)] in patients with left hemisphere damage in which the GMV increases were larger in the MG than in the ABG and in the CG. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood. This study adds on previous results, showing that music listening after stroke not only enhances behavioral recovery, but also induces fine-grained neuroanatomical changes in the recovering brain. PMID:24860466

  13. Structural changes induced by daily music listening in the recovering brain after middle cerebral artery stroke: a voxel-based morphometry study.

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    Särkämö, Teppo; Ripollés, Pablo; Vepsäläinen, Henna; Autti, Taina; Silvennoinen, Heli M; Salli, Eero; Laitinen, Sari; Forsblom, Anita; Soinila, Seppo; Rodríguez-Fornells, Antoni

    2014-01-01

    Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM) analysis utilizing cost function masking was performed on the acute and 6-month post-stroke stage structural magnetic resonance imaging data of the patients (n = 49) who either listened to their favorite music [music group (MG), n = 16] or verbal material [audio book group (ABG), n = 18] or did not receive any listening material [control group (CG), n = 15] during the 6-month recovery period. Although all groups showed significant gray matter volume (GMV) increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral striatum (VS)] in patients with left hemisphere damage in which the GMV increases were larger in the MG than in the ABG and in the CG. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood. This study adds on previous results, showing that music listening after stroke not only enhances behavioral recovery, but also induces fine-grained neuroanatomical changes in the recovering brain.

  14. Structural changes induced by daily music listening in the recovering brain after middle cerebral artery stroke: a voxel-based morphometry study

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    Teppo eSärkämö

    2014-04-01

    Full Text Available Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery (MCA stroke. Extending this study, a voxel-based morphometry (VBM analysis utilizing cost-function masking was performed on the acute and 6-month post-stroke stage structural MRI data of the patients (n = 49 who either listened to their favourite music (music group, n = 16 or verbal material (audio book group, n = 18 or did not receive any listening material (control group, n = 15 during the 6-month recovery period. Although all groups showed significant grey matter volume (GMV increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG, right medial SFG] and limbic areas [left ventral / subgenual anterior cingulate cortex (SACC and right ventral striatum (VS] in patients with left hemisphere damage in which the GMV increases were larger in the music group than in the audio book and control groups. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood. This study adds on previous results, showing that music listening after stroke not only enhances behavioural recovery, but also induces fine-grained neuroanatomical changes in the recovering brain.

  15. Generating and measuring photochemical changes inside the brain using optical fibers: exploring stroke.

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    Tsiminis, Georgios; Klarić, Thomas S; Schartner, Erik P; Warren-Smith, Stephen C; Lewis, Martin D; Koblar, Simon A; Monro, Tanya M

    2014-11-01

    We report here on the development of a method for inducing a stroke in a specific location within a mouse brain through the use of an optical fiber. By capturing the emitted fluorescence signal generated using the same fiber it is possible to monitor photochemical changes within the brain in real-time, and directly measure the concentration of the stroke-inducing dye, Rose Bengal, at the infarct site. This technique reduces the requirement for post-operative histology to determine if a stroke has successfully been induced within the animal, and therefore opens up the opportunity to explore the recovery of the brain after the stroke event.

  16. Bilateral brain reorganization with memantine and constraint-induced aphasia therapy in chronic post-stroke aphasia: An ERP study.

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    Barbancho, Miguel A; Berthier, Marcelo L; Navas-Sánchez, Patricia; Dávila, Guadalupe; Green-Heredia, Cristina; García-Alberca, José M; Ruiz-Cruces, Rafael; López-González, Manuel V; Dawid-Milner, Marc S; Pulvermüller, Friedemann; Lara, J Pablo

    2015-01-01

    Changes in ERP (P100 and N400) and root mean square (RMS) were obtained during a silent reading task in 28 patients with chronic post-stroke aphasia in a randomized, double-blind, placebo-controlled trial of both memantine and constraint-induced aphasia therapy (CIAT). Participants received memantine/placebo alone (weeks 0-16), followed by drug treatment combined with CIAT (weeks 16-18), and then memantine/placebo alone (weeks 18-20). ERP/RMS values (week 16) decreased more in the memantine group than in the placebo group. During CIAT application (weeks 16-18), improvements in aphasia severity and ERP/RMS values were amplified by memantine and changes remained stable thereafter (weeks 18-20). Changes in ERP/RMS occurred in left and right hemispheres and correlated with gains in language performance. No changes in ERP/RMS were found in a healthy group in two separated evaluations. Our results show that aphasia recovery induced by both memantine alone and in combination with CIAT is indexed by bilateral cortical potentials. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies.

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    Yannick Béjot

    Full Text Available BACKGROUND: Whereas brain-derived neurotrophic factor (BDNF levels are measured in the brain in animal models of stroke, neurotrophin levels in stroke patients are measured in plasma or serum samples. The present study was designed to investigate the meaning of circulating BDNF levels in stroke patients. METHODS AND RESULTS: Unilateral ischemic stroke was induced in rats by the injection of various numbers of microspheres into the carotid circulation in order to mimic the different degrees of stroke severity observed in stroke patients. Blood was serially collected from the jugular vein before and after (4 h, 24 h and 8 d embolization and the whole brains were collected at 4, 24 h and 8 d post-embolization. Rats were then selected from their degree of embolization, so that the distribution of stroke severity in the rats at the different time points was large but similar. Using ELISA tests, BDNF levels were measured in plasma, serum and brain of selected rats. Whereas plasma and serum BDNF levels were not changed by stroke, stroke induced an increase in brain BDNF levels at 4 h and 24 h post-embolization, which was not correlated with stroke severity. Individual plasma BDNF levels did not correlate with brain levels at any time point after stroke but a positive correlation (r = 0.67 was observed between individual plasma BDNF levels and stroke severity at 4 h post-embolization. CONCLUSION: Circulating BDNF levels do not mirror brain BDNF levels after stroke, and severe stroke is associated with high plasma BDNF in the very acute stage.

  18. A functional MRI study of the brain in stroke patients with upper-limb paralysis treated with constraint-induced movement therapy

    International Nuclear Information System (INIS)

    Wen Bo; Ma Lin; Weng Changshui; Zheng Zhixin; Sun Tong

    2009-01-01

    Objective: To investigate and compare the activation patterns of stroke patients with upper-limb paralysis using functional MRI before and after treatment with constraint-induced movement therapy (CIMT) so as to explore the mechanism of CIMT. Methods: Six patients in chronic stage of brain infarction who have functional disturbance in right upper-limb and 9 normal controls were entered into the study. All of the patients were asked to perform the thumb-to-index finger tapping task and underwent functional MRI before and two weeks after CIMT. The controls underwent fMRI of same protocol once. The patients' upper-limb function scores before and after CIMT were analyzed with SPSS 11.5 by paired t test. The fMRI data were analyzed with analysis of functional neurolmages (AFNI) software. The percentage of blood oxygenation level dependent (BOLD) signal change for the normal control was analyzed by one-sample t test to indentify the activated brain regions. The percentage change of BOLD signal for the patients before and after CIMT was compared to control's data by independent-samples t test. The percentage change of BOLD signal for the patients before and after CIMT was analyzed by paired-samples t test. The significant difference level was set P<0.05. Results: The fMRI showed the patients' activated brain regions before CIMT were similar to that of the controls', while the activation level was lower. There were wide areas activated to compensate the impaired function especially for the fight upper-limb. Before CIMT, the patients' score for fight upper-limb on the action research arm test was 27±4. After CIMT, the patients' score was 40±3, and the difference was significant (t=14.626, P<0.05), which indicated the improved function. These subjects also displayed cortical reorganization after CIMT on fMRI. The areas responsible for the right hand movement showed increased activation and the activation level at bilateral corpora striata thalami, and cerebella increased

  19. Exacerbation of oxygen-glucose deprivation-induced blood-brain barrier disruption: potential pathogenic role of interleukin-9 in ischemic stroke.

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    Tan, Sha; Shan, Yilong; Wang, Yuge; Lin, Yinyao; Liao, Siyuan; Deng, Zhezhi; Zhou, Li; Cai, Wei; Zeng, Qin; Zhang, Lei; Zhang, Bingjun; Men, Xuejiao; Li, Haiyan; Hu, Xueqiang; Wu, Changyou; Peng, Lisheng; Lu, Zhengqi

    2017-07-01

    Interleukin (IL)-9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke (IS). We recruited 42 patients newly diagnosed with IS and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3 + CD4 + IL-9 + and CD3 + CD8 + IL-9 + cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals. We also investigated the effects of IL-9 on the blood-brain barrier (BBB) following oxygen-glucose deprivation (OGD) and the potential downstream signaling pathways. We found that patients with IS had higher IL-9 expression levels and increased percentages of IL-9-producing T cells in their PBMCs. The percentages of CD3 + CD4 + IL-9 + and CD3 + CD8 + IL-9 + T cells were positively correlated with the severity of illness. In in vitro experiments using bEnd.3 cells, exogenously administered IL-9 exacerbated the loss of tight junction proteins (TJPs) in cells subjected to OGD plus reoxygenation (RO). This effect was mediated via activation of IL-9 receptors, which increased the level of endothelial nitric oxide synthase (eNOS), as well as through up-regulated phosphorylation of signal transducer and activator of transcription 1 and 3 and down-regulated phosphorylated protein kinase B/phosphorylated phosphatidylinositol 3-kinase signaling. These results indicate that IL-9 has a destructive effect on the BBB following OGD, at least in part by inducing eNOS production, and raise the possibility of targetting IL-9 for therapeutic intervention in IS. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  20. Drug-induced Hypothermia by 5HT1A Agonists Provide Neuroprotection in Experimental Stroke

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    Johansen, Flemming Fryd; Hasseldam, Henrik; Nybro Smith, Matthias

    2014-01-01

    BACKGROUND: Drug-induced hypothermia reduces brain damage in animal stroke models and is an undiscovered potential in human stroke treatment. We studied hypothermia induced by the serotonergic agonists S14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine) and ipsapirone in a rat...... therapeutic hypothermia....

  1. Stroke

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    ... doctor Preventing falls Stroke - discharge Swallowing problems Images Brain Carotid stenosis, x-ray of the left artery Carotid stenosis, x-ray of the right artery Stroke Brainstem function Cerebellum - function Circle of Willis Left cerebral hemisphere - ...

  2. Structural MRI markers of brain aging early after ischemic stroke.

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    Werden, Emilio; Cumming, Toby; Li, Qi; Bird, Laura; Veldsman, Michele; Pardoe, Heath R; Jackson, Graeme; Donnan, Geoffrey A; Brodtmann, Amy

    2017-07-11

    To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. First-ever stroke was associated with smaller hippocampal volume ( p = 0.025) and greater WMH volume ( p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke ( p = 0.017) and controls ( p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls ( p = 0.056), but the association became significant after further adjustment for atrial fibrillation ( p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  3. An associative Brain-Computer-Interface for acute stroke patients

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    Mrachacz-Kersting, Natalie; Stevenson, Andrew James Thomas; Aliakbaryhosseinabadi, Susan

    2016-01-01

    An efficient innovative Brain-Computer-Interface system that empowers chronic stroke patients to control an artificial activation of their lower limb muscle through task specific motor intent has been tested in the past. In the current study it was applied to acute stroke patients. The system...

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

    Science.gov (United States)

    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.

  5. Blood-brain barrier and cerebral blood flow: Age differences in hemorrhagic stroke

    Directory of Open Access Journals (Sweden)

    Semyachkina-Glushkovskaya Oxana

    2015-11-01

    Full Text Available Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits. There are important differences in the factors, clinical events and outcomes associated with the stroke in infants and adults. However, mechanisms underlying age differences in the stroke development remain largely unknown. Therefore, treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children. The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke. Here, we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats. Using histological methods and magnetic resonance imaging, we found age differences in the type of intracranial hemorrhages. Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum. Using Doppler optical coherent tomography, we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs. adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs. adult brain in rats. However, adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier (BBB permeability. The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB (occludin and claudin-5 in neonatal vs. mature brain in rats.

  6. Perturbation of Brain Oscillations after Ischemic Stroke: A Potential Biomarker for Post-Stroke Function and Therapy

    Directory of Open Access Journals (Sweden)

    Gratianne Rabiller

    2015-10-01

    Full Text Available Brain waves resonate from the generators of electrical current and propagate across brain regions with oscillation frequencies ranging from 0.05 to 500 Hz. The commonly observed oscillatory waves recorded by an electroencephalogram (EEG in normal adult humans can be grouped into five main categories according to the frequency and amplitude, namely δ (1–4 Hz, 20–200 μV, θ (4–8 Hz, 10 μV, α (8–12 Hz, 20–200 μV, β (12–30 Hz, 5–10 μV, and γ (30–80 Hz, low amplitude. Emerging evidence from experimental and human studies suggests that groups of function and behavior seem to be specifically associated with the presence of each oscillation band, although the complex relationship between oscillation frequency and function, as well as the interaction between brain oscillations, are far from clear. Changes of brain oscillation patterns have long been implicated in the diseases of the central nervous system including ischemic stroke, in which the reduction of cerebral blood flow as well as the progression of tissue damage have direct spatiotemporal effects on the power of several oscillatory bands and their interactions. This review summarizes the current knowledge in behavior and function associated with each brain oscillation, and also in the specific changes in brain electrical activities that correspond to the molecular events and functional alterations observed after experimental and human stroke. We provide the basis of the generations of brain oscillations and potential cellular and molecular mechanisms underlying stroke-induced perturbation. We will also discuss the implications of using brain oscillation patterns as biomarkers for the prediction of stroke outcome and therapeutic efficacy.

  7. The image of a brain stroke in a computed tomograph

    International Nuclear Information System (INIS)

    Just, E.G.

    1982-01-01

    On the basis of 100 findings from patients who suffered brain strokes and by the use of 1500 ensured stroke images it was tested whether or not the stroke-predilection typologie outlined by Zuelch is based on a coincidental summation of individual cases. The radio-computed tomography with the possibility of evaluation of non-lethal cases proved itself as a suited method for confirmation or repudiation of this stroke theory. By means of the consistently achieved association of the frontal, respectively horizontal sectional image for the typology it could be proven and - with the exception of a few rather seldom types - also demonstrated that the basic and predilection types of brain stroke repeated themselves in their pattern. In individual cases a specification of lower types could also be undertaken. (orig./TRV) [de

  8. Use of computerized tomography in brain stroke

    Energy Technology Data Exchange (ETDEWEB)

    Landmark, K.; Aursnes, I.; Eldvik, P.; Lilleaas, F.G.

    1988-04-01

    In a retrospective study in 115 patients consecutively admitted to a ''stroke unit'', 108 were found to have been subjected to one or more cerebral CT-scans, of which ten revealed cerebral haemorrhage, two tumor cerebri and one subdural haematoma. The latter patient was successfully operated upon. The clinical diagnosis of stroke in progression was made in seven patients, whereas embolic stroke was diagnosed in 22. After haemorrhage had been excluded by CT, anticoagulant therapy (warfarin/heparin) was started for various reasons in 35 patients altogether. It is concluded that CT, if available locally, should be performed routinely during the first days following acute stroke.

  9. Use of computerized tomography in brain stroke

    International Nuclear Information System (INIS)

    Landmark, K.; Aursnes, I.; Eldvik, P.; Lilleaas, F.G.

    1988-01-01

    In a retrospective study in 115 patients consecutively admitted to a ''stroke unit'', 108 were found to have been subjected to one or more cerebral CT-scans, of which ten revealed cerebral haemorrhage, two tumor cerebri and one subdural haematoma. The latter patient was successfully operated upon. The clinical diagnosis of stroke in progression was made in seven patients, whereas embolic stroke was diagnosed in 22. After haemorrhage had been excluded by CT, anticoagulant therapy (warfarin/heparin) was started for various reasons in 35 patients altogether. It is concluded that CT, if available locally, should be performed routinely during the first days following acute stroke

  10. Constraint-induced movement therapy after stroke

    NARCIS (Netherlands)

    Kwakkel, G.; Veerbeek, J.M.; van Wegen, E.E.H.; Wolf, S.L.

    2015-01-01

    Constraint-induced movement therapy (CIMT) was developed to overcome upper limb impairments after stroke and is the most investigated intervention for the rehabilitation of patients. Original CIMT includes constraining of the non-paretic arm and task-oriented training. Modified versions also apply

  11. Blood-brain barrier alterations provide evidence of subacute diaschisis in an ischemic stroke rat model.

    Directory of Open Access Journals (Sweden)

    Svitlana Garbuzova-Davis

    Full Text Available Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas.In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO, significant BBB alterations characterized by large Evans Blue (EB parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices.These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke.

  12. Exacerbation of Brain Injury by Post-Stroke Exercise Is Contingent Upon Exercise Initiation Timing

    Directory of Open Access Journals (Sweden)

    Fengwu Li

    2017-10-01

    Full Text Available Accumulating evidence has demonstrated that post-stroke physical rehabilitation may reduce morbidity. The effectiveness of post-stroke exercise, however, appears to be contingent upon exercise initiation. This study assessed the hypothesis that very early exercise exacerbates brain injury, induces reactive oxygen species (ROS generation, and promotes energy failure. A total of 230 adult male Sprague-Dawley rats were subjected to middle cerebral artery (MCA occlusion for 2 h, and randomized into eight groups, including two sham injury control groups, three non-exercise and three exercise groups. Exercise was initiated after 6 h, 24 h and 3 days of reperfusion. Twenty-four hours after completion of exercise (and at corresponding time points in non-exercise controls, infarct volumes and apoptotic cell death were examined. Early brain oxidative metabolism was quantified by examining ROS, ATP and NADH levels 0.5 h after completion of exercise. Furthermore, protein expressions of angiogenic growth factors were measured in order to determine whether post-stroke angiogenesis played a role in rehabilitation. As expected, ischemic stroke resulted in brain infarction, apoptotic cell death and ROS generation, and diminished NADH and ATP production. Infarct volumes and apoptotic cell death were enhanced (p < 0.05 by exercise that was initiated after 6 h of reperfusion, but decreased by late exercise (24 h, 3 days. This exacerbated brain injury at 6 h was associated with increased ROS levels (p < 0.05, and decreased (p < 0.05 NADH and ATP levels. In conclusion, very early exercise aggravated brain damage, and early exercise-induced energy failure with ROS generation may underlie the exacerbation of brain injury. These results shed light on the manner in which exercise initiation timing may affect post-stroke rehabilitation.

  13. Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

    Science.gov (United States)

    Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

    2017-06-01

    Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

  14. Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

    Science.gov (United States)

    Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

    2013-05-01

    Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Non invasive brain stimulation to enhance post-stroke recovery

    OpenAIRE

    Nathalie Kubis; Nathalie Kubis

    2016-01-01

    Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first days, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical exci...

  16. Do brain lesions in stroke affect basic emotions and attachment?

    Science.gov (United States)

    Farinelli, Marina; Panksepp, Jaak; Gestieri, Laura; Maffei, Monica; Agati, Raffaele; Cevolani, Daniela; Pedone, Vincenzo; Northoff, Georg

    2015-01-01

    The aim of the current study was to investigate basic emotions and attachment in a sample of 86 stroke patients. We included a control group of 115 orthopedic patients (matched for age and cognitive status) without brain lesions to control for unspecific general illness effects of a traumatic recent event on basic emotions and attachment. In order to measure basic emotions and attachment style we applied the Affective Neuroscience Personality Scale (ANPS) and the Attachment Style Questionnaire (ASQ). The stroke patients showed significantly different scores in the SEEKING, SADNESS, and ANGER subscales of the ANPS as well as in the Relationship as Secondary Attachment dimension of the ASQ when compared to the control group. These differences show a pattern influenced by lesion location mainly as concerns basic emotions. Anterior, medial, left, and subcortical patients provide scores significantly lower in ANPS-SEEKING than the control group; ANPS-SADNESS scores in anterior, right, medial, and subcortical patients were significantly higher than those of the control group. ANPS-ANGER scores in posterior, right, and lateral patients were significantly higher than those in the control group; finally, the ANPS-FEAR showed slightly lower scores in posterior patients than in the control group. Minor effects on brain lesions were also individuated in the attachment style. Anterior lesion patients showed a significantly higher average score in the ASQ-Need for Approval subscale than the control group. ASQ-Confidence subscale scores differed significantly in stroke patients with lesions in medial brain regions when compared to control subjects. Scores at ANPS and ASQ subscales appear significantly more correlated in stroke patients than in the control group. Such finding of abnormalities, especially concerning basic emotions in stroke brain-lesioned patients, indicates that the effect of brain lesions may enhance the interrelation between basic emotions and attachment with

  17. Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study.

    Science.gov (United States)

    Hoffmann, Sarah; Harms, Hendrik; Ulm, Lena; Nabavi, Darius G; Mackert, Bruno-Marcel; Schmehl, Ingo; Jungehulsing, Gerhard J; Montaner, Joan; Bustamante, Alejandro; Hermans, Marcella; Hamilton, Frank; Göhler, Jos; Malzahn, Uwe; Malsch, Carolin; Heuschmann, Peter U; Meisel, Christian; Meisel, Andreas

    2017-12-01

    Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

  18. Transcranial brain stimulation to promote functional recovery after stroke

    DEFF Research Database (Denmark)

    Raffin, Estelle; Siebner, Hartwig R

    2014-01-01

    as a therapeutic tool. RECENT FINDINGS: Recent meta-analyses showed that the treatment effects of NIBS in patients with stroke are rather inconsistent across studies and the evidence for therapeutic efficacy is still uncertain. This raises the question of how NIBS can be developed further to improve its...... therapeutic efficacy. SUMMARY: This review addressed six questions: How does NIBS facilitate the recovery of function after stroke? Which brain regions should be targeted by NIBS? Is there a particularly effective NIBS modality that should be used? Does the location of the stroke influence the therapeutic...... will be critical to fully unfold the therapeutic effects of NIBS and will pave the way towards adaptive NIBS protocols, in which NIBS is tailored to the individual patient....

  19. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B

    1999-01-01

    CBF) SPECT-scanning using 99mTc-HMPAO as flow tracer was performed in the patients. Mean water content (SD) in the infarct area was 37.7 (5.1); 41.8 (4.8); 35.2 (5.4); and 39.3 (5.1) mol x [kg wet weight](-1) at 0-3; 4-7; 8-21; and >180 days after stroke, respectively. Water content increased between Day 0......CBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water...... as an internal standard in stroke patients....

  20. Diffusion tensor and volumetric magnetic resonance imaging using an MR-compatible hand-induced robotic device suggests training-induced neuroplasticity in patients with chronic stroke.

    Science.gov (United States)

    Lazaridou, Asimina; Astrakas, Loukas; Mintzopoulos, Dionyssios; Khanicheh, Azadeh; Singhal, Aneesh B; Moskowitz, Michael A; Rosen, Bruce; Tzika, Aria A

    2013-11-01

    Stroke is the third leading cause of mortality and a frequent cause of long-term adult impairment. Improved strategies to enhance motor function in individuals with chronic disability from stroke are thus required. Post‑stroke therapy may improve rehabilitation and reduce long-term disability; however, objective methods for evaluating the specific impact of rehabilitation are rare. Brain imaging studies on patients with chronic stroke have shown evidence for reorganization of areas showing functional plasticity after a stroke. In this study, we hypothesized that brain mapping using a novel magnetic resonance (MR)-compatible hand device in conjunction with state‑of‑the‑art magnetic resonance imaging (MRI) can serve as a novel biomarker for brain plasticity induced by rehabilitative motor training in patients with chronic stroke. This hypothesis is based on the premises that robotic devices, by stimulating brain plasticity, can assist in restoring movement compromised by stroke-induced pathological changes in the brain and that these changes can then be monitored by advanced MRI. We serially examined 15 healthy controls and 4 patients with chronic stroke. We employed a combination of diffusion tensor imaging (DTI) and volumetric MRI using a 3-tesla (3T) MRI system using a 12-channel Siemens Tim coil and a novel MR-compatible hand‑induced robotic device. DTI data revealed that the number of fibers and the average tract length significantly increased after 8 weeks of hand training by 110% and 64%, respectively (probotics in the molecular medicine era.

  1. Neural precursor cells in the ischemic brain - integration, cellular crosstalk and consequences for stroke recovery

    Directory of Open Access Journals (Sweden)

    Dirk M. Hermann

    2014-09-01

    Full Text Available After an ischemic stroke, neural precursor cells (NPCs proliferate within major germinal niches of the brain. Endogenous NPCs subsequently migrate towards the ischemic lesion where they promote tissue remodelling and neural repair. Unfortunately, this restorative process is generally insufficient and thus unable to support a full recovery of lost neurological functions. Supported by solid experimental and preclinical data, the transplantation of exogenous NPCs has emerged as a potential tool for stroke treatment. Transplanted NPCs are thought to act mainly via trophic and immune modulatory effects, thereby complementing the restorative responses initially executed by the endogenous NPC population. Recent studies have attempted to elucidate how the therapeutic properties of transplanted NPCs vary depending on the route of transplantation. Systemic NPC delivery leads to potent immune modulatory actions, which prevent secondary neuronal degeneration, reduces glial scar formation, diminishes oxidative stress and stabilizes blood-brain barrier integrity. On the contrary, local stem cell delivery, allows for the accumulation of large numbers of transplanted NPCs in the brain, thus achieving high levels of locally available tissue trophic factors, which may better induce a strong endogenous NPC proliferative response.Herein we describe the diverse capabilities of exogenous (systemically vs locally transplanted NPCs in enhancing the endogenous neurogenic response after stroke, and how the route of transplantation may affect migration, survival, bystander effects and integration of the cellular graft. It is the authors’ claim that understanding these aspects will be of pivotal importance in discerning how transplanted NPCs exert their therapeutic effects in stroke.

  2. The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke

    DEFF Research Database (Denmark)

    Ruscher, Karsten; Shamloo, Mehrdad; Rickhag, Karl Mattias

    2011-01-01

    Stroke leads to brain damage with subsequent slow and incomplete recovery of lost brain functions. Enriched housing of stroke-injured rats provides multi-modal sensorimotor stimulation, which improves recovery, although the specific mechanisms involved have not been identified. In rats housed in ...... of biomolecules required for brain repair, thereby stimulating brain plasticity. Pharmacological targeting of the sigma-1 receptor provides new opportunities for stroke treatment beyond the therapeutic window of neuroprotection....

  3. Automated delineation of stroke lesions using brain CT images

    Directory of Open Access Journals (Sweden)

    Céline R. Gillebert

    2014-01-01

    Full Text Available Computed tomographic (CT images are widely used for the identification of abnormal brain tissue following infarct and hemorrhage in stroke. Manual lesion delineation is currently the standard approach, but is both time-consuming and operator-dependent. To address these issues, we present a method that can automatically delineate infarct and hemorrhage in stroke CT images. The key elements of this method are the accurate normalization of CT images from stroke patients into template space and the subsequent voxelwise comparison with a group of control CT images for defining areas with hypo- or hyper-intense signals. Our validation, using simulated and actual lesions, shows that our approach is effective in reconstructing lesions resulting from both infarct and hemorrhage and yields lesion maps spatially consistent with those produced manually by expert operators. A limitation is that, relative to manual delineation, there is reduced sensitivity of the automated method in regions close to the ventricles and the brain contours. However, the automated method presents a number of benefits in terms of offering significant time savings and the elimination of the inter-operator differences inherent to manual tracing approaches. These factors are relevant for the creation of large-scale lesion databases for neuropsychological research. The automated delineation of stroke lesions from CT scans may also enable longitudinal studies to quantify changes in damaged tissue in an objective and reproducible manner.

  4. Late-onset radiation-induced vasculopathy and stroke in a child with medulloblastoma.

    Science.gov (United States)

    Bansal, Lalit R; Belair, Jeffrey; Cummings, Dana; Zuccoli, Giulio

    2015-05-01

    We report a case of a 15-year-old boy who presented to our institution with left-sided weakness and slurred speech. He had a history of medulloblastoma diagnosed at 3 years of age, status postsurgical resection and craniospinal radiation. Magnetic resonance imaging (MRI) of brain revealed a right paramedian pontine infarction, suspected secondary to late-onset radiation-induced vasculopathy of the vertebrobasilar system. Radiation to the brain is associated with increased incidence of ischemic stroke. Clinicians should have a high index of suspicion for stroke when these patients present with new neurologic symptoms. © The Author(s) 2014.

  5. Structural changes induced by daily music listening in the recovering brain after middle cerebral artery stroke: a voxel-based morphometry study

    OpenAIRE

    Särkämö, Teppo; Ripollés, Pablo; Vepsäläinen, Henna; Autti, Taina; Silvennoinen, Heli M.; Salli, Eero; Laitinen, Sari; Forsblom, Anita; Soinila, Seppo; Rodríguez Fornells, Antoni

    2014-01-01

    [Abstract.] Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neuro- logical rehabilitation. In our previous randomized controlled study, we found that listening to music...

  6. Brain perfusion CT in acute stroke: current status

    Energy Technology Data Exchange (ETDEWEB)

    Koenig, Matthias E-mail: matthias.koenig@ruhr-uni-bochum.de

    2003-03-01

    Dynamic perfusion CT has become a widely accepted imaging modality for the diagnostic workup of acute stroke patients. Although compared with standard spiral CT the use of multislice CT has broadened the range from which perfusion data may be derived in a single scan run. The advent of multidetector row technology has not really overcome the limited 3D capability of this technique. Multidetector CT angiography (CTA) of the cerebral arteries may in part compensate for this by providing additional information about the cerebrovascular status. This article describes the basics of cerebral contrast bolus scanning with a special focus on optimization of contrast/noise in order to ensure high quality perfusion maps. Dedicated scan protocols including low tube voltage (80 kV) as well as the use of highly concentrated contrast media are amongst the requirements to achieve optimum contrast signal from the short bolus passage through the brain. Advanced pre and postprocessing algorithms may help reduce the noise level, which may become critical in unconscious stroke victims. Two theoretical concepts have been described for the calculation of tissue perfusion from contrast bolus studies, both of which can be equally employed for brain perfusion imaging. For each perfusion model there are some profound limitations regarding the validity of perfusion values derived from ischemic brain areas. This makes the use of absolute quantitative cerebral blood flow (CBF) values for the discrimination of the infarct core from periinfarct ischemia questionable. Multiparameter imaging using maps of CBF, cerebral blood volume (CBV), and a time parameter of the local bolus transit enables analyzing of the cerebral perfusion status in detail. Perfusion CT exceeds plain CT in depicting cerebral hypoperfusion at its earliest stage yielding a sensitivity of about 90% for the detection of embolic and hemodynamic lesions within cerebral hemispheres. Qualitative assessment of brain perfusion can be

  7. Harnessing the potential of biomaterials for brain repair after stroke

    Science.gov (United States)

    Tuladhar, Anup; Payne, Samantha L.; Shoichet, Molly S.

    2018-03-01

    Stroke is a devastating disease for which no clinical treatment exists to regenerate lost tissue. Strategies for brain repair in animal models of stroke include the delivery of drug or cell-based therapeutics; however, the complex anatomy and functional organization of the brain presents many challenges. Biomaterials may alleviate some of these challenges by providing a scaffold, localizing the therapy to the site of action, and/or modulating cues to brain cells. Here, the challenges associated with delivery of therapeutics to the brain and the biomaterial strategies used to overcome these challenges are described. For example, innovative hydrogel delivery systems have been designed to provide sustained trophic factor delivery for endogenous repair and to support transplanted cell survival and integration. Novel treatments, such as electrical stimulation of transplanted cells and the delivery of factors for the direct reprogramming of astrocytes into neurons, may be further enhanced by biomaterial delivery systems. Ultimately, improved clinical translation will be achieved by combining clinically relevant therapies with biomaterials strategies.

  8. β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain

    Directory of Open Access Journals (Sweden)

    Teppei Fujioka

    2017-02-01

    Full Text Available Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration.

  9. Neurosteroids and Ischemic Stroke: Progesterone a Promising Agent in Reducing the Brain Injury in Ischemic Stroke.

    Science.gov (United States)

    Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

    2017-01-01

    Progesterone (P4), a well-known neurosteroid, is produced by ovaries and placenta in females and by adrenal glands in both sexes. Progesterone is also synthesized by central nervous system (CNS) tissues to perform various vital neurological functions in the brain. Apart from performing crucial reproductive functions, it also plays a pivotal role in neurogenesis, regeneration, cognition, mood, inflammation, and myelination in the CNS. A substantial body of experimental evidence from animal models documents the neuroprotective role of P4 in various CNS injury models, including ischemic stroke. Extensive data have revealed that P4 elicits neuroprotection through multiple mechanisms and systems in an integrated manner to prevent neuronal and glial damage, thus reducing mortality and morbidity. Progesterone has been described as safe for use at the clinical level through different routes in several studies. Data regarding the neuroprotective role of P4 in ischemic stroke are of great interest due to their potential clinical implications. In this review, we succinctly discuss the biosynthesis of P4 and distribution of P4 receptors (PRs) in the brain. We summarize our work on the general mechanisms of P4 mediated via the modulation of different PR and neurotransmitters. Finally, we describe the neuroprotective mechanisms of P4 in ischemic stroke models and related clinical prospects.

  10. ASTROCYTES IN THE NEUROPROTECTION AFTER BRAIN STROKE

    Directory of Open Access Journals (Sweden)

    Gloria Patricia Cardona Gomez

    2015-03-01

    Full Text Available Astrocytes are specialized glial cells of the nervous system, which have multiple homeostatic functions for the survival and maintenance of the neurovascular unit. It has been shown that astrocytes have critical role in the dynamics pro survival conferring neuroprotective, angiogenic, immunomodulatory, neurogenic, antioxidants and regulatory synapse functions (Shen et al 2012; Gimsa et al 2013; Proschel et al 2014; making them excellent candidates as the source of neuroprotection and neurorestauration of tissue affected by events ischemia and / or reperfusion. However, these cells also may be involved in negative responses such as reactive astrocytes and glial scar under chronic excitotoxic responses generated by these events. To know what are the key points in the pro and anti-survival responses of astrocytes, would allow use them as targets in cellular therapies. This review has aim to study the mechanisms for neuroprotection in these cells (Posada-Duque et al submitted, which would make them targets of cell therapy, through of inducing regeneration, such as vehicle for corrective molecular systems and trigger endogenous cellular events that can recover the tissue homeostasis, which is lost after progressive damage.

  11. Protein-Energy Malnutrition Exacerbates Stroke-Induced Forelimb Abnormalities and Dampens Neuroinflammation.

    Science.gov (United States)

    Alaverdashvili, Mariam; Caine, Sally; Li, Xue; Hackett, Mark J; Bradley, Michael P; Nichol, Helen; Paterson, Phyllis G

    2018-02-03

    Protein-energy malnutrition (PEM) pre-existing at stroke onset is believed to worsen functional outcome, yet the underlying mechanisms are not fully understood. Since brain inflammation is an important modulator of neurological recovery after stroke, we explored the impact of PEM on neuroinflammation in the acute period in relation to stroke-initiated sensori-motor abnormalities. Adult rats were fed a low-protein (LP) or normal protein (NP) diet for 28 days before inducing photothrombotic stroke (St) in the forelimb region of the motor cortex or sham surgery; the diets continued for 3 days after the stroke. Protein-energy status was assessed by a combination of body weight, food intake, serum acute phase proteins and corticosterone, and liver lipid content. Deficits in motor function were evaluated in the horizontal ladder walking and cylinder tasks at 3 days after stroke. The glial response and brain elemental signature were investigated by immunohistochemistry and micro-X-ray fluorescence imaging, respectively. The LP-fed rats reduced food intake, resulting in PEM. Pre-existing PEM augmented stroke-induced abnormalities in forelimb placement accuracy on the ladder; LP-St rats made more errors (29 ± 8%) than the NP-St rats (15 ± 3%; P < 0.05). This was accompanied by attenuated astrogliosis in the peri-infarct area by 18% and reduced microglia activation by up to 41 and 21% in the peri-infarct area and the infarct rim, respectively (P < 0.05). The LP diet altered the cortical Zn, Ca, and Cl signatures (P < 0.05). Our data suggest that proactive treatment of pre-existing PEM could be essential for optimal post-stroke recovery.

  12. Effects of vibratory stimulation-induced kinesthetic illusions on the neural activities of patients with stroke.

    Science.gov (United States)

    Kodama, Takayuki; Nakano, Hideki; Ohsugi, Hironori; Murata, Shin

    2016-01-01

    [Purpose] This study evaluated the influence of vibratory stimulation-induced kinesthetic illusion on brain function after stroke. [Subjects] Twelve healthy individuals and 13 stroke patients without motor or sensory loss participated. [Methods] Electroencephalograms were taken at rest and during vibratory stimulation. As a neurophysiological index of brain function, we measured the μ-rhythm, which is present mainly in the kinesthetic cortex and is attenuated by movement or motor imagery and compared the data using source localization analyses in the Standardized Low Resolution Brain Electromagnetic Tomography (sLORETA) program. [Results] At rest, μ-rhythms appeared in the sensorimotor and supplementary motor cortices in both healthy controls and stroke patients. Under vibratory stimulation, no μ-rhythm appeared in the sensorimotor cortex of either group. Moreover, in the supplementary motor area, which stores the motor imagery required for kinesthetic illusions, the μ-rhythms of patients were significantly stronger than those of the controls, although the μ-rhythms of both groups were reduced. Thus, differences in neural activity in the supplementary motor area were apparent between the subject groups. [Conclusion] Kinesthetic illusions do occur in patients with motor deficits due to stroke. The neural basis of the supplementary motor area in stroke patients may be functionally different from that found in healthy controls.

  13. CT perfusion scanning of the brain in stroke and beyond

    International Nuclear Information System (INIS)

    Riedel, Christian

    2011-01-01

    CT perfusion scanning (CTP) allows for quantitative analysis of cerebral blood flow (CBF) and cerebral blood volume (CBV). Until recently, it was only possible to study brain perfusion parameters in a small stack of CT-slices close to the skull base. With the introduction of multidetector CT scanners with 64 and more detector rows it has become possible to assess perfusion of the entire brain. An optimal choice of scanning parameters like the new 'shuttle'-technique combined with a well adapted regimen for contrast administration is required to guarantee reliable perfusion measurements while still keeping the X-ray dose absorbed by the patient at a minimum. With these techniques, CTP is not only an important modality in the work-up of patients suffering from acute ischemic stroke but can also be valuable in other emergency situations such as in prolonged epileptic seizures or to monitor patients with subacute subarachnoid hemorrhage. (orig.)

  14. Prediction of stroke thrombolysis outcome using CT brain machine learning

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    Paul Bentley

    2014-01-01

    Full Text Available A critical decision-step in the emergency treatment of ischemic stroke is whether or not to administer thrombolysis — a treatment that can result in good recovery, or deterioration due to symptomatic intracranial haemorrhage (SICH. Certain imaging features based upon early computerized tomography (CT, in combination with clinical variables, have been found to predict SICH, albeit with modest accuracy. In this proof-of-concept study, we determine whether machine learning of CT images can predict which patients receiving tPA will develop SICH as opposed to showing clinical improvement with no haemorrhage. Clinical records and CT brains of 116 acute ischemic stroke patients treated with intravenous thrombolysis were collected retrospectively (including 16 who developed SICH. The sample was split into training (n = 106 and test sets (n = 10, repeatedly for 1760 different combinations. CT brain images acted as inputs into a support vector machine (SVM, along with clinical severity. Performance of the SVM was compared with established prognostication tools (SEDAN and HAT scores; original, or after adaptation to our cohort. Predictive performance, assessed as area under receiver-operating-characteristic curve (AUC, of the SVM (0.744 compared favourably with that of prognostic scores (original and adapted versions: 0.626–0.720; p < 0.01. The SVM also identified 9 out of 16 SICHs, as opposed to 1–5 using prognostic scores, assuming a 10% SICH frequency (p < 0.001. In summary, machine learning methods applied to acute stroke CT images offer automation, and potentially improved performance, for prediction of SICH following thrombolysis. Larger-scale cohorts, and incorporation of advanced imaging, should be tested with such methods.

  15. Time Is Brain: The Stroke Theory of Relativity.

    Science.gov (United States)

    Gomez, Camilo R

    2018-04-25

    Since the introduction of the philosophical tenet "Time is Brain!," multiple lines of research have demonstrated that other factors contribute to the degree of ischemic injury at any one point in time, and it is now clear that the therapeutic window of acute ischemic stroke is more protracted than it was first suspected. To define a more realistic relationship between time and the ischemic process, we used computational modeling to assess how these 2 variables are affected by collateral circulatory competence. Starting from the premise that the expression "Time=Brain" is mathematically false, we reviewed the existing literature on the attributes of cerebral ischemia over time, with particular attention to relevant clinical parameters, and the effect of different variables, particularly collateral circulation, on the time-ischemia relationship. We used this information to construct a theoretical computational model and applied it to categorically different yet abnormal cerebral perfusion scenarios, allowing comparison of their behavior both overall (i.e., final infarct volume) and in real-time (i.e., instantaneous infarct growth rate). Optimal collateral circulatory competence was predictably associated with slower infarct growth rates and prolongation of therapeutic window. Modeling of identifiable specific types of perfusion maps allows forecasting of the fate of the ischemic process over time. Distinct cerebral perfusion map patterns can be readily identified in patients with acute ischemic stroke. These patterns have inherently different behaviors relative to the time-ischemia construct, allowing the possibility of improving parsing and treatment allocation. It is clearly evident that the effect of time on the ischemic process is relative. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Heat stroke induced cerebellar dysfunction: A “forgotten syndrome”

    Science.gov (United States)

    Kosgallana, Athula D; Mallik, Shreyashee; Patel, Vishal; Beran, Roy G

    2013-01-01

    We report a case of heat stroke induced acute cerebellar dysfunction, a rare neurological disease characterized by gross cerebellar dysfunction with no acute radiographic changes, in a 61 years old ship captain presenting with slurred speech and gait ataxia. A systematic review of the literature on heat stroke induced cerebellar dysfunction was performed, with a focus on investigations, treatment and outcomes. After review of the literature and detailed patient investigation it was concluded that this patient suffered heat stroke at a temperature less than that quoted in the literature. PMID:24340279

  17. Stroke and Drug Delivery--In Vitro Models of the Ischemic Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Tornabene, Erica; Brodin, Birger

    2016-01-01

    of permeation pathways across the barrier in ischemic and postischemic brain endothelium is important for development of new medical treatments. The blood-brain barrier, that is, the endothelial monolayer lining the brain capillaries, changes properties during an ischemic event. In vitro models of the blood-brain......Stroke is a major cause of death and disability worldwide. Both cerebral hypoperfusion and focal cerebral infarcts are caused by a reduction of blood flow to the brain, leading to stroke and subsequent brain damage. At present, only few medical treatments of stroke are available, with the Food...... and Drug Administration-approved tissue plasminogen activator for treatment of acute ischemic stroke being the most prominent example. A large number of potential drug candidates for treatment of ischemic brain tissue have been developed and subsequently failed in clinical trials. A deeper understanding...

  18. Systematic Analysis of RNA Regulatory Network in Rat Brain after Ischemic Stroke

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    Juan Liu

    2018-01-01

    Full Text Available Although extensive studies have identified large number of microRNAs (miRNAs and long noncoding RNAs (lncRNAs in ischemic stroke, the RNA regulation network response to focal ischemia remains poorly understood. In this study, we simultaneously interrogate the expression profiles of lncRNAs, miRNAs, and mRNAs changes during focal ischemia induced by transient middle cerebral artery occlusion. A set of 1924 novel lncRNAs were identified and may involve brain injury and DNA repair as revealed by coexpression network analysis. Furthermore, many short interspersed elements (SINE mediated lncRNA:mRNA duplexes were identified, implying that lncRNAs mediate Staufen1-mediated mRNA decay (SMD which may play a role during focal ischemia. Moreover, based on the competitive endogenous RNA (ceRNA hypothesis, a stroke regulatory ceRNA network which reveals functional lncRNA:miRNA:mRNA interactions was revealed in ischemic stroke. In brief, this work reports a large number of novel lncRNAs responding to focal ischemia and constructs a systematic RNA regulation network which highlighted the role of ncRNAs in ischemic stroke.

  19. Inhibition of myeloperoxidase oxidant production by N-acetyl lysyltyrosylcysteine amide reduces brain damage in a murine model of stroke.

    Science.gov (United States)

    Yu, Guoliang; Liang, Ye; Huang, Ziming; Jones, Deron W; Pritchard, Kirkwood A; Zhang, Hao

    2016-05-24

    Oxidative stress plays an important and causal role in the mechanisms by which ischemia/reperfusion (I/R) injury increases brain damage after stroke. Accordingly, reducing oxidative stress has been proposed as a therapeutic strategy for limiting damage in the brain after stroke. Myeloperoxidase (MPO) is a highly potent oxidative enzyme that is capable of inducing both oxidative and nitrosative stress in vivo. To determine if and the extent to which MPO-generated oxidants contribute to brain I/R injury, we treated mice subjected to middle cerebral artery occlusion (MCAO) with N-acetyl lysyltyrosylcysteine amide (KYC), a novel, specific and non-toxic inhibitor of MPO. Behavioral testing, ischemic damage, blood-brain-barrier disruption, apoptosis, neutrophils infiltration, microglia/macrophage activation, and MPO oxidation were analyzed within a 7-day period after MCAO. Our studies show that KYC treatment significantly reduces neurological severity scores, infarct size, IgG extravasation, neutrophil infiltration, loss of neurons, apoptosis, and microglia/macrophage activation in the brains of MCAO mice. Immunofluorescence studies show that KYC treatment reduces the formation of chlorotyrosine (ClTyr), a fingerprint biomarker of MPO oxidation, nitrotyrosine (NO2Tyr), and 4-hydroxynonenal (4HNE) in MCAO mice. All oxidative products colocalized with MPO in the infarcted brains, suggesting that MPO-generated oxidants are involved in forming the oxidative products. MPO-generated oxidants play detrimental roles in causing brain damage after stroke which is effectively reduced by KYC.

  20. Evaluation of role of brain SPECT in diagnosis of post stroke dementia

    International Nuclear Information System (INIS)

    Yousepour, G.; Alavi, M.

    2003-01-01

    Post stroke dementia is one of the most common complications of stroke that is preventable and relatively treatable too. The purpose of the study is comparison between the positive findings in the brain CT scan and brain perfusion SPECT. 15 patients who were complicated by dementia after cerebrovascular accident and also 5 patients as a control group enrolled in this study. Brain CT scan and brain SPECT were performed during at most one week after stroke. Abnormal findings in both brain CT scan and SPECT were seen in 46% of patients. Brain CT scan disclosed more abnormal findings compared to brain SPECT (33.3%). While brain SPECT findings were more information than brain CT scan (20%) this study is indicating that brain CT scan and the brain SPECT concomitantly for each other in better diagnosis of post stroke dementia. We did not find any specific diagnostic pattern in brain SPECT of patients suffering from post stroke dementia. The low quality of brain SPECT in spite of uniformity of gamma camera may be suggestive of low quality of Iran produced ECD kit that needs further evaluation

  1. Non invasive brain stimulation to enhance post-stroke recovery

    Directory of Open Access Journals (Sweden)

    Nathalie Kubis

    2016-07-01

    Full Text Available Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first days, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS and prognosis has been established according to the presence of motor evoked potentials (MEP at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS or transcranial direct current stimulation (tDCS have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (> 3 Hz rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤ 1 Hz, aiming to reduce excitability of the contralateral homonymous cortex, or

  2. Visualization of venous vessels in cerebral arteriograms in various types of brain strokes

    International Nuclear Information System (INIS)

    Kruszewska, J.; Trzebicki, J.; Binkiewicz, M.

    1982-01-01

    1468 internal carotin angiograms including 945 performed in patients with strokes and 523 with brain tumours were analysed. Three phases were evaluated: arterial, middle and venous, directing attention to brain venous system filling in the arterial phase. Carotid arteriography carried out within 14 days after stroke onset visualizes early filling of the veins and this sign may be helpful in localizing the site brain damage. (author)

  3. Clinical evaluation of patients with migraine induced stroke in mashhad, iran.

    Science.gov (United States)

    Ghandehari, Kavian; Sharifi, Atena; Nikbin, Zeynab; Fadaei, Sahar; Meybodi, Meysam Aghaei; Moshfegh, Mehdi; Hosseini, Mohammad Reza; Sarabi, Mohammad Reza Gerami; Maarufi, Parham

    2010-01-01

    Migraine Induced Stroke (MIS) is an important cause of brain infarction in the young people. Consecutive patients with MIS admitted in Ghaem hospital, Mashhad during 2006-2010 enrolled a prospective clinical study. All of the patients suspected to MIS had brain MRI with a 0.5 Tesla generation, Philips NT Intra, Netherland. All of the MIS patients underwent a standard battery of diagnostic investigations for detecting etiology of stroke. Disability of MIS patients was detected based on the modified Rankin scale at 90 days post stroke. 32 MIS patients (18 females, 14 males) with mean age 37.2 ± 3.8 years ranged 15-58 years were evaluated. Hypodense area of infarction corresponding to clinical manifestations was detected in MRI in 32% of our MIS patients. The mean disability score in our MIS patients was 1.09 ± 0.32, which is significantly lower than other stroke patients (z = 2.55, P = 0.007) MIS is an important cause of stroke in Persian young adults which have good prognosis.

  4. Functional Brain Correlates of Upper Limb Spasticity and Its Mitigation following Rehabilitation in Chronic Stroke Survivors

    Directory of Open Access Journals (Sweden)

    Svetlana Pundik

    2014-01-01

    Full Text Available Background. Arm spasticity is a challenge in the care of chronic stroke survivors with motor deficits. In order to advance spasticity treatments, a better understanding of the mechanism of spasticity-related neuroplasticity is needed. Objective. To investigate brain function correlates of spasticity in chronic stroke and to identify specific regional functional brain changes related to rehabilitation-induced mitigation of spasticity. Methods. 23 stroke survivors (>6 months were treated with an arm motor learning and spasticity therapy (5 d/wk for 12 weeks. Outcome measures included Modified Ashworth scale, sensory tests, and functional magnetic resonance imaging (fMRI for wrist and hand movement. Results. First, at baseline, greater spasticity correlated with poorer motor function (P=0.001 and greater sensory deficits (P=0.003. Second, rehabilitation produced improvement in upper limb spasticity and motor function (P<0.0001. Third, at baseline, greater spasticity correlated with higher fMRI activation in the ipsilesional thalamus (rho=0.49, P=0.03. Fourth, following rehabilitation, greater mitigation of spasticity correlated with enhanced fMRI activation in the contralesional primary motor (r=-0.755, P=0.003, premotor (r=−0.565, P=0.04, primary sensory (r=−0.614, P=0.03, and associative sensory (r=−0.597, P=0.03 regions while controlling for changes in motor function. Conclusions. Contralesional motor regions may contribute to restoring control of muscle tone in chronic stroke.

  5. Stroke Treatments

    Science.gov (United States)

    ... Stroke Association.org Professionals for Stroke Association.org Shop for Stroke Association.org Support for Stroke Association. ... works by dissolving the clot and improving blood flow to the part of the brain being deprived ...

  6. Spontaneous ischaemic stroke lesions in a dog brain

    DEFF Research Database (Denmark)

    Thomsen, Barbara Blicher; Gredal, Hanne; Nielsen, Martin Wirenfeldt

    2017-01-01

    Background Dogs develop spontaneous ischaemic stroke with a clinical picture closely resembling human ischaemic stroke patients. Animal stroke models have been developed, but it has proved difficult to translate results obtained from such models into successful therapeutic strategies in human...... stroke patients. In order to face this apparent translational gap within stroke research, dogs with ischaemic stroke constitute an opportunity to study the neuropathology of ischaemic stroke in an animal species. Case presentation A 7 years and 8 months old female neutered Rottweiler dog suffered....../macrophages and astrocytes. Conclusions The neuropathological changes reported in the present study were similar to findings in human patients with ischaemic stroke. The dog with spontaneous ischaemic stroke is of interest as a complementary spontaneous animal model for further neuropathological studies....

  7. Post-stroke acquired amusia: A comparison between right- and left-brain hemispheric damages.

    Science.gov (United States)

    Jafari, Zahra; Esmaili, Mahdiye; Delbari, Ahmad; Mehrpour, Masoud; Mohajerani, Majid H

    2017-01-01

    Although extensive research has been published about the emotional consequences of stroke, most studies have focused on emotional words, speech prosody, voices, or facial expressions. The emotional processing of musical excerpts following stroke has been relatively unexplored. The present study was conducted to investigate the effects of chronic stroke on the recognition of basic emotions in music. Seventy persons, including 25 normal controls (NC), 25 persons with right brain damage (RBD) from stroke, and 20 persons with left brain damage (LBD) from stroke between the ages of 31-71 years were studied. The Musical Emotional Bursts (MEB) test, which consists of a set of short musical pieces expressing basic emotional states (happiness, sadness, and fear) and neutrality, was used to test musical emotional perception. Both stroke groups were significantly poorer than normal controls for the MEB total score and its subtests (p right hemisphere dominance in processing negative emotions.

  8. A prospective study of brain natriuretic peptide levels in three subgroups: Stroke with hypertension, stroke without hypertension, and hypertension alone

    Directory of Open Access Journals (Sweden)

    Cakir Zeynep

    2010-01-01

    Full Text Available Aim: To study brain natriuretic peptide (BNP levels in three subgroups: patients having stroke with hypertension (HT, those having stroke without HT, and those with HT alone. We also tried to identify whether BNP levels predict the length of stay in hospital and mortality. Materials and Methods: The groups were formed by patients who had been admitted to the emergency department in the first 4-12 h after the onset of symptoms. There were 30 stroke patients with a history of HT (group I, 30 stroke patients without a history of HT (group II, and 20 HT patients without stroke (group III. Patients with congestive heart failure, chronic cor pulmonale, severe valvular heart disease, chronic renal failure, liver insufficiency, diabetes mellitus, atrial fibrillation, and those with a history of stroke were excluded from the study since these diseases can affect the plasma BNP levels. Results: The demographic characteristics, except the age distribution, were similar among the groups. The mean BNP levels in the three groups were 168.8 ± 223.9 pg/ml, 85.0 ± 75.1 pg/ml, and 84.8 ± 178.3 pg/ml, respectively. The differences between the groups were statistically significant. Conclusion: The mean BNP levels were affected by HT and/or stroke. The simultaneous presence of HT and stroke results in a more significant increase BNP than the presence of either stroke or HT alone. When diseases that can affect the plasma BNP levels are excluded, the BNP levels in stroke patients without a history of HT are similar to the levels seen in patients with only HT.

  9. The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation

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    Sena Minjoli

    2017-01-01

    Full Text Available Transcranial magnetic stimulation (TMS and transcranial direct current stimulation (TDCS are two types of non-invasive transcranial brain stimulation (TBS. They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large cerebral lesions, which are commonly accompanied by a secondary enlargement of the ventricles and atrophy. These structural alterations substantially change the conductivity distribution inside the head, which may have potentially important consequences for both brain stimulation methods. We therefore aimed to characterize the impact of these changes on the spatial distribution of the electric field generated by both TBS methods. In addition to confirming the safety of TBS in the presence of large stroke-related structural changes, our aim was to clarify whether targeted stimulation is still possible. Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative to the lesion were tested. For TDCS, the finite-element method was used to simulate a standard approach with two electrode pads, and the position of one electrode was systematically varied. For both TMS and TDCS, the lesion caused electric field “hot spots” in the cortex. However, these maxima were not substantially stronger than those seen in a healthy control. The electric field pattern induced by TMS was not substantially changed by the lesions. However, the average field strength generated by TDCS was substantially decreased. This effect occurred for both head models and even when both electrodes were distant to the lesion, caused by increased current shunting through the lesion and enlarged ventricles. Judging from the similar peak field strengths compared

  10. The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation.

    Science.gov (United States)

    Minjoli, Sena; Saturnino, Guilherme B; Blicher, Jakob Udby; Stagg, Charlotte J; Siebner, Hartwig R; Antunes, André; Thielscher, Axel

    2017-01-01

    Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) are two types of non-invasive transcranial brain stimulation (TBS). They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large cerebral lesions, which are commonly accompanied by a secondary enlargement of the ventricles and atrophy. These structural alterations substantially change the conductivity distribution inside the head, which may have potentially important consequences for both brain stimulation methods. We therefore aimed to characterize the impact of these changes on the spatial distribution of the electric field generated by both TBS methods. In addition to confirming the safety of TBS in the presence of large stroke-related structural changes, our aim was to clarify whether targeted stimulation is still possible. Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative to the lesion were tested. For TDCS, the finite-element method was used to simulate a standard approach with two electrode pads, and the position of one electrode was systematically varied. For both TMS and TDCS, the lesion caused electric field "hot spots" in the cortex. However, these maxima were not substantially stronger than those seen in a healthy control. The electric field pattern induced by TMS was not substantially changed by the lesions. However, the average field strength generated by TDCS was substantially decreased. This effect occurred for both head models and even when both electrodes were distant to the lesion, caused by increased current shunting through the lesion and enlarged ventricles. Judging from the similar peak field strengths compared to the healthy

  11. Exogenous stem cells pioneer a biobridge to the advantage of host brain cells following stroke: New insights for clinical applications

    Directory of Open Access Journals (Sweden)

    Marci G Crowley

    2017-01-01

    Full Text Available Stroke continues to maintain its status as one of the top causes of mortality within the United States. Currently, the only Food and Drug Administration (FDA-approved drug in place for stroke patients, tissue plasminogen activator (tPA, has a rigid therapeutic window, closing at approximately 4.5 h after stroke onset. Due to this short time frame and other restrictions, such as any condition that increases a patient's risk for hemorrhaging, it has been predicted that <5% of ischemic stroke patients benefit from tPA. Given that rehabilitation therapy remains the only other option for stroke victims, there is a clear unmet clinical need for treatment available for the remaining 95%. While still considered an experimental treatment, the utilization of stem cell therapies for stroke holds consistent promise. Copious preclinical studies report the capacity for transplanted stem cells to rescue the brain parenchyma surrounding the stroke-induced infarct core. At present, the exact mechanisms in which stem cells contribute a robust therapeutic benefit remains unclear. Following stem cell administration, researchers have observed cell replacement, an increase in growth factors, and a reduction in inflammation. With a deeper understanding of the precise mechanism of stem cells, these therapies can be optimized in the clinic to afford the greatest therapeutic benefit. Recent studies have depicted a unique method of endogenous stem cell activation as a result of stem cell therapy. In both traumatic brain injury and stroke models, transplanted mesenchymal stromal cells (MSCs facilitated a pathway between the neurogenic niches of the brain and the damaged area through extracellular matrix remodeling. The biobridge pioneered by the MSCs was utilized by the endogenous stem cells, and these cells were able to travel to the damaged areas distal to the neurogenic niches, a feat unachievable without prior remodeling. These studies broaden our understanding of stem

  12. Relationships between brain and body temperature, clinical and imaging outcomes after ischemic stroke

    Science.gov (United States)

    Karaszewski, Bartosz; Carpenter, Trevor K; Thomas, Ralph G R; Armitage, Paul A; Lymer, Georgina Katherine S; Marshall, Ian; Dennis, Martin S; Wardlaw, Joanna M

    2013-01-01

    Pyrexia soon after stroke is associated with severe stroke and poor functional outcome. Few studies have assessed brain temperature after stroke in patients, so little is known of its associations with body temperature, stroke severity, or outcome. We measured temperatures in ischemic and normal-appearing brain using 1H-magnetic resonance spectroscopy and its correlations with body (tympanic) temperature measured four-hourly, infarct growth by 5 days, early neurologic (National Institute of Health Stroke Scale, NIHSS) and late functional outcome (death or dependency). Among 40 patients (mean age 73 years, median NIHSS 7, imaged at median 17 hours), temperature in ischemic brain was higher than in normal-appearing brain on admission (38.6°C-core, 37.9°C-contralateral hemisphere, P=0.03) but both were equally elevated by 5 days; both were higher than tympanic temperature. Ischemic lesion temperature was not associated with NIHSS or 3-month functional outcome; in contrast, higher contralateral normal-appearing brain temperature was associated with worse NIHSS, infarct expansion and poor functional outcome, similar to associations for tympanic temperature. We conclude that brain temperature is higher than body temperature; that elevated temperature in ischemic brain reflects a local tissue response to ischemia, whereas pyrexia reflects the systemic response to stroke, occurs later, and is associated with adverse outcomes. PMID:23571281

  13. Risk and mortality of traumatic brain injury in stroke patients: two nationwide cohort studies.

    Science.gov (United States)

    Chou, Yi-Chun; Yeh, Chun-Chieh; Hu, Chaur-Jong; Meng, Nai-Hsin; Chiu, Wen-Ta; Chou, Wan-Hsin; Chen, Ta-Liang; Liao, Chien-Chang

    2014-01-01

    Patients with stroke had higher incidence of falls and hip fractures. However, the risk of traumatic brain injury (TBI) and post-TBI mortality in patients with stroke was not well defined. Our study is to investigate the risk of TBI and post-TBI mortality in patients with stroke. Using reimbursement claims from Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study of 7622 patients with stroke and 30 488 participants without stroke aged 20 years and older as reference group. Data were collected on newly developed TBI after stroke with 5 to 8 years' follow-up during 2000 to 2008. Another nested cohort study including 7034 hospitalized patients with TBI was also conducted to analyze the contribution of stroke to post-TBI in-hospital mortality. Compared with the nonstroke cohort, the adjusted hazard ratio of TBI risk among patients with stroke was 2.80 (95% confidence interval = 2.58-3.04) during the follow-up period. Patients with stroke had higher mortality after TBI than those without stroke (10.2% vs 3.2%, P stroke (RR = 1.60), hemorrhagic stroke (RR = 1.68), high medical expenditure for stroke (RR = 1.80), epilepsy (RR = 1.79), neurosurgery (RR = 1.94), and hip fracture (RR = 2.11) were all associated with significantly higher post-TBI mortality among patients with stroke. Patients with stroke have an increased risk of TBI and in-hospital mortality after TBI. Various characteristics of stroke severity were all associated with higher post-TBI mortality. Special attention is needed to prevent TBI among these populations.

  14. Acute Psychosis Associated with Subcortical Stroke: Comparison between Basal Ganglia and Mid-Brain Lesions

    Directory of Open Access Journals (Sweden)

    Aaron McMurtray

    2014-01-01

    Full Text Available Acute onset of psychosis in an older or elderly individual without history of previous psychiatric disorders should prompt a thorough workup for neurologic causes of psychiatric symptoms. This report compares and contrasts clinical features of new onset of psychotic symptoms between two patients, one with an acute basal ganglia hemorrhagic stroke and another with an acute mid-brain ischemic stroke. Delusions and hallucinations due to basal ganglia lesions are theorized to develop as a result of frontal lobe dysfunction causing impairment of reality checking pathways in the brain, while visual hallucinations due to mid-brain lesions are theorized to develop due to dysregulation of inhibitory control of the ponto-geniculate-occipital system. Psychotic symptoms occurring due to stroke demonstrate varied clinical characteristics that depend on the location of the stroke within the brain. Treatment with antipsychotic medications may provide symptomatic relief.

  15. Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation

    DEFF Research Database (Denmark)

    Undén, Johan; Strandberg, Karin; Malm, Jan

    2009-01-01

    INTRODUCTION: A simple and accurate method of differentiating ischemic stroke and intracerebral hemorrhage (ICH) is potentially useful to facilitate acute therapeutic management. Blood measurements of biomarkers of brain damage and activation of the coagulation system may potentially serve as nov...

  16. Reduced blood brain barrier breakdown in P-selectin deficient mice following transient ischemic stroke: a future therapeutic target for treatment of stroke

    Directory of Open Access Journals (Sweden)

    Petterson Jodie

    2010-02-01

    Full Text Available Abstract Background The link between early blood- brain barrier (BBB breakdown and endothelial cell activation in acute stroke remain poorly defined. We hypothesized that P-selectin, a mediator of the early phase of leukocyte recruitment in acute ischemia is also a major contributor to early BBB dysfunction following stroke. This was investigated by examining the relationship between BBB alterations following transient ischemic stroke and expression of cellular adhesion molecule P-selectin using a combination of magnetic resonance molecular imaging (MRMI, intravital microscopy and immunohistochemistry. MRMI was performed using the contrast, gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA conjugated to Sialyl Lewis X (Slex where the latter is known to bind to activated endothelium via E- or P selectins. Middle cerebral artery occlusion was induced in male C57/BL 6 wild-type (WT mice and P-selectin-knockout (KO mice. At 24 hours following middle cerebral artery occlusion, T1 maps were acquired prior to and following contrast injection. In addition to measuring P- and E-selectin expression in brain homogenates, alterations in BBB function were determined immunohistochemically by assessing the extravasation of immunoglobulin G (IgG or staining for polymorphonuclear (PMN leukocytes. In vivo assessment of BBB dysfunction was also investigated optically using intravital microscopy of the pial circulation following the injection of Fluorescein Isothiocyanate (FITC-dextran (MW 2000 kDa. Results MRI confirmed similar infarct sizes and T1 values at 24 hours following stroke for both WT and KO animals. However, the blood to brain transfer constant for Gd DTPA (Kgd demonstrated greater tissue extravasation of Gd DTPA in WT animals than KO mice (P 1 stroke -Δ T1 contralateral control cortex, decreased significantly in the Gd-DTPA(sLeX group compared to Gd-DTPA, indicative of sLeX mediated accumulation of the targeted contrast agent. Regarding BBB

  17. Spontaneous ischaemic stroke lesions in a dog brain: neuropathological characterisation and comparison to human ischaemic stroke

    DEFF Research Database (Denmark)

    Thomsen, Barbara Blicher; Gredal, Hanne; Wirenfeldt, Martin

    2017-01-01

    Background Dogs develop spontaneous ischaemic stroke with a clinical picture closely resembling human ischaemic stroke patients. Animal stroke models have been developed, but it has proved difficult to translate results obtained from such models into successful therapeutic strategies in human str...

  18. Correlation between brain injury and dysphagia in adult patients with stroke

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    Nunes, Maria Cristina de Alencar

    2012-01-01

    Full Text Available Introduction: In the literature, the incidence of oropharyngeal dysphagia in patients with cerebrovascular accident (AVE ranges 20-90%. Some studies correlate the location of a stroke with dysphagia, while others do not. Objective: To correlate brain injury with dysphagia in patients with stroke in relation to the type and location of stroke. Method: A prospective study conducted at the Hospital de Clinicas with 30 stroke patients: 18 women and 12 men. All patients underwent clinical evaluation and swallowing nasolaryngofibroscopy (FEES®, and were divided based on the location of the injury: cerebral cortex, cerebellar cortex, subcortical areas, and type: hemorrhagic or transient ischemic. Results: Of the 30 patients, 18 had ischemic stroke, 10 had hemorrhagic stroke, and 2 had transient stroke. Regarding the location, 10 lesions were in the cerebral cortex, 3 were in the cerebral and cerebellar cortices, 3 were in the cerebral cortex and subcortical areas, and 3 were in the cerebral and cerebellar cortices and subcortical areas. Cerebral cortex and subcortical area ischemic strokes predominated in the clinical evaluation of dysphagia. In FEES®, decreased laryngeal sensitivity persisted following cerebral cortex and ischemic strokes. Waste in the pharyngeal recesses associated with epiglottic valleculae predominated in the piriform cortex in all lesion areas and in ischemic stroke. A patient with damage to the cerebral and cerebellar cortices from an ischemic stroke exhibited laryngeal penetration and tracheal aspiration of liquid and honey. Conclusion: Dysphagia was prevalent when a lesion was located in the cerebral cortex and was of the ischemic type.

  19. Language-specific dysgraphia in Korean patients with right brain stroke: influence of unilateral spatial neglect.

    Science.gov (United States)

    Jang, Dae-Hyun; Kim, Min-Wook; Park, Kyoung Ha; Lee, Jae Woo

    2015-03-01

    The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

  20. Brain magnetic resonance imaging findings in cryptogenic stroke patients under 60 years with patent foramen ovale

    Energy Technology Data Exchange (ETDEWEB)

    Boutet, Claire, E-mail: claire.boutet@chu-st-etienne.fr [Department of Radiology, University Hospital of Saint-Etienne (France); Thrombosis Research Group EA 3065, Jean Monnet University, Saint-Etienne (France); Rouffiange-Leclair, Laure, E-mail: laurerouffiange@hotmail.com [Department of Radiology, University Hospital of Saint-Etienne (France); Garnier, Pierre, E-mail: pierre.garnier@chu-st-etienne.fr [Thrombosis Research Group EA 3065, Jean Monnet University, Saint-Etienne (France); Department of Neurology, University Hospital of Saint-Etienne (France); Quenet, Sara, E-mail: sara.quenet@chu-st-etienne.fr [Thrombosis Research Group EA 3065, Jean Monnet University, Saint-Etienne (France); Delsart, Daphné, E-mail: daphne.delsart@hotmail.fr [Thrombosis Research Group EA 3065, Jean Monnet University, Saint-Etienne (France); Department of Therapeutic Medicine, CHU Saint-Etienne, Hôpital Nord, Saint-Etienne (France); Inserm, CIE3, F-42055 Saint-Etienne (France); Varvat, Jérôme, E-mail: jvarvat@9online.fr [Thrombosis Research Group EA 3065, Jean Monnet University, Saint-Etienne (France); Department of Neurology, University Hospital of Saint-Etienne (France); Epinat, Magali, E-mail: magali.epinat@chu-st-etienne.fr [Thrombosis Research Group EA 3065, Jean Monnet University, Saint-Etienne (France); Department of Neurology, University Hospital of Saint-Etienne (France); Schneider, Fabien, E-mail: fabien.schneider@univ-st-etienne.fr [Department of Radiology, University Hospital of Saint-Etienne (France); Thrombosis Research Group EA 3065, Jean Monnet University, Saint-Etienne (France); Antoine, Jean-Christophe, E-mail: j.christophe.antoine@chu-st-etienne.fr [Department of Neurology, University Hospital of Saint-Etienne (France); Lyon Neuroscience Research Center, INSERM U1028 – CNRS UMR5292 (France); EA 4338, Jean Monnet University, Saint-Etienne (France); and others

    2014-05-15

    Purpose: To compare magnetic resonance imaging (MRI) brain feature in cryptogenic stroke patients with patent foramen ovale (PFO), cryptogenic stroke patients without PFO and patients with cardioembolic stroke. Materials and methods: The ethics committee required neither institutional review board approval nor informed patient consent for retrospective analyses of the patients’ medical records and imaging data. The patients’ medical files were retrospectively reviewed in accordance with human subject research protocols. Ninety-two patients under 60 years of age were included: 15 with cardioembolic stroke, 32 with cryptogenic stroke with PFO and 45 with cryptogenic stroke without PFO. Diffusion-weighted imaging of brain MRI was performed by a radiologist blinded to clinical data. Univariate, Fischer's exact test for qualitative data and non-parametric Wilcoxon test for quantitative data were used. Results: There was no statistically significant difference found between MRI features of patients with PFO and those with cardioembolic stroke (p < .05). Patients without PFO present more corticosubcortical single lesions (p < .05) than patients with PFO. Patients with PFO have more often subcortical single lesions larger than 15 mm, involvement of posterior cerebral arterial territory and intracranial occlusion (p < .05) than patients with cryptogenic stroke without PFO. Conclusion: Our study suggests a cardioembolic mechanism in ischemic stroke with PFO.

  1. Ipsilateral motor pathways after stroke: implications for noninvasive brain stimulation

    Directory of Open Access Journals (Sweden)

    Lynley V Bradnam

    2013-05-01

    Full Text Available In humans the two cerebral hemispheres have essential roles in controlling the upper limb. The purpose of this article is to draw attention to the potential importance of ipsilateral descending pathways for functional recovery after stroke, and the use of noninvasive brain stimulation (NBS protocols of the contralesional primary motor cortex (M1. Conventionally NBS is used to suppress contralesional M1, and to attenuate transcallosal inhibition onto the ipsilesional M1. There has been little consideration of the fact that contralesional M1 suppression may also reduce excitability of ipsilateral descending pathways that may be important for paretic upper limb control for some patients. One such ipsilateral pathway is the cortico-reticulo-propriospinal pathway (CRPP. In this review we outline a neurophysiological model to explain how contralesional M1 may gain control of the paretic arm via the CRPP. We conclude that the relative importance of the CRPP for motor control in individual patients must be considered before using NBS to suppress contralesional M1. Neurophysiological, neuroimaging and clinical assessments can assist this decision making and facilitate the translation of NBS into the clinical setting.

  2. Enhancing Physical Activity and Brain Reorganization after Stroke

    Directory of Open Access Journals (Sweden)

    Janet H. Carr

    2011-01-01

    Full Text Available It is becoming increasingly clear that, if reorganization of brain function is to be optimal after stroke, there needs to be a reorganisation of the methods used in physical rehabilitation and the time spent in specific task practice, strength and endurance training, and aerobic exercise. Frequency and intensity of rehabilitation need to be increased so that patients can gain the energy levels and vigour necessary for participation in physical activity both during rehabilitation and after discharge. It is evident that many patients are discharged from inpatient rehabilitation severely deconditioned, meaning that their energy levels are too low for active participation in daily life. Physicians, therapists, and nursing staff responsible for rehabilitation practice should address this issue not only during inpatient rehabilitation but also after discharge by promoting and supporting community-based exercise opportunities. During inpatient rehabilitation, group sessions should be frequent and need to include specific aerobic training. Physiotherapy must take advantage of the training aids available, including exercise equipment such as treadmills, and of new developments in computerised feedback systems, robotics, and electromechanical trainers. For illustrative purposes, this paper focuses on the role of physiotherapists, but the necessary changes in practice and in attitude will require cooperation from many others.

  3. Therapeutic Hypothermia in Stroke and Traumatic Brain Injury

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    Alireza eFaridar

    2011-12-01

    Full Text Available Therapeutic hypothermia (TH is considered to improve survival with favorable neurological outcome in the case of global cerebral ischemia after cardiac arrest and perinatal asphyxia. The efficacy of hypothermia in acute ischemic stroke (AIS and traumatic brain injury (TBI, however, is not well studied. Induction of TH typically requires a multimodal approach, including the use of both pharmacological agents and physical techniques. To date, clinical outcomes for patients with either AIS or TBI who received TH have yielded conflicting results; thus, no adequate therapeutic consensus has been reached. Nevertheless, it seems that by determining optimal TH parameters and also appropriate applications, cooling therapy still has the potential to become a valuable neuroprotective intervention.Among the various methods for hypothermia induction, intravascular cooling (IVC may have the most promise in the awake patient in terms of clinical outcomes. Currently, the IVC method has the capability of more rapid target temperature attainment and more precise control of temperature. However, this technique requires expertise in endovascular surgery that can preclude its application in the field and/or in most emergency settings. It is very likely that combining neuroprotective strategies will yield better outcomes than utilizing a single approach.

  4. Deep into the Brain: Artificial Intelligence in Stroke Imaging.

    Science.gov (United States)

    Lee, Eun-Jae; Kim, Yong-Hwan; Kim, Namkug; Kang, Dong-Wha

    2017-09-01

    Artificial intelligence (AI), a computer system aiming to mimic human intelligence, is gaining increasing interest and is being incorporated into many fields, including medicine. Stroke medicine is one such area of application of AI, for improving the accuracy of diagnosis and the quality of patient care. For stroke management, adequate analysis of stroke imaging is crucial. Recently, AI techniques have been applied to decipher the data from stroke imaging and have demonstrated some promising results. In the very near future, such AI techniques may play a pivotal role in determining the therapeutic methods and predicting the prognosis for stroke patients in an individualized manner. In this review, we offer a glimpse at the use of AI in stroke imaging, specifically focusing on its technical principles, clinical application, and future perspectives.

  5. Deficiency of vasodilator-stimulated phosphoprotein (VASP increases blood-brain-barrier damage and edema formation after ischemic stroke in mice.

    Directory of Open Access Journals (Sweden)

    Peter Kraft

    2010-12-01

    Full Text Available Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification.Focal cerebral ischemia was induced in Vasp(-/- mice and wild-type (WT littermates by transient middle cerebral artery occlusion (tMCAO. Evan's Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p0.05 towards worse neurological outcomes.Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage.

  6. Small brain lesions and incident stroke and mortality: A cohort study

    Science.gov (United States)

    Windham, B Gwen; Deere, Bradley; Griswold, Michael E.; Wang, Wanmei; Bezerra, Daniel C; Shibata, Dean; Butler, Kenneth; Knopman, David; Gottesman, Rebecca F; Heiss, Gerardo; Mosley, Thomas H

    2015-01-01

    Background Although cerebral lesions ≥3mm on imaging are associated with incident stroke, lesions stroke risks associated with subclinical brain lesions by size (stroke; average 14.5 years follow-up. Measurements MRI lesions: none (n=1611), stroke (n=157), overall mortality (n=576), stroke mortality (n=50). Hazard Ratios (HR) estimated with proportional hazards models. Results Compared to no lesions, stroke risk was tripled with lesions Stroke risk doubled with WMH ≥3 (HR=2.14, 95% CI:1.45-3.16). Stroke mortality risk tripled with lesions stroke events (n=147), especially hemorrhagic (n=15); limited numbers of participants with only lesions ≤3mm (n=50) or with both lesions ≤3mm and 3–20mm (n=35). Conclusions Very small cerebrovascular lesions may be associated with increased risks of stroke and mortality; having both < 3 mm and ≥3 mm lesions may represent a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates. PMID:26148278

  7. Clinical course of brain stroke in the persons exposed to ionizing radiation under the production conditions

    International Nuclear Information System (INIS)

    Bouchmanov, A.

    2000-01-01

    The purpose was to study the risk factors and clinical course of brain strokes in professionally exposed workers being employed in plutonium production in comparison with a control group. The method and materials of study -clinical supervision and clinical database creation on 162 cases of brain stroke (128 males and 34 females) developed among professionally exposed workers. Age of patient varied from 21 to 68 years (in average -51.6 y.). The control group consisted of patients with the same diagnosis, worked on the same enterprise, but non-exposed to radiation. Data on the totally accumulated dose of external gamma radiation were received on the base of the individual dosimeters (from 0.1 cSv to 52 cSv, in average about 13 cSv); the plutonium-239 body content was estimated accordingly to the level of urine radionuclide excretion (from 0.4 kBq to 1.6 kBq, in average about 0.33 kBq). Muscle's hypertinsion and pathological great-toe reflexes in paretic legs and hands, hemianopsia, impressive and ataxic aphasia prevailed in the patients with ischemic brain strokes in system of internal carotid artery, exposed to radiation. The changes of muscle's tension, ataxia and nystagmus were marked more often in the professionals with ischemic brain strokes in system of vertebrobasilar artery. The illness proceeded more easy and with smaller frequency of frustration of consciousness and algesthesia, irrespective of a type ischemic brain strokes in the people exposed to ionizing radiation, than in patients of non-irradiated group. It was found that the arterial hypertension appeared to be the main risk factor for the brain stroke in both groups of patients (in 81.48% and 91.15% of cases). There was no marked differences in significance of risk factors and in main clinical parameters of various types of ischemic brain strokes among the patients professionally exposed to radiation in comparison with a control group. (author)

  8. Thrombolysis in Stroke within 30 Minutes: Results of the Acute Brain Care Intervention Study

    NARCIS (Netherlands)

    Zinkstok, Sanne M.; Beenen, Ludo F.; Luitse, Jan S.; Majoie, Charles B.; Nederkoorn, Paul J.; Roos, Yvo B.

    2016-01-01

    Time is brain: benefits of intravenous thrombolysis (IVT) in ischemic stroke last for 4.5 hours but rapidly decrease as time progresses following symptom onset. The goal of the Acute Brain Care (ABC) intervention study was to reduce the door-to-needle time (DNT) to ≤30 minutes by optimizing

  9. Locally induced hypothermia for treatment of acute ischaemic stroke: A physical feasibility study

    International Nuclear Information System (INIS)

    Slotboom, J.; Kiefer, C.; Brekenfeld, C.; Ozdoba, C.; Remonda, L.; Nedeltchev, K.; Schroth, G.; Arnold, M.; Mattle, H.

    2004-01-01

    During the treatment of stroke by local intra-arterial thrombolysis (LIT) it is frequently possible to pass the blood clot with a micro-catheter, allowing perfusion of brain tissue distally to the occlusion. This possibility allows for new early treatments of ischaemic brain tissue, even before the blood clot has been removed. One potential new approach to preserve brain tissue at risk may be locally induced endovascular hypothermia. Physical parameters such as the required micro-catheter input pressure, output velocity and flow rates, and a heat exchange model, applicable in the case of a micro-catheter placed within a guiding catheter, are presented. Also, a simple cerebral temperature model is derived that models the temperature response of the brain to the perfusion with coolant fluids. Based on this model, an expression has been derived for the time needed to reach a certain cerebral target temperature. Experimental in vitro measurements are presented that confirm the usability of standard commercially available micro-catheters to induce local hypothermia of the brain. If applied in vivo, the model predicts a local cooling rate of ischaemic brain tissue of 300 g of approximately 1 C in 1 min, which is up to a factor 30-times faster than the time-consuming systemic hypothermia via the skin. Systemic body temperature is only minimally affected by application of local hypothermia, thus avoiding many limitations and complications known in systemic hypothermia. (orig.)

  10. Locally induced hypothermia for treatment of acute ischaemic stroke: A physical feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Slotboom, J.; Kiefer, C.; Brekenfeld, C.; Ozdoba, C.; Remonda, L.; Nedeltchev, K.; Schroth, G. [Inselspital, Institute of Diagnostic and Interventional Neuroradiology, University of Bern, Berne (Switzerland); Arnold, M.; Mattle, H. [University of Bern, Department of Neurology, Berne (Switzerland)

    2004-11-01

    During the treatment of stroke by local intra-arterial thrombolysis (LIT) it is frequently possible to pass the blood clot with a micro-catheter, allowing perfusion of brain tissue distally to the occlusion. This possibility allows for new early treatments of ischaemic brain tissue, even before the blood clot has been removed. One potential new approach to preserve brain tissue at risk may be locally induced endovascular hypothermia. Physical parameters such as the required micro-catheter input pressure, output velocity and flow rates, and a heat exchange model, applicable in the case of a micro-catheter placed within a guiding catheter, are presented. Also, a simple cerebral temperature model is derived that models the temperature response of the brain to the perfusion with coolant fluids. Based on this model, an expression has been derived for the time needed to reach a certain cerebral target temperature. Experimental in vitro measurements are presented that confirm the usability of standard commercially available micro-catheters to induce local hypothermia of the brain. If applied in vivo, the model predicts a local cooling rate of ischaemic brain tissue of 300 g of approximately 1 C in 1 min, which is up to a factor 30-times faster than the time-consuming systemic hypothermia via the skin. Systemic body temperature is only minimally affected by application of local hypothermia, thus avoiding many limitations and complications known in systemic hypothermia. (orig.)

  11. Evaluation of Gene Therapy as an Intervention Strategy to Treat Brain Injury from Stroke

    Directory of Open Access Journals (Sweden)

    Amanda J Craig

    2016-05-01

    Full Text Available Stroke is a leading cause of death and disability, with a lack of treatments available to prevent cell death, regenerate damaged cells and pathways, or promote neurogenesis. The extended period of hours to weeks over which tissue damage continues to occur makes this disorder a candidate for gene therapy. This review highlights the development of gene therapy in the area of stroke, with the evolution of viral administration, in experimental stroke models, from pre-injury to clinically relevant timeframes of hours to days post-stroke. The putative therapeutic proteins being examined include anti-apoptotic, pro-survival, anti-inflammatory, and guidance proteins, targeting multiple pathways within the complex pathology, with promising results. The balance of findings from animal models suggests that gene therapy provides a viable translational platform for treatment of ischaemic brain injury arising from stroke.

  12. The effect of ultrasound on thromboembolic model of brain stroke in rat

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    Shabanzadeh A

    2007-08-01

    Full Text Available Background: Ultrasound (US has been used in neuroprotection after cerebral ischemia; however, its use is controversial. Application of US in combination with fibrinolytic agents may improve fibrinolytic effects. In this study the effects of US, alone or in combination with tissue plasminogen activator (tPA, on brain ischemic injury were examined and we studied whether US is protective in the brain injured by ischemia under normothermic conditions. Methods: We performed two studies. In the first study, rectal and brain temperatures were compared. In the second study, we studied whether US alone or in combination with tPA is neuroprotective in thromboembolic stroke. To induce focal cerebral ischemia, a clot was formed in a catheter. Once the clot had formed, the catheter was advanced 17 mm in the internal carotid artery until its tip was 1-2 mm away from the origin of the middle cerebral artery (MCA. The preformed clot in the catheter was then injected, and the catheter was removed. The wound was then closed and the infarction volume, edema and neurological deficits were measured after MCA occlusion. Results: The temperature in the brain was approximately 0.50 ºC lower than the rectal temperature. In the control, US+low tPA, low tPA, US+high tPA and, high tPA groups, the infarct volume (% was 34.56±4.16, 17.09±6.72, 21.25±7.8, 13.5±10.72 and 20.61±6.17 (mean ±SD at 48 h after MCA occlusion, respectively. The results indicate that US alone reduces the infarct volume by 30% compared to that of the control group (P<0.05. US improved neurological deficits and reduced brain edema significantly (p<0.05. Conclusions: This study indicate that US appears to have a protective effect, alone and in combination with tPA, in an embolic model of stroke.

  13. Robotic devices and brain-machine interfaces for hand rehabilitation post-stroke

    OpenAIRE

    McConnell, Alistair C; Moioli, Renan C; Brasil, Fabricio L; Vallejo, Marta; Corne, David W; Vargas, Patricia A; Stokes, Adam A

    2017-01-01

    OBJECTIVE: To review the state of the art of robotic-aided hand physiotherapy for post-stroke rehabilitation, including the use of brain-machine interfaces. Each patient has a unique clinical history and, in response to personalized treatment needs, research into individualized and at-home treatment options has expanded rapidly in recent years. This has resulted in the development of many devices and design strategies for use in stroke rehabilitation.METHODS: The development progression of ro...

  14. Objective Ventricle Segmentation in Brain CT with Ischemic Stroke Based on Anatomical Knowledge

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    Xiaohua Qian

    2017-01-01

    Full Text Available Ventricle segmentation is a challenging technique for the development of detection system of ischemic stroke in computed tomography (CT, as ischemic stroke regions are adjacent to the brain ventricle with similar intensity. To address this problem, we developed an objective segmentation system of brain ventricle in CT. The intensity distribution of the ventricle was estimated based on clustering technique, connectivity, and domain knowledge, and the initial ventricle segmentation results were then obtained. To exclude the stroke regions from initial segmentation, a combined segmentation strategy was proposed, which is composed of three different schemes: (1 the largest three-dimensional (3D connected component was considered as the ventricular region; (2 the big stroke areas were removed by the image difference methods based on searching optimal threshold values; (3 the small stroke regions were excluded by the adaptive template algorithm. The proposed method was evaluated on 50 cases of patients with ischemic stroke. The mean Dice, sensitivity, specificity, and root mean squared error were 0.9447, 0.969, 0.998, and 0.219 mm, respectively. This system can offer a desirable performance. Therefore, the proposed system is expected to bring insights into clinic research and the development of detection system of ischemic stroke in CT.

  15. Non-invasive brain stimulation: an interventional tool for enhancing behavioral training after stroke

    Directory of Open Access Journals (Sweden)

    Maximilian Jonas Wessel

    2015-05-01

    Full Text Available Stroke is the leading cause of disability among adults. Motor deficit is the most common impairment after stroke. Especially, deficits in fine motor skills impair numerous activities of daily life. Re-acquisition of motor skills resulting in improved or more accurate motor performance is paramount to regain function, and is the basis of behavioral motor therapy after stroke. Within the past years, there has been a rapid technological and methodological development in neuroimaging leading to a significant progress in the understanding of the neural substrates that underlie motor skill acquisition and functional recovery in stroke patients. Based on this and the development of novel non-invasive brain stimulation techniques, new adjuvant interventional approaches that augment the response to behavioral training have been proposed. Transcranial direct current (tDCS, transcranial magnetic (TMS and paired associative (PAS stimulation are noninvasive brain stimulation techniques that can modulate cortical excitability, neuronal plasticity and interact with learning and memory in both healthy individuals and stroke patients. These techniques can enhance the effect of practice and facilitate the retention of tasks that mimic daily life activities. The purpose of the present review is to provide a comprehensive overview of neuroplastic phenomena in the motor system during learning of a motor skill, recovery after brain injury, and of interventional strategies to enhance the beneficial effects of customarily used neurorehabilitation after stroke.

  16. The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation

    DEFF Research Database (Denmark)

    Minjoli, Sena; Saturnino, Guilherme B.; Blicher, Jakob Udby

    2017-01-01

    Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) are two types of non-invasive transcranial brain stimulation (TBS). They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large...... cerebral lesions, which are commonly accompanied by a secondary enlargement of the ventricles and atrophy. These structural alterations substantially change the conductivity distribution inside the head, which may have potentially important consequences for both brain stimulation methods. We therefore....... Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative...

  17. Brain perfusion-CT in acute stroke patients

    International Nuclear Information System (INIS)

    Andreev, T.; Totsev, N.; Tzvetanov, P.

    2013-01-01

    Since 1979 when Grodfrey Hounsfield and Allan Corman introduced the computed tomography new generations of CT were developed that improved the special resolution and time of acquisition. The role of neuro-imaging in the evaluation of acute stroke has changed dramatically in the past decade. Previously, neuro-imaging was used in this set-ting to provide anatomic imaging that indicated the presence or absence of acute cerebral ischemia and excluded lesions that produce symptoms or signs mimicking those of stroke, such as hemorrhage and neoplasms. More recently, the introduction of thrombolysis has changed the goals of neuro-imaging from providing solely anatomic information to providing physiologic information that could help to determine which patients might benefit from therapy. In particular, significant emphasis has been placed on the delineation of the ischemic penumbra, also called tissue at risk. Modem CT survey, consisting of three indissociable elements; noncontrast CT (NCT) of course, perfusion-CT (PCT) and CT-angiography (CTA), fulfill all the requirements for hyperacute stroke imaging. CTA can define the occlusion site, depict arterial dissection, grade collateral blood flow, and characterize atherosclerotic disease, whereas PCT accurately defines the infarct core and the ischemic penumbra. CT offers a number of practical advantages over other cerebral perfusion imaging methods, including its wide availability. Using PCT and CTA to define new individualized strategies for acute reperfusion will allow more acute stroke patients to benefit from thrombolytic therapy. Key words: Stroke. Penumbra. Computed Tomography. Perfusion-CT. CT Angiography. Outcome

  18. Emerging Molecular Targets for Brain Repair after Stroke

    Directory of Open Access Journals (Sweden)

    Jerzy Krupinski

    2013-01-01

    Full Text Available The field of neuroprotection generated consistent preclinical findings of mechanisms of cell death but these failed to be translated into clinics. The approaches that combine the modulation of the inhibitory environment together with the promotion of intrinsic axonal outgrowth needs further work before combined therapeutic strategies will be transferable to clinic trials. It is likely that only when some answers have been found to these issues will our therapeutic efforts meet our expectations. Stroke is a clinically heterogeneous disease and combinatorial treatments require much greater work in pharmacological and toxicological testing. Advances in genetics and results of the Whole Human Genome Project (HGP provided new unknown information in relation to stroke. Genetic factors are not the only determinants of responses to some diseases. It was recognized early on that “epigenetic” factors were major players in the aetiology and progression of many diseases like stroke. The major players are microRNAs that represent the best-characterized subclass of noncoding RNAs. Epigenetic mechanisms convert environmental conditions and physiological stresses into long-term changes in gene expression and translation. Epigenetics in stroke are in their infancy but offer great promise for better understanding of stroke pathology and the potential viability of new strategies for its treatment.

  19. Automated Quantification of Stroke Damage on Brain Computed Tomography Scans: e-ASPECTS

    Directory of Open Access Journals (Sweden)

    James Hampton-Till

    2015-08-01

    Full Text Available Emergency radiological diagnosis of acute ischaemic stroke requires the accurate detection and appropriate interpretation of relevant imaging findings. Non-contrast computed tomography (CT provides fast and low-cost assessment of the early signs of ischaemia and is the most widely used diagnostic modality for acute stroke. The Alberta Stroke Program Early CT Score (ASPECTS is a quantitative and clinically validated method to measure the extent of ischaemic signs on brain CT scans. The CE-marked electronic-ASPECTS (e-ASPECTS software automates the ASPECTS score. Anglia Ruskin Clinical Trials Unit (ARCTU independently carried out a clinical investigation of the e-ASPECTS software, an automated scoring system which can be integrated into the diagnostic pathway of an acute ischaemic stroke patient, thereby assisting the physician with expert interpretation of the brain CT scan. Here we describe a literature review of the clinical importance of reliable assessment of early ischaemic signs on plain CT scans, and of technologies automating these processed scoring systems in ischaemic stroke on CT scans focusing on the e-ASPECTS software. To be suitable for critical appraisal in this evaluation, the published studies needed a sample size of a minimum of 10 cases. All randomised studies were screened and data deemed relevant to demonstration of performance of ASPECTS were appraised. The literature review focused on three domains: i interpretation of brain CT scans of stroke patients, ii the application of the ASPECTS score in ischaemic stroke, and iii automation of brain CT analysis. Finally, the appraised references are discussed in the context of the clinical impact of e-ASPECTS and the expected performance, which will be independently evaluated by a non-inferiority study conducted by the ARCTU.

  20. Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

    Science.gov (United States)

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-05-01

    Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

  1. Non-invasive brain stimulation: an interventional tool for enhancing behavioral training after stroke.

    Science.gov (United States)

    Wessel, Maximilian J; Zimerman, Máximo; Hummel, Friedhelm C

    2015-01-01

    Stroke is the leading cause of disability among adults. Motor deficit is the most common impairment after stroke. Especially, deficits in fine motor skills impair numerous activities of daily life. Re-acquisition of motor skills resulting in improved or more accurate motor performance is paramount to regain function, and is the basis of behavioral motor therapy after stroke. Within the past years, there has been a rapid technological and methodological development in neuroimaging leading to a significant progress in the understanding of the neural substrates that underlie motor skill acquisition and functional recovery in stroke patients. Based on this and the development of novel non-invasive brain stimulation (NIBS) techniques, new adjuvant interventional approaches that augment the response to behavioral training have been proposed. Transcranial direct current, transcranial magnetic, and paired associative (PAS) stimulation are NIBS techniques that can modulate cortical excitability, neuronal plasticity and interact with learning and memory in both healthy individuals and stroke patients. These techniques can enhance the effect of practice and facilitate the retention of tasks that mimic daily life activities. The purpose of the present review is to provide a comprehensive overview of neuroplastic phenomena in the motor system during learning of a motor skill, recovery after brain injury, and of interventional strategies to enhance the beneficial effects of customarily used neurorehabilitation after stroke.

  2. Modulation of brain plasticity in stroke: a novel model for neurorehabilitation.

    Science.gov (United States)

    Di Pino, Giovanni; Pellegrino, Giovanni; Assenza, Giovanni; Capone, Fioravante; Ferreri, Florinda; Formica, Domenico; Ranieri, Federico; Tombini, Mario; Ziemann, Ulf; Rothwell, John C; Di Lazzaro, Vincenzo

    2014-10-01

    Noninvasive brain stimulation (NIBS) techniques can be used to monitor and modulate the excitability of intracortical neuronal circuits. Long periods of cortical stimulation can produce lasting effects on brain function, paving the way for therapeutic applications of NIBS in chronic neurological disease. The potential of NIBS in stroke rehabilitation has been of particular interest, because stroke is the main cause of permanent disability in industrial nations, and treatment outcomes often fail to meet the expectations of patients. Despite promising reports from many clinical trials on NIBS for stroke recovery, the number of studies reporting a null effect remains a concern. One possible explanation is that the interhemispheric competition model--which posits that suppressing the excitability of the hemisphere not affected by stroke will enhance recovery by reducing interhemispheric inhibition of the stroke hemisphere, and forms the rationale for many studies--is oversimplified or even incorrect. Here, we critically review the proposed mechanisms of synaptic and functional reorganization after stroke, and suggest a bimodal balance-recovery model that links interhemispheric balancing and functional recovery to the structural reserve spared by the lesion. The proposed model could enable NIBS to be tailored to the needs of individual patients.

  3. Prolonged drug-induced hypothermia in experimental stroke

    DEFF Research Database (Denmark)

    Johansen, Flemming Fryd; Jørgensen, Henrik Stig; Reith, Jakob

    2007-01-01

    In experimental and human stroke, hypothermia is strongly related to a favorable outcome. Previous attempts to manipulate the core temperature in focal cerebral ischemia have been based on mechanical cooling. The purpose of the study is to establish a model for long-term drug-induced hypothermia...... in focal ischemia by pharmacological alteration of the central thermoregulatory set-point. We tested the hypothesis that the dopaminergic agonist Talipexole, which induces hypothermia, reduces infarct size. Body temperature was monitored by a radio-pill-implant. Rats had reversible occlusion of the middle...... that the core body temperature was reduced by 1.7 degrees C for 24 hours after MCAO in rats treated with Talipexole. This treatment induced a significant reduction of infarct volume at 7 days after focal ischemia by 47%. We suggest that the reduction in infarct volume is related to drug-induced hypothermia...

  4. Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

    Science.gov (United States)

    2011-01-01

    Background Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. Methods We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(-) group (n = 83) and, who admitted between April 2004 and March 2005, into the edaravone(+) group (n = 93). Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI)/iffusion-weighted magnetic resonance images (DWI)] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset), early chronic (3-6 month), late chronic (7-12 months) and old (≥13 months) stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. Results Stroke lesion size was significantly attenuated in the edaravone(+) group compared with the edaravone(-) group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. Conclusion Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute period, especially

  5. Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

    Directory of Open Access Journals (Sweden)

    Suzuki Akifumi

    2011-03-01

    Full Text Available Abstract Background Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. Methods We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(- group (n = 83 and, who admitted between April 2004 and March 2005, into the edaravone(+ group (n = 93. Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI/iffusion-weighted magnetic resonance images (DWI] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset, early chronic (3-6 month, late chronic (7-12 months and old (≥13 months stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. Results Stroke lesion size was significantly attenuated in the edaravone(+ group compared with the edaravone(- group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. Conclusion Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute

  6. Brain perfusion-CT in acute stroke patients

    International Nuclear Information System (INIS)

    Wintermark, M.

    2005-01-01

    The role of neuro-imaging in the evaluation of acute stroke has changed dramatically in the past decade. Previously, neuro-imaging was used in this setting to provide anatomic imaging that indicated the presence or absence of acute cerebral ischemia and excluded lesions that produce symptoms or signs mimicking those of stroke, such as hemorrhage and neoplasms. More recently, the introduction of thrombolysis has changed the goals of neuro-imaging from providing solely anatomic information to providing physiologic information that could help to determine which patients might benefit from therapy. In particular, significant emphasis has been placed on the delineation of the ischemic penumbra, also called tissue at risk. Modern CT survey, consisting of three indissociable elements: noncontrast CT (NCT) of course, perfusion-CT (PCT) and CT-angiography (CTA), fulfill all the requirements for hyper-acute stroke imaging. CTA can define the occlusion site, depict arterial dissection, grade collateral blood flow, and characterize atherosclerotic disease, whereas PCT accurately delineates the infarct core and the ischemic penumbra. CT offers a number of practical advantages over other cerebral perfusion imaging methods, including its wide availability. Using PCT and CTA to define new individualized strategies for acute reperfusion will allow more acute stroke patients to benefit from thrombolytic therapy. (orig.)

  7. Role of Transporters in Central Nervous System Drug Delivery and Blood-Brain Barrier Protection: Relevance to Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Hrvoje Brzica

    2017-03-01

    Full Text Available Ischemic stroke is a leading cause of morbidity and mortality in the United States. The only approved pharmacologic treatment for ischemic stroke is thrombolysis via recombinant tissue plasminogen activator (r-tPA. A short therapeutic window and serious adverse events (ie, hemorrhage, excitotoxicity greatly limit r-tPA therapy, which indicates an essential need to develop novel stroke treatment paradigms. Transporters expressed at the blood-brain barrier (BBB provide a significant opportunity to advance stroke therapy via central nervous system delivery of drugs that have neuroprotective properties. Examples of such transporters include organic anion–transporting polypeptides (Oatps and organic cation transporters (Octs. In addition, multidrug resistance proteins (Mrps are transporter targets in brain microvascular endothelial cells that can be exploited to preserve BBB integrity in the setting of stroke. Here, we review current knowledge on stroke pharmacotherapy and demonstrate how endogenous BBB transporters can be targeted for improvement of ischemic stroke treatment.

  8. Cardiorespiratory fitness, cognition and brain structure after TIA or minor ischemic stroke.

    Science.gov (United States)

    Boss, H Myrthe; Van Schaik, Sander M; Witkamp, Theo D; Geerlings, Mirjam I; Weinstein, Henry C; Van den Berg-Vos, Renske M

    2017-10-01

    Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = -.004 (95% CI -.007; -.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke.

  9. Analysis of Time-Dependent Brain Network on Active and MI Tasks for Chronic Stroke Patients.

    Directory of Open Access Journals (Sweden)

    Da-Hye Kim

    Full Text Available Several researchers have analyzed brain activities by investigating brain networks. However, there is a lack of the research on the temporal characteristics of the brain network during a stroke by EEG and the comparative studies between motor execution and imagery, which became known to have similar motor functions and pathways. In this study, we proposed the possibility of temporal characteristics on the brain networks of a stroke. We analyzed the temporal properties of the brain networks for nine chronic stroke patients by the active and motor imagery tasks by EEG. High beta band has a specific role in the brain network during motor tasks. In the high beta band, for the active task, there were significant characteristics of centrality and small-worldness on bilateral primary motor cortices at the initial motor execution. The degree centrality significantly increased on the contralateral primary motor cortex, and local efficiency increased on the ipsilateral primary motor cortex. These results indicate that the ipsilateral primary motor cortex constructed a powerful subnetwork by influencing the linked channels as compensatory effect, although the contralateral primary motor cortex organized an inefficient network by using the connected channels due to lesions. For the MI task, degree centrality and local efficiency significantly decreased on the somatosensory area at the initial motor imagery. Then, there were significant correlations between the properties of brain networks and motor function on the contralateral primary motor cortex and somatosensory area for each motor execution/imagery task. Our results represented that the active and MI tasks have different mechanisms of motor acts. Based on these results, we indicated the possibility of customized rehabilitation according to different motor tasks. We expect these results to help in the construction of the customized rehabilitation system depending on motor tasks by understanding temporal

  10. Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery

    OpenAIRE

    Kubis, Nathalie

    2016-01-01

    Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excit...

  11. Real-time monitoring of ischemic and contralateral brain pO2 during stroke by variable length multisite resonators.

    Science.gov (United States)

    Hou, Huagang; Li, Hongbin; Dong, Ruhong; Khan, Nadeem; Swartz, Harold

    2014-06-01

    Electron paramagnetic resonance (EPR) oximetry using variable length multi-probe implantable resonator (IR), was used to investigate the temporal changes in the ischemic and contralateral brain pO2 during stroke in rats. The EPR signal to noise ratio (S/N) of the IR with four sensor loops at a depth of up to 11 mm were compared with direct implantation of lithium phthalocyanine (LiPc, oximetry probe) deposits in vitro. These IRs were used to follow the temporal changes in pO2 at two sites in each hemisphere during ischemia induced by left middle cerebral artery occlusion (MCAO) in rats breathing 30% O2 or 100% O2. The S/N ratios of the IRs were significantly greater than the LiPc deposits. A similar pO2 at two sites in each hemisphere prior to the onset of ischemia was observed in rats breathing 30% O2. However, a significant decline in the pO2 of the left cortex and striatum occurred during ischemia, but no change in the pO2 of the contralateral brain was observed. A significant increase in the pO2 of only the contralateral non-ischemic brain was observed in the rats breathing 100% O2. No significant difference in the infarct volume was evident between the animals breathing 30% O2 or 100% O2 during ischemia. EPR oximetry with IRs can repeatedly assess temporal changes in the brain pO2 at four sites simultaneously during stroke. This oximetry approach can be used to test and develop interventions to rescue ischemic tissue by modulating cerebral pO2 during stroke. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Transcranial brain stimulation (TMS and tDCS for post-stroke aphasia rehabilitation: Controversies

    Directory of Open Access Journals (Sweden)

    Lucia Iracema Zanotto de Mendonça

    Full Text Available Transcranial brain stimulation (TS techniques have been investigated for use in the rehabilitation of post-stroke aphasia. According to previous reports, functional recovery by the left hemisphere improves recovery from aphasia, when compared with right hemisphere participation. TS has been applied to stimulate the activity of the left hemisphere or to inhibit homotopic areas in the right hemisphere. Various factors can interfere with the brain's response to TS, including the size and location of the lesion, the time elapsed since the causal event, and individual differences in the hemispheric language dominance pattern. The following questions are discussed in the present article: [a] Is inhibition of the right hemisphere truly beneficial?; [b] Is the transference of the language network to the left hemisphere truly desirable in all patients?; [c] Is the use of TS during the post-stroke subacute phase truly appropriate? Different patterns of neuroplasticity must occur in post-stroke aphasia.

  13. Cerebellar stroke presenting with isolated dizziness: Brain MRI in 136 patients.

    Science.gov (United States)

    Perloff, Michael D; Patel, Nimesh S; Kase, Carlos S; Oza, Anuja U; Voetsch, Barbara; Romero, Jose R

    2017-11-01

    To evaluate occurrence of cerebellar stroke in Emergency Department (ED) presentations of isolated dizziness (dizziness with a normal exam and negative neurological review of systems). A 5-year retrospective study of ED patients presenting with a chief complaint of "dizziness or vertigo", without other symptoms or signs in narrative history or on exam to suggest a central nervous system lesion, and work-up included a brain MRI within 48h. Patients with symptoms commonly peripheral in etiology (nystagmus, tinnitus, gait instability, etc.) were included in the study. Patient demographics, stroke risk factors, and gait assessments were recorded. One hundred and thirty-six patients, who had a brain MRI for isolated dizziness, were included. There was a low correlation of gait assessment between ED physician and Neurologist (49 patients, Spearman's correlation r 2 =0.17). Based on MRI DWI sequence, 3.7% (5/136 patients) had acute cerebellar strokes, limited to or including, the medial posterior inferior cerebellar artery vascular territory. In the 5 cerebellar stroke patients, mean age, body mass index (BMI), hemoglobin A1c, gender distribution, and prevalence of hypertension were similar to the non-cerebellar stroke patient group. Mean LDL/HDL ratio was 3.63±0.80 and smoking prevalence was 80% in the cerebellar stroke group compared to 2.43±0.79 and 22% (respectively, p valuesstroke group. Though there was preselection bias for stroke risk factors, our study suggests an important proportion of cerebellar stroke among ED patients with isolated dizziness, considering how common this complaint is. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke.

    Science.gov (United States)

    Zavaglia, Melissa; Forkert, Nils D; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C

    2015-01-01

    Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a 'map of stroke'.

  15. Clinical course of brain stroke in the persons exposed to ionizing radiation under the production conditions

    Energy Technology Data Exchange (ETDEWEB)

    Bouchmanov, A. [State Research Center of Russia, Moscow (Russian Federation). Inst. of Biophysics

    2000-05-01

    The purpose was to study the risk factors and clinical course of brain strokes in professionally exposed workers being employed in plutonium production in comparison with a control group. The method and materials of study -clinical supervision and clinical database creation on 162 cases of brain stroke (128 males and 34 females) developed among professionally exposed workers. Age of patient varied from 21 to 68 years (in average -51.6 y.). The control group consisted of patients with the same diagnosis, worked on the same enterprise, but non-exposed to radiation. Data on the totally accumulated dose of external gamma radiation were received on the base of the individual dosimeters (from 0.1 cSv to 52 cSv, in average about 13 cSv); the plutonium-239 body content was estimated accordingly to the level of urine radionuclide excretion (from 0.4 kBq to 1.6 kBq, in average about 0.33 kBq). Muscle's hypertinsion and pathological great-toe reflexes in paretic legs and hands, hemianopsia, impressive and ataxic aphasia prevailed in the patients with ischemic brain strokes in system of internal carotid artery, exposed to radiation. The changes of muscle's tension, ataxia and nystagmus were marked more often in the professionals with ischemic brain strokes in system of vertebrobasilar artery. The illness proceeded more easy and with smaller frequency of frustration of consciousness and algesthesia, irrespective of a type ischemic brain strokes in the people exposed to ionizing radiation, than in patients of non-irradiated group. It was found that the arterial hypertension appeared to be the main risk factor for the brain stroke in both groups of patients (in 81.48% and 91.15% of cases). There was no marked differences in significance of risk factors and in main clinical parameters of various types of ischemic brain strokes among the patients professionally exposed to radiation in comparison with a control group. (author)

  16. [Correlation between post-stroke pneumonia and outcome in patients with acute brain infarction].

    Science.gov (United States)

    Li, S J; Hu, H Q; Wang, X L; Cao, B Z

    2016-09-20

    Objective: To investigate the correlation between post-stroke pneumonia and outcome in patients with acute brain infarction. Methods: Consecutive acute cerebral infarction patients who were hospitalized in Department of Neurology, Jinan Military General Hospital were prospectively recruited from August 2010 to August 2014. The baseline data including age, sex, the National Institute of Health Stroke Scale (NIHSS) scores, type of Oxfordshire Community Stroke Project (OCSP: total anterior circulation infarct, partial anterior circulation infarct, posterior circulation infarct and lacunar infarct), fasting blood glucose etc. after admission were recorded. Post-stroke pneumonia was diagnosed by treating physician according to criteria for hospital-acquired pneumonia of the Centers for Disease Control and Prevention. Recovery was assessed by modified Rankin Scale (mRS) 180 days after stroke by telephone interview (mRS≤2 reflected good prognosis, and mRS>2 reflected unfavorable prognosis). Multinominal Logistic regression analysis, Kaplan-Meier curve and log rank test were used. Results: A total of 1 249 patients were enrolled, among them 173 patients were lost during follow-up. A total of 159 patients had post-stroke pneumonia, while 1 090 patients were without post-stroke. Compared with patients without post-stoke pneumonia, patients with post-stroke pneumonia were older (67±13 vs 63±12 years, P =0.000), more severe (NIHSS, 15(14) vs 4(4), P =0.000). Compared with patients without post-stoke pneumonia, more patients with post-stroke pneumonia suffered from heart failure (12.58% vs 3.40%, P =0.000), atrial fibrillation (26.42% vs 8.81%, P =0.000), myocardial infarction (10.06% vs 5.05%, P =0.016), recurrent brain infarction (30.19% vs 22.66%, P =0.045), total anterior circulation infarct type of OCSP (46.54% vs 19.63%, P =0.000), posterior circulation infarct of OCSP (39.62% vs 25.51%, P =0.001); more patients suffered from disorder of consciousness (60.38% vs 9

  17. Neurosurgical management of L-asparaginase induced haemorrhagic stroke.

    LENUS (Irish Health Repository)

    Ogbodo, Elisha

    2012-01-01

    The authors describe a case of L-asparaginase induced intracranial thrombosis and subsequent haemorrhage in a newly diagnosed 30-year-old man with acute lymphoblastic leukaemia who was successfully managed by surgical intervention. At presentation, he had a Glasgow Coma Score of 7\\/15, was aphasic and had dense right hemiplegia. Neuroimaging revealed an acute anterior left middle cerebral artery infarct with parenchymal haemorrhagic conversion, mass effect and subfalcine herniation. He subsequently underwent left frontal craniotomy and evacuation of large frontal haematoma and decompressive craniectomy for cerebral oedema. Six months postoperatively he underwent titanium cranioplasty. He had made good clinical recovery and is currently mobilising independently with mild occasional episodes of expressive dysphasia, difficulty with fine motor movement on the right side, and has remained seizure free. This is the first documented case of L-asparaginase induced haemorrhagic stroke managed by neurosurgical intervention. The authors emphasise the possible role of surgery in managing chemotherapy induced intracranial complications.

  18. Functional organization and restoration of the brain motor-execution network after stroke and rehabilitation

    Directory of Open Access Journals (Sweden)

    Sahil eBajaj

    2015-03-01

    Full Text Available Multiple cortical areas of the human brain motor system interact coherently in the low frequency range (< 0.1 Hz, even in the absence of explicit tasks. Following stroke, cortical interactions are functionally disturbed. How these interactions are affected and how the functional organization is regained from rehabilitative treatments as people begin to recover motor behaviors has not been systematically studied. We recorded the intrinsic functional magnetic resonance imaging (fMRI signals from 30 participants: 17 young healthy controls and 13 aged stroke survivors. Stroke participants underwent mental practice (MP or both mental practice and physical therapy (MP + PT within 14-51 days following stroke. We investigated the network activity of five core areas in the motor-execution network, consisting of the left primary motor area (LM1, the right primary motor area (RM1, the left pre-motor cortex (LPMC, the right pre-motor cortex (RPMC and the supplementary motor area (SMA. We discovered that (i the network activity dominated in the frequency range 0.06 Hz – 0.08 Hz for all the regions, and for both able-bodied and stroke participants (ii the causal information flow between the regions: LM1 and SMA, RPMC and SMA, RPMC and LM1, SMA and RM1, SMA and LPMC, was reduced significantly for stroke survivors (iii the flow did not increase significantly after MP alone and (iv the flow among the regions during MP+PT increased significantly. We also found that sensation and motor scores were significantly higher and correlated with directed functional connectivity measures when the stroke-survivors underwent MP+PT but not MP alone. The findings provide evidence that a combination of mental practice and physical therapy can be an effective means of treatment for stroke survivors to recover or regain the strength of motor behaviors, and that the spectra of causal information flow can be used as a reliable biomarker for evaluating rehabilitation in stroke

  19. The issues in the study of brain plasticity after stroke

    International Nuclear Information System (INIS)

    Zuo Chuantao

    2004-01-01

    Nowadays, the study on the plasticity of the brain is one of the hotspots in nerve scientific research. PET and fMRI provided powerful weapon to study brain plasticity, but some metholody can conflict the brain function study. The review elucide the the metholody questions from the choice of pantiets and control, defining motor recovery, the choice of motor task, the effect of brian morphological, interpreting changes in activation and analysis methods of PET images. (authors)

  20. Computed tomography and brain scintigraphy in ischemic stroke

    International Nuclear Information System (INIS)

    Chiu, L.C.; Fodor, L.B.; Cornell, S.H.; Christie, J.H.

    1976-01-01

    Radionuclide and computed tomographic (CT) scans were reviewed in 215 patients with ischemic stroke. The findings vary depending on the site of vascular occlusion. In middle cerebral artery occlusion, four distinct patterns may be seen on the scintigrams. The CT scans show little variation in appearance. The tentorial confluence sign is an important finding on scintigrams of patients with occipital infarction; the absence of this sign should suggest another diagnosis. During the first week and after the fourth week following an ischemic stroke, the scintigram is usually negative, whereas the lesion is visible by CT. However, there are a significant number of false negative CT scans; therefore, both examinations are advocated in difficult cases

  1. The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation

    DEFF Research Database (Denmark)

    Minjoli, Sena; Saturnino, Guilherme B.; Blicher, Jakob Udby

    2017-01-01

    . Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative...... to the lesion were tested. For TDCS, the finite-element method was used to simulate a standard approach with two electrode pads, and the position of one electrode was systematically varied. For both TMS and TDCS, the lesion caused electric field " hot spots" in the cortex. However, these maxima were......Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) are two types of non-invasive transcranial brain stimulation (TBS). They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large...

  2. Current trends in stroke rehabilitation. A review with focus on brain plasticity.

    Science.gov (United States)

    Johansson, B B

    2011-03-01

    Current understanding of brain plasticity has lead to new approaches in ischemic stroke rehabilitation. Stroke units that combine good medical and nursing care with task-oriented intense training in an environment that provides confidence, stimulation and motivation significantly improve outcome. Repetitive trans-cranial magnetic stimulation (rTMS), and trans-cranial direct current stimulation (tDCS) are applied in rehabilitation of motor function. The long-term effect, optimal way of stimulation and possibly efficacy in cognitive rehabilitation need evaluation. Methods based on multisensory integration of motor, cognitive, and perceptual processes including action observation, mental training, and virtual reality are being tested. Different approaches of intensive aphasia training are described. Recent data on intensive melodic intonation therapy indicate that even patients with very severe non-fluent aphasia can regain speech through homotopic white matter tract plasticity. Music therapy is applied in motor and cognitive rehabilitation. To avoid the confounding effect of spontaneous improvement, most trials are preformed ≥3 months post stroke. Randomized controlled trials starting earlier after strokes are needed. More attention should be given to stroke heterogeneity, cognitive rehabilitation, and social adjustment and to genetic differences, including the role of BDNF polymorphism in brain plasticity. © 2010 John Wiley & Sons A/S.

  3. Diagnosis of small posterior fossa stroke on brain CT: effect of iterative reconstruction designed for brain CT on detection performance

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Taihei; Yoshida, Morikatsu; Yokoyama, Koichi [Amakusa Medical Center, Department of Radiology, Amakusa, Kumamoto (Japan); Nakaura, Takeshi; Hirata, Kenichiro; Kidoh, Masafumi; Oda, Seitaro; Utsunomiya, Daisuke; Yamashita, Yasuyuki [Kumamoto University, Department of Diagnostic Radiology, Graduate School of Life Sciences, Kumamoto (Japan); Harada, Kazunori [Amakusa Medical Center, Department of Surgery, Kumamoto (Japan)

    2017-09-15

    In this study, we aimed to determine whether iterative model reconstruction designed for brain CT (IMR-neuro) would improve the accuracy of posterior fossa stroke diagnosis on brain CT. We enrolled 37 patients with ischaemic stroke in the posterior fossa and 37 patients without stroke (controls). Using axial images reconstructed using filtered back-projection (FBP) and IMR-neuro, we compared the CT numbers in infarcted areas, image noise in the pons, and contrast-to-noise ratios (CNRs) of infarcted and non-infarcted areas on scans subjected to IMR-neuro and FBP. To analyse the performance of hypo-attenuation detection, we used receiver-operating characteristic (ROC) curve techniques. The image noise was significantly lower (2.2 ± 0.5 vs. 5.1 ± 0.9 Hounsfield units, p < 0.01) and the difference in CNR between the infarcted and non-infarcted areas was significantly higher with IMR-neuro than with FBP (2.2 ± 1.7 vs. 4.0 ± 3.6, p < 0.01). Furthermore, the average area under the ROC curve was significantly higher with IMR-neuro (0.90 vs. 0.86 for FBP, p = 0.04). IMR-neuro yielded better image quality and improved hypo-attenuation detection in patients with ischaemic stroke. (orig.)

  4. Diagnosis of small posterior fossa stroke on brain CT: effect of iterative reconstruction designed for brain CT on detection performance

    International Nuclear Information System (INIS)

    Inoue, Taihei; Yoshida, Morikatsu; Yokoyama, Koichi; Nakaura, Takeshi; Hirata, Kenichiro; Kidoh, Masafumi; Oda, Seitaro; Utsunomiya, Daisuke; Yamashita, Yasuyuki; Harada, Kazunori

    2017-01-01

    In this study, we aimed to determine whether iterative model reconstruction designed for brain CT (IMR-neuro) would improve the accuracy of posterior fossa stroke diagnosis on brain CT. We enrolled 37 patients with ischaemic stroke in the posterior fossa and 37 patients without stroke (controls). Using axial images reconstructed using filtered back-projection (FBP) and IMR-neuro, we compared the CT numbers in infarcted areas, image noise in the pons, and contrast-to-noise ratios (CNRs) of infarcted and non-infarcted areas on scans subjected to IMR-neuro and FBP. To analyse the performance of hypo-attenuation detection, we used receiver-operating characteristic (ROC) curve techniques. The image noise was significantly lower (2.2 ± 0.5 vs. 5.1 ± 0.9 Hounsfield units, p < 0.01) and the difference in CNR between the infarcted and non-infarcted areas was significantly higher with IMR-neuro than with FBP (2.2 ± 1.7 vs. 4.0 ± 3.6, p < 0.01). Furthermore, the average area under the ROC curve was significantly higher with IMR-neuro (0.90 vs. 0.86 for FBP, p = 0.04). IMR-neuro yielded better image quality and improved hypo-attenuation detection in patients with ischaemic stroke. (orig.)

  5. Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

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    Joko Widodo

    2016-05-01

    Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

  6. Blood Brain Barrier and Neuroinflammation Are Critical Targets of IGF-1-Mediated Neuroprotection in Stroke for Middle-Aged Female Rats

    Science.gov (United States)

    Bake, Shameena; Selvamani, Amutha; Cherry, Jessica; Sohrabji, Farida

    2014-01-01

    Ischemia-induced cerebral infarction is more severe in older animals as compared to younger animals, and is associated with reduced availability of insulin-like growth factor (IGF)-1. This study determined the effect of post-stroke IGF-1 treatment, and used microRNA profiling to identify mechanisms underlying IGF-1’s neuroprotective actions. Post-stroke ICV administration of IGF-1 to middle-aged female rats reduced infarct volume by 39% when measured 24h later. MicroRNA analyses of ischemic tissue collected at the early post-stroke phase (4h) indicated that 8 out of 168 disease-related miRNA were significantly downregulated by IGF-1. KEGG pathway analysis implicated these miRNA in PI3K-Akt signaling, cell adhesion/ECM receptor pathways and T-and B-cell signaling. Specific components of these pathways were subsequently analyzed in vehicle and IGF-1 treated middle-aged females. Phospho-Akt was reduced by ischemia at 4h, but elevated by IGF-1 treatment at 24h. IGF-1 induced Akt activation was preceded by a reduction of blood brain barrier permeability at 4h post-stroke and global suppression of cytokines including IL-6, IL-10 and TNF-α. A subset of these cytokines including IL-6 was also suppressed by IGF-1 at 24h post-stroke. These data are the first to show that the temporal and mechanistic components of post-stroke IGF-1 treatment in older animals, and that cellular components of the blood brain barrier may serve as critical targets of IGF-1 in the aging brain. PMID:24618563

  7. Robotic devices and brain-machine interfaces for hand rehabilitation post-stroke.

    Science.gov (United States)

    McConnell, Alistair C; Moioli, Renan C; Brasil, Fabricio L; Vallejo, Marta; Corne, David W; Vargas, Patricia A; Stokes, Adam A

    2017-06-28

    To review the state of the art of robotic-aided hand physiotherapy for post-stroke rehabilitation, including the use of brain-machine interfaces. Each patient has a unique clinical history and, in response to personalized treatment needs, research into individualized and at-home treatment options has expanded rapidly in recent years. This has resulted in the development of many devices and design strategies for use in stroke rehabilitation. The development progression of robotic-aided hand physiotherapy devices and brain-machine interface systems is outlined, focussing on those with mechanisms and control strategies designed to improve recovery outcomes of the hand post-stroke. A total of 110 commercial and non-commercial hand and wrist devices, spanning the 2 major core designs: end-effector and exoskeleton are reviewed. The growing body of evidence on the efficacy and relevance of incorporating brain-machine interfaces in stroke rehabilitation is summarized. The challenges involved in integrating robotic rehabilitation into the healthcare system are discussed. This review provides novel insights into the use of robotics in physiotherapy practice, and may help system designers to develop new devices.

  8. Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study

    Directory of Open Access Journals (Sweden)

    Ping Wu

    2016-01-01

    Full Text Available Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = -0.609, P = 0.047 and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = -0.737, P = 0.010. Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

  9. Brain strokes related to aortic aneurysma – the analysis of three cases

    Directory of Open Access Journals (Sweden)

    Pastuszak Żanna

    2017-04-01

    Full Text Available Brain stroke connected with aortic blood flow disturbances is a rare disease and its incidence is difficult to assume. Nevertheless, 10-50% of patients with aortic dissection may not experience any pain. In case of 18-30% patients with aortic dissection neurological signs are first disease presentation and among them ischemic stroke is the most common. The most popular aortic dissection classification is with use of Stanford system. Type A involves the ascending aorta and type B is occurring distal to the subclavian artery. Aortic dissection risk factors include hypertension, cystic medionecrosis, bicuspid aortic valve and Marfan’s or Ehlers-Danlos syndrome.

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

    Science.gov (United States)

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

    2012-01-01

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

  11. Optical scatter imaging of cellular and mitochondrial swelling in brain tissue models of stroke

    Science.gov (United States)

    Johnson, Lee James

    2001-08-01

    The severity of brain edema resulting from a stroke can determine a patient's survival and the extent of their recovery. Cellular swelling is the microscopic source of a significant part of brain edema. Mitochondrial swelling also appears to be a determining event in the death or survival of the cells that are injured during a stroke. Therapies for reducing brain edema are not effective in many cases and current treatments of stroke do not address mitochondrial swelling at all. This dissertation is motivated by the lack of a complete understanding of cellular swelling resulting from stroke and the lack of a good method to begin to study mitochondrial swelling resulting from stroke in living brain tissue. In this dissertation, a novel method of detecting mitochondrial and cellular swelling in living hippocampal slices is developed and validated. The system is used to obtain spatial and temporal information about cellular and mitochondrial swelling resulting from various models of stroke. The effect of changes in water content on light scatter and absorption are examined in two models of brain edema. The results of this study demonstrate that optical techniques can be used to detect changes in water content. Mie scatter theory, the theoretical basis of the dual- angle scatter ratio imaging system, is presented. Computer simulations based on Mie scatter theory are used to determine the optimal angles for imaging. A detailed account of the early systems is presented to explain the motivations for the system design, especially polarization, wavelength and light path. Mitochondrial sized latex particles are used to determine the system response to changes in scattering particle size and concentration. The dual-angle scatter ratio imaging system is used to distinguish between osmotic and excitotoxic models of stroke injury. Such distinction cannot be achieved using the current techniques to study cellular swelling in hippocampal slices. The change in the scatter ratio is

  12. A comparison of different models of stroke on behaviour and brain morphology.

    Science.gov (United States)

    Gonzalez, C L R; Kolb, B

    2003-10-01

    We compared the effects of three models of permanent ischemia, as well as cortical aspiration, on behaviour and brain morphology. Rats received a stroke either by devascularization or by two different procedures of medial cerebral artery occlusion (MCAO; small vs. large). Animals were trained in a reaching task, forepaw asymmetry, forepaw inhibition, sunflower seed task and tongue extension. Behaviour was assessed 1 week after the lesion and at 2-week intervals for a total of 9 weeks. One week after the surgery all animals were severely impaired on all tasks and although they improved over time they only reached preoperative base lines on tongue extension. Animals with small MCAOs performed better in reaching and sunflower tasks; no other behavioural differences were detected among the groups. Pyramidal cells in forelimb and cingulate areas as well as spiny neurons of the striatum were examined for dendritic branching and spine density using a Golgi-Cox procedure. Each lesion type had a different impact on cell morphology. Overall, different changes (atrophy or hypertrophy) were observed with each kind of lesion and these changes were specific for the region (forelimb, cingulate, striatum) and the condition (intact vs. damaged hemisphere). These results suggest that: (i) different lesions to the motor cortex produce subtle differences in behaviour, and (ii) the method used to induce the lesion produces striking differences in cortical and subcortical plasticity.

  13. Minocycline Attenuates Iron-Induced Brain Injury.

    Science.gov (United States)

    Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

    2016-01-01

    Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism.

  14. Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

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    Melissa Zavaglia

    2015-01-01

    Full Text Available Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA, to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS. The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’.

  15. Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

    Science.gov (United States)

    Zavaglia, Melissa; Forkert, Nils D.; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C.

    2015-01-01

    Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’. PMID:26448908

  16. Decreased integration and information capacity in stroke measured by whole brain models of resting state activity.

    Science.gov (United States)

    Adhikari, Mohit H; Hacker, Carl D; Siegel, Josh S; Griffa, Alessandra; Hagmann, Patric; Deco, Gustavo; Corbetta, Maurizio

    2017-04-01

    While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to

  17. Using Brain Oscillations and Corticospinal Excitability to Understand and Predict Post-Stroke Motor Function

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    Aurore Thibaut

    2017-05-01

    Full Text Available What determines motor recovery in stroke is still unknown and finding markers that could predict and improve stroke recovery is a challenge. In this study, we aimed at understanding the neural mechanisms of motor function recovery after stroke using neurophysiological markers by means of cortical excitability (transcranial magnetic stimulation—TMS and brain oscillations (electroencephalography—EEG. In this cross-sectional study, 55 subjects with chronic stroke (62 ± 14 yo, 17 women, 32 ± 42 months post-stroke were recruited in two sites. We analyzed TMS measures (i.e., motor threshold—MT—of the affected and unaffected sides and EEG variables (i.e., power spectrum in different frequency bands and different brain regions of the affected and unaffected hemispheres and their correlation with motor impairment as measured by Fugl-Meyer. Multiple univariate and multivariate linear regression analyses were performed to identify the predictors of good motor function. A significant interaction effect of MT in the affected hemisphere and power in beta bandwidth over the central region for both affected and unaffected hemispheres was found. We identified that motor function positively correlates with beta rhythm over the central region of the unaffected hemisphere, while it negatively correlates with beta rhythm in the affected hemisphere. Our results suggest that cortical activity in the affected and unaffected hemisphere measured by EEG provides new insights on the association between high-frequency rhythms and motor impairment, highlighting the role of an excess of beta in the affected central cortical region in poor motor function in stroke recovery.

  18. Intrahemispheric Perfusion in Chronic Stroke-Induced Aphasia

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    Cynthia K. Thompson

    2017-01-01

    Full Text Available Stroke-induced alterations in cerebral blood flow (perfusion may contribute to functional language impairments and recovery in chronic aphasia. Using MRI, we examined perfusion in the right and left hemispheres of 35 aphasic and 16 healthy control participants. Across 76 regions (38 per hemisphere, no significant between-subjects differences were found in the left, whereas blood flow in the right was increased in the aphasic compared to the control participants. Region-of-interest (ROI analyses showed a varied pattern of hypo- and hyperperfused regions across hemispheres in the aphasic participants; however, there were no significant correlations between perfusion values and language abilities in these regions. These patterns may reflect autoregulatory changes in blood flow following stroke and/or increases in general cognitive effort, rather than maladaptive language processing. We also examined blood flow in perilesional tissue, finding the greatest hypoperfusion close to the lesion (within 0–6 mm, with greater hypoperfusion in this region compared to more distal regions. In addition, hypoperfusion in this region was significantly correlated with language impairment. These findings underscore the need to consider cerebral perfusion as a factor contributing to language deficits in chronic aphasia as well as recovery of language function.

  19. Stroke And Substance Abuse

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    A Chitsaz

    2017-02-01

    Full Text Available Introduction: stroke in recreational substance users can be an indirect complication, like endocarditis and cardio embolism in parenteral drug users. With some drug like cocaine, stroke appear to be the result of a direct effect. In young subjects without other risk factors provide persuasive evidence for causality . OPIATES: Heroine is the most abused opiate drug, which is administered by injection, by snorting or by smoking. Stroke affects heroin users by diverse mechanisms,. Injectors are at risk of infections endocarditis, which carries risk for both ischemic and hemorrhagic stroke. Cerebral or subarachnoid hemorrhage usually occurs after rupture of a septic (mycotic aneurysm. Heroine users can are also at risk for hemorrhagic stroke secondary to liver failure with deranged clotting and to heroin nephropathy with uremia or malignant hypertension. In some heroin users the drug it self is directly causal due to vasculitis, hypersensitivity and immunologic changes. Embolization of foreign material to brain due to mixed of heroine with quinine can cause cerebral embolism. AMPHETAMINE AND other psychostimulants: In abuser of amphetamine hemorrhagic stroke can occur, oral, intravenous, nasal, and inhalational routes of administration have been reported. Most were chronic user, but in several patients, stroke followed a first exposure. Some of amphetamine induced intracranial hemorrhages are secondary to acute hypertension, some to cerebral vacuities, and some to a combination of two. Decongestants and diet pills: Phenylpropanolamine (PPA, an amphetamine – like drug, in decongestants and diet pills, induce acute hypertension, sever headache, psychiatric symptoms, seizures and hemorrhagic stroke. Ephedrine and pseudo ephedrine are present in decongestants and bronchodilators and induce headache, tachyarrhythmia, hypertensive emergency, and hemorrhagic and occlusive stroke. Ecstasy, 3,4 Methylenedioxymethamphetamin (MDMA with amphetamine like can

  20. Radiation-induced brain damage in children

    International Nuclear Information System (INIS)

    Oi, Shizuo; Kokunai, Takashi; Ijichi, Akihiro; Matsumoto, Satoshi; Raimondi, A.J.

    1990-01-01

    The nature and sequence of the radiation-induced changes in the brain were studied postmortem in 34 children with glioma, 22 of whom underwent central nervous system radiation therapy. Twenty received whole-brain or whole-neuroaxis radiation at a total mean dosage of 4063 cGy. Brain tissue alternations were analyzed histologically by means of various staining methods, including immunohistochemical techniques. The histological features of irradiated brains were compared with those of non-irradiated brains. Microscopic findings included demyelination (seven cases), focal necrosis (six cases), cortical atrophy (four cases), endothelial proliferation (four cases), and telangiectatic vascular proliferation with vascular thickening and oozing of a thick fluid (one case). Such findings were rare in non-irradiated patients. Demyelination was observed earliest in a patient who died 5 months after radiation therapy and was more common after 9 months. Focal necrosis was first observed 9 months post-irradiation but was more advanced and extensive after 1 year. Calcified foci were found only after 60 months. Various vascular changes such as vascular thickening and thrombosis suggested ischemic insult to the brain as a late effect of radiation injury. The results of this study suggest that the immature brain may be more sensitive to radiation than is the adult brain, and that the manifestations of radiation-induced injury depend on the time elapsed after irradiation. (author)

  1. Induction of neuroplasticity and recovery in post-stroke aphasia by non-invasive brain stimulation

    Directory of Open Access Journals (Sweden)

    Priyanka eShah

    2013-12-01

    Full Text Available Stroke victims tend to prioritize speaking, writing and walking as the three most important rehabilitation goals. Of note is that two of these goals involve communication. This underscores the significance of developing successful approaches to aphasia treatment for the several hundred thousand new aphasia patients each year and over 1 million stroke survivors with chronic aphasia in the U.S. alone. After several years of growth as a research tool, noninvasive brain stimulation (NBS is gradually entering the arena of clinical aphasiology. In this review, we first examine the current state of knowledge of post-stroke language recovery including the contributions from the dominant and non-dominant hemispheres. Next, we briefly discuss the methods and the physiologic basis of the use of inhibitory and excitatory repetitive transcranial magnetic stimulation (rTMS and transcranial direct current stimulation (tDCS as research tools in patients who experience post-stroke aphasia. Finally, we provide a critical review of the most influential evidence behind the potential use of these two brain stimulation methods as clinical rehabilitative tools.

  2. 99mTc-HMPAO perfusion indices and brain-mapping in stroke patients

    International Nuclear Information System (INIS)

    Minchev, D.; Klisarova, A.

    1997-01-01

    It is the purpose of the study to establish correlations between 99mTc-HMPAO (hexamethylpropylenaminoxym) perfusion indices and changes in brain-mapping among patients with acute stroke. Forty-six patients with definitely proved stroke syndrome are investigated in the first 72 hours and 15 days after the onset of cerebrovascular accident using clinical, neuro-physiological and 99mTc-HMPAO SPECT methods. Regional and hemispheric perfusion asymmetry correlate with the brain-mapping cerebral disturbance (p < 0.001). In patients presenting focal hypoperfusion there is a significant correlation between perfusion indices and local EEG disturbance (r = 0.87). The dynamic study demonstrates a significant correlation between perfusion indices and electrical cerebral disturbance in the first 72 hours after the onset of the cerebrovascular accident. Fifteen days later no such correlation is documented. The obtained results demonstrate the essential practical bearing of 99mTc-HMPAO SPECT indices on the objective assessment of perfusion hemispheric and regional asymmetry in stroke patients, and the possibility of being used for indirect estimation of the regional cerebral blood flow in acute stroke patients against the background of visual and quantitative EEG changes (author)

  3. Induction of neuroplasticity and recovery in post-stroke aphasia by non-invasive brain stimulation.

    Science.gov (United States)

    Shah, Priyanka P; Szaflarski, Jerzy P; Allendorfer, Jane; Hamilton, Roy H

    2013-12-24

    Stroke victims tend to prioritize speaking, writing, and walking as the three most important rehabilitation goals. Of note is that two of these goals involve communication. This underscores the significance of developing successful approaches to aphasia treatment for the several hundred thousand new aphasia patients each year and over 1 million stroke survivors with chronic aphasia in the U.S. alone. After several years of growth as a research tool, non-invasive brain stimulation (NBS) is gradually entering the arena of clinical aphasiology. In this review, we first examine the current state of knowledge of post-stroke language recovery including the contributions from the dominant and non-dominant hemispheres. Next, we briefly discuss the methods and the physiologic basis of the use of inhibitory and excitatory repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) as research tools in patients who experience post-stroke aphasia. Finally, we provide a critical review of the most influential evidence behind the potential use of these two brain stimulation methods as clinical rehabilitative tools.

  4. In vivo real-time multiphoton imaging of T lymphocytes in the mouse brain after experimental stroke

    DEFF Research Database (Denmark)

    Fumagalli, Stefano; Coles, Jonathan A; Ejlerskov, Patrick

    2011-01-01

    To gain a better understanding of T cell behavior after stroke, we have developed real-time in vivo brain imaging of T cells by multiphoton microscopy after middle cerebral artery occlusion.......To gain a better understanding of T cell behavior after stroke, we have developed real-time in vivo brain imaging of T cells by multiphoton microscopy after middle cerebral artery occlusion....

  5. Radiation-induced brain injury: A review

    Directory of Open Access Journals (Sweden)

    Michael eRobbins

    2012-07-01

    Full Text Available Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (> 6 months to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses > 30 Gy; white matter necrosis occurs at fractionated doses > 60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain

  6. The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

    OpenAIRE

    David Israeli, David Tanne, Dianne Daniels, David Last, Ran Shneor, David Guez, Efrat Landau, Yiftach Roth, Aharon Ocherashvilli, Mati Bakon, Chen Hoffman, Amit Weinberg, Talila Volk, Yael Mardor

    2011-01-01

    The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI...

  7. The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

    OpenAIRE

    Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

    2010-01-01

    The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI...

  8. Brain Stroke Detection by Microwaves Using Prior Information from Clinical Databases

    Directory of Open Access Journals (Sweden)

    Natalia Irishina

    2013-01-01

    Full Text Available Microwave tomographic imaging is an inexpensive, noninvasive modality of media dielectric properties reconstruction which can be utilized as a screening method in clinical applications such as breast cancer and brain stroke detection. For breast cancer detection, the iterative algorithm of structural inversion with level sets provides well-defined boundaries and incorporates an intrinsic regularization, which permits to discover small lesions. However, in case of brain lesion, the inverse problem is much more difficult due to the skull, which causes low microwave penetration and highly noisy data. In addition, cerebral liquid has dielectric properties similar to those of blood, which makes the inversion more complicated. Nevertheless, the contrast in the conductivity and permittivity values in this situation is significant due to blood high dielectric values compared to those of surrounding grey and white matter tissues. We show that using brain MRI images as prior information about brain's configuration, along with known brain dielectric properties, and the intrinsic regularization by structural inversion, allows successful and rapid stroke detection even in difficult cases. The method has been applied to 2D slices created from a database of 3D real MRI phantom images to effectively detect lesions larger than 2.5 × 10−2 m diameter.

  9. [Functional neuroimaging of the brain structures associated with language in healthy individuals and patients with post-stroke aphasia].

    Science.gov (United States)

    Alferova, V V; Mayorova, L A; Ivanova, E G; Guekht, A B; Shklovskij, V M

    2017-01-01

    The introduction of non-invasive functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI), in the practice of scientific and clinical research can increase our knowledge about the organization of cognitive processes, including language, in normal and reorganization of these cognitive functions in post-stroke aphasia. The article discusses the results of fMRI studies of functional organization of the cortex of a healthy adult's brain in the processing of various voice information as well as the main types of speech reorganization after post-stroke aphasia in different stroke periods. The concepts of 'effective' and 'ineffective' brain plasticity in post-stroke aphasia were considered. It was concluded that there was an urgent need for further comprehensive studies, including neuropsychological testing and several complementary methods of functional neuroimaging, to develop a phased treatment plan and neurorehabilitation of patients with post-stroke aphasia.

  10. Hyper-attenuating brain lesions on CT after ischemic stroke and thrombectomy are associated with final brain infarction.

    Science.gov (United States)

    Cabral, F B; Castro-Afonso, L H; Nakiri, G S; Monsignore, L M; Fábio, Src; Dos Santos, A C; Pontes-Neto, O M; Abud, D G

    2017-12-01

    Purpose Hyper-attenuating lesions, or contrast staining, on a non-contrast brain computed tomography (NCCT) scan have been investigated as a predictor for hemorrhagic transformation after endovascular treatment of acute ischemic stroke (AIS). However, the association of hyper-attenuating lesions and final ischemic areas are poorly investigated in this setting. The aim of the present study was to assess correlations between hyper-attenuating lesions and final brain infarcted areas after thrombectomy for AIS. Methods Data from patients with AIS of the anterior circulation who underwent endovascular treatment were retrospectively assessed. Images of the brain NCCT scans were analyzed in the first hours and late after treatment. The hyper-attenuating areas were compared to the final ischemic areas using the Alberta Stroke Program Early CT Score (ASPECTS). Results Seventy-one of the 123 patients (65.13%) treated were included. The association between the hyper-attenuating region in the post-thrombectomy CT scan and final brain ischemic area were sensitivity (58.3% to 96.9%), specificity (42.9% to 95.6%), positive predictive values (71.4% to 97.7%), negative predictive values (53.8% to 79.5%), and accuracy values (68% to 91%). The highest sensitivity values were found for the lentiform (96.9%) and caudate nuclei (80.4%) and for the internal capsule (87.5%), and the lowest values were found for the M1 (58.3%) and M6 (66.7%) cortices. Conclusions Hyper-attenuating lesions on head NCCT scans performed after endovascular treatment of AIS may predict final brain infarcted areas. The prediction appears to be higher in the deep brain regions compared with the cortical regions.

  11. Stroke

    Science.gov (United States)

    ... travels from another part of the body and lodges within an artery in the brain. When an ... artery, breaks loose, travels towards the brain and lodges in a cerebral artery. The blocked artery deprives ...

  12. Role of brain natriuretic peptide as a novel prognostic biomarker in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Bindu Menon

    2016-01-01

    Full Text Available Aim: We investigated to study the prognostic importance of brain natriuretic peptide (BNP in ischemic stroke. Materials and Methods: We prospectively enrolled 100 patients with acute ischemic stroke and measured plasma BNP levels and compared with age- and sex-matched healthy controls. Risk factors, biochemical parameters, lipid profile, carotid and vertebral Doppler, imaging, and cardiac evaluation were done. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS score on admission and functional disability by Barthel Index (BI at 3 months. Ischemic stroke subtype was classified according to the Oxfordshire Community Stroke Project (OCSP. Data were entered in MS Excel, and appropriate statistical analysis was done using the SPSS software version 21.0. A P = 0.05 was considered as significant. Results: Mean age of patients was 55.17 ± 11.37 years with a male:female ratio 3:1. OCSP showed total anterior circulation infarct (TACI 35, partial anterior circulation infarct 9, lacunar infarct 12, and posterior circulation infarct 44. NIHSS on admission was average 10 ± 7 and BI was 57 ± 30. BNP in patients (435 ng/ml was very high as compared to controls (<60 ng/ml (P < 0.001. There was a positive correlation between age and BNP (R2 = 0.34; P < 0.00; NIHSS and BNP (R2 = 0.255; P < 0.01, negative correlation between BI and BNP (R2 = −0.064; P < 0.01. Mean BNP levels across the OCSP showed higher values in TACI (F = 4.609 P = 0.005. Regression analysis showed that BNP can predict BI which was statistically significant. Conclusion: Plasma BNP levels was significantly elevated in patients with ischemic stroke. Our study concludes that high BNP levels are seen in large anterior circulation stroke and is a predictor for the poor functional outcome at 3 months. Determination of BNP levels as a biomarker could be helpful in predicting the outcome in stroke patients.

  13. Changes in Electroencephalography Complexity using a Brain Computer Interface-Motor Observation Training in Chronic Stroke Patients: A Fuzzy Approximate Entropy Analysis

    Directory of Open Access Journals (Sweden)

    Rui Sun

    2017-09-01

    Full Text Available Entropy-based algorithms have been suggested as robust estimators of electroencephalography (EEG predictability or regularity. This study aimed to examine possible disturbances in EEG complexity as a means to elucidate the pathophysiological mechanisms in chronic stroke, before and after a brain computer interface (BCI-motor observation intervention. Eleven chronic stroke subjects and nine unimpaired subjects were recruited to examine the differences in their EEG complexity. The BCI-motor observation intervention was designed to promote functional recovery of the hand in stroke subjects. Fuzzy approximate entropy (fApEn, a novel entropy-based algorithm designed to evaluate complexity in physiological systems, was applied to assess the EEG signals acquired from unimpaired subjects and stroke subjects, both before and after training. The results showed that stroke subjects had significantly lower EEG fApEn than unimpaired subjects (p < 0.05 in the motor cortex area of the brain (C3, C4, FC3, FC4, CP3, and CP4 in both hemispheres before training. After training, motor function of the paretic upper limb, assessed by the Fugl-Meyer Assessment-Upper Limb (FMA-UL, Action Research Arm Test (ARAT, and Wolf Motor Function Test (WMFT improved significantly (p < 0.05. Furthermore, the EEG fApEn in stroke subjects increased considerably in the central area of the contralesional hemisphere after training (p < 0.05. A significant correlation was noted between clinical scales (FMA-UL, ARAT, and WMFT and EEG fApEn in C3/C4 in the contralesional hemisphere (p < 0.05. This finding suggests that the increase in EEG fApEn could be an estimator of the variance in upper limb motor function improvement. In summary, fApEn can be used to identify abnormal EEG complexity in chronic stroke, when used with BCI-motor observation training. Moreover, these findings based on the fApEn of EEG signals also expand the existing interpretation of training-induced functional

  14. Neuroprotection of dietary virgin olive oil on brain lipidomics during stroke.

    Science.gov (United States)

    Rabiei, Zahra; Bigdeli, Mohammad Reza; Rasoulian, Bahram

    2013-08-01

    Recent studies suggest that dietary virgin olive oil reduces hypoxia-reoxygenation injury in rat brain. This study investigated the effect of pretreatment with different doses of dietary virgin olive oil on brain lipidomics during stroke. In this experimental trial, 60 male Wistar rats were studied in 5 groups of 12 each. The control group received distilled water while three treatment groups received oral virgin olive oil for 30 days (0.25, 0.5 and 0.75 ml/kg/day respectively). Also the sham group received distilled water. Two hours after the last dose, the animals divided two groups. The middle cerebral artery occlusion (MCAO) group subjected to 60 min of middle cerebral artery occlusion (MCAO) and intact groups for brain lipids analysis. The brain phosphatidylcholine, cholesterol ester and cholesterol levels increased significantly in doses of 0.5 and 0.75 ml/kg/day compare with control group. VOO in all three doses increased the brain triglyceride levels. VOO with dose 0.75 ml/kg increased the brain cerebroside levels when compared with control group. VOO pretreatment for 30 days decreased the brain ceramide levels in doses of 0.5 and 0.75 ml/kg/day (p<0.05). Although further studies are needed, the results indicate that the VOO pretreatment improved the injury of ischemia and reperfusion and might be beneficial in patients with these disorders and seems to partly exert their effects via change in brain lipid levels in rat.

  15. Moderately delayed post-insult treatment with normobaric hyperoxia reduces excitotoxin-induced neuronal degeneration but increases ischemia-induced brain damage

    Directory of Open Access Journals (Sweden)

    Haelewyn Benoit

    2011-04-01

    Full Text Available Abstract Background The use and benefits of normobaric oxygen (NBO in patients suffering acute ischemic stroke is still controversial. Results Here we show for the first time to the best of our knowledge that NBO reduces both NMDA-induced calcium influxes in vitro and NMDA-induced neuronal degeneration in vivo, but increases oxygen and glucose deprivation-induced cell injury in vitro and ischemia-induced brain damage produced by middle cerebral artery occlusion in vivo. Conclusions Taken together, these results indicate that NBO reduces excitotoxin-induced calcium influx and subsequent neuronal degeneration but favors ischemia-induced brain damage and neuronal death. These findings highlight the complexity of the mechanisms involved by the use of NBO in patients suffering acute ischemic stroke.

  16. Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling

    DEFF Research Database (Denmark)

    Kammersgaard, L P; Rasmussen, B H; Jørgensen, Henrik Stig

    2000-01-01

    Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients...

  17. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Huang, Zhangjian [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009 (China); Li, Ping [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Li, Jia [National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shoujing Road, Shanghai 201203 (China); Zhang, Luyong [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Saavedra, Juan M. [Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States); Liao, Hong, E-mail: liaohong56@hotmail.com [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Pang, Tao, E-mail: tpang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States)

    2015-12-01

    Totarol activates PI3K/Akt pathway in neurons. • Totarol induces HO-1, GSH and SOD expression in vitro and in vivo. • Totarol exhibits neuroprotective effects in rat brain ischemic stroke model.

  18. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    International Nuclear Information System (INIS)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi; Huang, Zhangjian; Li, Ping; Li, Jia; Zhang, Luyong; Saavedra, Juan M.; Liao, Hong; Pang, Tao

    2015-01-01

    Totarol activates PI3K/Akt pathway in neurons. • Totarol induces HO-1, GSH and SOD expression in vitro and in vivo. • Totarol exhibits neuroprotective effects in rat brain ischemic stroke model.

  19. Know your tools - concordance of different methods for measuring brain volume change after ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Yassi, Nawaf; Campbell, Bruce C.V.; Davis, Stephen M.; Bivard, Andrew [The University of Melbourne, Departments of Medicine and Neurology, Melbourne Brain Centre rate at The Royal Melbourne Hospital, Parkville, Victoria (Australia); Moffat, Bradford A.; Steward, Christopher; Desmond, Patricia M. [The University of Melbourne, Department of Radiology, The Royal Melbourne Hospital, Parkville (Australia); Churilov, Leonid [The University of Melbourne, The Florey Institute of Neurosciences and Mental Health, Parkville (Australia); Parsons, Mark W. [University of Newcastle and Hunter Medical Research Institute, Priority Research Centre for Translational Neuroscience and Mental Health, Newcastle (Australia)

    2015-07-15

    Longitudinal brain volume changes have been investigated in a number of cerebral disorders as a surrogate marker of clinical outcome. In stroke, unique methodological challenges are posed by dynamic structural changes occurring after onset, particularly those relating to the infarct lesion. We aimed to evaluate agreement between different analysis methods for the measurement of post-stroke brain volume change, and to explore technical challenges inherent to these methods. Fifteen patients with anterior circulation stroke underwent magnetic resonance imaging within 1 week of onset and at 1 and 3 months. Whole-brain as well as grey- and white-matter volume were estimated separately using both an intensity-based and a surface watershed-based algorithm. In the case of the intensity-based algorithm, the analysis was also performed with and without exclusion of the infarct lesion. Due to the effects of peri-infarct edema at the baseline scan, longitudinal volume change was measured as percentage change between the 1 and 3-month scans. Intra-class and concordance correlation coefficients were used to assess agreement between the different analysis methods. Reduced major axis regression was used to inspect the nature of bias between measurements. Overall agreement between methods was modest with strong disagreement between some techniques. Measurements were variably impacted by procedures performed to account for infarct lesions. Improvements in volumetric methods and consensus between methodologies employed in different studies are necessary in order to increase the validity of conclusions derived from post-stroke cerebral volumetric studies. Readers should be aware of the potential impact of different methods on study conclusions. (orig.)

  20. Know your tools - concordance of different methods for measuring brain volume change after ischemic stroke

    International Nuclear Information System (INIS)

    Yassi, Nawaf; Campbell, Bruce C.V.; Davis, Stephen M.; Bivard, Andrew; Moffat, Bradford A.; Steward, Christopher; Desmond, Patricia M.; Churilov, Leonid; Parsons, Mark W.

    2015-01-01

    Longitudinal brain volume changes have been investigated in a number of cerebral disorders as a surrogate marker of clinical outcome. In stroke, unique methodological challenges are posed by dynamic structural changes occurring after onset, particularly those relating to the infarct lesion. We aimed to evaluate agreement between different analysis methods for the measurement of post-stroke brain volume change, and to explore technical challenges inherent to these methods. Fifteen patients with anterior circulation stroke underwent magnetic resonance imaging within 1 week of onset and at 1 and 3 months. Whole-brain as well as grey- and white-matter volume were estimated separately using both an intensity-based and a surface watershed-based algorithm. In the case of the intensity-based algorithm, the analysis was also performed with and without exclusion of the infarct lesion. Due to the effects of peri-infarct edema at the baseline scan, longitudinal volume change was measured as percentage change between the 1 and 3-month scans. Intra-class and concordance correlation coefficients were used to assess agreement between the different analysis methods. Reduced major axis regression was used to inspect the nature of bias between measurements. Overall agreement between methods was modest with strong disagreement between some techniques. Measurements were variably impacted by procedures performed to account for infarct lesions. Improvements in volumetric methods and consensus between methodologies employed in different studies are necessary in order to increase the validity of conclusions derived from post-stroke cerebral volumetric studies. Readers should be aware of the potential impact of different methods on study conclusions. (orig.)

  1. Nutrition for brain recovery after ischemic stroke: an added value to rehabilitation.

    Science.gov (United States)

    Aquilani, Roberto; Sessarego, Paolo; Iadarola, Paolo; Barbieri, Annalisa; Boschi, Federica

    2011-06-01

    In patients who undergo rehabilitation after ischemic stroke, nutrition strategies are adopted to provide tube-fed individuals with adequate nutrition and/or to avoid the body wasting responsible for poor functional outcome and prolonged stay in the hospital. Investigations have documented that nutrition interventions can enhance the recovery of neurocognitive function in individuals with ischemic stroke. Experimental studies have shown that protein synthesis is suppressed in the ischemic penumbra. In clinical studies on rehabilitation patients designed to study the effects of counteracting or limiting this reduction of protein synthesis by providing protein supplementation, patients receiving such supplementation had enhanced recovery of neurocognitive function. Cellular damage in cerebral ischemia is also partly caused by oxidative damage secondary to free radical formation and lipid peroxidation. Increased oxidative stress negatively affects a patient's life and functional prognosis. Some studies have documented that nutrition supplementation with B-group vitamins may mitigate oxidative damage after acute ischemic stroke. Experimental investigations have also shown that cerebral ischemia changes synaptic zinc release and that acute ischemia increases zinc release, aggravating neuronal injury. In clinical practice, patients with ischemic stroke were found to have a lower than recommended dietary intake of zinc. Patients in whom daily zinc intake was normalized had better recovery of neurological deficits than subjects given a placebo. The aim of this review is to highlight those brain metabolic alterations susceptible to nutrition correction in clinical practice. The mechanisms underlying the relationship between cerebral ischemia and nutrition metabolic conditions are discussed.

  2. Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients.

    Science.gov (United States)

    Boggio, Paulo S; Nunes, Alice; Rigonatti, Sergio P; Nitsche, Michael A; Pascual-Leone, Alvaro; Fregni, Felipe

    2007-01-01

    Recent evidence has suggested that a simple technique of noninvasive brain stimulation - transcranial direct current stimulation (tDCS) - is associated with a significant motor function improvement in stroke patients. We tested the motor performance improvement in stroke patients following 4 weekly sessions of sham, anodal- and cathodal tDCS (experiment 1) and the effects of 5 consecutive daily sessions of cathodal tDCS (experiment 2). A blinded rater evaluated motor function using the Jebsen-Taylor Hand Function Test. There was a significant main effect of stimulation condition (p=0.009) in experiment 1. Furthermore there was a significant motor function improvement after either cathodal tDCS of the unaffected hemisphere (p=0.016) or anodal tDCS of the affected hemisphere (p=0.046) when compared to sham tDCS. There was no cumulative effect associated with weekly sessions of tDCS, however consecutive daily sessions of tDCS (experiment 2) were associated with a significant effect on time (pmotor function improvement in stroke patients; and support that consecutive daily sessions of tDCS might increase its behavioral effects. Because the technique of tDCS is simple, safe and non-expensive; our findings support further research on the use of this technique for the rehabilitation of patients with stroke.

  3. Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

    Science.gov (United States)

    Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Sharma, Latisha K; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

    2018-05-01

    The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome. Copyright © 2018 by the American Society of Neuroimaging.

  4. Potential therapeutic and protective effect of curcumin against stroke in the male albino stroke-induced model rats.

    Science.gov (United States)

    Zhang, Yuanyuan; Yan, Yi; Cao, Yi; Yang, Yongtao; Zhao, Qing; Jing, Rui; Hu, Jiayi; Bao, Juan

    2017-08-15

    The present study was carried out to understand the therapeutic effect of curcumin (CUR) against stroke in the experimental animal model. The study investigates the healing effect of CUR on mitochondrial dysfunction and inflammation. Male albino, Wistar strain rats were used for the induction of middle cerebral artery occlusion (MCAO), and reperfusion. Enzyme-linked immunosorbent assay (ELISA) was used for the determination of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the brain region. Western blot analysis was used to determine the protein expression levels of Bax, Bcl-2, p53, and Sirt1. The water level was determined in brain region by using standard method. Experimental results indicated that the use of CUR significantly reduced brain edema and water content. IL-6 and TNF-α were significantly reduced in the brain region following use of CUR. Mitochondrial membrane potential (MMP) also reduced significantly after CUR treatment. Protein expression of p53 and Bax were significantly reduced, whereas Bcl-2 and Sirt1 were increased following CUR treatment. Taking all these data together, it is suggested that the use of CUR may be a potential therapeutic agent for the treatment of stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Revised and updated recommendations for the establishment of primary stroke centers: a summary statement from the brain attack coalition.

    Science.gov (United States)

    Alberts, Mark J; Latchaw, Richard E; Jagoda, Andy; Wechsler, Lawrence R; Crocco, Todd; George, Mary G; Connolly, E S; Mancini, Barbara; Prudhomme, Stephen; Gress, Daryl; Jensen, Mary E; Bass, Robert; Ruff, Robert; Foell, Kathy; Armonda, Rocco A; Emr, Marian; Warren, Margo; Baranski, Jim; Walker, Michael D

    2011-09-01

    The formation and certification of Primary Stroke Centers has progressed rapidly since the Brain Attack Coalition's original recommendations in 2000. The purpose of this article is to revise and update our recommendations for Primary Stroke Centers to reflect the latest data and experience. We conducted a literature review using MEDLINE and PubMed from March 2000 to January 2011. The review focused on studies that were relevant for acute stroke diagnosis, treatment, and care. Original references as well as meta-analyses and other care guidelines were also reviewed and included if found to be valid and relevant. Levels of evidence were added to reflect current guideline development practices. Based on the literature review and experience at Primary Stroke Centers, the importance of some elements has been further strengthened, and several new areas have been added. These include (1) the importance of acute stroke teams; (2) the importance of Stroke Units with telemetry monitoring; (3) performance of brain imaging with MRI and diffusion-weighted sequences; (4) assessment of cerebral vasculature with MR angiography or CT angiography; (5) cardiac imaging; (6) early initiation of rehabilitation therapies; and (7) certification by an independent body, including a site visit and disease performance measures. Based on the evidence, several elements of Primary Stroke Centers are particularly important for improving the care of patients with an acute stroke. Additional elements focus on imaging of the brain, the cerebral vasculature, and the heart. These new elements may improve the care and outcomes for patients with stroke cared for at a Primary Stroke Center.

  6. Radiation-induced brain injury: A review

    Energy Technology Data Exchange (ETDEWEB)

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Wheeler, Kenneth T. [Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Department of Radiology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Chan, Michael D., E-mail: mrobbins@wakehealth.edu [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States)

    2012-07-19

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  7. Radiation-induced brain injury: A review

    International Nuclear Information System (INIS)

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G.; Wheeler, Kenneth T.; Chan, Michael D.

    2012-01-01

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  8. Immunological profile of silent brain infarction and lacunar stroke.

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    Paola Sarchielli

    Full Text Available Neuroinflammation is believed to be involved in the pathophysiological mechanisms of silent brain infarcts (SBI. However, the immunological profile of SBI has been scarcely investigated. In the context of a national research project named SILENCE, aimed at investigating clinical, biochemical and pathogenic features of SBI, we have measured the plasma profile of some inflammatory-related molecules in SBI patients (n = 21, patients with recent lacunar infarcts (LI, n = 28 and healthy controls (n = 31, consecutively enrolled in four Italian centres. A panel of chemokines (MIG, CTACK, IL16, SDF1a, MCP1, growth factors (SCF, SCGFb, HGF, IL3, immunoglobulin-type adhesion molecules (ICAM1, VCAM1, proinflammatory cytokines (IL18, INFa2, MIF, IL12p40, cell surface receptors on T-cells (IL2Ra, and inductors of apoptosis (TRAIL was assessed in plasma samples by Luminex xMAP™ technology. Immunological parameters were compared using non-parametric statistics and performance to distinguish SBI and LI was evaluated by receiver operating characteristic (ROC analysis. Plasma levels of ICAM1 were significantly higher in both SBI and LI patients as compared to controls (SBI≥LI>Ctrl. A different trend was observed for IL16 (SBICtrl, SCF (LICtrl and SCGFb (SBI>LICtrl and IL18 when compared to LI patients (Ctrl≤SBI>LI. All the other immunological markers did not significantly differ among groups. According to ROC analysis, the best predictor for SBI condition was the chemokine MIG (AUC = 0.84, sensitivity 86%, specificity 77%, while SCF had the best performance in distinguishing LI patients (AUC = 0.84, sensitivity 86%, specificity 68%. These results confirm the involvement of inflammatory processes in cerebrovascular disorders, particularly in SBI, a very common age-related condition. The differences in plasma profile of inflammatory molecules may underlie different pathological mechanisms in SBI and LI patients.

  9. Cytokine Response, Tract-Specific Fractional Anisotropy, and Brain Morphometry in Post-Stroke Cognitive Impairment.

    Science.gov (United States)

    Kulesh, Aleksey; Drobakha, Viktor; Kuklina, Elena; Nekrasova, Irina; Shestakov, Vladimir

    2018-07-01

    Post-stroke cognitive impairment is a clinically heterogeneous condition and its types have a different course and prognosis. The aim of the present study is to address the roles of inflammation, white matter pathology, and brain atrophy in different neuropsychological types of cognitive impairment in the acute period of ischemic stroke. In 92 patients, we performed an assessment of the cognitive status and measured concentrations of cytokines (interleukin [IL]-1β, IL-6, tumor necrosis factor-alpha, IL-10) in liquor and serum, as well as a number of magnetic resonance imaging (MRI) morphometric parameters and fractional anisotropy. The control group consisted of 14 individuals without cerebrovascular disease. All patients had a higher level of IL-10 in serum than the control group. Patients with dysexecutive cognitive impairment had a higher concentration of IL-1β and IL-10 in liquor, IL-6 level in serum, and a lower fractional anisotropy of the ipsilateral thalamus than patients with normal cognition. Patients with mixed cognitive impairment were characterized by a lower fractional anisotropy of contralateral fronto-occipital fasciculus, compared with patients with dysexecutive cognitive impairment. Patients with both dysexecutive and mixed cognitive deficit had a wide area of leukoaraiosis and a reduced fractional anisotropy of the contralateral cingulum, compared with patients without cognitive impairment. Also, we found numerous correlations between cognitive status and levels of cytokines, MRI morphometric parameters, and fractional anisotropy of certain regions of the brain. The concentrations of cytokines in serum and cerebrospinal fluid studied in combination with MRI morphometric parameters and fractional anisotropy appear to be informative biomarkers of clinical types of post-stroke cognitive impairment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  10. Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke.

    Science.gov (United States)

    Orbe, J; Alexandru, N; Roncal, C; Belzunce, M; Bibiot, P; Rodriguez, J A; Meijers, J C M; Georgescu, A; Paramo, J A

    2015-08-01

    Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI-/-) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI-/-. to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI-/- mice. Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry. Compared with saline, tPA significantly increased the infarct size in TAFI-/- mice (p<0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI-/- mice (p<0.05). Interestingly, higher numbers of MPs were found in TAFI-/- plasma as compared to wild type, after stroke (p<0.05). TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. EFFECT OF MODIFIED CONSTRAINT INDUCED THERAPY ON UPPERLIMB FUNCTIONAL RECOVERY IN YOUNG STROKE SUBJECTS

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    Kiran Prakash Pappala

    2014-10-01

    Full Text Available Background: The aim of this study is to evaluate the effect of modified constraint induced therapy on upper limb functional recovery in young stroke subjects. Most of the stroke rehabilitation units following conventional rehabilitation methods for treatment of the stroke patients where these methods have been proved to be less useful especially in the young stroke subjects. Hence the purpose of this study is to see the effect of modified constraint induced therapy which is a task specific training method for upperlimb in young stroke subjects. Methods: Total of 40 young stroke subjects who is having minimal motor criterion and met other inclusion criteria were recruited from department of physiotherapy, g.s.l.general hospital. Pre and post intervention measures were taken using Wolf motor function test and Jebsen Taylor hand function test. Results: In this study had shown significant improvements in the modified constraint induced therapy group when compared to the conventional rehabilitation alone. P value between groups was < 0.05. Conclusion: In this study concludes that addition of 15 minutes modified constraint induced movement therapy to conventional physiotherapy is a useful adjunct in functional recovery of upper limb among young stroke subjects

  12. BRAIN NATRIURETIC PEPTIDE (BNP: BIOMARKER FOR RISK STRATIFICATION AND FUNCTIONAL RECOVERY PREDICTION IN ISCHEMIC STROKE

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    STANESCU Ioana

    2015-02-01

    Full Text Available Functional outcome after cardiovascular and cerebrovascular events is traditionally predicted using demographic and clinical variables like age, gender, blood pressure, cholesterol levels, diabetes status, smoking habits or pre-existing morbidity. Identification of new variables will improve the risk stratification of specific categories of patients. Numerous blood-based biomarkers associated with increased cardiovascular risk have been identified; some of them even predict cardiovascular events. Investigators have tried to produce prediction models by incorporating traditional risk factors and biomarkers. (1. Widely-available, rapidly processed and less expensive biomarkers could be used in the future to guide management of complex cerebrovascular patients in order to maximize their recovery (2 Recently, studies have demonstrated that biomarkers can predict not only the risk for a specific clinical event, but also the risk of death of vascular cause and the functional outcome after cardiovascular or cerebrovascular events. Early prediction of fatal outcome after stroke may improve therapeutic strategies (such as the use of more aggressive treatments or inclusion of patients in clinical trials and guide decision-making processes in order to maximize patient’s chances for survival and recovery. (3 Long term functional outcome after stroke is one of the most difficult variables to predict. Elevated serum levels of brain natriuretic peptide (BNP are powerful predictor of outcomes in patients with cardiovascular disease (heart failure, atrial fibrillation. Potential role of BNP in predicting atrial fibrillation occurrence, cardio-embolic stroke and post-stroke mortality have been proved in many studies. However, data concerning the potential role of BNP in predicting short term and long term functional outcomes after stroke remain controversial.

  13. PELATIHAN MIRROR NEURON SYSTEM SAMA DENGAN PELATIHAN CONSTRAINT INDUCED MOVEMENT THERAPY DALAM MENINGKATKAN KEMAMPUAN FUNGSIONAL ANGGOTA GERAK ATAS PASIEN STROKE

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    Abdul chalik meidian

    2014-03-01

    Full Text Available Stroke is an interruption of blood vasculature system in the brain that causes suddenly neurological dysfunction, resulted in clinically brain tissue damage in a relatively long time period, decreased physical mobility and functional ability impaired of upper limb. The purpose of this study is to know an increasing in upper limb functional ability among stroke patients after mirror neuron system exercise and constraint induced movement therapy exercise and to know the comparison of both exercise. This study uses an experimental research with pre-test and post-test control group design. Number of samples of the first group is 13 patients given mirror neuron system exercise for 30-60 minutes , while the second group 13 patients were given constraint induced movement therapy exercise for 30-60 minutes. The research was conducted in 2 month period time. Each patient is taught a variety of upper limb functional ability in accordance with the operational concept guidance and patients were asked to repeat the exercise independently at home as directed. Measuring test of upper limb functional ability is using the wolf motor function test instruments. The result is an increase the upper limb functional ability of 21.7% in the mirror neuron system exercise group and proved a significant difference (p<0.05 and an increase in the upper limb functional ability of 17.1% in the constraint induced movement therapy exercise group and proved a significant difference (p<0.05 while the difference of increasing of upper limb functional ability of the two groups showed no significant difference (p>0,05. It was concluded that the mirror neuron system exercise is similar with constraint induced movement therapy exercise in increasing the upper limb functional ability among stroke patients.

  14. The application of MRI for depiction of subtle blood brain barrier disruption in stroke.

    Science.gov (United States)

    Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

    2010-12-26

    The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in

  15. Attenuating brain inflammation, ischemia, and oxidative damage by hyperbaric oxygen in diabetic rats after heat stroke

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    Kai-Li Lee

    2013-08-01

    Conclusion: Our results suggest that, in diabetic animals, HBO2 therapy may improve outcomes of HS in part by reducing heat-induced activated inflammation and ischemic and oxidative damage in the hypothalamus and other brain regions.

  16. Assessment of brain perfusion with MRI: methodology and application to acute stroke

    International Nuclear Information System (INIS)

    Grandin, C.B.

    2003-01-01

    We review the methodology of brain perfusion measurements with MRI and their application to acute stroke, with particular emphasis on the work awarded by the 6th Lucien Appel Prize for Neuroradiology. The application of the indicator dilution theory to the dynamic susceptibility-weighted bolus-tracking method is explained, as is the approach to obtaining quantitative measurements of cerebral blood flow (CBF) and volume (CBV). Our contribution to methodological developments, such as CBV measurement with the frequency-shifted burst sequence, development of the PRESTO sequence, comparison of different deconvolution methods and of spin- and gradient-echo sequences, and the validation of MRI measurements against positron emission tomography is summarised. The pathophysiology of brain ischaemia and the role of neuroimaging in the setting of acute stroke are reviewed, with an introduction to the concepts of ischaemic penumbra and diffusion/perfusion mismatch. Our work on the determination of absolute CBF and CBV thresholds for predicting the area of infarct growth, identification of the best perfusion parameters (relative or absolute) for predicting the area of infarct growth and the role of MR angiography is also summarised. We conclude that MRI is a very powerful way to assess brain perfusion and that its use might help in selecting patients who will benefit most from treatment such as thrombolysis. (orig.)

  17. Routine physiotherapy does not induce a cardiorespiratory training effect post-stroke, regardless of walking ability.

    Science.gov (United States)

    Kuys, Suzanne; Brauer, Sandra; Ada, Louise

    2006-12-01

    Cardiorespiratory fitness is increasingly being recognized as an impairment requiring physiotherapy intervention after stroke. The present study seeks to investigate if routine physiotherapy treatment is capable of inducing a cardiorespiratory training effect and if stroke patients attending physiotherapy who are unable to walk experience less cardiorespiratory stress during physiotherapy when compared to those who are able to walk. A descriptive, observational study, with heart rate monitoring and video-recording of physiotherapy rehabilitation, was conducted. Thirty consecutive stroke patients from a geriatric and rehabilitation unit of a tertiary metropolitan hospital, admitted for rehabilitation, and requiring physiotherapy were included in the study. The main measures of the study were duration (time) and intensity (percentage of heart rate reserve) of standing and walking activities during physiotherapy rehabilitation for non-walking and walking stroke patients. Stroke patients spent an average of 21 minutes participating in standing and walking activities that were capable of inducing a cardiorespiratory training effect. Stroke patients who were able to walk spent longer in these activities during physiotherapy rehabilitation than non-walking stroke patients (p physiotherapy rehabilitation had insufficient duration and intensity to result in a cardiorespiratory training effect in our group of stroke patients.

  18. Relationship between Brain Lesion Location and Aphasia Type in Persian Speaking Patients with Stroke

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    Hossein Rezai

    2011-01-01

    Full Text Available Objective: It has been many years that brain lesion analysis of different aphasia Syndromes has led the foundation to investigate the language representation and organization in the brain. The aim of this study was to examine the relationship between brain lesion location and Broca's aphasia and Wernecke's aphasia in Persian speakers with stroke. Materials & Methods: In a single system design study, from 120 patients with stroke attending Emam Khomeyni and Loghman hospitals, Rofeyde, Karaj neurology, and Tabassom speech clinics and according to the Farsi Aphasia Test (FAT, syntactic comprehension subscale of Bilingual Aphasia Test (BAT, Farsi Aphasia Naming Test, and Apraxia Assessment inventory, only 9 patients with Broca’s aphasia and 2 with Wernicke’s aphasia were qualified to participate in this study. Patients’ brain lesion sites were determined by MRI. Patients with Broca’s aphasia were 5 male and 4 female Wernecke’s aphasia patients were 2 male. Results: External capsule-insula, rolandic operculum, inferior frontal gyrus, (precentral gyrus and postcentarl gyrus, and the anterior part of temporal gyrus were damaged in Broca’s aphasia patients (64±12.51 years old and the lesions of external capsule-insula, posterior part of temporal gyrus, anterior part of temporal gyrus, inferior parietal lobule were observed in Wernicke’s aphasia patients (66±8.48 years old. Conclusion: In no patient with Broca’s aphasia or Wernicke’s aphasia brain lesion confined only to Broca’s area or Wernicke’s area respectively. However, due to the limited number of participants in the present study, the extrapolation of the findings to other subjects with Broca’s or Wernicke’s aphasia would certainly be difficult.

  19. An emboligenic pulmonary abscess leading to ischemic stroke and secondary brain abscess

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    Albrecht Philipp

    2012-11-01

    Full Text Available Abstract Background Ischemic stroke by septic embolism occurs primarily in the context of infective endocarditis or in patients with a right-to-left shunt and formation of a secondary cerebral abscess is a rare event. Erosion of pulmonary veins by a pulmonary abscess can lead to transcardiac septic embolism but to our knowledge no case of septic embolic ischemic stroke from a pulmonary abscess with secondary transformation into a brain abscess has been reported to date. Case presentation We report the case of a patient with a pulmonary abscess causing a septic embolic cerebral infarction which then transformed into a cerebral abscess. After antibiotic therapy and drainage of the abscess the patient could be rehabilitated and presented an impressive improvement of symptoms. Conclusion Septic embolism should be considered as cause of ischemic stroke in patients with pulmonary abscess and can be followed by formation of a secondary cerebral abscess. Early antibiotic treatment and repeated cranial CT-scans for detection of a secondary abscess should be performed.

  20. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature.

    Science.gov (United States)

    Kleinschnitz, Christoph; Kraft, Peter; Dreykluft, Angela; Hagedorn, Ina; Göbel, Kerstin; Schuhmann, Michael K; Langhauser, Friederike; Helluy, Xavier; Schwarz, Tobias; Bittner, Stefan; Mayer, Christian T; Brede, Marc; Varallyay, Csanad; Pham, Mirko; Bendszus, Martin; Jakob, Peter; Magnus, Tim; Meuth, Sven G; Iwakura, Yoichiro; Zernecke, Alma; Sparwasser, Tim; Nieswandt, Bernhard; Stoll, Guido; Wiendl, Heinz

    2013-01-24

    We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke and this protective effect was preserved at later stages of infarct development. The specificity of this detrimental Treg effect was confirmed by adoptive transfer experiments in wild-type mice and in Rag1(-/-) mice lacking lymphocytes. Mechanistically, Tregs induced microvascular dysfunction in vivo by increased interaction with the ischemic brain endothelium via the LFA-1/ICAM-1 pathway and platelets and these findings were confirmed in vitro. Ablation of Tregs reduced microvascular thrombus formation and improved cerebral reperfusion on stroke, as revealed by ultra-high-field magnetic resonance imaging at 17.6 Tesla. In contrast, established immunoregulatory characteristics of Tregs had no functional relevance. We define herein a novel and unexpected role of Tregs in a primary nonimmunologic disease state.

  1. Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke.

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    Zahra Hassani

    Full Text Available Stem cell transplantation is to date one of the most promising therapies for chronic ischemic stroke. The human conditionally immortalised neural stem cell line, CTX0E03, has demonstrable efficacy in a rodent model of stroke and is currently in clinical trials. Nonetheless, the mechanisms by which it promotes brain repair are not fully characterised. This study investigated the cellular events occurring after CTX0E03 transplantation in the brains of rats that underwent ischemic stroke.We focused on the endogenous proliferative activity of the host brain in response to cell transplantation and determined the identity of the proliferating cells using markers for young neurons (doublecortin, Dcx and microglia (CD11b. So as to determine the chronology of events occurring post-transplantation, we analysed the engrafted brains one week and four weeks post-transplantation.We observed a significantly greater endogenous proliferation in the striatum of ischemic brains receiving a CTX0E03 graft compared to vehicle-treated ischemic brains. A significant proportion of these proliferative cells were found to be Dcx+ striatal neuroblasts. Further, we describe an enhanced immune response after CTX0E03 engraftment, as shown by a significant increase of proliferating CD11b+ microglial cells.Our study demonstrates that few Dcx+ neuroblasts are proliferative in normal conditions, and that this population of proliferative neuroblasts is increased in response to stroke. We further show that CTX0E03 transplantation after stroke leads to the maintenance of this proliferative activity. Interestingly, the preservation of neuronal proliferative activity upon CTX0E03 transplantation is preceded and accompanied by a high rate of proliferating microglia. Our study suggests that microglia might mediate in part the effect of CTX0E03 transplantation on neuronal proliferation in ischemic stroke conditions.

  2. The 'Hub Disruption Index', a reliable index sensitive to the brain networks reorganization. A study of the contralesional hemisphere in stroke

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    Maite Termenon

    2016-08-01

    Full Text Available Stroke, resulting in focal structural damage, induces changes in brain function at both local and global levels. Following stroke, cerebral networks present structural and functional reorganization to compensate for the dysfunctioning provoked by the lesion itself and its remote effects. As some recent studies underlined the role of the contralesional hemisphere during recovery, we studied its role %of the contralesional hemispherein the reorganization of brain function of stroke patients using resting state fMRI and graph theory. We explored this reorganization using the 'hub disruption index' (kappa, a global index sensitive to the reorganization of nodes within the graph. For a given graph metric, kappa of a subject corresponds to the slope of the linear regression model between the mean local network measures of a reference group, and the difference between that reference and the subject under study. In order to translate the use of kappa in clinical context, a prerequisite to achieve meaningful results is to investigate the reliability of this index. In a preliminary part, we studied the reliability of kappa by computing the intraclass correlation coefficient in a cohort of 100 subjects from the Human Connectome Project. Then, we measured intra-hemispheric kappa index in the contralesional hemisphere of 20 subacute stroke patients compared to 20 age-matched healthy controls. Finally, due to the small number of patients, we tested the robustness of our results repeating the experiment 1000 times by bootstrapping on the Human Connectome Project database. Statistical analysis showed a significant reduction of kappa for the contralesional hemisphere of right stroke patients compared to healthy controls. Similar results were observed for the right contralesional hemisphere of left stroke patients. We showed that kappa, is more reliable than global graph metrics and more sensitive to detect differences between groups of patients as compared to

  3. Non-invasive brain stimulation for fine motor improvement after stroke: a meta-analysis.

    Science.gov (United States)

    O'Brien, A T; Bertolucci, F; Torrealba-Acosta, G; Huerta, R; Fregni, F; Thibaut, A

    2018-05-09

    The aim of this study was to determine whether non-invasive brain stimulation (NIBS) techniques improve fine motor performance in stroke. We searched PubMed, EMBASE, Web of Science, SciELO and OpenGrey for randomized clinical trials on NIBS for fine motor performance in stroke patients and healthy participants. We computed Hedges' g for active and sham groups, pooled data as random-effects models and performed sensitivity analysis on chronicity, montage, frequency of stimulation and risk of bias. Twenty-nine studies (351 patients and 152 healthy subjects) were reviewed. Effect sizes in stroke populations for transcranial direct current stimulation and repeated transcranial magnetic stimulation were 0.31 [95% confidence interval (CI), 0.08-0.55; P = 0.010; Tau 2 , 0.09; I 2 , 34%; Q, 18.23; P = 0.110] and 0.46 (95% CI, 0.00-0.92; P = 0.05; Tau 2 , 0.38; I 2 , 67%; Q, 30.45; P = 0.007). The effect size of non-dominant healthy hemisphere transcranial direct current stimulation on non-dominant hand function was 1.25 (95% CI, 0.09-2.41; P = 0.04; Tau 2 , 1.26; I 2 , 93%; Q, 40.27; P < 0.001). Our results show that NIBS is associated with gains in fine motor performance in chronic stroke patients and healthy subjects. This supports the effects of NIBS on motor learning and encourages investigation to optimize their effects in clinical and research settings. © 2018 EAN.

  4. FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Artzi, Moran, E-mail: artzimy@gmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Aizenstein, Orna, E-mail: ornaaize@gmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Jonas-Kimchi, Tali, E-mail: talijk@tlvmc.gov.il [Radiology Department, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Myers, Vicki, E-mail: vicki_myers@hotmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Hallevi, Hen, E-mail: hen.hallevi@gmail.com [Neurology Department, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Ben Bashat, Dafna, E-mail: dafnab@tlvmc.gov.il [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-09-15

    Background: Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methods: FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. Results: FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. Conclusion: This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice.

  5. FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

    International Nuclear Information System (INIS)

    Artzi, Moran; Aizenstein, Orna; Jonas-Kimchi, Tali; Myers, Vicki; Hallevi, Hen; Ben Bashat, Dafna

    2013-01-01

    Background: Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methods: FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. Results: FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. Conclusion: This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice

  6. Shortened constraint-induced movement therapy in subacute stroke - no effect of using a restraint

    DEFF Research Database (Denmark)

    Brogårdh, Christina; Vestling, Monika; Sjölund, Bengt H

    2009-01-01

    OBJECTIVE: To examine the effect of using a mitt during shortened constraint-induced movement therapy for patients in the subacute phase after stroke. SUBJECTS: Twenty-four patients with stroke (mean age 57.6 (standard deviation (SD) 8.5) years; average 7 weeks post-stroke) with mild to moderate......, no statistically significant differences between the groups were found in any measures at any point in time. CONCLUSION: In this study, no effect of using a restraint in patients with subacute stroke was found. Thus, this component in the constraint-induced therapy concept seems to be of minor importance...... Scale, the Sollerman hand function test, the 2-Point Discrimination test and Motor Activity Log test. RESULTS: Patients in both groups showed significant improvements in arm and hand motor performance and on self-reported motor ability after 2 weeks of therapy and at 3 months follow-up. However...

  7. Effects of virtual reality-based bilateral upper-extremity training on brain activity in post-stroke patients.

    Science.gov (United States)

    Lee, Su-Hyun; Kim, Yu-Mi; Lee, Byoung-Hee

    2015-07-01

    [Purpose] This study investigated the therapeutic effects of virtual reality-based bilateral upper-extremity training on brain activity in patients with stroke. [Subjects and Methods] Eighteen chronic stroke patients were divided into two groups: the virtual reality-based bilateral upper-extremity training group (n = 10) and the bilateral upper-limb training group (n = 8). The virtual reality-based bilateral upper-extremity training group performed bilateral upper-extremity exercises in a virtual reality environment, while the bilateral upper-limb training group performed only bilateral upper-extremity exercise. All training was conducted 30 minutes per day, three times per week for six weeks, followed by brain activity evaluation. [Results] Electroencephalography showed significant increases in concentration in the frontopolar 2 and frontal 4 areas, and significant increases in brain activity in the frontopolar 1 and frontal 3 areas in the virtual reality-based bilateral upper-extremity training group. [Conclusion] Virtual reality-based bilateral upper-extremity training can improve the brain activity of stroke patients. Thus, virtual reality-based bilateral upper-extremity training is feasible and beneficial for improving brain activation in stroke patients.

  8. Xylometazoline abuse induced ischemic stroke in a young adult.

    Science.gov (United States)

    Leupold, Daniela; Wartenberg, Katja E

    2011-01-01

    substance abuse is an important cause of ischemic stroke in the young. This includes over-the-counter dietary supplements and cough and cold remedies, which were reported to be an independent risk factor for hemorrhagic stroke. this article describes a young male patient with acute ischemic infarctions in the posterior inferior cerebellar and posterior cerebral artery territories bilaterally, the right cerebral peduncle, the left pontine tegmentum, and lateral pons following abuse of xylometazoline-containing nasal decongestant for 10 years. this is the first report in the literature of posterior circulation strokes because of chronic xylometazoline abuse. We hope to contribute to increase knowledge and awareness of the public about these serious complications of cough-and-cold remedies as well as dietary supplements containing sympathomimetics.

  9. Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association.

    Science.gov (United States)

    Gorelick, Philip B; Furie, Karen L; Iadecola, Costantino; Smith, Eric E; Waddy, Salina P; Lloyd-Jones, Donald M; Bae, Hee-Joon; Bauman, Mary Ann; Dichgans, Martin; Duncan, Pamela W; Girgus, Meighan; Howard, Virginia J; Lazar, Ronald M; Seshadri, Sudha; Testai, Fernando D; van Gaal, Stephen; Yaffe, Kristine; Wasiak, Hank; Zerna, Charlotte

    2017-10-01

    Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHA's Life's Simple 7: 4 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHA's Life's Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHA's Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health

  10. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

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    Mónica Millán

    2008-01-01

    Full Text Available Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA.

  11. Brain stimulation and constraint for perinatal stroke hemiparesis: The PLASTIC CHAMPS Trial.

    Science.gov (United States)

    Kirton, Adam; Andersen, John; Herrero, Mia; Nettel-Aguirre, Alberto; Carsolio, Lisa; Damji, Omar; Keess, Jamie; Mineyko, Aleksandra; Hodge, Jacquie; Hill, Michael D

    2016-05-03

    To determine whether the addition of repetitive transcranial magnetic stimulation (rTMS) and/or constraint-induced movement therapy (CIMT) to intensive therapy increases motor function in children with perinatal stroke and hemiparesis. A factorial-design, blinded, randomized controlled trial (clinicaltrials.gov/NCT01189058) assessed rTMS and CIMT effects in hemiparetic children (aged 6-19 years) with MRI-confirmed perinatal stroke. All completed a 2-week, goal-directed, peer-supported motor learning camp randomized to daily rTMS, CIMT, both, or neither. Primary outcomes were the Assisting Hand Assessment and the Canadian Occupational Performance Measure at baseline, and 1 week, 2 and 6 months postintervention. Outcome assessors were blinded to treatment. Interim safety analyses occurred after 12 and 24 participants. Intention-to-treat analysis examined treatment effects over time (linear mixed effects model). All 45 participants completed the trial. Addition of rTMS, CIMT, or both doubled the chances of clinically significant improvement. Assisting Hand Assessment gains at 6 months were additive and largest with rTMS + CIMT (β coefficient = 5.54 [2.57-8.51], p = 0.0004). The camp alone produced large improvements in Canadian Occupational Performance Measure scores, maximal at 6 months (Cohen d = 1.6, p = 0.002). Quality-of-life scores improved. Interventions were well tolerated and safe with no decrease in function of either hand. Hemiparetic children participating in intensive, psychosocial rehabilitation programs can achieve sustained functional gains. Addition of CIMT and rTMS increases the chances of improvement. This study provides Class II evidence that combined rTMS and CIMT enhance therapy-induced functional motor gains in children with stroke-induced hemiparetic cerebral palsy. © 2016 American Academy of Neurology.

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

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    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.

  13. New approach to detect and classify stroke in skull CT images via analysis of brain tissue densities.

    Science.gov (United States)

    Rebouças Filho, Pedro P; Sarmento, Róger Moura; Holanda, Gabriel Bandeira; de Alencar Lima, Daniel

    2017-09-01

    Cerebral vascular accident (CVA), also known as stroke, is an important health problem worldwide and it affects 16 million people worldwide every year. About 30% of those that have a stroke die and 40% remain with serious physical limitations. However, recovery in the damaged region is possible if treatment is performed immediately. In the case of a stroke, Computed Tomography (CT) is the most appropriate technique to confirm the occurrence and to investigate its extent and severity. Stroke is an emergency problem for which early identification and measures are difficult; however, computer-aided diagnoses (CAD) can play an important role in obtaining information imperceptible to the human eye. Thus, this work proposes a new method for extracting features based on radiological density patterns of the brain, called Analysis of Brain Tissue Density (ABTD). The proposed method is a specific approach applied to CT images to identify and classify the occurrence of stroke diseases. The evaluation of the results of the ABTD extractor proposed in this paper were compared with extractors already established in the literature, such as features from Gray-Level Co-Occurrence Matrix (GLCM), Local binary patterns (LBP), Central Moments (CM), Statistical Moments (SM), Hu's Moment (HM) and Zernike's Moments (ZM). Using a database of 420 CT images of the skull, each extractor was applied with the classifiers such as MLP, SVM, kNN, OPF and Bayesian to classify if a CT image represented a healthy brain or one with an ischemic or hemorrhagic stroke. ABTD had the shortest extraction time and the highest average accuracy (99.30%) when combined with OPF using the Euclidean distance. Also, the average accuracy values for all classifiers were higher than 95%. The relevance of the results demonstrated that the ABTD method is a useful algorithm to extract features that can potentially be integrated with CAD systems to assist in stroke diagnosis. Copyright © 2017 Elsevier B.V. All rights

  14. UCAO (UNILATERAL CEREBRAL ARTERY OCCLUSSION METHOD INCREASES THE LEVEL OF MMP- 9 BRAIN TISSUE IN RATS MODEL OF ISCHEMIC STROKE

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    M. Rasjad Indra

    2016-07-01

    Full Text Available Background. For the last 5 years, 15.4% of total population died because of stroke, which 42.9% of those are caused by ischemic stroke. UCAO (Unilateral Cerebral Artery Occlusion is a stroke induction method by ligating mice’s carotid artery for 45 minutes. Thus, giving a hypoxic condition similar to stroke attack in human. This method is less complicated and far more efficient. MMP-9 is a stroke marker which is assayed by ELISA from the blood of test animal. Objective. This research was conducted to prove UCAO (Unilateral Cerebral Artery Occlusion method is capable to raise MMP-9 concentration in mice’s blood. Methods. This research was an experimental laboratory research with post-test only controlled group design. 8 male rats (8-10 weeks were divided into 2 groups, control and treatment which would be inducted into stroke by UCAO method. A day after the treatment group had been induced to stroke, both group were tested to measure the MMP-9 blood concentration through ELISA. Results. In this research, UCAO method had increased MMP-9 blood concentration in treatment group, compared to the control group. It is proved by the statistic tests, Mann-Whitney and Kruskal-Wallis, which showed a significant increase in treatment group (p < 0.05. Conclusion. Based on this result, it can be concluded that UCAO method is accepted as a method to create an ischemic stroke mice model.

  15. Succinate-induced neuronal mitochondrial fission and hexokinase II malfunction in ischemic stroke: Therapeutical effects of kaempferol.

    Science.gov (United States)

    Wu, Bin; Luo, Hong; Zhou, Xu; Cheng, Cai-Yi; Lin, Lin; Liu, Bao-Lin; Liu, Kang; Li, Ping; Yang, Hua

    2017-09-01

    Mitochondrial dysfunction is known as one of causative factors in ischemic stroke, leading to neuronal cell death. The present work was undertaken to investigate whether succinate induces neuron apoptosis by regulating mitochondrial morphology and function. In neurons, oxygen-glucose deprivation induced succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation, leading to mitochondrial fission. Kaempferol inhibited mitochondrial fission and maintained mitochondrial HK-II through activation of Akt, and thereby protected neurons from succinate-mediated ischemi injury. Knockdown of Akt2 with siRNA diminished the effect of kaempferol, indicating that kaempferol suppressed dynamin-related protein 1 (Drp1) activation and promoted HK-II mitochondrial binding dependently on Akt. Moreover, we demonstrated that kaempferol potentiated autophagy during oxygen and glucose deprivation, contributing to protecting neuron survival against succinate insult. In vivo, oral administration of kaempferol in mice attenuated the infract volume after ischemic and reperfusion (I/R) injury and reproduced the similar mitochondrial protective effect in the brain infract area. This study indicates that succinate accumulation plays a pivotal role in I/R injury-induced neuronal mitochondrial dysfunction, and suggests that modulation of Drp1 phosphorylation might be potential therapeutic strategy to protect neuron mitochondrial integrity and treat ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery.

    Science.gov (United States)

    Kubis, Nathalie

    2016-01-01

    Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS) and prognosis has been established according to the presence of motor evoked potentials (MEP) at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS) have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤1 Hz), aiming to reduce excitability of the contralateral homonymous cortex, or combined therapies

  17. The Influence of Acute Hyperglycemia in an Animal Model of Lacunar Stroke That Is Induced by Artificial Particle Embolization

    Science.gov (United States)

    Tsai, Ming-Jun; Lin, Ming-Wei; Huang, Yaw-Bin; Kuo, Yu-Min; Tsai, Yi-Hung

    2016-01-01

    Animal and clinical studies have revealed that hyperglycemia during ischemic stroke increases the stroke's severity and the infarct size in clinical and animal studies. However, no conclusive evidence demonstrates that acute hyperglycemia worsens post-stroke outcomes and increases infarct size in lacunar stroke. In this study, we developed a rat model of lacunar stroke that was induced via the injection of artificial embolic particles during full consciousness. We then used this model to compare the acute influence of hyperglycemia in lacunar stroke and diffuse infarction, by evaluating neurologic behavior and the rate, size, and location of the infarction. The time course of the neurologic deficits was clearly recorded from immediately after induction to 24 h post-stroke in both types of stroke. We found that acute hyperglycemia aggravated the neurologic deficit in diffuse infarction at 24 h after stroke, and also aggravated the cerebral infarct. Furthermore, the infarct volumes of the basal ganglion, thalamus, hippocampus, and cerebellum but not the cortex were positively correlated with serum glucose levels. In contrast, acute hyperglycemia reduced the infarct volume and neurologic symptoms in lacunar stroke within 4 min after stroke induction, and this effect persisted for up to 24 h post-stroke. In conclusion, acute hyperglycemia aggravated the neurologic outcomes in diffuse infarction, although it significantly reduced the size of the cerebral infarct and improved the neurologic deficits in lacunar stroke. PMID:27226775

  18. Cognitive and Neurophysiological Effects of Non-invasive Brain Stimulation in Stroke Patients after Motor Rehabilitation.

    Science.gov (United States)

    D'Agata, Federico; Peila, Elena; Cicerale, Alessandro; Caglio, Marcella M; Caroppo, Paola; Vighetti, Sergio; Piedimonte, Alessandro; Minuto, Alice; Campagnoli, Marcello; Salatino, Adriana; Molo, Maria T; Mortara, Paolo; Pinessi, Lorenzo; Massazza, Giuseppe

    2016-01-01

    The primary aim of this study was to evaluate and compare the effectiveness of two specific Non-Invasive Brain Stimulation (NIBS) paradigms, the repetitive Transcranial Magnetic Stimulation (rTMS), and transcranial Direct Current Stimulation (tDCS), in the upper limb rehabilitation of patients with stroke. Short and long term outcomes (after 3 and 6 months, respectively) were evaluated. We measured, at multiple time points, the manual dexterity using a validated clinical scale (ARAT), electroencephalography auditory event related potentials, and neuropsychological performances in patients with chronic stroke of middle severity. Thirty four patients were enrolled and randomized. The intervention group was treated with a NIBS protocol longer than usual, applying a second cycle of stimulation, after a washout period, using different techniques in the two cycles (rTMS/tDCS). We compared the results with a control group treated with sham stimulation. We split the data analysis into three studies. In this first study we examined if a cumulative effect was clinically visible. In the second study we compared the effects of the two techniques. In the third study we explored if patients with minor cognitive impairment have most benefit from the treatment and if cognitive and motor outcomes were correlated. We found that the impairment in some cognitive domains cannot be considered an exclusion criterion for rehabilitation with NIBS. ERP improved, related to cognitive and attentional processes after stimulation on the motor cortex, but transitorily. This effect could be linked to the restoration of hemispheric balance or by the effects of distant connections. In our study the effects of the two NIBS were comparable, with some advantages using tDCS vs. rTMS in stroke rehabilitation. Finally we found that more than one cycle (2-4 weeks), spaced out by washout periods, should be used, only in responder patients, to obtain clinical relevant results.

  19. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  20. Pretreatment with Shuanghe-Tang Extract Attenuates Postischemic Brain Injury and Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui Bogam

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    Min Jae Kim

    2018-01-01

    Full Text Available Aim. Although stroke is among the leading causes of death and long-term disability, there are few effective treatments for limiting the severity of neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke symptoms in a mouse model of cerebral ischemia. Methods. Focal cerebral ischemia was induced via photothrombosis. Infarct volume, brain edema, and neurological deficits were evaluated. Immunofluorescence staining for tight junction proteins and aquaporin 4 (AQP4 was performed following ischemic injury. Results. Based on our initial findings, we examined the effects of two prescriptions in which the candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct volume, decreased blood-brain barrier (BBB breakdown, attenuated edema, and improved neurological and motor functions in a dose-dependent manner (30, 100, and 300 mg/kg, while no such effects were observed in mice pretreated with Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in ipsilateral occludin and zonula occludens 1 (ZO-1 expression in Shuanghe-tang-pretreated mice, as well as increased AQP4 immunofluorescence. Conclusions. These results indicate that Shuanghe-tang may protect against brain injury and promote recovery of neurological function following ischemia.

  1. Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice.

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    Hong-Jhang Chen

    Full Text Available Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD, a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877, 1.71% (15/877, and 2.62% (23/877 of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood-brain barrier (BBB (Alb, Fga, and Trf, suppressed excitotoxicity (Grm5, Gnai, and Gdi, and enhanced energy metabolism (Bdh, thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3 and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.

  2. Cryptogenic Stroke

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    Mohammad Saadatnia

    2017-02-01

    Full Text Available Cryptogenic stroke is defined as brain infarction that is not attributable to a source of definite embolism, large artery atherosclerosis, or small artery disease despite a thorough vascular, cardiac, and serologic evaluation. Despite many advances in our understanding of ischemic stroke, cryptogenic strokes remain a diagnostic and therapeutic challenge. The pathophysiology of cryptogenic stroke is likely various. Probable mechanisms include cardiac embolism secondary to occult paroxysmal atrial fibrillation, aortic atheromatous disease or other cardiac sources, paradoxical embolism from atrial septal abnormalities such as patent foramen ovale, hypercoagulable states, and preclinical or subclinical cerebrovascular disease.  Cryptogenic stroke is one-fourth among cerebral infarction, but most of them could be ascribed to embolic stroke. A significant proportion of cryptogenic strokes adhere to embolic infarct topography on brain imaging and improvement in our ability to detect paroxysmal atrial fibrillation in patients with cryptogenic stroke has strengthened the idea that these strokes are embolic in nature. a significant proportion of cryptogenic strokes adhere to embolic infarct topography on brain imaging.embolic stroke of undetermined sources(ESUS was planned for unifying embolic stroke of undetermined source.  The etiologies underlying ESUS included minor-risk potential cardioembolic sources, covert paroxysmal atrial fibrillation, cancer-associated coagulopathy and embolism, arteriogenic emboli, and paroxysmal embolism. Extensive evaluation including transesophageal echocardiography and cardiac monitoring for long time could identify the etiology of these patients. Therefore cryptogenic stroke is a diagnosis of exclusion. Compared with other stroke subtypes, cryptogenic stroke tends to have a better prognosis and lower long-term risk of recurrence.

  3. Role of neuroinflammation in ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Rui Liu; Meng-Xian Pan; Jun-Chun Tang; Ya Zhang; Hua-Bao Liao; Yang Zhuang; Dan Zhao; Qi Wan

    2017-01-01

    Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia participates in the neuroinflammatory process by phagocytosing the injured brain cells and producing the pro- and anti-inflammatory mediators. In this review, the authors present an overview of the role of microglia in mediating neuroinflammation in ischemic stroke.

  4. In vivo bioimpedance measurement of healthy and ischaemic rat brain: implications for stroke imaging using electrical impedance tomography

    International Nuclear Information System (INIS)

    Dowrick, T; Blochet, C; Holder, D

    2015-01-01

    In order to facilitate the imaging of haemorrhagic and ischaemic stroke using frequency difference electrical impedance tomography (EIT), impedance measurements of normal and ischaemic brain, and clotted blood during haemorrhage, were gathered using a four-terminal technique in an in vivo animal model, a first for ischaemic measurements. Differences of 5–10% in impedance were seen between the frequency spectrums of healthy and ischaemic brain, over the frequency range 0–3 kHz, while the spectrum of blood was predominately uniform. The implications of imaging blood/ischaemia in the brain using electrical impedance tomography are discussed, supporting the notion that it will be possible to differentiate stroke from haemorrhage. (paper)

  5. Interventions for dysarthria due to stroke and other adult-acquired, non-progressive brain injury.

    Science.gov (United States)

    Mitchell, Claire; Bowen, Audrey; Tyson, Sarah; Butterfint, Zoe; Conroy, Paul

    2017-01-25

    Dysarthria is an acquired speech disorder following neurological injury that reduces intelligibility of speech due to weak, imprecise, slow and/or unco-ordinated muscle control. The impact of dysarthria goes beyond communication and affects psychosocial functioning. This is an update of a review previously published in 2005. The scope has been broadened to include additional interventions, and the title amended accordingly. To assess the effects of interventions to improve dysarthric speech following stroke and other non-progressive adult-acquired brain injury such as trauma, infection, tumour and surgery. We searched the Cochrane Stroke Group Trials Register (May 2016), CENTRAL (Cochrane Library 2016, Issue 4), MEDLINE, Embase, and CINAHL on 6 May 2016. We also searched Linguistics and Language Behavioral Abstracts (LLBA) (1976 to November 2016) and PsycINFO (1800 to September 2016). To identify further published, unpublished and ongoing trials, we searched major trials registers: WHO ICTRP, the ISRCTN registry, and ClinicalTrials.gov. We also handsearched the reference lists of relevant articles and contacted academic institutions and other researchers regarding other published, unpublished or ongoing trials. We did not impose any language restrictions. We selected randomised controlled trials (RCTs) comparing dysarthria interventions with 1) no intervention, 2) another intervention for dysarthria (this intervention may differ in methodology, timing of delivery, duration, frequency or theory), or 3) an attention control. Three review authors selected trials for inclusion, extracted data, and assessed risk of bias. We attempted to contact study authors for clarification and missing data as required. We calculated standardised mean difference (SMD) and 95% confidence interval (CI), using a random-effects model, and performed sensitivity analyses to assess the influence of methodological quality. We planned to conduct subgroup analyses for underlying clinical

  6. Brain Natriuretic Peptide Is a Powerful Predictor of Outcome in Stroke Patients with Atrial Fibrillation

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    Kenji Maruyama

    2017-03-01

    Full Text Available Background: Since stroke patients with nonvalvular atrial fibrillation (NVAF have poor outcomes in general, the prediction of outcomes following discharge is of utmost concern for these patients. We previously reported that brain natriuretic peptide (BNP levels were significantly higher in NVAF patients with larger infarcts, higher modified Rankin Scale (mRS score, and higher CHADS2 score. In the present study, we evaluated an array of variables, including BNP, in order to determine significant predictors for functional outcome in patients with NVAF after acute ischemic stroke (AIS. Methods: A total of 615 consecutive patients with AIS within 48 h of symptom onset, admitted to our hospital between April 2010 and October 2015, were retrospectively searched. Among these patients, we enrolled consecutive patients with NVAF. We evaluated the mRS score 3 months after onset of stroke and investigated associations between mRS score and the following clinical and echocardiographic variables. Categorical variables included male sex, current smoking, alcohol intake, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, peripheral artery disease, use of antiplatelet drugs, anticoagulants, or tissue plasminogen activator (tPA, and infarct size. Continuous variables included age, systolic blood pressure (SBP, diastolic blood pressure, hemoglobin, creatinine, D-dimer, brain natriuretic peptide (BNP, left atrial diameter, left ventricular ejection fraction (EF, and early mitral inflow velocity/diastolic mitral annular velocity (E/e’. We also analyzed the association of prestroke CHADS2, CHA2DS2-VASc, and R2CHADS2 scores, and National Institutes of Health Stroke Scale (NIHSS score on admission with mRS score 3 months after the onset of stroke. Patients were classified into 2 groups according to mRS score: an mRS score ≤2 was defined as good outcome, an mRS score ≥3 was defined as poor outcome. To clarify the correlations between

  7. Neuroprotective effect of Feronia limonia on ischemia reperfusion induced brain injury in rats.

    Science.gov (United States)

    Rakhunde, Purushottam B; Saher, Sana; Ali, Syed Ayaz

    2014-01-01

    Brain stroke is a leading cause of death without effective treatment. Feronia limonia have potent antioxidant activity and can be proved as neuroprotective against ischemia-reperfusion induced brain injury. We studied the effect of methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) and Vitamin E as reference standard drug on 30 min induced ischemia, followed by reperfusion by testing the neurobehavioral tests such as neurodeficit score, rota rod test, hanging wire test, beam walk test and elevated plus maze. The biochemical parameters, which were measured in animals brain were catalase, superoxide dismutase (SOD), malondialdehyde and nitric oxide in control and treated rats. The methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) treated groups showed a statistically significant improvement in the neurobehavioral parameters such as motor performance (neurological status, significant increase in grasping ability, forelimb strength improvement in balance and co-ordination). The biochemical parameters in the brains of rats showed a significant reduction in the total nitrite (P < 0.01) and lipid peroxidation (P < 0.01), also a significant enhanced activity of enzymatic antioxidants such as catalase (P < 0.01) and SOD (P < 0.05). These observations suggest the neuroprotective and antioxidant activity of F. limonia and Vitamin E on ischemia reperfusion induced brain injury and may require further evaluation.

  8. Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient.

    Science.gov (United States)

    Datta, Abhishek; Baker, Julie M; Bikson, Marom; Fridriksson, Julius

    2011-07-01

    Although numerous published reports have demonstrated the beneficial effects of transcranial direct-current stimulation (tDCS) on task performance, fundamental questions remain regarding the optimal electrode configuration on the scalp. Moreover, it is expected that lesioned brain tissue will influence current flow and should therefore be considered (and perhaps leveraged) in the design of individualized tDCS therapies for stroke. The current report demonstrates how different electrode configurations influence the flow of electrical current through brain tissue in a patient who responded positively to a tDCS treatment targeting aphasia. The patient, a 60-year-old man, sustained a left hemisphere ischemic stroke (lesion size = 87.42 mL) 64 months before his participation. In this study, we present results from the first high-resolution (1 mm(3)) model of tDCS in a brain with considerable stroke-related damage; the model was individualized for the patient who received anodal tDCS to his left frontal cortex with the reference cathode electrode placed on his right shoulder. We modeled the resulting brain current flow and also considered three additional reference electrode positions: right mastoid, right orbitofrontal cortex, and a "mirror" configuration with the anode over the undamaged right cortex. Our results demonstrate the profound effect of lesioned tissue on resulting current flow and the ability to modulate current pattern through the brain, including perilesional regions, through electrode montage design. The complexity of brain current flow modulation by detailed normal and pathologic anatomy suggest: (1) That computational models are critical for the rational interpretation and design of individualized tDCS stroke-therapy; and (2) These models must accurately reproduce head anatomy as shown here. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Using non-invasive brain stimulation to augment motor training-induced plasticity

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    Pascual-Leone Alvaro

    2009-03-01

    Full Text Available Abstract Therapies for motor recovery after stroke or traumatic brain injury are still not satisfactory. To date the best approach seems to be the intensive physical therapy. However the results are limited and functional gains are often minimal. The goal of motor training is to minimize functional disability and optimize functional motor recovery. This is thought to be achieved by modulation of plastic changes in the brain. Therefore, adjunct interventions that can augment the response of the motor system to the behavioural training might be useful to enhance the therapy-induced recovery in neurological populations. In this context, noninvasive brain stimulation appears to be an interesting option as an add-on intervention to standard physical therapies. Two non-invasive methods of inducing electrical currents into the brain have proved to be promising for inducing long-lasting plastic changes in motor systems: transcranial magnetic stimulation (TMS and transcranial direct current stimulation (tDCS. These techniques represent powerful methods for priming cortical excitability for a subsequent motor task, demand, or stimulation. Thus, their mutual use can optimize the plastic changes induced by motor practice, leading to more remarkable and outlasting clinical gains in rehabilitation. In this review we discuss how these techniques can enhance the effects of a behavioural intervention and the clinical evidence to date.

  10. Efficacy of brain-computer interface-driven neuromuscular electrical stimulation for chronic paresis after stroke.

    Science.gov (United States)

    Mukaino, Masahiko; Ono, Takashi; Shindo, Keiichiro; Fujiwara, Toshiyuki; Ota, Tetsuo; Kimura, Akio; Liu, Meigen; Ushiba, Junichi

    2014-04-01

    Brain computer interface technology is of great interest to researchers as a potential therapeutic measure for people with severe neurological disorders. The aim of this study was to examine the efficacy of brain computer interface, by comparing conventional neuromuscular electrical stimulation and brain computer interface-driven neuromuscular electrical stimulation, using an A-B-A-B withdrawal single-subject design. A 38-year-old male with severe hemiplegia due to a putaminal haemorrhage participated in this study. The design involved 2 epochs. In epoch A, the patient attempted to open his fingers during the application of neuromuscular electrical stimulation, irrespective of his actual brain activity. In epoch B, neuromuscular electrical stimulation was applied only when a significant motor-related cortical potential was observed in the electroencephalogram. The subject initially showed diffuse functional magnetic resonance imaging activation and small electro-encephalogram responses while attempting finger movement. Epoch A was associated with few neurological or clinical signs of improvement. Epoch B, with a brain computer interface, was associated with marked lateralization of electroencephalogram (EEG) and blood oxygenation level dependent responses. Voluntary electromyogram (EMG) activity, with significant EEG-EMG coherence, was also prompted. Clinical improvement in upper-extremity function and muscle tone was observed. These results indicate that self-directed training with a brain computer interface may induce activity- dependent cortical plasticity and promote functional recovery. This preliminary clinical investigation encourages further research using a controlled design.

  11. Traditional Mongolian medicine Eerdun Wurile improves stroke recovery through regulation of gene expression in rat brain.

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    Gaowa, Saren; Bao, Narisi; Da, Man; Qiburi, Qiburi; Ganbold, Tsogzolmaa; Chen, Lu; Altangerel, Altanzul; Temuqile, Temuqile; Baigude, Huricha

    2018-05-16

    Eerdun Wurile (EW) is one of the key Mongolian medicines for treatment of neurological and cardiological disorders. EW is ranked most regularly used Mongolian medicine in clinic. Components of EW which mainly originate from natural products are well defined and are unique to Mongolian medicine. Although the recipe of EW contains known neuroactive chemicals originated from plants, its mechanism of action has never been elucidated at molecular level. The objective of the present study is to explore the mechanism of neuroregenerative activity of EW by focusing on the regulation of gene expression in the brain of rat model of stroke. Rat middle cerebral artery occlusion (MCAO) models were treated with EW for 15 days. Then, total RNAs from the cerebral cortex of rat MCAO models treated with either EW or control (saline) were extracted and analyzed by transcriptome sequencing. Differentially expressed genes were analyzed for their functions during the recovery of ischemic stroke. The expression level of significantly differentially expressed genes such as growth factors, microglia markers and secretive enzymes in the lesion was further validated by RT-qPCR and immunohistochemistry. Previously identified neuroactive compounds, such as geniposide (Yu et al., 2009), myristicin (Shin et al., 1988), costunolide (Okugawa et al., 1996), toosendanin (Shi and Chen, 1999) were detected in EW formulation. Bederson scale indicated that the treatment of rat MCAO models with EW showed significantly lowered neurological deficits (p < 0.01). The regional cerebral blood circulation was also remarkably higher in rat MCAO models treated with EW compared to the control group. A total of 186 genes were upregulated in the lesion of rat MCAO models treated with EW compared to control group. Among them, growth factors such as Igf1 (p < 0.05), Igf2 (p < 0.01), Grn (p < 0.01) were significantly upregulated in brain after treatment of rat MCAO models with EW. Meanwhile, greatly

  12. TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke

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    Buckwalter Marion S

    2010-10-01

    Full Text Available Abstract Background TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging. Methods We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia. Results TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes. Conclusions We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial

  13. TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke.

    Science.gov (United States)

    Doyle, Kristian P; Cekanaviciute, Egle; Mamer, Lauren E; Buckwalter, Marion S

    2010-10-11

    TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging. We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia. TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes. We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial scar formation and the immune response to stroke.

  14. Dizziness in stroke

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    M. V. Zamergrad

    2015-01-01

    Full Text Available Differential diagnosis of new-onset acute vestibular vertigo is chiefly made between vestibular neuronitis and stroke. Dizziness in stroke is usually accompanied by other focal neurological symptoms of brainstem and cerebellar involvement. However, stroke may appear as isolated vestibular vertigo in some cases. An analysis of history data and the results of neurovestibular examination and brain magnetic resonance imaging allows stroke to be diagnosed in patients with acute isolated dizziness. The treatment of patients with stroke-induced dizziness involves a wide range of medications for the reduction of the degree of dizziness and unsteadiness and for the secondary prevention of stroke. Vestibular rehabilitation is an important component of treatment. The paper describes an observation of a patient with poorly controlled hypertension, who developed new-onset acute systemic dizziness. Vestibular neuronitis might be presumed to be a peripheral cause of vestibular disorders, by taking into account the absence of additional obvious neurological symptoms (such as pareses, defective sensation, diplopia, etc. and the nature of nystagmus. However, intention tremor in fingernose and heel-knee tests on the left side, a negative Halmagyi test, and results of Romberg’s test could suggest that stroke was a cause ofdizziness.

  15. Subacute brain atrophy induced by radiation therapy to the malignant brain tumors

    International Nuclear Information System (INIS)

    Asai, Akio; Matsutani, Masao; Takakura, Kintomo.

    1987-01-01

    In order to analyze brain atrophy after radiation therapy to the brain tumors, we calculated a CSF-cranial volume ratio on CT scan as an index of brain atrophy, and estimated dementia-score by Hasegawa's method in 91 post-irradiated patients with malignant brain tumors. Radiation-induced brain atrophy was observed in 51 out of 91 patients (56 %) and dementia in 23 out of 47 patients (49 %). These two conditions were closely related, and observed significantly more often in aged and whole-brain-irradiated patients. As radiation-induced brain atrophy accompanied by dementia appeared 2 - 3 months after the completion of radiation therapy, it should be regarded as a subacute brain injury caused by radiation therapy. (author)

  16. Induced pluripotent stem cells for the treatment of stroke: the potential and the pitfalls.

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    Yu, Fenggang; Li, Yingying; Morshead, Cindi M

    2013-09-01

    The extraordinary discovery of induced pluripotent stem cells (iPSCs) has led to the very real possibility that patient-specific cell therapy can be realized. The potential to develop cell replacement therapies outside the ethical and legal limitations, has initiated a new era of hope for regenerative strategies to treat human neurological disease including stroke. In this article, we will review and compare the current approaches to derive iPSCs from different somatic cells, and the induction into neuronal phenotypes, considering the advantages and disadvantages to the methodologies of derivation. We will highlight the work relating to the use of iPSC-based therapies in models of stroke and their potential use in clinical trials. Finally, we will consider future directions and areas of exploration which may promote the realization of iPSC-based cell replacement strategies for the treatment of stroke.

  17. Structural plasticity of remote cortical brain regions is determined by connectivity to the primary lesion in subcortical stroke.

    Science.gov (United States)

    Cheng, Bastian; Schulz, Robert; Bönstrup, Marlene; Hummel, Friedhelm C; Sedlacik, Jan; Fiehler, Jens; Gerloff, Christian; Thomalla, Götz

    2015-09-01

    Cortical atrophy as demonstrated by measurement of cortical thickness (CT) is a hallmark of various neurodegenerative diseases. In the wake of an acute ischemic stroke, brain architecture undergoes dynamic changes that can be tracked by structural and functional magnetic resonance imaging studies as soon as 3 months after stroke. In this study, we measured changes of CT in cortical areas connected to subcortical stroke lesions in 12 patients with upper extremity paresis combining white-matter tractography and semi-automatic measurement of CT using the Freesurfer software. Three months after stroke, a significant decrease in CT of -2.6% (median, upper/lower boundary of 95% confidence interval -4.1%/-1.1%) was detected in areas connected to ischemic lesions, whereas CT in unconnected cortical areas remained largely unchanged. A cluster of significant cortical thinning was detected in the superior frontal gyrus of the stroke hemisphere using a surface-based general linear model correcting for multiple comparisons. There was no significant correlation of changes in CT with clinical outcome parameters. Our results show a specific impact of subcortical lesions on distant, yet connected cortical areas explainable by secondary neuro-axonal degeneration of distant areas.

  18. Robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery from stroke: updates and advances.

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    Boninger, Michael L; Wechsler, Lawrence R; Stein, Joel

    2014-11-01

    The aim of this study was to describe the current state and latest advances in robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery for stroke. The authors of this summary recently reviewed this work as part of a national presentation. The article represents the information included in each area. Each area has seen great advances and challenges as products move to market and experiments are ongoing. Robotics, stem cells, and brain-computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial.

  19. Stroke Rehabilitation

    Science.gov (United States)

    ... of the effects of a stroke Trouble swallowing (dysphagia) Problems with bowel or bladder control Fatigue Difficulty ... NINDS Focus on Disorders Alzheimer's & Related Dementias Epilepsy Parkinson's Disease Spinal Cord Injury Traumatic Brain Injury Focus ...

  20. Cerebroprotective Effect of Moringa oleifera against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion

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    Woranan Kirisattayakul

    2013-01-01

    Full Text Available The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whether Moringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke. M. oleifera leaves extract at doses of 100, 200 and 400 mg·kg−1 was orally given to male Wistar rats (300–350 g once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration.

  1. Stem cell therapies in preclinical models of stroke. Is the aged brain microenvironment refractory to cell therapy?

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    Sandu, Raluca Elena; Balseanu, Adrian Tudor; Bogdan, Catalin; Slevin, Mark; Petcu, Eugen; Popa-Wagner, Aurel

    2017-08-01

    Stroke is a devastating disease demanding vigorous search for new therapies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments that may be related to unfavorable age-associated environments. Recent results using a variety of drug, cell therapy or combination thereof suggest that, (i) treatment with Granulocyte-Colony Stimulating Factor (G-CSF) in aged rats has primarily a beneficial effect on functional outcome most likely via supportive cellular processes such as neurogenesis; (ii) the combination therapy, G-CSF with mesenchymal cells (G-CSF+BM-MSC or G-CSF+BM-MNC) did not further improve behavioral indices, neurogenesis or infarct volume as compared to G-CSF alone in aged animals; (iii) better results with regard to integration of transplanted cells in the aged rat environment have been obtained using iPS of human origin; (iv) mesenchymal cells may be used as drug carriers for the aged post-stroke brains. While the middle aged brain does not seem to impair drug and cell therapies, in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time. Copyright © 2017. Published by Elsevier Inc.

  2. Systematic review of clinical practice guidelines to identify recommendations for rehabilitation after stroke and other acquired brain injuries

    Science.gov (United States)

    Lannin, Natasha A; Hoffmann, Tammy

    2018-01-01

    Objectives Rehabilitation clinical practice guidelines (CPGs) contain recommendation statements aimed at optimising care for adults with stroke and other brain injury. The aim of this study was to determine the quality, scope and consistency of CPG recommendations for rehabilitation covering the acquired brain injury populations. Design Systematic review. Interventions Included CPGs contained recommendations for inpatient rehabilitation or community rehabilitation for adults with an acquired brain injury diagnosis (stroke, traumatic or other non-progressive acquired brain impairments). Electronic databases (n=2), guideline organisations (n=4) and websites of professional societies (n=17) were searched up to November 2017. Two independent reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and textual syntheses were used to appraise and compare recommendations. Results From 427 papers screened, 20 guidelines met the inclusion criteria. Only three guidelines were rated high (>75%) across all domains of AGREE-II; highest rated domains were ‘scope and purpose’ (85.1, SD 18.3) and ‘clarity’ (76.2%, SD 20.5). Recommendations for assessment and for motor therapies were most commonly reported, however, varied in the level of detail across guidelines. Conclusion Rehabilitation CPGs were consistent in scope, suggesting little difference in rehabilitation approaches between vascular and traumatic brain injury. There was, however, variability in included studies and methodological quality. PROSPERO registration number CRD42016026936. PMID:29490958

  3. Hyperbaric Oxygen Therapy Can Induce Angiogenesis and Regeneration of Nerve Fibers in Traumatic Brain Injury Patients

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    Sigal Tal

    2017-10-01

    Full Text Available Background: Recent clinical studies in stroke and traumatic brain injury (TBI victims suffering chronic neurological injury present evidence that hyperbaric oxygen therapy (HBOT can induce neuroplasticity.Objective: To assess the neurotherapeutic effect of HBOT on prolonged post-concussion syndrome (PPCS due to TBI, using brain microstructure imaging.Methods: Fifteen patients afflicted with PPCS were treated with 60 daily HBOT sessions. Imaging evaluation was performed using Dynamic Susceptibility Contrast-Enhanced (DSC and Diffusion Tensor Imaging (DTI MR sequences. Cognitive evaluation was performed by an objective computerized battery (NeuroTrax.Results: HBOT was initiated 6 months to 27 years (10.3 ± 3.2 years from injury. After HBOT, DTI analysis showed significantly increased fractional anisotropy values and decreased mean diffusivity in both white and gray matter structures. In addition, the cerebral blood flow and volume were increased significantly. Clinically, HBOT induced significant improvement in the memory, executive functions, information processing speed and global cognitive scores.Conclusions: The mechanisms by which HBOT induces brain neuroplasticity can be demonstrated by highly sensitive MRI techniques of DSC and DTI. HBOT can induce cerebral angiogenesis and improve both white and gray microstructures indicating regeneration of nerve fibers. The micro structural changes correlate with the neurocognitive improvements.

  4. Dual activities of the anti-cancer drug candidate PBI-05204 provide neuroprotection in brain slice models for neurodegenerative diseases and stroke.

    Science.gov (United States)

    Van Kanegan, Michael J; Dunn, Denise E; Kaltenbach, Linda S; Shah, Bijal; He, Dong Ning; McCoy, Daniel D; Yang, Peiying; Peng, Jiangnan; Shen, Li; Du, Lin; Cichewicz, Robert H; Newman, Robert A; Lo, Donald C

    2016-05-12

    We previously reported neuroprotective activity of the botanical anti-cancer drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, in brain slice and in vivo models of ischemic stroke. We showed that one component of this neuroprotective activity is mediated through its principal cardiac glycoside constituent, oleandrin, via induction of the potent neurotrophic factor brain-derived neurotrophic factor (BDNF). However, we also noted that the concentration-relation for PBI-05204 in the brain slice oxygen-glucose deprivation (OGD) model is considerably broader than that for oleandrin as a single agent. We thus surmised that PBI-05204 contains an additional neuroprotective component(s), distinct from oleandrin. We report here that neuroprotective activity is also provided by the triterpenoid constituents of PBI-05204, notably oleanolic acid. We demonstrate that a sub-fraction of PBI-05204 (Fraction 0-4) containing oleanolic and other triterpenoids, but without cardiac glycosides, induces the expression of cellular antioxidant gene transcription programs regulated through antioxidant transcriptional response elements (AREs). Finally, we show that Fraction 0-4 provides broad neuroprotection in organotypic brain slice models for neurodegeneration driven by amyloid precursor protein (APP) and tau implicated in Alzheimer's disease and frontotemporal dementias, respectively, in addition to ischemic injury modeled by OGD.

  5. Increased brain damage after ischaemic stroke in mice lacking the chemokine receptor CCR5

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    Sorce, S; Bonnefont, J; Julien, S; Marq-Lin, N; Rodriguez, I; Dubois-Dauphin, M; Krause, KH

    2010-01-01

    Background and purpose: The chemokine receptor CCR5 is well known for its function in immune cells; however, it is also expressed in the brain, where its specific role remains to be elucidated. Because genetic factors may influence the risk of developing cerebral ischaemia or affect its clinical outcome, we have analysed the role of CCR5 in experimental stroke. Experimental approach: Permanent cerebral ischaemia was performed by occlusion of the middle cerebral artery in wild-type and CCR5-deficient mice. Locomotor behaviour, infarct size and histochemical alterations were analysed at different time points after occlusion. Key results: The cerebral vasculature was comparable in wild-type and CCR5-deficient mice. However, the size of the infarct and the motor deficits after occlusion were markedly increased in CCR5-deficient mice as compared with wild type. No differences between wild-type and CCR5-deficient mice were elicited by occlusion with respect to the morphology and abundance of astrocytes and microglia. Seven days after occlusion the majority of CCR5-deficient mice displayed neutrophil invasion in the infarct region, which was not observed in wild type. As compared with wild type, the infarct regions of CCR5-deficient mice were characterized by increased neuronal death. Conclusions and implications: Lack of CCR5 increased the severity of brain injury following occlusion of the middle cerebral artery. This is of particular interest with respect to the relatively frequent occurrence of CCR5 deficiency in the human population (1–2% of the Caucasian population) and the advent of CCR5 inhibitors as novel drugs. PMID:20423342

  6. Computerized detection of acute ischemic stroke in brain computed tomography images

    International Nuclear Information System (INIS)

    Nagashima, Hiroyuki; Shiraishi, Akihisa; Harakawa, Tetsumi; Shiraishi, Junji; Doi, Kunio; Sunaga, Shinichi

    2009-01-01

    The interpretation of acute ischemic stroke (AIS) in computed tomography (CT) images is a very difficult challenge for radiologists. To assist radiologists in CT image interpretation, we have developed a computerized method for the detection of AIS using 100 training cases and 60 testing cases. In our computerized method, the inclination of the isotropic brain CT volume data is corrected by rotation and shifting. The subtraction data for the contralateral volume is then derived by subtraction from the mirrored (right-left reversed) volume data. Initial candidates suspected to have experienced AIS were identified using multiple-thresholding and filtering techniques. Twenty-one image features of these candidates were extracted and applied to a rule-based test to identify final candidates for AIS. The detection sensitivity values for the training cases and for the testing cases were 95.0% with 3.1 false positives per case and 85.7% with 3.4 false positives per case, respectively. Our computerized method showed good performance in the detection of AIS by CT and is expected to be useful in decision-making by radiologists. (author)

  7. Brain-Computer Interfaces With Multi-Sensory Feedback for Stroke Rehabilitation: A Case Study.

    Science.gov (United States)

    Irimia, Danut C; Cho, Woosang; Ortner, Rupert; Allison, Brendan Z; Ignat, Bogdan E; Edlinger, Guenter; Guger, Christoph

    2017-11-01

    Conventional therapies do not provide paralyzed patients with closed-loop sensorimotor integration for motor rehabilitation. This work presents the recoveriX system, a hardware and software platform that combines a motor imagery (MI)-based brain-computer interface (BCI), functional electrical stimulation (FES), and visual feedback technologies for a complete sensorimotor closed-loop therapy system for poststroke rehabilitation. The proposed system was tested on two chronic stroke patients in a clinical environment. The patients were instructed to imagine the movement of either the left or right hand in random order. During these two MI tasks, two types of feedback were provided: a bar extending to the left or right side of a monitor as visual feedback and passive hand opening stimulated from FES as proprioceptive feedback. Both types of feedback relied on the BCI classification result achieved using common spatial patterns and a linear discriminant analysis classifier. After 10 sessions of recoveriX training, one patient partially regained control of wrist extension in her paretic wrist and the other patient increased the range of middle finger movement by 1 cm. A controlled group study is planned with a new version of the recoveriX system, which will have several improvements. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  8. Application of noninvasive brain stimulation for post-stroke dysphagia rehabilitation.

    Science.gov (United States)

    Wang, Zhuo; Song, Wei-Qun; Wang, Liang

    2017-02-01

    Noninvasive brain stimulation (NIBS), commonly consisting of transcranial magnetic stimulation (TMS), transcranial direct-current stimulation (tDCS), as well as paired associative stimulation (PAS), has attracted increased interest and been applied experimentally in the treatment of post-stroke dysphagia (PSD). This review presented a synopsis of the current research for the application of NIBS on PSD. The intention here was to understand the current research progress and limitations in this field and to stimulate potential research questions not yet investigated for the application of NIBS on patients with PSD. Here we successively reviewed advances of repetitive TMS (rTMS), tDCS, and PAS techniques on both healthy participants and PSD patients in three aspects, including scientific researches about dysphagia mechanism, applied studies about stimulation parameters, and clinical trials about their therapeutic effects. The techniques of NIBS, especially rTMS, have been used by the researchers to explore the different mechanisms between swallowing recovery and extremity rehabilitation. The key findings included the important role of intact hemisphere reorganization for PSD recovery, and the use of NIBS on the contra-lesional side as a therapeutic potential for dysphagia rehabilitation. Though significant results were achieved in most studies by using NIBS on swallowing rehabilitation, it is still difficult to draw conclusions for the efficacy of these neurostimulation techniques, considering the great disparities between studies. Copyright © 2016. Published by Elsevier Taiwan.

  9. GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats.

    Science.gov (United States)

    Wang, Wei; Li, Mingchang; Wang, Yuefei; Li, Qian; Deng, Gang; Wan, Jieru; Yang, Qingwu; Chen, Qianxue; Wang, Jian

    2016-12-01

    Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke who are treated with tissue plasminogen activator (tPA). It is associated with high morbidity and mortality, but no effective treatments are currently available to reduce HT risk. Therefore, methods to prevent HT are urgently needed. In this study, we used TWS119, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt/β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke and then were administered rtPA, rtPA combined with TWS119, or vehicle at 4 h. The animals were sacrificed 24 h after infarct induction. Rats treated with rtPA showed evident HT, had more severe neurologic deficit, brain edema, and blood-brain barrier breakdown, and had larger infarction volume than did the vehicle group. Rats treated with TWS119 had significantly improved outcomes compared with those of rats treated with rtPA alone. In addition, Western blot analysis showed that TWS119 increased the protein expression of β-catenin, claudin-3, and ZO-1 while suppressing the expression of GSK-3β. These results suggest that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke.

  10. Prospective multicentre cohort study of heparin-induced thrombocytopenia in acute ischaemic stroke patients

    Science.gov (United States)

    Kawano, Hiroyuki; Yamamoto, Haruko; Miyata, Shigeki; Izumi, Manabu; Hirano, Teruyuki; Toratani, Naomi; Kakutani, Isami; Sheppard, Jo-Ann I; Warkentin, Theodore E; Kada, Akiko; Sato, Shoichiro; Okamoto, Sadahisa; Nagatsuka, Kazuyuki; Naritomi, Hiroaki; Toyoda, Kazunori; Uchino, Makoto; Minematsu, Kazuo

    2011-01-01

    Acute ischaemic stroke patients sometimes receive heparin for treatment and/or prophylaxis of thromboembolic complications. This study was designed to elucidate the incidence and clinical features of heparin-induced thrombocytopenia (HIT) in acute stroke patients treated with heparin. We conducted a prospective multicentre cohort study of 267 patients who were admitted to three stroke centres within 7 d after stroke onset. We examined clinical data until discharge and collected blood samples on days 1 and 14 of hospitalization to test anti-platelet factor 4/heparin antibodies (anti-PF4/H Abs) using an enzyme-linked immunosorbent assay (ELISA); platelet-activating antibodies were identified by serotonin-release assay (SRA). Patients with a 4Ts score ≥4 points, positive-ELISA, and positive-SRA were diagnosed as definite HIT. Heparin was administered to 172 patients (64·4%: heparin group). Anti-PF4/H Abs were detected by ELISA in 22 cases (12·8%) in the heparin group. Seven patients had 4Ts ≥ 4 points. Among them, three patients (1·7% overall) were also positive by both ELISA and SRA. National Institutes of Health Stroke Scale score on admission was high (range, 16–23) and in-hospital mortality was very high (66·7%) in definite HIT patients. In this study, the incidence of definite HIT in acute ischaemic stroke patients treated with heparin was 1·7% (95% confidence interval: 0·4–5·0). The clinical severity and outcome of definite HIT were unfavourable. PMID:21671895

  11. Patent foramen ovale closure with GORE HELEX or CARDIOFORM Septal Occluder vs. antiplatelet therapy for reduction of recurrent stroke or new brain infarct in patients with prior cryptogenic stroke: Design of the randomized Gore REDUCE Clinical Study.

    Science.gov (United States)

    Kasner, Scott E; Thomassen, Lars; Søndergaard, Lars; Rhodes, John F; Larsen, Coby C; Jacobson, Joth

    2017-12-01

    Rationale The utility of patent foramen ovale (PFO) closure for secondary prevention in patients with prior cryptogenic stroke is uncertain despite multiple randomized trials completed to date. Aims The Gore REDUCE Clinical Study (REDUCE) aims to establish superiority of patent foramen ovale closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke. Methods and design This controlled, open-label trial randomized 664 subjects with cryptogenic stroke at 63 multinational sites in a 2:1 ratio to either antiplatelet therapy plus patent foramen ovale closure (with GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder) or antiplatelet therapy alone. Subjects will be prospectively followed for up to five years. Neuroimaging is required for all subjects at baseline and at two years or study exit. Study outcomes The two co-primary endpoints for the study are freedom from recurrent clinical ischemic stroke through at least 24 months post-randomization and incidence of new brain infarct (defined as clinical ischemic stroke or silent brain infarct) through 24 months. The primary analyses are an unadjusted log-rank test and a binomial test of subject-based proportions, respectively, both on the intent-to-treat population, with adjustment for testing multiplicity. Discussion The REDUCE trial aims to target a patient population with truly cryptogenic strokes. Medical therapy is limited to antiplatelet agents in both arms thereby reducing confounding. The trial should determine whether patent foramen ovale closure with the Gore septal occluders is safe and more effective than medical therapy alone for the prevention of recurrent clinical ischemic stroke or new silent brain infarct; the neuroimaging data will provide an opportunity to further support the proof of concept. The main results are anticipated in 2017

  12. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    Science.gov (United States)

    Weaver, John; Yang, Yirong; Purvis, Rebecca; Weatherwax, Theodore; Rosen, Gerald M.; Liu, Ke Jian

    2014-01-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O2 may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O2 is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO2 in vivo remains largely uncharacterized. This study investigated striatal tissue pO2 changes in male C57BL/6 mice (16–20g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO2 in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO2 was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO2 to 64%. More importantly, pO2 did not recover fully to control levels even 24 hrs after administration of a single dose of METH. and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO2 indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO2, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. PMID:24412707

  13. Stroke in thrombotic thrombocytopenic purpura induced by thyrotoxicosis: a case report.

    Science.gov (United States)

    Bellante, Flavio; Redondo Saez, Patricia; Springael, Cecile; Dethy, Sophie

    2014-07-01

    Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease involving the platelet aggregation and resulting in hemolytic anemia, thrombocytopenia, and microvascular occlusion. Although frequent neurologic features are headache and confusion, focal deficit is described in 30% of the cases. There are a lot of causes inducing thrombotic thrombocytopenic, but reports are lacking when associated with Grave disease. We describe the case of a 51-year-old Caucasian woman presenting a 24-hour story of sudden onset of dysarthria and left superior limb palsy. Four months before, she developed severe hyperthyroidism associated with petechiae, hemolytic anemia, thrombocytopenia, and schistocytes at blood film examination. Relapse of TTP in association with Grave disease was diagnosed. There are few reports describing association between Grave disease and TTP with only mild neurologic involvement. We described, to our knowledge, the first case of acute ischemic stroke secondary to thrombotic thrombocytopenic induced by thyrotoxicosis. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Transcranial direct-current stimulation induced in stroke patients with aphasia: a prospective experimental cohort study

    OpenAIRE

    Santos,Michele Devido; Gagliardi,Rubens José; Mac-Kay,Ana Paula Machado Goyano; Boggio,Paulo Sergio; Lianza,Roberta; Fregni,Felipe

    2013-01-01

    CONTEXT AND OBJECTIVE: Previous animal and human studies have shown that transcranial direct current stimulation can induce significant and lasting neuroplasticity and may improve language recovery in patients with aphasia. The objective of the study was to describe a cohort of patients with aphasia after stroke who were treated with transcranial direct current stimulation. DESIGN AND SETTING: Prospective cohort study developed in a public university hospital. METHODS: Nineteen patients with ...

  15. Combination of brain-computer interface training and goal-directed physical therapy in chronic stroke: a case report.

    Science.gov (United States)

    Broetz, Doris; Braun, Christoph; Weber, Cornelia; Soekadar, Surjo R; Caria, Andrea; Birbaumer, Niels

    2010-09-01

    There is no accepted and efficient rehabilitation strategy to reduce focal impairments for patients with chronic stroke who lack residual movements. A 67-year-old hemiplegic patient with no active finger extension was trained with a brain-computer interface (BCI) combined with a specific daily life-oriented physiotherapy. The BCI used electrical brain activity (EEG) and magnetic brain activity (MEG) to drive an orthosis and a robot affixed to the patient's affected upper extremity, which enabled him to move the paralyzed arm and hand driven by voluntary modulation of micro-rhythm activity. In addition, the patient practiced goal-directed physiotherapy training. Over 1 year, he completed 3 training blocks. Arm motor function, gait capacities (using Fugl-Meyer Assessment, Wolf Motor Function Test, Modified Ashworth Scale, 10-m walk speed, and goal attainment score), and brain reorganization (functional MRI, MEG) were repeatedly assessed. The ability of hand and arm movements as well as speed and safety of gait improved significantly (mean 46.6%). Improvement of motor function was associated with increased micro-oscillations in the ipsilesional motor cortex. This proof-of-principle study suggests that the combination of BCI training with goal-directed, active physical therapy may improve the motor abilities of chronic stroke patients despite apparent initial paralysis.

  16. Motor Imagery-Based Brain-Computer Interface Coupled to a Robotic Hand Orthosis Aimed for Neurorehabilitation of Stroke Patients

    Directory of Open Access Journals (Sweden)

    Jessica Cantillo-Negrete

    2018-01-01

    Full Text Available Motor imagery-based brain-computer interfaces (BCI have shown potential for the rehabilitation of stroke patients; however, low performance has restricted their application in clinical environments. Therefore, this work presents the implementation of a BCI system, coupled to a robotic hand orthosis and driven by hand motor imagery of healthy subjects and the paralysed hand of stroke patients. A novel processing stage was designed using a bank of temporal filters, the common spatial pattern algorithm for feature extraction and particle swarm optimisation for feature selection. Offline tests were performed for testing the proposed processing stage, and results were compared with those computed with common spatial patterns. Afterwards, online tests with healthy subjects were performed in which the orthosis was activated by the system. Stroke patients’ average performance was 74.1 ± 11%. For 4 out of 6 patients, the proposed method showed a statistically significant higher performance than the common spatial pattern method. Healthy subjects’ average offline and online performances were of 76.2 ± 7.6% and 70 ± 6.7, respectively. For 3 out of 8 healthy subjects, the proposed method showed a statistically significant higher performance than the common spatial pattern method. System’s performance showed that it has a potential to be used for hand rehabilitation of stroke patients.

  17. Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model

    International Nuclear Information System (INIS)

    Koh, Seong-Ho; Chang, Dae-Il; Kim, Hee-Tae; Kim, Juhan; Kim, Myung-Ho; Kim, Kyung Suk; Bae, Inhee; Kim, Haekwon; Kim, Dong Won; Kim, Seung Hyun

    2005-01-01

    We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-κB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10 min before the occlusion of the left middle cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-κB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-κB, and MPO activities were significantly reduced in 3-AB group at each time point (p < 0.05). Plasma MMP-9 increased maximally at 4 h and then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted until 72 h, and NF-κB increased maximally at 24 h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-κB and the infiltration of neutrophils in ischemic stroke

  18. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    Science.gov (United States)

    Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

    2008-01-01

    Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

  19. Reperfusion facilitates reversible disruption of the human blood-brain barrier following acute ischaemic stroke

    International Nuclear Information System (INIS)

    Liu, Chang; Zhang, Sheng; Yan, Shenqiang; Zhang, Ruiting; Shi, Feina; Lou, Min; Ding, Xinfa; Parsons, Mark

    2018-01-01

    We aimed to detect early changes of the blood-brain barrier permeability (BBBP) in acute ischaemic stroke (AIS), with or without reperfusion, and find out whether BBBP can predict clinical outcomes. Consecutive AIS patients imaged with computed tomographic perfusion (CTP) before and 24 h after treatment were included. The relative permeability-surface area product (rPS) was calculated within the hypoperfused region (rPS hypo-i ), non-hypoperfused region of ischaemic hemisphere (rPS nonhypo-i ) and their contralateral mirror regions (rPS hypo-c and rPS nonhypo-c ). The changes of rPS were analysed using analysis of variance (ANOVA) with repeated measures. Logistic regression was used to identify independent predictors of unfavourable outcome. Fifty-six patients were included in the analysis, median age was 76 (IQR 62-81) years and 28 (50%) were female. From baseline to 24 h after treatment, rPS hypo-i , rPS nonhypo-i and rPS hypo-c all decreased significantly. The decreases in rPS hypo-i and rPS hypo-c were larger in the reperfusion group than non-reperfusion group. The rPS hypo-i at follow-up was a predictor for unfavourable outcome (OR 1.131; 95% CI 1.018-1.256; P = 0.022). Early disruption of BBB in AIS is reversible, particularly when greater reperfusion is achieved. Elevated BBBP at 24 h after treatment, not the pretreatment BBBP, predicts unfavourable outcome. (orig.)

  20. Reperfusion facilitates reversible disruption of the human blood-brain barrier following acute ischaemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chang; Zhang, Sheng; Yan, Shenqiang; Zhang, Ruiting; Shi, Feina; Lou, Min [The Second Affiliated Hospital of Zhejiang University, School of Medicine, Department of Neurology, Hangzhou (China); Ding, Xinfa [The Second Affiliated Hospital of Zhejiang University, School of Medicine, Department of Radiology, Hangzhou (China); Parsons, Mark [John Hunter Hospital, University of Newcastle, Department of Neurology, Newcastle (Australia)

    2018-02-15

    We aimed to detect early changes of the blood-brain barrier permeability (BBBP) in acute ischaemic stroke (AIS), with or without reperfusion, and find out whether BBBP can predict clinical outcomes. Consecutive AIS patients imaged with computed tomographic perfusion (CTP) before and 24 h after treatment were included. The relative permeability-surface area product (rPS) was calculated within the hypoperfused region (rPS{sub hypo-i}), non-hypoperfused region of ischaemic hemisphere (rPS{sub nonhypo-i}) and their contralateral mirror regions (rPS{sub hypo-c} and rPS{sub nonhypo-c}). The changes of rPS were analysed using analysis of variance (ANOVA) with repeated measures. Logistic regression was used to identify independent predictors of unfavourable outcome. Fifty-six patients were included in the analysis, median age was 76 (IQR 62-81) years and 28 (50%) were female. From baseline to 24 h after treatment, rPS{sub hypo-i}, rPS{sub nonhypo-i} and rPS{sub hypo-c} all decreased significantly. The decreases in rPS{sub hypo-i} and rPS{sub hypo-c} were larger in the reperfusion group than non-reperfusion group. The rPS{sub hypo-i} at follow-up was a predictor for unfavourable outcome (OR 1.131; 95% CI 1.018-1.256; P = 0.022). Early disruption of BBB in AIS is reversible, particularly when greater reperfusion is achieved. Elevated BBBP at 24 h after treatment, not the pretreatment BBBP, predicts unfavourable outcome. (orig.)

  1. Combined rTMS and virtual reality brain-computer interface training for motor recovery after stroke

    Science.gov (United States)

    Johnson, N. N.; Carey, J.; Edelman, B. J.; Doud, A.; Grande, A.; Lakshminarayan, K.; He, B.

    2018-02-01

    Objective. Combining repetitive transcranial magnetic stimulation (rTMS) with brain-computer interface (BCI) training can address motor impairment after stroke by down-regulating exaggerated inhibition from the contralesional hemisphere and encouraging ipsilesional activation. The objective was to evaluate the efficacy of combined rTMS  +  BCI, compared to sham rTMS  +  BCI, on motor recovery after stroke in subjects with lasting motor paresis. Approach. Three stroke subjects approximately one year post-stroke participated in three weeks of combined rTMS (real or sham) and BCI, followed by three weeks of BCI alone. Behavioral and electrophysiological differences were evaluated at baseline, after three weeks, and after six weeks of treatment. Main results. Motor improvements were observed in both real rTMS  +  BCI and sham groups, but only the former showed significant alterations in inter-hemispheric inhibition in the desired direction and increased relative ipsilesional cortical activation from fMRI. In addition, significant improvements in BCI performance over time and adequate control of the virtual reality BCI paradigm were observed only in the former group. Significance. When combined, the results highlight the feasibility and efficacy of combined rTMS  +  BCI for motor recovery, demonstrated by increased ipsilesional motor activity and improvements in behavioral function for the real rTMS  +  BCI condition in particular. Our findings also demonstrate the utility of BCI training alone, as shown by behavioral improvements for the sham rTMS  +  BCI condition. This study is the first to evaluate combined rTMS and BCI training for motor rehabilitation and provides a foundation for continued work to evaluate the potential of both rTMS and virtual reality BCI training for motor recovery after stroke.

  2. Inhibitory non-invasive brain stimulation to homologous language regions as an adjunct to speech and language therapy in post-stroke aphasia: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Begonya eOtal

    2015-04-01

    Full Text Available Chronic communication impairment is common after stroke, and conventional speech and language therapy (SLT strategies have limited effectiveness in post-stroke aphasia. Neurorehabilitation with non-invasive brain stimulation techniques (NIBS ‒ particularly repetitive transcranial magnetic stimulation (rTMS or transcranial direct current stimulation (tDCS ‒ may enhance the effects of SLT in selected patients. Applying inhibitory NIBS to specific homologous language regions may induce neural reorganization and reduce interhemispheric competition. This mini review highlights randomized controlled trials (RCTs and randomized cross-over trials using low-frequency rTMS or cathodal tDCS over the non-lesioned non-language dominant hemisphere and performs an exploratory meta-analysis of those trials considered combinable. Using a random-effects model, a meta-analysis of nine eligible trials involving 215 participants showed a significant mean effect size of 0.51 (95% CI = 0.24 to 0.79 for the main outcome accuracy of naming in language assessment. No heterogeneity was observed (I2 = 0%. More multicenter RCTs with larger populations and homogenous intervention protocols are required to confirm these and the longer-term effects.

  3. Laser-induced breakdown ignition in a gas fed two-stroke engine

    Science.gov (United States)

    Loktionov, E. Y.; Pasechnikov, N. A.; Telekh, V. D.

    2018-01-01

    Laser-induced ignition for internal combustion engines is investigated intensively after demonstration of a compact ‘laser plug’ possibility. Laser spark benefits as compared to traditional spark plugs are higher compression rate, and possibility of almost any fuel ignition, so lean mixtures burning with lower temperatures could reduce harmful exhausts (NO x , CH, etc). No need in electrode and possibility for multi-point, linear or circular ignition can make combustion even more effective. Laser induced combustion wave appears faster and is more stable in time, than electric one, so can be used for ramjets, chemical thrusters, and gas turbines. To the best of our knowledge, we have performed laser spark ignition of a gas fed two-stroke engine for the first time. Combustion temperature and pressure, exhaust composition, ignition timing were investigated at laser and compared to a regular electric spark ignition in a two-stroke model engine. Presented results show possibility for improvement of two-stroke engines performance, in terms of rotation rate increase and NO x emission reduction. Such compact engines using locally mined fuel could be highly demanded in remote Arctic areas.

  4. Changes of brain response induced by simulated weightlessness

    Science.gov (United States)

    Wei, Jinhe; Yan, Gongdong; Guan, Zhiqiang

    The characteristics change of brain response was studied during 15° head-down tilt (HDT) comparing with 45° head-up tilt (HUT). The brain responses evaluated included the EEG power spectra change at rest and during mental arithmetic, and the event-related potentials (ERPs) of somatosensory, selective attention and mental arithmetic activities. The prominent feature of brain response change during HDT revealed that the brain function was inhibited to some extent. Such inhibition included that the significant increment of "40Hz" activity during HUT arithmetic almost disappeared during HDT arithmetic, and that the positive-potential effect induced by HDT presented in all kinds of ERPs measured, but the slow negative wave reflecting mental arithmetic and memory process was elongated. These data suggest that the brain function be affected profoundly by the simulated weightlessness, therefore, the brain function change during space flight should be studied systematically.

  5. Glutamate excitoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

    Science.gov (United States)

    Campos, Francisco; Pérez-Mato, María; Agulla, Jesús; Blanco, Miguel; Barral, David; Almeida, Angeles; Brea, David; Waeber, Christian; Castillo, José; Ramos-Cabrer, Pedro

    2012-01-01

    Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

  6. Predictors and brain connectivity changes associated with arm motor function improvement from intensive practice in chronic stroke [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    George F. Wittenberg

    2017-02-01

    Full Text Available Background and Purpose: The brain changes that underlie therapy-induced improvement in motor function after stroke remain obscure. This study sought to demonstrate the feasibility and utility of measuring motor system physiology in a clinical trial of intensive upper extremity rehabilitation in chronic stroke-related hemiparesis. Methods: This was a substudy of two multi-center clinical trials of intensive robotic and intensive conventional therapy arm therapy in chronic, significantly hemiparetic, stroke patients. Transcranial magnetic stimulation was used to measure motor cortical output to the biceps and extensor digitorum communus muscles. Magnetic resonance imaging (MRI was used to determine the cortical anatomy, as well as to measure fractional anisotropy, and blood oxygenation (BOLD during an eyes-closed rest state. Region-of-interest time-series correlation analysis was performed on the BOLD signal to determine interregional connectivity. Functional status was measured with the upper extremity Fugl-Meyer and Wolf Motor Function Test. Results: Motor evoked potential (MEP presence was associated with better functional outcomes, but the effect was not significant when considering baseline impairment. Affected side internal capsule fractional anisotropy was associated with better function at baseline. Affected side primary motor cortex (M1 activity became more correlated with other frontal motor regions after treatment. Resting state connectivity between affected hemisphere M1 and dorsal premotor area (PMAd predicted recovery. Conclusions: Presence of motor evoked potentials in the affected motor cortex and its functional connectivity with PMAd may be useful in predicting recovery. Functional connectivity in the motor network shows a trends towards increasing after intensive robotic or non-robotic arm therapy. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00372411 \\& NCT00333983.

  7. Segregation of Spontaneous and Training Induced Recovery from Visual Field Defects in Subacute Stroke Patients

    Directory of Open Access Journals (Sweden)

    Douwe P. Bergsma

    2017-12-01

    Full Text Available Whether rehabilitation after stroke profits from an early start is difficult to establish as the contributions of spontaneous recovery and treatment are difficult to tease apart. Here, we use a novel training design to dissociate these components for visual rehabilitation of subacute stroke patients with visual field defects such as hemianopia. Visual discrimination training was started within 6 weeks after stroke in 17 patients. Spontaneous and training-induced recoveries were distinguished by training one-half of the defect for 8 weeks, while monitoring spontaneous recovery in the other (control half of the defect. Next, trained and control regions were swapped, and training continued for another 8 weeks. The same paradigm was also applied to seven chronic patients for whom spontaneous recovery can be excluded and changes in the control half of the defect point to a spillover effect of training. In both groups, field stability was assessed during a no-intervention period. Defect reduction was significantly greater in the trained part of the defect than in the simultaneously untrained part of the defect irrespective of training onset (p = 0.001. In subacute patients, training contributed about twice as much to their defect reduction as the spontaneous recovery. Goal Attainment Scores were significantly and positively correlated with the total defect reduction (p = 0.01, percentage increase reading speed was significantly and positively correlated with the defect reduction induced by training (epoch 1: p = 0.0044; epoch 2: p = 0.023. Visual training adds significantly to the spontaneous recovery of visual field defects, both during training in the early and the chronic stroke phase. However, field recovery as a result of training in this subacute phase was as large as in the chronic phase. This suggests that patients benefited primarily of early onset training by gaining access to a larger visual field sooner.

  8. Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen and glucose deprivation in acute brain slices

    Directory of Open Access Journals (Sweden)

    Laurent Chazalviel

    2016-01-01

    Full Text Available Normobaric oxygen (NBO and hyperbaric oxygen (HBO are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO 2 = 1 atmospheres absolute (ATA = 0.1 MPa and HBO (pO 2 = 2.5 ATA = 0.25 MPa through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support of the brain parenchyma requires oxygen partial pressure higher than 1 ATA.

  9. The therapeutic effect of Xueshuan Xinmai tablets on memory injury and brain activity in post-stroke patients: a pilot placebo controlled fMRI study

    OpenAIRE

    Wei, Dongfeng; Lv, Chenlong; Zhang, Junying; Peng, Dantao; Hu, Liangping; Zhang, Zhanjun; Wang, Yongyan

    2015-01-01

    Objective: The purpose of this study was to explore the effects of Xueshuan Xinmai tablets (XXMT) for the treatment of cognition, brain activation in the rehabilitation period of ischemic stroke patients. Methods: 28 adults patients, aged 50-80 years, in the rehabilitation period of ischemic stroke were divided into XXMT treatment group and placebo control group. Patients received 3 months treatment (oral 0.8 g, 3 times per day). Before and after treatment, all patients were evaluated by a se...

  10. Machine Learning Classification to Identify the Stage of Brain-Computer Interface Therapy for Stroke Rehabilitation Using Functional Connectivity

    Directory of Open Access Journals (Sweden)

    Rosaleena Mohanty

    2018-05-01

    Full Text Available Interventional therapy using brain-computer interface (BCI technology has shown promise in facilitating motor recovery in stroke survivors; however, the impact of this form of intervention on functional networks outside of the motor network specifically is not well-understood. Here, we investigated resting-state functional connectivity (rs-FC in stroke participants undergoing BCI therapy across stages, namely pre- and post-intervention, to identify discriminative functional changes using a machine learning classifier with the goal of categorizing participants into one of the two therapy stages. Twenty chronic stroke participants with persistent upper-extremity motor impairment received neuromodulatory training using a closed-loop neurofeedback BCI device, and rs-functional MRI (rs-fMRI scans were collected at four time points: pre-, mid-, post-, and 1 month post-therapy. To evaluate the peak effects of this intervention, rs-FC was analyzed from two specific stages, namely pre- and post-therapy. In total, 236 seeds spanning both motor and non-motor regions of the brain were computed at each stage. A univariate feature selection was applied to reduce the number of features followed by a principal component-based data transformation used by a linear binary support vector machine (SVM classifier to classify each participant into a therapy stage. The SVM classifier achieved a cross-validation accuracy of 92.5% using a leave-one-out method. Outside of the motor network, seeds from the fronto-parietal task control, default mode, subcortical, and visual networks emerged as important contributors to the classification. Furthermore, a higher number of functional changes were observed to be strengthening from the pre- to post-therapy stage than the ones weakening, both of which involved motor and non-motor regions of the brain. These findings may provide new evidence to support the potential clinical utility of BCI therapy as a form of stroke

  11. Traumatic brain injury and obesity induce persistent central insulin resistance.

    Science.gov (United States)

    Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M

    2016-04-01

    Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. RESVERATROL PRECONDITIONING INDUCES A NOVEL EXTENDED WINDOW OF ISCHEMIC TOLERANCE IN THE MOUSE BRAIN

    Science.gov (United States)

    Koronowski, Kevin B.; Dave, Kunjan R.; Saul, Isabel; Camarena, Vladimir; Thompson, John W.; Neumann, Jake T.; Young, Juan I.; Perez-Pinzon, Miguel A.

    2015-01-01

    Background and Purpose Prophylactic treatments that afford neuroprotection against stroke may emerge from the field of preconditioning. Resveratrol mimics ischemic preconditioning, reducing ischemic brain injury when administered two days prior to global ischemia in rats. This protection is linked to Sirt1 and enhanced mitochondrial function possibly through its repression of UCP2. BDNF is another neuroprotective protein associated with Sirt1. In this study we sought to identify the conditions of resveratrol preconditioning (RPC) that most robustly induce neuroprotection against focal ischemia in mice. Methods We tested four different RPC paradigms against a middle cerebral artery occlusion (MCAo) model of stroke. Infarct volume and neurological score were calculated 24 hours following MCAo. Sirt1-chromatin binding was evaluated by ChIP-qPCR. Percoll gradients were used to isolate synaptic fractions and changes in protein expression were determined via Western blot analysis. BDNF concentration was measured using a BDNF-specific ELISA assay. Results While repetitive RPC induced neuroprotection from MCAo, strikingly one application of RPC 14 days prior to MCAo showed the most robust protection, reducing infarct volume by 33% and improving neurological score by 28%. Fourteen days following RPC, Sirt1 protein was increased 1.5 fold and differentially bound to the UCP2 and BDNF promoter regions. Accordingly, synaptic UCP2 protein decreased by 23% and cortical BDNF concentration increased 26%. Conclusions RPC induces a novel extended window of ischemic tolerance in the brain that lasts for at least 14 days. Our data suggest that this tolerance may be mediated by Sirt1, through upregulation of BDNF and downregulation of UCP2. PMID:26159789

  13. Patent foramen ovale closure with GORE HELEX or CARDIOFORM Septal Occluder vs. antiplatelet therapy for reduction of recurrent stroke or new brain infarct in patients with prior cryptogenic stroke

    DEFF Research Database (Denmark)

    Kasner, Scott E; Thomassen, Lars; Søndergaard, Lars

    2017-01-01

    Rationale The utility of patent foramen ovale (PFO) closure for secondary prevention in patients with prior cryptogenic stroke is uncertain despite multiple randomized trials completed to date. Aims The Gore REDUCE Clinical Study (REDUCE) aims to establish superiority of patent foramen ovale...... with truly cryptogenic strokes. Medical therapy is limited to antiplatelet agents in both arms thereby reducing confounding. The trial should determine whether patent foramen ovale closure with the Gore septal occluders is safe and more effective than medical therapy alone for the prevention of recurrent...... closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke. Methods and design This controlled, open-label trial randomized 664 subjects...

  14. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

    Science.gov (United States)

    Michinaga, Shotaro; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Koyama, Yutaka

    2014-01-01

    Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  15. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

    Directory of Open Access Journals (Sweden)

    Shotaro Michinaga

    Full Text Available Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice. Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV administration of BQ788 (ETB antagonist, IRL-2500 (ETB antagonist, or FR139317 (ETA antagonist prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  16. Inhibition of Aquaporin-4 Improves the Outcome of Ischaemic Stroke and Modulates Brain Paravascular Drainage Pathways.

    Science.gov (United States)

    Pirici, Ionica; Balsanu, Tudor Adrian; Bogdan, Catalin; Margaritescu, Claudiu; Divan, Tamir; Vitalie, Vacaras; Mogoanta, Laurentiu; Pirici, Daniel; Carare, Roxana Octavia; Muresanu, Dafin Fior

    2017-12-23

    Aquaporin-4 (AQP4) is the most abundant water channel in the brain, and its inhibition before inducing focal ischemia, using the AQP4 inhibitor TGN-020, has been showed to reduce oedema in imaging studies. Here, we aimed to evaluate, for the first time, the histopathological effects of a single dose of TGN-020 administered after the occlusion of the medial cerebral artery (MCAO). On a rat model of non-reperfusion ischemia, we have assessed vascular densities, albumin extravasation, gliosis, and apoptosis at 3 and 7 days after MCAO. TGN-020 significantly reduced oedema, glial scar, albumin effusion, and apoptosis, at both 3 and 7 days after MCAO. The area of GFAP-positive gliotic rim decreased, and 3D fractal analysis of astrocytic processes revealed a less complex architecture, possibly indicating water accumulating in the cytoplasm. Evaluation of the blood vessels revealed thicker basement membranes colocalizing with exudated albumin in the treated animals, suggesting that inhibition of AQP4 blocks fluid flow towards the parenchyma in the paravascular drainage pathways of the interstitial fluid. These findings suggest that a single dose of an AQP4 inhibitor can reduce brain oedema, even if administered after the onset of ischemia, and AQP4 agonists/antagonists might be effective modulators of the paravascular drainage flow.

  17. Money is Brain: Financial Barriers and Consequences for Canadian Stroke Patients.

    Science.gov (United States)

    Ganesh, Aravind; King-Shier, Kathryn; Manns, Braden J; Hill, Michael D; Campbell, David J T

    2017-03-01

    Stroke patients of lower socioeconomic status have worse outcomes. It remains poorly understood whether this is due to illness severity or personal or health system barriers. We explored the experiences of stroke patients with financial barriers in a qualitative descriptive pilot study, seeking to capture perceived challenges that interfere with their poststroke health and recovery. We interviewed six adults with a history of stroke and financial barriers in Alberta, Canada, inquiring about their: (1) experiences after stroke; (2) experience of financial barriers; (3) perceived reasons for financial barriers; (4) health consequences of financial barriers; and (5) mechanisms for coping with financial barriers. Two reviewers analyzed data using inductive thematic analysis. The participants developed new or worsened financial circumstances as a consequence of stroke-related disability. Poststroke impairments and financial barriers took a toll on their mental health. They struggled to access several aspects of long-term poststroke care, including allied health professional services, medications, and proper nutrition. They described opportunity costs and tradeoffs when accessing health services. In several cases, they were unaware of health resources available to them and were hesitant to disclose their struggles to their physicians and even their families. Some patients with financial barriers perceive challenges to accessing various aspects of poststroke care. They may have inadequate knowledge of resources available to them and may not disclose their concerns to their health care team. This suggests that providers themselves might consider asking stroke patients about financial barriers to optimize their long-term poststroke care.

  18. Topography of acute stroke in a sample of 439 right brain damaged patients.

    Science.gov (United States)

    Sperber, Christoph; Karnath, Hans-Otto

    2016-01-01

    Knowledge of the typical lesion topography and volumetry is important for clinical stroke diagnosis as well as for anatomo-behavioral lesion mapping analyses. Here we used modern lesion analysis techniques to examine the naturally occurring lesion patterns caused by ischemic and by hemorrhagic infarcts in a large, representative acute stroke patient sample. Acute MR and CT imaging of 439 consecutively admitted right-hemispheric stroke patients from a well-defined catchment area suffering from ischemia (n = 367) or hemorrhage (n = 72) were normalized and mapped in reference to stereotaxic anatomical atlases. For ischemic infarcts, highest frequencies of stroke were observed in the insula, putamen, operculum and superior temporal cortex, as well as the inferior and superior occipito-frontal fascicles, superior longitudinal fascicle, uncinate fascicle, and the acoustic radiation. The maximum overlay of hemorrhages was located more posteriorly and more medially, involving posterior areas of the insula, Heschl's gyrus, and putamen. Lesion size was largest in frontal and anterior areas and lowest in subcortical and posterior areas. The large and unbiased sample of stroke patients used in the present study accumulated the different sub-patterns to identify the global topographic and volumetric pattern of right hemisphere stroke in humans.

  19. D-galactose-induced brain ageing model

    DEFF Research Database (Denmark)

    Sadigh-Eteghad, Saeed; Majdi, Alireza; McCann, Sarah K.

    2017-01-01

    Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent...

  20. Integrated Technologies Like Noninvasive Brain Stimulation (NIBS for Stroke Rehabilitation; New Hopes for Patients, Neuroscientists, and Clinicians in Iran

    Directory of Open Access Journals (Sweden)

    Shahid Bashir

    2010-08-01

    Full Text Available A B S T R A C TThe applications of neurophysiological therapy techniques range far and few in the realm of modern day medicine. However, the concept of electromagnetic stimulation, the basis for many noninvasive brain stimulation (NIBS techniques today, has been of interest to the scientific community since the late nineteenth century. Recently, transcranial direct current stimulation (tDCS and transcranial magnetic stimulation (TMS, two noninvasive neurostimulation techniques, have begun to gain popularity and acceptance in the clinical neurophysiology, neurorehabilitaion, neurology, neuroscience, and psychiatry has spread widely, mostly in research applications, but increasingly with clinical aims in mind. These two neurophysiological techniques have proven to be valuable assets in not only the diagnosis, but also the treatment of many neurological disorders (post-stroke motor deficits, tinnitus, fibromyalgia, depression, epilepsy, autism, ageing and parkinson’s disease. Its effects can be modulated by combination with pharmacological treatment that has undergone resurgence in recent years. In this review we discuss how these integrated technology like NIBS for evaluation in the clinical evidence to date and what mechanism it work for stroke rehabilitation particularly. Then, we will review the current situation of stroke rehabilitation in Iran and new hopes that NIBS could bring for clinicians and patients in this nationally prioritized field.

  1. Changes in functional connectivity correlate with behavioral gains in stroke patients after therapy using a brain-computer interface device

    Directory of Open Access Journals (Sweden)

    Brittany Mei Young

    2014-07-01

    Full Text Available Brain-computer interface (BCI technology is being incorporated into new stroke rehabilitation devices, but little is known about brain changes associated with its use. We collected anatomical and functional MRI of 9 stroke patients with persistent upper extremity motor impairment before, during, and after therapy using a BCI system. Subjects were asked to perform finger tapping of the impaired hand during fMRI. Action Research Arm Test (ARAT, 9-Hole Peg Test (9-HPT, and Stroke Impact Scale (SIS domains of Hand Function (HF and Activities of Daily Living (ADL were also assessed. Group-level analyses examined changes in whole-brain task-based functional connectivity (FC to seed regions in the motor network observed during and after BCI therapy. Whole-brain FC analyses seeded in each thalamus showed FC increases from baseline at mid-therapy and post-therapy (p< 0.05. Changes in FC between seeds at both the network and the connection levels were examined for correlations with changes in behavioral measures. Average motor network FC was increased post-therapy, and changes in average network FC correlated (p < 0.05 with changes in performance on ARAT (R2=0.21, 9-HPT (R2=0.41, SIS HF (R2=0.27, and SIS ADL (R2=0.40. Multiple individual connections within the motor network were found to correlate in change from baseline with changes in behavioral measures. Many of these connections involved the thalamus, with change in each of four behavioral measures significantly correlating with change from baseline FC of at least one thalamic connection. These preliminary results show changes in FC that occur with the administration of rehabilitative therapy using a BCI system. The correlations noted between changes in FC measures and changes in behavioral outcomes indicate that both adaptive and maladaptive changes in FC may develop with this therapy and also suggest a brain-behavior relationship that may be stimulated by the neuromodulatory component of BCI therapy.

  2. Blood brain barrier and brain tissue injury by Gd-DTPA in uremia-induced rabbits

    International Nuclear Information System (INIS)

    Choi, Sun Seob; Huh, Ki Yeong; Han, Jin Yeong; Lee, Yong Chul; Eun, Choong Gi; Yang, Yeong Il

    1996-01-01

    An experimental study was carried out to evaluate the morphological changes in the blood brain barrier and neighbouring brain tissue caused by Gd-DTPA in uremia-induced rabbits. Bilateral renal arteries and veins of ten rabbits were ligated. Gd-DTPA(0.2mmol/kg) was intravenously injected into seven rabbits immediately after ligation. After MRI, they were sacrificed 2 or 3 days after ligation in order to observe light and electron microscopic changes in the blood brain barrier and brain tissue. MRI findings were normal, except for enhancement of the superior and inferior sagittal sinuses on T1 weighted images in uremia-induced rabbits injected with Gd-DTPA. On light microscopic examination, these rabbits showed perivascular edema and glial fibrillary acidic protein expression: electron microscopic examination showed separation of tight junctions of endothelial cells, duplication/rarefaction of basal lamina, increased lysosomes of neurons with neuronal death, demyelination of myelin, and extravasation of red blood cells. Uremia-induced rabbits injected with Gd-DTPA showed more severe changes than those without Gd-DTPA injection. Injuries to the blood brain barrier and neighbouring brain tissue were aggravated by Gd-DTPA administration in uremia-induced rabbits. These findings appear to be associated with the neurotoxicity of Gd-DTPA

  3. Biomechanical mechanisms underlying exosuit-induced improvements in walking economy after stroke.

    Science.gov (United States)

    Bae, Jaehyun; Awad, Louis N; Long, Andrew; O'Donnell, Kathleen; Hendron, Katy; Holt, Kenneth G; Ellis, Terry D; Walsh, Conor J

    2018-03-07

    Stroke-induced hemiparetic gait is characteristically asymmetric and metabolically expensive. Weakness and impaired control of the paretic ankle contribute to reduced forward propulsion and ground clearance - walking subtasks critical for safe and efficient locomotion. Targeted gait interventions that improve paretic ankle function after stroke are therefore warranted. We have developed textile-based, soft wearable robots that transmit mechanical power generated by off-board or body-worn actuators to the paretic ankle using Bowden cables (soft exosuits) and have demonstrated the exosuits can overcome deficits in paretic limb forward propulsion and ground clearance, ultimately reducing the metabolic cost of hemiparetic walking. This study elucidates the biomechanical mechanisms underlying exosuit-induced reductions in metabolic power. We evaluated the relationships between exosuit-induced changes in the body center of mass (COM) power generated by each limb, individual joint power and metabolic power. Compared with walking with an exosuit unpowered, exosuit assistance produced more symmetrical COM power generation during the critical period of the step-to-step transition (22.4±6.4% more symmetric). Changes in individual limb COM power were related to changes in paretic ( R 2 =0.83, P= 0.004) and non-paretic ( R 2 = 0.73, P= 0.014) ankle power. Interestingly, despite the exosuit providing direct assistance to only the paretic limb, changes in metabolic power were related to changes in non-paretic limb COM power ( R 2 =0.80, P= 0.007), not paretic limb COM power ( P> 0.05). These findings contribute to a fundamental understanding of how individuals post-stroke interact with an exosuit to reduce the metabolic cost of hemiparetic walking. © 2018. Published by The Company of Biologists Ltd.

  4. Brain mapping for long-term recovery of gait after supratentorial stroke: A retrospective cross-sectional study.

    Science.gov (United States)

    Kim, Dae Hyun; Kyeong, Sunghyon; Do, Kyung Hee; Lim, Seong Kyu; Cho, Hyong Keun; Jung, Suk; Kim, Hye Won

    2018-04-01

    The recovery of independent gait after stroke is a main goal of patients and understanding the relationship between brain lesions and the recovery of gait can help physicians set viable rehabilitation plans. Our study investigated the association between variables of gait parameters and brain lesions.Fifty poststroke patients with a mean age of 67.5 ± 1.3 years and an average duration after onset of 62.2 ± 7.9 months were included. Three-dimensional gait analysis and magnetic resonance imaging were conducted for all patients. Twelve quantified gait parameters of temporal-spatial, kinematic, and kinetic data were used. To correlate gait parameters with specific brain lesions, we used a voxel-based lesion symptom mapping analysis. Statistical significance was set to an uncorrected P value 10 voxels.Based on the location of a brain lesion, the following results were obtained: The posterior limb of the internal capsule was significantly associated with gait speed and increased knee extension in the stance phase. The hippocampus and frontal lobe were significantly associated with cadence. The proximal corona radiata was significantly associated with stride length and affected the hip maximal extension angle in the stance phase. The paracentral lobule was significantly associated with the affected knee maximal flexion angle in the swing phase and with the affected ankle maximal dorsiflexion angle in the stance phase. The frontal lobe, thalamus, and the lentiform nucleus were associated with kinetic gait parameters.Cortical, proximal white matter, and learning-related and motor-related areas are mainly associated with one's walking ability after stroke.

  5. Acupuncture inhibits cue-induced heroin craving and brain activation.

    Science.gov (United States)

    Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

    2012-11-25

    Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving.

  6. The effect of neurofeedback on a brain wave and visual perception in stroke: a randomized control trial.

    Science.gov (United States)

    Cho, Hwi-Young; Kim, Kitae; Lee, Byounghee; Jung, Jinhwa

    2015-03-01

    [Purpose] This study investigated a brain wave and visual perception changes in stroke subjects using neurofeedback (NFB) training. [Subjects] Twenty-seven stroke subjects were randomly allocated to the NFB (n = 13) group and the control group (n=14). [Methods] Two expert therapists provided the NFB and CON groups with traditional rehabilitation therapy in 30 thirst-minute sessions over the course of 6 weeks. NFB training was provided only to the NFB group. The CON group received traditional rehabilitation therapy only. Before and after the 6-week intervention, a brain wave test and motor free visual perception test (MVPT) were performed. [Results] Both groups showed significant differences in their relative beta wave values and attention concentration quotients. Moreover, the NFB group showed a significant difference in MVPT visual discrimination, form constancy, visual memory, visual closure, spatial relation, raw score, and processing time. [Conclusion] This study demonstrated that NFB training is more effective for increasing concentration and visual perception changes than traditional rehabilitation. In further studies, detailed and diverse investigations should be performed considering the number and characteristics of subjects, and the NFB training period.

  7. Hemodynamic and metabolic state of hyperfixation with 99mTc-HMPAO brain SPECT in subacute stroke

    International Nuclear Information System (INIS)

    Cho, Ihnho; Hayashida, Kohei; Imakita, Satoshi; Kume, Norihiko; Fukuchi, Kazuki

    2000-01-01

    By means of positron emission tomography (PET), we investigated the hemodynamic and metabolic state of the hyperfixation identified as the increased accumulation with 99m Tc-d, l-hexamethylpropyleneamine oxime (HMPAO) by single photon emission computed tomography (SPECT) in patients with subacute stroke. We studied four patients with subacute stroke having hyperfixed areas evaluated with CBF, CMRO 2 , OEF and CBV by PET. The hyperfixation rate with 99m Tc-HMPAO was obtained by comparing the surplus rate with standardized CBF. The OEF and CMRO 2 values in the hyperfixed areas of 4 patients were significantly lower than those in normal 5 controls (p 99m Tc-HMPAO in the infarct area revealing a mismatch between CMRO 2 and CBF meant relative luxury perfusion. The hyperfixation rate determined by 99m Tc-HMPAO brain SPECT correlated with CBV in the PET study. We can conclude that one of the main factors which caused hyperfixation was vasodilatation as well as the blood brain barrier disruption and the neovascularization. (author)

  8. Netrin-1 Ameliorates Blood-Brain Barrier Impairment Secondary to Ischemic Stroke via the Activation of PI3K Pathway

    Directory of Open Access Journals (Sweden)

    Jian Yu

    2017-12-01

    Full Text Available Secondary impairment of blood-brain barrier (BBB occurs in the remote thalamus after ischemic stroke. Netrin-1, an axonal guidance molecule, presents bifunctional effects on blood vessels through receptor-dependent pathways. This study investigates whether netrin-1 protects BBB against secondary injury. Netrin-1 (600 ng/d for 7 days was intracerebroventricularly infused 24 h after middle cerebral artery occlusion (MCAO in hypertensive rats. Neurological function was assessed 8 and 14 days after MCAO, and the permeability of BBB in the ipsilateral thalamus was detected. The viability of brain microvascular endothelial cells was determined after being disposed with netrin-1 (50 ng/mL before oxygen-glucose deprivation (OGD. The role of netrin-1 was further explored by examining its receptors and their function. We found that netrin-1 infusion improved neurological function, attenuated secondary impairment of BBB by up-regulating the levels of tight junction proteins and diminishing extravasation of albumin, with autophagy activation 14 days after MCAO. Netrin-1 also enhanced cell survival and autophagy activity in OGD-treated cells, inhibited by UNC5H2 siRNA transfection. Furthermore, the beneficial effects of netrin-1 were suppressed by PI3K inhibitors 3-Methyladenine and LY294002. Our results showed that netrin-1 ameliorated BBB impairment secondary to ischemic stroke by promoting tight junction function and endothelial survival. PI3K-mediated autophagy activation depending on UNC5H2 receptor could be an underlying mechanism.

  9. Patterns of Post-Stroke Brain Damage that Predict Speech Production Errors in Apraxia of Speech and Aphasia Dissociate

    Science.gov (United States)

    Basilakos, Alexandra; Rorden, Chris; Bonilha, Leonardo; Moser, Dana; Fridriksson, Julius

    2015-01-01

    Background and Purpose Acquired apraxia of speech (AOS) is a motor speech disorder caused by brain damage. AOS often co-occurs with aphasia, a language disorder in which patients may also demonstrate speech production errors. The overlap of speech production deficits in both disorders has raised questions regarding if AOS emerges from a unique pattern of brain damage or as a sub-element of the aphasic syndrome. The purpose of this study was to determine whether speech production errors in AOS and aphasia are associated with distinctive patterns of brain injury. Methods Forty-three patients with history of a single left-hemisphere stroke underwent comprehensive speech and language testing. The Apraxia of Speech Rating Scale was used to rate speech errors specific to AOS versus speech errors that can also be associated with AOS and/or aphasia. Localized brain damage was identified using structural MRI, and voxel-based lesion-impairment mapping was used to evaluate the relationship between speech errors specific to AOS, those that can occur in AOS and/or aphasia, and brain damage. Results The pattern of brain damage associated with AOS was most strongly associated with damage to cortical motor regions, with additional involvement of somatosensory areas. Speech production deficits that could be attributed to AOS and/or aphasia were associated with damage to the temporal lobe and the inferior pre-central frontal regions. Conclusion AOS likely occurs in conjunction with aphasia due to the proximity of the brain areas supporting speech and language, but the neurobiological substrate for each disorder differs. PMID:25908457

  10. Brain Edema and Neurologic Deficits in Rat Stroke Model: The Effect of Hydroalcoholic Extract of Salvia Officinalis

    Directory of Open Access Journals (Sweden)

    elham ghasemloo

    2015-11-01

    Full Text Available Bachground & Objectives: In the brain ischemia, the production of free radicals increases. Salvia is a rich source of antioxidant compounds; therefore, in this study we will examine the effects of Salvia extracts on brain edema and score of neurological deficits.  Materials & Methods: In this experimental study, 35 male Wistar rats were randomly divided into 5 groups, each containing 7 rats. The control group received distilled water, and the other three groups received intrapertioneally hydroalcoholic extracts of Salvia officinalis with dosages of 50, 75, and 100 mg/kg for 3 weeks (1+3=4, Where is the other group? There should be five groups but there are only four groups here.. Thereafter, each main group underwent 60 min middle cerebral artery occlusion 2 hours after the last injection of Salvia extracts .This occlusion caused ischemia in the right hemisphere. Then, the brain edema was assessed, and the neurologic deficits were analyzed. The sham group was not treated and no induction of brain ischemia. Brain edema was analyzed through SPSS18 software and LSD method, while the analysis of neurologic deficits was carried out by Mann-Whitney U. Results: Our study results indicate that the hydroalcoholic extracts of Salvia reduced permeability brain edema in three dosages of 50, 75, and 100mg/kg (83/29±0/42 , 82/10±0/32 and 81/29±0/48, respectively compared with the control group (85/31±0/58. They also reduced the neurologic deficits in experimental groups of 75 and 100 mg/kg (1/43±0/37 and 1±0/31, respectively compared with the control group (3/71±0/42 (p<0.05. Conclusion: Salvia officinalis apparently have a protective effect against stroke damage due to the reduced brain edema and neurological disorders.

  11. Brain control of volitional ankle tasks in people with chronic stroke and in healthy individuals.

    Science.gov (United States)

    Beaulieu, L D; Massé-Alarie, H; Brouwer, B; Schneider, C

    2014-03-15

    This study explored the relationships between motor cortical control of ankle dorsiflexors and clinical impairments of volitional ankle dorsiflexion in people with chronic stroke. Eighteen persons with stroke and 14 controls were evaluated. Clinical tools were used to assess ankle dorsiflexion amplitude and isometric strength. Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) tested the functional integrity of cortical circuits controlling the tibialis anterior (TA). All clinical scores and most TMS outcomes were impaired in people with chronic stroke. The lower clinical scores were related to the reduction of the strength of corticospinal projections onto spinal motoneurons. Concurrent TMS and clinical testing in chronic stroke provided original data demonstrating relationships between the integrity of cortical and corticospinal components of TA motor control and volitional ankle tasks. Our study proposes that volitional ankle mobilization in chronic stroke may be explained by the residual abnormal M1 circuits which may be responsive for rehabilitation intervention. This should be confirmed in longitudinal studies with larger samples to determine whether TMS outcomes associated with lower limb muscles are predictive of clinical changes or vice versa. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Determining Optimal Post-Stroke Exercise (DOSE)

    Science.gov (United States)

    2018-02-13

    Cerebrovascular Accident; Stroke; Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

  13. Pathological links between stroke and cardiac arrest

    Institute of Scientific and Technical Information of China (English)

    Shaila Ghanekar; Sydney Corey; Trenton Lippert; Cesar V.Borlongan

    2017-01-01

    There may be a pathological connection between cardiac failure and ischemic stroke.In this article we describe pertinent research that demonstrates subsequent death of cardiac and neural myocytes in the post ischemic stroke brain.Current stroke therapy overlooks the connection between cardiac and cerebrovascular events and fails to address the shared risk factors.Current pre-clinical stroke investigations have provided evidence that suggests the presence of an indirect cell death pathway in which toxic molecules emanate from the stroke brain and trigger cardiac cell death.On the other hand,other studies highlight the presence of a reverse cell death cascade in which toxic molecules from the heart,following cardiac arrest,travel to the brain and induce ischemic cell death.Further examination of these putative cell death pathways between ischemic stroke and cardiac arrest will prompt the advancement of innovative treatments specifically targeting both diseases,leading to ameliorated clinical results of patients diagnosed with heart failure and ischemic stroke.

  14. The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation

    DEFF Research Database (Denmark)

    Minjoli, Sena; Saturnino, Guilherme B.; Blicher, Jakob Udby

    2017-01-01

    aimed to characterize the impact of these changes on the spatial distribution of the electric field generated by both TBS methods. In addition to confirming the safety of TBS in the presence of large stroke-related structural changes, our aim was to clarify whether targeted stimulation is still possible....... Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative...... to the lesion were tested. For TDCS, the finite-element method was used to simulate a standard approach with two electrode pads, and the position of one electrode was systematically varied. For both TMS and TDCS, the lesion caused electric field " hot spots" in the cortex. However, these maxima were...

  15. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    International Nuclear Information System (INIS)

    Weaver, John; Yang, Yirong; Purvis, Rebecca; Weatherwax, Theodore; Rosen, Gerald M.; Liu, Ke Jian

    2014-01-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O 2 may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O 2 is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO 2 in vivo remains largely uncharacterized. This study investigated striatal tissue pO 2 changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO 2 in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO 2 was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO 2 to 64%. More importantly, pO 2 did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO 2 indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO 2 , which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO 2 in vivo after METH administration by EPR oximetry. • pO 2 was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO 2 did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO 2 may be associated with a decrease in CBF. • Administration of methamphetamine may lead to hypoxic

  16. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, John, E-mail: jmweaver@salud.unm.edu [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Yang, Yirong [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Purvis, Rebecca [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Weatherwax, Theodore [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Rosen, Gerald M. [Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD 21201 (United States); Center for EPR Imaging In Vivo Physiology, University of Maryland, Baltimore, MD 21201 (United States); Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States); Liu, Ke Jian [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    2014-03-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O{sub 2} may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O{sub 2} is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO{sub 2}in vivo remains largely uncharacterized. This study investigated striatal tissue pO{sub 2} changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO{sub 2}in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO{sub 2} was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO{sub 2} to 64%. More importantly, pO{sub 2} did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO{sub 2} indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO{sub 2}, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO{sub 2}in vivo after METH administration by EPR oximetry. • pO{sub 2} was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO{sub 2} did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO{sub 2} may be associated with a decrease in

  17. The Therapeutic Potential of Induced Pluripotent Stem Cells After Stroke : Evidence from Rodent Models

    NARCIS (Netherlands)

    Zents, Karlijn; Copray, Sjef

    2016-01-01

    Stroke is the second most common cause of death and the leading cause of disability in the world. About 30% of the people that are affected by stroke die within a year; 25% of the patients that survive stroke remain in need of care after a year. Therefore, stroke is a major burden for health care

  18. Changes in resting-state functional connectivity after stroke in a mouse brain lacking extracellular matrix components.

    Science.gov (United States)

    Quattromani, Miriana Jlenia; Hakon, Jakob; Rauch, Uwe; Bauer, Adam Q; Wieloch, Tadeusz

    2018-04-01

    In the brain, focal ischemia results in a local region of cell death and disruption of both local and remote functional neuronal networks. Tissue reorganization following stroke can be limited by factors such as extracellular matrix (ECM) molecules that prevent neuronal growth and synaptic plasticity. The brain's ECM plays a crucial role in network formation, development, and regeneration of the central nervous system. Further, the ECM is essential for proper white matter tract development and for the formation of structures called perineuronal nets (PNNs). PNNs mainly surround parvalbumin/GABA inhibitory interneurons, of importance for processing sensory information. Previous studies have shown that downregulating PNNs after stroke reduces the neurite-inhibitory environment, reactivates plasticity, and promotes functional recovery. Resting-state functional connectivity (RS-FC) within and across hemispheres has been shown to correlate with behavioral recovery after stroke. However, the relationship between PNNs and RS-FC has not been examined. Here we studied a quadruple knock-out mouse (Q4) that lacks four ECM components: brevican, neurocan, tenascin-C and tenascin-R. We applied functional connectivity optical intrinsic signal (fcOIS) imaging in Q4 mice and wild-type (129S1 mice) before and 14 days after photothrombotic stroke (PT) to understand how the lack of crucial ECM components affects neuronal networks and functional recovery after stroke. Limb-placement ability was evaluated at 2, 7 and 14 days of recovery through the paw-placement test. Q4 mice exhibited significantly impaired homotopic RS-FC compared to wild-type mice, especially in the sensory and parietal regions. Changes in RS-FC were significantly correlated with the number of interhemispheric callosal crossings in those same regions. PT caused unilateral damage to the sensorimotor cortex and deficits of tactile-proprioceptive placing ability in contralesional fore- and hindlimbs, but the two

  19. Recovery of brain abscess-induced stuttering after neurosurgical intervention.

    Science.gov (United States)

    Sudo, Daisuke; Doutake, Youichi; Yokota, Hidenori; Watanabe, Eiju

    2018-05-12

    Stuttering occurs in approximately 5% of all children and 1% of adults. One type, neurogenic stuttering, is usually attributable to strokes or other structural damages to the brain areas that are responsible for language fluency. Here, we present the first case of neurogenic stuttering caused by a brain abscess. The patient was a 60-year-old man admitted for a seizure and administered an anticonvulsant, after which he began stuttering. MRI revealed a brain abscess in the left frontal lobe that extended to the dorsolateral prefrontal cortex (BA (Brodmann's area) 9 and 46), frontal eye field (BA 8) and premotor cortex and supplementary motor area (BA 6). After neurosurgical drainage and antibiotic treatment, the symptoms had resolved. This case is unique in that the therapeutic effects and localisation of the cause of stuttering were rapidly identified, allowing for a more accurate description of the neural circuitry related to stuttering. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Gender differences in alcohol-induced neurotoxicity and brain damage.

    Science.gov (United States)

    Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

    2013-09-06

    Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Experiences of participation in goal setting for people with stroke-induced aphasia in Norway. A qualitative study.

    Science.gov (United States)

    Berg, Karianne; Askim, Torunn; Balandin, Susan; Armstrong, Elizabeth; Rise, Marit By

    2017-06-01

    The body of research into client participation in aphasia rehabilitation is increasing, but the evidence on how it is implemented into clinical practice is still scarce. Particularly, the importance of including the "insider's perspective" has been demanded. The aim of this study was to explore how people with aphasia experienced client participation during the process of goal setting and clinical decision making in language rehabilitation. Fifteen people with stroke-induced aphasia participated in semi-structured in-depth interviews. A qualitative analysis using Systematic Text Condensation was undertaken. Analysis revealed four main themes: (1) pleased with services, (2) vagueness in language rehabilitation, (3) personal goals exist, and (4) desired level of participation. Even though people with stroke-induced aphasia overall are pleased with the language rehabilitation, there is a need for greater emphasis on making the framework of language rehabilitation less vague. Therapists should also spend more time on collaboration with people with stroke-induced aphasia and use available methods to support communication and collaboration. The findings underscore the need for further exploration of the potential outcomes of implementing client participation in goal setting and clinical decision making for persons with stroke-induced aphasia. Implications for rehabilitation All persons with stroke induced aphasia should be asked about their goals for rehabilitation not only once, but during the whole continuum of their rehabilitation journey. Rehabilitation professionals should place greater emphasis on client participation by asking people with stroke induced aphasia how they prefer to participate at different stages of rehabilitation. To ensure active participation for those who wants it, existing tools and techniques which promoted collaborative goal setting should be better incorporated.

  2. Zinc movement in the brain under kainate-induced seizures.

    Science.gov (United States)

    Takeda, Atsushi; Hirate, Maki; Tamano, Haruna; Oku, Naoto

    2003-05-01

    On the basis of the evidence that elimination of 65Zn from the brain of epilepsy (EL) mice is facilitated by induction of seizures, zinc movement in the brain was studied in mice injected with kainate (12 mg/kg x 3), which exhibited status epilepticus within 120 min after the last injection of kainate. Zinc concentrations in the brain were determined 24 h after the last injection of kainate. Zinc concentrations in the hippocampus, amygdala and cerebral cortex, in which zinc-containing glutamatergic neuron terminals exist, were significantly decreased by the treatment with kainate, while that in the cerebellum was not decreased. Timm's stain in the brain was extensively attenuated 24 h after the last injection of kainate. These results indicate that zinc homeostasis in the brain is affected by kainate-induced seizures. In the hippocampus of rats injected with kainate (10 mg/kg), furthermore, the release of zinc and glutamate into the extracellular fluid was studied using in vivo microdialysis. The levels of zinc and glutamate in the perfusate were increased along with seizure severity after injection of kainate. It is likely that zinc concentration in the synaptic vesicles is decreased by the excess excitation of glutamatergic neurons. The present study suggests that the excessive release of zinc and glutamate from the neuron terminals under kainate-induced seizures is associated with the loss of zinc from the brain.

  3. Five-Year Follow-Up on Transplanted Organs From Donors After Brain Death After Acute Stroke.

    Science.gov (United States)

    Spatenkova, Vera; Pokorna, Eva; Suchomel, Petr

    2017-08-01

    Efficient intensive care donor management can help alleviate the shortage of organs for transplant. The aim of this study was to investigate the efficiency of management of donors after brain death from our neurointensive care unit. We conducted a prospective observational 5-year follow-up on 29 transplanted organs from 14 brain-dead donors after acute stroke (7 subarachnoid and 4 intracerebral hemorrhages, 3 ischemic strokes). Mean age of donors was 56.2 ± 8.70 years, and mean number of days of artificial ventilation was 5.0 ± 3.84. We transplanted 27 kidneys and 2 livers to 29 patients with mean age of 55.3 ± 9.76 years. No hearts or lungs were transplanted from these donors. Of the 27 patients who underwent kidney transplant, 21 patients (78%) lived 5 years; of those, 17 patients (63%) had functional grafts. One patient (4%) had a primary afunctional graft, and 3 patients (11%) had graft rejection (at 3, 15, and 41 mo). Six patients (22%) died after kidney transplant, with 1 patient in this group having a functional graft, 1 patient having a primary afunctional graft, and 4 patients (15%) having graft rejection (at 1, 12, 44, and 56 mo). The 2 patients with liver transplants lived 5 years with functional grafts. The 5-year follow-up showed that organs from 14 brain-dead donors improved and saved 19 lives, with 17 patients receiving kidney transplants and 2 patients receiving liver transplants. Another 7 patients had only partially improved quality of life.

  4. Non-pharmacological interventions for perceptual disorders following stroke and other adult-acquired, non-progressive brain injury.

    Science.gov (United States)

    Bowen, Audrey; Knapp, Peter; Gillespie, David; Nicolson, Donald J; Vail, Andy

    2011-04-13

    Stroke and other adult-acquired brain injury may impair perception leading to distress and increased dependence on others. Perceptual rehabilitation includes functional training, sensory stimulation, strategy training and task repetition. To examine the evidence for improvement in activities of daily living (ADL) six months post randomisation for active intervention versus placebo or no treatment. We searched the trials registers of the Cochrane Stroke Group and the Cochrane Infectious Diseases Group (May 2009) but not the Injuries Group, the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1950 to August 2009), EMBASE (1980 to August 2009), CINAHL (1982 to August 2009), PsycINFO (1974 to August 2009), REHABDATA and PsycBITE (May to June 2009). We also searched trials and research registers, handsearched journals, searched reference lists and contacted authors. Randomised controlled trials of adult stroke or acquired brain injury. Our definition of perception excluded visual field deficits, neglect/inattention and apraxia. One review author assessed titles, abstracts and keywords for eligibility. At least two review authors independently extracted data. We requested unclear or missing information from corresponding authors. We included six single-site trials in rehabilitation settings, involving 338 participants. Four trials included people with only stroke. All studies provided sensory stimulation, sometimes with another intervention. Sensory stimulation typically involved practising tasks that required visuo-perceptual processing with occupational therapist assistance. Repetition was never used and only one study included functional training. No trials provided data on longer term improvement in ADL scores. Only three trials provided any data suitable for analysis. Two of these trials compared active to placebo intervention. There was no evidence of a difference in ADL scores at the scheduled end of intervention: mean

  5. Tissue is more important than time: insights into acute ischemic stroke from modern brain imaging.

    Science.gov (United States)

    Bivard, Andrew; Parsons, Mark

    2018-02-01

    The clinical practice of acute ischemic stroke treatment has undergone a major change over the last 5 years, as multimodal imaging becomes more accessible, and evidence mounts that individualized treatment is possible. Multimodal imaging performed before treatment provides invaluable information to treating clinicians, which includes confirmation of the diagnosis, and provides guidance on the appropriateness and the likely outcome of intravenous or endovascular treatment for individual patients (and their families). However, often health systems struggle to keep pace with science; thus, a one-size fits all protocol-driven basic imaging approach is still the norm in many stroke centers. Comprehensive multimodal computed tomography (CT) (incorporating noncontrast CT, CT angiography, and perfusion CT) provides rapid, reliable information about stroke pathophysiology that cannot be provided by more limited imaging prior to treatment. Multimodal CT identifies treatment responders for both intravenous thrombolysis and endovascular therapy. Now we are in the era of thrombectomy, the use of multimodal imaging routinely to guide treatment can no longer be avoided. In light of the ground breaking thrombectomy trial results and previous studies validating the use of multimodal imaging, there is now a strong rationale for performing comprehensive multimodal CT assessments before treatment as a standard of care for all stroke patients.

  6. Mechanisms of Aphasia Recovery after Stroke and the Role of Noninvasive Brain Stimulation

    Science.gov (United States)

    Hamilton, Roy H.; Chrysikou, Evangelia G.; Coslett, Branch

    2011-01-01

    One of the most frequent symptoms of unilateral stroke is aphasia, the impairment or loss of language functions. Over the past few years, behavioral and neuroimaging studies have shown that rehabilitation interventions can promote neuroplastic changes in aphasic patients that may be associated with the improvement of language functions. Following…

  7. MRI-induced heating of deep brain stimulation leads

    International Nuclear Information System (INIS)

    Mohsin, Syed A; Sheikh, Noor M; Saeed, Usman

    2008-01-01

    The radiofrequency (RF) field used in magnetic resonance imaging is scattered by medical implants. The scattered field of a deep brain stimulation lead can be very intense near the electrodes stimulating the brain. The effect is more pronounced if the lead behaves as a resonant antenna. In this paper, we examine the resonant length effect. We also use the finite element method to compute the near field for (i) the lead immersed in inhomogeneous tissue (fat, muscle, and brain tissues) and (ii) the lead connected to an implantable pulse generator. Electric field, specific absorption rate and induced temperature rise distributions have been obtained in the brain tissue surrounding the electrodes. The worst-case scenario has been evaluated by neglecting the effect of blood perfusion. The computed values are in good agreement with in vitro measurements made in the laboratory.

  8. Can earth's magnetic micropulsations induce brain activities modifications?

    International Nuclear Information System (INIS)

    Assis, Altair Souza de

    2008-01-01

    Full text: We present in this paper preliminary study on which level earth's magnetic micro pulsations might interact with human brain activities. Magnetic micro pulsations are magnetospheric plasma wave Eigenmodes that are generated at the earth's magnetosphere and, via magnetospheric-ionospheric coupling induce ionospheric currents, and this ionospheric current pattern creates surface geomagnetic perturbations, which induce earth's surface electrical currents, and they are easily detected by earth's based magnetometers. These Eigenmodes are basically of Alfven type, and can be generated, for instance, by magnetic storms, situation where they are more intense and, in principle, might be felt by a more sensible human brain. Here, we also show how the modes are generated and present theirs basic physical properties. Finally, we compare the magnetic field level at the brain with the micro pulsation magnetic intensity. (author)

  9. Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

    Directory of Open Access Journals (Sweden)

    Saldanha Colin J

    2011-07-01

    Full Text Available Abstract Background Estrogens from peripheral sources as well as central aromatization are neuroprotective in the vertebrate brain. Under normal conditions, aromatase is only expressed in neurons, however following anoxic/ischemic or mechanical brain injury; aromatase is also found in astroglia. This increased glial aromatization and the consequent estrogen synthesis is neuroprotective and may promote neuronal survival and repair. While the effects of estradiol on neuroprotection are well studied, what induces glial aromatase expression remains unknown. Methods Adult male zebra finches (Taeniopygia guttata were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohisotchemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA, an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test. Results Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression. Conclusions These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.

  10. The effect of pre-nutrition of hydroalcoholic extractof Origanum vulgare on brain edema and neurologic deficits in a rat stroke model

    Directory of Open Access Journals (Sweden)

    Meysam Foroozandeh

    2015-10-01

    Full Text Available Background and Aim: Stroke is one of the most important factors of mortality and disability in the world. Free radicals are produced following ischemic stroke and they play a central role in breaking the blood-brain barrier and  causing brain edema formation. The aim of the current study was to evaluate the effect of hydro- alcoholic extract of Origanum vulgare on brain edema and neurologic deficit in a rat stroke model. Materials and Methods: In thisexperimental study, 35 male Wistar rats were randomly divided into 5 equal groups.  The first  two groups (control and Sham received distilled water, while three treatment groups received oral Origanum vulgare extract for 30days (50,75and 100 mg/kgdaily, respectively.  Two hours after the last dose of Origanum vulgare extract,each main group underwent  a 60 min middle cerebral artery occlusion.  Then, the assessment of blood brain edema, and neurologic deficits analysis were done . Brain edema (brain water content was analyzed by One-Way ANOVA using LSD method and neurologic deficits analysis by means of Mann-Whitney U, and P<0.05 was taken as the significant level. Results: Origanum vulgare extract reduced brain edema in the experimental groups of 50 (82.49±0.47, 75 (80.89±0.63 and 100 mg/kg/day (80.80±0.66 compared to the control group (84.46±0.67. The neurologic deficit scores in the experimental groups of 75and 100mg/kg/day, compared with control group, but neurologic deficit scores did not affect the group receiving the dose 50 mg/kg. Conclusion:  The obtained data indicate that Origanum vulgar extract via reduction of brain edema and neurologic deficits scorescan have a protective effect on the stroke model.

  11. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation

    NARCIS (Netherlands)

    Hoeger, S.; Bergstraesser, C.; Selhorst, J.; Fontana, J.; Birck, R.; Waldherr, R.; Beck, G.; Sticht, C.; Seelen, M. A.; van Son, W. J.; Leuvenink, H.; Ploeg, R.; Schnuelle, P.; Yard, B. A.

    Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability

  12. Head movement during CT brain perfusion acquisition of patients with suspected acute ischemic stroke

    International Nuclear Information System (INIS)

    Fahmi, F.; Beenen, L.F.M.; Streekstra, G.J.; Janssen, N.Y.; Jong, H.W. de; Riordan, A.; Roos, Y.B.; Majoie, C.B.; Bavel, E. van; Marquering, H.A.

    2013-01-01

    Objective: Computed Tomography Perfusion (CTP) is a promising tool to support treatment decision for acute ischemic stroke patients. However, head movement during acquisition may limit its applicability. Information of the extent of head motion is currently lacking. Our purpose is to qualitatively and quantitatively assess the extent of head movement during acquisition. Methods: From 103 consecutive patients admitted with suspicion of acute ischemic stroke, head movement in 220 CTP datasets was qualitatively categorized by experts as none, minimal, moderate, or severe. The movement was quantified using 3D registration of CTP volume data with non-contrast CT of the same patient; yielding 6 movement parameters for each time frame. The movement categorization was correlated with National Institutes of Health Stroke Scale (NIHSS) score and baseline characteristic using multinomial logistic regression and student's t-test respectively. Results: Moderate and severe head movement occurred in almost 25% (25/103) of all patients with acute ischemic stroke. The registration technique quantified head movement with mean rotation angle up to 3.6° and 14°, and mean translation up to 9.1 mm and 22.6 mm for datasets classified as moderate and severe respectively. The rotation was predominantly in the axial plane (yaw) and the main translation was in the scan direction. There was no statistically significant association between movement classification and NIHSS score and baseline characteristics. Conclusions: Moderate or severe head movement during CTP acquisition of acute stroke patients is quite common. The presented registration technique can be used to automatically quantify the movement during acquisition, which can assist identification of CTP datasets with excessive head movement

  13. Prevalence of stenoses and occlusions of brain-supplying arteries in young stroke patients.

    LENUS (Irish Health Repository)

    von Sarnowski, Bettina

    2013-03-06

    OBJECTIVE: Atherosclerosis is believed to be a minor cause of TIA and stroke in younger and middle-aged patients. However, data from large cohorts are limited. This study investigates the prevalence of extracranial and intracranial atherosclerosis in stroke and TIA patients aged 18-55 years in the multinational sifap1 study. METHODS: From the sifap1 cohort (n = 5,023), we analyzed a subset of patients with complete data from carotid ultrasound studies. Patients with arterial dissections, vasculitis, and mobile thrombi were excluded. Among the remaining 2,187 patients (men: n = 1,319; 18-44 years: n = 744), intracranial arteries were additionally examined with ultrasonography in 1,612 patients (73.7%). Patients were stratified by sex and age groups (younger: 18-44 years; middle-aged: 45-55 years). RESULTS: In patients with ischemic stroke, the overall prevalence of carotid artery stenoses and occlusions was 8.9% (younger: 4.9%; middle-aged: 11.0%), of which 81% were symptomatic. Nonstenotic carotid plaques were more common in men than in women (15.8% vs 7.7%; p < 0.001), and in middle-aged than in younger patients (17.0% vs 4.9%; p < 0.001). Supratentorial intracranial artery stenoses and occlusions amounted to 11.8%. Supratentorial stenoses occurred more frequently in middle-aged patients (13.0% vs 7.8%; p < 0.001), whereas occlusions were equally common (both 3.2%; not significant). CONCLUSIONS: We observed a substantial proportion of atherosclerotic carotid artery stenoses and occlusions in younger stroke patients. Intracranial stenoses and occlusions were even more prevalent than extracranial carotid artery disease. Together with nonstenotic plaques, one-fifth of patients (21.2%) had symptomatic or asymptomatic large-artery atherosclerosis, which should encourage future stroke prevention campaigns to target risk factor modification in young people.

  14. Head movement during CT brain perfusion acquisition of patients with suspected acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Fahmi, F., E-mail: f.fahmi@amc.uva.nl [Department of Biomedical Engineering and Physics, AMC, Amsterdam (Netherlands); Beenen, L.F.M., E-mail: l.f.beenen@amc.uva.nl [Department of Radiology, AMC, Amsterdam (Netherlands); Streekstra, G.J., E-mail: g.j.streekstra@amc.uva.nl [Department of Biomedical Engineering and Physics, AMC, Amsterdam (Netherlands); Janssen, N.Y., E-mail: n.n.janssen@amc.uva.nl [Department of Biomedical Engineering and Physics, AMC, Amsterdam (Netherlands); Jong, H.W. de, E-mail: H.W.A.M.deJong@umcutrecht.nl [Department of Radiology, UMC Utrecht, 3584CX, Utrecht (Netherlands); Riordan, A., E-mail: alan.riordan@gmail.com [Department of Radiology, UMC Utrecht, 3584CX, Utrecht (Netherlands); Roos, Y.B., E-mail: y.b.roos@amc.uva.nl [Department of Neurology, AMC, Amsterdam (Netherlands); Majoie, C.B., E-mail: c.b.majoie@amc.uva.nl [Department of Radiology, AMC, Amsterdam (Netherlands); Bavel, E. van, E-mail: e.vanbavel@amc.uva.nl [Department of Biomedical Engineering and Physics, AMC, Amsterdam (Netherlands); Marquering, H.A., E-mail: h.a.marquering@amc.uva.nl [Department of Biomedical Engineering and Physics, AMC, Amsterdam (Netherlands); Department of Radiology, AMC, Amsterdam (Netherlands)

    2013-12-01

    Objective: Computed Tomography Perfusion (CTP) is a promising tool to support treatment decision for acute ischemic stroke patients. However, head movement during acquisition may limit its applicability. Information of the extent of head motion is currently lacking. Our purpose is to qualitatively and quantitatively assess the extent of head movement during acquisition. Methods: From 103 consecutive patients admitted with suspicion of acute ischemic stroke, head movement in 220 CTP datasets was qualitatively categorized by experts as none, minimal, moderate, or severe. The movement was quantified using 3D registration of CTP volume data with non-contrast CT of the same patient; yielding 6 movement parameters for each time frame. The movement categorization was correlated with National Institutes of Health Stroke Scale (NIHSS) score and baseline characteristic using multinomial logistic regression and student's t-test respectively. Results: Moderate and severe head movement occurred in almost 25% (25/103) of all patients with acute ischemic stroke. The registration technique quantified head movement with mean rotation angle up to 3.6° and 14°, and mean translation up to 9.1 mm and 22.6 mm for datasets classified as moderate and severe respectively. The rotation was predominantly in the axial plane (yaw) and the main translation was in the scan direction. There was no statistically significant association between movement classification and NIHSS score and baseline characteristics. Conclusions: Moderate or severe head movement during CTP acquisition of acute stroke patients is quite common. The presented registration technique can be used to automatically quantify the movement during acquisition, which can assist identification of CTP datasets with excessive head movement.

  15. 99mTc-bicisate reliably images CBF in chronic brain diseases but fails to show reflow hyperemia in subacute stroke

    DEFF Research Database (Denmark)

    Lassen, N A; Sperling, B

    1994-01-01

    of 115 cases were collected, and of these 105 were considered technically adequate, comprising 18 normal subjects, 18 senile dementia, eight epilepsy, one brain tumor, eight chronic head trauma, and 52 stroke cases. As expected, bicisate gave better spatial resolution than Xe. Agreement between...... the results of the two methods was noted in 98 cases, but not in the remaining 7, all belonging to the stroke group. These seven all suffered from a subacute stroke (11-23 days after onset), and the disagreement in all cases consisted of bicisate showing low count rate in the area of the infarct and Xe...... a normal or elevated flow (luxury perfusion) as sign of spontaneous thrombolysis with reperfusion; in fact, these seven cases comprised all the reperfusion cases in the series. The results validate bicisate as a tracer of CBF in normal humans and in chronic brain diseases. Only in a subgroup of subacute...

  16. Clinical and diagnostic approach to patients with hypopituitarism due to traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and ischemic stroke (IS).

    Science.gov (United States)

    Karamouzis, Ioannis; Pagano, Loredana; Prodam, Flavia; Mele, Chiara; Zavattaro, Marco; Busti, Arianna; Marzullo, Paolo; Aimaretti, Gianluca

    2016-06-01

    The hypothalamic-pituitary dysfunction attributable to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH), and ischemic stroke (IS) has been lately highlighted. The diagnosis of TBI-induced-hypopituitarism, defined as a deficient secretion of one or more pituitary hormones, is made similarly to the diagnosis of classical hypopituitarism because of hypothalamic/pituitary diseases. Hypopituitarism is believed to contribute to TBI-associated morbidity and to functional and cognitive final outcome, and quality-of-life impairment. Each pituitary hormone must be tested separately, since there is a variable pattern of hormone deficiency among patients with TBI-induced-hypopituitarism. Similarly, the SAH and IS may lead to pituitary dysfunction although the literature in this field is limited. The drive to diagnose hypopituitarism is the suspect that the secretion of one/more pituitary hormone may be subnormal. This suspicion can be based upon the knowledge that the patient has an appropriate clinical context in which hypopituitarism can be present, or a symptom known as caused by hypopituitarism. Hypopituitarism should be diagnosed as a combination of low peripheral and inappropriately normal/low pituitary hormones although their basal evaluation may be not distinctive due to pulsatile, circadian, or situational secretion of some hormones. Evaluation of the somatotroph and corticotroph axes require dynamic stimulation test (ITT for both axes, GHRH + arginine test for somatotroph axis) in order to clearly separate normal from deficient responses.

  17. Healthy Living after Stroke

    Science.gov (United States)

    ... Nutrition Cooking for Health Food for Thought: Heart-healthy Diet is Also Good For Your Brain Physical Activity Get Moving and Boost Your Brain Power Understanding Risky Conditions Converging Risk Factors for Stroke ...

  18. Association of antidepressant medication therapy with inpatient rehabilitation outcomes for stroke, traumatic brain injury, or traumatic spinal cord injury.

    Science.gov (United States)

    Weeks, Douglas L; Greer, Christopher L; Bray, Brenda S; Schwartz, Catrina R; White, John R

    2011-05-01

    To study whether outcomes in patients who have undergone inpatient rehabilitation for stroke, traumatic brain injury (TBI), or traumatic spinal cord injury (TSCI) differ based on antidepressant medication (ADM) use. Retrospective cohort study of 867 electronic medical records of patients receiving inpatient rehabilitation for stroke, TBI, or TSCI. Four cohorts were formed within each rehabilitation condition: patients with no history of ADM use and no indication of history of depression; patients with no history of ADM use but with a secondary diagnostic code for a depressive illness; patients with a history of ADM use prior to and during inpatient rehabilitation; and patients who began ADM therapy in inpatient rehabilitation. Freestanding inpatient rehabilitation facility (IRF). Patients diagnosed with stroke (n=625), TBI (n=175), and TSCI (n=67). Not applicable. FIM, rehabilitation length of stay (LOS), deviation between actual LOS and expected LOS, and functional gain per day. In each impairment condition, patients initiating ADM therapy in inpatient rehabilitation had longer LOS than patients in the same impairment condition on ADM at IRF admission, and had significantly longer LOS than patients with no history of ADM use and no diagnosis of depression (Pstroke and TBI groups initiating ADM in IRF than their counterparts with no history of ADM use, illustrating that the group initiating ADM therapy in rehabilitation significantly exceeded expected LOS. Increased LOS did not translate into functional gains, and in fact, functional gain per day was lower in the group initiating ADM therapy in IRF. Explanations for unexpectedly long LOS in patients initiating ADM in inpatient rehabilitation focus on the potential for ADM to inhibit therapy-driven remodeling of the nervous system when initiated close in time to nervous system injury, or the possibility that untreated sequelae (eg, depressive symptoms or fatigue) were limiting progress in therapy, which triggered

  19. Whole-brain perfusion CT using a toggling table technique to predict final infarct volume in acute ischemic stroke.

    Science.gov (United States)

    Schrader, I; Wilk, D; Jansen, O; Riedel, C

    2013-09-01

    To evaluate how accurately final infarct volume in acute ischemic stroke can be predicted with perfusion CT (PCT) using a 64-MDCT unit and the toggling table technique. Retrospective analysis of 89 patients with acute ischemic stroke who underwent CCT, CT angiography (CTA) and PCT using the "toggling table" technique within the first three hours after symptom onset. In patients with successful thrombolytic therapy (n = 48) and in those without effective thrombolytic therapy (n = 41), the infarct volume and the volume of the penumbra on PCT were compared to the infarct size on follow-up images (CT or MRI) performed within 8 days. The feasibility of complete infarct volume prediction by 8 cm cranio-caudal coverage was evaluated. The correlation between the volume of hypoperfusion on PCT defined by cerebral blood volume reduction and final infarct volume was strongest in patients with successful thrombolytic therapy with underestimation of the definite infarct volume by 8.5 ml on average. The CBV map had the greatest prognostic value. In patients without successful thrombolytic therapy, the final infarct volume was overestimated by 12.1 ml compared to the MTT map on PCT. All infarcts were detected completely. There were no false-positive or false-negative results. Using PCT and the "toggling table" technique in acute stroke patients is helpful for the rapid and accurate quantification of the minimal final infarct and is therefore a prognostic parameter which has to be evaluated in further studies to assess its impact on therapeutic decision. ▶ Using PCT and the “toggling table technique” allows accurate quantification of the infarct core and penumbra. ▶ It is possible to record dynamic perfusion parameters quickly and easily of almost the entire supratentorial brain volume on a 64-slice MDCT unit. ▶ The technique allows identification of those patients who could profit from thrombolytic therapy outside the established time intervals. © Georg Thieme Verlag

  20. Development of 99mTc-ethyl cysteinate dimer (Neurolite) for imaging brain blood flow in stroke and other disorders

    International Nuclear Information System (INIS)

    Liteplo, M.P.

    1992-01-01

    Compounds labeled with 99m Tc are widely used for imaging in diagnostic medicine to provide information on physiological functions of the body not obtainable with other imaging techniques that give primarily anatomical information, such as X-ray and magnetic resonance imaging. These radiopharmaceuticals are typically injected intravenously and allowed to distribute in the body; the patient is then imaged using a scintillation gamma camera. For example, in patients suspected of coronary artery disease, 99m Tc-Sestamibi (Cardiolite reg-sign) is injected into the blood stream during a stress test and is rapidly extracted by the heart muscle in proportion to its regional blood supply. The resulting images of the heart clearly distinguish areas of normal heart muscle form areas where the blood supply is compromised by coronary artery disease. In recent years, there has been considerable interest in the application of 99m Tc compounds to the diagnosis of brain diseases and disorders. This paper describes the development of 99m Tc-ethyl cysteinate dimer ( 99m Tc-ECD, Neurolite reg-sign) as a radiopharmaceutical for imaging the blood supply to the brain in patients with stroke or head trauma. In research, this agent is also useful in studying the effect of sensory stimuli, therapeutic drugs, and drugs of abuse on brain blood flow

  1. A hybrid brain-machine interface based on EEG and EMG activity for the motor rehabilitation of stroke patients.

    Science.gov (United States)

    Sarasola-Sanz, Andrea; Irastorza-Landa, Nerea; Lopez-Larraz, Eduardo; Bibian, Carlos; Helmhold, Florian; Broetz, Doris; Birbaumer, Niels; Ramos-Murguialday, Ander

    2017-07-01

    Including supplementary information from the brain or other body parts in the control of brain-machine interfaces (BMIs) has been recently proposed and investigated. Such enriched interfaces are referred to as hybrid BMIs (hBMIs) and have been proven to be more robust and accurate than regular BMIs for assistive and rehabilitative applications. Electromyographic (EMG) activity is one of the most widely utilized biosignals in hBMIs, as it provides a quite direct measurement of the motion intention of the user. Whereas most of the existing non-invasive EEG-EMG-hBMIs have only been subjected to offline testings or are limited to one degree of freedom (DoF), we present an EEG-EMG-hBMI that allows the simultaneous control of 7-DoFs of the upper limb with a robotic exoskeleton. Moreover, it establishes a biologically-inspired hierarchical control flow, requiring the active participation of central and peripheral structures of the nervous system. Contingent visual and proprioceptive feedback about the user's EEG and EMG activity is provided in the form of velocity modulation during functional task training. We believe that training with this closed-loop system may facilitate functional neuroplastic processes and eventually elicit a joint brain and muscle motor rehabilitation. Its usability is validated during a real-time operation session in a healthy participant and a chronic stroke patient, showing encouraging results for its application to a clinical rehabilitation scenario.

  2. [Elements of system semiotics of the brain and head with cranial vessels of patients with stroke and with risk of stroke development].

    Science.gov (United States)

    Makomela, N M

    2007-01-01

    By means of a multispiral computer and magnetic resonance tomography 211 patients with an ischemic stroke, 109 patients with hemorrhagic stroke, 41 patients with an arterial hypertensia, 43 patients with aneurism, 58 patients with discirculation encephalopathy, 125 patients with ischemic illness of heart, practically healthy 62 have been observed. The author found high frequency of pathological deformations of carotid and vertebral arteries of not closed arterial circle, calcification of the pineal body and vascular plexus of lateral ventricles. cysts of maxillary sinuses of patients with stroke in comparison with patients at risk of the development of stroke and practically healthy subjects.

  3. Finding an optimal rehabilitation paradigm after stroke: Enhancing fiber growth and training of the brain at the right moment

    Directory of Open Access Journals (Sweden)

    Anna-Sophia eWahl

    2014-06-01

    Full Text Available After stroke the central nervous system reveals a spectrum of intrinsic capacities to react as a highly dynamic system which can change the properties of its circuits, form new contacts, erase others, and remap related cortical and spinal cord regions. This plasticity can lead to a surprising degree of spontaneous recovery. It includes the activation of neuronal molecular mechanisms of growth and of extrinsic growth promoting factors and guidance signals in the tissue. Rehabilitative training and pharmacological interventions may modify and boost these neuronal processes, but almost nothing is known on the optimal timing of the different processes and therapeutic interventions and on their detailed interactions. Finding optimal rehabilitation paradigms requires an optimal orchestration of the internal processes of re‐organization and the therapeutic interventions in accordance with defined plastic time windows.In this review we summarize the mechanisms of spontaneous plasticity after stroke and experimental interventions to enhance growth and plasticity, with an emphasis on anti‐Nogo‐A immunotherapy. We highlight critical time windows of growth and of rehabilitative training and consider different approaches of combinatorial rehabilitative schedules. Finally, we discuss potential future strategies for designing repair and rehabilitation paradigms by introducing a 3 step model: determination of the metabolic and plastic status of the brain, pharmacological enhancement of its plastic mechanisms, and stabilization of newly formed functional connections by rehabilitative training.

  4. Transtentorial diachisis in stroke patients demonstrated by I-123 HIPDM brain imaging

    International Nuclear Information System (INIS)

    Shih, W.J.; DeKosky, S.; Coupal, J.J.; Clark, D.; Ryo, U.Y.; Kung, H.F.

    1988-01-01

    SPECT and planar images of 35 patients with stroke were compared with images of 26 patients with Alzheimer disease, two with Creutzfeldt-Jakob disease, and one with schizoaffective disorder. Transtentorial diaschisis (TTD) with decreased cerebellar activity was shown in 18 patients with large infarcts of middle cerebral artery (MCA) territory and in four patients with internal capsule and basal ganglia infarcts. No TTD was shown in the 29 patients without stroke and those with small infarcts. Decreased cerebral activity contralateral to cerebral infarct due to interruption of cerebellar flow in TTD was hypothesized. The authors concluded that TTD occurs exclusively in an extensive cerebral infarct of the MCA territory, and an absent cortical perfusion abnormality with presence of TTD may indicate basal ganglia and/or internal capsule infarct

  5. Acute cerebral stroke imaging and brain perfusion with the use of high-concentration contrast media

    Energy Technology Data Exchange (ETDEWEB)

    Miles, K.A. [Wesley Research Inst., The Wesley Hospital, Brisbane (Australia); Brighton and Sussex Medical School, Univ. of Sussex, Falmer, Brighton (United Kingdom)

    2003-12-01

    Acute cerebral stroke remains a major cause of death among adults and the emergence of new therapies has created a need for early and rapid imaging at a time when conventional CT is either normal or demonstrates subtle abnormalities that are easy to misinterpret. Perfusion CT uses the temporal changes in cerebral and blood attenuation during a rapid series of images acquired without table movement following an intravenous bolus of contrast medium to generate images of mean transit time (MTT) cerebral blood volume (CBV) and perfusion. Reduced perfusion with preserved CBV is indicative of reversible ischaemia, whereas a matched reduction in perfusion and CBV implies infarction. The CT perfusion imaging can positively identify patients with non-haemorrhagic stroke in the presence of a normal conventional CT, provide an indication as to prognosis and potentially select those patients for whom thrombolysis is appropriate. Perfusion CT offers a powerful adjunct to MDCT based imaging of cerebrovascular disease, but further clinical validation is required. (orig.)

  6. Investigations of primary blast-induced traumatic brain injury

    Science.gov (United States)

    Sawyer, T. W.; Josey, T.; Wang, Y.; Villanueva, M.; Ritzel, D. V.; Nelson, P.; Lee, J. J.

    2018-01-01

    The development of an advanced blast simulator (ABS) has enabled the reproducible generation of single-pulse shock waves that simulate free-field blast with high fidelity. Studies with rodents in the ABS demonstrated the necessity of head restraint during head-only exposures. When the head was not restrained, violent global head motion was induced by pressures that would not produce similar movement of a target the size and mass of a human head. This scaling artefact produced changes in brain function that were reminiscent of traumatic brain injury (TBI) due to impact-acceleration effects. Restraint of the rodent head eliminated these, but still produced subtle changes in brain biochemistry, showing that blast-induced pressure waves do cause brain deficits. Further experiments were carried out with rat brain cell aggregate cultures that enabled the conduct of studies without the gross movement encountered when using rodents. The suspension nature of this model was also exploited to minimize the boundary effects that complicate the interpretation of primary blast studies using surface cultures. Using this system, brain tissue was found not only to be sensitive to pressure changes, but also able to discriminate between the highly defined single-pulse shock waves produced by underwater blast and the complex pressure history exposures experienced by aggregates encased within a sphere and subjected to simulated air blast. The nature of blast-induced primary TBI requires a multidisciplinary research approach that addresses the fidelity of the blast insult, its accurate measurement and characterization, as well as the limitations of the biological models used.

  7. Have clinicians adopted the use of brain MRI for patients with TIA and minor stroke?

    Science.gov (United States)

    Chaturvedi, Seemant; Ofner, Susan; Baye, Fitsum; Myers, Laura J; Phipps, Mike; Sico, Jason J; Damush, Teresa; Miech, Edward; Reeves, Mat; Johanning, Jason; Williams, Linda S; Arling, Greg; Cheng, Eric; Yu, Zhangsheng; Bravata, Dawn

    2017-01-17

    Use of MRI with diffusion-weighted imaging (DWI) can identify infarcts in 30%-50% of patients with TIA. Previous guidelines have indicated that MRI-DWI is the preferred imaging modality for patients with TIA. We assessed the frequency of MRI utilization and predictors of MRI performance. A review of TIA and minor stroke patients evaluated at Veterans Affairs hospitals was conducted with regard to medical history, use of diagnostic imaging within 2 days of presentation, and in-hospital care variables. Chart abstraction was performed in a subset of hospitals to assess clinical variables not available in the administrative data. A total of 7,889 patients with TIA/minor stroke were included. Overall, 6,694 patients (84.9%) had CT or MRI, with 3,396/6,694 (50.7%) having MRI. Variables that were associated with increased odds of CT performance were age >80 years, prior stroke, history of atrial fibrillation, heart failure, coronary artery disease, anxiety, and low hospital complexity, while blood pressure >140/90 mm Hg and high hospital complexity were associated with increased likelihood of MRI. Diplopia (87% had MRI, p = 0.03), neurologic consultation on the day of presentation (73% had MRI, p 6 hours (74% had MRI, p = 0.0009) were associated with MRI performance. Within a national health system, about 40% of patients with TIA/minor stroke had MRI performed within 2 days. Performance of MRI appeared to be influenced by several patient and facility-level variables, suggesting that there has been partial acceptance of the previous guideline that endorsed MRI for patients with TIA. © 2016 American Academy of Neurology.

  8. Serial measurements of N-terminal pro-brain natriuretic peptide after acute ischemic stroke

    DEFF Research Database (Denmark)

    Jensen, J.K.; Mickley, H.; Bak, S.

    2006-01-01

    consecutive patients with acute ischemic stroke. RESULTS: NT-proBNP peaked the day after onset of symptoms (p = 0.007) followed by a decrease until day 5 (p = 0.001, ANOVA). At 6-month follow-up the difference in the level of NT-proBNP was unchanged compared to day 5 (p = 0.42). NT-proBNP levels > or =615 pg...

  9. Music for the ageing brain: Cognitive, emotional, social, and neural benefits of musical leisure activities in stroke and dementia.

    Science.gov (United States)

    Särkämö, Teppo

    2017-01-01

    Music engages an extensive network of auditory, cognitive, motor, and emotional processing regions in the brain. Coupled with the fact that the emotional and cognitive impact of music is often well preserved in ageing and dementia, music is a powerful tool in the care and rehabilitation of many ageing-related neurological diseases. In addition to formal music therapy, there has been a growing interest in self- or caregiver-implemented musical leisure activities or hobbies as a widely applicable means to support psychological wellbeing in ageing and in neurological rehabilitation. This article reviews the currently existing evidence on the cognitive, emotional, and neural benefits of musical leisure activities in normal ageing as well as in the rehabilitation and care of two of the most common and ageing-related neurological diseases: stroke and dementia.

  10. Delayed radiation-induced necrosis of the brain stem

    International Nuclear Information System (INIS)

    Yukawa, Osamu; Kodama, Yasunori; Kyoda, Jun; Yuki, Kiyoshi; Taniguchi, Eiji; Katayama, Shoichi; Hiroi, Tadashi; Uozumi, Toru.

    1993-01-01

    A 46-year-old man had surgery for a mixed glioma of the frontotemporal lobe. Postoperatively he received 50 Gy of irradiation. Sixteen months later he developed left hemiparesis and left facial palsy. MRI revealed lesion brain stem and basal ganglia. Despite chemotherapy and an additional 50 Gy dose, the patient deteriorated. Autopsy revealed a wide spread radiation-induced necrosis in the right cerebral hemisphere, midbrain and pons. In radiation therapy, great care must be taken to protect the normal brain tissue. (author)

  11. Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study.

    OpenAIRE

    Grau-Sánchez, Jennifer; Amengual, Julià L.; Rojo, Nuria; Veciana de las Heras, Misericordia; Montero Homs, Jordi; Rubio Borrego, Francisco Ramón; Altenmüller, Eckart; Münte, Thomas F.; Rodríguez Fornells, Antoni

    2013-01-01

    Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician's brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority...

  12. Bobath Concept versus constraint-induced movement therapy to improve arm functional recovery in stroke patients: a randomized controlled trial.

    Science.gov (United States)

    Huseyinsinoglu, Burcu Ersoz; Ozdincler, Arzu Razak; Krespi, Yakup

    2012-08-01

    To compare the effects of the Bobath Concept and constraint-induced movement therapy on arm functional recovery among stroke patients with a high level of function on the affected side. A single-blinded, randomized controlled trial. Outpatient physiotherapy department of a stroke unit. A total of 24 patients were randomized to constraint-induced movement therapy or Bobath Concept group. The Bobath Concept group was treated for 1 hour whereas the constraint-induced movement therapy group received training for 3 hours per day during 10 consecutive weekdays. Main measures were the Motor Activity Log-28, the Wolf Motor Function Test, the Motor Evaluation Scale for Arm in Stroke Patients and the Functional Independence Measure. The two groups were found to be homogeneous based on demographic variables and baseline measurements. Significant improvements were seen after treatment only in the 'Amount of use' and 'Quality of movement' subscales of the Motor Activity Log-28 in the constraint-induced movement therapy group over the the Bobath Concept group (P = 0.003; P = 0.01 respectively). There were no significant differences in Wolf Motor Function Test 'Functional ability' (P = 0.137) and 'Performance time' (P = 0.922), Motor Evaluation Scale for Arm in Stroke Patients (P = 0.947) and Functional Independence Measure scores (P = 0.259) between the two intervention groups. Constraint-induced movement therapy and the Bobath Concept have similar efficiencies in improving functional ability, speed and quality of movement in the paretic arm among stroke patients with a high level of function. Constraint-induced movement therapy seems to be slightly more efficient than the Bobath Concept in improving the amount and quality of affected arm use.

  13. Tumor sterilization dose and radiation induced change of the brain tissue in radiotherapy of brain tumors

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Maki, Yutaka; Takano, Shingo

    1987-01-01

    Ninety-seven patients with brain tumors (38 gliomas, 26 brain metastases, 18 sellar tumors, 15 others) were treated by cobalt gamma ray or proton radiotherapy. In this study, normal brain injury due to radiation was analysed in terms of time-dose-fractionation (TDF), nominal standard dose (NSD) by the Ellis formula and NeuNSD by a modification in which the N exponent was -0.44 and the T exponent was -0.06. Their calculated doses were analysed in relationship to the normal brain radiation induced change (RIC) and the tumor sterilization dose. All brain tumors with an exception of many patients with brain metastases were received a surgical extirpation subtotally or partially prior to radiotherapy. And all patients with glioma and brain metastasis received also immuno-chemotherapy in the usual manner during radiotherapy. The calculated dose expressed by NeuNSD and TDF showed a significant relationship between a therapeutic dose and a postradiation time in terms of the appearance of RIC. It was suggested that RIC was caused by a dose over 800 in NeuNSD and a dose over 70 in TDF. Furthermore, it was suggested that an aged patient and a patient who had the vulnerable brain tissue to radiation exposure in the irradiated field had the high risk of RIC. On the other hand, our results suggested that the tumor sterilization dose should be over 1,536 NeuNSD and the irradiated method should be further considered in addition to the radiobiological concepts for various brain tumors. (author)

  14. Altered Coupling between Motion-Related Activation and Resting-State Brain Activity in the Ipsilesional Sensorimotor Cortex after Cerebral Stroke

    Directory of Open Access Journals (Sweden)

    Jianping Hu

    2017-07-01

    Full Text Available Functional connectivity maps using resting-state functional magnetic resonance imaging (rs-fMRI can closely resemble task fMRI activation patterns, suggesting that resting-state brain activity may predict task-evoked activation or behavioral performance. However, this conclusion was mostly drawn upon a healthy population. It remains unclear whether the predictive ability of resting-state brain activity for task-evoked activation would change under different pathological conditions. This study investigated dynamic changes of coupling between patterns of resting-state functional connectivity (RSFC and motion-related activation in different stages of cerebral stroke. Twenty stroke patients with hand motor function impairment were involved. rs-fMRI and hand motion-related fMRI data were acquired in the acute, subacute, and early chronic stages of cerebral stroke on a 3-T magnetic resonance (MR scanner. Sixteen healthy participants were enrolled as controls. For each subject, an activation map of the affected hand was first created using general linear model analysis on task fMRI data, and then an RSFC map was determined by seeding at the peak region of hand motion activation during the intact hand task. We then measured the extent of coupling between the RSFC maps and motion-related activation maps. Dynamic changes of the coupling between the two fMRI maps were estimated using one-way repeated measures analysis of variance across the three stages. Moreover, imaging parameters were correlated with motor performances. Data analysis showed that there were different coupling patterns between motion-related activation and RSFC maps associating with the affected motor regions during the acute, subacute, and early chronic stages of stroke. Coupling strengths increased as the recovery from stroke progressed. Coupling strengths were correlated with hand motion performance in the acute stage, while coupling recovery was negatively correlated with the recovery

  15. Using transcranial magnetic stimulation of the undamaged brain to identify lesion sites that predict language outcome after stroke.

    Science.gov (United States)

    Lorca-Puls, Diego L; Gajardo-Vidal, Andrea; Seghier, Mohamed L; Leff, Alexander P; Sethi, Varun; Prejawa, Susan; Hope, Thomas M H; Devlin, Joseph T; Price, Cathy J

    2017-06-01

    unguided lesion overlap map; and (iii) a region identified from voxel-based lesion-symptom mapping. Finally, consistent with prior findings from functional imaging and transcranial magnetic stimulation in healthy participants, we show how damage to our transcranial magnetic stimulation-guided regions affected performance on phonologically more than semantically demanding tasks. The observation that phonological processing abilities were impaired years after the stroke, suggests that other brain regions were not able to fully compensate for the contribution that the transcranial magnetic stimulation-guided regions make to language tasks. More generally, our novel transcranial magnetic stimulation-guided lesion-deficit mapping approach shows how non-invasive stimulation of the healthy brain can be used to guide the identification of regions where brain damage is likely to cause persistent behavioural effects. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  16. Characterizing the protocol for early modified constraint-induced movement therapy in the EXPLICIT-stroke trial

    NARCIS (Netherlands)

    Nijland, R van; Wegen, E. van; Krogt, H. van der; Bakker, C.D.; Buma, F.; Klomp, A.; Kordelaar, J. van; Kwakkel, G.; Geurts, A.C.; Kuijk, A.A. van; Lindeman, E.; Visser-Meily, J.M.A.; Arendzen, H.J.; Meskers, C.G.; Helm, F.C.T. van der; Vlugt, E. de

    2013-01-01

    Constraint-induced movement therapy (CIMT) is a commonly used rehabilitation intervention to improve upper limb function after stroke. CIMT was originally developed for patients with a chronic upper limb paresis. Although there are indications that exercise interventions should start as early as

  17. Effect of atorvastatin on hyperglycemia-induced brain oxidative stress and neuropathy induced by diabetes

    Directory of Open Access Journals (Sweden)

    Nastaran Faghihi

    2015-04-01

    Conclusion: The findings of the present study reveal that atorvastatin is able to prevent hyperglycemia-induced diabetic neuropathy and inhibit brain oxidative stress during diabetes. It is probable that reduction of urea is one of the reasons for atorvastatin prevention of hyperglycemia-induced neuropathy.

  18. Pharmacological targeting of secondary brain damage following ischemic or hemorrhagic stroke, traumatic brain injury, and bacterial meningitis - a systematic review and meta-analysis.

    Science.gov (United States)

    Beez, Thomas; Steiger, Hans-Jakob; Etminan, Nima

    2017-12-07

    The effectiveness of pharmacological strategies exclusively targeting secondary brain damage (SBD) following ischemic stroke, aneurysmal subarachnoid hemorrhage, aSAH, intracerebral hemorrhage (ICH), traumatic brain injury (TBI) and bacterial meningitis is unclear. This meta-analysis studied the effect of SBD targeted treatment on clinical outcome across the pathological entities. Randomized, controlled, double-blinded trials on aforementioned entities with 'death' as endpoint were identified. Effect sizes were analyzed and expressed as pooled risk ratio (RR) estimates with 95% confidence intervals (CI). 123 studies fulfilled the criteria, with data on 66,561 patients. In the pooled analysis, there was a minor reduction of mortality for aSAH [RR 0.93 (95% CI:0.85-1.02)], ICH [RR 0.92 (95% CI:0.82-1.03)] and bacterial meningitis [RR 0.86 (95% CI:0.68-1.09)]. No reduction of mortality was found for ischemic stroke [RR 1.05 (95% CI:1.00-1.11)] and TBI [RR 1.03 (95% CI:0.93-1.15)]. Additional analysis of "poor outcome" as endpoint gave similar results. Subgroup analysis with respect to effector mechanisms showed a tendency towards a reduced mortality for the effector mechanism category "oxidative metabolism/stress" for aSAH with a risk ratio of 0.86 [95% CI: 0.73-1.00]. Regarding specific medications, a statistically significant reduction of mortality and poor outcome was confirmed only for nimodipine for aSAH and dexamethasone for bacterial meningitis. Our results show that only a few selected SBD directed medications are likely to reduce the rate of death and poor outcome following aSAH, and bacterial meningitis, while no convincing evidence could be found for the usefulness of SBD directed medications in ischemic stroke, ICH and TBI. However, a subtle effect on good or excellent outcome might remain undetected. These results should lead to a new perspective of secondary reactions following cerebral injury. These processes should not be seen as suicide mechanisms

  19. A Pharmacogenetic Discovery: Cystamine Protects Against Haloperidol-Induced Toxicity and Ischemic Brain Injury.

    Science.gov (United States)

    Zhang, Haili; Zheng, Ming; Wu, Manhong; Xu, Dan; Nishimura, Toshihiko; Nishimura, Yuki; Giffard, Rona; Xiong, Xiaoxing; Xu, Li Jun; Clark, J David; Sahbaie, Peyman; Dill, David L; Peltz, Gary

    2016-05-01

    Haloperidol is an effective antipsychotic agent, but it causes Parkinsonian-like extrapyramidal symptoms in the majority of treated subjects. To address this treatment-limiting toxicity, we analyzed a murine genetic model of haloperidol-induced toxicity (HIT). Analysis of a panel of consomic strains indicated that a genetic factor on chromosome 10 had a significant effect on susceptibility to HIT. We analyzed a whole-genome SNP database to identify allelic variants that were uniquely present on chromosome 10 in the strain that was previously shown to exhibit the highest level of susceptibility to HIT. This analysis implicated allelic variation within pantetheinase genes (Vnn1 and Vnn3), which we propose impaired the biosynthesis of cysteamine, could affect susceptibility to HIT. We demonstrate that administration of cystamine, which is rapidly metabolized to cysteamine, could completely prevent HIT in the murine model. Many of the haloperidol-induced gene expression changes in the striatum of the susceptible strain were reversed by cystamine coadministration. Since cystamine administration has previously been shown to have other neuroprotective actions, we investigated whether cystamine administration could have a broader neuroprotective effect. Cystamine administration caused a 23% reduction in infarct volume after experimentally induced cerebral ischemia. Characterization of this novel pharmacogenetic factor for HIT has identified a new approach for preventing the treatment-limiting toxicity of an antipsychotic agent, which could also be used to reduce the extent of brain damage after stroke. Copyright © 2016 by the Genetics Society of America.

  20. Implicit sequence-specific motor learning after sub-cortical stroke is associated with increased prefrontal brain activations: An fMRI study

    Science.gov (United States)

    Meehan, Sean K.; Randhawa, Bubblepreet; Wessel, Brenda; Boyd, Lara A.

    2010-01-01

    Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence-specific motor learning as compared to general improvements in motor control. Nine healthy participants and 9 individuals with chronic, right focal sub-cortical stroke performed a continuous joystick-based tracking task during an initial fMRI session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence-specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequences during early practice and again at the retention test. Both groups demonstrated implicit sequence-specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased BOLD response in left dorsal premotor cortex (BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence-specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal-based attentional network for implicit motor learning after stroke. The present study is the first to highlight the importance of the prefrontal cortex for implicit sequence-specific motor learning after stroke. PMID:20725908

  1. Default Mode Network Connectivity in Stroke Patients.

    Science.gov (United States)

    Tuladhar, Anil Man; Snaphaan, Liselore; Shumskaya, Elena; Rijpkema, Mark; Fernandez, Guillén; Norris, David G; de Leeuw, Frank-Erik

    2013-01-01

    The pathophysiology of episodic memory dysfunction after infarction is not completely understood. It has been suggested that infarctions located anywhere in the brain can induce widespread effects causing disruption of functional networks of the cortical regions. The default mode network, which includes the medial temporal lobe, is a functional network that is associated with episodic memory processing. We investigated whether the default mode network activity is reduced in stroke patients compared to healthy control subjects in the resting state condition. We assessed the whole brain network properties during resting state functional MRI in 21 control subjects and 20 'first-ever' stroke patients. Patients were scanned 9-12 weeks after stroke onset. Stroke lesions were located in various parts of the brain. Independent component analyses were conducted to identify the default mode network and to compare the group differences of the default mode network. Furthermore, region-of-interest based analysis was performed to explore the functional connectivity between the regions of the default mode network. Stroke patients performed significantly worse than control subjects on the delayed recall score on California verbal learning test. We found decreased functional connectivity in the left medial temporal lobe, posterior cingulate and medial prefrontal cortical areas within the default mode network and reduced functional connectivity between these regions in stroke patients compared with controls. There were no significant volumetric differences between the groups. These results demonstrate that connectivity within the default mode network is reduced in 'first-ever' stroke patients compared to control subjects. This phenomenon might explain the occurrence of post-stroke cognitive dysfunction in stroke patients.

  2. A review of Constraint-Induced Therapy applied to aphasia rehabilitation in stroke patients

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    Joana Bisol Balardin

    Full Text Available Abstract Constraint-induced aphasia therapy (CIAT is an intensive therapy model based on the forced use of verbal oral language as the sole channel of communication, while any alternative communication mode such as writing, gesturing or pointing are prevented. Objectives: This critical review involved the analysis of studies examining CIAT applied to stroke patients. Methods and Results: Using keywords, the Medline database was searched for relevant studies published between 2001 and 2008 (Medline 2001-2008. The critical evaluation of the articles was based on the classifications described by the ASNS (Cicerone adaptation. Two studies were categorized as level Ia, two as level II and one study as level IV. Conclusions: These recommendations should be interpreted with caution, given the small number of studies involved, but serve as a guideline for future studies in aphasia therapy.

  3. Anabolic steroids abuse-induced cardiomyopathy and ischaemic stroke in a young male patient.

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    Shamloul, Reham Mohammed; Aborayah, Ahmed Fathy; Hashad, Assem; Abd-Allah, Foad

    2014-02-26

    We report a case of a 37-year-old man presented with acute stroke and hepatorenal impairment which were associated with anabolic-androgenic steroids (AAS) abuse over 2 years. Despite the absence of apparent symptoms and signs of congestive heart failure at presentation, an AAS-induced dilated cardiomyopathy with multiple thrombi in the left ventricle was attributed to be the underlying cause of his condition. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and improved the liver and kidney functions. However, the patient was exposed to a second severe ischaemic event, which led to his death. This unique and complex presentation of AAS complications opens for better recognition and treatment of their potentially fatal effects.

  4. Syntactic and Morphosyntactic Processing in Stroke-Induced and Primary Progressive Aphasia

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    Cynthia K. Thompson

    2013-01-01

    Full Text Available The paper reports findings derived from three experiments examining syntactic and morphosyntactic processing in individuals with agrammatic and logopenic variants of primary progressive aphasia (PPA-G and PPA-L, respectively and stroke-induced agrammatic and anomic aphasia (StrAg and StrAn, respectively. We examined comprehension and production of canonical and noncanonical sentence structures and production of tensed and nontensed verb forms using constrained tasks in experiments 1 and 2, using the Northwestern Assessment of Verbs and Sentences (NAVS [57] and the Northwestern Assessment of Verb Inflection (NAVI, Thompson and Lee, experimental version test batteries, respectively. Experiment 3 examined free narrative samples, focusing on syntactic and morphosyntactic measures, i.e. production of grammatical sentences, noun to verb ratio, open-class to closed-class word production ratio, and the production of correctly inflected verbs. Results indicate that the two agrammatic groups (i.e., PPA-G and StrAg pattern alike on syntactic and morphosyntactic measures, showing more impaired noncanonical compared to canonical sentence comprehension and production and greater difficulties producing tensed compared to nontensed verb forms. Their spontaneous speech also contained significantly fewer grammatical sentences and correctly inflected verbs, and they produced a greater proportion of nouns compared to verbs, than healthy speakers. In contrast, PPA-L and StrAn individuals did not display these deficits, and performed significantly better than the agrammatic groups on these measures. The findings suggest that agrammatism, whether induced by degenerative disease or stroke, is associated with characteristic deficits in syntactic and morphosyntactic processing. We therefore recommend that linguistically sophisticated tests and narrative analysis procedures be used to systematically evaluate the linguistic ability of individuals with PPA, contributing to

  5. NOSH-NBP, a Novel Nitric Oxide and Hydrogen Sulfide- Releasing Hybrid, Attenuates Ischemic Stroke-Induced Neuroinflammatory Injury by Modulating Microglia Polarization

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    Jing Ji

    2017-05-01

    Full Text Available NOSH-NBP, a novel nitric oxide (NO and hydrogen sulfide (H2S-releasing hybrid, protects brain from ischemic stroke. This study mainly aimed to investigate the therapeutic effect of NOSH-NBP on ischemic stroke and the underlying mechanisms. In vivo, transient middle cerebral artery occlusion (tMCAO was performed in C57BL/6 mice, with NO-NBP and H2S-NBP as controls. NO and H2S scavengers, carboxy-PTIO and BSS, respectively, were used to quench NO and H2S of NOSH-NBP. In vitro, BV2 microglia/BMDM were induced to the M1/2 phenotype, and conditioned medium (CM experiments in BV2 microglia, neurons and b.End3 cerebral microvascular endothelial cells (ECs were performed. Microglial/macrophage activation/polarization was assessed by flow cytometry, Western blot, RT-qPCR, and ELISA. Neuronal and EC survival was measured by TUNEL, flow cytometry, MTT and LDH assays. Transmission electron microscopy, EB extravasation, brain water content, TEER measurement and Western blot were used to detect blood–brain barrier (BBB integrity and function. Interestingly, NOSH-NBP significantly reduced cerebral infarct volume and ameliorated neurological deficit, with superior effects compared with NO-NBP and/or H2S-NBP in mice after tMCAO. Both NO and H2S-releasing groups contributed to protection by NOSH-NBP. Additionally, NOSH-NBP decreased neuronal death and attenuated BBB dysfunction in tMCAO-treated mice. Furthermore, NOSH-NBP promoted microglia/macrophage switch from an inflammatory M1 phenotype to the protective M2 phenotype in vivo and in vitro. Moreover, the TLR4/MyD88/NF-κB pathway and NLRP3 inflammasome were involved in the inhibitory effects of NOSH-NBP on M1 polarization, while peroxisome proliferator activated receptor gamma signaling contributed to NOSH-NBP induced M2 polarization. These findings indicated that NOSH-NBP is a potential therapeutic agent that preferentially promotes microglial/macrophage M1–M2 switch in ischemic stroke.

  6. Early Rehabilitation After Stroke: a Narrative Review.

    Science.gov (United States)

    Coleman, Elisheva R; Moudgal, Rohitha; Lang, Kathryn; Hyacinth, Hyacinth I; Awosika, Oluwole O; Kissela, Brett M; Feng, Wuwei

    2017-11-07

    Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain's dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. Overall, trials of rehabilitation in the first 2 weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24 h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2 weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial. Commencing intensive therapy in the first 24 h may be harmful.

  7. Post-stroke Rehabilitation Training with a Motor-Imagery-Based Brain-Computer Interface (BCI)-Controlled Hand Exoskeleton: A Randomized Controlled Multicenter Trial.

    Science.gov (United States)

    Frolov, Alexander A; Mokienko, Olesya; Lyukmanov, Roman; Biryukova, Elena; Kotov, Sergey; Turbina, Lydia; Nadareyshvily, Georgy; Bushkova, Yulia

    2017-01-01

    Repeated use of brain-computer interfaces (BCIs) providing contingent sensory feedback of brain activity was recently proposed as a rehabilitation approach to restore motor function after stroke or spinal cord lesions. However, there are only a few clinical studies that investigate feasibility and effectiveness of such an approach. Here we report on a placebo-controlled, multicenter clinical trial that investigated whether stroke survivors with severe upper limb (UL) paralysis benefit from 10 BCI training sessions each lasting up to 40 min. A total of 74 patients participated: median time since stroke is 8 months, 25 and 75% quartiles [3.0; 13.0]; median severity of UL paralysis is 4.5 points [0.0; 30.0] as measured by the Action Research Arm Test, ARAT, and 19.5 points [11.0; 40.0] as measured by the Fugl-Meyer Motor Assessment, FMMA. Patients in the BCI group ( n = 55) performed motor imagery of opening their affected hand. Motor imagery-related brain electroencephalographic activity was translated into contingent hand exoskeleton-driven opening movements of the affected hand. In a control group ( n = 19), hand exoskeleton-driven opening movements of the affected hand were independent of brain electroencephalographic activity. Evaluation of the UL clinical assessments indicated that both groups improved, but only the BCI group showed an improvement in the ARAT's grasp score from 0 [0.0; 14.0] to 3.0 [0.0; 15.0] points ( p exoskeleton-assisted physical therapy can improve post-stroke rehabilitation outcomes. Both maximum and mean values of the percentage of successfully decoded imagery-related EEG activity, were higher than chance level. A correlation between the classification accuracy and the improvement in the upper extremity function was found. An improvement of motor function was found for patients with different duration, severity and location of the stroke.

  8. Systemic progesterone for modulating electrocautery-induced secondary brain injury.

    Science.gov (United States)

    Un, Ka Chun; Wang, Yue Chun; Wu, Wutian; Leung, Gilberto Ka Kit

    2013-09-01

    Bipolar electrocautery is an effective and commonly used haemostatic technique but it may also cause iatrogenic brain trauma due to thermal injury and secondary inflammatory reactions. Progesterone has anti-inflammatory and neuroprotective actions in traumatic brain injury. However, its potential use in preventing iatrogenic brain trauma has not been explored. We conducted a pilot animal study to investigate the effect of systemic progesterone on brain cellular responses to electrocautery-induced injury. Adult male Sprague-Dawley rats received standardized bipolar electrocautery (40 W for 2 seconds) over the right cerebral cortex. The treatment group received progesterone intraperitoneally 2 hours prior to surgery; the control group received the drug vehicle only. Immunohistochemical studies showed that progesterone could significantly reduce astrocytic hypertrophy on postoperative day 1, 3 and 7, as well as macrophage infiltration on day 3. The number of astrocytes, however, was unaffected. Our findings suggest that progesterone should be further explored as a neuroprotective agent against electrocautery-induced or other forms of iatrogenic trauma during routine neurosurgical procedures. Future studies may focus on different dosing regimens, neuronal survival, functional outcome, and to compare progesterone with other agents such as dexamethasone. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Prostaglandin E2 EP2 Receptor Deletion Attenuates Intracerebral Hemorrhage-Induced Brain Injury and Improves Functional Recovery

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    Jenna L. Leclerc

    2015-04-01

    Full Text Available Intracerebral hemorrhage (ICH is a devastating type of stroke characterized by bleeding into the brain parenchyma and secondary brain injury resulting from strong neuroinflammatory responses to blood components. Production of prostaglandin E2 (PGE2 is significantly upregulated following ICH and contributes to this inflammatory response in part through its E prostanoid receptor subtype 2 (EP2. Signaling through the EP2 receptor has been shown to affect outcomes of many acute and chronic neurological disorders; although, not yet explored in the context of ICH. Wildtype (WT and EP2 receptor knockout (EP2−/− mice were subjected to ICH, and various anatomical and functional outcomes were assessed by histology and neurobehavioral testing, respectively. When compared with age-matched WT controls, EP2−/− mice had 41.9 ± 4.7% smaller ICH-induced brain lesions and displayed significantly less ipsilateral hemispheric enlargement and incidence of intraventricular hemorrhage. Anatomical outcomes correlated with improved functional recovery as identified by neurological deficit scoring. Histological staining was performed to begin investigating the mechanisms involved in EP2-mediated neurotoxicity after ICH. EP2−/− mice exhibited 45.5 ± 5.8% and 41.4 ± 8.1% less blood and ferric iron accumulation, respectively. Furthermore, significantly less striatal and cortical microgliosis, striatal and cortical astrogliosis, blood–brain barrier breakdown, and peripheral neutrophil infiltration were seen in EP2−/− mice. This study is the first to suggest a deleterious role for the PGE2-EP2 signaling axis in modulating brain injury, inflammation, and functional recovery following ICH. Targeting the EP2 G protein-coupled receptor may represent a new therapeutic avenue for the treatment of hemorrhagic stroke.

  10. Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

    Science.gov (United States)

    Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

    2017-01-01

    Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

  11. Pediatric Stroke

    Science.gov (United States)

    ... and Patient Resources Home » Patients & Families » About Stroke » Pediatric Stroke » Introduction Introduction What is a Stroke? Ischemic Stroke Intracerebral Hemorrhage Subarachnoid Hemorrhage Pediatric Stroke Introduction Types of Stroke Diagnosis and Treatment ...

  12. Motor rehabilitation after traumatic brain injury and stroke - Advances in assessment and therapy.

    Science.gov (United States)

    Platz, Thomas; Hesse, S.; Mauritz, K.-H.

    1999-01-01

    A long-term goal in motor rehabilitation is that treatment is not selected on the basis of 'schools of thought', but rather, based on knowledge about efficacy and effectiveness of specific interventions for specific situations (e.g. functional syndromes). Motor dysfunction after stroke or TBI can be caused by many different functional syndromes such as paresis, ataxia, deafferentaion, visuo-perceptual deficits, or apraxia. Examples are provided showing that theory-based analysis of motor behavior makes it possible to describe 'syndrome-specific motor deficits'. Its potential implications for motor rehabilitation are that our understanding of altered motor behavior as well as specific therapeutic approaches might be promoted. A methodological prerequisite for clinical trials in rehabilitation is knowledge about test properties of assessment tools in follow-up situations such as test-retest reliability and responsiveness to change. Test-retest reliability assesses whether a test can produce stable measures with test repetition, while sensitivity to change reflects whether a test detects changes that occur over time. Exemplifying these considerations, a reliability and validity study of a kinematic arm movement analysis is summarized. In terms of new therapeutic developments, two examples of clinical therapeutic studies are provided assessing the efficacy of specific inter-ventions for specific situations in arm and gait rehabilitation: the Arm Ability Training for high functioning hemiparetic stroke and TBI patients, and the treadmill training for non-ambulatory hemiparetic patients. In addition, a new technical development, a machine-controlled gait trainer ist introduced.

  13. Functional brain imaging to investigate the higher brain dysfunction induced by diffuse brain injury

    International Nuclear Information System (INIS)

    Nariai, Tadashi; Inaji, Motoki; Ohno, Kikuo; Hiura, Mikio; Ishii, Kenji; Hosoda, Chihiro

    2011-01-01

    Higher brain dysfunction is the major problem of patients who recover from neurotrauma the prevents them from returning to their previous social life. Many such patients do not have focal brain damage detected with morphological imaging. We focused on studying the focal brain dysfunction that can be detected only with functional imaging with positron emission tomography (PET) in relation to the score of various cognition batteries. Patients who complain of higher brain dysfunction without apparent morphological cortical damage were recruited for this study. Thirteen patients with diffuse axonal injury (DAI) or cerebral concussion was included. They underwent a PET study to image glucose metabolism by 18 F-fluorodeoxyglucose (FDG), and central benodiazepine receptor (cBZD-R) (marker of neuronal body) by 11 C-flumazenil, together with cognition measurement by WAIS-R, WMS-R, and WCST etc. PET data were compared with age matched normal controls using statistical parametric mapping (SPM)2. DAI patients had a significant decrease in glucose matabolism and cBZD-R distribution in the cingulated cortex than normal controls. Patients diagnosed with concussion because of shorter consciousness disturbance also had abnormal FDG uptake and cBZD-R distribution. Cognition test scores were variable among patients. Degree of decreased glucose metabolism and cBZD-R distribution in the dominant hemishphere corresponded well to the severity of cognitive disturbance. PET molecular imaging was useful to depict focal cortical dysfunction of neurotrauma patients even when morphological change was not apparent. This method may be promising to clarify the pathophysiology of higher brain dysfunction of patients with diffuse axonal injury or chronic traumatic encephalopathy. (author)

  14. Delayed brain ischemia tolerance induced by electroacupuncture pretreatment is mediated via MCP-induced protein 1

    Science.gov (United States)

    2013-01-01

    Background Emerging studies have demonstrated that pretreatment with electroacupuncture (EA) induces significant tolerance to focal cerebral ischemia. The present study seeks to determine the involvement of monocyte chemotactic protein-induced protein 1 (MCPIP1), a recently identified novel modulator of inflammatory reactions, in the cerebral neuroprotection conferred by EA pretreatment in the animal model of focal cerebral ischemia and to elucidate the mechanisms of EA pretreatment-induced ischemic brain tolerance. Methods Twenty-four hours after the end of the last EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 minutes in male C57BL/6 mice and MCPIP1 knockout mice. Transcription and expression of MCPIP1 gene was monitored by qRT-PCR, Western blot and immunohistochemistry. The neurobehavioral scores, infarction volumes, proinflammatory cytokines and leukocyte infiltration in brain and NF-κB signaling were evaluated after ischemia/reperfusion. Results MCPIP1 protein and mRNA levels significantly increased specifically in mouse brain undergoing EA pretreatment. EA pretreatment significantly attenuated the infarct volume, neurological deficits, upregulation of proinflammatory cytokines and leukocyte infiltration in the brain of wild-type mice after MCAO compared with that of the non-EA group. MCPIP1-deficient mice failed to evoke EA pretreatment-induced tolerance compared with that of the control MCPIP1 knockout group without EA treatment. Furthermore, the activation of NF-κB signaling was significantly reduced in EA-pretreated wild-type mice after MCAO compared to that of the non-EA control group and MCPIP1-deficient mice failed to confer the EA pretreatment-induced inhibition of NF-κB signaling after MCAO. Conclusions Our data demonstrated that MCPIP1 deficiency caused significant lack of EA pretreatment-induced cerebral protective effects after MCAO compared with the control group and that MCPIP1 is

  15. Protective effect of embelin from Embelia ribes Burm. against transient global ischemia-induced brain damage in rats.

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    Thippeswamy, B S; Nagakannan, P; Shivasharan, B D; Mahendran, S; Veerapur, V P; Badami, S

    2011-11-01

    Embelia ribes is being used in Indian traditional herbal medicine for the treatment of mental disorders and as brain tonic. The present study was designed to investigate the protective effects of embelin from E. ribes on global ischemia/reperfusion-induced brain injury in rats. Transient global ischemia was induced by occluding bilateral common carotid arteries for 30 min followed by 24-h reperfusion. Neurological functions were measured using sensorimotor tests. Ischemia/reperfusion-induced neuronal injury was assessed by cerebral infarct area, biochemical and histopathological examination. Pretreatment of embelin (25 and 50 mg/kg, p.o.) significantly increased locomotor activity and hanging latency time and decreased beam walking latency when compared with ischemic control. The treatment also reduced significantly the lipid peroxidation and increased the total thiol content and glutathione-S-transferase activity in brain homogenates. The decreased cerebral infarction area in embelin-treated groups and histopathological observations confirmed the above findings. These observations suggested that embelin is a neuroprotective agent and may prove to be useful adjunct in the treatment of stroke.

  16. Exercise Therapy Augments the Ischemia-Induced Proangiogenic State and Results in Sustained Improvement after Stroke

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    Man He

    2013-04-01

    Full Text Available The induction of angiogenesis will stimulate endogenous recovery mechanisms, which are involved in the long-term repair and restoration process of the brain after an ischemic event. Here, we tested whether exercise influences the pro-angiogenic factors and outcomes after cerebral infarction in rats. Wistar rats were exposed to two hours of middle-cerebral artery occlusion and reperfusion. Different durations of treadmill training were performed on the rats. The expression of matrix metalloproteinase 2 (MMP2 and vascular endothelial growth factor (VEGF-related genes and proteins were higher over time post-ischemia, and exercise enhanced their expression. Sixteen days post-ischemia, the regional cerebral blood flow in the ischemic striatum was significantly increased in the running group over the sedentary. Although no difference was seen in infarct size between the running and sedentary groups, running evidently improved the neurobehavioral score. The effects of running on MMP2 expression, regional cerebral blood flow and outcome were abolished when animals were treated with bevacizumab (BEV, a VEGF-targeting antibody. Exercise therapy improves long-term stroke outcome by MMP2-VEGF-dependent mechanisms related to improved cerebral blood flow.

  17. B vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke: the VITAmins TO Prevent Stroke (VITATOPS) MRI-substudy.

    Science.gov (United States)

    Cavalieri, Margherita; Schmidt, Reinhold; Chen, Christopher; Mok, Vincent; de Freitas, Gabriel R; Song, Swithin; Yi, Qilong; Ropele, Stefan; Grazer, Anja; Homayoon, Nina; Enzinger, Christian; Loh, Katherine; Wong, Ka Sing Lawrence; Wong, Adrian; Xiong, Yunyun; Chang, Hui Meng; Wong, Meng Cheong; Fazekas, Franz; Eikelboom, John W; Hankey, Graeme J

    2012-12-01

    Elevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). B-vitamin supplementation with folate and vitamins B12 and B6 reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of once-daily supplements of B vitamins would reduce the progression of CSVD-related brain lesions. A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to double-blind treatment with placebo or b vitamins, underwent brain MRI at randomization and after 2 years of B-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of B-vitamin supplementation on the incidence of other ischemic abnormalities. After 2 years of treatment with b vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13 cm3; P=0.419) and incidence of lacunes (8.0% vs 5.9%, P=0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, b-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7 cm3; P=0.039). Daily B-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD. http://vitatops.highway1.com.au/. Unique identifier: NCT00097669 and ISRCTN74743444.

  18. Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study.

    Science.gov (United States)

    Grau-Sánchez, Jennifer; Amengual, Julià L; Rojo, Nuria; Veciana de Las Heras, Misericordia; Montero, Jordi; Rubio, Francisco; Altenmüller, Eckart; Münte, Thomas F; Rodríguez-Fornells, Antoni

    2013-01-01

    Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician's brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.

  19. Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: A TMS study

    Directory of Open Access Journals (Sweden)

    Jennifer eGrau-Sánchez

    2013-09-01

    Full Text Available Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician’s brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning. Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.

  20. Therapy-Induced Neuroplasticity of Language in Chronic Post Stroke Aphasia: A Mismatch Negativity Study of (A)Grammatical and Meaningful/less Mini-Constructions

    Science.gov (United States)

    Lucchese, Guglielmo; Pulvermüller, Friedemann; Stahl, Benjamin; Dreyer, Felix R.; Mohr, Bettina

    2017-01-01

    Clinical language performance and neurophysiological correlates of language processing were measured before and after intensive language therapy in patients with chronic (time post stroke >1 year) post stroke aphasia (PSA). As event-related potential (ERP) measure, the mismatch negativity (MMN) was recorded in a distracted oddball paradigm to short spoken sentences. Critical ‘deviant’ sentence stimuli where either well-formed and meaningful, or syntactically, or lexico-semantically incorrect. After 4 weeks of speech-language therapy (SLT) delivered with high intensity (10.5 h per week), clinical language assessment with the Aachen Aphasia Test battery demonstrated significant linguistic improvements, which were accompanied by enhanced MMN responses. More specifically, MMN amplitudes to grammatically correct and meaningful mini-constructions and to ‘jabberwocky’ sentences containing a pseudoword significantly increased after therapy. However, no therapy-related changes in MMN responses to syntactically incorrect strings including agreement violations were observed. While MMN increases to well-formed meaningful strings can be explained both at the word and construction levels, the neuroplastic change seen for ‘jabberwocky’ sentences suggests an explanation in terms of constructions. The results confirm previous reports that intensive SLT leads to improvements of linguistic skills in chronic aphasia patients and now demonstrate that this clinical improvement is associated with enhanced automatic brain indexes of construction processing, although no comparable change is present for ungrammatical strings. Furthermore, the data confirm that the language-induced MMN is a useful tool to map functional language recovery in PSA. PMID:28111545

  1. Radiation-induced apoptosis and developmental disturbance of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Inouye, Minoru [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

    1995-03-01

    The developing mammalian brain is highly susceptible to ionizing radiation. A significant increase in small head size and mental retardation has been noted in prenatally exposed survivors of the atomic bombing, with the highest risk in those exposed during 8-15 weeks after fertilization. This stage corresponds to day 13 of pregnancy for mice and day 15 for rats in terms of brain development. The initial damage produced by radiation at this stage is cell death in the ventricular zone (VZ) of the brain mantle, the radiosensitive germinal cell population. During histogenesis of the cerebellum the external granular layer (EGL) is also radiosensitive. Although extensive cell death results in microcephaly and histological abnormlity, both VZ and EGL have an ability to recover from a considerable cell loss and form the normal structure of the central nervous system. The number of cell deaths to induce tissue abnormalities in adult brain rises in the range of 15-25% of the germinal cell population; and the threshold doses are about 0.3 Gy for cerebral defects and 1 Gy for cerebellar anomalies in both mice and rats. A similar threshold level is suggested in human cases in induction of mental retardation. Radiation-induced cell death in the VZ and EGL has been revealed as apoptosis, by the nuclear and cytoplasmic condensation, transglutaminase activation, required macromolecular synthesis, and internucleosomal DNA cleavage. Apoptosis of the germinal cell is assumed to eliminate acquired genetic damage. Once an abnormality in DNA has been induced and fixed in a germinal cell, it would be greatly amplified during future proliferation. These cells would commit suicide when injured for replacement by healthy cells, rather than undertake DNA repair. In fact they show very slow repair of cellular damage. Thus the high sensitivity of undifferentiated neural cells to the lethal effect of radiation may constitute a biological defense mechanism. (author) 69 refs.

  2. Radiation-induced apoptosis and developmental disturbance of the brain

    International Nuclear Information System (INIS)

    Inouye, Minoru

    1995-01-01

    The developing mammalian brain is highly susceptible to ionizing radiation. A significant increase in small head size and mental retardation has been noted in prenatally exposed survivors of the atomic bombing, with the highest risk in those exposed during 8-15 weeks after fertilization. This stage corresponds to day 13 of pregnancy for mice and day 15 for rats in terms of brain development. The initial damage produced by radiation at this stage is cell death in the ventricular zone (VZ) of the brain mantle, the radiosensitive germinal cell population. During histogenesis of the cerebellum the external granular layer (EGL) is also radiosensitive. Although extensive cell death results in microcephaly and histological abnormlity, both VZ and EGL have an ability to recover from a considerable cell loss and form the normal structure of the central nervous system. The number of cell deaths to induce tissue abnormalities in adult brain rises in the range of 15-25% of the germinal cell population; and the threshold doses are about 0.3 Gy for cerebral defects and 1 Gy for cerebellar anomalies in both mice and rats. A similar threshold level is suggested in human cases in induction of mental retardation. Radiation-induced cell death in the VZ and EGL has been revealed as apoptosis, by the nuclear and cytoplasmic condensation, transglutaminase activation, required macromolecular synthesis, and internucleosomal DNA cleavage. Apoptosis of the germinal cell is assumed to eliminate acquired genetic damage. Once an abnormality in DNA has been induced and fixed in a germinal cell, it would be greatly amplified during future proliferation. These cells would commit suicide when injured for replacement by healthy cells, rather than undertake DNA repair. In fact they show very slow repair of cellular damage. Thus the high sensitivity of undifferentiated neural cells to the lethal effect of radiation may constitute a biological defense mechanism. (author) 69 refs

  3. [Brain repair after ischemic stroke: role of neurotransmitters in post-ischemic neurogenesis].

    Science.gov (United States)

    Sánchez-Mendoza, Eduardo; Bellver-Landete, Víctor; González, María Pilar; Merino, José Joaquín; Martínez-Murillo, Ricardo; Oset-Gasque, María Jesús

    2012-11-01

    Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs. The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons. Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.

  4. Efficient neuroplasticity induction in chronic stroke patients by an associative brain-computer interface

    DEFF Research Database (Denmark)

    Mrachacz-Kersting, Natalie; Jiang, Ning; Stevenson, Andrew James Thomas

    2016-01-01

    Brain-computer interfaces (BCIs) have the potential to improve functionality in chronic stoke patients when applied over a large number of sessions. Here, we evaluate the effect and the underlying mechanisms of three BCI training sessions in a double-blind-sham-controlled design. The applied BCI......-associative group. Fugl-Meyer motor scores (0.8±0.46 point difference p=0.01), foot (but not finger) tapping frequency, and 10-m walking speed improved significantly for the BCIassociative group, indicating clinically relevant improvements. For the BCI as applied here, the precise coupling between the brain command...

  5. Perfusion measurements of the brain: using dynamic CT for the quantitative assessment of cerebral ischemia in acute stroke

    International Nuclear Information System (INIS)

    Klotz, Ernst; Koenig, Matthias

    1999-01-01

    Objective: Perfusion CT has been successfully used as a functional imaging technique for the differential diagnosis of patients with hyperacute stroke. We investigated to what extent this technique can also be used for the quantitative assessment of cerebral ischemia. Methods and material: We studied linearity, spatial resolution and noise behaviour of cerebral blood flow (CBF) determination with computer simulations and phantom measurements. Statistical ROI based analysis of CBF images of a subset of 38 patients from a controlled clinical stroke study with currently more than 75 patients was done to check the power of relative cerebral blood flow (rCBF) values to predict definite infarction and ischemic penumbra. Classification was performed using follow-up CT and MR data. Results: Absolute CBF values were systematically underestimated, the degree depended on the cardiac output of the patients. Phantom measurements and simulations indicated very good linearity allowing reliable calculation of rCBF values. Infarct and penumbra areas in 19 patients receiving standard heparin therapy had mean rCBF values of 0.19 and 0.62, respectively. The corresponding values for 19 patients receiving local intraarterial fibrinolysis were 0.18 and 0.57. The difference between infarct and penumbra values was highly significant (P<0.0001) in both groups. No penumbra area was found with an rCBF value of less than 0.20. While in the heparin group only 25% of all areas with an rCBF between 0.20 and 0.35 survived, in the fibrinolytic group 61% of these areas could be saved (P<0.05). Conclusion: Perfusion CT is a fast and practical technique for routine clinical application. It provides substantial and important additional information for the selection of the optimal treatment strategy for patients with hyperacute stroke. Relative values of cerebral blood flow discriminate very well between areas of reversible and irreversible ischemia; an rCBF value of 0.20 appears to be a definite lower

  6. Induction by mercury compounds of brain metallothionein in rats: Hg{sup 0} exposure induces long-lived brain metallothionein

    Energy Technology Data Exchange (ETDEWEB)

    Yasutake, Akira; Nakano, Atsuhiro [Biochemistry Section, National Institute for Minamata Disease, Kumamoto (Japan); Hirayama, Kimiko [Kumamoto University, College of Medical Science (Japan)

    1998-03-01

    Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to most heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and cause neurological damage. Rats treated with MeHg (40 {mu}mol/kg per day x 5 days, p.o.) showed brain Hg levels as high as 18 {mu}g/g with slight neurological signs 10 days after final administration, but brain MT levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7-8 {mu}g Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Although brain Hg levels fell gradually with a half-life of 26 days, MT levels induced by Hg exposure remained unchanged for >2 weeks. Gel fractionation revealed that most Hg was in the brain cytosol fraction and thus bound to MT. Hybridization analysis showed that, despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was less affected. Although significant Hg accumulation and MT induction were observed also in kidney and liver of Hg vapor-exposed rats, these decreased more quickly than in brain. The long-lived MT in brain might at least partly be accounted for by longer half-life of Hg accumulated there. The present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT. (orig.) With 4 figs., 1 tab., 27 refs.

  7. Effects of glycyrrhizin pre-treatment on transient ischemic brain ...

    African Journals Online (AJOL)

    Effects of glycyrrhizin pre-treatment on transient ischemic brain injury in mice. ... on transient ischemic brain injury in mice. Chiyeon Lim, Sehyun Lim, Young-Jun Lee, Bokcheul Kong, Byoungho Lee, Chang-Hyun Kim, Buyeo Kim, Suin Cho ... induced brain damage. Keywords: Glycyrrhizin, licorice, stroke, apoptosis ...

  8. Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study

    OpenAIRE

    Qi, Ji; Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Qu, Shanshan

    2014-01-01

    Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revea...

  9. Attention Functions in Traumatic Brain Injury and Stroke: An Exploration of the Predictors of Daily Living Difficulties and the Correlates of the CogniPlus Vigilance Training Programme

    OpenAIRE

    Shehab, Al Amira Safa

    2012-01-01

    Attention deficits are common in traumatic brain injury and stroke. These difficulties can impact the individual’s everyday life, affecting activities of daily living such as running errands, increasing cognitive errors such as failing to notice signs, and minimising community integration. They also call for specific training to improve these functions. We investigated the relationship between attention functions and these daily living aspects, as well as the correlates of the CogniPlus VIG t...

  10. LSD-induced entropic brain activity predicts subsequent personality change.

    Science.gov (United States)

    Lebedev, A V; Kaelen, M; Lövdén, M; Nilsson, J; Feilding, A; Nutt, D J; Carhart-Harris, R L

    2016-09-01

    Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when "ego-dissolution" was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp 37:3203-3213, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Exercise-induced muscle fatigue in the unaffected knee joint and its influence on postural control and lower limb kinematics in stroke patients

    Directory of Open Access Journals (Sweden)

    Sun Wook Park

    2017-01-01

    Full Text Available This study aimed to investigate the effects of exercise-induced muscle fatigue in the unaffected knee joint on postural control and kinematic changes in stroke patients. Forty participants (20 stroke patients, 20 age-matched healthy participants were recruited. To induce fatigue, maximum voluntary isometric contractions were performed in the unaffected knee joint in a Leg Extension Rehab exercise machine using the pneumatic resistance. We measured static and dynamic balance and lower-limb kinematics during gait. Changes in postural control parameters anteroposterior sway speed and total center of pressure distance differed significantly between the stroke and control groups. In addition, changes in gait kinematic parameters knee and ankle angles of initial contact differed significantly between stroke (paretic and non-paretic and control groups. Muscle fatigue in the unaffected knee and ankle impaired postural control and debilitates kinematic movement of ipsilateral and contralateral lower limbs, and may place the fatigued stroke patients at greater risk for falls.

  12. Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Stefanie Endesfelder

    2017-01-01

    Full Text Available Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6 corresponds to that of a human fetal brain at 28–32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC, promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1, down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB, reduced pro-apoptotic effectors (poly (ADP-ribose polymerase-1 (PARP-1, apoptosis inducing factor (AIF, and caspase-3, and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP 2, and inhibitor of metalloproteinase (TIMP 1/2. Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

  13. Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy.

    Science.gov (United States)

    Levite, Mia

    2014-08-01

    .g., chronic progressive limbic Encephalitis, Paraneoplastic Encephalitis or Herpes Simplex Virus Encephalitis), Schizophrenia, Mania, Stroke, or Sjorgen syndrome. In some patients, the anti-NMDA-NR2A/B antibodies are present in both the serum and the CSF. Some of the anti-NMDA-NR2A/B antibodies cross-react with dsDNA, while others do not. Some of the anti-NMDA-NR2A/B antibodies associate with neuropsychiatric/cognitive/behavior/mood impairments in SLE patients, while others do not. The anti-NMDA-NR2A/B antibodies can undoubtedly be very pathogenic, since they can kill neurons by activating NMDA receptors and inducing 'Excitotoxicity', damage the brain, cause dramatic decrease of membranal NMDA receptors expressed in hippocampal neurons, and also induce behavioral cognitive impairments in animal models. Yet, the concentration of the anti-NMDA-NR2A/B antibodies seems to determine if they have positive or negative effects on the activity of glutamate receptors and on the survival of neurons. Thus, at low concentration, the anti-NMDA-NR2A/B antibodies were found to be positive modulators of receptor function and increase the size of NMDA receptor-mediated excitatory postsynaptic potentials, whereas at high concentration they are pathogenic as they promote 'Excitotoxcity' through enhanced mitochondrial permeability transition. (4) Anti-mGluR1 antibodies were found thus far in very few patients with Paraneoplastic Cerebellar Ataxia, and in these patients they are produced intrathecally and therefore present in much higher levels in the CSF than in the serum. The anti-mGluR1 antibodies can be very pathogenic in the brain since they can reduce the basal neuronal activity, block the induction of long-term depression of Purkinje cells, and altogether cause cerebellar motor coordination deficits by a combination of rapid effects on both the acute and the plastic responses of Purkinje cells, and by chronic degenerative effects. Strikingly, within 30 min after injection of anti-mGluR1

  14. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study.

    Science.gov (United States)

    Laskowitz, Daniel T; Kasner, Scott E; Saver, Jeffrey; Remmel, Kerri S; Jauch, Edward C

    2009-01-01

    One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit. A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach. A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform. These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a

  15. Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets.

    Science.gov (United States)

    Sun, Na; Keep, Richard F; Hua, Ya; Xi, Guohua

    2016-10-01

    Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

  16. The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke

    DEFF Research Database (Denmark)

    Joseph, Jason P; Mecca, Adam P; Regenhardt, Robert W

    2014-01-01

    Evidence indicates that angiotensin II type 2 receptors (AT2R) exert cerebroprotective actions during stroke. A selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exert beneficial effects in models of cardiac and renal disease, as well as hemorrhagic stroke. Here, we hypothe...

  17. Rodent stroke induced by photochemical occlusion of proximal middle cerebral artery: Evolution monitored with MR imaging and histopathology

    International Nuclear Information System (INIS)

    Chen Feng; Suzuki, Yasuhiro; Nagai, Nobuo; Jin, Lixin; Yu Jie; Wang Huaijun; Marchal, Guy; Ni Yicheng

    2007-01-01

    Purpose: To longitudinally investigate stroke in rats after photothrombotic occlusion of proximal middle cerebral artery (MCA) with magnetic resonance imaging (MRI) in correlation with histopathology. Materials and methods: Forty-two rats were subjected to photochemical MCA occlusion and MRI at 1.5 T, and sacrificed in seven groups (n = 6 each) at the following time points: 1, 3, 6 and 12 h, and at day 1, 3 and 9. T2-weighted (T2WI) and diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) map was performed in all rats. Contrast-enhanced T1-weighted imaging (CE-T1WI) was compared to intravital staining with Evans blue in one group for assessing blood-brain barrier (BBB) integrity. The brain was stained histochemically with triphenyl tetrazolium chloride (TTC) and processed for pathological assessment. The evolutional changes of relative lesion volume, signal intensity (SI), and the BBB integrity on MRI with corresponding histopathology were evaluated. Results: The ischemic lesion volume reached a maximum around 12 h to day 1 as visualized successively by DWI, ADC map and T2WI, implicating the evolving pathology from cytotoxic edema through vasogenic edema to tissue death. The ADC of brain infarction underwent a significant reversion after 12 h, reflecting the colliquative necrosis. On CE-T1WI, BBB leakage peaked at 6 h and at day 3 with a transitional partial recovery around 24 h. The infarct volume on T2WI, DWI and ADC map matched well with that on TTC staining at 12 h and at day 1 (p > 0.05). Conclusion: The evolution of the present photothrombotic stroke model in rats could be characterized by MRI. The obtained information may help longitudinal studies of cerebral ischemia and anti-stroke agents using the same model

  18. Development of stroke-induced quadriplegia after endovascular repair of blunt aortic injury pseudoaneurysm.

    Science.gov (United States)

    Amoudi, Abdullah S; Merdad, Anas A; Makhdoom, Ahmed Q; Jamjoom, Reda A

    2015-01-01

    Endovascular repair of blunt aortic injury is now a first-line approach in management. This can warrant coverage of the left subclavian artery (LSA), which could lead to posterior strokes. In this case report, we present a severe complication of endovascular repair of a traumatic aortic aneurysm. A 53-year-old man presented with blunt aortic injury, endovascular repair was carried out where the left subclavian artery was covered. The intervention had a 100% technical success. Twelve hours later, he was discovered to have quadriplegia, a CT scan showed a large left cerebellar infarction extending to the medulla oblongata and proximal spinal cord. Strokes complicate 3% of thoracic endovascular aortic repairs, 80% of those strokes occur in patients who had their LSA`s covered. Most patients however, tolerate the coverage. Although our patient had a dominant right vertebral artery, and lacked risks for these strokes, he developed an extensive stroke that left him quadriplegic.

  19. Transcranial direct-current stimulation induced in stroke patients with aphasia: a prospective experimental cohort study

    Directory of Open Access Journals (Sweden)

    Michele Devido Santos

    Full Text Available CONTEXT AND OBJECTIVE: Previous animal and human studies have shown that transcranial direct current stimulation can induce significant and lasting neuroplasticity and may improve language recovery in patients with aphasia. The objective of the study was to describe a cohort of patients with aphasia after stroke who were treated with transcranial direct current stimulation. DESIGN AND SETTING: Prospective cohort study developed in a public university hospital. METHODS: Nineteen patients with chronic aphasia received 10 transcranial direct current stimulation sessions lasting 20 minutes each on consecutive days, using a current of 2 mA. The anode was positioned over the supraorbital area and the cathode over the contralateral motor cortex. The following variables were analyzed before and after the 10 neuromodulation sessions: oral language comprehension, copying, dictation, reading, writing, naming and verbal fluency. RESULTS: There were no adverse effects in the study. We found statistically significant differences from before to after stimulation in relation to simple sentence comprehension (P = 0.034, naming (P = 0.041 and verbal fluency for names of animals (P = 0.038. Improved scores for performing these three tasks were seen after stimulation. CONCLUSIONS: We observed that excitability of the primary motor cortex through transcranial direct current stimulation was associated with effects on different aspects of language. This can contribute towards future testing in randomized controlled trials.

  20. Transcranial direct-current stimulation induced in stroke patients with aphasia: a prospective experimental cohort study.

    Science.gov (United States)

    Santos, Michele Devido; Gagliardi, Rubens José; Mac-Kay, Ana Paula Machado Goyano; Boggio, Paulo Sergio; Lianza, Roberta; Fregni, Felipe

    2013-01-01

    Previous animal and human studies have shown that transcranial direct current stimulation can induce significant and lasting neuroplasticity and may improve language recovery in patients with aphasia. The objective of the study was to describe a cohort of patients with aphasia after stroke who were treated with transcranial direct current stimulation. Prospective cohort study developed in a public university hospital. Nineteen patients with chronic aphasia received 10 transcranial direct current stimulation sessions lasting 20 minutes each on consecutive days, using a current of 2 mA. The anode was positioned over the supraorbital area and the cathode over the contralateral motor cortex. The following variables were analyzed before and after the 10 neuromodulation sessions: oral language comprehension, copying, dictation, reading, writing, naming and verbal fluency. There were no adverse effects in the study. We found statistically significant differences from before to after stimulation in relation to simple sentence comprehension (P = 0.034), naming (P = 0.041) and verbal fluency for names of animals (P = 0.038). Improved scores for performing these three tasks were seen after stimulation. We observed that excitability of the primary motor cortex through transcranial direct current stimulation was associated with effects on different aspects of language. This can contribute towards future testing in randomized controlled trials.

  1. Recovery in stroke rehabilitation through the rotation of preferred directions induced by bimanual movements: a computational study.

    Directory of Open Access Journals (Sweden)

    Ken Takiyama

    Full Text Available Stroke patients recover more effectively when they are rehabilitated with bimanual movement rather than with unimanual movement; however, it remains unclear why bimanual movement is more effective for stroke recovery. Using a computational model of stroke recovery, this study suggests that bimanual movement facilitates the reorganization of a damaged motor cortex because this movement induces rotations in the preferred directions (PDs of motor cortex neurons. Although the tuning curves of these neurons differ during unimanual and bimanual movement, changes in PD, but not changes in modulation depth, facilitate such reorganization. In addition, this reorganization was facilitated only when encoding PDs are rotated, but decoding PDs are not rotated. Bimanual movement facilitates reorganization because this movement changes neural activities through inter-hemispheric inhibition without changing cortical-spinal-muscle connections. Furthermore, stronger inter-hemispheric inhibition between motor cortices results in more effective reorganization. Thus, this study suggests that bimanual movement is effective for stroke rehabilitation because this movement rotates the encoding PDs of motor cortex neurons.

  2. Sit-to-Stand in People with Stroke: Effect of Lower Limb Constraint-Induced Movement Strategies

    Directory of Open Access Journals (Sweden)

    Charla Krystine Gray

    2014-01-01

    Full Text Available Background. Weight-bearing asymmetry and impaired balance may contribute to the increased fall risk in people with stroke when rising to stand from sitting. Objective. This study investigated the effect of constraint-induced movement (CIM strategies on weight-bearing symmetry and balance during sit-to-stand in people with stroke. Methods. A nonrandom convenience sample of fifteen people with stroke performed the sit-to-stand task using three CIM strategies including a solid or compliant (foam block strategy, with the unaffected limb placed on the block, and an asymmetrical foot position strategy, with the unaffected limb placed ahead of the affected limb. Duration of the task, affected limb weight-bearing, and centre of pressure and centre of mass displacement were measured in the frontal and sagittal plane. Results. Affected limb weight-bearing was increased and frontal plane centre of pressure and centre of mass moved toward the affected limb compared to baseline with all CIM strategies. Centre of mass displacement in the sagittal plane was greater with the compliant block and asymmetrical foot strategies. Conclusions. The CIM strategies demonstrated greater loading of the affected limb and movement of the centre of pressure and centre of mass toward the affected limb. The compliant block and asymmetrical foot conditions may challenge sagittal plane balance during sit-to-stand in people with stroke.

  3. Fluoxetine Opens Window to Improve Motor Recovery After Stroke

    Science.gov (United States)

    2018-05-01

    Stroke; Cerebrovascular Accident; Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

  4. Aging exacerbates intracerebral hemorrhage-induced brain injury.

    Science.gov (United States)

    Lee, Jae-Chul; Cho, Geum-Sil; Choi, Byung-Ok; Kim, Hyoung Chun; Kim, Won-Ki

    2009-09-01

    Aging may be an important factor affecting brain injury by intracerebral hemorrhage (ICH). In the present study, we investigated the responses of glial cells and monocytes to intracerebral hemorrhage in normal and aged rats. ICH was induced by microinjecting autologous whole blood (15 microL) into the striatum of young (4 month old) and aged (24 month old) Sprague-Dawley rats. Age-dependent relations of brain tissue damage with glial and macrophageal responses were evaluated. Three days after ICH, activated microglia/macrophages with OX42-positive processes and swollen cytoplasm were more abundantly distributed around and inside the hemorrhagic lesions. These were more dramatic in aged versus the young rats. Western blot and immunohistochemistry analyses showed that the expression of interleukin-1beta protein after ICH was greater in aged rats, whereas the expression of GFAP and ciliary neurotrophic factor protein after ICH was significantly lower in aged rats. These results suggest that ICH causes more severe brain injury in aged rats most likely due to overactivation of microglia/macrophages and concomitant repression of reactive astrocytes.

  5. Bacoside A: Role in Cigarette Smoking Induced Changes in Brain

    Directory of Open Access Journals (Sweden)

    G. Vani

    2015-01-01

    Full Text Available Cigarette smoking (CS is a major health hazard that exerts diverse physiologic and biochemical effects mediated by the components present and generated during smoking. Recent experimental studies have shown predisposition to several biological consequences from both active and passive cigarette smoke exposure. In particular, passive smoking is linked to a number of adverse health effects which are equally harmful as active smoking. A pragmatic approach should be considered for designing a pharmacological intervention to combat the adverse effects of passive smoking. This review describes the results from a controlled experimental condition, testing the effect of bacoside A (BA on the causal role of passive/secondhand smoke exposure that caused pathological and neurological changes in rat brain. Chronic exposure to cigarette smoke induced significant changes in rat brain histologically and at the neurotransmitter level, lipid peroxidation states, mitochondrial functions, membrane alterations, and apoptotic damage in rat brain. Bacoside A is a neuroactive agent isolated from Bacopa monnieri. As a neuroactive agent, BA was effective in combating these changes. Future research should examine the effects of BA at molecular level and assess its functional effects on neurobiological and behavioral processes associated with passive smoke.

  6. Volumetric Integral Phase-shift Spectroscopy for Noninvasive Detection of Hemispheric Bioimpedance Asymmetry in Acute Brain Pathology

    Science.gov (United States)

    2018-05-10

    Stroke; Stroke, Acute; Ischemic Stroke; Hemorrhage; Clot (Blood); Brain; Subarachnoid Hemorrhage; Cerebral Infarction; Cerebral Hemorrhage; Cerebral Stroke; Intracerebral Hemorrhage; Intracerebral Injury

  7. Complexity in differentiating the expression of truncated or matured forms of MMP-2 and MMP-9 through zymography in rat brain tissues after acute ischaemic stroke.

    Science.gov (United States)

    Alam, Mustafa; Shuaib, Ashfaq

    2013-05-30

    Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of ischaemic stroke. In particular, the mature forms of MMPs 2 and 9 have similar sizes and share gelatine as a common substrate. Both MMPs are upregulated in ischaemic stroke and play detrimental roles during stroke pathogenesis. Throughout this study, we demonstrated that pro-MMP-2 and pro-MMP-9 from ischaemic rat brain tissue homogenate is detected either through immunoblotting or zymography because of the remarkable size difference between these enzymes (72 versus 95 kDa, respectively). However, the mature MMP-2 and MMP-9 cannot be discriminated through zymography because of the almost identical sizes of these forms (66 and 67 kDa, respectively). The use of gelatine zymography on ischaemic rat brain tissue homogenate revealed a 65-kDa MMP band, corresponding to the heterogeneous band of mature MMP-2 and/or MMP-9. Furthermore, we also detected mature MMPs of 65 kDa generated from both recombinant human MMP-2 and MMP-9. Using a pull down assay in rat brain tissue homogenate with gelatine-agarose beads, we showed increased activities for both the pro and mature forms of MMP-2 and MMP-9. However, we could not determine the origin of the respective mature MMPs from the heterogeneous band. Thus, in this study, we demonstrated that the identification and quantification of mature MMP-2 and MMP-9 could not be achieved using zymography alone. Therefore, the development of a reliable technique to identify and measure the respective MMPs is needed to test new stroke therapies targeting MMP-2 and MMP-9. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. The protective role of isorhamnetin on human brain microvascular endothelial cells from cytotoxicity induced by methylglyoxal and oxygen-glucose deprivation.

    Science.gov (United States)

    Li, Wenlu; Chen, Zhigang; Yan, Min; He, Ping; Chen, Zhong; Dai, Haibin

    2016-02-01

    As the first target of stroke, cerebral endothelial cells play a key role in brain vascular repair and maintenance, and their function is impeded in diabetes. Methylglyoxal (MGO), a reactive dicarbonyl produced during glucose metabolism, accumulates in diabetic patients. MGO and MGO-induced advanced glycation end-products (AGEs) could ameliorate stroke-induced brain vascular damage, closely related with ECs dysfunction. Using MGO plus oxygen-glucose deprivation (OGD) to mimic diabetic stroke, we reported the protective effect of isorhamnetin on OGD-induced cytotoxicity after MGO treatment on primary human brain microvascular endothelial cells (HBMEC) and explored the underlying mechanisms. Treatment of MGO for 24 h significantly enhanced 3-h OGD-induced HBMEC toxic effect, which was inhibited by pretreatment of isorhamnetin (100 μmol/L). Moreover, the protective effect of isorhamnetin is multiple function dependent, which includes anti-inflammation, anti-oxidative stress and anti-apoptosis effects. Besides its well-known inhibition on the mitochondria-dependent or intrinsic apoptotic pathway, isorhamnetin also reduced activation of the extrinsic apoptotic pathway, as characterized by the decreased expression and activity of caspase 3 and caspase 8. Furthermore, pretreatment with isorhamnetin specifically inhibited FAS/FASL expression and suppressed nuclear factor-kappa B nuclear translocation. Taken together, our results indicated that isorhamnetin protected against OGD-induced cytotoxicity after MGO treatment in cultured HBMEC due to its multiple protective effects and could inhibit Fas-mediated extrinsic apoptosis. Therefore, isorhamnetin is a promising reagent for the treatment of hyperglycemia and ischemia-induced cerebral vascular degeneration. A proposed model of the potential protective mechanism of isorhamnetin, a metabolite of quercetin, on methylglyoxal (MGO) treatment plus oxygen-glucose deprivation (OGD) exposure-induced cytotoxicity in cultured human

  9. Feasibility of task-specific brain-machine interface training for upper-extremity paralysis in patients with chronic hemiparetic stroke.

    Science.gov (United States)

    Nishimoto, Atsuko; Kawakami, Michiyuki; Fujiwara, Toshiyuki; Hiramoto, Miho; Honaga, Kaoru; Abe, Kaoru; Mizuno, Katsuhiro; Ushiba, Junichi; Liu, Meigen

    2018-01-10

    Brain-machine interface training was developed for upper-extremity rehabilitation for patients with severe hemiparesis. Its clinical application, however, has been limited because of its lack of feasibility in real-world rehabilitation settings. We developed a new compact task-specific brain-machine interface system that enables task-specific training, including reach-and-grasp tasks, and studied its clinical feasibility and effectiveness for upper-extremity motor paralysis in patients with stroke. Prospective beforeâ€"after study. Twenty-six patients with severe chronic hemiparetic stroke. Participants were trained with the brain-machine interface system to pick up and release pegs during 40-min sessions and 40 min of standard occupational therapy per day for 10 days. Fugl-Meyer upper-extremity motor (FMA) and Motor Activity Log-14 amount of use (MAL-AOU) scores were assessed before and after the intervention. To test its feasibility, 4 occupational therapists who operated the system for the first time assessed it with the Quebec User Evaluation of Satisfaction with assistive Technology (QUEST) 2.0. FMA and MAL-AOU scores improved significantly after brain-machine interface training, with the effect sizes being medium and large, respectively (pmachine interface system is feasible for use in real-world clinical settings.

  10. Middle cerebral artery occlusion in Macaca fascicularis: acute and chronic stroke evolution.

    Science.gov (United States)

    D'Arceuil, Helen E; Duggan, Michael; He, Julian; Pryor, Johnny; de Crespigny, Alex

    2006-04-01

    An intravascular stroke model designed for magnetic resonance imaging was developed in Macaca fascicularis (M. fascicularis) to characterize serial stroke lesion evolution. This model produces a range of stroke lesion sizes which closely mimics human stroke evolution. This paper describes the care of animals undergoing this stroke procedure, the range of outcomes we experienced and the cause of mortality in this model. Anesthesia was induced with atropine and ketamine and maintained with isoflurane or propofol. Non-invasive blood pressure, oxygen saturation, heart rate, respiration rate, temperature and end tidal CO2 were monitored continuously. The stroke was created by occluding a distal branch of the middle cerebral artery. During catheter placement animals were heparinized and vasospasm was minimized using verapamil. Anesthetic induction and maintenance were smooth. Animals with small strokes showed very rapid recovery, were able to ambulate and self-feed within 2 hours of recovery. Animals with strokes of >or=4% of the hemispheric volume required lengthy observation during recovery and parenteral nutrition. Large strokes resulted in significant brain edema, herniation and brainstem compression. Intracerebral hemorrhage and or subarachnoid hemorrhage coupled with a stroke of any size was acutely fatal. In the absence of an effective acute stroke therapy, the spectrum of outcomes seen in our primate model is very similar to that observed in human stroke patients.

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

    Science.gov (United States)

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

    2015-11-01

    Vascular bed calcification is a common feature of ends stage renal disease that may lead to a complication in cardiovascular and cerebrovascular beds, which is a promoting cause of myocardial infarction, stroke, dementia and aneurysms. Sodium thiosulfate (STS) due to its multiple properties such as antioxidant and calcium chelation has been reported to prevent vascular calcification in uremic rats, without mentioning its impact on cerebral function. Moreover, the previous studies have not explored the effect of STS on the mitochondrial dysfunction, one of the main pathophysiological features associated with the disease and the main site for STS metabolism. The present study addresses this limitation by using a rat model where 0.75% adenine was administered to induce vascular calcification and 400 mg/kg b wt. of STS was given as preventive and curative agent. The blood and urine chemistries along with histopathology of aorta confirms the renal protective effect of STS in two modes of administration. The brain oxidative stress assessment was made through TBARS level, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, found to be in the near normal level. STS administration not only reduced the mitochondrial oxidative stress (measured by TBARS, SOD, GPx and CAT) but also preserved the mitochondrial respiratory enzyme activities (NADH dehydrogenase, Succinate dehydrogenase and Malate dehydrogenase) and its physiology (measured by P/O ratio and RCR). In fact, the protective effect of STS was prominent, when it was administered as a curative agent, where low H2S and high thiosulfate level was observed along with low cystathionine β synthase activity, confirms thiosulfate mediated renal protection. In conclusion, STS when given after induction of calcification is protective to the brain by preserving its mitochondria, compared to the treatment given concomitantly. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Mapping cortical hand motor representation using TMS: A method to assess brain plasticity and a surrogate marker for recovery of function after stroke?

    Science.gov (United States)

    Lüdemann-Podubecká, Jitka; Nowak, Dennis Alexander

    2016-10-01

    Stroke is associated with reorganization within motor areas of both hemispheres. Mapping the cortical hand motor representation using transcranial magnetic stimulation may help to understand the relationship between motor cortex reorganization and motor recovery of the affected hand after stroke. A standardized review of the pertinent literature was performed. We identified 20 trials, which analyzed the relationship between the extent and/or location of cortical hand motor representation using transcranial magnetic stimulation and motor function and recovery of the affected hand. Several correlations were found between cortical reorganization and measures of hand motor impairment and recovery. A better understanding of the relationships between the extent and location of cortical hand motor representation and the motor impairment and motor recovery of the affected hand after stroke may contribute to a targeted use of non-invasive brain stimulation protocols. In the future motor mapping may help to guide brain stimulation techniques to the most effective motor area in an affected individual. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Post-stroke Rehabilitation Training with a Motor-Imagery-Based Brain-Computer Interface (BCI-Controlled Hand Exoskeleton: A Randomized Controlled Multicenter Trial

    Directory of Open Access Journals (Sweden)

    Alexander A. Frolov

    2017-07-01

    Full Text Available Repeated use of brain-computer interfaces (BCIs providing contingent sensory feedback of brain activity was recently proposed as a rehabilitation approach to restore motor function after stroke or spinal cord lesions. However, there are only a few clinical studies that investigate feasibility and effectiveness of such an approach. Here we report on a placebo-controlled, multicenter clinical trial that investigated whether stroke survivors with severe upper limb (UL paralysis benefit from 10 BCI training sessions each lasting up to 40 min. A total of 74 patients participated: median time since stroke is 8 months, 25 and 75% quartiles [3.0; 13.0]; median severity of UL paralysis is 4.5 points [0.0; 30.0] as measured by the Action Research Arm Test, ARAT, and 19.5 points [11.0; 40.0] as measured by the Fugl-Meyer Motor Assessment, FMMA. Patients in the BCI group (n = 55 performed motor imagery of opening their affected hand. Motor imagery-related brain electroencephalographic activity was translated into contingent hand exoskeleton-driven opening movements of the affected hand. In a control group (n = 19, hand exoskeleton-driven opening movements of the affected hand were independent of brain electroencephalographic activity. Evaluation of the UL clinical assessments indicated that both groups improved, but only the BCI group showed an improvement in the ARAT's grasp score from 0 [0.0; 14.0] to 3.0 [0.0; 15.0] points (p < 0.01 and pinch scores from 0.0 [0.0; 7.0] to 1.0 [0.0; 12.0] points (p < 0.01. Upon training completion, 21.8% and 36.4% of the patients in the BCI group improved their ARAT and FMMA scores respectively. The corresponding numbers for the control group were 5.1% (ARAT and 15.8% (FMMA. These results suggests that adding BCI control to exoskeleton-assisted physical therapy can improve post-stroke rehabilitation outcomes. Both maximum and mean values of the percentage of successfully decoded imagery-related EEG activity, were higher

  14. Stroke - risk factors

    Science.gov (United States)

    ... oxygen. Brain cells can die, causing lasting damage. Risk factors are things that increase your chance of ... a disease or condition. This article discusses the risk factors for stroke and things you can do ...

  15. Stroke mimic diagnoses presenting to a hyperacute stroke unit.

    Science.gov (United States)

    Dawson, Ang; Cloud, Geoffrey C; Pereira, Anthony C; Moynihan, Barry J

    2016-10-01

    Stroke services have been centralised in several countries in recent years. Diagnosing acute stroke is challenging and a high proportion of patients admitted to stroke units are diagnosed as a non-stroke condition (stroke mimics). This study aims to describe the stroke mimic patient group, including their impact on stroke services. We analysed routine clinical data from 2,305 consecutive admissions to a stroke unit at St George's Hospital, London. Mimic groupings were derived from 335 individual codes into 17 groupings. From 2,305 admissions, 555 stroke mimic diagnoses were identified (24.2%) and 72% of stroke mimics had at least one stroke risk factor. Common mimic diagnoses were headache, seizure and syncope. Medically unexplained symptoms and decompensation of underlying conditions were also common. Median length of stay was 1 day; a diagnosis of dementia (p=0.028) or needing MRI (p=0.006) was associated with a longer stay. Despite emergency department assessment by specialist clinicians and computed tomography brain, one in four suspected stroke patients admitted to hospital had a non-stroke diagnosis. Stroke mimics represent a heterogeneous patient group with significant impacts on stroke services. Co-location of stroke and acute neurology services may offer advantages where service reorganisation is being considered. © Royal College of Physicians 2016. All rights reserved.

  16. Reactive Balance in Individuals With Chronic Stroke: Biomechanical Factors Related to Perturbation-Induced Backward Falling.

    Science.gov (United States)

    Salot, Pooja; Patel, Prakruti; Bhatt, Tanvi

    2016-03-01

    An effective compensatory stepping response is the first line of defense for preventing a fall during sudden large external perturbations. The biomechanical factors that contribute to heightened fall risk in survivors of stroke, however, are not clearly understood. It is known that impending sensorimotor and balance deficits poststroke predispose these individuals to a risk of fall during sudden external perturbations. The purpose of this study was to examine the mechanism of fall risk in survivors of chronic stroke when exposed to sudden, slip-like forward perturbations in stance. This was a cross-sectional study. Fourteen individuals with stroke, 14 age-matched controls (AC group), and 14 young controls (YC group) were exposed to large-magnitude forward stance perturbations. Postural stability was computed as center of mass (COM) position (XCOM/BOS) and velocity (ẊCOM/BOS) relative to the base of support (BOS) at first step lift-off (LO) and touch-down (TD) and at second step TD. Limb support was quantified as vertical hip descent (Zhip) from baseline after perturbation onset. All participants showed a backward balance loss, with 71% of the stroke group experiencing a fall compared with no falls in the control groups (AC and YC groups). At first step LO, no between-group differences in XCOM/BOS and ẊCOM/BOS were noted. At first step TD, however, the stroke group had a significantly posterior XCOM/BOS and backward ẊCOM/BOS compared with the control groups. At second step TD, individuals with stroke were still more unstable (more posterior XCOM/BOS and backward ẊCOM/BOS) compared with the AC group. Individuals with stroke also showed greater peak Zhip compared with the control groups. Furthermore, the stroke group took a larger number of steps with shorter step length and delayed step initiation compared with the control groups. Although the study highlights the reactive balance deficits increasing fall risk in survivors of stroke compared with healthy

  17. In vivo experimental stroke and in vitro organ culture induce similar changes in vasoconstrictor receptors and intracellular calcium handling in rat cerebral arteries

    DEFF Research Database (Denmark)

    Povlsen, Gro Klitgaard; Waldsee, Roya; Ahnstedt, Hilda

    2012-01-01

    Cerebral arteries subjected to different types of experimental stroke upregulate their expression of certain G-protein-coupled vasoconstrictor receptors, a phenomenon that worsens the ischemic brain damage. Upregulation of contractile endothelin B (ET(B)) and 5-hydroxytryptamine 1B (5-HT(1B......)) receptors has been demonstrated after subarachnoid hemorrhage and global ischemic stroke, but the situation is less clear after focal ischemic stroke. Changes in smooth muscle calcium handling have been implicated in different vascular diseases but have not hitherto been investigated in cerebral arteries...... and extracellular sources, whereas 5-HT(1B) receptor-mediated contraction was solely dependent on extracellular calcium. Organ culture and stroke increased basal intracellular calcium levels in MCA smooth muscle cells and decreased the expression of inositol triphosphate receptor and transient receptor potential...

  18. Family History in Young Patients With Stroke.

    Science.gov (United States)

    Thijs, Vincent; Grittner, Ulrike; Dichgans, Martin; Enzinger, Christian; Fazekas, Franz; Giese, Anne-Katrin; Kessler, Christof; Kolodny, Edwin; Kropp, Peter; Martus, Peter; Norrving, Bo; Ringelstein, Erich Bernd; Rothwell, Peter M; Schmidt, Reinhold; Tanislav, Christian; Tatlisumak, Turgut; von Sarnowski, Bettina; Rolfs, Arndt

    2015-07-01

    Family history of stroke is an established risk factor for stroke. We evaluated whether family history of stroke predisposed to certain stroke subtypes and whether it differed by sex in young patients with stroke. We used data from the Stroke in Fabry Patients study, a large prospective, hospital-based, screening study for Fabry disease in young patients (aged stroke in whom cardiovascular risk factors and family history of stroke were obtained and detailed stroke subtyping was performed. A family history of stroke was present in 1578 of 4232 transient ischemic attack and ischemic stroke patients (37.3%). Female patients more often had a history of stroke in the maternal lineage (P=0.027) than in the paternal lineage. There was no association with stroke subtype according to Trial of Org 10172 in Acute Stroke Treatment nor with the presence of white matter disease on brain imaging. Patients with dissection less frequently reported a family history of stroke (30.4% versus 36.3%; P=0.018). Patients with a parental history of stroke more commonly had siblings with stroke (3.6% versus 2.6%; P=0.047). Although present in about a third of patients, a family history of stroke is not specifically related to stroke pathogenic subtypes in patients with young stroke. Young women with stroke more often report stroke in the maternal lineage. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2015 American Heart Association, Inc.

  19. 3D movement correction of CT brain perfusion image data of patients with acute ischemic stroke

    International Nuclear Information System (INIS)

    Fahmi, Fahmi; Marquering, Henk A.; Streekstra, Geert J.; Borst, Jordi; Beenen, Ludo F.M.; Majoie, Charles B.L.; Niesten, Joris M.; Velthuis, Birgitta K.; VanBavel, Ed

    2014-01-01

    Head movement during CT brain perfusion (CTP) acquisition can deteriorate the accuracy of CTP analysis. Most CTP software packages can only correct in-plane movement and are limited to small ranges. The purpose of this study is to validate a novel 3D correction method for head movement during CTP acquisition. Thirty-five CTP datasets that were classified as defective due to head movement were included in this study. All CTP time frames were registered with non-contrast CT data using a 3D rigid registration method. Location and appearance of ischemic area in summary maps derived from original and registered CTP datasets were qualitative compared with follow-up non-contrast CT. A quality score (QS) of 0 to 3 was used to express the degree of agreement. Furthermore, experts compared the quality of both summary maps and assigned the improvement score (IS) of the CTP analysis, ranging from -2 (much worse) to 2 (much better). Summary maps generated from corrected CTP significantly agreed better with appearance of infarct on follow-up CT with mean QS 2.3 versus mean QS 1.8 for summary maps from original CTP (P = 0.024). In comparison to original CTP data, correction resulted in a quality improvement with average IS 0.8: 17 % worsened (IS = -2, -1), 20 % remained unchanged (IS = 0), and 63 % improved (IS = +1, +2). The proposed 3D movement correction improves the summary map quality for CTP datasets with severe head movement. (orig.)

  20. Radiation-induced dementia in patients cured of brain metastases

    International Nuclear Information System (INIS)

    DeAngelis, L.M.; Delattre, J.Y.; Posner, J.B.

    1989-01-01

    When a patient with cancer develops a brain metastasis, death is usually imminent, but aggressive treatment in some patients with limited or no systemic disease yields long-term survival. In such patients, delayed deleterious effects of therapy are particularly tragic. We report 12 patients who developed delayed complications of whole brain radiotherapy (WBRT) given as sole treatment (4 patients) or in combination with surgical resection (8 patients). Within 5 to 36 months (median, 14) all patients developed progressive dementia, ataxia, and urinary incontinence causing severe disability in all and leading to death in 7. No patient had tumor recurrence when neurologic symptoms began. Cortical atrophy and hypodense white matter were identified by CT in all. Contrast-enhancing lesions were seen in 3 patients; 2 of the lesions yielded radionecrosis on biopsy. Autopsies on 2 patients revealed diffuse chronic edema of the hemispheric white matter in the absence of tumor recurrence. Corticosteroids and ventriculoperitoneal shunt offered significant but incomplete improvement in some patients. The total dose of WBRT was only 2,500 to 3,900 cGy, but daily fractions of 300 to 600 cGy were employed. We believe that these fractionation schedules, several of which are used commonly, predispose to delayed neurologic toxicity, and that more protracted schedules should be employed for the safe and efficacious treatment of good-risk patients with brain metastases. The incidence of WBRT-induced dementia was only 1.9 to 5.1% in the 2 populations reviewed here; however, this underestimates the incidence because only severely affected patients could be identified from chart review

  1. Moving Beyond the Brain: Transcutaneous Spinal Direct Current Stimulation in Post-Stroke Aphasia

    Directory of Open Access Journals (Sweden)

    Paola Marangolo

    2017-08-01

    Full Text Available Over the last 20 years, major advances in cognitive neuroscience have clearly shown that the language function is not restricted into the classical language areas but it involves brain regions, which had never previously considered. Indeed, recent lines of evidence have suggested that the processing of words associated to motor schemata, such as action verbs, modulates the activity of the sensorimotor cortex, which, in turn, facilitates its retrieval. To date, no studies have investigated whether the spinal cord, which is functionally connected to the sensorimotor system, might also work as an auxiliary support for language processing. We explored the combined effect of transcutaneous spinal direct current stimulation (tsDCS and language treatment in a randomized double-blind design for the recovery of verbs and nouns in 14 chronic aphasics. During each treatment, each subject received tsDCS (20 min, 2 mA over the thoracic vertebrae (10th vertebra in three different conditions: (1 anodic, (2 cathodic and (3 sham, while performing a verb and noun naming tasks. Each experimental condition was run in five consecutive daily sessions over 3 weeks. Overall, a significant greater improvement in verb naming was found during the anodic condition with respect to the other two conditions, which persisted at 1 week after the end of the treatment. No significant differences were present for noun naming among the three conditions. The hypothesis is advanced that anodic tsDCS might have influenced activity along the ascending somatosensory pathways, ultimately eliciting neurophysiological changes into the sensorimotor areas which, in turn, supported the retrieval of verbs. These results further support the evidence that action words, due to their sensorimotor semantic properties, are partly represented into the sensorimotor cortex. Moreover, they also document, for the first time, that tsDCS enhances verb recovery in chronic aphasia and it may

  2. Moving Beyond the Brain: Transcutaneous Spinal Direct Current Stimulation in Post-Stroke Aphasia

    Science.gov (United States)

    Marangolo, Paola; Fiori, Valentina; Shofany, Jacob; Gili, Tommaso; Caltagirone, Carlo; Cucuzza, Gabriella; Priori, Alberto

    2017-01-01

    Over the last 20 years, major advances in cognitive neuroscience have clearly shown that the language function is not restricted into the classical language areas but it involves brain regions, which had never previously considered. Indeed, recent lines of evidence have suggested that the processing of words associated to motor schemata, such as action verbs, modulates the activity of the sensorimotor cortex, which, in turn, facilitates its retrieval. To date, no studies have investigated whether the spinal cord, which is functionally connected to the sensorimotor system, might also work as an auxiliary support for language processing. We explored the combined effect of transcutaneous spinal direct current stimulation (tsDCS) and language treatment in a randomized double-blind design for the recovery of verbs and nouns in 14 chronic aphasics. During each treatment, each subject received tsDCS (20 min, 2 mA) over the thoracic vertebrae (10th vertebra) in three different conditions: (1) anodic, (2) cathodic and (3) sham, while performing a verb and noun naming tasks. Each experimental condition was run in five consecutive daily sessions over 3 weeks. Overall, a significant greater improvement in verb naming was found during the anodic condition with respect to the other two conditions, which persisted at 1 week after the end of the treatment. No significant differences were present for noun naming among the three conditions. The hypothesis is advanced that anodic tsDCS might have influenced activity along the ascending somatosensory pathways, ultimately eliciting neurophysiological changes into the sensorimotor areas which, in turn, supported the retrieval of verbs. These results further support the evidence that action words, due to their sensorimotor semantic properties, are partly represented into the sensorimotor cortex. Moreover, they also document, for the first time, that tsDCS enhances verb recovery in chronic aphasia and it may represent a

  3. Lifetime stress cumulatively programs brain transcriptome and impedes stroke recovery: benefit of sensory stimulation.

    Directory of Open Access Journals (Sweden)

    Fabíola C R Zucchi

    Full Text Available Prenatal stress (PS represents a critical variable affecting lifetime health trajectories, metabolic and vascular functions. Beneficial experiences may attenuate the effects of PS and its programming of health outcomes in later life. Here we investigated in a rat model (1 if PS modulates recovery following cortical ischemia in adulthood; (2 if a second hit by adult stress (AS exaggerates stress responses and ischemic damage; and (3 if tactile stimulation (TS attenuates the cumulative effects of PS and AS. Prenatally stressed and non-stressed adult male rats underwent focal ischemic motor cortex lesion and were tested in skilled reaching and skilled walking tasks. Two groups of rats experienced recurrent restraint stress in adulthood and one of these groups also underwent daily TS therapy. Animals that experienced both PS and AS displayed the most severe motor disabilities after lesion. By contrast, TS promoted recovery from ischemic lesion and reduced hypothalamic-pituitary-adrenal axis activity. The data also showed that cumulative effects of adverse and beneficial lifespan experiences interact with disease outcomes and brain plasticity through the modulation of gene expression. Microarray analysis of the lesion motor cortex revealed that cumulative PS and AS interact with genes related to growth factors and transcription factors, which were not affected by PS or lesion alone. TS in PS+AS animals reverted these changes, suggesting a critical role for these factors in activity-dependent motor cortical reorganization after ischemic lesion. These findings suggest that beneficial experience later in life can moderate adverse consequences of early programming to improve cerebrovascular health.

  4. Brain glucose and lactate levels during ventilator-induced hypo- and hypercapnia

    NARCIS (Netherlands)

    van Hulst, R. A.; Lameris, T. W.; Haitsma, J. J.; Klein, J.; Lachmann, B.

    2004-01-01

    OBJECTIVE: Levels of glucose and lactate were measured in the brain by means of microdialysis in order to evaluate the effects of ventilator-induced hypocapnia and hypercapnia on brain metabolism in healthy non-brain-traumatized animals. DESIGN AND SETTING: Prospective animal study in a university

  5. Signal Transduction Pathways Involved in Brain Death-Induced Renal Injury

    NARCIS (Netherlands)

    Bouma, H. R.; Ploeg, R. J.; Schuurs, T. A.

    Kidneys derived from brain death organ donors show an inferior survival when compared to kidneys derived from living donors. Brain death is known to induce organ injury by evoking an inflammatory response in the donor. Neuronal injury triggers an inflammatory response in the brain, leading to

  6. Comparison of ADC map with trace map in the normal and infarct areas of the brains of stroke patients

    International Nuclear Information System (INIS)

    Kim, Seung Hyung; Yoon, Pyeong Ho; Jeong, Eun Kee; Oh, Young Taick; Kim, Dong Ik

    1999-01-01

    To compare ADC mapping with trace mapping in normal and infarct areas of the brains of stroke patients. Eighteen patients diagnosed on the basis of clinical and brain MRI examinations as suffering from brain infarction were included in this study (hyperacute-1, acute-4, subacute-12, chronic-1). Diffusion weighted images of three orthogonal directions of a patient's brain were obtained by means of a single shot EPI pulse sequence, using a diffusion gradient with four serial b-factors. Three ADC maps were then reconstructed by post-image processing and were summed pixel by pixel to yield a trace map. ROIs were selected in the normal areas of white matter, gray matter and CSF of one hemisphere, and other ROIs of the same size were selected at the same site of the contralateral hemisphere. ADC and trace values were measured and right/left ratios of ADC and trace values were calculated. Using these values, we then compared the ADC map with the trace map, and compared the degree of anisotropic diffusion between white matter, gray matter and CSF. Except for three, whose infarct lesions were small and lay over white and gray matter, patients were divided into two groups. Those with infarct in the white matter (n=10) were assigned to one group, and those with infarct in the gray matter (n=5) to the other. ROIs were selected in the infarct area and other ROIs of the same size were selected at the same site of the contralateral hemisphere. ADC and trace values were measured and infarct/contralateral ratios were calculated. We then compared ADC ratio with trace ratio in white matter and gray matter infarct. In normal white matter, the Dxx ratio was 0.980±0.098, the Dyy ratio 1.019±0.086, the Dzz ratio 0.999±0.111, and the trace ratio 0.995±0.031. In normal gray matter, the Dxx ratio was 1.001±0.058, the Dyy ratio 0.996±0.063, Dzz ratio 1.005±0.070, and the trace ratio 1.001±0.028. In CSF, the Dxx ratio was 1.002±0.064, the Dyy ratio 1.023±0.055, the Dzz ratio 0.999

  7. Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients.

    Directory of Open Access Journals (Sweden)

    Qiuhong Ji

    Full Text Available The aims of this study were to examine the alternation in serum exosome concentrations and the levels of serum exosomal miR-9 and miR-124, two brain-specific miRNAs, in acute ischemic stroke (AIS patients and to explore the predictive values of these miRNAs for AIS diagnosis and damage evaluation. Sixty-five patients with AIS at the acute stage were enrolled and 66 non-stroke volunteers served as controls. Serum exosomes isolated by ExoQuick precipitations were characterized by transmission electron microscopy, nanoparticle-tracking analysis and western blotting. The levels of exosomal miR-9 and miR-124 were determined by real-time quantitative PCR. Compared with controls, the concentration of serum exosomes and the median levels of serum exosomal miR-9 and miR-124 were significantly higher in AIS patients (p<0.01. The levels of both miR-9 and miR-124 were positively correlated with National Institutes of Health Stroke Scale (NIHSS scores, infarct volumes and serum concentrations of IL-6. The areas under the curve for exosomal miR-9 and miR-124 were 0.8026 and 0.6976, respectively. This proof of concept study suggests that serum exosomal miR-9 and miR-124 are promising biomarkers for diagnosing AIS and evaluating the degree of damage caused by ischemic injury. However, further studies are needed to explore the potential roles of the exosomes released from brain tissues in post stroke complications.

  8. Primary blast-induced traumatic brain injury: lessons from lithotripsy

    Science.gov (United States)

    Nakagawa, A.; Ohtani, K.; Armonda, R.; Tomita, H.; Sakuma, A.; Mugikura, S.; Takayama, K.; Kushimoto, S.; Tominaga, T.

    2017-11-01

    Traumatic injury caused by explosive or blast events is traditionally divided into four mechanisms: primary, secondary, tertiary, and quaternary blast injury. The mechanisms of blast-induced traumatic brain injury (bTBI) are biomechanically distinct and can be modeled in both in vivo and in vitro systems. The primary bTBI injury mechanism is associated with the response of brain tissue to the initial blast wave. Among the four mechanisms of bTBI, there is a remarkable lack of information regarding the mechanism of primary bTBI. On the other hand, 30 years of research on the medical application of shock waves (SWs) has given us insight into the mechanisms of tissue and cellular damage in bTBI, including both air-mediated and underwater SW sources. From a basic physics perspective, the typical blast wave consists of a lead SW followed by shock-accelerated flow. The resultant tissue injury includes several features observed in primary bTBI, such as hemorrhage, edema, pseudo-aneurysm formation, vasoconstriction, and induction of apoptosis. These are well-described pathological findings within the SW literature. Acoustic impedance mismatch, penetration of tissue by shock/bubble interaction, geometry of the skull, shear stress, tensile stress, and subsequent cavitation formation are all important factors in determining the extent of SW-induced tissue and cellular injury. In addition, neuropsychiatric aspects of blast events need to be taken into account, as evidenced by reports of comorbidity and of some similar symptoms between physical injury resulting in bTBI and the psychiatric sequelae of post-traumatic stress. Research into blast injury biophysics is important to elucidate specific pathophysiologic mechanisms of blast injury, which enable accurate differential diagnosis, as well as development of effective treatments. Herein we describe the requirements for an adequate experimental setup when investigating blast-induced tissue and cellular injury; review SW physics

  9. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

    Science.gov (United States)

    Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

    2016-01-01

    Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions

  10. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

    Directory of Open Access Journals (Sweden)

    Gemma Chiva-Blanch

    Full Text Available Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke.Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls.Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions.Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger

  11. Exploratory study on the effects of a robotic hand rehabilitation device on changes in grip strength and brain activity after stroke.

    Science.gov (United States)

    Pinter, Daniela; Pegritz, Sandra; Pargfrieder, Christa; Reiter, Gudrun; Wurm, Walter; Gattringer, Thomas; Linderl-Madrutter, Regina; Neuper, Claudia; Fazekas, Franz; Grieshofer, Peter; Enzinger, Christian

    2013-01-01

    The brain mechanisms underlying successful recovery of hand fuenction after stroke are still not fully understood, although functional MRI (fMRI) studies underline the importance of neuronal plasticity. We explored potential changes in brain activity in 7 patients with subacute to chronic stroke (69 ± 8 years) with moderate- to high-grade distal paresis of the upper limb (Motricity Index: 59.4) after standardized robotic finger-hand rehabilitation training, in addition to conventional rehabilitation therapy for 3 weeks. Behavioral and fMRI assessments were carried out before and after training to characterize changes in brain activity and behavior. The Motricity Index (pre: 59.4, post: 67.2, P hand increased significantly after rehabilitation. On fMRI, active movement of the affected (left) hand resulted in contralesional (ie, ipsilateral) activation of the primary sensorimotor cortex prior to rehabilitation. After rehabilitation, activation appeared "normalized," including the ipsilesional primary sensorimotor cortex and supplementary motor area (SMA). No changes and no abnormalities of activation maps were seen during movement of the unaffected hand. Subsequent region-of-interest analyses showed no significant ipsilesional activation increases after rehabilitation. Despite behavioral improvements, we failed to identify consistent patterns of functional reorganization in our sample. This warrants caution in the use of fMRI as a tool to explore neural plasticity in heterogeneous samples lacking sufficient statistical power.

  12. Surface and volume three-dimensional displays of Tc-99m HMPAO brain SPECT images in stroke patients with three-head gamma camera

    International Nuclear Information System (INIS)

    Shih, W.J.; Slevin, J.T.; Schleenbaker, R.E.; Mills, B.J.; Magoun, S.L.; Ryo, U.Y.

    1991-01-01

    This paper evaluates volume and surface 3D displays in Tc-99m HMPAO brain SPECT imaging in stroke patients. Using a triple-head gamma camera interfaced with a 64-bit supercomputer, 20 patients with stroke were studied. Each patient was imaged 30-60 minutes after an intravenous injection of 20 mCi of Tc-99m HMPAO. SPECT images as well as planar images were routinely obtained; volume and surface 3D display then proceeded, with the process requiring 5-10 minutes. Volume and surface 3D displays show the brain from all angles; thus the location and extension of lesion(s) in the brain are much easier to appreciate. While a cerebral lesion(s) was more clearly delineated by surface 3D imaging, crossed cerebellar diaschisis in seven patients was clearly exhibited with volume 3D but not with surface 3D imaging. Volume and surface 3D displays enhance continuity of structures and understanding of spatial relationships

  13. Platelet activating factor induces transient blood-brain barrier opening to facilitate edaravone penetration into the brain.

    Science.gov (United States)

    Fang, Weirong; Zhang, Rui; Sha, Lan; Lv, Peng; Shang, Erxin; Han, Dan; Wei, Jie; Geng, Xiaohan; Yang, Qichuan; Li, Yunman

    2014-03-01

    The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into

  14. Neuroimaging Correlates of Post-Stroke Aphasia Rehabilitation in a Pilot Randomized Trial of Constraint-Induced Aphasia Therapy.

    Science.gov (United States)

    Nenert, Rodolphe; Allendorfer, Jane B; Martin, Amber M; Banks, Christi; Ball, Angel; Vannest, Jennifer; Dietz, Aimee R; Szaflarski, Jerzy P

    2017-07-18

    BACKGROUND Recovery from post-stroke aphasia is a long and complex process with an uncertain outcome. Various interventions have been proposed to augment the recovery, including constraint-induced aphasia therapy (CIAT). CIAT has been applied to patients suffering from post-stroke aphasia in several unblinded studies to show mild-to-moderate linguistic gains. The aim of the present study was to evaluate the neuroimaging correlates of CIAT in patients with chronic aphasia related to left middle cerebral artery stroke. MATERIAL AND METHODS Out of 24 patients recruited in a pilot randomized blinded trial of CIAT, 19 patients received fMRI of language. Eleven of them received CIAT (trained) and eight served as a control group (untrained). Each patient participated in three fMRI sessions (before training, after training, and 3 months later) that included semantic decision and verb generation fMRI tasks, and a battery of language tests. Matching healthy control participants were also included (N=38; matching based on age, handedness, and sex). RESULTS Language testing showed significantly improved performance on Boston Naming Test (BNT; paphasia with no specific effect from CIAT training.

  15. Innate Immunity and Inflammation Post-Stroke: An α7-Nicotinic Agonist Perspective

    Directory of Open Access Journals (Sweden)

    Silke Neumann

    2015-12-01

    Full Text Available Stroke is one of the leading causes of death and long-term disability, with limited treatment options available. Inflammation contributes to damage tissue in the central nervous system across a broad range of neuropathologies, including Alzheimer’s disease, pain, Schizophrenia, and stroke. While the immune system plays an important role in contributing to brain damage produced by ischemia, the damaged brain, in turn, can exert a powerful immune-suppressive effect that promotes infections and threatens the survival of stroke patients. Recently the cholinergic anti-inflammatory pathway, in particular its modulation using α7-nicotinic acetylcholine receptor (α7-nAChR ligands, has shown potential as a strategy to dampen the inflammatory response and facilitate functional recovery in stroke patients. Here we discuss the current literature on stroke-induced inflammation and the effects of α7-nAChR modulators on innate immune cells.

  16. Sickle Mice Are Sensitive to Hypoxia/Ischemia-Induced Stroke but Respond to Tissue-Type Plasminogen Activator Treatment.

    Science.gov (United States)

    Sun, Yu-Yo; Lee, Jolly; Huang, Henry; Wagner, Mary B; Joiner, Clinton H; Archer, David R; Kuan, Chia-Yi

    2017-12-01

    The effects of lytic stroke therapy in patients with sickle cell anemia are unknown, although a recent study suggested that coexistent sickle cell anemia does not increase the risk of cerebral hemorrhage. This finding calls for systemic analysis of the effects of thrombolytic stroke therapy, first in humanized sickle mice, and then in patients. There is also a need for additional predictive markers of sickle cell anemia-associated vasculopathy. We used Doppler ultrasound to examine the carotid artery of Townes sickle mice tested their responses to repetitive mild hypoxia-ischemia- and transient hypoxia-ischemia-induced stroke at 3 or 6 months of age, respectively. We also examined the effects of tPA (tissue-type plasminogen activator) treatment in transient hypoxia-ischemia-injured sickle mice. Three-month-old sickle cell (SS) mice showed elevated resistive index in the carotid artery and higher sensitivity to repetitive mild hypoxia-ischemia-induced cerebral infarct. Six-month-old SS mice showed greater resistive index and increased flow velocity without obstructive vasculopathy in the carotid artery. Instead, the cerebral vascular wall in SS mice showed ectopic expression of PAI-1 (plasminogen activator inhibitor-1) and P-selectin, suggesting a proadhesive and prothrombotic propensity. Indeed, SS mice showed enhanced leukocyte and platelet adherence to the cerebral vascular wall, broader fibrin deposition, and higher mortality after transient hypoxia-ischemia. Yet, post-transient hypoxia-ischemia treatment with tPA reduced thrombosis and mortality in SS mice. Sickle mice are sensitive to hypoxia/ischemia-induced cerebral infarct but benefit from thrombolytic treatment. An increased resistive index in carotid arteries may be an early marker of sickle cell vasculopathy. © 2017 American Heart Association, Inc.

  17. Mechanisms of Short-Term Training-Induced Reaching Improvement in Severely Hemiparetic Stroke Patients: A TMS Study

    Science.gov (United States)

    Harris-Love, Michelle L.; Morton, Susanne M.; Perez, Monica A.; Cohen, Leonardo G.

    2011-01-01

    Background The neurophysiological mechanisms underlying improved upper-extremity motor skills have been partially investigated in patients with good motor recovery but are poorly understood in more impaired individuals, the majority of stroke survivors. Objective The authors studied changes in primary motor cortex (M1) excitability (motor evoked potentials [MEPs], contralateral and ipsilateral silent periods [CSPs and ISPs] using transcranial magnetic stimulation [TMS]) associated with training-induced reaching improvement in stroke patients with severe arm paresis (n = 11; Upper-Extremity Fugl-Meyer score (F-M) = 27 ± 6). Methods All patients underwent a single session of reaching training focused on moving the affected hand from a resting site to a target placed at 80% of maximum forward reaching amplitude in response to a visual “GO” cue. Triceps contribute primarily as agonist and biceps primarily as antagonist to the trained forward reaching movement. Response times were recorded for each reaching movement. Results Preceding training (baseline), greater interhemispheric inhibition (measured by ISP) in the affected triceps muscle, reflecting inhibition from the nonlesioned to the lesioned M1, was observed in patients with lower F-M scores (more severe motor impairment). Training-induced improvements in reaching were greater in patients with slower response times at baseline. Increased MEP amplitudes and decreased ISPs and CSPs were observed in the affected triceps but not in the biceps muscle after training. Conclusion These results indicate that along with training-induced motor improvements, training-specific modulation of intrahemispheric and interhemispheric mechanisms occurs after reaching practice in chronic stroke patients with substantial arm impairment. PMID:21343522

  18. Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage.

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    Kyeung Min Joo

    Full Text Available Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.

  19. THE USE OF A COMPLEX “BRAIN-COMPUTER INTERFACE AND EXO-SKELETON” AND MOVEMENT IMAGINATION TECHNIQUE FOR POST-STROKE REHABILITATION

    Directory of Open Access Journals (Sweden)

    S. V. Kotov

    2015-01-01

    Full Text Available Background: Efficacy of physical exercise and movement imagination for restoration of motor dysfunction after a stroke is seen as proven. However, the use of movement imagination is complicated by impossibility of objective and subjective control over  the exercise, as well as by the absence of their motor support. The brain-computer interface based on electroencephalography is a technique that enables a feedback during movement imagination.Materials and methods: We assessed 10 patients (6 men and 4 women aged from 30 to 66 years (mean age, 47 ± 7.7 years with an ischemic (n = 9 and hemorrhagic (n = 1 stroke during the last 2 months to 4 years. Online recognition of movement imagination was done by a classifier with a brain computer interface. An exo-skeleton supported passive movements in a paretic hand managed by the brain-computer interface. During 2 weeks the patients had 10 sessions of 45–90 minute duration each. For control, we used data from 5 stroke patients who, in addition to their standard treatment, underwent an imitation of rehabilitation procedures without movement imagination and feedback. To assess efficacy of treatment, we used a modified Ashworth scale, Fugl-Meyer scale, test for evaluation of hand functions ARAT, British scale for assessment of muscle force MRC-SS. Level of everyday activity and working ability was measured with a modified Rankin scale and Bartel index. Cognitive functions were assessed with Schulte tables.Results: Online recognition of movement imagination according to desynchronization of μ rhythm was registered in 50–75% of patients. All patients reported a subjective improvement of motor functions and working ability. Positive results for at least one parameter were observed in all patients; however, there were no significant difference between the parameters before and after rehabilitation procedures, excluding cognitive functions (degree of warming-up, p < 0.02.Conclusion: In post stroke patients

  20. Principles of Motor Recovery in Post-Stroke Patients using Hand Exoskeleton Controlled by the Brain-Computer Interface Based on Motor Imagery

    Czech Academy of Sciences Publication Activity Database

    Frolov, A. A.; Húsek, Dušan; Biryukova, E. V.; Bobrov, P.; Mokienko, O.; Alexandrov, A.V.

    2017-01-01

    Roč. 27, č. 1 (2017), s. 107-137 ISSN 1210-0552 Grant - others:Russian Ministry of Education and Science(RU) RFMEFI60715X0128 Institutional support: RVO:67985807 Keywords : brain computer interface * motor imagery * post-stroke and post-traumatic patients * arm and hand exoskeleton * proportional derivative controller * motor synergy * clinical application Subject RIV: IN - Informatics, Computer Science OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.394, year: 2016

  1. Study to assess the effectiveness of modified constraint-induced movement therapy in stroke subjects: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Priyanka Singh

    2013-01-01

    Full Text Available Background and Purpose: The purpose of this study was to assess the effectiveness of modified constraint induced movement therapy (m-CIMT in stroke subjects. Materials and Methods: A total of forty sub-acute stroke subjects were randomly assigned to either a m-CIMT (n = 20 or in a control group (n = 20. The m-CIMT group (14 men, 6 women; mean age = 55.2 years consisted of structured 2 h therapy sessions emphasizing affected arm use, occurring 5 times/week for 2 weeks. A mitt was used to restrain the unaffected arm for 10 h/day for 2 week. The control group (11 men, 9 women; mean age = 56.4 years consisted of conventional rehabilitation for time-matched exercise program. The outcome measures were evaluated at pre- and post-intervention by using the Wolf Motor Function Test (WMFT and Fugl-Meyer assessment (FMA of motor recovery after stroke. Results: After intervention significant effects were observed in m-CIMT group on WMFT (pre-test and post-test score was 28.04 ± 6.58, 13.59 ± 2.86; P =0.003. Similarly on FMA (pre- and post-test score was 31.15 ± 6.37, 55.7 ± 6.4; P = 0.00. Conclusion: There is a significant improvem ent in upper extremity function so it indicates that m-CIMT is effective in improving the motor function of the affected arm in stroke subjects. However, its long-term effect has not proved since there was no follow-up after intervention.

  2. Acupuncture therapy for stroke patients.

    Science.gov (United States)

    Li, Xin; Wang, Qiang

    2013-01-01

    Acupuncture is one of the most important parts of Traditional Chinese Medicine, has been used for more than 3000 years as prevention and treatment for various diseases in China as well as in adjacent regions, and is widely accepted in western countries in recent years. More and more clinical trials revealed that acupuncture shows positive effect in stroke, not only as a complementary and alternative medicine for poststroke rehabilitation but also as a preventive strategy which could induce cerebral ischemic tolerance, especially when combined with modern electrotherapy. Acupuncture has some unique characteristics, which include acupoint specificity and parameter-dependent effect. It also involves complicated mechanism to exert the beneficial effect on stroke. Series of clinical trials have shown that acupuncture primarily regulates the release of neurochemicals, hemorheology, cerebral microcirculation, metabolism, neuronal activity, and the function of specific brain region. Animal studies showed that the effects of acupuncture therapy on stroke were possibly via inhibition of postischemic inflammatory reaction, stimulation of neurogenesis and angiogenesis, and influence on neural plasticity. Mechanisms for its preconditioning effect include activity enhancement of antioxidant, regulation of the endocannabinoid system, and inhibition of apoptosis. Although being controversial, acupuncture is a promising preventive and treatment strategy for stroke, but further high-quality clinical trials would be needed to provide more confirmative evidence. © 2013 Elsevier Inc. All rights reserved.

  3. Edaravone Protected Human Brain Microvascular Endothelial Cells from Methylglyoxal-Induced Injury by Inhibiting AGEs/RAGE/Oxidative Stress

    Science.gov (United States)

    Li, Wenlu; Xu, Hongjiao; Hu, Yangmin; He, Ping; Ni, Zhenzhen; Xu, Huimin; Zhang, Zhongmiao; Dai, Haibin

    2013-01-01

    Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO) seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC), protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD) induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, cell account, lactate dehydrogenase (LDH) release and Rhodamine 123 staining. Advanced glycation end-products (AGEs) formation and receptor for advanced glycation end-products (RAGE) expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS) release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10–100 µmol/l. What’s more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress. PMID:24098758

  4. Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress.

    Directory of Open Access Journals (Sweden)

    Wenlu Li

    Full Text Available Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC, protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT formation, cell account, lactate dehydrogenase (LDH release and Rhodamine 123 staining. Advanced glycation end-products (AGEs formation and receptor for advanced glycation end-products (RAGE expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10-100 µmol/l. What's more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress.

  5. EFFECT OF SELF-SELECTED AND INDUCED SLOW AND FAST PADDLING ON STROKE KINEMATICS DURING 1000 M OUTRIGGER CANOEING ERGOMETRY

    Directory of Open Access Journals (Sweden)

    Rebecca M. Sealey

    2011-03-01

    Full Text Available This study aimed to identify the effect of different stroke rates on various kinematic parameters during 1000 m outrigger canoeing. Sixteen, experienced female outrigger canoeists completed three 1000 m outrigger ergometer time trials, one trial each using a self-selected, a Hawaiian ( 65 strokes·min-1 stroke rate. Stroke rate, stroke length, stroke time, proportion of time spent in propulsion and recovery, torso flexion angle and 'twist' were measured and compared with repeated measures ANOVAs. Stroke rate, stroke length and stroke time were significantly different across all interventions (p < 0.05 despite no difference in the percentage of time spent in the propulsive and recovery phases of the stroke. Stroke length and stroke time were negatively correlated to stroke rate for all interventions (r = -0.79 and -0.99, respectively. Female outrigger canoeists maintain consistent stroke kinematics throughout a 1000 m time trial, most likely as a learned skill to maximize crew paddling synchrony when paddling on-water. While the Hawaiian stroke rate resulted in the greatest trunk flexion movement and 'twist' action, this potential increased back injury risk may be offset by the slow stroke rate and long stroke length and hence slow rate of force development.

  6. The role of dual energy CT in differentiating between brain haemorrhage and contrast medium after mechanical revascularisation in acute ischaemic stroke

    International Nuclear Information System (INIS)

    Tijssen, M.P.M.; Stadler, A.A.R.; Zwam, W. van; Graaf, R. de; Postma, A.A.; Hofman, P.A.M.; Oostenbrugge, R.J. van; Klotz, E.; Wildberger, J.E.

    2014-01-01

    To assess the feasibility of dual energy computed tomography (DE-CT) in intra-arterially treated acute ischaemic stroke patients to discriminate between contrast extravasation and intracerebral haemorrhage. Thirty consecutive acute ischaemic stroke patients following intra-arterial treatment were examined with DE-CT. Simultaneous imaging at 80 kV and 140 kV was employed with calculation of mixed images. Virtual unenhanced non-contrast (VNC) images and iodine overlay maps (IOM) were calculated using a dedicated brain haemorrhage algorithm. Mixed images alone, as ''conventional CT'', and DE-CT interpretations were evaluated and compared with follow-up CT. Eight patients were excluded owing to a lack of follow-up or loss of data. Mixed images showed intracerebral hyperdense areas in 19/22 patients. Both haemorrhage and residual contrast material were present in 1/22. IOM suggested contrast extravasation in 18/22 patients; in 16/18 patients this was confirmed at follow-up. The positive predictive value (PPV) of mixed imaging alone was 25 %, with a negative predictive value (NPV) of 91 % and accuracy of 63 %. The PPV for detection of haemorrhage with DE-CT was 100 %, with an NPV of 89 % and accuracy improved to 89 %. Dual energy computed tomography improves accuracy and diagnostic confidence in early differentiation between intracranial haemorrhage and contrast medium extravasation in acute stroke patients following intra-arterial revascularisation. (orig.)

  7. Toward a P300 based Brain-Computer Interface for aphasia rehabilitation after stroke: Presentation of theoretical considerations and a pilot feasibility study

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    Sonja C Kleih

    2016-11-01

    Full Text Available People with post-stroke motor aphasia know what they would like to say but cannot express it through motor pathways due to disruption of cortical circuits. We present a theoretical background for our hypothesized connection between attention and aphasia rehabilitation and suggest why in this context, Brain-Computer Interfaces (BCI use might be beneficial for patients diagnosed with aphasia. Not only could BCI technology provide a communication tool, it might support neuronal plasticity by activating language circuits and thereby boost aphasia recovery. However, stroke may lead to heterogeneous symptoms that might hinder BCI use which is why the feasibility of this approach needed to be investigated first. In this pilot study, we included five participants diagnosed with post-stroke aphasia. Four participants were initially unable to use the visual P300 speller paradigm. By adjusting the paradigm to their needs, all participants could successfully learn to use the speller for communication with accuracies up to 100%. We describe necessary adjustments to the paradigm and present future steps to further investigate the here presented approach.

  8. Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Qi, Ji; Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Qu, Shanshan

    2014-02-01

    Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revealed activation in right parietal lobe (Brodmann areas 7 and 19), the right temporal lobe (Brodmann area 39), the right limbic lobe (Brodmann area 23) and bilateral occipital lobes (Brodmann area 18). Furthermore, inhibition of bilateral frontal lobes (Brodmann area 4, 6, and 45), right parietal lobe (Brodmann areas 1 and 5) and left temporal lobe (Brodmann area 21) were observed in the true point group. Activation in the precuneus of right parietal lobe (Brodmann area 7) and inhibition of the left superior frontal gyrus (Brodmann area 10) was observed in the sham group. Compared with sham acupuncture, acupuncture at Waiguan in stroke patients inhibited Brodmann area 5 on the healthy side. Results indicated that the altered specificity of sensation-associated cortex (Brodmann area 5) is possibly associated with a central mechanism of acupuncture at Waiguan for stroke patients.

  9. The role of dual energy CT in differentiating between brain haemorrhage and contrast medium after mechanical revascularisation in acute ischaemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Tijssen, M.P.M.; Stadler, A.A.R.; Zwam, W. van; Graaf, R. de; Postma, A.A. [Maastricht University Medical Centre, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands); Hofman, P.A.M. [Maastricht University Medical Centre, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands); Maastricht University, MhENS School for Mental Health and Neuroscience, Maastricht (Netherlands); Oostenbrugge, R.J. van [Maastricht University Medical Centre, Department of Neurology, P.O. Box 5800, Maastricht (Netherlands); Maastricht University, CARIM School for Cardiovascular Diseases, P.O. Box 616, Maastricht (Netherlands); Klotz, E. [Siemens Healthcare Sector, Computed Tomography, Forchheim (Germany); Wildberger, J.E. [Maastricht University Medical Centre, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands); Maastricht University, CARIM School for Cardiovascular Diseases, P.O. Box 616, Maastricht (Netherlands)

    2014-04-15

    To assess the feasibility of dual energy computed tomography (DE-CT) in intra-arterially treated acute ischaemic stroke patients to discriminate between contrast extravasation and intracerebral haemorrhage. Thirty consecutive acute ischaemic stroke patients following intra-arterial treatment were examined with DE-CT. Simultaneous imaging at 80 kV and 140 kV was employed with calculation of mixed images. Virtual unenhanced non-contrast (VNC) images and iodine overlay maps (IOM) were calculated using a dedicated brain haemorrhage algorithm. Mixed images alone, as ''conventional CT'', and DE-CT interpretations were evaluated and compared with follow-up CT. Eight patients were excluded owing to a lack of follow-up or loss of data. Mixed images showed intracerebral hyperdense areas in 19/22 patients. Both haemorrhage and residual contrast material were present in 1/22. IOM suggested contrast extravasation in 18/22 patients; in 16/18 patients this was confirmed at follow-up. The positive predictive value (PPV) of mixed imaging alone was 25 %, with a negative predictive value (NPV) of 91 % and accuracy of 63 %. The PPV for detection of haemorrhage with DE-CT was 100 %, with an NPV of 89 % and accuracy improved to 89 %. Dual energy computed tomography improves accuracy and diagnostic confidence in early differentiation between intracranial haemorrhage and contrast medium extravasation in acute stroke patients following intra-arterial revascularisation. (orig.)

  10. Physical Therapy Activities in Stroke, Knee Arthroplasty, and Traumatic Brain Injury Rehabilitation: Their Variation, Similarities, and Association With Functional Outcomes

    Science.gov (United States)

    Hsieh, Ching-Hui; Putman, Koen; Smout, Randall J.; Horn, Susan D.; Tian, Wenqiang

    2011-01-01

    Background The mix of physical therapy services is thought to be different with different impairment groups. However, it is not clear how much variation there is across impairment groups. Furthermore, the extent to which the same physical therapy activities are associated with functional outcomes across different types of patients is unknown. Objective The purposes of this study were: (1) to examine similarities and differences in the mix of physical therapy activities used in rehabilitation among patients from different impairment groups and (2) to examine whether the same physical therapy activities are associated with functional improvement across impairment groups. Design This was a prospective observational cohort study. Methods The study was conducted in inpatient rehabilitation facilities. The participants were 433 patients with stroke, 429 patients with total knee arthroplasty (TKA), and 207 patients with traumatic brain injury (TBI). Measures used in this study included: (1) the Comprehensive Severity Index to measure the severity of each patient's medical condition, (2) the Functional Independence Measure (FIM) to measure function, and (3) point-of-care instruments to measure time spent in specific physical therapy activities. Results All 3 groups had similar admission motor FIM scores but varying cognitive FIM scores. Patients with TKA spent more time on exercise than the other 2 groups (average=31.7 versus 6.2 minutes per day). Patients with TKA received the most physical therapy (average=65.3 minutes per day), whereas the TBI group received the least physical therapy (average=38.3 minutes per day). Multivariate analysis showed that only 2 physical therapy activities (gait training and community mobility) were both positively associated with discharge motor FIM outcomes across all 3 groups. Three physical therapy activities (assessment time, bed mobility, and transfers) were negatively associated with discharge motor FIM outcome. Limitations The study

  11. Physical therapy activities in stroke, knee arthroplasty, and traumatic brain injury rehabilitation: their variation, similarities, and association with functional outcomes.

    Science.gov (United States)

    DeJong, Gerben; Hsieh, Ching-Hui; Putman, Koen; Smout, Randall J; Horn, Susan D; Tian, Wenqiang

    2011-12-01

    The mix of physical therapy services is thought to be different with different impairment groups. However, it is not clear how much variation there is across impairment groups. Furthermore, the extent to which the same physical therapy activities are associated with functional outcomes across different types of patients is unknown. The purposes of this study were: (1) to examine similarities and differences in the mix of physical therapy activities used in rehabilitation among patients from different impairment groups and (2) to examine whether the same physical therapy activities are associated with functional improvement across impairment groups. This was a prospective observational cohort study. The study was conducted in inpatient rehabilitation facilities. The participants were 433 patients with stroke, 429 patients with total knee arthroplasty (TKA), and 207 patients with traumatic brain injury (TBI). Measures used in this study included: (1) the Comprehensive Severity Index to measure the severity of each patient's medical condition, (2) the Functional Independence Measure (FIM) to measure function, and (3) point-of-care instruments to measure time spent in specific physical therapy activities. All 3 groups had similar admission motor FIM scores but varying cognitive FIM scores. Patients with TKA spent more time on exercise than the other 2 groups (average=31.7 versus 6.2 minutes per day). Patients with TKA received the most physical therapy (average=65.3 minutes per day), whereas the TBI group received the least physical therapy (average=38.3 minutes per day). Multivariate analysis showed that only 2 physical therapy activities (gait training and community mobility) were both positively associated with discharge motor FIM outcomes across all 3 groups. Three physical therapy activities (assessment time, bed mobility, and transfers) were negatively associated with discharge motor FIM outcome. The study focused primarily on physical therapy without

  12. Measuring and Inducing Brain Plasticity in Chronic Aphasia

    Science.gov (United States)

    Fridriksson, Julius

    2011-01-01

    Brain plasticity associated with anomia recovery in aphasia is poorly understood. Here, I review four recent studies from my lab that focused on brain modulation associated with long-term anomia outcome, its behavioral treatment, and the use of transcranial brain stimulation to enhance anomia treatment success in individuals with chronic aphasia…

  13. Perlecan Domain V induces VEGf secretion in brain endothelial cells through integrin α5β1 and ERK-dependent signaling pathways.

    Directory of Open Access Journals (Sweden)

    Douglas N Clarke

    Full Text Available Perlecan Domain V (DV promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs following stroke. In this study, we define the specific mechanism of DV interaction with the α(5β(1 integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5β(1 and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction of DV with α(5β(1. Furthermore, we investigated the importance of AKT and ERK signaling in DV-induced VEGF expression and secretion. We show that DV increases the phosphorylation of ERK, which leads to subsequent activation and stabilization of eIF4E and HIF-1α. Inhibition of ERK activity by U0126 suppressed DV-induced expression and secretion of VEGR in BECs. While DV was capable of phosphorylating AKT we show that AKT phosphorylation does not play a role in DV's induction of VEGF expression or secretion using two separate inhibitors, LY294002 and Akt IV. Lastly, we demonstrate that VEGF activity is critical for DV increases in BEC proliferation, as well as angiogenesis in a BEC-neuronal co-culture system. Collectively, our findings expand our understanding of DV's mechanism of action on BECs, and further support its potential as a novel stroke therapy.

  14. Perlecan Domain V Induces VEGf Secretion in Brain Endothelial Cells through Integrin α5β1 and ERK-Dependent Signaling Pathways

    Science.gov (United States)

    Clarke, Douglas N.; Al Ahmad, Abraham; Lee, Boyeon; Parham, Christi; Auckland, Lisa; Fertala, Andrezj; Kahle, Michael; Shaw, Courtney S.; Roberts, Jill; Bix, Gregory J.

    2012-01-01

    Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α5β1 integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV’s angio-modulatory activity outside of the brain, binds poorly to α5β1 and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV’s DGR sequence as an important element for the interaction of DV with α5β1. Furthermore, we investigated the importance of AKT and ERK signaling in DV-induced VEGF expression and secretion. We show that DV increases the phosphorylation of ERK, which leads to subsequent activation and stabilization of eIF4E and HIF-1α. Inhibition of ERK activity by U0126 suppressed DV-induced expression and secretion of VEGR in BECs. While DV was capable of phosphorylating AKT we show that AKT phosphorylation does not play a role in DV’s induction of VEGF expression or secretion using two separate inhibitors, LY294002 and Akt IV. Lastly, we demonstrate that VEGF activity is critical for DV increases in BEC proliferation, as well as angiogenesis in a BEC-neuronal co-culture system. Collectively, our findings expand our understanding of DV’s mechanism of action on BECs, and further support its potential as a novel stroke therapy. PMID:23028886

  15. Comparison of Community Reintegration and Selected Stroke ...

    African Journals Online (AJOL)

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    Stroke Specific Characteristics in Nigerian Male and Female ... This study investigated the difference between community reintegration of male and female stroke survivors and the ..... of self identified goals by adults with traumatic brain injury:.

  16. Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses.

    Directory of Open Access Journals (Sweden)

    Ruo-Bing Guo

    Full Text Available Paeoniflorin (PF, the principal component of Paeoniae Radix prescribed in traditional Chinese medicine, has been reported to exhibit many pharmacological effects including protection against ischemic injury. However, the mechanisms underlying the protective effects of PF on cerebral ischemia are still under investigation. The present study showed that PF treatment for 14 days could significantly inhibit transient middle cerebral artery occlusion (MCAO-induced over-activation of astrocytes and microglia, and prevented up-regulations of pro-inflamamtory mediators (TNFα, IL-1β, iNOS, COX(2 and 5-LOX in plasma and brain. Further study demonstrated that chronic treatment with PF suppressed the activations of JNK and p38 MAPK, but enhanced ERK activation. And PF could reverse ischemia-induced activation of NF-κB signaling pathway. Moreover, our in vitro study revealed that PF treatment protected against TNFα-induced cell apoptosis and neuronal loss. Taken together, the present study demonstrates that PF produces a delayed protection in the ischemia-injured rats via inhibiting MAPKs/NF-κB mediated peripheral and cerebral inflammatory response. Our study reveals that PF might be a potential neuroprotective agent for stroke.

  17. Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses.

    Science.gov (United States)

    Guo, Ruo-Bing; Wang, Guo-Feng; Zhao, An-Peng; Gu, Jun; Sun, Xiu-Lan; Hu, Gang

    2012-01-01

    Paeoniflorin (PF), the principal component of Paeoniae Radix prescribed in traditional Chinese medicine, has been reported to exhibit many pharmacological effects including protection against ischemic injury. However, the mechanisms underlying the protective effects of PF on cerebral ischemia are still under investigation. The present study showed that PF treatment for 14 days could significantly inhibit transient middle cerebral artery occlusion (MCAO)-induced over-activation of astrocytes and microglia, and prevented up-regulations of pro-inflamamtory mediators (TNFα, IL-1β, iNOS, COX(2) and 5-LOX) in plasma and brain. Further study demonstrated that chronic treatment with PF suppressed the activations of JNK and p38 MAPK, but enhanced ERK activation. And PF could reverse ischemia-induced activation of NF-κB signaling pathway. Moreover, our in vitro study revealed that PF treatment protected against TNFα-induced cell apoptosis and neuronal loss. Taken together, the present study demonstrates that PF produces a delayed protection in the ischemia-injured rats via inhibiting MAPKs/NF-κB mediated peripheral and cerebral inflammatory response. Our study reveals that PF might be a potential neuroprotective agent for stroke.

  18. Protective effects of angiopoietin-like 4 on the blood-brain barrier in acute ischemic stroke treated with thrombolysis in mice.

    Science.gov (United States)

    Zhang, Bin; Xu, Xiaofeng; Chu, Xiuli; Yu, Xiaoyang; Zhao, Yuwu

    2017-04-03

    Given the risk of blood-brain barrier damage (BBB) caused by ischemic and tissue plasminogen activator thrombolysis, the preservation of vascular integrity is important. Angiopoietin-like 4 (ANGPTL4), a protein secreted in hypoxia, is involved in the regulation of vascular permeability. We hypothesized that Angptl4 might exert a protective effect in thrombolysis through stabilizing blood-brain barrier and inhibit hyper-permeability. We investigated the role of Angptl4 in stroke using a transient focal cerebral ischemia mouse model. The treated mice were administered Angptl4 1h after the ischemic event upon reperfusion. Our results showed that Angptl4 combined with thrombolysis greatly reduced the infarct volume and consequent neurological deficit. Western blot analyses and gelatin zymography revealed that Angptl4 protected the integrity of the endothelium damaged by thrombolysis. Angptl4 inhibited the up-regulation of vascular endothelial growth factor (VEGF) in the vascular endothelium after stroke, which was suppressed by counteracting VEGFR signaling and diminishing downstream Src signaling, and led to the increased stability of junctions and improved endothelial cell barrier integrity. These findings demonstrated that Angptl4 protects the permeability of the BBB damaged by ischemic and thrombolysis. Suggested that Angptl4 might be a promising target molecule in therapies for vasoprotection after thrombolysis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Comparison of lorazepam and zopiclone for insomnia in patients with stroke and brain injury: a randomized, crossover, double-blinded trial.

    Science.gov (United States)

    Li Pi Shan, Rodney S; Ashworth, Nigel L

    2004-06-01

    To determine if lorazepam or zopiclone is more effective in providing a restful night of sleep and to assess the effects of these medications on cognition. A randomized, double-blinded, crossover trial was performed at a tertiary care rehabilitation inpatient unit in a teaching hospital. A total of 18 brain-injured and stroke patients, aged 20-78 yrs, were administered lorazepam, 0.5-1.0 mg, orally at bedtime as needed for 7 days and zopiclone, 3.75-7.5 mg, orally at bedtime as needed for 7 days. Total sleep time and characteristics of sleep were measured. Effects on cognition were also measured using the Folstein Mini Mental Status Exam. There was no difference in average sleep duration or in subjective measures of sleep. Cognition as assessed by the Mini Mental Status Exam revealed no difference in the zopiclone arm compared with the lorazepam arm. Zopiclone is equally effective as lorazepam in the treatment of insomnia in stroke and brain-injured patients.

  20. Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain injury after stereotactic radiosurgery of brain metastases

    International Nuclear Information System (INIS)

    Ohguri, Takayuki; Imada, Hajime; Kohshi, Kiyotaka; Kakeda, Shingo; Ohnari, Norihiro; Morioka, Tomoaki; Nakano, Keita; Konda, Nobuhide; Korogi, Yukunori

    2007-01-01

    Purpose: The purpose of the present study was to evaluate the prophylactic effect of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients with brain metastasis treated with stereotactic radiosurgery (SRS). Methods and Materials: The data of 78 patients presenting with 101 brain metastases treated with SRS between October 1994 and September 2003 were retrospectively analyzed. A total of 32 patients with 47 brain metastases were treated with prophylactic HBO (HBO group), which included all 21 patients who underwent subsequent or prior radiotherapy and 11 patients with common predictors of longer survival, such as inactive extracranial tumors and younger age. The other 46 patients with 54 brain metastases did not undergo HBO (non-HBO group). Radiation-induced brain injuries were divided into two categories, white matter injury (WMI) and radiation necrosis (RN), on the basis of imaging findings. Results: Radiation-induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3 RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less frequent for the HBO group than for the non-HBO group (p = 0.05), although multivariate analysis by logistic regression showed that WMI was not significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of WMI was significantly better for the HBO group (2%) than for the non-HBO group (36%) (p < 0.05). Conclusions: The present study showed a potential value of prophylactic HBO for Radiation-induced WMIs, which justifies further evaluation to confirm its definite benefit

  1. Rapid treatment-induced brain changes in pediatric CRPS.

    Science.gov (United States)

    Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

    2016-03-01

    To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation.

  2. CSF transthyretin neuroprotection in a mouse model of brain ischemia

    DEFF Research Database (Denmark)

    Santos, Sofia Duque; Lambertsen, Kate Lykke; Clausen, Bettina Hjelm

    2010-01-01

    Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain ischemia can be induced surgically by permanent middle cerebral artery occlusion. Using this model, we studied the influence of transthyretin in ischemic stroke. ...

  3. ECT: its brain enabling effects. A review of electroconvulsive therapy-induced structural brain plasticity

    NARCIS (Netherlands)

    Bouckaert, F.; Sienaert, P.; Obbels, J.; Dols, A.; Vandenbulcke, M.; Stek, M.L.; Bolwig, T.

    2014-01-01

    BACKGROUND: Since the past 2 decades, new evidence for brain plasticity has caused a shift in both preclinical and clinical ECT research from falsifying the "brain damage hypothesis" toward exploring ECT's enabling brain (neuro)plasticity effects. METHODS: By reviewing the available animal and human

  4. Protein-energy malnutrition developing after global brain ischemia induces an atypical acute-phase response and hinders expression of GAP-43.

    Science.gov (United States)

    Smith, Shari E; Figley, Sarah A; Schreyer, David J; Paterson, Phyllis G

    2014-01-01

    Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia. In contrast, the effects of PEM developing in the post-ischemic period have not been studied. Since excessive inflammation can impede brain remodeling, we investigated the effects of post-ischemic malnutrition on neuroinflammation, the acute-phase reaction, and neuroplasticity-related proteins. Male, Sprague-Dawley rats were exposed to global forebrain ischemia using the 2-vessel occlusion model or sham surgery. The sham rats were assigned to control diet (18% protein) on day 3 after surgery, whereas the rats exposed to global ischemia were assigned to either control diet or a low protein (PEM, 2% protein) diet. Post-ischemic PEM decreased growth associated protein-43, synaptophysin and synaptosomal-associated protein-25 immunofluorescence within the hippocampal CA3 mossy fiber terminals on day 21, whereas the glial response in the hippocampal CA1 and CA3 subregions was unaltered by PEM. No systemic acute-phase reaction attributable to global ischemia was detected in control diet-fed rats, as reflected by serum concentrations of alpha-2-macroglobulin, alpha-1-acid glycoprotein, haptoglobin, and albumin. Acute exposure to the PEM regimen after global brain ischemia caused an atypical acute-phase response. PEM decreased the serum concentrations of albumin and haptoglobin on day 5, with the decreases sustained to day 21. Serum alpha-2-macroglobulin concentrations were significantly higher in malnourished rats on day 21. This provides the first direct evidence that PEM developing after brain ischemia exerts wide-ranging effects on mechanisms important to stroke recovery.

  5. Sevoflurane postconditioning against cerebral ischemic neuronal injury is abolished in diet-induced obesity: role of brain mitochondrial KATP channels.

    Science.gov (United States)

    Yang, Zecheng; Chen, Yunbo; Zhang, Yan; Jiang, Yi; Fang, Xuedong; Xu, Jingwei

    2014-03-01

    Obesity is associated with increased infarct volumes and adverse outcomes following ischemic stroke. However, its effect on anesthetic postconditioning‑induced neuroprotection has not been investigated. The present study examined the effect of sevoflurane postconditioning on focal ischemic brain injury in diet‑induced obesity. Sprague‑Dawley rats were fed a high‑fat diet (HF; 45% kcal as fat) for 12 weeks to develop obesity syndrome. Rats fed a low‑fat diet (LF; 10% kcal as fat) served as controls. The HF or LF‑fed rats were subjected to focal cerebral ischemia for 60 min, followed by 24 h of reperfusion. Postconditioning was performed by exposure to sevoflurane for 15 min immediately at the onset of reperfusion. The involvement of the mitochondrial KATP (mitoKATP) channel was analyzed by the administration of a selective inhibitor of 5‑hydroxydecanoate (5‑HD) prior to sevoflurane postconditioning or by administration of diazoxide (DZX), a mitoKATP channel opener, instead of sevoflurane. The cerebral infarct volume, neurological score and motor coordination were evaluated 24 h after reperfusion. The HF‑fed rats had larger infarct volumes, and lower neurological scores than the LF‑fed rats and also failed to respond to neuroprotection by sevoflurane or DZX. By contrast, sevoflurane and DZX reduced the infarct volumes and improved the neurological scores and motor coordination in the LF‑fed rats. Pretreatment with 5‑HD inhibited sevoflurane‑induced neuroprotection in the LF‑fed rats, whereas it had no effect in the HF‑fed rats. Molecular studies demonstrated that the expression of Kir6.2, a significant mitoKATP channel component, was reduced in the brains of the HF‑fed rats compared with the LF‑fed rats. The results of this study indicate that diet‑induced obesity eliminates the ability of anesthetic sevoflurane postconditioning to protect the brain against cerebral ischemic neuronal injury, most likely due to an impaired brain

  6. The impact of transcranial direct current stimulation (tDCS) combined with modified constraint-induced movement therapy (mCIMT) on upper limb function in chronic stroke: a double-blind randomized controlled trial.

    Science.gov (United States)

    Rocha, Sérgio; Silva, Evelyn; Foerster, Águida; Wiesiolek, Carine; Chagas, Anna Paula; Machado, Giselle; Baltar, Adriana; Monte-Silva, Katia

    2016-01-01

    This pilot double-blind sham-controlled randomized trial aimed to determine if the addition of anodal tDCS on the affected hemisphere or cathodal tDCS on unaffected hemisphere to modified constraint-induced movement therapy (mCIMT) would be superior to constraints therapy alone in improving upper limb function in chronic stroke patients. Twenty-one patients with chronic stroke were randomly assigned to receive 12 sessions of either (i) anodal, (ii) cathodal or (iii) sham tDCS combined with mCIMT. Fugl-Meyer assessment (FMA), motor activity log scale (MAL), and handgrip strength were analyzed before, immediately, and 1 month (follow-up) after the treatment. Minimal clinically important difference (mCID) was defined as an increase of ≥5.25 in the upper limb FMA. An increase in the FMA scores between the baseline and post-intervention and follow-up for active tDCS group was observed, whereas no difference was observed in the sham group. At post-intervention and follow-up, when compared with the sham group, only the anodal tDCS group achieved an improvement in the FMA scores. ANOVA showed that all groups demonstrated similar improvement over time for MAL and handgrip strength. In the active tDCS groups, 7/7 (anodal tDCS) 5/7 (cathodal tDCS) of patients experienced mCID against 3/7 in the sham group. The results support the merit of association of mCIMT with brain stimulation to augment clinical gains in rehabilitation after stroke. However, the anodal tDCS seems to have greater impact than the cathodal tDCS in increasing the mCIMT effects on motor function of chronic stroke patients. The association of mCIMT with brain stimulation improves clinical gains in rehabilitation after stroke. The improvement in motor recovery (assessed by Fugl-Meyer scale) was only observed after anodal tDCS. The modulation of damaged hemisphere demonstrated greater improvements than the modulation of unaffected hemispheres.

  7. Radiation-induced brain disorders in patients with pituitary tumours

    International Nuclear Information System (INIS)

    Bhansali, A.; Chanda, A.; Dash, R.J.; Banerjee, A.K.; Singh, P.; Sharma, S.C.; Mathuriya, S.N.

    2004-01-01

    Radiation-induced brain disorders (RIBD) are uncommon and they are grave sequelae of conventional radiotherapy. In the present report, we describe the clinical spectrum of RIBD in 11 patients who received post-surgery conventional megavoltage irradiation for residual pituitary tumours. Of these 11 patients (nine men, two women), seven had been treated for non-functioning pituitary tumours and four for somatotropinomas. At the time of irradiation the age of these patients ranged from 30 to 59 years (mean, 39.4 ± 8.3; median, 36) with a follow-up period of 696 months (mean, 18.3 ± 26.4; median, 11). The dose of radiation ranged from 45 to 90 Gy (mean, 51.3 ± 13.4; median, 45), which was given in 1530 fractions (mean, 18.6 ± 5.0; median, 15) with 2.8 ± 0.3 Gy (median, 3) per fraction. The biological effective dose calculated for late complications in these patients ranged from 78.7 to 180 Gy (mean, 99.1 ± 27.5; median, 90). The lag time between tumour irradiation and the onset of symptoms ranged from 6 to 168 months (mean, 46.3 ± 57.0; median, 57). The clinical spectrum of RIBD included new-onset visual abnormalities in five, cerebral radionecrosis in the form of altered sensorium in four, generalized seizures in four, cognitive dysfunction in five, dementia in three and motor deficits in two patients. Magnetic resonance imaging (MRI)/CT of the brain was suggestive of radionecrosis in eight, cerebral oedema in three, cerebral atrophy in two and second neoplasia in one patient. Associated hormone deficiencies at presentation were hypogonadism in eight, hypoadrenalism in six, hypothyroidism in four and diabetes insipidus in one patient. Autopsy in two patients showed primitive neuroectodermal tumour (PNET) and brainstem radionecrosis in one, and a cystic lesion in the left frontal lobe following radionecrosis in the other. We conclude that RIBD have distinctive but varying clinical and radiological presentations. Diabetes insipidus and PNET as a second neoplastic

  8. Tunicamycin-induced unfolded protein response in the developing mouse brain

    International Nuclear Information System (INIS)

    Wang, Haiping; Wang, Xin; Ke, Zun-Ji; Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A.; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2015-01-01

    Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific

  9. Tunicamycin-induced unfolded protein response in the developing mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Haiping; Wang, Xin [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-Ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203 (China); Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Zhang, Zhuo; Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States)

    2015-03-15

    Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific.

  10. Aging alters the immunological response to ischemic stroke.

    Science.gov (United States)

    Ritzel, Rodney M; Lai, Yun-Ju; Crapser, Joshua D; Patel, Anita R; Schrecengost, Anna; Grenier, Jeremy M; Mancini, Nickolas S; Patrizz, Anthony; Jellison, Evan R; Morales-Scheihing, Diego; Venna, Venugopal R; Kofler, Julia K; Liu, Fudong; Verma, Rajkumar; McCullough, Louise D

    2018-05-11

    The peripheral immune system plays a critical role in aging and in the response to brain injury. Emerging data suggest inflammatory responses are exacerbated in older animals following ischemic stroke; however, our understanding of these age-related changes is poor. In this work, we demonstrate marked differences in the composition of circulating and infiltrating leukocytes recruited to the ischemic brain of old male mice after stroke compared to young male mice. Blood neutrophilia and neutrophil invasion into the brain were increased in aged animals. Relative to infiltrating monocyte populations, brain-invading neutrophils had reduced phagocytic potential, and produced higher levels of reactive oxygen species and extracellular matrix-degrading enzymes (i.e., MMP-9), which were further exacerbated with age. Hemorrhagic transformation was more pronounced in aged versus young mice relative to infarct size. High numbers of myeloperoxidase-positive neutrophils were found in postmortem human brain samples of old (> 71 years) acute ischemic stroke subjects compared to non-ischemic controls. Many of these neutrophils were found in the brain parenchyma. A large proportion of these neutrophils expressed MMP-9 and positively correlated with hemorrhage and hyperemia. MMP-9 expression and hemorrhagic transformation after stroke increased with age. These changes in the myeloid response to stroke with age led us to hypothesize that the bone marrow response to stroke is altered with age, which could be important for the development of effective therapies targeting the immune response. We generated heterochronic bone marrow chimeras as a tool to determine the contribution of peripheral immune senescence to age- and stroke-induced inflammation. Old hosts that received young bone marrow (i.e., Young → Old) had attenuation of age-related reductions in bFGF and VEGF and showed improved locomotor activity and gait dynamics compared to isochronic (Old → Old) controls

  11. Transport of cryptotanshinone, a major active triterpenoid in Salvia miltiorrhiza Bunge widely used in the treatment of stroke and Alzheimer's disease, across the blood-brain barrier.

    Science.gov (United States)

    Yu, Xi-Yong; Lin, Shu-Guang; Chen, Xiao; Zhou, Zhi-Wei; Liang, Jun; Duan, Wei; Chowbay, Balram; Wen, Jing-Yuan; Chan, Eli; Cao, Jie; Li, Chun-Guang; Zhou, Shu-Feng

    2007-05-01

    Cryptotanshinone (CTS), a major constituent from the roots of Salvia miltiorrhiza (Danshen), is widely used in the treatment of coronary heart disease, stroke and less commonly Alzheimer's disease. Our recent study indicates that CTS is a substrate for P-glycoprotein (PgP/MDR1/ABCB1). This study has investigated the nature of the brain distribution of CTS across the brain-blood barrier (BBB) using several in vitro and in vivo rodent models. A polarized transport of CTS was found in rat primary microvascular endothelial cell (RBMVEC) monolayers, with facilitated efflux from the abluminal side to luminal side. Addition of a PgP (e.g. verapamil and quinidine) or multi-drug resistance protein 1/2 (MRP1/2) inhibitor (e.g. probenecid and MK-571) in both luminal and abluminal sides attenuated the polarized transport. In a bilateral in situ brain perfusion model, the uptake of CTS into the cerebrum increased from 0.52 +/- 0.1% at 1 min to 11.13 +/- 2.36 ml/100 g tissue at 30 min and was significantly greater than that of sucrose. Co-perfusion of a PgP/MDR1 (e.g. verapamil) or MRP1/2 inhibitor (e.g. probenecid) significantly increased the brain distribution of CTS by 35.1-163.6%. The brain levels of CTS were only about 21% of those in plasma, and were significantly increased when coadministered with verapamil or probenecid in rats. The brain levels of CTS in rats subjected to middle cerebral artery occlusion and rats treated with quinolinic acid (a neurotoxin) were about 2- to 2.5-fold higher than the control rats. Moreover, the brain levels in mdr1a(-/-) and mrp1(-/-) mice were 10.9- and 1.5-fold higher than those in the wild-type mice, respectively. Taken collectively, these findings indicate that PgP and Mrp1 limit the brain penetration of CTS in rodents, suggesting a possible role of PgP and MRP1 in limiting the brain penetration of CTS in patients and causing drug resistance to Danshen therapy and interactions with conventional drugs that are substrates of PgP and MRP1

  12. Swallowing Tablets and Capsules Increases the Risk of Penetration and Aspiration in Patients with Stroke-Induced Dysphagia.

    Science.gov (United States)

    Schiele, Julia T; Penner, Heike; Schneider, Hendrik; Quinzler, Renate; Reich, Gabriele; Wezler, Nikolai; Micol, William; Oster, Peter; Haefeli, Walter E

    2015-10-01

    We evaluated the prevalence of difficulties swallowing solid dosage forms in patients with stroke-induced dysphagia and whether swallowing tablets/capsules increases their risk of penetration and aspiration. Concurrently, we explored whether routinely performed assessment tests help identify patients at risk. Using video endoscopy, we evaluated how 52 patients swallowed four different placebos (round, oval, and oblong tablets and a capsule) with texture-modified water (TMW, pudding consistency) and milk and