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Sample records for experimental stroke severity

  1. Sleep deprivation attenuates experimental stroke severity in rats.

    PubMed

    Moldovan, Mihai; Constantinescu, Alexandra Oana; Balseanu, Adrian; Oprescu, Nicoleta; Zagrean, Leon; Popa-Wagner, Aurel

    2010-03-01

    Indirect epidemiological and experimental evidence suggest that the severity of injury during stroke is influenced by prior sleep history. The aim of our study was to test the effect of acute sleep deprivation on early outcome following experimental stroke. Young male Sprague-Dawley rats (n=20) were subjected to focal cerebral ischemia by reversible right middle cerebral artery occlusion (MCAO) for 90 min. In 10 rats, MCAO was performed just after 6-h of total sleep deprivation (TSD) by "gentle handling", whereas the other rats served as controls. Neurological function during the first week after stroke was monitored using a battery of behavioral tests investigating the asymmetry of sensorimotor deficit (tape removal test and cylinder test), bilateral sensorimotor coordination (rotor-rod and Inclined plane) and memory (T-maze and radial maze). Following MCAO, control rats had impaired behavioral performance in all tests. The largest impairment was noted in the tape test where the tape removal time from the left forelimb (contralateral to MCAO) was increased by approximately 10 fold (p<0.01). In contrast, rats subjected to TSD had complete recovery of sensorimotor performance consistent with a 2.5 fold smaller infarct volume and reduced morphological signs of neuronal injury at day 7 after MCAO. Our data suggest that brief TSD induces a neuroprotective response that limits the severity of a subsequent stroke, similar to rapid ischemic preconditioning. PMID:20045410

  2. Pre-stroke living situation and depression contribute to initial stroke severity and stroke recovery

    PubMed Central

    Aron, Abraham W.; Staff, Ilene; Fortunato, Gilbert; McCullough, Louise D.

    2014-01-01

    Substantial evidence from both experimental and clinical studies has demonstrated that social isolation can increase stroke incidence and impair recovery. Social isolation leads to higher rates of recurrent stroke but is often not reported as a risk factor. We examined prospectively collected stroke center database variables, which included pre-stroke living situation, to determine if social isolation could be determined from existing data using living arrangement as a proxy. Patients were categorized into 4 groups hypothesized to represent increasing levels of social isolation: Living with Spouse, Living with Family, Living alone with visiting services and Living Alone. Initial stroke severity and recovery were measured using the National Institutes of Health Stroke Scale and Barthel Index, respectively. A multivariate model was used to determine the relationship between pre-stroke living situation, stroke severity and functional outcome. Patients living alone had less severe strokes on admission and better recovery at 3 months compared to the other cohorts. Patients living alone or those that lived with a spouse had less severe strokes on presentation and better recovery at both 3 and 12 months after stroke compared to the other cohorts. However, upon detailed examination, it was found that these patients also had significantly higher pre-stroke function. Pre-existing depression was significantly higher in women and depressed patients had poorer outcomes 3 months after stroke. Information regarding isolation is notably absent from most large stroke databases. A more comprehensive evaluation of social interaction should be obtained to more accurately measure social isolation. PMID:25524014

  3. Severe stroke: which medicine for which results?

    PubMed

    Woimant, F; Biteye, Y; Chaine, P; Crozier, S

    2014-02-01

    In face of any severe stroke, the questions for health professionals in charge of the patient are: will the handicap be acceptable for the patient? But can we predict an acceptable handicap for the patient? For his family? When we know that the cognitive disorders, consequences of severe stroke often modify, in a major way, the behaviour of these patients? Given these difficulties for estimate vital and functional prognosis and even more the quality of life of patients with severe stroke, collective reflexions between physicians and nurses are essential, reflexions taking into account preferences and values of patients. Use of resuscitation resources for severe stroke patients implies to offer them the best rehabilitation. So, questions about health pathways for severe stroke are essential: which structures for these patients, which technologies, which medical, medico-social and social supports, which human accompaniment the society can propose to the patients and to their family, so that they have an acceptable quality of life. PMID:24388769

  4. Dimethylarginine levels in cerebrospinal fluid of hyperacute ischemic stroke patients are associated with stroke severity.

    PubMed

    Brouns, Raf; Marescau, Bart; Possemiers, Ilse; Sheorajpanday, Rishi; De Deyn, Peter P

    2009-09-01

    We hypothesise that asymmetric and symmetric dimethylarginine (ADMA, SDMA) are released in cerebrospinal fluid (CSF) due to ischemia-induced proteolysis and that CSF dimethylarginines are related to stroke severity. ADMA and SDMA were measured in CSF of 88 patients with ischemic stroke or TIA within 24 h after stroke onset (mean 8.6 h) and in 24 controls. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score at admission. Outcome was evaluated by institutionalization due to stroke and the modified Rankin scale. Dimethylarginine levels were higher in patients with stroke than in TIA patients, who had higher levels than controls and correlated with the NIHSS. Logistic regression analysis confirmed that dimethylarginines were independently associated with stroke severity. The SDMA/ADMA ratio did not differ significantly between controls and stroke patients. CSF dimethylarginine levels are increased in hyperacute ischemic stroke and are associated with stroke severity. PMID:19296217

  5. Stroke: 'time is brain' after stroke, regardless of age and severity.

    PubMed

    Audebert, Heinrich J; Sobesky, Jan

    2014-12-01

    Two recent studies highlight the importance of prompt, coordinated intervention after stroke. A meta-analysis confirms that intravenous thrombolysis is effective within 4.5 h of onset, irrespective of age (below or above 80 years) and stroke severity. Another study demonstrates successful reorganization of care through centralization of stroke services in England. PMID:25330727

  6. Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

    PubMed Central

    Hu, Heng; Doll, Danielle N.; Sun, Jiahong; Lewis, Sara E.; Wimsatt, Jeffrey H.; Kessler, Matthew J.; Simpkins, James W.; Ren, Xuefang

    2016-01-01

    Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for

  7. Risk of Stroke in Migraineurs Using Triptans. Associations with Age, Sex, Stroke Severity and Subtype

    PubMed Central

    Albieri, Vanna; Olsen, Tom Skyhøj; Andersen, Klaus Kaae

    2016-01-01

    Background Identifying migraineurs by triptan utilization we studied risk for stroke in migraineurs compared to the general population. Methods A cohort study including all citizens 25–80 years of age in Denmark 2003–2011 was conducted. All persons prescribed triptans, and all those hospitalized for a first stroke were identified in the Danish Registries. Information on stroke severity/subtype and cardiovascular risk factors was available for stroke patients. Findings Of the 49,711 patients hospitalized for a first stroke, 1084 were migraineurs using triptans. Adjusting for age, sex, income, and educational level, risk for stroke was higher among migraineurs in respect to all strokes (RR 1.07; CI 1.01–1.14) and ischemic strokes (RR 1.07; CI 1.00–1.14). Risk for hemorrhagic stroke was increased but only in women (RR 1.41; CI 1.11–1.79). Risk was for mild strokes (RR 1.31; CI 1.16–1.48) while risk for severe strokes was lower among migraineurs (RR 0.77; CI 0.65–0.91). Risk was age-related; highest among women 25–45 years (RR ≈ 1.7). Risk was unrelated to numbers of dispensations. Interpretation Migraineurs identified by triptan utilization had higher risk for stroke. Strokes were minor and cardiovascular risk factors were less prevalent pointing to a migraine-specific etiology of stroke different from that of thromboembolism. PMID:27211561

  8. Recombinant T Cell Receptor Ligand (RTL) Treats Experimental Stroke

    PubMed Central

    Subramanian, Sandhya; Zhang, Bing; Kosaka, Yasuharu; Burrows, Gregory G.; Grafe, Marjorie R.; Vandenbark, Arthur A.; Hurn, Patricia D.; Offner, Halina

    2009-01-01

    Background and Purpose Experimental stroke induces a biphasic effect on the immune response that involves early activation of peripheral leukocytes followed by severe immunodepression and atrophy of spleen and thymus. In tandem, the developing infarct is exacerbated by influx of numerous inflammatory cell types, including T and B lymphocytes. These features of stroke prompted our use of Recombinant T Cell Receptor Ligands (RTL), partial MHC class II molecules covalently bound to myelin peptides. We tested the hypothesis that RTL would improve ischemic outcome in brain without exacerbating defects in peripheral immune system function. Methods Four daily doses of RTL were administered subcutaneously to C57BL/6 mice after middle cerebral artery occlusion (MCAO), and lesion size and cellular composition were assessed in brain, and cell numbers were assessed in spleen and thymus. Results Treatment with RTL551 (I-Ab molecule linked to MOG-35−55 peptide) reduced cortical and total stroke lesion size by ∼50%, inhibited the accumulation of inflammatory cells, particularly macrophages/activated microglial cells and dendritic cells, and mitigated splenic atrophy. Treatment with RTL1000 (HLA-DR2 moiety linked to human MOG-35−55 peptide) similarly reduced the stroke lesion size in HLA-DR2 transgenic mice. In contrast, control RTL with a non-neuroantigen peptide or a mismatched MHC class II moiety had no effect on stroke lesion size. Conclusions These data are the first to demonstrate successful treatment of experimental stroke using a neuroantigen specific immunomodulatory agent administered after ischemia, suggesting therapeutic potential in human stroke. PMID:19443805

  9. Experimental acute thrombotic stroke in baboons

    SciTech Connect

    Del Zoppo, G.J.; Copeland, B.R.; Harker, L.A.; Waltz, T.A.; Zyroff, J.; Hanson, S.R.; Battenberg, E.

    1986-11-01

    To study the effects of antithrombotic therapy in experimental stroke, we have characterized a baboon model of acute cerebrovascular thrombosis. In this model an inflatable silastic balloon cuff has been implanted by transorbital approach around the right middle cerebral artery (MCA), proximal to the take-off of the lenticulostriate arteries (LSA). Inflation of the balloon for 3 hours in six animals produced a stereotypic sustained stroke syndrome characterized by contralateral hemiparesis. An infarction volume of 3.2 +/- 1.5 cm3 in the ipsilateral corpus striatum was documented by computerized tomographic (CT) scanning at 10 days following stroke induction and 3.9 +/- 1.9 cm3 (n = 4) at 14 days by morphometric neuropathologic determinations of brain specimens fixed in situ by pressure-perfusion with 10% buffered formalin. Immediate pressure-perfusion fixation following deflation of the balloon was performed in 16 additional animals given Evans blue dye intravenously prior to the 3 hour MCA balloon occlusion. Light microscopy and transmission electron microscopy consistently confirmed the presence of thrombotic material occluding microcirculatory branches of the right LSA in the region of Evans blue stain, but not those of the contralateral corpus striatum. When autologous 111In-platelets were infused intravenously in four animals from the above group prior to the transient 3 hour occlusion of the right MCA, gamma scintillation camera imaging of each perfused-fixed whole brain demonstrated the presence of a single residual focus of 111In-platelet activity involving only the Evans blue-stained right corpus striatum. Focal right hemispheric activity was equivalent to 0.55 +/- 0.49 ml of whole blood, and the occlusion score derived from histologic examination of the microcirculation of the Evans blue-stained corpus striatum averaged 34.8 +/- 2.8.

  10. Decoding upper limb residual muscle activity in severe chronic stroke

    PubMed Central

    Ramos-Murguialday, Ander; García-Cossio, Eliana; Walter, Armin; Cho, Woosang; Broetz, Doris; Bogdan, Martin; Cohen, Leonardo G; Birbaumer, Niels

    2015-01-01

    Objective Stroke is a leading cause of long-term motor disability. Stroke patients with severe hand weakness do not profit from rehabilitative treatments. Recently, brain-controlled robotics and sequential functional electrical stimulation allowed some improvement. However, for such therapies to succeed, it is required to decode patients' intentions for different arm movements. Here, we evaluated whether residual muscle activity could be used to predict movements from paralyzed joints in severely impaired chronic stroke patients. Methods Muscle activity was recorded with surface-electromyography (EMG) in 41 patients, with severe hand weakness (Fugl-Meyer Assessment [FMA] hand subscores of 2.93 ± 2.7), in order to decode their intention to perform six different motions of the affected arm, required for voluntary muscle activity and to control neuroprostheses. Decoding of paretic and nonparetic muscle activity was performed using a feed-forward neural network classifier. The contribution of each muscle to the intended movement was determined. Results Decoding of up to six arm movements was accurate (>65%) in more than 97% of nonparetic and 46% of paretic muscles. Interpretation These results demonstrate that some level of neuronal innervation to the paretic muscle remains preserved and can be used to implement neurorehabilitative treatments in 46% of patients with severe paralysis and extensive cortical and/or subcortical lesions. Such decoding may allow these patients for the first time after stroke to control different motions of arm prostheses through muscle-triggered rehabilitative treatments. PMID:25642429

  11. Biomaterial Applications in Cell-Based Therapy in Experimental Stroke

    PubMed Central

    Boisserand, Ligia S. B.; Kodama, Tomonobu; Papassin, Jérémie; Auzely, Rachel; Moisan, Anaïck; Rome, Claire; Detante, Olivier

    2016-01-01

    Stroke is an important health issue corresponding to the second cause of mortality and first cause of severe disability with no effective treatments after the first hours of onset. Regenerative approaches such as cell therapy provide an increase in endogenous brain structural plasticity but they are not enough to promote a complete recovery. Tissue engineering has recently aroused a major interesting development of biomaterials for use into the central nervous system. Many biomaterials have been engineered based on natural compounds, synthetic compounds, or a mix of both with the aim of providing polymers with specific properties. The mechanical properties of biomaterials can be exquisitely regulated forming polymers with different stiffness, modifiable physical state that polymerizes in situ, or small particles encapsulating cells or growth factors. The choice of biomaterial compounds should be adapted for the different applications, structure target, and delay of administration. Biocompatibilities with embedded cells and with the host tissue and biodegradation rate must be considerate. In this paper, we review the different applications of biomaterials combined with cell therapy in ischemic stroke and we explore specific features such as choice of biomaterial compounds and physical and mechanical properties concerning the recent studies in experimental stroke. PMID:27274738

  12. Piperlonguminine is neuroprotective in experimental rat stroke.

    PubMed

    Yang, Tiansong; Sun, Shixiao; Wang, Tiegang; Tong, Xin; Bi, Junhui; Wang, Yulin; Sun, Zhongren

    2014-12-01

    Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Piperlonguminine (PE) has been proved to have anti-inflammatory actions. In this study, we investigated the effects of PE on cultured neuronal cell line, SH-SY5Y in vitro and experimental rat ischemic stroke in vivo. For oxygen-glucose deprivation (OGD) and tumor necrosis factor-α (TNF-α) stimulated SH-SY5Y cell line in vitro, SH-SY5Y cells were incubated with PE. In vivo, rats were subjected to middle cerebral artery occlusion (MACO) for 1h, followed by reperfusion for 23 h. The results of this study showed that treatment of SH-SY5Y cells with PE reduced the OGD-induced cytotoxicity and apoptosis and blocked TNF-α-induced activation of NF-κB and MAPK. Intraperitoneal injection of PE (2.4 mg/kg) produced a significant neuroprotective potential in rats with cerebral ischemia. PE attenuated neurological deficit scores, brain infarct volume and brain water content in rats, and inhibited activation of NF-κB and MAPK. These data show that PE protects the brain against ischemic cerebral injury via alleviating blood-brain barrier (BBB) breakdown, which may be mediated via inhibiting NF-κB and MAPK signaling pathways. PMID:25257731

  13. Methodological standards for experimental research on stroke using scalp acupuncture.

    PubMed

    Zheng, Guo-qing

    2009-01-01

    Scalp acupuncture (SA) is a modality based on different physiologic functions of different brain areas, using needles to stimulate different scalp zones so as to excite the reflex-related nervous tissue. The findings of several studies showed that the clinical effect of SA on stroke was significant, but the exact mechanism is still unclear. In this research, some new ways of thinking and new methodological standards on stroke experiment using SA are put forward. They are as follows: A, establishment of standard animal model of stroke; B, simulation of head acupoint line on animal model following traditional Chinese medicine localization; C, acupuncture manipulation and quantity of stimulus for SA in animal model; D, optimal curative opportunity and instant effect of SA therapy on stroke; E, mechanism study of SA on stroke. This research may provide methodological reference for future mechanism study on stroke experiment using SA. PMID:19711771

  14. Stroke

    MedlinePlus

    ... Stay Connected Home » Stroke Heath and Aging Stroke What Is a Stroke? Stroke Is an Emergency. ... IGNORE THE SIGNS OF STROKE! What Is a Stroke? A stroke happens when something changes how blood ...

  15. Of mice and men: modelling post-stroke depression experimentally

    PubMed Central

    Kronenberg, G; Gertz, K; Heinz, A; Endres, M

    2014-01-01

    At least one-third of stroke survivors suffer from depression. The development of comorbid depression after stroke is clinically highly significant because post-stroke depression is associated with increased mortality, slows recovery and leads to worse functional outcomes. Here, we review the evidence that post-stroke depression can be effectively modelled in experimental rodents via a variety of approaches. This opens an exciting new window onto the neurobiology of depression and permits probing potential underlying mechanisms such as disturbed cellular plasticity, neuroendocrine dysregulation, neuroinflammation, and neurodegeneration in a novel context. From the point of view of translational stroke research, extending the scope of experimental investigations beyond the study of short-term end points and, in particular, acute lesion size, may help improve the relevance of preclinical results to human disease. Furthermore, accumulating evidence from both clinical and experimental studies offers the tantalizing prospect of 5-hydroxytryptaminergic antidepressants as the first pharmacological therapy for stroke that would be available during the subacute and chronic phases of recovery. Interdisciplinary neuropsychiatric research will be called on to dissect the mechanisms underpinning the beneficial effects of antidepressants on stroke recovery. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24838087

  16. Ultrasonic Vocalization Changes and FOXP2 expression after Experimental Stroke

    PubMed Central

    Doran, Sarah J; Trammel, Cassandra; Benashaski, Sharon E; Venna, Venugopal Reddy; McCullough, Louise D

    2015-01-01

    Speech impairments affect one in four stroke survivors. However, animal models of post-ischemic vocalization deficits are limited. Male mice vocalize at ultrasonic frequencies when exposed to an estrous female mouse. In this study we assessed vocalization patterns and quantity in male mice after cerebral ischemia. FOXP2, a gene associated with verbal dyspraxia in humans, with known roles in neurogenesis and synaptic plasticity, was also examined after injury. Using a transient middle cerebral artery occlusion (MCAO) model, we assessed correlates of vocal impairment at several time-points after stroke. Further, to identify possible lateralization of vocalization deficits induced by left and right hemispheric strokes were compared. Significant differences in vocalization quantity were observed between stroke and sham animals that persisted for a month after injury. Injury to the left hemisphere reduced early vocalizations more profoundly than those to the right hemisphere. Nuclear expression of Foxp2 was elevated early after stroke (at 6 hours), but significantly decreased 24 hours after injury in both the nucleus and the cytoplasm. Neuronal Foxp2 expression increased in stroke mice compared to sham animals 4 weeks after injury. This study demonstrates that quantifiable deficits in ultrasonic vocalizations (USVs) are seen after stroke. USV may be a useful tool to assess chronic behavioral recovery in murine models of stroke. PMID:25644653

  17. Ultrasonic vocalization changes and FOXP2 expression after experimental stroke.

    PubMed

    Doran, Sarah J; Trammel, Cassandra; Benashaski, Sharon E; Venna, Venugopal Reddy; McCullough, Louise D

    2015-04-15

    Speech impairments affect one in four stroke survivors. However, animal models of post-ischemic vocalization deficits are limited. Male mice vocalize at ultrasonic frequencies when exposed to an estrous female mouse. In this study we assessed vocalization patterns and quantity in male mice after cerebral ischemia. FOXP2, a gene associated with verbal dyspraxia in humans, with known roles in neurogenesis and synaptic plasticity, was also examined after injury. Using a transient middle cerebral artery occlusion (MCAO) model, we assessed correlates of vocal impairment at several time-points after stroke. Further, to identify possible lateralization of vocalization deficits induced by left and right hemispheric strokes were compared. Significant differences in vocalization quantity were observed between stroke and sham animals that persisted for a month after injury. Injury to the left hemisphere reduced early vocalizations more profoundly than those to the right hemisphere. Nuclear expression of Foxp2 was elevated early after stroke (at 6h), but significantly decreased 24h after injury in both the nucleus and the cytoplasm. Neuronal Foxp2 expression increased in stroke mice compared to sham animals 4 weeks after injury. This study demonstrates that quantifiable deficits in ultrasonic vocalizations (USVs) are seen after stroke. USV may be a useful tool to assess chronic behavioral recovery in murine models of stroke. PMID:25644653

  18. Methylene blue treatment in experimental ischemic stroke: a mini review

    PubMed Central

    Jiang, Zhao; Duong, Timothy Q

    2016-01-01

    Stroke is a leading cause of death and long-term disability. Methylene blue, a drug grandfathered by the Food and Drug Administration with a long history of safe usage in humans for treating methemoglobinemia and cyanide poisoning, has recently been shown to be neuroprotective in neurodegenerative diseases and brain injuries. The goal of this paper is to review studies on methylene blue in experimental stroke models. PMID:27042692

  19. Improvement of survival in Polish stroke patients is related to reduced stroke severity and better control of risk factors: the Krakow Stroke Database

    PubMed Central

    Swarowska, Marta; Burkot, Jacek; Janowska, Aleksandra; Klimkowicz-Mrowiec, Aleksandra; Pera, Joanna; Slowik, Agnieszka

    2016-01-01

    Introduction In the last decade, the stroke mortality rate in Poland significantly decreased. We hypothesised that stroke severity, the major determinant of outcome, is lowered in Polish stroke patients. Material and methods We compared the stroke severity in two cohorts of first-ever ischaemic stroke patients admitted within 24 h after stroke onset to the Department of Neurology, Jagiellonian University, Krakow in the years 1994–2000 and 2008–2012. To assess stroke severity we used the National Institute of Health Stroke Scale (NIHSS). We defined mild stroke as an NIHSS score ≤ 4. Results We included 816 patients hospitalised in the years 1994–2000 and 569 patients hospitalised in the years 2008–2012. NIHSS score on admission was higher in the former (mean: 12.0 ±7.0 vs. 8.0 ±6.0, p < 0.01), and the frequency of mild stroke was higher in the latter (12.7% vs. 41.8%, p < 0.01). Although the frequency of hypertension (67.3% vs. 81.2%, p < 0.01), diabetes mellitus (20.8% vs. 26.4%, p = 0.02) and atrial fibrillation (20.7% vs. 26.2%, p = 0.02) was higher in patients hospitalised in the years 2008–2012, the systolic and diastolic blood pressure values and the frequency of fasting hyperglycaemia were lower in this cohort. This cohort also less frequently suffered from hypercholesterolaemia (25.4% vs. 16.3%, p < 0.01). Conclusions Reduced stroke severity is associated with better recognition and control of risk factors and explains the improvement of survival in Polish stroke patients. PMID:27279847

  20. Knockout of silent information regulator 2 (SIRT2) preserves neurological function after experimental stroke in mice.

    PubMed

    Krey, Lea; Lühder, Fred; Kusch, Kathrin; Czech-Zechmeister, Bozena; Könnecke, Birte; Fleming Outeiro, Tiago; Trendelenburg, George

    2015-12-01

    Sirtuin-2 (Sirt2) is a member of the NAD(+)-dependent protein deacetylase family. Various members of the sirtuin class have been found to be involved in processes related to longevity, regulation of inflammation, and neuroprotection. Induction of Sirt2 mRNA was found in the whole hemisphere after experimental stroke in a recent screening approach. Moreover, Sirt2 protein is highly expressed in myelin-rich brain regions after stroke. To examine the effects of Sirt2 on ischemic stroke, we induced transient focal cerebral ischemia in adult male Sirt2-knockout and wild-type mice. Two stroke models with different occlusion times were applied: a severe ischemia (45 minutes of middle cerebral artery occlusion (MCAO)) and a mild one (15 minutes of MCAO), which was used to focus on subcortical infarcts. Neurological deficit was determined at 48 hours after 45 minutes of MCAO, and up to 7 days after induction of 15 minutes of cerebral ischemia. In contrast to recent data on Sirt1, Sirt2(-/-) mice showed less neurological deficits in both models of experimental stroke, with the strongest manifestation after 48 hours of reperfusion. However, we did not observe a significant difference of stroke volumes or inflammatory cell count between Sirt2-deficient and wild-type mice. Thus we postulate that Sirt2 mediates myelin-dependent neuronal dysfunction during the early phase after ischemic stroke. PMID:26219598

  1. Delayed reperfusion deficits after experimental stroke account for increased pathophysiology

    PubMed Central

    Burrows, Fiona E; Bray, Natasha; Denes, Adam; Allan, Stuart M; Schiessl, Ingo

    2015-01-01

    Cerebral blood flow and oxygenation in the first few hours after reperfusion following ischemic stroke are critical for therapeutic interventions but are not well understood. We investigate changes in oxyhemoglobin (HbO2) concentration in the cortex during and after ischemic stroke, using multispectral optical imaging in anesthetized mice, a remote filament to induce either 30 minute middle cerebral artery occlusion (MCAo), sham surgery or anesthesia alone. Immunohistochemistry establishes cortical injury and correlates the severity of damage with the change of oxygen perfusion. All groups were imaged for 6 hours after MCAo or sham surgery. Oxygenation maps were calculated using a pathlength scaling algorithm. The MCAo group shows a significant drop in HbO2 during occlusion and an initial increase after reperfusion. Over the subsequent 6 hours HbO2 concentrations decline to levels below those observed during stroke. Platelets, activated microglia, interleukin-1α, evidence of BBB breakdown and neuronal stress increase within the stroked hemisphere and correlate with the severity of the delayed reperfusion deficit but not with the ΔHbO2 during stroke. Despite initial restoration of HbO2 after 30 min MCAo there is a delayed compromise that coincides with inflammation and could be a target for improved stroke outcome after thrombolysis. PMID:25407273

  2. Neurological Symptom Severity after a Recent Non-cardioembolic Stroke and Recurrent Vascular Risk

    PubMed Central

    Park, Jong-Ho; Ovbiagele, Bruce

    2015-01-01

    Background There is a well-established relation of symptom severity with functional status and mortality after an index stroke. However, little is known about the impact of symptom severity of a recent index stroke on risk of recurrent vascular events. Methods We reviewed the dataset of a multicenter trial involving 3680 recent non-cardioembolic stroke patients aged ≥35 years and followed for 2 years. Independent associations of stroke severity (as measured by National Institutes of Health Stroke Scale [NIHSS] score) with recurrent stroke (primary outcome) and stroke/coronary heart disease (CHD)/vascular death (secondary outcome) were analyzed. NIHSS score was analyzed as a dichotomous (<4 vs. ≥4) and a continuous variable. Results Among study subjects, 550 (15%) had NIHSS scores ≥4 (overall scores ranged from 0 to 18, median score was 1 [25th to 75th percentile 0 to 2]). NIHSS was measured at a median 35 days after the index stroke. After adjusting for multiple covariates, NIHSS ≥4 was independently linked to higher risk of recurrent stroke (HR 1.37, 95% CI: 1.01–1.84) and risk of stroke/CHD/vascular death (HR 1.32, 95% CI: 1.07–1.64). Analysis of NIHSS score as a continuous variable also showed a higher risk of recurrent stroke (HR 1.06, 95% CI: 1.00–1.12) and stroke/CHD/vascular death (HR 1.05, 95% CI: 1.01–1.09) with increasing index stroke symptom severity. Conclusions Greater residual symptom severity after a recent stroke is associated with higher risk of recurrent vascular events. Future studies are needed to confirm this relationship and to clarify its underlying mechanisms. PMID:25817617

  3. Stroke

    MedlinePlus

    ... the blockages that lead to ischemic strokes. A hemorrhagic stroke occurs if an artery in the brain leaks ... risms) are examples of conditions that can cause hemorrhagic strokes. (Aneurysms are balloon-like bulges in an artery ...

  4. Stroke

    MedlinePlus

    ... to a hospital quickly to begin treatment. Acute stroke therapies try to stop a stroke while it is ... rehabilitation helps individuals overcome disabilities that result from stroke damage. Drug therapy with blood thinners is the most common treatment ...

  5. Prediction of Motor Recovery Using Diffusion Tensor Tractography in Supratentorial Stroke Patients With Severe Motor Involvement

    PubMed Central

    Kim, Kang Hee; Kim, Yun-Hee; Kim, Min Su; Park, Chang-hyun; Lee, Ahee

    2015-01-01

    Objective To investigate whether early stage diffusion tensor tractography (DTT) values predict motor function at 3 months after onset in supratentorial stroke patients with severe motor involvement. Methods A retrospective study design was used to analyze medical records and neuroimaging data of 49 supratentorial stroke patients with severe motor involvement. Diffusion tensor imaging was assessed within 3 weeks after stroke in all patients. Three-dimensional tractography of the ipsilateral corticospinal tract (CST) was performed using the fiber assignment of the continuous tracking algorithm. The two-step DTT analysis was used. The first step was classification according to ipsilateral CST visualization. The second step was a quantitative analysis of the visible-CST group parameters. Motor function was assessed at 2 weeks and at 3 months after stroke. Comparative and correlation analyses were performed between DTT-derived measures and motor assessment scores. Results Motor function of the upper extremity at 3 months after stroke was significantly higher in the visible-CST group than that in the nonvisible-CST group (p<0.05). Early stage fractional anisotropy was of DTT correlated significantly with upper extremity motor function at 3 months after stroke in the visible-CST group (p<0.05). Conclusion These results demonstrate that early DTT-derived measures predict motor recovery in the upper extremity at 3 months after onset in supratentorial stroke patients with severe motor involvement. PMID:26361593

  6. Stroke

    MedlinePlus

    ... emergency. Strokes happen when blood flow to your brain stops. Within minutes, brain cells begin to die. There are two kinds ... blocks or plugs a blood vessel in the brain. The other kind, called hemorrhagic stroke, is caused ...

  7. Age-related changes in brain support cells: Implications for stroke severity

    PubMed Central

    Sohrabji, Farida; Bake, Shameena; Lewis, Danielle K.

    2013-01-01

    Stroke is one of the leading causes of adult disability and the fourth leading cause of mortality in the US. Stroke disproportionately occurs among the elderly, where the disease is more likely to be fatal or lead to long-term supportive care. Animal models, where the ischemic insult can be controlled more precisely, also confirm that aged animals sustain more severe strokes as compared to young animals. Furthermore, the neuroprotection usually seen in younger females when compared to young males is not observed in older females. The preclinical literature thus provides a valuable resource for understanding why the aging brain is more susceptible to severe infarction. In this review, we discuss the hypothesis that stroke severity in the aging brain may be associated with reduced functional capacity of critical support cells. Specifically, we focus on astrocytes, that are critical for detoxification of the brain microenvironment and endothelial cells, which play a crucial role in maintaining the blood brain barrier. In view of the sex difference in stroke severity, this review also discusses studies of middle-aged acyclic females as well as the effects of the estrogen on astrocytes and endothelial cells PMID:23811611

  8. Genetically-Defined Deficiency of Mannose-Binding Lectin Is Associated with Protection after Experimental Stroke in Mice and Outcome in Human Stroke

    PubMed Central

    Cervera, Alvaro; Planas, Anna M.; Justicia, Carles; Urra, Xabier; Jensenius, Jens C.; Torres, Ferran; Lozano, Francisco; Chamorro, Angel

    2010-01-01

    Background The complement system is a major effector of innate immunity that has been involved in stroke brain damage. Complement activation occurs through the classical, alternative and lectin pathways. The latter is initiated by mannose-binding lectin (MBL) and MBL-associated serine proteases (MASPs). Here we investigated whether the lectin pathway contributes to stroke outcome in mice and humans. Methodology/Principal Findings Focal cerebral ischemia/reperfusion in MBL-null mice induced smaller infarctions, better functional outcome, and diminished C3 deposition and neutrophil infiltration than in wild-type mice. Accordingly, reconstitution of MBL-null mice with recombinant human MBL (rhMBL) enhanced brain damage. In order to investigate the clinical relevance of these experimental observations, a study of MBL2 and MASP-2 gene polymorphism rendering the lectin pathway dysfunctional was performed in 135 stroke patients. In logistic regression adjusted for age, gender and initial stroke severity, unfavourable outcome at 3 months was associated with MBL-sufficient genotype (OR 10.85, p = 0.008) and circulating MBL levels (OR 1.29, p = 0.04). Individuals carrying MBL-low genotypes (17.8%) had lower C3, C4, and CRP levels, and the proinflammatory cytokine profile was attenuated versus MBL-sufficient genotypes. Conclusions/Significance In conclusion, genetically defined MBL-deficiency is associated with a better outcome after acute stroke in mice and humans. PMID:20140243

  9. Training-induced modifications of corticospinal reactivity in severely affected stroke survivors.

    PubMed

    Barker, Ruth N; Brauer, Sandra G; Barry, Benjamin K; Gill, Toby J; Carson, Richard G

    2012-08-01

    When permitted access to the appropriate forms of rehabilitation, many severely affected stroke survivors demonstrate a capacity for upper limb functional recovery well in excess of that formerly considered possible. Yet, the mechanisms through which improvements in arm function occur in such profoundly impaired individuals remain poorly understood. An exploratory study was undertaken to investigate the capacity for brain plasticity and functional adaptation, in response to 12-h training of reaching using the SMART Arm device, in a group of severely affected stroke survivors with chronic upper limb paresis. Twenty-eight stroke survivors were enroled. Eleven healthy adults provided normative data. To assess the integrity of ipsilateral and contralateral corticospinal pathways, transcranial magnetic stimulation was applied to evoke responses in triceps brachii during an elbow extension task. When present, contralateral motor-evoked potentials (MEPs) were delayed and reduced in amplitude compared to those obtained in healthy adults. Following training, contralateral responses were more prevalent and their average onset latency was reduced. There were no reliable changes in ipsilateral MEPs. Stroke survivors who exhibited contralateral MEPs prior to training achieved higher levels of arm function and exhibited greater improvements in performance than those who did not initially exhibit contralateral responses. Furthermore, decreases in the onset latency of contralateral MEPs were positively related to improvements in arm function. Our findings demonstrate that when severely impaired stroke survivors are provided with an appropriate rehabilitation modality, modifications of corticospinal reactivity occur in association with sustained improvements in upper limb function. PMID:22777103

  10. Estradiol and G1 Reduce Infarct Size and Improve Immunosuppression after Experimental Stroke

    PubMed Central

    Zhang, Bing; Subramanian, Sandhya; Dziennis, Suzan; Jia, Jia; Uchida, Masayoshi; Akiyoshi, Kozaburo; Migliati, Elton; Lewis, Anne D.; Vandenbark, Arthur A.; Offner, Halina; Hurn, Patricia D.

    2011-01-01

    Reduced risk and severity of stroke in adult females is thought to depend on normal endogenous levels of estrogen, a well-known neuroprotectant and immunomodulator. In male mice, experimental stroke induces immunosuppression of the peripheral immune system, characterized by a reduction in spleen size and cell numbers and decreased cytokine and chemokine expression. However, stroke-induced immunosuppression has not been evaluated in female mice. To test the hypothesis that estradiol (E2) deficiency exacerbates immunosuppression after focal stroke in females, we evaluated the effect of middle cerebral artery occlusion on infarct size and peripheral and CNS immune responses in ovariectomized mice with or without sustained, controlled levels of 17-β–E2 administered by s.c. implant or the putative membrane estrogen receptor agonist, G1. Both E2- and G1-replacement decreased infarct volume and partially restored splenocyte numbers. Moreover, E2-replacement increased splenocyte proliferation in response to stimulation with anti-CD3/CD28 Abs and normalized aberrant mRNA expression for cytokines, chemokines, and chemokine receptors and percentage of CD4+CD25+FoxP3+ T regulatory cells observed in E2-deficient animals. These beneficial changes in peripheral immunity after E2 replacement were accompanied by a profound reduction in expression of the chemokine, MIP-2, and a 40-fold increased expression of CCR7 in the lesioned brain hemisphere. These results demonstrate for the first time that E2 replacement in ovariectomized female mice improves stroke-induced peripheral immunosuppression. PMID:20304826

  11. Use of telemedicine to manage severe ischaemic strokes in a rural area with an elderly population.

    PubMed

    Richard, Sébastien; Lavandier, K; Zioueche, Y; Pelletier, S; Vezain, A; Ducrocq, X

    2014-05-01

    The rural district of the Meuse (East France) has a high number of elderly patients for whom prognosis of ischaemic strokes is poor with high-haemorrhagic transformation risk of intravenous tissue plasminogen activator (rt-PA). This disadvantage is made worse by the distances a patient has to travel to the nearest stroke unit. We set out to assess the effectiveness of a telestroke system implemented in this area. Between October 2010 and February 2012, data from each "tele-expertised" patient were collected. 53 patients were examined. Diagnosis of ischaemic stroke was confirmed in 43 cases (81 %), and intravenous rt-PA treatment performed in 21 cases (40 %). In the treated patient group, median age was 73 years, with 29 % of octogenarians. Baseline National Institutes of Health Stroke Scale (NIHSS) was 16, with 29 % ≥ 20. The median onset to needle time was 169 min, and the median door to needle time was 69 min. Intracranial haemorrhage occurred in 3 cases (14 %), and was symptomatic in two (10 %). At 3 months, median NIHSS was 6, 6 patients (29 %) presented a favourable outcome (modified Rankin scale ≤ 1) and 3 (14 %) had died. In rural areas, for elderly patients with severe ischaemic strokes, telemedicine appears to be a way of improving accessibility and benefits of rt-PA treatment. PMID:24277200

  12. Arterial Hypertension Aggravates Innate Immune Responses after Experimental Stroke.

    PubMed

    Möller, Karoline; Pösel, Claudia; Kranz, Alexander; Schulz, Isabell; Scheibe, Johanna; Didwischus, Nadine; Boltze, Johannes; Weise, Gesa; Wagner, Daniel-Christoph

    2015-01-01

    Arterial hypertension is not only the leading risk factor for stroke, but also attributes to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood-brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs) were subjected to photothrombotic stroke. One and 3 days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines along with the post-stroke inflammatory response were analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains 4 days after stroke. Although comparable at day 1, lesion volumes were significantly larger in SHR at day 3. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and P-selectin (CD62P) was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte-leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may finally be responsible for

  13. Arterial Hypertension Aggravates Innate Immune Responses after Experimental Stroke

    PubMed Central

    Möller, Karoline; Pösel, Claudia; Kranz, Alexander; Schulz, Isabell; Scheibe, Johanna; Didwischus, Nadine; Boltze, Johannes; Weise, Gesa; Wagner, Daniel-Christoph

    2015-01-01

    Arterial hypertension is not only the leading risk factor for stroke, but also attributes to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood–brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs) were subjected to photothrombotic stroke. One and 3 days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines along with the post-stroke inflammatory response were analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains 4 days after stroke. Although comparable at day 1, lesion volumes were significantly larger in SHR at day 3. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and P-selectin (CD62P) was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte–leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may finally be responsible for

  14. Experimental animal models and inflammatory cellular changes in cerebral ischemic and hemorrhagic stroke

    PubMed Central

    Yan, Tao; Chopp, Michael; Chen, Jieli

    2015-01-01

    Stroke, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage, is the leading cause of long-term disability and death worldwide. Animal models have greatly contributed to our understanding of the risk factors and the pathophysiology of stroke, as well as the development of therapeutic strategies for its treatment. Further development and investigation of experimental models, however, are needed to elucidate the pathogenesis of stroke and to enhance and expand novel therapeutic targets. In this article, we provide an overview of the characteristics of commonly-used animal models of stroke and focus on the inflammatory responses to cerebral stroke, which may provide insights into a framework for developing effective therapies for stroke in humans. PMID:26625873

  15. Use of a Portable Assistive Glove to Facilitate Rehabilitation in Stroke Survivors With Severe Hand Impairment.

    PubMed

    Fischer, Heidi C; Triandafilou, Kristen M; Thielbar, Kelly O; Ochoa, Jose M; Lazzaro, Emily D C; Pacholski, Kathleen A; Kamper, Derek G

    2016-03-01

    Treatment options for stroke survivors with severe hand impairment are limited. Active task practice can be restricted by difficulty in voluntarily activating finger muscles and interference from involuntary muscle excitation. We developed a portable, actuated glove-orthosis, which could be employed to address both issues. We hypothesized that combining passive cyclical stretching (reducing motoneuronal hyperexcitability) imposed by the device with active-assisted, task-oriented training (rehabilitating muscle activation) would improve upper extremity motor control and task performance post-stroke. Thirteen participants who experienced a stroke 2-6 months prior to enrollment completed 15 treatment sessions over five weeks. Each session involved cyclically stretching the long finger flexors (30 min) followed by active-assisted task-oriented movement practice (60 min). Outcome measures were completed at six intervals: three before and three after treatment initiation. Overall improvement in post-training scores was observed across all outcome measures, including the Graded Wolf Motor Function Test, Action Research Arm Test, and grip and pinch strength ( p ≤ 0.02 ), except finger extension force. No significant change in spasticity was observed. Improvement in upper extremity capabilities is achievable for stroke survivors even with severe hand impairment through a novel intervention combining passive cyclical stretching and active-assisted task practice, a paradigm which could be readily incorporated into the clinic. PMID:26731772

  16. Outdoor air pollution, subtypes and severity of ischemic stroke – a small-area level ecological study

    PubMed Central

    2014-01-01

    Background Evidence linking outdoor air pollution and incidence of ischemic stroke subtypes and severity is limited. We examined associations between outdoor PM10 and NO2 concentrations modeled at a fine spatial resolution and etiological and clinical ischemic stroke subtypes and severity of ischemic stroke. Methods We used a small-area level ecological study design and a stroke register set up to capture all incident cases of first ever stroke (1995–2007) occurring in a defined geographical area in South London (948 census output areas; population of 267839). Modeled PM10 and NO2 concentrations were available at a very fine spatial scale (20 meter by 20 meter grid point resolution) and were aggregated to output area level using postcode population weighted averages. Ischemic stroke was classified using the Oxford clinical classification, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) etiological classification, National Institutes of Health Stroke Scale (NIHSS) score and a pragmatic clinical severity classification based on Glasgow coma score, ability to swallow, urinary continence and death <2 days of stroke onset. Results Mean (SD) concentrations were 25.1 (1.2) ug/m3 (range 23.3-36.4) for PM10 and 41.4 (3.0) ug/m3 (range 35.4-68.0) for NO2. There were 2492 incident cases of ischemic stroke. We found no evidence of association between these pollutants and the incidence of ischemic stroke subtypes classified using the Oxford and TOAST classifications. We found no significant association with stroke severity using NIHSS severity categories. However, we found that outdoor concentrations of both PM10 and NO2 appeared to be associated with increased incidence of mild but not severe ischemic stroke, classified using the pragmatic clinical severity classification. For mild ischemic stroke, the rate ratio in the highest PM10 category by tertile was 1.20 (1.05-1.38) relative to the lowest category. The rate ratio in the highest NO2 category was 1.22 (1

  17. Experimental reproduction of severe bluetongue in sheep.

    PubMed

    MacLachlan, N J; Crafford, J E; Vernau, W; Gardner, I A; Goddard, A; Guthrie, A J; Venter, E H

    2008-05-01

    Sheep inoculated with a virulent South African strain of bluetongue (BT) virus serotype 4 developed severe clinical signs and lesions characteristic of fulminant BT, including coronitis, hemorrhage and ulceration of the mucosal lining of the oral cavity and forestomaches, hemorrhage in the wall of the pulmonary artery, and focally extensive necrosis of skeletal muscle, especially of the neck. At necropsy, up to 14 days after infection, the infected sheep exhibited striking pulmonary edema, edema of the subcutaneous tissues and fascial planes of the head and neck, and pleural and pericardial effusion of varying severity. A reliable model for experimental reproduction of fulminant BT in sheep will facilitate future studies to better characterize the pathogenesis of this disease, particularly as it regards the mechanisms responsible for the increased vascular permeability that characterizes BT and related orbiviral diseases such as African horse sickness. PMID:18487487

  18. Effect of anticoagulation on cardioembolic stroke severity, outcomes and response to intravenous thrombolysis.

    PubMed

    Illán-Gala, Ignacio; Martínez-Sánchez, Patricia; Fuentes, Blanca; Llamas-Osorio, Yudy; Díaz de Terán, Javier; Báez, Melissa; Ruiz-Ares, Gerardo; Sanz-Cuesta, Borja Enrique; Lara-Lara, Manuel; Díez-Tejedor, Exuperio

    2016-07-01

    Our objective was to evaluate the effect of anticoagulation on cardioembolic stroke (CS) severity, outcomes, and response to intravenous thrombolysis (IVT). Observational study of CS patients admitted to a Stroke Center (2010-2013). The sample was classified into three groups based on pre-stroke oral anticoagulants (OAC) treatment (all acenocumarol) and the international normalized ratio (INR) on admission: (1) non-anticoagulated or anticoagulated patients with INR <1.5, (2) anticoagulated with INR 1.5-1.9 and (3) anticoagulated with INR ≥2. We compared demographic data, vascular risk factors, symptomatic intracranial hemorrhage, severity on admission (NIHSS) and 3 month outcomes (mRS). Overall 475 patients were included, 47.2 % male, mean age 75.5 (SD 10.7) years old, 31.8 % were on OAC. 76 % belonged to the INR <1.5 group, 13.3 % to the INR 1.5-1.9 and 10.5 % to the INR >2. 35 %of patients received IVT. Multivariate analyses showed that an INR ≥2 on admission was a factor associated with a higher probability of mild stroke (NIHSS <10) (OR 2.026, 95 % CI 1.006-4.082). Previous OAC in general (OR 2.109, 95 % CI 1.173-3.789) as well as INR 1.5-1.9 (OR 3.676, 95 % CI 1.510-8.946) were associated with favorable outcomes (mRS ≤2). OAC was not related to stroke outcomes in the subgroup of IVT patients. Therapeutic OAC levels are associated with lesser CS severity, and prior OAC treatment with favorable outcomes. In this study, OAC are not related with response to IVT. PMID:26860861

  19. Prevention of experimental stroke by hypercapnic-hypoxic preconditioning.

    PubMed

    Yakushev, N N; Bespalov, A G; Kulikov, V P

    2008-09-01

    The effectiveness of hypercapnic hypoxic training in the prevention of acute disturbances in cerebral circulation was studied under experimental conditions. Hypercapnic hypoxic training was followed by a significant decrease in the severity of neurological deficit and locomotor and coordination disorders after cerebral ischemic injury. PMID:19240841

  20. Sex differences and the role of PPAR alpha in experimental stroke.

    PubMed

    Dotson, Abby L; Wang, Jianming; Chen, Yingxin; Manning, Dustin; Nguyen, Ha; Saugstad, Julie A; Offner, Halina

    2016-06-01

    Males and females respond differently to stroke. Moreover, females often experience worse long-term stroke outcomes. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist has been shown to improve stroke outcome and resolve neuroinflammation in male mice. The present study compares the effect of pretreatment with fenofibrate versus vehicle control in male and female mice during experimental stroke. Mice were treated with low-dose fenofibrate 30 min before and once a day for three additional days after stroke onset. We observed a reduction in infarct volume in male mice 96 h post-stroke with low-dose fenofibrate pretreatment that was due to increase of an M2 macrophage phenotype in the brain and an increase in regulatory cells in the periphery. These outcomes were not replicated in females, likely due to the lower PPARα expression in cells and tissues in females vs males. We conclude that PPARα agonist treatment prior to stroke is neuroprotective in males but not females. These findings indicate PPARα as a probable mechanism of sex difference in stroke outcome and support the need for representation of females in stroke therapy research. PMID:26581674

  1. Characteristics of Dysphagia in Severe Traumatic Brain Injury Patients: A Comparison With Stroke Patients

    PubMed Central

    Lee, Won Kyung; Yeom, Jiwoon; Lee, Woo Hyung; Seo, Han Gil; Oh, Byung-Mo

    2016-01-01

    Objective To compare the swallowing characteristics of dysphagic patients with traumatic brain injury (TBI) with those of dysphagic stroke patients. Methods Forty-one patients with TBI were selected from medical records (between December 2004 to March 2013) and matched to patients with stroke (n=41) based on age, sex, and disease duration. Patients' swallowing characteristics were analyzed retrospectively using a videofluoroscopic swallowing study (VFSS) and compared between both groups. Following thorough review of medical records, patients who had a history of diseases that could affect swallowing function at the time of the study were excluded. Dysphagia characteristics and severity were evaluated using the American Speech-Language-Hearing Association National Outcome Measurement System swallowing scale, clinical dysphagia scale, and the videofluoroscopic dysphagia scale. Results There was a significant difference in radiological lesion location (p=0.024) between the two groups. The most common VFSS finding was aspiration or penetration, followed by decreased laryngeal elevation and reduced epiglottis inversion. Swallowing function, VFSS findings, or quantified dysphagia severity showed no significant differences between the groups. In a subgroup analysis of TBI patients, the incidence of tube feeding was higher in patients with surgical intervention than in those without (p=0.011). Conclusion The swallowing characteristics of dysphagic patients after TBI were comparable to those of dysphagic stroke patients. Common VFSS findings comprised aspiration or penetration, decreased laryngeal elevation, and reduced epiglottis inversion. Patients who underwent surgical intervention after TBI were at high risk of tube feeding requirement. PMID:27446779

  2. Warfarin and low-dose aspirin for stroke prevention from severe intracranial stenosis.

    PubMed

    Bekavac, I; Hanna, J P; Sila, C A; Furland, A J

    1999-01-01

    Management of symptomatic, intracranial, large-arterial atherosclerosis is controversial. We assessed the safety and efficacy of combining warfarin and low-dose aspirin to prevent stroke from intracranial atherosclerotic stenosis failing prior treatment with either aspirin or warfarin. Patients with severe intracranial stenosis were prescribed combination therapy, warfarin (international normalized ratio [INR] 2 to 3) and aspirin 81 mg daily. Ten men and six women treated with combination therapy had one recurrent ischemic event during 382 months of therapy. No patient suffered a myocardial infarction or sudden vascular death. No serious hemorrhagic complication occurred. The combination of warfarin and low-dose aspirin seems safe and effective in preventing recurrent stroke from symptomatic, intracranial, large-arterial occlusive disease after failure with either aspirin or warfarin monotherapy. PMID:17895135

  3. Severity of Spatial Neglect During Acute Inpatient Rehabilitation Predicts Community Mobility After Stroke

    PubMed Central

    Oh-Park, Mooyeon; Hung, Cynthia; Chen, Peii; Barrett, A.M.

    2014-01-01

    Objective To examine whether stroke survivors with more severe spatial neglect during their acute inpatient rehabilitation had poorer mobility after returning to their communities. Design A prospective observational study. Setting Acute inpatient rehabilitation and follow-up in the community. Participants Thirty-one consecutive stroke survivors with right-brain damage (women, n = 15 [48.4%]), with the mean (standard deviation) age of 60 ± 11.5 years, were included in the study if they demonstrated spatial neglect within 2 months after stroke. Methods Spatial neglect was assessed with the Behavioral Inattention Test (BIT) (range, 0-146 [a lower score indicates more severity]) and the Catherine Bergego Scale (range, 0-30 [a higher score indicates more severity]). A score of the Behavioral Inattention Test <129 or of the Catherine Bergego Scale >0 defined the presence of spatial neglect. Main Outcome Measurements The outcome measure is community mobility, defined by the extent and frequency of traveling within the home and in the community, and is assessed with the University of Alabama at Birmingham Study of Aging Life-Space Assessment (range, 0-120 [a lower score indicates less mobile]). This measure was assessed after participants returned home ≥6 months after stroke. The covariates were age, gender, functional independence at baseline; follow-up interval; and depressed mood, which may affect the relationship between spatial neglect and community mobility. Results A lower Behavioral Inattention Test score was a significant predictor of a lower Life-Space Assessment score after controlling for all the covariates (β = 0.009 [95% confidence interval, 0.008-0.017]); P = .020). The proportion of participants unable to travel independently beyond their homes was 0%, 27.3%, and 72.7% for those with mild, moderate, and severe acute neglect, respectively (Catherine Bergego Scale range, 1-10, 11-20, and 21-30, respectively). Conclusions Our result indicates that acute

  4. Decoding of motor intentions from epidural ECoG recordings in severely paralyzed chronic stroke patients

    NASA Astrophysics Data System (ADS)

    Spüler, M.; Walter, A.; Ramos-Murguialday, A.; Naros, G.; Birbaumer, N.; Gharabaghi, A.; Rosenstiel, W.; Bogdan, M.

    2014-12-01

    Objective. Recently, there have been several approaches to utilize a brain-computer interface (BCI) for rehabilitation with stroke patients or as an assistive device for the paralyzed. In this study we investigated whether up to seven different hand movement intentions can be decoded from epidural electrocorticography (ECoG) in chronic stroke patients. Approach. In a screening session we recorded epidural ECoG data over the ipsilesional motor cortex from four chronic stroke patients who had no residual hand movement. Data was analyzed offline using a support vector machine (SVM) to decode different movement intentions. Main results. We showed that up to seven hand movement intentions can be decoded with an average accuracy of 61% (chance level 15.6%). When reducing the number of classes, average accuracies up to 88% can be achieved for decoding three different movement intentions. Significance. The findings suggest that ipsilesional epidural ECoG can be used as a viable control signal for BCI-driven neuroprosthesis. Although patients showed no sign of residual hand movement, brain activity at the ipsilesional motor cortex still shows enough intention-related activity to decode different movement intentions with sufficient accuracy.

  5. Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients

    PubMed Central

    Zhang, Xiaoyu; Ding, Lingling; Yang, Lei; Qin, Wei; Yuan, Junliang; Li, Shujuan; Hu, Wenli

    2016-01-01

    Background Enlarged perivascular spaces (EPVS) correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS) are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke. Methods We prospectively identified patients with lacunar stroke (diameter on DWI ≤ 20mm) from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (± 1 year) and sex matched controls were also recruited in the same population (two controls for one case). Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4), white matter hyperintensities (WMH) (by Fazekas scale), brain atrophy (rated 0 to 6) were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS. Results During study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH) and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73) and deep WMH (OR = 1.88; 95%CI 1.24, 2.83) were independent risk factors for severe BG-EPVS. Conclusions Brain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia. PMID:26900696

  6. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke.

    PubMed

    Lorente, Leonardo; Martín, María M; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541-18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  7. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

    PubMed Central

    Lorente, Leonardo; Martín, María M.; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541–18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  8. Outcomes following sonothrombolysis in severe acute ischemic stroke:subgroup analysis of the CLOTBUST trial

    PubMed Central

    Barlinn, Kristian; Tsivgoulis, Georgios; Barreto, Andrew D; Alleman, John; Molina, Carlos A; Mikulik, Robert; Saqqur, Maher; Demchuk, Andrew M; Schellinger, Peter D; Howard, George; Alexandrov, Andrei V.

    2014-01-01

    Background Sonothrombolysis is safe and may increase the likelihood of early recanalization in acute ischemic stroke (AIS) patients Aims In preparation of a phase III clinical trial, we contrast the likelihood of achieving a sustained recanalization and functional independence in a post-hoc subgroup analysis of patients randomized to transcranial Doppler monitoring plus intravenous (IV) tPA (sonothrombolysis) compared to IV tPA alone in the CLOTBUST trial Methods We analyzed the data from all randomized AIS patients with pre-treatment NIHSS scores ≥10 points and proximal intracranial occlusions in the CLOTBUST trial. We compared sustained complete recanalization rate (TIBI flow grades 4-5) and functional independence (modified Rankin Scale [mRS] 0-1) at 90 days. Safety was evaluated by the rate of symptomatic intracranial hemorrhage (ICH) within 72 hours of stroke-onset Results Of 126 patients, a total of 85 AIS patients met our inclusion criteria: mean age 71±11years, 56% men, median NIHSS 17 (interquartile range 14-20). Of these patients, 41 (48%) and 44 (52%) were randomized to IV tPA alone and sonothrombolysis, respectively. More patients achieved sustained complete recanalization in the sonothrombolysis than in the IV tPA alone group (38.6% vs. 17.1%; p=0.032). Functional independence at 90 days was more frequently achieved in the sonothrombolysis than in the IV tPA alone group (37.2% vs. 15.8%; p=0.045). Symptomatic ICH rate was similar in both groups (4.9% vs. 4.6%; p=1.00) Conclusions Our results point to a signal of efficacy and provide information to guide the subsequent phase III randomized trial of sonothrombolysis in patients with severe ischemic strokes PMID:25079049

  9. Effectiveness of Acute Phase Hybrid Assistive Limb Rehabilitation in Stroke Patients Classified by Paralysis Severity

    PubMed Central

    FUKUDA, Hiroyuki; SAMURA, Kazuhiro; HAMADA, Omi; SAITA, Kazuya; OGATA, Toshiyasu; SHIOTA, Etsuji; SANKAI, Yoshiyuki; INOUE, Tooru

    The purpose of the present study was to investigate the effectiveness of acute phase hybrid assistive limb (HAL) rehabilitation training for patients after stroke by measuring the difference in the severity of paralysis. Fifty-three acute stroke patients were enrolled in this prospective cohort study. HAL training was administered about twice per week, and the mean number of sessions was 3.9 ± 2.7. The walking training was performed on a treadmill with individually adjustable body weight support and speed and there was a 10-m walk test (10MWT) before and after each session. Assessment at baseline and at endpoint consisted of the Glasgow Coma Scale (GCS), Revised Hasegawa’s Dementia Scale (HDS-R), Brunnstrom stage (Brs), Functional Independence Measure (FIM), Barthel index (BI), and 10MWT. We measured these assessments at the first walking training session and at the end of the final training session without the HAL. To evaluate the feasibility of training with the HAL, the outcome measures of BI, FIM, and speed and number of steps of 10MWT were compared before and after training using a paired Wilcoxon’s signed-rank test in different Brs. Except for Brs IV, the Brs III or higher subgroups displayed significant amelioration in BI, and the Brs III subgroup displayed significant amelioration in FIM. The Brs V and VI subgroups displayed significant amelioration in 10-m walking speed and steps. In acute phase rehabilitation after stroke, it is thought that the HAL is more effective for patients with less lower-limb paralysis, such as Brs III or higher. PMID:26041627

  10. Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

    PubMed Central

    Srinivasan, Vivek J.; Mandeville, Emiri T.; Can, Anil; Blasi, Francesco; Climov, Mihail; Daneshmand, Ali; Lee, Jeong Hyun; Yu, Esther; Radhakrishnan, Harsha; Lo, Eng H.; Sakadžić, Sava; Eikermann-Haerter, Katharina; Ayata, Cenk

    2013-01-01

    Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties. PMID:23940761

  11. Adapted Low Intensity Ergometer Aerobic Training for Early and Severely Impaired Stroke Survivors: A Pilot Randomized Controlled Trial to Explore Its Feasibility and Efficacy

    PubMed Central

    Wang, Zun; Wang, Lei; Fan, Hongjuan; Jiang, Wenjun; Wang, Sheng; Gu, Zhaohua; Wang, Tong

    2014-01-01

    [Purpose] To evaluate the feasibility and efficacy of adapted low intensity ergometer aerobic training for early and severely impaired stroke survivors. [Subjects] The subjects were forty-eight early stroke survivors. [Methods] Eligible subjects were recruited and randomly assigned to an experimental group and a control group. Both groups participated in comprehensive rehabilitation training. Low intensity aerobic training was only performed by the experimental group. Outcome measures were the Fugl-Meyer motor score, Barthel index, exercise test time, peak heart rate, plasma glucose level and serum lipid profiles. [Results] Patients in the experimental group finished 88.6% of the total aerobic training sessions prescribed. In compliant participants (adherence≥80%), aerobic training significantly improved the Barthel index (from 40.1±21.1 to 79.2±14.2), Fugl-Meyer motor score (from 26.4±19.4 to 45.4±12.7), exercise test time (from 12.2±3.62 min to 13.9±3.6 min), 2-hour glucose level (from 9.22±1.16 mmol/L to 7.21±1.36 mmol/L) and homeostasis model of assessment for insulin resistence index (from 1.72±1.01 to 1.28±0.88). [Conclusion] Preliminary findings suggest that early and severely impaired stroke patients may benefit from low intensity ergometer aerobic training. PMID:25276034

  12. Protection against Experimental Stroke by Ganglioside GM1 Is Associated with the Inhibition of Autophagy

    PubMed Central

    Li, Li; Tian, Jinghua; Long, Mitchell King-Wei; Chen, Yong; Lu, Jianfei; Zhou, Changman; Wang, Tianlong

    2016-01-01

    Ganglioside GM1, which is particularly abundant in the central nervous system (CNS), is closely associated with the protection against several CNS disorders. However, controversial findings have been reported on the role of GM1 following ischemic stroke. In the present study, using a rat middle cerebral artery occlusion (MCAO) model, we investigated whether GM1 can protect against ischemic brain injury and whether it targets the autophagy pathway. GM1 was delivered to Sprague-Dawley male rats at 3 doses (25 mg/kg, 50 mg/kg, 100 mg/kg) by intraperitoneal injection soon after reperfusion and then once daily for 2 days. The same volume of saline was given as a control. Tat–Beclin-1, a specific autophagy inducer, was administered by intraperitoneal injection at 24 and 48 hours post-MCAO. Infarction volume, mortality and neurological function were assessed at 72 hours after ischemic insult. Immunofluorescence and Western blotting were performed to determine the expression of autophagy-related proteins P62, LC3 and Beclin-1 in the penumbra area. No significant changes in mortality and physiological variables (heart rate, blood glucose levels and arterial blood gases) were observed between the different groups. However, MCAO resulted in enhanced conversion of LC3-I into LC3-II, P62 degradation, high levels of Beclin-1, a large area infarction (26.3±3.6%) and serious neurobehavioral deficits. GM1 (50 mg/kg) treatment significantly reduced the autophagy activation, neurobehavioral dysfunctions, and infarction volume (from 26.3% to 19.5%) without causing significant adverse side effects. However, this biological function could be abolished by Tat–Beclin-1. In conclusion: GM1 demonstrated safe and robust neuroprotective effects that are associated with the inhibition of autophagy following experimental stroke. PMID:26751695

  13. Monocarboxylate Transporter 2 and Stroke Severity in a Rodent Model of Sleep Apnea

    PubMed Central

    Wang, Yang; Guo, Shang-Z; Bonen, Arend; Li, Richard C.; Kheirandish-Gozal, Leila; Zhang, Shelley X.L.; Brittian, Kenneth R.; Gozal, David

    2011-01-01

    Stroke is not only more prevalent but is also associated with more severe adverse functional outcomes among patients with sleep apnea. Monocarboxylate transporters (MCT) are important regulators of cellular bioenergetics, have been implicated in brain susceptibility to acute severe hypoxia (ASH), and could underlie the unfavorable prognosis of cerebrovascular accidents in sleep apnea patients. Rodents were exposed to either intermittent hypoxia (IH) during sleep, a characteristic feature of sleep apnea, or to sustained hypoxia (SH), and expression of MCT1 and MCT2 was assessed. In addition, the functional recovery to MCAO in rats and hMCT2 transgenic mice and of hippocampal slices subjected to ASH was assessed, as well as the effects of MCT blocker and MCT2 antisense oligonucleotides and siRNAs. IH, but not SH, induced significant reductions in MCT2 expression over time at both the mRNA and protein levels, and in the functional recovery of hippocampal slices subjected to ASH. Similarly, MCAO-induced infarcts were significantly greater in IH-exposed rats and mice, and over-expression of hMCT2 in mice markedly attenuated the adverse effects of IH. Exogenous pyruvate treatment reduced infarct volumes in normoxic rats but not in IH-exposed rats. Administration of he MCT2 blocker 4CN, but not the MCT1 antagonist pCMBS, increased infarct size. Thus, prolonged exposures to IH mimicking sleep apnea are associated with increased CNS vulnerability to ischemia that is mediated, at least in part, by concomitant decreases in the expression and function of MCT2. Efforts to develop agonists of MCT2 should provide opportunities to ameliorate the overall outcome of stroke. PMID:21753001

  14. Blocking Sympathetic Nervous System Reverses Partially Stroke-Induced Immunosuppression but does not Aggravate Functional Outcome After Experimental Stroke in Rats.

    PubMed

    Deng, Qi-Wen; Yang, Heng; Yan, Fu-Ling; Wang, Huan; Xing, Fang-Lan; Zuo, Lei; Zhang, Han-Qing

    2016-08-01

    Stoke results in activation of the sympathetic nervous system (SNS), inducing systemic immunosuppression. However, the potential mechanisms underlying stroke-induced immunosuppression remain unclear. Here, we determined the SNS effects on functional outcome and explored the interactions among SNS, β-arrestin2 and nuclear factor-κB (NF-κB) after experimental stroke in rats. In the current study, stroke was induced by a transient middle cerebral artery occlusion (MCAO) in rats, and SNS activity was inhibited by intraperitoneal injection of 6-hydroxydopamine HBr (6-OHDA). 7.0 T Micro-MRI and Longa score were employed to assess the functional outcome after stroke. Flow cytometry and ELISA assay were used to measure the expression of MHC class II, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Western blot was conducted to analyze β-arrestin2 and NF-κB protein expression levels after experimental stroke. We found significantly increased infarct volumes and functional impairment after MCAO at different post-surgery time points, which were not aggravated by 6-OHDA treatment. SNS blockade partially reversed the expression of MHC class II after stroke over time, as well as TNF-α and IFN-γ levels in lipopolysaccharide-stimulated macrophages in vitro. Treatment of MCAO rats with SNS-inhibitor significantly diminished NF-κB activation and enhanced β-arrestin2 expression after stroke. This study suggests that pharmacological SNS inhibition dose not aggravate functional outcome after stroke. Stroke-induced immunosuppression may be involved in the SNS-β-arrestin2-NF-κB pathway. PMID:27059792

  15. Stroke

    MedlinePlus

    ... a clot within a blood vessel of the brain or neck, called thrombosis the movement of a clot from ... body, such as from the heart to the neck or brain, called an embolism a severe narrowing of an ...

  16. Altered hypothalamic inflammatory gene expression correlates with heat stroke severity in a conscious rodent model.

    PubMed

    Audet, Gerald N; Dineen, Shauna M; Quinn, Carrie M; Leon, Lisa R

    2016-04-15

    It has been suggested that heat-induced hypothalamic damage mediates core temperature (Tc) disturbances during heat stroke (HS) recovery; this is significant as hypothermia and/or fever have been linked to severity and overall pathological insult. However, to date there has been a lack of histological evidence in support of these claims. We hypothesized that local hypothalamic cytokines and/or chemokines, known regulators of Tc, are mediating the elevation in Tc during HS recovery even in the absence of histological damage. In experiment 1, the hypothalamus of Fischer 344 rats was examined for 84 cytokine/chemokine genes (real-time PCR) at multiple time points (Tc,Max, 1, 3, and 10 days) during mild HS recovery. In experiment 2, the hypothalamus of three different HS severities (MILD, moderate [MOD], and severe [SEV]) in rats were examined for the same genes as experiment 1 as well as six oxidative damage markers, at a single intermediate time point (1 day). Systemic cytokines were also analyzed in experiment 2 across the three severities. There were significant alterations in 25 cytokines/chemokines expression at Tc,Max, but little or no changes in expression at longer time points in experiment 1. In experiment 2 there were significant changes in gene expression in SEV rats only, with MILD and MOD rats showing baseline expression at 1 day, despite an absence of systemic cytokine expression in any severity. There was also no change in any oxidative marker of damage at 1 day, regardless of severity. In conclusion, we show only limited changes during long term recovery from HS, but demonstrate differences in hypothalamic gene expression patterns that may be driving HS pathology and morbidity. These findings contribute to our overall understanding of HS pathology in the CNS, as well as providing avenues for future pharmacological intervention. PMID:26876741

  17. Improved Therapeutic Benefits by Combining Physical Cooling With Pharmacological Hypothermia After Severe Stroke in Rats

    PubMed Central

    Lee, Jin Hwan; Wei, Ling; Gu, Xiaohuan; Won, Soonmi; Wei, Zheng Zachory; Dix, Thomas A.

    2016-01-01

    Background and Purpose— Therapeutic hypothermia is a promising strategy for treatment of acute stroke. Clinical translation of therapeutic hypothermia, however, has been hindered because of the lack of efficiency and adverse effects. We sought to enhance the clinical potential of therapeutic hypothermia by combining physical cooling (PC) with pharmacologically induced hypothermia after ischemic stroke. Methods— Wistar rats were subjected to 90-minute middle cerebral artery occlusion by insertion of an intraluminal filament. Mild-to-moderate hypothermia was induced 120 minutes after the onset of stroke by PC alone, a neurotensin receptor 1 (NTR1) agonist HPI-201 (formally ABS-201) alone or the combination of both. The outcomes of stroke were evaluated at 3 and 21 days after stroke. Results— PC or HPI-201 each showed hypothermic effect and neuroprotection in stroke rats. The combination of PC and HPI-201 exhibited synergistic effects in cooling process, reduced infarct formation, cell death, and blood-brain barrier damages and improved functional recovery after stroke. Importantly, coapplied HPI-201 completely inhibited PC-associated shivering and tachycardia. Conclusions— The centrally acting hypothermic drug HPI-201 greatly enhanced the efficiency and efficacy of conventional PC; this combined cooling therapy may facilitate clinical translation of hypothermic treatment for stroke. PMID:27301934

  18. [Withdrawal of artificial nutrition and hydration in severe stroke: medical, legal and ethical considerations].

    PubMed

    Tannier, C; Crozier, S; Zuber, M; Constantinides, Y; Delezie, E; Gisquet, E; Grignoli, N; Lamy, C; Louvet, F; Pinel, J-F

    2015-02-01

    In the majority of cases, severe stroke is accompanied by difficulty in swallowing and an altered state of consciousness requiring artificial nutrition and hydration. Because of their artificial nature, nutrition and hydration are considered by law as treatment rather basic care. Withdrawal of these treatments is dictated by the refusal of unreasonable obstinacy enshrined in law and is justified by the risk of severe disability and very poor quality of life. It is usually the last among other withholding and withdrawal decisions which have already been made during the long course of the disease. Reaching a collegial consensus on a controversial decision such as artificial nutrition and hydration withdrawal is a difficult and complex process. The reluctance for such decisions is mainly due to the symbolic value of food and hydration, to the fear of "dying badly" while suffering from hunger and thirst, and to the difficult distinction between this medical act and euthanasia. The only way to overcome such reluctance is to ensure flawless accompaniment, associating sedation and appropriate comfort care with a clear explanation (with relatives but also caregivers) of the rationale and implications of this type of decision. All teams dealing with this type of situation must have thoroughly thought through the medical, legal and ethical considerations involved in making this difficult decision. PMID:25575609

  19. Machine-based, self-guided home therapy for individuals with severe arm impairment after stroke: a randomized controlled trial

    PubMed Central

    Zondervan, DK; Augsburger, R; Bodenhoefer, B; Friedman, N; Reinkensmeyer, DJ; Cramer, SC

    2015-01-01

    Background Few therapeutic options exist for the millions of persons living with severe arm impairment after stroke to increase their dose of arm rehabilitation. This study compared self-guided, high-repetition home therapy with a mechanical device (the Resonating Arm Exerciser - RAE) to conventional therapy in patients with chronic stroke, and explored RAE use for patients with subacute stroke. Methods Sixteen participants with severe upper extremity impairment (mean Fugl-Meyer (FM) score = 21.4 ± 8.8 out of 66) > 6 months post stroke were randomized to three-weeks of exercise with RAE or conventional exercises. Primary outcome measure was FM score one month post-therapy. Secondary outcome measures included MAL, Visual Analog Pain scale, and Ashworth spasticity scale. After a one-month break, individuals in the conventional group also received a three-week course of RAE therapy. Results The change in FM score was significant in both the RAE and conventional groups after training (2.6 ± 1.4 and 3.4 ± 2.4, p = 0.008 and 0.016, respectively). These improvements were not significant at one-month. Exercise with RAE led to significantly greater improvements in distal FM score than conventional therapy at the one-month follow-up (p = 0.02). In a separate cohort of patients with subacute stroke, RAE was found feasible for exercise. Discussion In subjects with severe arm impairment after chronic stroke, home-based training with RAE was feasible and significantly reduced impairment without increasing pain or spasticity. Gains with RAE were comparable to those found with conventional training, and also included distal arm improvement. PMID:25273359

  20. Role of contralesional hemisphere in paretic arm reaching in patients with severe arm paresis due to stroke: A preliminary report.

    PubMed

    Mohapatra, Sambit; Harrington, Rachael; Chan, Evan; Dromerick, Alexander W; Breceda, Erika Y; Harris-Love, Michelle

    2016-03-23

    Stroke is highly prevalent and a leading cause of serious, long-term disability among American adults. Impaired movement (i.e. paresis) of the stroke-affected arm is a major contributor to post-stroke disability, yet the mechanisms of upper extremity motor recovery are poorly understood, particularly in severely impaired patients who lack hand function. To address this problem, we examined the functional relevance of the contralesional hemisphere in paretic arm motor performance in individuals with severe arm paresis. Twelve individuals with severe stroke-induced arm paresis (Upper Extremity Fugl-Meyer Assessment=17.1 ± 8.5; maximum score=66) participated in the study. Participants performed a reaching response time task with their paretic arm. At varying time intervals following a 'Go' cue, a pair of transcranial magnetic stimulation (TMS) pulses were delivered to contralesional hemisphere primary motor (M1) or dorsal pre-motor cortex (PMd) to momentarily disrupt the pattern of neural firing. Response time components and hand-path characteristics were compared across the 2 sites for trials with and without TMS disruption. There was no significant effect of TMS disruption on overall Response time or Reaction time, but Movement time was significantly longer (i.e. slower) with disruption of the contralesional hemisphere (p=0.015), regardless of which area was stimulated. Peak hand-path velocity and hand-path smoothness were also significantly lower (p=0.005 and p<0.0001, respectively) with TMS disruption of the contralesional hemisphere. The data from this study provide evidence supporting a functionally relevant role of contralesional hemisphere motor areas in paretic arm reaching movements in individuals with severe post-stroke arm impairment. PMID:26872851

  1. Clearance of serum solutes by hemofiltration in dogs with severe heat stroke

    PubMed Central

    2014-01-01

    Background We have previously reported that hemofiltration (HF) may be an effective additional means of treating heat stroke when rapid cooling is not effective. Methods Dogs were assigned to a heat stroke (control) or heat stroke + hemofiltration (HF) group (n = 8 each group). After heat stroke induction, dogs in the HF group received HF for 3 h. Serum concentrations of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-6, blood urea nitrogen (BUN) and creatinine were measured at baseline and 1, 2, and 3 h after heat stroke. Clearance rates of solutes were determined 1, 2, and 3 h after the start of HF. Results Serum concentrations of all solutes tended to increase with time after heat stroke in the control group, but decreased (BUN, creatinine) or remained relatively unchanged (TNF-α, IL-6, IL-10) with time in the HF group. Concentrations of all solutes were significantly lower in the HF group compared with the control group at 2 and 3 h (P < 0.05). Clearance rates for small molecular weight solutes were high, while those for larger molecular weight solutes were low. Conclusion HF prevents heat stroke-induced increases in serum cytokine concentrations and is effective for clearing small molecular weight solutes from serum, but less effective for clearing larger molecular weight solutes, including TNF-α, IL-6, and IL-10. PMID:25145441

  2. Optogenetic Stimulation of Neural Grafts Enhances Neurotransmission and Downregulates the Inflammatory Response in Experimental Stroke Model.

    PubMed

    Daadi, Marcel M; Klausner, Jill Q; Bajar, Bryce; Goshen, Inbal; Lee-Messer, Christopher; Lee, Soo Yeun; Winge, Mårten C G; Ramakrishnan, Charu; Lo, Maisie; Sun, Guohua; Deisseroth, Karl; Steinberg, Gary K

    2016-01-01

    Compelling evidence suggests that transplantation of neural stem cells (NSCs) from multiple sources ameliorates motor deficits after stroke. However, it is currently unknown to what extent the electrophysiological activity of grafted NSC progeny participates in the improvement of motor deficits and whether excitatory phenotypes of the grafted cells are beneficial or deleterious to sensorimotor performances. To address this question, we used optogenetic tools to drive the excitatory outputs of the grafted NSCs and assess the impact on local circuitry and sensorimotor performance. We genetically engineered NSCs to express the Channelrhodopsin-2 (ChR2), a light-gated cation channel that evokes neuronal depolarization and initiation of action potentials with precise temporal control to light stimulation. To test the function of these cells in a stroke model, rats were subjected to an ischemic stroke and grafted with ChR2-NSCs. The grafted NSCs identified with a human-specific nuclear marker survived in the peri-infarct tissue and coexpressed the ChR2 transgene with the neuronal markers TuJ1 and NeuN. Gene expression analysis in stimulated versus vehicle-treated animals showed a differential upregulation of transcripts involved in neurotransmission, neuronal differentiation, regeneration, axonal guidance, and synaptic plasticity. Interestingly, genes involved in the inflammatory response were significantly downregulated. Behavioral analysis demonstrated that chronic optogenetic stimulation of the ChR2-NSCs enhanced forelimb use on the stroke-affected side and motor activity in an open field test. Together these data suggest that excitatory stimulation of grafted NSCs elicits beneficial effects in experimental stroke model through cell replacement and non-cell replacement, anti-inflammatory/neurotrophic effects. PMID:26132738

  3. Predictive factors of brain death in severe stroke patients identified by organ procurement and transplant coordination in Lorrain, France.

    PubMed

    Humbertjean, Lisa; Mione, Gioia; Fay, Renaud; Durin, Laurent; Planel, Sophie; Lacour, Jean-Christophe; Enea, Ana-Maria; Richard, Sébastien

    2016-03-01

    There are no established predictive factors to identify patients at the acute phase of severe stroke with a high probability of presenting brain death (BD). We retrospectively collected clinical and paraclinical data of consecutive patients at the acute phase of severe stroke with a potential progression to BD through the hospital organ procurement and transplant coordination system in five centres in Lorrain (France) between 1 January 2012 and 31 December 2013. Final endpoint was adjudicated BD. Of 400 included patients, 91 (23%) presented adjudicated BD. Initial Glasgow Coma Scale score ≤6 (P = 0.008), herniation (P = 0.009), hydrocephalus (P = 0.019), initial systolic blood pressure >150 mmHg (P = 0.002), past history of alcohol abuse (P = 0.019) and stroke volume >65 ml (P = 0.040) were significantly associated with BD progression. Two prognostic scores for stroke with unquantifiable or quantifiable volume were built according to the number of risk factors presented. Following internal validation, the respective bias-corrected predictive performance (c-index) of the two scores was 72% (95% confidence interval: 67-78%) and 77% (95% confidence interval: 72-82%). These scores could form the basis of a simple tool of six criteria to help physicians make the difficult decision of intensive care unit management to preserve organs in potential donors. PMID:26402792

  4. A novel snake venom-derived GPIb antagonist, anfibatide, protects mice from acute experimental ischaemic stroke and reperfusion injury

    PubMed Central

    Li, Ting-Ting; Fan, Man-Li; Hou, Shi-Xiang; Li, Xiao-Yi; Barry, Devin M; Jin, Hui; Luo, Sheng-Yong; Kong, Feng; Lau, Lit-Fui; Dai, Xiang-Rong; Zhang, Guo-Hui; Zhou, Lan-Lan

    2015-01-01

    Background and Purpose Ischaemic stroke is a serious disease with limited therapy options. Glycoprotein (GP)Ib binding to von Willebrand factor (vWF) exposed at vascular injury initiates platelet adhesion and contributes to platelet aggregation. GPIb has been suggested as an effective target for antithrombotic therapy in stroke. Anfibatide is a GPIb antagonist derived from snake venom and we investigated its protective effect on experimental brain ischaemia in mice. Experimental Approach Focal cerebral ischaemia was induced by 90 min of transient middle cerebral artery occlusion (MCAO). These mice were then treated with anfibatide (4, 2, 1 μg·kg−1), injected i.v., after 90 min of MCAO, followed by 1 h of reperfusion. Tirofiban, a GPIIb/IIIα antagonist, was used as a positive control. Key Results Twenty-four hours after MCAO, anfibatide-treated mice showed significantly improved ischaemic lesions in a dose-dependent manner. The mice had smaller infarct volumes, less severe neurological deficits and histopathology of cerebrum tissues compared with the untreated MCAO mice. Moreover, anfibatide decreased the amount of GPIbα, vWF and accumulation of fibrin(ogen) in the vasculature of the ischaemic hemisphere. Tirofiban had similar effects on infarct size and fibrin(ogen) deposition compared with the MCAO group. Importantly, the anfibatide-treated mice showed a lower incidence of intracerebral haemorrhage and shorter tail bleeding time compared with the tirofiban-treated mice. Conclusions and Implications Our data indicate anfibatide is a safe GPIb antagonist that exerts a protective effect on cerebral ischaemia and reperfusion injury. Anfibatide is a promising candidate that could be beneficial for the treatment of ischaemic stroke. PMID:25917571

  5. Combining Robotic Training and Non-Invasive Brain Stimulation in Severe Upper Limb-Impaired Chronic Stroke Patients.

    PubMed

    Di Lazzaro, Vincenzo; Capone, Fioravante; Di Pino, Giovanni; Pellegrino, Giovanni; Florio, Lucia; Zollo, Loredana; Simonetti, Davide; Ranieri, Federico; Brunelli, Nicoletta; Corbetto, Marzia; Miccinilli, Sandra; Bravi, Marco; Milighetti, Stefano; Guglielmelli, Eugenio; Sterzi, Silvia

    2016-01-01

    Previous studies suggested that both robot-assisted rehabilitation and non-invasive brain stimulation can produce a slight improvement in severe chronic stroke patients. It is still unknown whether their combination can produce synergistic and more consistent improvements. Safety and efficacy of this combination has been assessed within a proof-of-principle, double-blinded, semi-randomized, sham-controlled trial. Inhibitory continuous Theta Burst Stimulation (cTBS) was delivered on the affected hemisphere, in order to improve the response to the following robot-assisted therapy via a homeostatic increase of learning capacity. Twenty severe upper limb-impaired chronic stroke patients were randomized to robot-assisted therapy associated with real or sham cTBS, delivered for 10 working days. Eight real and nine sham patients completed the study. Change in Fugl-Meyer was chosen as primary outcome, while changes in several quantitative indicators of motor performance extracted by the robot as secondary outcomes. The treatment was well-tolerated by the patients and there were no adverse events. All patients achieved a small, but significant, Fugl-Meyer improvement (about 5%). The difference between the real and the sham cTBS groups was not significant. Among several secondary end points, only the Success Rate (percentage of targets reached by the patient) improved more in the real than in the sham cTBS group. This study shows that a short intensive robot-assisted rehabilitation produces a slight improvement in severe upper-limb impaired, even years after the stroke. The association with homeostatic metaplasticity-promoting non-invasive brain stimulation does not augment the clinical gain in patients with severe stroke. PMID:27013950

  6. Combining Robotic Training and Non-Invasive Brain Stimulation in Severe Upper Limb-Impaired Chronic Stroke Patients

    PubMed Central

    Di Lazzaro, Vincenzo; Capone, Fioravante; Di Pino, Giovanni; Pellegrino, Giovanni; Florio, Lucia; Zollo, Loredana; Simonetti, Davide; Ranieri, Federico; Brunelli, Nicoletta; Corbetto, Marzia; Miccinilli, Sandra; Bravi, Marco; Milighetti, Stefano; Guglielmelli, Eugenio; Sterzi, Silvia

    2016-01-01

    Previous studies suggested that both robot-assisted rehabilitation and non-invasive brain stimulation can produce a slight improvement in severe chronic stroke patients. It is still unknown whether their combination can produce synergistic and more consistent improvements. Safety and efficacy of this combination has been assessed within a proof-of-principle, double-blinded, semi-randomized, sham-controlled trial. Inhibitory continuous Theta Burst Stimulation (cTBS) was delivered on the affected hemisphere, in order to improve the response to the following robot-assisted therapy via a homeostatic increase of learning capacity. Twenty severe upper limb-impaired chronic stroke patients were randomized to robot-assisted therapy associated with real or sham cTBS, delivered for 10 working days. Eight real and nine sham patients completed the study. Change in Fugl-Meyer was chosen as primary outcome, while changes in several quantitative indicators of motor performance extracted by the robot as secondary outcomes. The treatment was well-tolerated by the patients and there were no adverse events. All patients achieved a small, but significant, Fugl-Meyer improvement (about 5%). The difference between the real and the sham cTBS groups was not significant. Among several secondary end points, only the Success Rate (percentage of targets reached by the patient) improved more in the real than in the sham cTBS group. This study shows that a short intensive robot-assisted rehabilitation produces a slight improvement in severe upper-limb impaired, even years after the stroke. The association with homeostatic metaplasticity-promoting non-invasive brain stimulation does not augment the clinical gain in patients with severe stroke. PMID:27013950

  7. Multicenter Evaluation of Geometric Accuracy of MRI Protocols Used in Experimental Stroke.

    PubMed

    Milidonis, Xenios; Lennen, Ross J; Jansen, Maurits A; Mueller, Susanne; Boehm-Sturm, Philipp; Holmes, William M; Sena, Emily S; Macleod, Malcolm R; Marshall, Ian

    2016-01-01

    It has recently been suggested that multicenter preclinical stroke studies should be carried out to improve translation from bench to bedside, but the accuracy of magnetic resonance imaging (MRI) scanners routinely used in experimental stroke has not yet been evaluated. We aimed to assess and compare geometric accuracy of preclinical scanners and examine the longitudinal stability of one scanner using a simple quality assurance (QA) protocol. Six 7 Tesla animal scanners across six different preclinical imaging centers throughout Europe were used to scan a small structural phantom and estimate linear scaling errors in all orthogonal directions and volumetric errors. Between-scanner imaging consisted of a standard sequence and each center's preferred sequence for the assessment of infarct size in rat models of stroke. The standard sequence was also used to evaluate the drift in accuracy of the worst performing scanner over a period of six months following basic gradient calibration. Scaling and volumetric errors using the standard sequence were less variable than corresponding errors using different stroke sequences. The errors for one scanner, estimated using the standard sequence, were very high (above 4% scaling errors for each orthogonal direction, 18.73% volumetric error). Calibration of the gradient coils in this system reduced scaling errors to within ±1.0%; these remained stable during the subsequent 6-month assessment. In conclusion, despite decades of use in experimental studies, preclinical MRI still suffers from poor and variable geometric accuracy, influenced by the use of miscalibrated systems and various types of sequences for the same purpose. For effective pooling of data in multicenter studies, centers should adopt standardized procedures for system QA and in vivo imaging. PMID:27603704

  8. OBESITY INCREASES BLOOD PRESSURE, CEREBRAL VASCULAR REMODELING, AND SEVERITY OF STROKE IN THE ZUCKER RAT

    PubMed Central

    Osmond, Jessica M.; Mintz, James D.; Dalton, Brian; Stepp, David W.

    2009-01-01

    Obesity is a risk factor for stroke, but the mechanisms by which obesity increases stroke risk are unknown. Because microvascular architecture contributes to the outcome of stroke, we hypothesized that middle cerebral arteries (MCA) from obese Zucker rats (OZR) undergo inward remodeling and develop increased myogenic tone compared to lean Zucker rats (LZR). We further hypothesized that OZR have an increased infarct following cerebral ischemia and that changes in vascular structure and function correlate with the development of hypertension in OZR. Blood pressure was measured by telemetery in LZR and OZR from 6 to 17 weeks of age. Vessel structure and function were assessed in isolated MCAs. Stroke damage was assessed after ischemia was induced for 60 minutes followed by 24 hours of reperfusion. While mean arterial pressure (MAP) was similar between young rats (6–8 weeks old), MAP was higher in adult (14–17 weeks old) OZR than LZR. MCAs from OZR had a smaller lumen diameter and increased myogenic vasoconstriction compared to those from LZR. Following ischemia, infarction was 58% larger in OZR than LZR. Prior to the development of hypertension, MCA myogenic reactity and lumen diameter as well as infarct size were similar between young LZR and OZR. Our results indicate that the MCAs of OZR undergo structural remodeling and that these rats have greater cerebral injury following cerebral ischemia. These cerebrovascular changes correlate with the development of hypertension and suggest that the increased blood pressure may be the major determinant for stroke risk in obese individuals. PMID:19104000

  9. Different immunological mechanisms govern protection from experimental stroke in young and older mice with recombinant TCR ligand therapy

    PubMed Central

    Dotson, Abby L.; Zhu, Wenbin; Libal, Nicole; Alkayed, Nabil J.; Offner, Halina

    2014-01-01

    Stroke is a leading cause of death and disability in the United States. The lack of clinical success in stroke therapies can be attributed, in part, to inadequate basic research on aging rodents. The current study demonstrates that recombinant TCR ligand therapy uses different immunological mechanisms to protect young and older mice from experimental stroke. In young mice, RTL1000 therapy inhibited splenocyte efflux while reducing frequency of T cells and macrophages in the spleen. Older mice treated with RTL1000 exhibited a significant reduction in inflammatory cells in the brain and inhibition of splenic atrophy. Our data suggest age specific differences in immune response to stroke that allow unique targeting of stroke immunotherapies. PMID:25309326

  10. Effect of simvastatin on MMPs and TIMPs in human brain endothelial cells and experimental stroke.

    PubMed

    Reuter, Björn; Rodemer, Claus; Grudzenski, Saskia; Meairs, Stephen; Bugert, Peter; Hennerici, Michael G; Fatar, Marc

    2015-04-01

    Clinical studies demonstrated favorable effects of statins in stroke beyond lipid-lowering effects. In acute stroke, the disruption of the blood-brain barrier (BBB) is mediated by matrix metalloproteinases (MMPs). A modified MMP metabolism may account for the beneficial effects of statins. Cultured human brain microvascular endothelial cells (BMECs) were pretreated with simvastatin and subjected to oxygen glucose deprivation (OGD). Gene expression and protein secretion of MMP-2 and MMP-9 and the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were measured by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Simvastatin significantly dampened the expression but not secretion of MMP-2 under OGD. MMP-9 synthesis rate was low and unaffected by simvastatin treatment, while the gene expression and protein secretion of TIMP-1 and TIMP-2 were both strongly induced. Our results provide evidence for a positive effect of simvastatin on the MMP metabolism in human BMECs and experimental stroke mainly by means of the increased expression and secretion of TIMP-1 and TIMP-2. PMID:25476155

  11. Experimental Evaluation of a Method for Turbocharging Four-Stroke, Single Cylinder, Internal Combustion Engines

    NASA Astrophysics Data System (ADS)

    Buchman, Michael; Winter, Amos

    2015-11-01

    Turbocharging an engine increases specific power, improves fuel economy, reduces emissions, and lowers cost compared to a naturally aspirated engine of the same power output. These advantages make turbocharging commonplace for multi-cylinder engines. Single cylinder engineers are not commonly turbocharged due to the phase lag between the exhaust stroke, which powers the turbocharger, and the intake stroke, when air is pumped into the engine. Our proposed method of turbocharging single cylinder engines is to add an ``air capacitor'' to the intake manifold, an additional volume that acts as a buffer to store compressed air between the exhaust and intake strokes, and smooth out the pressure pulses from the turbocharger. This talk presents experimental results from a single cylinder, turbocharged diesel engine fit with various sized air capacitors. Power output from the engine was measured using a dynamometer made from a generator, with the electrical power dissipated with resistive heating elements. We found that intake air density increases with capacitor size as theoretically predicted, ranging from 40 to 60 percent depending on heat transfer. Our experiment was able to produce 29 percent more power compared to using natural aspiration. These results validated that an air capacitor and turbocharger may be a simple, cost effective means of increasing the power density of single cylinder engines.

  12. Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice.

    PubMed

    Schwengel, Katja; Namsolleck, Pawel; Lucht, Kristin; Clausen, Bettina H; Lambertsen, Kate L; Valero-Esquitino, Veronica; Thöne-Reineke, Christa; Müller, Susanne; Widdop, Robert E; Denton, Kate M; Horiuchi, Masatsugu; Iwai, Masaru; Boato, Francesco; Dahlöf, Björn; Hallberg, Anders; Unger, Thomas; Steckelings, U Muscha

    2016-08-01

    This study investigated the effect of post-stroke, direct AT2-receptor (AT2R) stimulation with the non-peptide AT2R-agonist compound 21 (C21) on infarct size, survival and neurological outcome after middle cerebral artery occlusion (MCAO) in mice and looked for potential underlying mechanisms. C57/BL6J or AT2R-knockout mice (AT2-KO) underwent MCAO for 30 min followed by reperfusion. Starting 45 min after MCAO, mice were treated once daily for 4 days with either vehicle or C21 (0.03 mg/kg ip). Neurological deficits were scored daily. Infarct volumes were measured 96 h post-stroke by MRI. C21 significantly improved survival after MCAO when compared to vehicle-treated mice. C21 treatment had no impact on infarct size, but significantly attenuated neurological deficits. Expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB) (receptor for BDNF) and growth-associated protein 43 (GAP-43) were significantly increased in the peri-infarct cortex of C21-treated mice when compared to vehicle-treated mice. Furthermore, the number of apoptotic neurons was significantly decreased in the peri-infarct cortex in mice treated with C21 compared to controls. There were no effects of C21 on neurological outcome, infarct size and expression of BDNF or GAP-43 in AT2-KO mice. From these data, it can be concluded that AT2R stimulation attenuates early mortality and neurological deficits after experimental stroke through neuroprotective mechanisms in an AT2R-specific way. Key message • AT2R stimulation after MCAO in mice reduces mortality and neurological deficits.• AT2R stimulation increases BDNF synthesis and protects neurons from apoptosis.• The AT2R-agonist C21 acts protectively when applied post-stroke and peripherally. PMID:26983606

  13. Experimental analysis of large capacity MR dampers with short- and long-stroke

    NASA Astrophysics Data System (ADS)

    Zemp, René; de la Llera, Juan Carlos; Weber, Felix

    2014-12-01

    The purpose of this article is to study and characterize experimentally two magneto-rheological dampers with short- and long-stroke, denoted hereafter as MRD-S and MRD-L. The latter was designed to improve the Earthquake performance of a 21-story reinforced concrete building equipped with two 160 ton tuned pendular masses. The MRD-L has a nominal force capacity of 300 kN and a stroke of ±1 m; the MRD-S has a nominal force capacity of 150 kN, and a stroke of ±0.1 m. The MRD-S was tested with two different magneto-rheological and one viscous fluid. Due to the presence of Eddy currents, both dampers show a time lag between current intensity and damper force as the magnetization on the damper changes in time. Experimental results from the MRD-L show a force drop-off behavior. A decrease in active-mode forces due to temperature increase is also analyzed for the MRD-S and the different fluids. Moreover, the observed increase in internal damper pressure due to energy dissipation is evaluated for the different fluids in both dampers. An analytical model to predict internal pressure increase in the damper is proposed that includes as a parameter the concentration of magnetic particles inside the fluid. Analytical dynamic pressure results are validated using the experimental tests. Finally, an extended Bingham fluid model, which considers compressibility of the fluid, is also proposed and validated using damper tests.

  14. Early Diagnosis of Pneumonia in Severe Stroke: Clinical Features and the Diagnostic Role of C-Reactive Protein

    PubMed Central

    Warusevitane, Anushka; Karunatilake, Dumin; Sim, Julius; Smith, Craig; Roffe, Christine

    2016-01-01

    Background Accurate diagnosis of pneumonia complicating severe stroke is challenging due to difficulties in physical examination, altered immune responses and delayed manifestations of radiological changes. The aims of this study were to describe early clinical features and to examine C-reactive protein (CRP) as a diagnostic marker of post-stroke pneumonia. Methods Patients who required nasogastric feeding and had no evidence of pneumonia within 7 days of stroke onset were included in the study and followed-up for 21 days with a daily clinical examination. Pneumonia was diagnosed using modified British Thoracic Society criteria. Results 60 patients were recruited (mean age 77 years, mean National Institutes of Health Stroke Scale Score 19.47). Forty-four episodes of pneumonia were identified. Common manifestations on the day of the diagnosis were new onset crackles (43/44, 98%), tachypnoea>25/min (42/44, 95%), and oxygen saturation <90% (41/44, 93%). Cough, purulent sputum, and pyrexia >38°C were observed in 27 (61%), 25 (57%) and 15 (34%) episodes respectively. Leucocytosis (WBC>11,000/ml) and raised CRP (>10 mg/l) were observed in 38 (86%) and 43 (97%) cases of pneumonia respectively. The area under the ROC curve for CRP was 0.827 (95% CI 0.720, 0.933). The diagnostic cut-off for CRP with an acceptable sensitivity (>0.8) was 25.60 mg/L (Youden index (J) 0.515; sensitivity 0.848; specificity 0.667). A cut-off of 64.65 mg/L had the highest diagnostic accuracy (J 0.562; sensitivity 0.636; specificity 0.926). Conclusion Patients with severe stroke frequently do not manifest key diagnostic features of pneumonia such as pyrexia, cough and purulent sputum early in their illness. The most common signs in this group are new-onset crackles, tachypnoea and hypoxia. Our results suggest that a CRP >25 mg/L should prompt investigations for pneumonia while values >65 mg/L have the highest diagnostic accuracy to justify consideration of this threshold as a diagnostic marker of

  15. Automating arm movement training following severe stroke: functional exercises with quantitative feedback in a gravity-reduced environment.

    PubMed

    Sanchez, Robert J; Liu, Jiayin; Rao, Sandhya; Shah, Punit; Smith, Robert; Rahman, Tariq; Cramer, Steven C; Bobrow, James E; Reinkensmeyer, David J

    2006-09-01

    An important goal in rehabilitation engineering is to develop technology that allows individuals with severe motor impairment to practice arm movement without continuous supervision from a rehabilitation therapist. This paper describes the development of such a system, called Therapy WREX or ("T-WREX"). The system consists of an orthosis that assists in arm movement across a large workspace, a grip sensor that detects hand grip pressure, and software that simulates functional activities. The arm orthosis is an instrumented, adult-sized version of the Wilmington Robotic Exoskeleton (WREX), which is a five degrees-of-freedom mechanism that passively counterbalances the weight of the arm using elastic bands. After providing a detailed design description of T-WREX, this paper describes two pilot studies of the system's capabilities. The first study demonstrated that individuals with chronic stroke whose arm function is compromised in a normal gravity environment can perform reaching and drawing movements while using T-WREX. The second study demonstrated that exercising the affected arm of five people with chronic stroke with T-WREX over an eight week period improved unassisted movement ability (mean change in Fugl-Meyer score was 5 points +/- 2 SD; mean change in range of motion of reaching was 10%, p < 0.001). These results demonstrate the feasibility of automating upper-extremity rehabilitation therapy for people with severe stroke using passive gravity assistance, a grip sensor, and simple virtual reality software. PMID:17009498

  16. Successful intravenous thrombolysis in a patient with antiphospholipid syndrome, acute ischemic stroke and severe thrombocytopenia.

    PubMed

    Camara-Lemarroy, Carlos R; Infante-Valenzuela, Adrian; Andrade-Vazquez, Catalina J; Enriquez-Noyola, Raul V; Garcia-Valadez, Erick A; Gongora-Rivera, Fernando

    2016-04-01

    Alteplase is the only approved drug for the treatment of acute ischemic stroke, but it is offered to a minority of patients, not only because of the short therapeutic window but also because of the numerous contraindications associated with thrombolysis, such as thrombocytopenia. There is some controversy on the true risk associated with thrombolysis in patients with thrombocytopenia. Here we report the case of a young patient, who developed an in-hospital acute ischemic stroke involving a large territory of the right middle cerebral artery, who was successfully treated with intravenous alteplase, despite having thrombocytopenia and prolonged prothrombin times due to systemic lupus erythematosus and antiphospholipid syndrome. This case exemplifies the need to reassess contraindications for thrombolysis, many based on expert opinion and not clinical evidence, especially in complex clinical situations. PMID:26575492

  17. A discussion of the several types of two-stroke-cycle engines

    NASA Technical Reports Server (NTRS)

    Venediger, Herbert J

    1935-01-01

    This report discusses different types of two-stroke engines as well as the three most important design factors: volume of scavenge and charge delivery, scavenging process (scavenging result), and result of charge. Some of the types of engines discussed include: single cylinder with crank-chamber scavenge pump and auxiliary suction piston linked to working connecting rod; and two cylinder engines with a rotary scavenge pump arrangement. Three and four cylinder engines are also discussed in various designs.

  18. Illuminating the Effects of Stroke on the Diabetic Brain: Insights From Imaging Neural and Vascular Networks in Experimental Animal Models.

    PubMed

    Reeson, Patrick; Jeffery, Andrew; Brown, Craig E

    2016-07-01

    Type 1 diabetes is known to cause circulatory problems in the eyes, heart, and limbs, and the brain is no exception. Because of the insidious effects of diabetes on brain circulation, patients with diabetes are two to four times more likely to have an ischemic stroke and are less likely to regain functions that are lost. To provide a more mechanistic understanding of this clinically significant problem, imaging studies have focused on how stroke affects neural and vascular networks in experimental models of type 1 diabetes. The emerging picture is that diabetes leads to maladaptive changes in the cerebrovascular system that ultimately limit neuronal rewiring and recovery of functions after stroke. At the cellular and systems level, diabetes is associated with abnormal cerebral blood flow in surviving brain regions and greater disruption of the blood-brain barrier. The abnormal vascular responses to stroke can be partly attributed to aberrant vascular endothelial growth factor (VEGF) signaling because genetic or pharmacological inhibition of VEGF signaling can mitigate vascular dysfunction and improve stroke recovery in diabetic animals. These experimental studies offer new insights and strategies for optimizing stroke recovery in diabetic populations. PMID:27329953

  19. In Vivo Inhibition of miR-155 Promotes Recovery after Experimental Mouse Stroke

    PubMed Central

    Caballero-Garrido, Ernesto; Pena-Philippides, Juan Carlos; Lordkipanidze, Tamar; Bragin, Denis; Yang, Yirong; Erhardt, Erik Barry

    2015-01-01

    A multifunctional microRNA, miR-155, has been recently recognized as an important modulator of numerous biological processes. In our previous in vitro studies, miR-155 was identified as a potential regulator of the endothelial morphogenesis. The present study demonstrates that in vivo inhibition of miR-155 supports cerebral vasculature after experimental stroke. Intravenous injections of a specific miR-155 inhibitor were initiated at 48 h after mouse distal middle cerebral artery occlusion (dMCAO). Microvasculature in peri-infarct area, infarct size, and animal functional recovery were assessed at 1, 2, and 3 weeks after dMCAO. Using in vivo two-photon microscopy, we detected improved blood flow and microvascular integrity in the peri-infarct area of miR-155 inhibitor-injected mice. Electron microscopy revealed that, in contrast to the control group, these animals demonstrated well preserved capillary tight junctions (TJs). Western blot analysis data indicate that improved TJ integrity in the inhibitor-injected animals could be associated with stabilization of the TJ protein ZO-1 and mediated by the miR-155 target protein Rheb. MRI analysis showed significant (34%) reduction of infarct size in miR-155 inhibitor-injected animals at 21 d after dMCAO. Reduced brain injury was confirmed by electron microscopy demonstrating decreased neuronal damage in the peri-infarct area of stroke. Preservation of brain tissue was reflected in efficient functional recovery of inhibitor-injected animals. Based on our findings, we propose that in vivo miR-155 inhibition after ischemia supports brain microvasculature, reduces brain tissue damage, and improves the animal functional recovery. SIGNIFICANCE STATEMENT In the present study, we investigated an effect of the in vivo inhibition of a microRNA, miR-155, on brain recovery after experimental cerebral ischemia. To our knowledge, this is the first report describing the efficiency of intravenous anti-miRNA injections in a mouse model

  20. A novel HLA-DRα1-MOG-35-55 construct treats experimental stroke

    PubMed Central

    Benedek, Gil; Zhu, Wenbin; Libal, Nicole; Casper, Amanda; Yu, Xiaolin; Meza-Romero, Roberto; Vandenbark, Arthur A.; Alkayed, Nabil J.

    2014-01-01

    Chemoattraction of leukocytes into the brain after induction of middle cerebral artery occlusion (MCAO) increases the lesion size and worsens disease outcome. Our previous studies demonstrated that partial MHC class II constructs can reverse this process. However, the potential application of pMHC to human stroke is limited by the need to rapidly match recipient MHC class II with the β1 domain of the pMHC construct. We designed a novel recombinant protein comprised of the HLA-DRα1 domain linked to MOG-35-55 peptide but lacking the β1 domain found in pMHC and treated MCAO after 4 h reperfusion in humanized DR2 mice. Infarct volumes were quantified after 96 h reperfusion and immune cells from the periphery and CNS were evaluated for expression of CD74 and other cell surface, cytokine and pathway markers. This study demonstrates that four daily treatments with DRα1-MOG-35-55 reduced infarct size by 40 % in the cortex, striatum and hemisphere, inhibited the migration of activated CD11b+CD45high cells from the periphery to the brain and reversed splenic atrophy. Furthermore, DRα1-MOG-35-55 bound to CD74 on monocytes and blocked both binding and downstream signaling of macrophage migration inhibition factor (MIF) that may play a key role in infarct development. The novel DRα1-MOG-35-55 construct is highly therapeutic in experimental stroke and could be given to all patients at least 4 h after stroke onset without the need for tissue typing due to universal expression of DRα1 in humans. PMID:24122483

  1. Post-stroke depression therapy: where are we now?

    PubMed

    Nabavi, Seyed Fazel; Turner, Alyna; Dean, Olivia; Sureda, Antoni; Mohammad, Seyed

    2014-01-01

    Post-stroke depression is an important psychological consequence of ischemic stroke, and affects around one third of stroke patients at any time post-stroke. It has a negative impact on patient morbidity and mortality, and as such development of effective post-stroke recognition and treatment strategies are very important. There are several therapeutic strategies for post-stroke depression, including both pharmacological and non-pharmacological approaches. In this review, we present evidence regarding the underlying biology of post-stroke depression, commonalities between post-stroke depression and Major Depressive Disorder and explore several treatment approaches, including antidepressant therapy, psychotherapy, surgical therapy, electroconvulsive therapy, acupuncture, music therapy and natural products. Further experimental and clinical studies are required, particularly in emerging fields such as the role of nutraceuticals in the treatment of stroke. PMID:24852795

  2. Enteral ecoimmunonutrition reduced enteral permeability and serum ghrelin activity in severe cerebral stroke patients with lung infection.

    PubMed

    Xu, Xiao-Di; Shao, Feng

    2015-01-01

    The study analyzed how enteral ecoimmunonutrition, which comprises probiotics, glutamine, fish oil, and Enteral Nutritional Suspension (TPF), can impact on the enteral permeability and serum Ghrelin activity in severe cerebral stroke patients with lung infection. Among 190 severe cerebral stroke patients with tolerance to TPF, they were randomized into control and treatment groups after antibiotics treatment due to lung infections. There were 92 patients in the control group and 98 patients in treatment group. The control group was treated with TPF and the treatment group was treated with enteral ecoimmunonutrition, which comprises probiotics, glutamine, fish oil, and Enteral Nutritional Suspension. All patients received continuous treatments through nasoenteral or nasogastric tubes. 7, 14, and 21 days after the treatments, the enteral tolerance to nutrition was observed in both groups. The tests included abdominal pain, bloating, diarrhea, and lactulose/mannitol (L/M) ratio. Serum Ghrelin levels were determined by ELISA. The incidence of abdominal pain, bloating, diarrhea was lower in the treatment group and enteral tolerance to nutrition was also superior to the control group. No difference in serum Ghrelin level was observed between the control and treatment groups with enteral intolerance to nutrition. However, in patients with enteral tolerance to nutrition, the treatment group showed lower enteral nutrition and lower enteral permeability compared to the control group. In severe cerebral stroke patients with lung infection, enteral ecoimmunonutrition after antibiotics treatment improved enteral tolerance to nutrition and reduced enteral permeability; meanwhile, it lowered the serum Ghrelin activity, which implied the high serum Ghrelin reduces enteral permeability. PMID:25142270

  3. Cannabinoids in experimental stroke: a systematic review and meta-analysis

    PubMed Central

    England, Timothy J; Hind, William H; Rasid, Nadiah A; O'Sullivan, Saoirse E

    2015-01-01

    Cannabinoids (CBs) show promise as neuroprotectants with some agents already licensed in humans for other conditions. We systematically reviewed CBs in preclinical stroke to guide further experimental protocols. We selected controlled studies assessing acute administration of CBs for experimental stroke, identified through systematic searches. Data were extracted on lesion volume, outcome and quality, and analyzed using random effect models. Results are expressed as standardized mean difference (SMD) with 95% confidence intervals (CIs). In all, 144 experiments (34 publications) assessed CBs on infarct volume in 1,473 animals. Cannabinoids reduced infarct volume in transient (SMD −1.41 (95% CI −1.71), −1.11) P<0.00001) and permanent (−1.67 (−2.08, −1.27), P<0.00001) ischemia and in all subclasses: endocannabinoids (−1.72 (−2.62, −0.82), P=0.0002), CB1/CB2 ligands (−1.75 (−2.19, −1.31), P<0.00001), CB2 ligands (−1.65 (−2.09, −1.22), P<0.00001), cannabidiol (−1.20 (−1.63, −0.77), P<0.00001), Δ9-tetrahydrocannabinol (−1.43 (−2.01, −0.86), P<0.00001), and HU-211 (−2.90 (−4.24, −1.56), P<0.0001). Early and late neuroscores significantly improved with CB use (−1.27 (−1.58, −0.95), P<0.00001; −1.63 (−2.64, −0.62), P<0.002 respectively) and there was no effect on survival. Statistical heterogeneity and publication bias was present, median study quality was 4 (range 1 to 6/8). Overall, CBs significantly reduced infarct volume and improve functional outcome in experimental stroke. Further studies in aged, female and larger animals, with other co-morbidities are required. PMID:25492113

  4. Simultaneous growth of several materials using a single experimental setup

    NASA Astrophysics Data System (ADS)

    Moovendaran, K.; Kalyana Sundar, J.; Natarajan, S.

    2011-11-01

    Sankaranarayanan and Ramasamy have introduced a new method (known as the SR method) to obtain unidirectional crystals of large sizes from solution, by slow evaporation. The authors have designed a new experimental setup to conduct several crystal growth experiments (SR method) simultaneously. The design is given in detail. This setup will be useful to obtain more quantity of single crystals, within a given period of time. It will be useful for research laboratories and industrial crystallization purposes.

  5. Glibenclamide enhances the effects of delayed hypothermia after experimental stroke in rats.

    PubMed

    Wu, Zhou; Zhu, Shu-Zhen; Hu, Ya-Fang; Gu, Yong; Wang, Sheng-Nan; Lin, Zhen-Zhou; Xie, Zuo-Shan; Pan, Su-Yue

    2016-07-15

    In order to evaluate whether glibenclamide can extend the therapeutic window during which induced hypothermia can protect against stroke, we subjected adult male Sprague-Dawley rats to middle cerebral artery occlusion (MCAO). We first verified the protective effects of hypothermia induced at 0, 2, 4 or 6h after MCAO onset, and then we assessed the effects of the combination of glibenclamide and hypothermia at 6, 8 or 10h after MCAO onset. At 24h after MCAO, we assessed brain edema, infarct volume, modified neurological severity score, Evans Blue leakage and expression of Sulfonylurea receptor 1 (SUR1) protein and pro-inflammatory factors. No protective effects were observed when hypothermia was induced too long after MCAO. At 6h after MCAO onset, hypothermia alone failed to decrease cerebral edema and infarct volume, but the combination of glibenclamide and hypothermia decreased both. The combination also improved neurological outcome, ameliorated blood-brain barrier damage and decreased levels of COX-2, TNF-α and IL-1β. These results suggest that glibenclamide enhances and extends the therapeutic effects of delayed hypothermia against ischemia stroke, potentially by ameliorating blood-brain barrier damage and declining levels of pro-inflammatory factors. PMID:27134036

  6. Pyruvate protects against experimental stroke via an anti-inflammatory mechanism

    PubMed Central

    Wang, Qing; van Hoecke, Michael; Tang, Xiannan; Lee, Hokyou; Zheng, Zheng; Swanson, Raymond A.; Yenari, Midori A.

    2009-01-01

    Pyruvate, a key intermediate in glucose metabolism, was explored as a potential treatment in models of experimental stroke and inflammation. Pyruvate was administered to rodents after the onset of middle cerebral artery occlusion (MCAO). Since the extent of inflammation is often proportional to the size of the infarct, we also studied a group of animals given lipopolysaccharide (LPS) to cause brain inflammation without cell death. Following MCAO, pyruvate did not affect physiological parameters but significantly reduced infarct volume, improved behavioral tests and reduced numbers of neutrophils, microglial and NF-kB activation. Animals given LPS showed increased microglial and NF-kB activation which was almost completely abolished by pyruvate. Lactate, a major metabolite of pyruvate, was increased after pyruvate administration. However, administration of lactate itself did not have any anti-inflammatory effects. Pyruvate protects against ischemia possibly by blocking inflammation, but lactate itself does not appear to explain pyruvate's anti-inflammatory properties. PMID:19635562

  7. Reduced severity of ischemic stroke and improvement of mitochondrial function after dietary treatment with the anaplerotic substance triheptanoin.

    PubMed

    Schwarzkopf, T M; Koch, K; Klein, J

    2015-08-01

    Triheptanoin, an oily substance, consists of glycerol bound to three molecules of heptanoic acid, a C7 odd-chain fatty acid. A triheptanoin-rich diet has anaplerotic effects because heptanoate metabolism yields succinate which delivers substrates to the Krebs cycle. While previous studies on the effects of triheptanoin focused on metabolic disorders and epilepsy, we investigated triheptanoin's effect on ischemic stroke. Mice were fed a triheptanoin-enriched diet for 14days; controls received soybean oil. Only mice fed triheptanoin had measurable quantities of odd-numbered fatty acids in the plasma and brain. Transient ischemia was induced in the brain by occlusion of the middle cerebral artery (MCAO) for 60min. One day later, mice were tested for neurological function (chimney, rotarod and corner tests) which was found to be better preserved in the triheptanoin group. Microdialysis demonstrated that the strong, neurotoxic increase of extracellular glutamate, which was observed in the mouse striatum during MCAO, was strongly reduced in triheptanoin-fed mice while glucose levels were not affected. Triheptanoin diet reduced the infarct area in stroked mice by about 40%. In ex vivo-experiments with isolated mitochondria, ischemia was found to cause a reduction of mitochondrial respiratory activity. This reduction was attenuated by triheptanoin diet in complex II and IV. In parallel measurements, ATP levels and mitochondrial membrane potential were reduced in control animals but were preserved in triheptanoin-fed mice. We conclude that triheptanoin-fed mice which sustained an experimental stroke had a significantly improved neurological outcome. This beneficial effect is apparently due to an improvement of mitochondrial function and preservation of the cellular energy state. Our findings identify triheptanoin as a promising new dietary agent for neuroprotection. PMID:25982559

  8. Novel Complement Inhibitor Limits Severity of Experimentally Myasthenia Gravis

    PubMed Central

    Soltys, Jindrich; Kusner, Linda L.; Young, Andrew; Richmonds, Chelliah; Hatala, Denise; Gong, Bendi; Shanmugavel, Vaithesh; Kaminski, Henry J.

    2011-01-01

    Objective Complement mediated injury of the neuromuscular junction is considered a primary disease mechanism in human myasthenia gravis and animal models of experimentally acquired myasthenia gravis (EAMG). We utilized active and passive models of EAMG to investigate the efficacy of a novel C5 complement inhibitor rEV576, recombinantly produced protein derived from tick saliva, in moderating disease severity. Methods Standardized disease severity assessment, serum complement hemolytic activity, serum cytotoxicity, acetylcholine receptor (AChR) antibody concentration, IgG subclassification, and C9 deposition at the neuromuscular junction were used to assess the effect of complement inhibition on EAMG induced by administration of AChR antibody or immunization with purified AChR. Results Administration of rEV576 in passive transfer EAMG limited disease severity as evidenced by 100% survival rate and a low disease severity score. In active EAMG, rats with severe and mild EAMG were protected from worsening of disease and had limited weight loss. Serum complement activity (CH50) in severe and mild EAMG was reduced to undetectable levels during treatment, and C9 deposition at the neuromuscular junction was reduced. Treatment with rEV576 resulted in reduction of toxicity of serum from severe and mild EAMG rats. Levels of total AChR IgG, and IgG2a antibodies were similar, but unexpectedly, the concentration of complement fixing IgG1 antibodies was lower in a group of rEV576-treated animals, suggesting an effect of rEV576 on cellular immunity. Interpretation Inhibition of complement significantly reduced weakness in two models of EAMG. C5 inhibition could prove to be of significant therapeutic value in human myasthenia gravis. PMID:19194881

  9. Stroke: current concepts.

    PubMed

    Albertson, Megan; Sharma, Jitendra

    2014-11-01

    Cerebrovascular accidents (CVAs) are the leading cause of disability and the fourth leading cause of death in the U.S. The WHO defines stroke as "rapidly developing clinical signs of focal disturbance of cerebral function lasting more than 24 hours with no apparent cause other than of vascular origin." Strokes are subdivided into two major classifications: ischemic (80-87 percent) andhemorrhagic (13-20 percent). Ischemic strokes occur from thrombi, emboli, or global hypoperfusion. Hemorrhagic strokes are either parenchymal (10 percent of all strokes) or subarachnoid (3 percent of all strokes). There are a variety of recognized risk factors for stroke which include: age, race, family history, hypertension, diabetes mellitus, atherosclerosis, cardiac arrhythmias, prosthetic valves, hyperlipidemia, cigarette smoking, and others (drugs or hormones). The initial assessment of a patient suspected of stroke should be done quickly enough to ensure maximal reperfusion of brain tissue. The steps to achieve this goal are: 1) exclude an intracranial hemorrhage, 2) assess for contraindications to thrombolytics, 3) characterize the infarct. The workup for a patient should first include a history (especially the time when neurologic symptoms began), a physical exam (including the NIHSS), and imaging studies (to rule out hemorrhagic components). In addition, several lab studies can also be obtained including: PT/INR, glucose, complete blood count, metabolic panel, creatine kinase, ECG, echocardiogram, lipid panel, carotid Doppler, MRA or CTA. Acute management of a stroke is primarily focused on stabilizing the patient and allowing as much reperfusion as possible for at-risk brain tissue. Stroke management in the acute setting includes: use of thrombolytics if indicated, and re-assessment to monitor progression. Several trials have been completed in pursuit of safety and effectiveness of intra-arterial stroke therapy for patients outside the recommended thrombolytic time window

  10. Stroke: current concepts.

    PubMed

    Albertson, Megan; Sharma, Jitendra

    2014-11-01

    Cerebrovascular accidents (CVAs) are the leading cause of disability and the fourth leading cause of death in the U.S. The WHO defines stroke as "rapidly developing clinical signs of focal disturbance of cerebral function lasting more than 24 hours with no apparent cause other than of vascular origin." Strokes are subdivided into two major classifications: ischemic (80-87 percent) andhemorrhagic (13-20 percent). Ischemic strokes occur from thrombi, emboli, or global hypoperfusion. Hemorrhagic strokes are either parenchymal (10 percent of all strokes) or subarachnoid (3 percent of all strokes). There are a variety of recognized risk factors for stroke which include: age, race, family history, hypertension, diabetes mellitus, atherosclerosis, cardiac arrhythmias, prosthetic valves, hyperlipidemia, cigarette smoking, and others (drugs or hormones). The initial assessment of a patient suspected of stroke should be done quickly enough to ensure maximal reperfusion of brain tissue. The steps to achieve this goal are: 1) exclude an intracranial hemorrhage, 2) assess for contraindications to thrombolytics, 3) characterize the infarct. The workup for a patient should first include a history (especially the time when neurologic symptoms began), a physical exam (including the NIHSS), and imaging studies (to rule out hemorrhagic components). In addition, several lab studies can also be obtained including: PT/INR, glucose, complete blood count, metabolic panel, creatine kinase, ECG, echocardiogram, lipid panel, carotid Doppler, MRA or CTA. Acute management of a stroke is primarily focused on stabilizing the patient and allowing as much reperfusion as possible for at-risk brain tissue. Stroke management in the acute setting includes: use of thrombolytics if indicated, and re-assessment to monitor progression. Several trials have been completed in pursuit of safety and effectiveness of intra-arterial stroke therapy for patients outside the recommended thrombolytic time window

  11. Central inflammatory response to experimental stroke is inhibited by a neuroprotective dose of dietary soy.

    PubMed

    Shambayati, Maryam; Patel, Maharshi; Ma, Yulin; Cunningham, Rebecca L; Schreihofer, Derek A

    2014-12-17

    Dietary soy and soy isoflavones are neuroprotective in experimental cerebral ischemia. Because the isoflavones in soy that are responsible for this neuroprotective effect act as phytoestrogens, we hypothesized that they would mimic the beneficial effects of estrogens on the innate inflammatory response to cerebral ischemia. Ovariectomized Sprague-Dawley rats were fed a soy free diet or a diet containing high dietary levels of soy for 5 weeks, after which they were subjected to transient middle cerebral artery occlusion (tMCAO) for 90min. Dietary soy was associated with a reduced inflammatory response in the cerebral cortex during the acute innate period 4 and 24h after tMCAO, including significant (>2-fold) reductions in interleukins 1 beta, 2, and 13, and the chemokine CXCL1. However, there was no effect of soy on tumor necrosis factor-alpha or interferon-gamma. Dietary soy was also associated with a 40 percent reduction in the nuclear translocation of p65 nuclear factor kappa B despite an increase in the expression of p65 RELA mRNA. In support of an early effect on the innate immune response to stroke, soy-fed rats had 44 percent fewer activated microglia in the infarct core than soy free rats. Interestingly, despite increased expression following injury, the steady state mRNA levels of inflammatory factors were not altered in soy-fed rats even though inflammatory proteins were. These data suggest that dietary soy isoflavones, like estrogens, inhibit of the innate immune response to injury. However, post-transcriptional mechanisms may play an important role in the mechanism of this action. Coupled with previously published data, these results support an early and rapid effect of dietary soy on the evolution of brain injury following stroke. PMID:25261694

  12. In vivo and ex vivo magnetic resonance spectroscopy of the infarct and the subventricular zone in experimental stroke

    PubMed Central

    Jiménez-Xarrié, Elena; Davila, Myriam; Gil-Perotín, Sara; Jurado-Rodríguez, Andrés; Candiota, Ana Paula; Delgado-Mederos, Raquel; Lope-Piedrafita, Silvia; García-Verdugo, José Manuel; Arús, Carles; Martí-Fàbregas, Joan

    2015-01-01

    Ex vivo high-resolution magic-angle spinning (HRMAS) provides metabolic information with higher sensitivity and spectral resolution than in vivo magnetic resonance spectroscopy (MRS). Therefore, we used both techniques to better characterize the metabolic pattern of the infarct and the neural progenitor cells (NPCs) in the ipsilateral subventricular zone (SVZi). Ischemic stroke rats were divided into three groups: G0 (non-stroke controls, n=6), G1 (day 1 after stroke, n=6), and G7 (days 6 to 8 after stroke, n=12). All the rats underwent MRS. Three rats per group were analyzed by HRMAS. The remaining rats were used for immunohistochemical studies. In the infarct, both techniques detected significant metabolic changes. The most relevant change was in mobile lipids (2.80 ppm) in the G7 group (a 5.53- and a 3.95-fold increase by MRS and HRMAS, respectively). In the SVZi, MRS did not detect any significant metabolic change. However, HRMAS detected a 2.70-fold increase in lactate and a 0.68-fold decrease in N-acetylaspartate in the G1 group. None of the metabolites correlated with the 1.37-fold increase in NPCs detected by immunohistochemistry in the G7 group. In conclusion, HRMAS improves the metabolic characterization of the brain in experimental ischemic stroke. However, none of the metabolites qualifies as a surrogate biomarker of NPCs. PMID:25605287

  13. Detrimental role of the EP1 prostanoid receptor in blood-brain barrier damage following experimental ischemic stroke

    PubMed Central

    Frankowski, Jan C.; DeMars, Kelly M.; Ahmad, Abdullah S.; Hawkins, Kimberly E.; Yang, Changjun; Leclerc, Jenna L.; Doré, Sylvain; Candelario-Jalil, Eduardo

    2015-01-01

    Cyclooxygenase-2 (COX-2) is activated in response to ischemia and significantly contributes to the neuroinflammatory process. Accumulation of COX-2-derived prostaglandin E2 (PGE2) parallels the substantial increase in stroke-mediated blood-brain barrier (BBB) breakdown. Disruption of the BBB is a serious consequence of ischemic stroke, and is mainly mediated by matrix metalloproteinases (MMPs). This study aimed to investigate the role of PGE2 EP1 receptor in neurovascular injury in stroke. We hypothesized that pharmacological blockade or genetic deletion of EP1 protects against BBB damage and hemorrhagic transformation by decreasing the levels and activity of MMP-3 and MMP-9. We found that post-ischemic treatment with the EP1 antagonist, SC-51089, or EP1 genetic deletion results in a significant reduction in BBB disruption and reduced hemorrhagic transformation in an experimental model of transient focal cerebral ischemia. These neurovascular protective effects of EP1 inactivation are associated with a significant reduction in MMP-9/-3, less peripheral neutrophil infiltration, and a preservation of tight junction proteins (ZO-1 and occludin) composing the BBB. Our study identifies the EP1 signaling pathway as an important link between neuroinflammation and MMP-mediated BBB breakdown in ischemic stroke. Targeting the EP1 receptor could represent a novel approach to diminish the devastating consequences of stroke-induced neurovascular damage. PMID:26648273

  14. Progress in the experimental therapy of severe arenaviral infections

    PubMed Central

    Gowen, Brian B.; Bray, Mike

    2012-01-01

    Summary A number of viruses in the family Arenaviridae cause severe illness in humans. Lassa virus in West Africa and a number of agents in South America produce hemorrhagic fever (HF) in persons exposed to aerosolized excretions of the pathogens’ rodent hosts. Because arenaviruses are not transmitted by arthropods, and person-to-person spread is rare, human infections occur singly and sporadically, and are usually not diagnosed until the patient is severely ill. Because the arenaviruses are naturally transmitted by the airborne route, they also pose a potential threat as aerosolized bioterror weapons. The broad-spectrum antiviral drug ribavirin was shown to reduce mortality from Lassa fever, and has been tested against Argentine HF, but it is not an approved treatment for either disease. Human immune convalescent plasma was proven to be effective for Argentine HF in a controlled trial. New treatments are needed to block viral replication without causing toxicity and to prevent the increased vascular permeability that is responsible for hypotension and shock. In this paper, we review current developments in the experimental therapy of severe arenaviral infections, focusing on drugs that have been tested in animal models, and provide a perspective on future research. PMID:22122440

  15. Brain-computer interface with somatosensory feedback improves functional recovery from severe hemiplegia due to chronic stroke

    PubMed Central

    Ono, Takashi; Shindo, Keiichiro; Kawashima, Kimiko; Ota, Naoki; Ito, Mari; Ota, Tetsuo; Mukaino, Masahiko; Fujiwara, Toshiyuki; Kimura, Akio; Liu, Meigen; Ushiba, Junichi

    2014-01-01

    Recent studies have shown that scalp electroencephalogram (EEG) based brain-computer interface (BCI) has a great potential for motor rehabilitation in stroke patients with severe hemiplegia. However, key elements in BCI architecture for functional recovery has yet to be clear. We in this study focused on the type of feedback to the patients, which is given contingently to their motor-related EEG in a BCI context. The efficacy of visual and somatosensory feedbacks was compared by a two-group study with the chronic stroke patients who are suffering with severe motor hemiplegia. Twelve patients were asked an attempt of finger opening in the affected side repeatedly, and the event-related desynchronization (ERD) in EEG of alpha and beta rhythms was monitored over bilateral parietal regions. Six patients were received a simple visual feedback in which the hand open/grasp picture on screen was animated at eye level, following significant ERD. Six patients were received a somatosensory feedback in which the motor-driven orthosis was triggered to extend the paralyzed fingers from 90 to 50°. All the participants received 1-h BCI treatment with 12–20 training days. After the training period, while no changes in clinical scores and electromyographic (EMG) activity were observed in visual feedback group after training, voluntary EMG activity was newly observed in the affected finger extensors in four cases and the clinical score of upper limb function in the affected side was also improved in three participants in somatosensory feedback group. Although the present study was conducted with a limited number of patients, these results imply that BCI training with somatosensory feedback could be more effective for rehabilitation than with visual feedback. This pilot trial positively encouraged further clinical BCI research using a controlled design. PMID:25071543

  16. Cerebral Hemodynamics and Vascular Reactivity in Mild and Severe Ischemic Rodent Middle Cerebral Artery Occlusion Stroke Models

    PubMed Central

    Sim, Jeongeun; Jo, Areum; Kang, Bok-Man; Lee, Sohee; Bang, Oh Young; Heo, Chaejeong; Jhon, Gil-Ja; Lee, Youngmi

    2016-01-01

    Ischemia can cause decreased cerebral neurovascular coupling, leading to a failure in the autoregulation of cerebral blood flow. This study aims to investigate the effect of varying degrees of ischemia on cerebral hemodynamic reactivity using in vivo real-time optical imaging. We utilized direct cortical stimulation to elicit hyper-excitable neuronal activation, which leads to induced hemodynamic changes in both the normal and middle cerebral artery occlusion (MCAO) ischemic stroke groups. Hemodynamic measurements from optical imaging accurately predict the severity of occlusion in mild and severe MCAO animals. There is neither an increase in cerebral blood volume nor in vessel reactivity in the ipsilateral hemisphere (I.H) of animals with severe MCAO. The pial artery in the contralateral hemisphere (C.H) of the severe MCAO group reacted more slowly than both hemispheres in the normal and mild MCAO groups. In addition, the arterial reactivity of the I.H in the mild MCAO animals was faster than the normal animals. Furthermore, artery reactivity is tightly correlated with histological and behavioral results in the MCAO ischemic group. Thus, in vivo optical imaging may offer a simple and useful tool to assess the degree of ischemia and to understand how cerebral hemodynamics and vascular reactivity are affected by ischemia. PMID:27358581

  17. Rivaroxaban does not increase hemorrhage after thrombolysis in experimental ischemic stroke

    PubMed Central

    Ploen, Robert; Sun, Li; Zhou, Wei; Heitmeier, Stefan; Zorn, Markus; Jenetzky, Ekkehart; Veltkamp, Roland

    2014-01-01

    The management of acute ischemic stroke during anticoagulation with a novel oral anticoagulant (NOAC) is challenging because intravenous thrombolysis is contraindicated because of a putative increased risk of intracerebral hemorrhagic complications. We examined the risk of secondary postischemic hemorrhage after thrombolysis in rodents pretreated with rivaroxaban or warfarin. Mice were pretreated with either rivaroxaban (30 mg/kg), warfarin (target international normalized ratio 2 to 3) or vehicle. After 2 or 3 hours, middle cerebral artery occlusion (MCAO), mice received 9 mg/kg recombinant tissue plasminogen activator. Twenty-four hours after MCAO, secondary hemorrhage was quantified using a macroscopic hemorrhage score and hemoglobin spectrophotometry. Blood–brain barrier (BBB) permeability was measured by Evans Blue spectrofluorometry. To increase the validity of our findings, experiments were also performed using a thromboembolic model in anticoagulated rats. Infarct size did not differ among groups. Pretreatment with warfarin led to significantly more secondary hemorrhage compared with rivaroxaban and nonanticoagulated controls after 2- and 3-hour ischemia in mice as well as in rats. Blood–brain barrier permeability was significantly higher in the warfarin group compared with rivaroxaban and control. Thus, rivaroxaban in contrast to warfarin does not increase secondary hemorrhage after thrombolysis in experimental cerebral ischemia. Less effects of rivaroxaban on postischemic BBB permeability may account for this difference. PMID:24346690

  18. Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study.

    PubMed

    Wali, Bushra; Ishrat, Tauheed; Won, Soonmi; Stein, Donald G; Sayeed, Iqbal

    2014-02-01

    Currently, the only approved treatment for ischaemic stroke is tissue plasminogen activator, a clot-buster. This treatment can have dangerous consequences if not given within the first 4 h after stroke. Our group and others have shown progesterone to be beneficial in preclinical studies of stroke, but a progesterone dose-response and time-window study is lacking. We tested male Sprague-Dawley rats (12 months old) with permanent middle cerebral artery occlusion or sham operations on multiple measures of sensory, motor and cognitive performance. For the dose-response study, animals received intraperitoneal injections of progesterone (8, 16 or 32 mg/kg) at 1 h post-occlusion, and subcutaneous injections at 6 h and then once every 24 h for 7 days. For the time-window study, the optimal dose of progesterone was given starting at 3, 6 or 24 h post-stroke. Behavioural recovery was evaluated at repeated intervals. Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume. Both 8 and 16 mg/kg doses of progesterone produced attenuation of infarct volume compared with the placebo, and improved functional outcomes up to 3 weeks after stroke on locomotor activity, grip strength, sensory neglect, gait impairment, motor coordination and spatial navigation tests. In the time-window study, the progesterone group exhibited substantial neuroprotection as late as 6 h after stroke onset. Compared with placebo, progesterone showed a significant reduction in infarct size with 3- and 6-h delays. Moderate doses (8 and 16 mg/kg) of progesterone reduced infarct size and improved functional deficits in our clinically relevant model of stroke. The 8 mg/kg dose was optimal in improving motor, sensory and memory function, and this effect was observed over a large therapeutic time window. Progesterone shows promise as a potential therapeutic agent and should be examined for safety and efficacy in a clinical trial for ischaemic stroke. PMID:24374329

  19. Arginine-Vasopressin Receptor Blocker Conivaptan Reduces Brain Edema and Blood-Brain Barrier Disruption after Experimental Stroke in Mice

    PubMed Central

    Zeynalov, Emil; Jones, Susan M.; Seo, Jeong-Woo; Snell, Lawrence D.; Elliott, J. Paul

    2015-01-01

    Background Stroke is a major cause of morbidity and mortality. Stroke is complicated by brain edema and blood-brain barrier (BBB) disruption, and is often accompanied by increased release of arginine-vasopressin (AVP). AVP acts through V1a and V2 receptors to trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. The AVP receptor blockers conivaptan (V1a and V2) and tolvaptan (V2) are used to correct hyponatremia, but their effect on post-ischemic brain edema and BBB disruption remains to be elucidated. Therefore, we conducted this study to investigate if these drugs can prevent brain edema and BBB disruption in mice after stroke. Methods Experimental mice underwent the filament model of middle cerebral artery occlusion (MCAO) with reperfusion. Mice were treated with conivaptan, tolvaptan, or vehicle. Treatments were initiated immediately at reperfusion and administered IV (conivaptan) or orally (tolvaptan) for 48 hours. Physiological variables, neurological deficit scores (NDS), plasma and urine sodium and osmolality were recorded. Brain water content (BWC) and Evans Blue (EB) extravasation index were evaluated at the end point. Results Both conivaptan and tolvaptan produced aquaresis as indicated by changes in plasma and urine sodium levels. However plasma and urine osmolality was changed only by conivaptan. Unlike tolvaptan, conivaptan improved NDS and reduced BWC in the ipsilateral hemisphere: from 81.66 ± 0.43% (vehicle) to 78.28 ± 0.48% (conivaptan, 0.2 mg, p < 0.05 vs vehicle). Conivaptan also attenuated the EB extravasation from 1.22 ± 0.08 (vehicle) to 1.01 ± 0.02 (conivaptan, 0.2 mg, p < 0.05). Conclusion Continuous IV infusion with conivaptan for 48 hours after experimental stroke reduces brain edema, and BBB disruption. Conivaptan but not tolvaptan may potentially be used in patients to prevent brain edema after stroke. PMID:26275173

  20. Evidence for the Use of Isoflurane as a Replacement for Chloral Hydrate Anesthesia in Experimental Stroke: An Ethical Issue

    PubMed Central

    Maud, Pétrault; Thavarak, Ouk; Cédrick, Lachaud; Michèle, Bastide; Vincent, Bérézowski; Olivier, Pétrault; Régis, Bordet

    2014-01-01

    Since an ethical issue has been raised regarding the use of the well-known anesthetic agent chloral hydrate, owing to its mutagenic and carcinogenic effects in animals, attention of neuroscientists has turned to finding out an alternative agent able to meet not only potency, safety, and analgesic efficacy, but also reduced neuroprotective effect for stroke research. The aim of this study was to compare the potential of chloral hydrate and isoflurane for both modulating the action of the experimental neuroprotectant MK801 and exerting analgesia. After middle cerebral artery occlusion in rats, no difference was observed in 24 h survival rate, success of ischemia, or infarct volume reduction between both anesthetics. However, isoflurane exerted a more pronounced analgesic effect than chloral hydrate as evidenced by formalin test 3 hours after anesthesia onset, thus encouraging the use of isoflurane in experimental stroke models. PMID:24719888

  1. Renin-angiotensin system as a potential therapeutic target in stroke and retinopathy: experimental and clinical evidence.

    PubMed

    Fouda, Abdelrahman Y; Artham, Sandeep; El-Remessy, Azza B; Fagan, Susan C

    2016-02-01

    As our knowledge expands, it is now clear that the renin-angiotensin (Ang) system (RAS) mediates functions other than regulating blood pressure (BP). The RAS plays a central role in the pathophysiology of different neurovascular unit disorders including stroke and retinopathy. Moreover, the beneficial actions of RAS modulation in brain and retina have been documented in experimental research, but not yet exploited clinically. The RAS is a complex system with distinct yet interconnected components. Understanding the different RAS components and their functions under brain and retinal pathological conditions is crucial to reap their benefits. The aim of the present review is to provide an experimental and clinical update on the role of RAS in the pathophysiology and treatment of stroke and retinopathy. Combining the evidence from both these disorders allows a unique opportunity to move both fields forward. PMID:26769658

  2. Superiority of preventive antibiotic treatment compared with standard treatment of poststroke pneumonia in experimental stroke: a bed to bench approach

    PubMed Central

    Hetze, Susann; Engel, Odilo; Römer, Christine; Mueller, Susanne; Dirnagl, Ulrich; Meisel, Christian; Meisel, Andreas

    2013-01-01

    Stroke patients are prone to life-threatening bacterial pneumonia. Previous experimental stroke studies have demonstrated that preventive antibiotic treatment (PAT) improves outcome compared with placebo treatment, which however does not model the clinical setting properly. Here we investigate whether PAT is superior to the current clinical ‘gold standard' for treating poststroke infections. Therefore, we modeled stroke care according to the current stroke guidelines recommending early antibiotic treatment after diagnosing infections. To reliably diagnose pneumonia in living mice, we established a general health score and a magnetic resonance imaging protocol for radiologic confirmation. Compared with standard treatment after diagnosis by these methods, PAT not only abolished pneumonia successfully but also improved general medical outcome. Both, preventive and standard antibiotic treatment using enrofloxacin improved survival in a similar way compared with placebo treatment. However, in contrast to standard treatment, only PAT improved functional outcome assessed by gait analysis. In conclusion, standard and preventive treatment approach reduced poststroke mortality, however at the cost of a worse neurologic outcome compared with preventive approach. These data support the concept of PAT for treating patients at risk for poststroke infections and warrant phase III trials to prove this concept in clinical setting. PMID:23361393

  3. Treatment of Fever After Stroke: Conflicting Evidence

    PubMed Central

    Wrotek, Sylwia E.; Kozak, Wieslaw E.; Hess, David C.; Fagan, Susan C.

    2014-01-01

    Approximately 50% of patients hospitalized for stroke develop fever. In fact, experimental evidence suggests that high body temperature is significantly correlated to initial stroke severity, lesion size, mortality, and neurologic outcome. Fever occurring after stroke is associated with poor outcomes. We investigated the etiology of fever after stroke and present evidence evaluating the efficacy and safety of interventions used to treat stroke-associated fever. Oral antipyretics are only marginally effective in lowering elevated body temperature in this population and may have unintended adverse consequences. Nonpharmacologic approaches to cooling have been more effective in achieving normothermia, but whether stroke outcomes can be improved remains unclear. We recommend using body temperature as a biomarker and a catalyst for aggressive investigation for an infectious etiology. Care must be taken not to exceed the new standard of a maximum acetaminophen does of 3 g/day to avoid patient harm. PMID:22026396

  4. Heat stroke.

    PubMed

    Leon, Lisa R; Bouchama, Abderrezak

    2015-04-01

    Heat stroke is a life-threatening condition clinically diagnosed as a severe elevation in body temperature with central nervous system dysfunction that often includes combativeness, delirium, seizures, and coma. Classic heat stroke primarily occurs in immunocompromised individuals during annual heat waves. Exertional heat stroke is observed in young fit individuals performing strenuous physical activity in hot or temperature environments. Long-term consequences of heat stroke are thought to be due to a systemic inflammatory response syndrome. This article provides a comprehensive review of recent advances in the identification of risk factors that predispose to heat stroke, the role of endotoxin and cytokines in mediation of multi-organ damage, the incidence of hypothermia and fever during heat stroke recovery, clinical biomarkers of organ damage severity, and protective cooling strategies. Risk factors include environmental factors, medications, drug use, compromised health status, and genetic conditions. The role of endotoxin and cytokines is discussed in the framework of research conducted over 30 years ago that requires reassessment to more clearly identify the role of these factors in the systemic inflammatory response syndrome. We challenge the notion that hypothalamic damage is responsible for thermoregulatory disturbances during heat stroke recovery and highlight recent advances in our understanding of the regulated nature of these responses. The need for more sensitive clinical biomarkers of organ damage is examined. Conventional and emerging cooling methods are discussed with reference to protection against peripheral organ damage and selective brain cooling. PMID:25880507

  5. Accessing Inpatient Rehabilitation after Acute Severe Stroke: Age, Mobility, Prestroke Function and Hospital Unit Are Associated with Discharge to Inpatient Rehabilitation

    ERIC Educational Resources Information Center

    Hakkennes, Sharon; Hill, Keith D.; Brock, Kim; Bernhardt, Julie; Churilov, Leonid

    2012-01-01

    The objective of this study was to identify the variables associated with discharge to inpatient rehabilitation following acute severe stroke and to determine whether hospital unit contributed to access. Five acute hospitals in Victoria, Australia participated in this study. Patients were eligible for inclusion if they had suffered an acute severe…

  6. Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

    PubMed Central

    Campos-Martorell, Mireia; Cano-Sarabia, Mary; Simats, Alba; Hernández-Guillamon, Mar; Rosell, Anna; Maspoch, Daniel; Montaner, Joan

    2016-01-01

    Background and aims Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. Materials and methods In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt) surgery and treated (intravenous [IV]) with fluorescent-labeled liposomes with different net surface charges. Ninety minutes after the administration of liposomes, the brain, blood, liver, lungs, spleen, and kidneys were evaluated ex vivo using the Xenogen IVIS® Spectrum imaging system to detect the load of fluorescent liposomes. In a second substudy, simvastatin was assessed upon reaching the brain, comparing free and encapsulated simvastatin (IV) administration. For this purpose, simvastatin levels in brain homogenates from sham or MCAOt rats at 2 hours or 4 hours after receiving the treatment were detected through ultra-high-protein liquid chromatography. Results Whereas positively charged liposomes were not detected in brain or plasma 90 minutes after their administration, neutral and negatively charged liposomes were able to reach the brain and accumulate specifically in the infarcted area. Moreover, neutral liposomes exhibited higher bioavailability in plasma 4 hours after being administered. The detection of simvastatin by ultra-high-protein liquid chromatography confirmed its ability to cross the blood–brain barrier, when administered either as a free drug or encapsulated into liposomes. Conclusion This study confirms that liposome charge is critical to promote its accumulation in the brain infarct after MCAOt. Furthermore, simvastatin can be delivered after being encapsulated. Thus, simvastatin encapsulation might be a promising

  7. Severe paraneoplastic hypoglycemia secondary to a gastrointestinal stromal tumour masquerading as a stroke

    PubMed Central

    Gopalakrishnan, K; Rao, R; Grammatopoulos, D K; Randeva, H S; Weickert, M O; Murthy, N

    2015-01-01

    Summary We report the case of a 70-year-old previously healthy female who presented acutely to the Accident and Emergency department with left-sided vasomotor symptoms including reduced muscle tone, weakness upon walking and slurred speech. Physical examination confirmed hemiparesis with VIIth nerve palsy and profound hepatomegaly. A random glucose was low at 1.7 mmol/l, which upon correction resolved her symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 3 months to which she did not give much attention. While hospitalized, she continued having episodes of symptomatic hypoglycaemia during most nights, requiring treatment with i.v. dextrose and/or glucagon. Blood tests including insulin and C-peptide were invariably suppressed, in correlation with low glucose. A Synacthen stimulation test was normal (Cort (0′) 390 nmol/l, Cort (30′) 773 nmol/l). A computed tomography scan showed multiple lobulated masses in the abdomen, liver and pelvis. An ultrasound guided biopsy of one of the pelvic masses was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. A diagnosis of a non islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=96.5 nmol/l; IGF2:IGF1 ratio 18.9, ULN <10). Treatment with growth hormone resolved the patient's hypoglycaemic symptoms and subsequent targeted therapy with Imatinib was successful in controlling disease progression over an 8-year observation period. Learning points NICTH can be a rare complication of GISTs that may manifest with severe hypoglycaemia and neuroglucopenic symptoms. NICTH can masquerade as other pathologies thus causing diagnostic confusion. Histological confirmation of GIST induced NICTH and exclusion of other conditions causing hypoglycaemia is essential. Mutational analysis of GISTs should be carried out in all

  8. Noninvasive ventilatory correction as an adjunct to an experimental systemic reperfusion therapy in acute ischemic stroke.

    PubMed

    Barlinn, Kristian; Balucani, Clotilde; Palazzo, Paola; Zhao, Limin; Sisson, April; Alexandrov, Andrei V

    2010-01-01

    Background. Obstructive sleep apnea (OSA) is a common condition in patients with acute ischemic stroke and associated with early clinical deterioration and poor functional outcome. However, noninvasive ventilatory correction is hardly considered as a complementary treatment option during the treatment phase of acute ischemic stroke. Summary of Case. A 55-year-old woman with an acute middle cerebral artery (MCA) occlusion received intravenous tissue plasminogen activator (tPA) and enrolled into a thrombolytic research study. During tPA infusion, she became drowsy, developed apnea episodes, desaturated and neurologically deteriorated without recanalization, re-occlusion or intracerebral hemorrhage. Urgent noninvasive ventilatory correction with biphasic positive airway pressure (BiPAP) reversed neurological fluctuation. Her MCA completely recanalized 24 hours later. Conclusions. Noninvasive ventilatory correction should be considered more aggressively as a complementary treatment option in selected acute stroke patients. Early initiation of BiPAP can stabilize cerebral hemodynamics and may unmask the true potential of other therapies. PMID:21052540

  9. Therapeutic outcomes of transplantation of amniotic fluid-derived stem cells in experimental ischemic stroke

    PubMed Central

    Tajiri, Naoki; Acosta, Sandra; Portillo-Gonzales, Gabriel S.; Aguirre, Daniela; Reyes, Stephanny; Lozano, Diego; Pabon, Mibel; Dela Peña, Ike; Ji, Xunming; Yasuhara, Takao; Date, Isao; Solomita, Marianna A.; Antonucci, Ivana; Stuppia, Liborio; Kaneko, Yuji; Borlongan, Cesar V.

    2014-01-01

    Accumulating preclinical evidence suggests the use of amnion as a source of stem cells for investigations of basic science concepts related to developmental cell biology, but also for stem cells’ therapeutic applications in treating human disorders. We previously reported isolation of viable rat amniotic fluid-derived stem (AFS) cells. Subsequently, we recently reported the therapeutic benefits of intravenous transplantation of AFS cells in a rodent model of ischemic stroke. Parallel lines of investigations have provided safety and efficacy of stem cell therapy for treating stroke and other neurological disorders. This review article highlights the need for investigations of mechanisms underlying AFS cells’ therapeutic benefits and discusses lab-to-clinic translational gating items in an effort to optimize the clinical application of the cell transplantation for stroke. PMID:25165432

  10. Peri-infarct depolarizations during focal ischemia in the awake Spontaneously Hypertensive Rat. Minimizing anesthesia confounds in experimental stroke.

    PubMed

    Kudo, K; Zhao, L; Nowak, T S

    2016-06-14

    Anesthesia profoundly impacts peri-infarct depolarizations (PIDs), but only one prior report has described their monitoring during experimental stroke in awake animals. Since temporal patterns of PID occurrence are model specific, the current study examined PID incidence during focal ischemia in the awake Spontaneously Hypertensive Rat (SHR), and documented the impact of both prior and concurrent isoflurane anesthesia. For awake recordings, electrodes were implanted under isoflurane anesthesia 1day to 5weeks prior to occlusion surgery. Rats were then subjected to permanent or transient (2h) tandem occlusion of the middle cerebral and ipsilateral common carotid arteries, followed by PID monitoring for up to 3days. Comparison perfusion imaging studies evaluated PID-associated hyperemic transients during permanent ischemia under anesthesia at varied intervals following prior isoflurane exposure. Prior anesthesia attenuated PID number at intervals up to 1week, establishing 2weeks as a practical recovery duration following surgical preparation to avoid isoflurane preconditioning effects. PIDs in awake SHR were limited to the first 4h after permanent occlusions. Maintaining anesthesia during this interval reduced PID number, and prolonged their occurrence through several hours following anesthesia termination. Although PID number otherwise correlated with infarct size, PID suppression by anesthesia was not protective in the absence of reperfusion. PIDs persisted up to 36h after transient occlusions. These results differ markedly from the one previous report of such monitoring in awake Sprague-Dawley rats, which found an extended biphasic PID time course during 24h after both permanent and transient filament occlusions. PID occurrence closely reflects the time course of infarct progression in the respective models, and may be more useful than absolute PID number as an index of ongoing pathology. PMID:27026594

  11. Propensity of Withania somnifera to Attenuate Behavioural, Biochemical, and Histological Alterations in Experimental Model of Stroke.

    PubMed

    Sood, Abhilasha; Kumar, Aditya; Dhawan, Devinder K; Sandhir, Rajat

    2016-10-01

    The present study was designed to evaluate the beneficial effects of Withania somnifera (WS) pre-supplementation on middle cerebral artery occlusion (MCAO) model of ischemic stroke. Ischemic stroke was induced in the rats by inserting intraluminal suture for 90 min, followed by reperfusion injury for 24 h. The animals were assessed for locomotor functions (by neurological deficit scores, narrow beam walk and rotarod test), cognitive and anxiety-like behavioural functions (by morris water maze and elevated plus maze test). MCAO animals showed significant impairment in locomotor and cognitive functions. Neurobehavioural changes were accompanied by decreased acetylcholinesterase activity, increased oxidative stress in terms of enhanced lipid peroxidation and lowered thiol levels in the MCAO animals. In addition, MCAO animals had cerebral infarcts and the presence of pycnotic nuclei. Single-photon emission computerized tomography (SPECT) of MCAO animals revealed a cerebral infarct as a hypoactive area. On the other hand, pre-supplementation with WS (300 mg/kg body weight) for 30 days to MCAO animals was effective in restoring the acetylcholinesterase activity, lipid peroxidation, thiols and attenuated MCAO induced behavioural deficits. WS significantly reduced the cerebral infarct volume and ameliorated histopathological alterations. Improved blood flow was observed in the SPECT images from the brain regions of ischemic rats pre-treated with WS. The results of the study showed a protective effect of WS supplementation in ischemic stroke and are suggestive of its potential application in stroke management. PMID:26718711

  12. Critical role of sphingosine-1-phosphate receptor-2 in the disruption of cerebrovascular integrity in experimental stroke

    PubMed Central

    Kim, Gab Seok; Yang, Li; Zhang, Guoqi; Zhao, Honggang; Selim, Magdy; McCullough, Louise D.; Kluk, Michael J.; Sanchez, Teresa

    2015-01-01

    The use and effectiveness of current stroke reperfusion therapies are limited by the complications of reperfusion injury, which include increased cerebrovascular permeability and haemorrhagic transformation. Sphingosine-1-phosphate (S1P) is emerging as a potent modulator of vascular integrity via its receptors (S1PR). By using genetic approaches and a S1PR2 antagonist (JTE013), here we show that S1PR2 plays a critical role in the induction of cerebrovascular permeability, development of intracerebral haemorrhage and neurovascular injury in experimental stroke. In addition, inhibition of S1PR2 results in decreased matrix metalloproteinase (MMP)-9 activity in vivo and lower gelatinase activity in cerebral microvessels. S1PR2 immunopositivity is detected only in the ischemic microvessels of wild-type mice and in the cerebrovascular endothelium of human brain autopsy samples. In vitro, S1PR2 potently regulates the responses of the brain endothelium to ischaemic and inflammatory injury. Therapeutic targeting of this novel pathway could have important translational relevance to stroke patients. PMID:26243335

  13. Meta-Analysis and Systematic Review of Neural Stem Cells therapy for experimental ischemia stroke in preclinical studies

    PubMed Central

    Chen, Lukui; Zhang, Guilong; Gu, Yuchun; Guo, Xiaoyuan

    2016-01-01

    To evaluate the preclinical studies using NSCs transplantation therapy for experimental ischemic stroke, and determine the effect size of NSCs therapy and the correlations between different clinical measures. We firstly searched literatures to identify studies of NSCs therapy in animal cerebral ischemia models, and then calculated the quality score of studies, assessed the effect size of NSCs therapy relative to behavioral and histologic endpoints by meta-analysis. A total of 37 studies and 54 independent treated interventions were used for systematic review and meta-analysis. The median quality score was 5 of 10. 36 studies (53 intervention arms) reported functional outcome, 22 studies (34 intervention arms) reported structural outcome. After adjusted by subgroup and sensitivity analysis, the mean effect sizes were improved by 1.35 for mNSS, 1.84 for rotarod test, 0.61 for cylinder test, and 0.84 for infarct volume. Furthermore, effect size had a certain interaction with clinical variables, for example early NSCs therapy etc. In this preclinical studies, we demonstrated that transplanted NSCs significantly improved outcomes (both functional and structural outcome) in ischemic stroke. It is suggested that future preclinical animal model studies of stroke should improve study quality validity and reduce potentially confounded publication bias. PMID:27554433

  14. Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model

    PubMed Central

    Selvamani, Amutha; Williams, Madison H.; Miranda, Rajesh C.; Sohrabji, Farida

    2015-01-01

    Small non-coding RNA [miRNA (microRNA)] found in the circulation have been used successfully as biomarkers and mechanistic targets for chronic and acute disease. The present study investigated the impact of age and sex on miRNA expression following ischaemic stroke in an animal model. Adult (6 month) and middle-aged (11–12 months) female and male rats were subject to MCAo (middle cerebral artery occlusion) using ET-1 (endothelin-1). Circulating miRNAs were analysed in blood samples at 2 and 5 days post-stroke, and brain miRNAs were analysed at 5 days post-stroke. Although stroke-associated infarction was observed in all groups, infarct volume and sensory-motor deficits were significantly reduced in adult females compared with middle-aged females, adult males or middle-aged males. At 2 days post-stroke, 21 circulating miRNAs were differentially regulated and PCA (principal component analysis) confirmed that most of the variance was due to age. At 5 days post-stroke, 78 circulating miRNAs exhibited significantly different regulation, and most of the variance was associated with sex. A small cohort (five) of miRNAs, miR-15a, miR-19b, miR-32 miR-136 and miR-199a-3p, were found to be highly expressed exclusively in adult females compared with middle-aged females, adult males and middle-aged males. Predicted gene targets for these five miRNAs analysed for KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed that the top ten KEGG pathways were related to growth factor signalling, cell structure and PI3K (phosphoinositide 3-kinase)/Akt and mTOR (mammalian target of rapamycin) signalling. Overall, the pattern of circulating miRNA expression suggests an early influence of age in stroke pathology, with a later emergence of sex as a factor for stroke severity. PMID:24428837

  15. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis.

    PubMed

    Hathaway, Lucy J; Grandgirard, Denis; Valente, Luca G; Täuber, Martin G; Leib, Stephen L

    2016-03-01

    Streptococcus pneumoniaebacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  16. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis

    PubMed Central

    Grandgirard, Denis; Valente, Luca G.; Täuber, Martin G.; Leib, Stephen L.

    2016-01-01

    Streptococcus pneumoniae bacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  17. The potential for utilizing the "mirror neurone system" to enhance recovery of the severely affected upper limb early after stroke: a review and hypothesis.

    PubMed

    Pomeroy, Valerie M; Clark, Christopher A; Miller, J Simon G; Baron, Jean-Claude; Markus, Hugh S; Tallis, Raymond C

    2005-03-01

    Recovery of upper limb movement control after stroke might be enhanced by repetitive goal-directed functional activities. Providing such activity is challenging in the presence of severe paresis. A possible new approach is based on the discovery of mirror neurons in the monkey cortical area F5, which are active both in observing and executing a movement. Indirect evidence for a comparable human "mirror neurone system" is provided by functional imaging. The primary motor cortex, the premotor cortex, other brain areas, and muscles appropriate for the action being observed are probably activated in healthy volunteers observing another's movement. These findings raise the hypothesis that observation of another's movement might train the movement execution system of stroke patients who have severe paresis to bring them to the point at which they could actively participate in rehabilitation consisting of goal-directed activities. The point of providing an observation therapy would be to facilitate the voluntary production of movement; therefore, the condition of interest would be observation with intent to imitate. However, there is as yet insufficient evidence to enable the testing of this hypothesis in stroke patients. Studies in normal subjects are needed to determine which brain sites are activated in response to observation with intent to imitate. Studies in stroke subjects are needed to determine how activation is affected after damage to different brain areas. The information from such studies should aid identification of those stroke patients who might be most likely to benefit from observation to imitate and therefore guide phase I clinical studies. PMID:15673838

  18. NADPH Oxidase: A Potential Target for Treatment of Stroke

    PubMed Central

    Zhang, Li; Wu, Jie; Duan, Xiaochun; Tian, Xiaodi; Shen, Haitao; Sun, Qing; Chen, Gang

    2016-01-01

    Stroke is the third leading cause of death in industrialized nations. Oxidative stress is involved in the pathogenesis of stroke, and excessive generation of reactive oxygen species (ROS) by mitochondria is thought to be the main cause of oxidative stress. NADPH oxidase (NOX) enzymes have recently been identified and studied as important producers of ROS in brain tissues after stroke. Several reports have shown that knockout or deletion of NOX exerts a neuroprotective effect in three major experimental stroke models. Recent studies also confirmed that NOX inhibitors ameliorate brain injury and improve neurological outcome after stroke. However, the physiological and pathophysiological roles of NOX enzymes in the central nervous system (CNS) are not known well. In this review, we provide a comprehensive summary of our current understanding about expression and physiological function of NOX enzymes in the CNS and its pathophysiological roles in the three major types of stroke: ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. PMID:26941888

  19. In Vivo Non-Invasive Tracking of Macrophage Recruitment to Experimental Stroke.

    PubMed

    Selt, Marion; Tennstaedt, Annette; Beyrau, Andreas; Nelles, Melanie; Schneider, Gabriele; Löwik, Clemens; Hoehn, Mathias

    2016-01-01

    Brain-infiltrating monocyte-derived macrophages are one of the key players in the local immune response after stroke. It is now widely accepted that the inflammatory response is not an exclusively destructive process. However, the underlying molecular mechanisms needed for proper regulation still remain to be elucidated. Here, we propose an in vitro labelling strategy for multimodal in vivo observation of macrophage dynamics distinguished from brain-residing microglia response. Prior to intracerebral transplantation into the striatum of recipient mice or systemic administration, monocytes and macrophages, isolated from luciferase-expressing mice, were labelled with superparamagnetic iron oxide particles. Temporo-spatial localization was monitored by magnetic resonance imaging, whereas survival of grafted cells was investigated using bioluminescence imaging. The labelling procedure of the isolated cells did not significantly influence cell characteristics and resulted in detection of as few as 500 labelled cells in vivo. Two weeks after stereotactic transplantation, the luciferase signal was sustained traceable, with approximately 18% of the original luciferase signal detectable for monocytes and about 30% for macrophages. Hypointensity in MRI of the graft appeared unaltered in spatial location. In a therapeutically relevant approach, systemic cell administration after stroke resulted in accumulation mostly in thoracic regions, as could be visualized with BLI. For detection of homing to ischemic brain tissue more cells need to be administered. Nevertheless, during parallel MRI sessions recruitment of i.v. injected cells to the lesion site could be detected by day 2 post stroke as scattered hypointense signal voids. With further increase in sensitivity, our multi-facetted labelling strategy will provide the basis for in vivo tracking and fate specification of tissue-infiltrating macrophages and their distinct role in stroke-related neuro-inflammation. PMID:27341631

  20. In Vivo Non-Invasive Tracking of Macrophage Recruitment to Experimental Stroke

    PubMed Central

    Selt, Marion; Tennstaedt, Annette; Beyrau, Andreas; Nelles, Melanie; Schneider, Gabriele; Löwik, Clemens; Hoehn, Mathias

    2016-01-01

    Brain-infiltrating monocyte-derived macrophages are one of the key players in the local immune response after stroke. It is now widely accepted that the inflammatory response is not an exclusively destructive process. However, the underlying molecular mechanisms needed for proper regulation still remain to be elucidated. Here, we propose an in vitro labelling strategy for multimodal in vivo observation of macrophage dynamics distinguished from brain-residing microglia response. Prior to intracerebral transplantation into the striatum of recipient mice or systemic administration, monocytes and macrophages, isolated from luciferase-expressing mice, were labelled with superparamagnetic iron oxide particles. Temporo-spatial localization was monitored by magnetic resonance imaging, whereas survival of grafted cells was investigated using bioluminescence imaging. The labelling procedure of the isolated cells did not significantly influence cell characteristics and resulted in detection of as few as 500 labelled cells in vivo. Two weeks after stereotactic transplantation, the luciferase signal was sustained traceable, with approximately 18% of the original luciferase signal detectable for monocytes and about 30% for macrophages. Hypointensity in MRI of the graft appeared unaltered in spatial location. In a therapeutically relevant approach, systemic cell administration after stroke resulted in accumulation mostly in thoracic regions, as could be visualized with BLI. For detection of homing to ischemic brain tissue more cells need to be administered. Nevertheless, during parallel MRI sessions recruitment of i.v. injected cells to the lesion site could be detected by day 2 post stroke as scattered hypointense signal voids. With further increase in sensitivity, our multi-facetted labelling strategy will provide the basis for in vivo tracking and fate specification of tissue-infiltrating macrophages and their distinct role in stroke-related neuro-inflammation. PMID:27341631

  1. Proper housing conditions in experimental stroke studies—special emphasis on environmental enrichment

    PubMed Central

    Mering, Satu; Jolkkonen, Jukka

    2015-01-01

    Environmental enrichment provides laboratory animals with novelty and extra space, allowing different forms of multisensory stimulation ranging from social grouping to enhanced motor activity. At the extreme end of the spectrum, one can have a super-enriched environment. Environmental enrichment is believed to result in improved cognitive and sensorimotor functions both in naïve rodents and in animals with brain lesions such as those occurring after a stroke. Robust behavioral effects in animals which have suffered a stroke are probably related not only to neuronal plasticity in the perilesional cortex but also in remote brain areas. There is emerging evidence to suggest that testing restorative therapies in an enriched environment can maximize treatment effects, e.g., the perilesional milieu seems to be more receptive to concomitant pharmacotherapy and/or cell therapy. This review provides an updated overview on the effect of an enriched environment in stroke animals from the practical points to be considered when planning experiments to the mechanisms explaining why combined therapies can contribute to behavioral improvement in a synergistic manner. PMID:25870536

  2. Airplane stroke syndrome.

    PubMed

    Humaidan, Hani; Yassi, Nawaf; Weir, Louise; Davis, Stephen M; Meretoja, Atte

    2016-07-01

    Only 37 cases of stroke during or soon after long-haul flights have been published to our knowledge. In this retrospective observational study, we searched the Royal Melbourne Hospital prospective stroke database and all discharge summaries from 1 September 2003 to 30 September 2014 for flight-related strokes, defined as patients presenting with stroke within 14days of air travel. We hypothesised that a patent foramen ovale (PFO) is an important, but not the only mechanism, of flight-related stroke. We describe the patient, stroke, and flight characteristics. Over the study period, 131 million passengers arrived at Melbourne airport. Our centre admitted 5727 stroke patients, of whom 42 (0.73%) had flight-related strokes. Flight-related stroke patients were younger (median age 65 versus 73, p<0.001), had similar stroke severity, and received intravenous thrombolysis more often than non-flight-related stroke patients. Seven patients had flight-related intracerebral haemorrhage. The aetiology of the ischaemic strokes was cardioembolic in 14/35 (40%), including seven patients with confirmed PFO, one with atrial septal defect, four with atrial fibrillation, one with endocarditis, and one with aortic arch atheroma. Paradoxical embolism was confirmed in six patients. Stroke related to air travel is a rare occurrence, less than one in a million. Although 20% of patients had a PFO, distribution of stroke aetiologies was diverse and was not limited to PFO and paradoxical embolism. PMID:26898578

  3. [Experimental study on early multiple organ failure after severe burns].

    PubMed

    Chen, F M

    1992-03-01

    Forty-three male mongrel dogs (12.5 +/- 2.5 kg) were divided into normal control (n = 7), immediate infusion (n = 8), non-infusion (n = 13) and delayed infusion (n = 15) groups. A 50% TBSA third degree surface burn was produced by igniting 3% napalm for 30 seconds on the shaved back. Cardiac, pulmonary, hepatic, renal and gastrointestinal functions were monitored following the thermal injury. The findings of these studies showed that mean arterial pressure, cardiac index, left ventricular work, right ventricular work, ADP/O ratio and ATP were all significantly decreased (P less than 0.05). However pulmonary artery wedge pressure, pulmonary vascular resistance, systemic vascular resistance, P(A-a)O2, Beef, Cr, UN, ALT, LDH, TB, DB, and MDA were markedly increased (P less than 0.05). Severe shock occurred soon after burns. Thirteen dogs died within 12 hours in the non-infusion group. All the dogs were resuscitated when immediate infusion of lactic acid Ringers solution was given according to Parkland formula, and all of them tide over shock stage smoothly without obvious changes in visceral functions. However, dogs were not resuscitated when infusion was delayed 6 hours postburn. The changes in visceral were even more severe in this group than those in non-infusion group. These results demonstrated that delayed resuscitation was an important factor of MOF in the early postburn stage. The marked increase in MDA in the myocardiac, lung, liver, renal and gastrointestinal tissues indicated that lipoperoxidation by free oxygen radicals was closely related with visceral damages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1596785

  4. Human Placenta-Derived Adherent Cell Treatment of Experimental Stroke Promotes Functional Recovery after Stroke in Young Adult and Older Rats

    PubMed Central

    Shehadah, Amjad; Chen, Jieli; Pal, Ajai; He, Shuyang; Zeitlin, Andrew; Cui, Xu; Zacharek, Alex; Cui, Yisheng; Roberts, Cynthia; Lu, Mei; Hariri, Robert; Chopp, Michael

    2014-01-01

    Background Human Placenta-Derived Adherent Cells (PDAC®) are a novel mesenchymal-like cell population derived from normal human placental tissue. PDA-001 is a clinical formulation of PDAC® developed for intravenous administration. In this study, we investigated the efficacy of PDA-001 treatment in a rat model of transient middle cerebral artery occlusion (MCAo) in young adult (2–3 month old) and older rats (10–12 months old). Methods To evaluate efficacy and determine the optimal number of transplanted cells, young adult Wistar rats were subjected to MCAo and treated 1 day post MCAo with 1×106, 4×106 or 8×106 PDA-001 cells (i.v.), vehicle or cell control. 4×106 or 8×106 PDA-001 cells were also tested in older rats after MCAo. Treatment response was evaluated using a battery of functional outcome tests, consisting of adhesive-removal test, modified Neurological Severity Score (mNSS) and foot-fault test. Young adult rats were sacrificed 56 days after MCAo, older rats were sacrificed 29 days after MCAo, and lesion volumes were measured using H&E. Immunohistochemical stainings for bromodeoxyuridine (BrdU) and von Willebrand Factor (vWF), and synaptophysin were performed. Results In young adult rats, treatment with 4×106 PDA-001 cells significantly improved functional outcome after stroke (p<0.05). In older rats, significant functional improvement was observed with PDA-001 cell therapy in both of the 4×106 and 8×106 treatment groups. Functional benefits in young adult and older rats were associated with significant increases in the number of BrdU immunoreactive endothelial cells, vascular density and perimeter in the ischemic brain, as well as significantly increased synaptophysin expression in the ischemic border zone (p<0.05). Conclusion PDA-001 treatment significantly improved functional outcome after stroke in both young adult and older rats. The neurorestorative effects induced by PDA-001 treatment may be related to increased vascular density and

  5. Numerical modeling and experimental validation of steady-state hydrocarbon emissions from small utility four-stroke engines

    SciTech Connect

    Sun, X.; Assanis, D.; Brereton, G.

    1996-12-31

    A hydrocarbon emissions model was developed to study the hydrocarbon emissions mechanisms pertinent to small utility engines. The model considered unburned hydrocarbon emissions from oil film absorption and desorption, and crevice flows. The model was calibrated and validated using experimental data from three typical, small utility engines. These engines were four-stroke, forced-air cooled, carbureted, spark-ignition designs. A specially designed low inertia hydraulic dynamometer was used to test the engines under the SAE J1088 A Cycle at different loads, speeds, and air-fuel ratios. The exhaust emissions of the engines were analyzed using dilute sampling. Reasonably good agreement between model predictions and experimental results was obtained. Subsequently, parametric studies indicated that the model can correctly predict expected hydrocarbon emission trends at different engine operating conditions.

  6. Factors that determine the severity of experimental myasthenia gravis.

    PubMed

    Drachman, D B; McIntosh, K R; Yang, B

    1998-05-13

    R antibody production than T cells with specificity for other Torpedo AChR epitopes. This results in production of greater amounts of AChR antibodies, including a critical subset that cross-reacts with autologous mouse AChR. The higher autoantibody levels contribute to the greater susceptibility to EAMG and to the greater severity of manifestations in the B6 strain compared with the bm12 strain. (4) There is a bias in B6 mice toward the production of AChR antibodies of IgG2b isotype. We suggest that T cells specific for alpha 146-162 may contribute to this isotype bias. The IgG2b antibodies appear to have particularly potent "myasthenogenic" effects in rats and mice. (5) Finally, it should be emphasized that these differences in immunological and clinical aspects of EAMG in B6 and bm12 mice are relative rather than absolute. T cells that respond to AChR epitopes other than alpha 146-162 can also provide help for AChR antibody production, albeit less potent. In a sense, this model represents a special case of molecular mimicry. In this case, the source of the foreign antigenic molecule is injection rather than the more usual route of infection. The antigen (Torpedo AChR) is one that these mice would never naturally encounter, and the critical amino acid (lysine 155) of the key epitope (alpha 146-162) is present only in the AChR of electric organs of electric fish and not in the AChR of mice, chickens, cows, or humans. The important point is that a detail of the structure of the foreign antigen--that is, a particular peptide of Torpedo AChR--can determine the severity of an antibody-mediated autoimmune disease, depending on how it interacts with a detail of the structure of the MHC Class II molecule and, in turn, on how the peptide/MHC Class II complex interacts with the available T cell repertoire. (ABSTRACT TRUNCATED) PMID:9668247

  7. Hydrogen Sulfide Attenuates Tissue Plasminogen Activator-Induced Cerebral Hemorrhage Following Experimental Stroke.

    PubMed

    Liu, Hui; Wang, Yi; Xiao, Yunqi; Hua, Zichun; Cheng, Jian; Jia, Jia

    2016-06-01

    Tissue plasminogen activator (tPA), the only approved drug for the treatment of ischemic stroke, increases the risk of cerebral hemorrhage. Here, we investigated whether the newly identified gaso-transmitter hydrogen sulfide (H2S), when used in combination with tPA, reduced the hemorrhagic transformation following stroke. In a mouse model of middle cerebral artery occlusion (MCAO), intravenous injection of tPA enhanced cerebral hemorrhage, which was significantly attenuated by the co-administration of two structurally unrelated H2S donors, ADT-OH and NaHS. By assessing extravasation of Evans blue into the ischemic hemisphere as well as brain edema following MCAO, we further showed that a tPA-exacerbated BBB disruption was significantly ameliorated by the co-administration of ADT-OH. In the mouse MCAO model, tPA upregulated Akt activation, vascular endothelial growth factor (VEGF) expression, and metalloproteinase 9 (MMP9) activity in the ischemic brain, which was remarkably attenuated by ADT-OH. In the in vitro glucose-oxygen deprivation (OGD) model, ADT-OH markedly attenuated tPA-enhanced Akt activation and VEGF expression in brain microvascular endothelial cells. Finally, ADT-OH improved functional outcomes in mice subjected to MCAO and tPA infusion. In conclusion, H2S donors reduced tPA-induced cerebral hemorrhage by possibly inhibiting the Akt-VEGF-MMP9 cascade. Administration of H2S donors has potential as a novel modality to improve the safety of tPA following stroke. PMID:27018013

  8. A quasi-experimental study on a new service option for short-term residential care of older stroke patients

    PubMed Central

    Chau, Pui-hing; Yeung, Fannie; Chan, Tsz-wai; Woo, Jean

    2013-01-01

    We conducted a quasi-experimental study to compare the effectiveness of a new short-term residential care option for stroke rehabilitation with that of usual day hospital care. Primary data were collected from stroke patients and their caregivers from June 2009 to May 2012. New service option users and their caregivers were recruited for the intervention group, while users of usual public geriatric day hospital care and their caregivers were recruited for the control group. The primary outcome measures were Modified Barthel Index (MBI) and Mini-Mental Status Examination (MMSE) scores. Trained research assistants assessed the outcome measures at the beginning of the rehabilitation program (baseline) and at a 4-month follow-up. Sixty and 128 stroke patients were recruited for the intervention and control groups, respectively; 50 and 105 participants, respectively, completed the 4-month follow-up. At 4-month follow-up, the intervention group had an increased MBI score of 15.3 (95% confidence interval [CI] 10.8–19.8) and an MMSE score of 1.3 (95% CI 0.4–2.1). In comparison, the control group had an increased MBI score of 13.3 (95% CI 9.7–16.8) and an MMSE score of 1.1 (95% CI 0.4–1.9). Both groups showed a significant improvement in MBI and MMSE scores after 4 months, and there was no significant between-group difference. To conclude, the new service option and the usual care option showed similar improvement in rehabilitation outcomes at 4 months after baseline. Initiatives to provide alternative care options on a user-pay model should be encouraged to ensure a sustainable health care system. PMID:24039413

  9. Multimodal imaging reveals temporal and spatial microglia and matrix metalloproteinase activity after experimental stroke.

    PubMed

    Zinnhardt, Bastian; Viel, Thomas; Wachsmuth, Lydia; Vrachimis, Alexis; Wagner, Stefan; Breyholz, Hans-Jörg; Faust, Andreas; Hermann, Sven; Kopka, Klaus; Faber, Cornelius; Dollé, Frédéric; Pappata, Sabina; Planas, Anna M; Tavitian, Bertrand; Schäfers, Michael; Sorokin, Lydia M; Kuhlmann, Michael T; Jacobs, Andreas H

    2015-11-01

    Stroke is the most common cause of death and disability from neurologic disease in humans. Activation of microglia and matrix metalloproteinases (MMPs) is involved in positively and negatively affecting stroke outcome. Novel, noninvasive, multimodal imaging methods visualizing microglial and MMP alterations were employed. The spatio-temporal dynamics of these parameters were studied in relation to blood flow changes. Micro positron emission tomography (μPET) using [(18)F]BR-351 showed MMP activity within the first days after transient middle cerebral artery occlusion (tMCAo), followed by increased [(18)F]DPA-714 uptake as a marker for microglia activation with a maximum at 14 days after tMCAo. The inflammatory response was spatially located in the infarct core and in adjacent (penumbral) tissue. For the first time, multimodal imaging based on PET, single photon emission computed tomography, and magnetic resonance imaging revealed insight into the spatio-temporal distribution of critical parameters of poststroke inflammation. This allows further evaluation of novel treatment paradigms targeting the postischemic inflammation. PMID:26126867

  10. Early identification of potentially salvageable tissue with MRI-based predictive algorithms after experimental ischemic stroke

    PubMed Central

    Bouts, Mark J R J; Tiebosch, Ivo A C W; van der Toorn, Annette; Viergever, Max A; Wu, Ona; Dijkhuizen, Rick M

    2013-01-01

    Individualized stroke treatment decisions can be improved by accurate identification of the extent of salvageable tissue. Magnetic resonance imaging (MRI)-based approaches, including measurement of a ‘perfusion-diffusion mismatch' and calculation of infarction probability, allow assessment of tissue-at-risk; however, the ability to explicitly depict potentially salvageable tissue remains uncertain. In this study, five predictive algorithms (generalized linear model (GLM), generalized additive model, support vector machine, adaptive boosting, and random forest) were tested in their potency to depict acute cerebral ischemic tissue that can recover after reperfusion. Acute T2-, diffusion-, and perfusion-weighted MRI, and follow-up T2 maps were collected from rats subjected to right-sided middle cerebral artery occlusion without subsequent reperfusion, for training of algorithms (Group I), and with spontaneous (Group II) or thrombolysis-induced reperfusion (Group III), to determine infarction probability-based viability thresholds and prediction accuracies. The infarction probability difference between irreversible—i.e., infarcted after reperfusion—and salvageable tissue injury—i.e., noninfarcted after reperfusion—was largest for GLM (20±7%) with highest accuracy of risk-based identification of acutely ischemic tissue that could recover on subsequent reperfusion (Dice's similarity index=0.79±0.14). Our study shows that assessment of the heterogeneity of infarction probability with MRI-based algorithms enables estimation of the extent of potentially salvageable tissue after acute ischemic stroke. PMID:23571283

  11. Sequential Therapy with Minocycline and Candesartan Improves Long Term Recovery after Experimental Stroke

    PubMed Central

    Soliman, Sahar; Ishrat, Tauheed; Fouda, Abdelrahman Y.; Patel, Ami; Pillai, Bindu; Fagan, Susan C.

    2015-01-01

    Background Minocycline and candesartan have both shown promise as candidate therapeutics in ischemic stroke, with multiple, and somewhat contrasting, molecular mechanisms. Minocycline is an anti-inflammatory, antioxidant and anti-apoptotic agent and a known inhibitor of matrix metalloproteinases (MMPs). Yet, minocycline exerts antiangiogenic effects both in vivo and in vitro. Candesartan promotes angiogenesis and activates MMPs. Aligning these therapies with the dynamic processes of injury and repair after ischemia is likely to improve success of treatment. Objective In this study, we hypothesize that opposing actions of minocycline and candesartan on angiogenesis, when administered simultaneously, will reduce the benefit of candesartan treatment. Therefore, we propose a sequential combination treatment regimen to yield a better outcome and preserve the proangiogenic potential of candesartan. Methods In vitro angiogenesis was assessed using human brain endothelial cells. In vivo, Wistar rats subjected to 90-minute middle cerebral artery occlusion (MCAO) were randomized into 4 groups: saline, candesartan, minocycline and sequential combination of minocycline and candesartan. Neurobehavioral tests were performed 1, 3, 7 and 14 days after stroke. Brain tissue was collected on day 14 for assessment of infarct size and vascular density. Results Minocycline, when added simultaneously, decreased the proangiogenic effect of candesartan treatment in vitro. Sequential treatment, however, preserved the proangiogenic potential of candesartan both in vivo and in vitro, improved neurobehavioral outcome and reduced infarct size. Conclusion Sequential combination therapy with minocycline and candesartan improves long term recovery and maintains candesartan’s proangiogenic potential. PMID:26004281

  12. Multimodal imaging reveals temporal and spatial microglia and matrix metalloproteinase activity after experimental stroke

    PubMed Central

    Zinnhardt, Bastian; Viel, Thomas; Wachsmuth, Lydia; Vrachimis, Alexis; Wagner, Stefan; Breyholz, Hans-Jörg; Faust, Andreas; Hermann, Sven; Kopka, Klaus; Faber, Cornelius; Dollé, Frédéric; Pappata, Sabina; Planas, Anna M; Tavitian, Bertrand; Schäfers, Michael; Sorokin, Lydia M; Kuhlmann, Michael T; Jacobs, Andreas H

    2015-01-01

    Stroke is the most common cause of death and disability from neurologic disease in humans. Activation of microglia and matrix metalloproteinases (MMPs) is involved in positively and negatively affecting stroke outcome. Novel, noninvasive, multimodal imaging methods visualizing microglial and MMP alterations were employed. The spatio-temporal dynamics of these parameters were studied in relation to blood flow changes. Micro positron emission tomography (μPET) using [18F]BR-351 showed MMP activity within the first days after transient middle cerebral artery occlusion (tMCAo), followed by increased [18F]DPA-714 uptake as a marker for microglia activation with a maximum at 14 days after tMCAo. The inflammatory response was spatially located in the infarct core and in adjacent (penumbral) tissue. For the first time, multimodal imaging based on PET, single photon emission computed tomography, and magnetic resonance imaging revealed insight into the spatio-temporal distribution of critical parameters of poststroke inflammation. This allows further evaluation of novel treatment paradigms targeting the postischemic inflammation. PMID:26126867

  13. Lightning return stroke models

    NASA Technical Reports Server (NTRS)

    Lin, Y. T.; Uman, M. A.; Standler, R. B.

    1980-01-01

    We test the two most commonly used lightning return stroke models, Bruce-Golde and transmission line, against subsequent stroke electric and magnetic field wave forms measured simultaneously at near and distant stations and show that these models are inadequate to describe the experimental data. We then propose a new return stroke model that is physically plausible and that yields good approximations to the measured two-station fields. Using the new model, we derive return stroke charge and current statistics for about 100 subsequent strokes.

  14. Recombinant T-cell Receptor Ligand Treatment Improves Neurological Outcome in the Presence of Tissue Plasminogen Activator in Experimental Ischemic Stroke

    PubMed Central

    Zhu, Wenbin; Libal, Nicole L.; Casper, Amanda; Bodhankar, Sheetal; Offner, Halina; Alkayed, Nabil J.

    2014-01-01

    RTL1000 is a partial human MHC molecule coupled to a human myelin peptide. We previously demonstrated that RTL1000 was protective against experimental ischemic stroke in HLA-DR2 transgenic (DR2-Tg) mice. Since thrombolysis with recombinant tissue plasminogen activator (t-PA) is a standard therapy for stroke, we determined if RTL1000 efficacy is altered when combined with t-PA in experimental stroke. Male DR2-Tg mice underwent 60 min of intraluminal middle cerebral artery occlusion (MCAO). t-PA or vehicle was infused intravenously followed by either a single or 4 daily subcutaneous injections of RTL1000 or vehicle. Infarct size was measured by 2, 3, 5-triphenyltetrazolium chloride staining at 24h or 96 h of reperfusion. Our data showed that t-PA alone reduced infarct size when measured at 24 h but not at 96 h after MCAO. RTL1000 alone reduced infarct size both at 24 and 96h after MCAO. Combining RTL1000 with t-PA did not alter its ability to reduce infarct size at either 24 or 96 h after MCAO and provides additional protection in t-PA treated mice at 24 h after ischemic stroke. Taken together, RTL1000 treatment alone improves outcome and provides additional protection in t-PA treated mice in experimental ischemic stroke. PMID:24953050

  15. Ischemic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

  16. Pediatric Stroke

    MedlinePlus

    ... Trials News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis ... UT Southwestern Medical Center. Copyright © 1997-2016 - The Internet Stroke Center. All rights reserved. The information contained ...

  17. Histological and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice

    PubMed Central

    2011-01-01

    Background Stroke models are essential tools in experimental stroke. Although several models of stroke have been developed in a variety of animals, with the development of transgenic mice there is the need to develop a reliable and reproducible stroke model in mice, which mimics as close as possible human stroke. Methods BALB/Ca-RAG2-/-γc-/- mice were subjected to cauterization or thrombosis stroke model and sacrificed at different time points (48hr, 1wk, 2wk and 4wk) after stroke. Mice received BrdU to estimate activation of cell proliferation in the SVZ. Brains were processed for immunohistochemical and EM. Results In both stroke models, after inflammation the same glial scar formation process and damage evolution takes place. After stroke, necrotic tissue is progressively removed, and healthy tissue is preserved from injury through the glial scar formation. Cauterization stroke model produced unspecific damage, was less efficient and the infarct was less homogeneous compared to thrombosis infarct. Finally, thrombosis stroke model produces activation of SVZ proliferation. Conclusions Our results provide an exhaustive analysis of the histopathological changes (inflammation, necrosis, tissue remodeling, scarring...) that occur after stroke in the ischemic boundary zone, which are of key importance for the final stroke outcome. This analysis would allow evaluating how different therapies would affect wound and regeneration. Moreover, this stroke model in RAG 2-/- γC -/- allows cell transplant from different species, even human, to be analyzed. PMID:22008614

  18. Use of a robotic device for the rehabilitation of severe upper limb paresis in subacute stroke: exploration of patient/robot interactions and the motor recovery process.

    PubMed

    Duret, Christophe; Courtial, Ophélie; Grosmaire, Anne-Gaëlle; Hutin, Emilie

    2015-01-01

    This pioneering observational study explored the interaction between subacute stroke inpatients and a rehabilitation robot during upper limb training. 25 stroke survivors (age 55 ± 17 years; time since stroke, 52 ± 21 days) with severe upper limb paresis carried out 16 sessions of robot-assisted shoulder/elbow training (InMotion 2.0, IMT, Inc., MA, USA) combined with standard therapy. The values of 3 patient/robot interaction parameters (a guidance parameter: Stiffness, a velocity-related parameter: Slottime, and Robotic Power) were compared between sessions 1 (S1), 4 (S4), 8 (S8), 12 (S12), and 16 (S16). Pre/post Fugl-Meyer Assessment (FMA) scores were compared in 18 patients. Correlations between interaction parameters and clinical and kinematic outcome measures were evaluated. Slottime decreased at S8 (P = 0.003), while Guidance decreased at S12 (P = 0.008). Robotic Power tended to decrease until S16. FMA scores improved from S1 to S16 (+49%, P = 0.002). Changes in FMA score were correlated with the Stiffness parameter (R = 0.4, P = 0.003). Slottime was correlated with movement velocity. This novel approach demonstrated that a robotic device is a useful and reliable tool for the quantification of interaction parameters. Moreover, changes in these parameters were correlated with clinical and kinematic changes. These results suggested that robot-based recordings can provide new insights into the motor recovery process. PMID:25821804

  19. [An acute severe heat stroke patient showing abnormal diffuse high intensity of the cerebellar cortex in diffusion weighted image: a case report].

    PubMed

    Fujioka, Yusuke; Yasui, Keizo; Hasegawa, Yasuhiro; Takahashi, Akira; Sobue, Gen

    2009-10-01

    A 47-year-old man was admitted to the hospital because of general convulsion, loss of consciousness and hyperthermia. A diagnosis of acute heat stroke was made clinically and neuroradiologically. As the consciousness level ameliorated, he developed severe abulia and mutism, then cerebellar ataxic syndrome (viz. truncal ataxia, hypermetria, ataxic speech and nystagmus). An MRI (diffusion weighted image; DWI) disclosed abnormal diffuse high signal intensity of the cerebellar cortex with reduced apparent diffusion coefficient (ADC). Two months later after the onset, truncal ataxia and dysarthria significantly improved, while dysmetria of the extremities rather worsened. At that time, the abnormal signal intensity of the cerebellar cortex disappeared, and the cerebellum became atrophic. The cerebellar blood flow was significantly decreased on brain SPECT (99mTc-ECD). The abnormal DWI signal intensity of the cerebellar cortex in the present patient may represent the cytotoxic edema of Purkinje cells resulting from heat stroke-related hyperthermia It is essential to repeat MRI examination for cerebellar pathology and to obtain better insight into sequelae in patients with acute heat stroke. Protirelin tartrate seemed to be valid for improvement of abulia in the present patient. Further study is indicated. PMID:19999144

  20. Use of a Robotic Device for the Rehabilitation of Severe Upper Limb Paresis in Subacute Stroke: Exploration of Patient/Robot Interactions and the Motor Recovery Process

    PubMed Central

    Courtial, Ophélie; Grosmaire, Anne-Gaëlle; Hutin, Emilie

    2015-01-01

    This pioneering observational study explored the interaction between subacute stroke inpatients and a rehabilitation robot during upper limb training. 25 stroke survivors (age 55 ± 17 years; time since stroke, 52 ± 21 days) with severe upper limb paresis carried out 16 sessions of robot-assisted shoulder/elbow training (InMotion 2.0, IMT, Inc., MA, USA) combined with standard therapy. The values of 3 patient/robot interaction parameters (a guidance parameter: Stiffness, a velocity-related parameter: Slottime, and Robotic Power) were compared between sessions 1 (S1), 4 (S4), 8 (S8), 12 (S12), and 16 (S16). Pre/post Fugl-Meyer Assessment (FMA) scores were compared in 18 patients. Correlations between interaction parameters and clinical and kinematic outcome measures were evaluated. Slottime decreased at S8 (P = 0.003), while Guidance decreased at S12 (P = 0.008). Robotic Power tended to decrease until S16. FMA scores improved from S1 to S16 (+49%, P = 0.002). Changes in FMA score were correlated with the Stiffness parameter (R = 0.4, P = 0.003). Slottime was correlated with movement velocity. This novel approach demonstrated that a robotic device is a useful and reliable tool for the quantification of interaction parameters. Moreover, changes in these parameters were correlated with clinical and kinematic changes. These results suggested that robot-based recordings can provide new insights into the motor recovery process. PMID:25821804

  1. Recovery of post stroke proximal arm function, driven by complex neuroplastic bilateral brain activation patterns and predicted by baseline motor dysfunction severity

    PubMed Central

    Pundik, Svetlana; McCabe, Jessica P.; Hrovat, Ken; Fredrickson, Alice Erica; Tatsuoka, Curtis; Feng, I Jung; Daly, Janis J.

    2015-01-01

    Objectives: Neuroplastic changes that drive recovery of shoulder/elbow function after stroke have been poorly understood. The purpose of this study was to determine the relationship between neuroplastic brain changes related to shoulder/elbow movement control in response to treatment and recovery of arm motor function in chronic stroke survivors.Methods: Twenty-three chronic stroke survivors were treated with 12 weeks of arm rehabilitation. Outcome measures included functional Magnetic Resonance Imaging (fMRI) for the shoulder/elbow components of reach and a skilled motor function test (Arm Motor Abilities Test, AMAT), collected before and after treatment.Results: We observed two patterns of neuroplastic changes that were associated with gains in motor function: decreased or increased task-related brain activation. Those with significantly better motor function at baseline exhibited a decrease in brain activation in response to treatment, evident in the ipsilesional primary motor and contralesional supplementary motor regions; in contrast, those with greater baseline motor impairment, exhibited increased brain activation in response to treatment. There was a linear relationship between greater functional gain (AMAT) and increased activation in bilateral primary motor, contralesional primary and secondary sensory regions, and contralesional lateral premotor area, after adjusting for baseline AMAT, age, and time since stroke.Conclusions: Recovery of functional reach involves recruitment of several contralesional and bilateral primary motor regions. In response to intensive therapy, the direction of functional brain change (i.e., increase or decrease in task-related brain recruitment) for shoulder/elbow reach components depends on baseline level of motor function and may represent either different phases of recovery or different patterns of neuroplasticity that drive functional recovery. PMID:26257623

  2. Stroke in Asia.

    PubMed

    Thammaroj, Jureerat; Subramaniam, Valarmathi; Bhattacharya, Joti J

    2005-05-01

    The epidemic of cardiovascular disease across most of Asia is at a different stage from that in the West; the incidence and prevalence of stroke are increasing steadily, associated with nutritional changes and aging of the population. Epidemiologic data, crucial in combating stroke, have been relatively sparse in Asian populations, but a few international collaborative studies on stroke have been in progress for several years. Through these, we now know that ischemic stroke is actually the most frequent type of cerebrovascular accident in Asia, although hemorrhagic stroke remains more common in Asia than in the West. Also, the percentage of ischemic stroke attributable to intracranial vascular disease is much higher than in the West. In Japan and a few other countries, stroke rates are declining; however, increasing rates in most other countries make primary prevention of critical importance in minimizing the severe impact of this epidemic in Asia. PMID:16198940

  3. Genetic Stroke Syndromes

    PubMed Central

    Barrett, Kevin M.; Meschia, James F.

    2014-01-01

    Purpose of Review: This review describes the clinical and radiographic features, genetic determinants, and treatment options for the most well-characterized monogenic disorders associated with stroke. Recent Findings: Stroke is a phenotype of many clinically important inherited disorders. Recognition of the clinical manifestations of genetic disorders associated with stroke is important for accurate diagnosis and prognosis. Genetic studies have led to the discovery of specific mutations associated with the clinical phenotypes of many inherited stroke syndromes. Summary: Several inherited causes of stroke have established and effective therapies, further underscoring the importance of timely diagnosis. PMID:24699489

  4. Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study.

    PubMed

    Spitoni, Grazia Fernanda; Pireddu, Giorgio; Galati, Gaspare; Sulpizio, Valentina; Paolucci, Stefano; Pizzamiglio, Luigi

    2016-01-01

    Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient's left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20), in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions. PMID:27028404

  5. Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study

    PubMed Central

    2016-01-01

    Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient’s left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20), in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions. PMID:27028404

  6. Neuropsychiatric sequelae of stroke.

    PubMed

    Ferro, José M; Caeiro, Lara; Figueira, Maria Luísa

    2016-05-01

    Stroke survivors are often affected by psychological distress and neuropsychiatric disturbances. About one-third of stroke survivors experience depression, anxiety or apathy, which are the most common neuropsychiatric sequelae of stroke. Neuropsychiatric sequelae are disabling, and can have a negative influence on recovery, reduce quality of life and lead to exhaustion of the caregiver. Despite the availability of screening instruments and effective treatments, neuropsychiatric disturbances attributed to stroke are currently underdiagnosed and undertreated. Stroke severity, stroke-related disabilities, cerebral small vessel disease, previous psychiatric disease, poor coping strategies and unfavourable psychosocial environment influence the presence and severity of the psychiatric sequelae of stroke. Although consistent associations between psychiatric disturbances and specific stroke locations have yet to be confirmed, functional MRI studies are beginning to unveil the anatomical networks that are disrupted in stroke-associated psychiatric disorders. Evidence regarding biochemical and genetic biomarkers for stroke-associated psychiatric disorders is still limited, and better understanding of the biological determinants and pathophysiology of these disorders is needed. Investigation into the management of these conditions must be continued, and should include pilot studies to assess the benefits of innovative behavioural interventions and large-scale cooperative randomized controlled pharmacological trials of drugs that are safe to use in patients with stroke. PMID:27063107

  7. Assessing Phagocytic Clearance of Cell Death in Experimental Stroke by Ligatable Fluorescent Probes

    PubMed Central

    Minchew, Candace L.; Didenko, Vladimir V.

    2014-01-01

    We describe a new histochemical approach for visualization of phagocytic clearance in focal brain ischemia. The approach permits the study of elimination of dead cells in stroke by waste-management phagocytes of any cellular lineage. Although numerous cells of different origins that are capable of phagocytosis are present in ischemic brain, only part of them actively engulf and digest cell corpses. The selective visualization, quantification and analysis of such active phagocytic waste-management are helpful in assessing brain response to ischemia. Efficient cell death clearance is important for brain recovery from ischemic injury, as it opens the way for the subsequent regenerative processes. The failure to clean the corpses would result in a toxic reaction caused by non-degraded DNA and proteins. The described procedure uses fluorescent probes selectively ligated by a viral topoisomerase to characteristic DNA breaks produced in all phagocytes during engulfment and digestion of cells irreversibly damaged by ischemia. The method is a new tool for the investigation of brain reaction to ischemic injury. PMID:24894100

  8. Arterial Spin Labeling Measurements of Cerebral Perfusion Territories in Experimental Ischemic Stroke

    PubMed Central

    Leoni, Renata F.; Paiva, Fernando F.; Kang, Byeong-Teck; Henning, Erica C.; Nascimento, George C.; Tannús, Alberto; De Araújo, Dráulio B.; Silva, Afonso C.

    2016-01-01

    Collateral circulation, defined as the supplementary vascular network that maintains cerebral blood flow (CBF) when the main vessels fail, constitutes one important defense mechanism of the brain against ischemic stroke. In the present study, continuous arterial spin labeling (CASL) was used to quantify CBF and obtain perfusion territory maps of the major cerebral arteries in spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. Results show that both WKY and SHR have complementary, yet significantly asymmetric perfusion territories. Right or left dominances were observed in territories of the anterior (ACA), middle and posterior cerebral arteries, and the thalamic artery. Magnetic resonance angiography showed that some of the asymmetries were correlated with variations of the ACA. The leptomeningeal circulation perfusing the outer layers of the cortex was observed as well. Significant and permanent changes in perfusion territories were obtained after temporary occlusion of the right middle cerebral artery in both SHR and WKY, regardless of their particular dominance. However, animals with right dominance presented a larger volume change of the left perfusion territory (23 ± 9%) than animals with left dominance (7 ± 5%, P < 0.002). The data suggest that animals with contralesional dominance primarily safeguard local CBF values with small changes in contralesional perfusion territory, while animals with ipsilesional dominance show a reversal of dominance and a substantial increase in contralesional perfusion territory. These findings show the usefulness of CASL to probe the collateral circulation. PMID:24323754

  9. Antidepressant fluvoxamine reduces cerebral infarct volume and ameliorates sensorimotor dysfunction in experimental stroke.

    PubMed

    Sato, Shinsuke; Kawamata, Takakazu; Kobayashi, Tomonori; Okada, Yoshikazu

    2014-07-01

    The sigma-1 receptor has been reported to be associated with diverse biological activities including cellular differentiation, neuroplasticity, neuroprotection, and cognitive functioning of the brain. Fluvoxamine, one of the currently known antidepressants, is a sigma-1 receptor agonist; its effectiveness in treating acute cerebral ischemia has not been reported. We studied the in-vivo effects of this compound using an animal model of focal cerebral ischemia. Forty male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion and assigned to five treatment groups (n=8 each). Postischemic neurological deficits and infarct volume were determined 24 h after stroke-inducing surgery. Significant reductions in infarct volume (total and cortical) were found in group 2 (fluvoxamine 20 mg/kg given 6 h before and immediately after ischemic onset) and group 3 (fluvoxamine given immediately after ischemic onset and 2 h later) compared with controls. Fluvoxamine induced significant amelioration of sensorimotor dysfunction, as indicated by the scores of forelimb and hindlimb placing tests. Moreover, NE-100, a selective sigma-1 receptor antagonist, completely blocked the neuroprotective effect of fluvoxamine. The present findings suggest that the sigma-1 receptor agonist fluvoxamine reduces infarct volume and ameliorates neurological impairment even on postischemic treatment. From the clinical viewpoint, fluvoxamine may be a promising new therapeutic approach for cerebral infarction. PMID:24709917

  10. FUNCTIONAL RECOVERY FOLLOWING MOTOR CORTEX LESIONS IN NON-HUMAN PRIMATES: EXPERIMENTAL IMPLICATIONS FOR HUMAN STROKE PATIENTS

    PubMed Central

    Darling, Warren G.; Pizzimenti, Marc A.; Morecraft, Robert J.

    2013-01-01

    This review discusses selected classical works and contemporary research on recovery of contralesional fine hand motor function following lesions to motor areas of the cerebral cortex in non-human primates. Findings from both the classical literature and contemporary studies show that lesions of cortical motor areas induce paresis initially, but are followed by remarkable recovery of fine hand/digit motor function that depends on lesion size and post-lesion training. Indeed, in recent work where considerable quantification of fine digit function associated with grasping and manipulating small objects has been observed, very favorable recovery is possible with minimal forced use of the contralesional limb. Studies of the mechanisms underlying recovery have shown that following small lesions of the digit areas of primary motor cortex (M1), there is expansion of the digit motor representations into areas of M1 that did not produce digit movements prior to the lesion. However, after larger lesions involving the elbow, wrist and digit areas of M1, no such expansion of the motor representation was observed, suggesting that recovery was due to other cortical or subcortical areas taking over control of hand/digit movements. Recently, we showed that one possible mechanism of recovery after lesion to the arm areas of M1 and lateral premotor cortex is enhancement of corticospinal projections from the medially located supplementary motor area (M2) to spinal cord laminae containing neurons which have lost substantial input from the lateral motor areas and play a critical role in reaching and digit movements. Because human stroke and brain injury patients show variable, and usually poorer, recovery of hand motor function than that of nonhuman primates after motor cortex damage, we conclude with a discussion of implications of this work for further experimentation to improve recovery of hand function in human stroke patients. PMID:21960307

  11. Salvianolic acid B attenuates apoptosis and inflammation via SIRT1 activation in experimental stroke rats.

    PubMed

    Lv, Hongdi; Wang, Ling; Shen, Jinchang; Hao, Shaojun; Ming, Aimin; Wang, Xidong; Su, Feng; Zhang, Zhengchen

    2015-06-01

    Silent information regulator 1 (SIRT1), a histone deacetylase, has been suggested to be effective in ischemic brain diseases. Salvianolic acid B (SalB) is a polyphenolic and one of the active components of Salvia miltiorrhiza Bunge. Previous studies suggested that SalB is protective against ischemic stroke. However, the role of SIRT1 in the protective effect of SalB against cerebral ischemia has not been explored. In this study, the rat brain was subjected to middle cerebral artery occlusion (MCAO). Before this surgery, rats were intraperitoneally administrated SalB with or without EX527, a specific SIRT1 inhibitor. The infarct volume, neurological score and brain water content were assessed. In addition, levels of TNF-α and IL-1β in the brain tissues were detected by commercial ELISA kits. And the expression levels of SIRT, Ac-FOXO1, Bcl-2 and Bax were detected by Western blot. The results suggested that SalB exerted a cerebral-protective effect, as shown by reduced infarct volume, lowered brain edema and increased neurological scores. SalB also exerted anti-inflammatory effects as indicated by the decreased TNF-α and IL-1β levels in the brain tissue. Moreover, SalB upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of Ac-FOXO1 and Bax. These effects of SalB were abolished by EX527 treatment. In summary, our results demonstrate that SalB treatment attenuates brain injury induced by ischemic stoke via reducing apoptosis and inflammation through the activation of SIRT1 signaling. PMID:25981395

  12. Reduced infarct size in neuroglobin-null mice after experimental stroke in vivo

    PubMed Central

    2012-01-01

    Background Neuroglobin is considered to be a novel important pharmacological target in combating stroke and neurodegenerative disorders, although the mechanism by which this protection is accomplished remains an enigma. We hypothesized that if neuroglobin is directly involved in neuroprotection, then permanent cerebral ischemia would lead to larger infarct volumes in neuroglobin-null mice than in wild-type mice. Methods Using neuroglobin-null mice, we estimated the infarct volume 24 hours after permanent middle cerebral artery occlusion using Cavalieri’s Principle, and compared the infarct volume in neuroglobin-null and wild-type mice. Neuroglobin antibody staining was used to examine neuroglobin expression in the infarct area of wild-type mice. Results Infarct volumes 24 hours after permanent middle cerebral artery occlusion were significantly smaller in neuroglobin-null mice than in wild-types (p < 0.01). Neuroglobin immunostaining of the penumbra area revealed no visible up-regulation of neuroglobin protein in ischemic wild-type mice when compared to uninjured wild-type mice. In uninjured wild-type mice, neuroglobin protein was seen throughout cortical layer II and sparsely in layer V. In contrast, no neuroglobin-immunoreactive neurons were observed in the aforementioned layers of the ischemia injured cortical area, or in the surrounding penumbra of ischemic wild-type mice. This suggests no selective sparing of neuroglobin expressing neurons in ischemia. Conclusions Neuroglobin-deficiency resulted in reduced tissue infarction, suggesting that, at least at endogenous expression levels, neuroglobin in itself is non-protective against ischemic injury. PMID:22901501

  13. Neuroprotection afforded by antagonists of endothelin-1 receptors in experimental stroke.

    PubMed

    Moldes, Octavio; Sobrino, Tomás; Blanco, Miguel; Agulla, Jesús; Barral, David; Ramos-Cabrer, Pedro; Castillo, José

    2012-12-01

    Endothelin-1 (ET-1) is involved on the development of cerebral edema in acute ischemic stroke. As edema is a therapeutic target in cerebral ischemia, our aim was to study the effect of antagonists for ET-1 receptors (Clazosentan® and BQ-788, specific antagonists for receptors A and B, respectively) on the development of edema, infarct volume and sensorial-motor deficits in rats subjected to ischemia by occlusion of the middle cerebral artery (MCAO). We used Wistar rats (280-320 g) submitted to ischemia by intraluminal transient (90 min) MCAO. After ischemia, rats were randomized into 4 groups (n = 6) treated with; 1) control group (saline), 2) Clazosentan® group (10 mg/kg iv), 3) BQ-788 group (3 mg/kg iv), and 4) combined treatment (Clazosentan® 10 mg/kg plus BQ-788 3 mg/kg iv). We observed that rats treated with Clazosentan® showed a reduction of edema, measured by MRI, at 72 h (hours) and at day 7 (both p < 0.0001), and a decrease in the serum levels of ET-1 at 72 h (p < 0.0001) and at day 7 (p = 0.009). The combined treatment also induced a reduction of edema at 24 h (p = 0.004), 72 h (p < 0.0001) and at day 7 (p < 0.0001), a reduction on infarct volume, measured by MRI, at 24 and 72 h, and at day 7 (all p < 0.01), and a better sensorimotor recovery at 24 and 72 h, and at day 7 (all p < 0.01). Moreover, Clazosentan® induced a decrease in AQP4 expression, while BQ-788 induced an increase in AQP9 expression. These results suggest that antagonists for ET-1 receptors may be a good therapeutic target for cerebral ischemia. PMID:22975409

  14. Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats

    PubMed Central

    Weise, Gesa; Lorenz, Marlene; Pösel, Claudia; Maria Riegelsberger, Ute; Störbeck, Veronika; Kamprad, Manja; Kranz, Alexander; Wagner, Daniel-Christoph; Boltze, Johannes

    2014-01-01

    Previous studies have highlighted the enormous potential of cell-based therapies for stroke not only to prevent ischemic brain damage, but also to amplify endogenous repair processes. Considering its widespread availability and low immunogenicity human umbilical cord blood (HUCB) is a particularly attractive stem cell source. Our goal was to investigate the neurorestorative potential of cryopreserved HUCB mononuclear cells (MNC) after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). Human umbilical cord blood MNC or vehicle solution was administered intravenously 24 hours after MCAO. Experimental groups were as follows: (1) quantitative polymerase chain reaction (PCR) of host-derived growth factors up to 48 hours after stroke; (2) immunohistochemical analysis of astroglial scarring; (3) magnetic resonance imaging (MRI) and weekly behavioral tests for 2 months after stroke. Long-term functional outcome and lesion development on MRI were not beneficially influenced by HUCB MNC therapy. Furthermore, HUCB MNC treatment did not change local growth factor levels and glial scarring extent. In summary, we could not demonstrate neurorestorative properties of HUCB MNC after stroke in SHR. Our results advise caution regarding a prompt translation of cord blood therapy into clinical stroke trials as long as deepened knowledge about its precise modes of action is missing. PMID:24169850

  15. Sex differences in stroke

    PubMed Central

    Haast, Roy A M; Gustafson, Deborah R; Kiliaan, Amanda J

    2012-01-01

    Sex differences in stroke are observed across epidemiologic studies, pathophysiology, treatments, and outcomes. These sex differences have profound implications for effective prevention and treatment and are the focus of this review. Epidemiologic studies reveal a clear age-by-sex interaction in stroke prevalence, incidence, and mortality. While premenopausal women experience fewer strokes than men of comparable age, stroke rates increase among postmenopausal women compared with age-matched men. This postmenopausal phenomenon, in combination with living longer, are reasons for women being older at stroke onset and suffering more severe strokes. Thus, a primary focus of stroke prevention has been based on sex steroid hormone-dependent mechanisms. Sex hormones affect different (patho)physiologic functions of the cerebral circulation. Clarifying the impact of sex hormones on cerebral vasculature using suitable animal models is essential to elucidate male–female differences in stroke pathophysiology and development of sex-specific treatments. Much remains to be learned about sex differences in stroke as anatomic and genetic factors may also contribute, revealing its multifactorial nature. In addition, the aftermath of stroke appears to be more adverse in women than in men, again based on older age at stroke onset, longer prehospital delays, and potentially, differences in treatment. PMID:23032484

  16. Ischemic Stroke

    MedlinePlus

    ... Spread the Word Advocate Share Spread the Word Contact Us Contact Us 1-800-STROKES (787-6537) 9707 E. ... Stroke En Espanol Stroke Facts Come Back Strong Contact Us 1-800-787-6537 9707 E. Easter ...

  17. Stroke Rehabilitation

    MedlinePlus

    A stroke can cause lasting brain damage. People who survive a stroke need to relearn skills they lose because of ... damage. Rehabilitation can help them relearn those skills. Stroke can cause five types of disabilities: Paralysis or ...

  18. Hemorrhagic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Hemorrhagic stroke is the less common type. It happens when ... an artery wall that breaks open. Symptoms of stroke are Sudden numbness or weakness of the face, ...

  19. Mental Practice Combined with Motor Rehabilitation to Treat Upper Limb Hemiparesis of Post-Stroke Patients: Clinical and Experimental Evidence

    PubMed Central

    Machado, Sergio; Lattari, Eduardo; Paes, Flávia; Rocha, Nuno B.F.; Nardi, Antonio E.; Arias-Carrión, Oscar; Mura, Gioia; Yuan, Ti-Fei; Carta, Mauro G.; Campos, Carlos

    2016-01-01

    Stroke is one of the major causes of disability in the world. Due to the extended lifetime of the world's population, the number of people affected by stroke has increased substantially over the last years. Stroke may lead to sensorimotor deficits, usually causing hemiplegia or hemiparesia. In order to reduce motor deficits and accelerate functional recovery, MP combined with motor rehabilitation was introduced to the rehabilitation process of post-stroke patients. Evidence has shown that MP combining with motor rehabilitation based on activities of daily living was more effective than conventional motor rehabilitation used per se. This combination proved very useful and effective, with significant results in improvement of motor deficits in post-stroke patients. However, further studies must be conducted to determine specific parameters, such as type of imagery, frequency or duration.

  20. A new mechanical arm trainer to intensify the upper limb rehabilitation of severely affected patients after stroke: design, concept and first case series.

    PubMed

    Hesse, S; Schmidt, H; Werner, C; Rybski, C; Puzich, U; Bardeleben, A

    2007-12-01

    Description and case series on a new mechanical arm trainer with three degrees of freedom (DoF), the REHA-SLIDE (RS), for stroke rehabilitation are presented. Similar to a rolling pin, it consists of two handles at either side of a connecting rod, the handles are bilaterally moved forward and backward, sideways, and rotated, the base plate is inclinable. A computer mouse attached to the rod enables playing games offering computer-biofeedback. Two patients, 6 and 5 weeks after a first-time supratentorial stroke, suffering from a flaccid non-functional upper extremity have been studied. Interventions performed were additional 30 min of RS-training every workday for 6 weeks; one session included 400 repetitions evenly distributed between the forward backward movement and drawing a circle clock- and counter clockwise. Afterwards the patients could play games. Upper extremity portion of the Fugl-Meyer Motor Assessment Score (FM, 0-66), and muscle strength by a Medical Research Council (MRC) sum score (0-45), the FM assessment was blinded. In the 2 patients, the FM (0-66) improved from 7 to 37, and from 17 to 43, their initial (terminal) MRC sum scores were 6 (36) and 13 (31). With the REHA-Slide (RS), severely affected patients practiced a bilateral 3 DoF movement. No conclusions can be drawn so far and a controlled clinical study must be the next step. PMID:18084168

  1. Very-late-antigen-4 (VLA-4)-mediated brain invasion by neutrophils leads to interactions with microglia, increased ischemic injury and impaired behavior in experimental stroke.

    PubMed

    Neumann, Jens; Riek-Burchardt, Monika; Herz, Josephine; Doeppner, Thorsten R; König, Rebecca; Hütten, Heiko; Etemire, Eloho; Männ, Linda; Klingberg, Anika; Fischer, Thomas; Görtler, Michael W; Heinze, Hans-Jochen; Reichardt, Peter; Schraven, Burkhart; Hermann, Dirk M; Reymann, Klaus G; Gunzer, Matthias

    2015-02-01

    Neuronal injury from ischemic stroke is aggravated by invading peripheral immune cells. Early infiltrates of neutrophil granulocytes and T-cells influence the outcome of stroke. So far, however, neither the timing nor the cellular dynamics of neutrophil entry, its consequences for the invaded brain area, or the relative importance of T-cells has been extensively studied in an intravital setting. Here, we have used intravital two-photon microscopy to document neutrophils and brain-resident microglia in mice after induction of experimental stroke. We demonstrated that neutrophils immediately rolled, firmly adhered, and transmigrated at sites of endothelial activation in stroke-affected brain areas. The ensuing neutrophil invasion was associated with local blood-brain barrier breakdown and infarct formation. Brain-resident microglia recognized both endothelial damage and neutrophil invasion. In a cooperative manner, they formed cytoplasmic processes to physically shield activated endothelia and trap infiltrating neutrophils. Interestingly, the systemic blockade of very-late-antigen-4 immediately and very effectively inhibited the endothelial interaction and brain entry of neutrophils. This treatment thereby strongly reduced the ischemic tissue injury and effectively protected the mice from stroke-associated behavioral impairment. Behavioral preservation was also equally well achieved with the antibody-mediated depletion of myeloid cells or specifically neutrophils. In contrast, T-cell depletion more effectively reduced the infarct volume without improving the behavioral performance. Thus, neutrophil invasion of the ischemic brain is rapid, massive, and a key mediator of functional impairment, while peripheral T-cells promote brain damage. Acutely depleting T-cells and inhibiting brain infiltration of neutrophils might, therefore, be a powerful early stroke treatment. PMID:25391494

  2. Stroke rehabilitation.

    PubMed

    Langhorne, Peter; Bernhardt, Julie; Kwakkel, Gert

    2011-05-14

    Stroke is a common, serious, and disabling global health-care problem, and rehabilitation is a major part of patient care. There is evidence to support rehabilitation in well coordinated multidisciplinary stroke units or through provision of early supported provision of discharge teams. Potentially beneficial treatment options for motor recovery of the arm include constraint-induced movement therapy and robotics. Promising interventions that could be beneficial to improve aspects of gait include fitness training, high-intensity therapy, and repetitive-task training. Repetitive-task training might also improve transfer functions. Occupational therapy can improve activities of daily living; however, information about the clinical effect of various strategies of cognitive rehabilitation and strategies for aphasia and dysarthria is scarce. Several large trials of rehabilitation practice and of novel therapies (eg, stem-cell therapy, repetitive transcranial magnetic stimulation, virtual reality, robotic therapies, and drug augmentation) are underway to inform future practice. PMID:21571152

  3. Experimental investigation on the wing-wake interaction at the mid stroke in hovering flight of dragonfly

    NASA Astrophysics Data System (ADS)

    Lai, GuoJun; Shen, GongXin

    2012-11-01

    This paper focuses on flow structures of the wing-wake interaction between the hind wing and the wake of the forewing in hovering flight of a dragonfly since there are arguments whether the wing-wake interaction is useful or not. A mechanical flapping model with two tandem wings is used to study the interaction. In the device, two identical simplified model wings are mounted to the flapping model and they are both scaled up to keep the Reynolds number similar to those of dragonfly in hovering flight since our experiment is conducted in a water tank. The kinetic pattern of dragonfly ( Aeschna juncea) is chosen because of its special interesting asymmetry. A multi-slice phase-locked stereo particle image velocimetry (PIV) system is used to record flow structures around the hind wing at the mid downstroke ( t/ T=0.25) and the mid upstroke ( t/ T=0.75). To make comparison of the flow field between with and without the influence of the wake, flow structures around a single flapping wing (hind wing without the existence of the forewing) at these two stroke phases are also recorded. A local vortex identification scheme called swirling strength is applied to determine the vortices around the wing and they are visualized with the iso-surface of swirling strength. This paper also presents contour lines of ω z at each spanwise position of the hind wing, the vortex core position of the leading edge vortex (LEV) of hind wing with respect to the upper surface of hind wing, the circulation of the hind wing LEV at each spanwise position and so on. Experimental results show that dimension and strength of the hind wing LEV are impaired at the mid stroke in comparison with the single wing LEV because of the downwash from the forewing. Our results also reveal that a wake vortex from the forewing traverses the upper surface of the hind wing at the mid downstroke and its distance to the upper surface is about 40% of the wing chord length. At the instant, the distance of the hind wing

  4. Correlation between Sleep Duration and Risk of Stroke.

    PubMed

    Patyar, Sazal; Patyar, Rakesh Raman

    2015-05-01

    Modern lifestyle and job requirements have changed the sleep habits of most of the adult population. Various population-based studies have associated an increase in mortality with either shortened sleep or long sleep duration. Thus a U-shaped relationship between sleep duration and all-cause mortality in both men and women has been suggested. Several studies have found an association between sleep duration and risk of cardiovascular diseases also. Efforts to understand the etiology of stroke have indicated an association between sleep and stroke too. Obstructive sleep apnea, a sleep-related disorder, has been reported to significantly increase the risk of stroke. Moreover, many studies have shown that both short and long sleep durations are related to increased likelihood of diabetes and hypertension, which themselves are risk factors for stroke. Therefore, this review focuses on the correlation between sleep duration and risk of stroke based on the experimental and epidemiologic studies. Although a few experimental studies have reported that partial sleep deprivation may reduce stroke incidence and severity, yet, most experimental and observational studies have indicated a strong association between short/long sleep durations and higher risk of stroke. PMID:25817615

  5. An Economic Evaluation Comparing Stroke Telemedicine to Conventional Stroke Medicine

    ERIC Educational Resources Information Center

    Budhram, Stanley Chandra

    2011-01-01

    Stroke is not only a serious medical problem, but it also poses an enormous economic burden on society. Stroke ranks the third as the leading cause of death in the United States behind heart disease and cancer. The survivors of stroke suffer from various degrees of long-term disability which create a severe financial burden on society. University…

  6. Recombinant T-cell Receptor Ligand RTL1000 Limits inflammation and Decreases Infarct Size after Experimental Ischemic Stroke in Middle-Aged Mice

    PubMed Central

    Zhu, W.; Dotson, A. L.; Libal, N. L.; Lapato, A. S.; Bodhankar, S.; Offner, H.; Alkayed, N. J.

    2015-01-01

    We have previously demonstrated that recombinant T-cell receptor ligand 1000 (RTL1000) reduces infarct size and improves long-term functional recovery after experimental stroke in young transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). In this study, we determined the effect of RTL1000 on infarct size in 12-month old middle-aged DR2-Tg mice, and investigated its mechanism of action. Twelve months old male DR2-Tg mice underwent 60 min of intraluminal reversible middle cerebral artery occlusion (MCAO). Vehicle or RTL1000 was injected 4, 24, 48 and 72 h after MCAO. Cortical, striatal and total hemispheric infarcts were measured 96 h after stroke. The spleen and brain tissue were collected 96 h after stroke for immunological analysis. Our data showed that RTL1000 significantly reduced infarct size 96 h after MCAO in middle-aged male DR2-Tg mice. RTL1000 decreased the number of activated monocytes/microglia cells (CD11b+CD45hi) and CD3+ T cells in the ischemic hemisphere. RTL1000 also reduced the percentage of total T cells and inflammatory neutrophils in spleen. These findings suggest that RTL1000 protects against ischemic stroke in middle-aged male mice by limiting post-ischemic inflammation. PMID:25556831

  7. Phytochemicals in Ischemic Stroke.

    PubMed

    Kim, Joonki; Fann, David Yang-Wei; Seet, Raymond Chee Seong; Jo, Dong-Gyu; Mattson, Mark P; Arumugam, Thiruma V

    2016-09-01

    Stroke is the second foremost cause of mortality worldwide and a major cause of long-term disability. Due to changes in lifestyle and an aging population, the incidence of stroke continues to increase and stroke mortality predicted to exceed 12 % by the year 2030. However, the development of pharmacological treatments for stroke has failed to progress much in over 20 years since the introduction of the thrombolytic drug, recombinant tissue plasminogen activator. These alarming circumstances caused many research groups to search for alternative treatments in the form of neuroprotectants. Here, we consider the potential use of phytochemicals in the treatment of stroke. Their historical use in traditional medicine and their excellent safety profile make phytochemicals attractive for the development of therapeutics in human diseases. Emerging findings suggest that some phytochemicals have the ability to target multiple pathophysiological processes involved in stroke including oxidative stress, inflammation and apoptotic cell death. Furthermore, epidemiological studies suggest that the consumption of plant sources rich in phytochemicals may reduce stroke risk, and so reinforce the possibility of developing preventative or neuroprotectant therapies for stroke. In this review, we describe results of preclinical studies that demonstrate beneficial effects of phytochemicals in experimental models relevant to stroke pathogenesis, and we consider their possible mechanisms of action. PMID:27193940

  8. The burden of stroke in Pakistan.

    PubMed

    Khealani, Bhojo A; Wasay, Mohammad

    2008-11-01

    Epidemiologic literature on stroke burden, patterns of stroke is almost non existent from Pakistan. However, several hospital-based case series on the subject are available, mainly published in local medical journals. Despite the fact that true stroke incidence and prevalence of stroke in Pakistan is not known, the burden is assumed to be high because of highly prevalent stroke risk factors (hypertension, diabetes mellitus, coronary artery disease, dyslipidemia and smoking) in the community. High burden of these conventional stroke risk factors is further compounded by lack of awareness, poor compliance hence poor control, and inappropriate management/treatment practices. In addition certain risk factors like rheumatic valvular heart disease may be more prevalent in Pakistan. We reviewed the existing literature on stroke risk factors in community, the risk factor prevalence among stroke patients, patterns of stroke, out come of stroke, availability of diagnostic services/facilities related to stroke and resources for stroke care in Pakistan. PMID:18811747

  9. Inflammatory Disequilibrium in Stroke.

    PubMed

    Petrovic-Djergovic, Danica; Goonewardena, Sascha N; Pinsky, David J

    2016-06-24

    Over the past several decades, there have been substantial advances in our knowledge of the pathophysiology of stroke. Understanding the benefits of timely reperfusion has led to the development of thrombolytic therapy as the cornerstone of current management of ischemic stroke, but there remains much to be learned about mechanisms of neuronal ischemic and reperfusion injury and associated inflammation. For ischemic stroke, novel therapeutic targets have continued to remain elusive. When considering modern molecular biological techniques, advanced translational stroke models, and clinical studies, a consistent pattern emerges, implicating perturbation of the immune equilibrium by stroke in both central nervous system injury and repair responses. Stroke triggers activation of the neuroimmune axis, comprised of multiple cellular constituents of the immune system resident within the parenchyma of the brain, leptomeninges, and vascular beds, as well as through secretion of biological response modifiers and recruitment of immune effector cells. This neuroimmune activation can directly impact the initiation, propagation, and resolution phases of ischemic brain injury. To leverage a potential opportunity to modulate local and systemic immune responses to favorably affect the stroke disease curve, it is necessary to expand our mechanistic understanding of the neuroimmune axis in ischemic stroke. This review explores the frontiers of current knowledge of innate and adaptive immune responses in the brain and how these responses together shape the course of ischemic stroke. PMID:27340273

  10. Theoretical, Experimental, and Computational Evaluation of Several Vane-Type Slow-Wave Structures

    NASA Technical Reports Server (NTRS)

    Wallett, Thomas M.; Qureshi, A. Haq

    1994-01-01

    Several types of periodic vane slow-wave structures were fabricated. The dispersion characteristics were found by theoretical analysis, experimental testing, and computer simulation using the MAFIA code. Computer-generated characteristics agreed to approximately within 2 percent of the experimental characteristics for all structures. The theoretical characteristics, however, deviated increasingly as the width to height ratio became smaller. Interaction impedances were also computed based on the experimental and computer-generated resonance frequency shifts due to the introduction of a perturbing dielectric rod.

  11. Effect of lavender oil (Lavandula angustifolia) on cerebral edema and its possible mechanisms in an experimental model of stroke.

    PubMed

    Vakili, Abedin; Sharifat, Shaghayegh; Akhavan, Maziar Mohammad; Bandegi, Ahmad Reza

    2014-02-22

    Lavender belongs to the family Labiatae and has a variety of cosmetic uses as well as therapeutic purposes in herbal medicine. The present study was conducted to evaluate the protective effect of lavender oil against brain edema and its possible mechanisms in an experimental model of stroke. Under Laser-Doppler Flowmetry, focal cerebral ischemia was induced by the transient occlusion of the middle cerebral artery for 1h in rats. Lavender oil (100, 200, and 400 mg/kg ip (and/or vehicle was injected at the onset of ischemia. Infarct size, cerebral edema, functional outcome, and oxidative stress biomarkers were evaluated using standard methods. Western blotting was used to determine the protein expression of VEGF, Bax, and Bcl-2. Treatment with lavender oil at doses of 200 and 400 mg/kg significantly diminished infarct size, brain edema, and improved functional outcome after cerebral ischemia (P<0.001). Lavender oil (200 mg/kg) also reduced the content of malondialdehyde and increased the activities of superoxide dismutase, glutathione peroxidase, and total antioxidant capacity (P<0.001). Although lavender oil enhanced VEGF expression (P=0.026), it could not decrease the Bax-to-Bcl-2 ratio (pro- to anti-apoptotic proteins) in the rat brain (P>0.05). The results indicated that lavender oil has neuroprotective activity against cerebral ischemia and alleviated neurological function in rats, and the mechanism may be related to augmentation in endogenous antioxidant defense, inhibiting oxidative stress, and increasing VEGF expression in the rat brain. However, lavender oil could not suppress the apoptosis pathway. PMID:24384140

  12. Cognitive Impairment After Stroke

    PubMed Central

    Gauba, Charu; Chaudhari, Dinesh

    2015-01-01

    Background: Vascular dementia is extremely common and contributes to stroke-associated morbidity and mortality. The study of vascular dementia may help to plan preventive interventions. Aims: To study the frequency of cognitive impairment after stroke in a series of consecutive patients with acute stroke, along with factors which influence it. Methods: Fifty adults with acute infarct or hemorrhage (as seen on computed tomography of the brain) were included in the study. The National Institute of Health Stroke Scale (NIHSS) and Barthel’s Index scores were done. Cognitive testing was done by PGI Battery of Brain Dysfunction (PGI-BBD) and Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly (SIQCODE). Statistical analysis was by Student’s t-test, Chi-square test, Fisher’s exact test, and Mann-Whitney U test. Results: Mean age of patients was 61.82 years; males and ischemic strokes predominated. Dementia was seen in 30%, cognitive impairment no dementia (CIND) in 42%, and normal cognition in 28% patients. Factors associated with vascular cognitive impairment included old age, male sex, low education, hemorrhages, recurrent or severe stroke, silent infarcts, severe cortical atrophy, and left hemispheric or subcortical involvement. Conclusions: Up to 72% of patients have some form of cognitive impairment after a stroke. Secondary stroke prevention could reduce the incidence of vascular dementia. PMID:26543693

  13. Spatio-temporal course of macrophage-like cell accumulation after experimental embolic stroke depending on treatment with tissue plasminogen activator and its combination with hyperbaric oxygenation

    PubMed Central

    Michalski, D.; Heindl, M.; Kacza, J.; Laignel, F.; Küppers-Tiedt, L.; Schneider, D.; Grosche, J.; Boltze, J.; Löhr, M.; Hobohm, C.; Härtig, W.

    2012-01-01

    Inflammation following ischaemic stroke attracts high priority in current research, particularly using human-like models and long-term observation periods considering translational aspects. The present study aimed on the spatio-temporal course of macrophage-like cell accumulation after experimental thromboembolic stroke and addressed microglial and astroglial reactions in the ischaemic border zone. Further, effects of tissue plasminogen activator (tPA) as currently best treatment for stroke and the potentially neuroprotective co-administration of hyperbaric oxygen (HBO) were investigated. Rats underwent middle cerebral artery occlusion and were assigned to control, tPA or tPA+HBO. Twenty-four hours, 7, 14 and 28 days were determined as observation time points. The accumulation of macrophage-like cells was semiquantitatively assessed by CD68 staining in the ischaemic area and ischaemic border zone, and linked to the clinical course. CD11b, ionized calcium binding adaptor molecule 1 (Iba), glial fibrillary acidic protein (GFAP) and Neuronal Nuclei (NeuN) were applied to reveal delayed glial and neuronal alterations. In all groups, the accumulation of macrophage-like cells increased distinctly from 24 hours to 7 days post ischaemia. tPA+HBO tended to decrease macrophage-like cell accumulation at day 14 and 28. Overall, a trend towards an association of increased accumulation and pronounced reduction of the neurological deficit was found. Concerning delayed inflammatory reactions, an activation of microglia and astrocytes with co-occurring neuronal loss was observed on day 28. Thereby, astrogliosis was found circularly in contrast to microglial activation directly in the ischaemic area. This study supports previous data on long-lasting inflammatory processes following experimental stroke, and additionally provides region-specific details on glial reactions. The tendency towards a decreasing macrophage-like cell accumulation after tPA+HBO needs to be discussed

  14. [Cerebellar stroke].

    PubMed

    Paradowski, Michał; Zimny, Anna; Paradowski, Bogusław

    2015-01-01

    Cerebellar stroke belongs to a group of rare diseases of vascular origin. Cerebellum, supplied by three pairs of arteries (AICA, PICA, SCA) with many anastomoses between them is less susceptible for a stroke, especially ischemic one. Diagnosis of the stroke in this region is harder due to lower sensibility of commonly used CT of the head in case of stroke suspicion. The authors highlight clinical symptoms distinguishing between vascular territories or topographical locations of the stroke, diagnostic procedures, classical and surgical treatment, the most common misdiagnoses are also mentioned. The authors suggest a diagnostic and therapeutic algorithm development, including rtPA treatment criteria for ischemic cerebellar stroke. PMID:26181157

  15. Severe slugging in a flexible S-shaped riser system: Experimental studies and transient simulation

    NASA Astrophysics Data System (ADS)

    Li, Wensheng; Guo, Liejin; Li, Nailiang

    2013-07-01

    Severe slugging, which could induce large-amplitude pressure and flow rate fluctuations, is a major and expensive problem in multiphase transportation systems of offshore oil production system. To avoid such problem is a basic requirement for flow assurance management. This study is an experimental and numerical investigation of severe slugging in a relatively long pipeline-riser system. A series of experiments on two-phase, air-water flow in a flexible Sshaped riser were carried out. The experimental system has a 114m long horizontal pipeline connected to a 19m long pipe which is inclined to -2degree from horizontal, followed by a 15.3m high riser operating at atmospheric end pressure. Four types of flow patterns were found and characterized by the pressure fluctuations at the bottom of the riser. A flow patter map for the prediction of severe slugging was developed based on the experimental results. The detailed characteristics of severe slugging such as pressure fluctuations, liquid holdup, under different gas-liquid superficial velocities were provided. A transient model to predict the flow behavior in the pipeline-S-shaped riser system was developed based on an existing model (OLGA). The modified model, which was tested against new experimental results obtained in this study, showed that the four types of flow patterns observed in the experiment were predicted with acceptable discrepancies. The flow pattern map was obtained using present model, as well as the detailed characteristics of severe slugging. In addition, the reasons for the difference between experimental and numerical results were analysed in this article. The motive of the numerical studies was to identify the areas that could not be reproduced by the present model and to give some suggestions for future models.

  16. Stem Cells May Offer New Hope to Stroke Survivors

    MedlinePlus

    ... news/fullstory_159163.html Stem Cells May Offer New Hope to Stroke Survivors Experimental procedure helped restore ... into the brain may give stroke patients a new shot at recovery long after their stroke occurred. " ...

  17. Stroke Rehabilitation

    MedlinePlus

    ... relearn skills they lose because of the damage. Rehabilitation can help them relearn those skills. Stroke can ... Problems with thinking and memory Emotional disturbances Stroke rehabilitation involves many kinds of health professionals. The goal ...

  18. Stroke Stories

    MedlinePlus

    ... this page please turn Javascript on. Feature: Stroke Rehabilitation Stroke Stories Past Issues / Spring 2013 Table of ... she has returned to an active life after rehabilitation. Tedy Bruschi: The New England Patriots linebacker was ...

  19. Preventing stroke

    MedlinePlus

    ... Partially-hydrogenated or hydrogenated fats Medical problems may lead to stroke Control your cholesterol and diabetes with ... increase the chance of blood clots, which can lead to stroke. Clots are more likely in women ...

  20. Stroke - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100218.htm Stroke - series—Part 1 To use the sharing features ... M. Editorial team. Related MedlinePlus Health Topics Ischemic Stroke A.D.A.M., Inc. is accredited by ...

  1. Know Stroke

    MedlinePlus

    ... Home Current Issue Past Issues Special Section Know Stroke Past Issues / Summer 2007 Table of Contents For ... D. Director, National Institute of Neurological Disorders and Stroke Photo courtesy of NIH/NINDS Welcome to this ...

  2. Pediatric Stroke

    PubMed Central

    Jeong, Goun; Lim, Byung Chan

    2015-01-01

    Pediatric stroke is relatively rare but may lead to significant morbidity and mortality. Along with the advance of brain imaging technology and clinical awareness, diagnosis of pediatric stroke is increasing wordwide. Pediatric stroke differs from adults in variable risk factor/etiologies, diverse and nonspecific clinical presentation depending on ages. This review will be discussed pediatric stroke focusing on their clinical presentations, diagnosis and etiologies/risk factors. PMID:26180605

  3. Is there an association between the prevalence of atrial fibrillation and severity and control of hypertension? The REasons for Geographic And Racial Differences in Stroke study.

    PubMed

    Bhatt, Hemal; Gamboa, Christopher M; Safford, Monika M; Soliman, Elsayad Z; Glasser, Stephen P

    2016-07-01

    The association of atrial fibrillation (AF) with the severity and control of hypertension (HTN) remains unclear. We analyzed data from the national biracial cohort of REasons for Geographic And Racial Differences in Stroke study. The AF prevalence ratios were estimated and full multivariable adjustment included demographics, risk factors, medication adherence, HTN duration, and antihypertensive medication classes. Of the 30,018 study participants (8.6% with AF), 4386 had normotension (4.3% with AF), 5916 had prehypertension (4.3 with AF%), 12,294 had controlled HTN (11.2% with AF), 5587 had uncontrolled HTN (8.1% with AF), 547 had controlled apparent treatment-resistant hypertension (aTRH) (19.2% with AF), and 1288 had uncontrolled aTRH (15.5% with AF). Compared with normotension, the AF prevalence ratios for prehypertension, controlled HTN, uncontrolled HTN, controlled aTRH, and uncontrolled aTRH groups in fully adjusted model were 1.01 (95% confidence interval: 0.84, 1.21), 1.42 (1.18, 1.71), 1.37 (1.14, 1.65), 1.17 (0.86, 1.58), and 1.42 (1.10, 1.84), respectively (P < .001). The prevalence of AF was similar among persons with HTN regardless of blood pressure level and antihypertensive treatment resistance. PMID:27324843

  4. Decline of microtubule-associated protein tau after experimental stroke in differently aged wild-type and 3xTg mice with Alzheimer-like alterations.

    PubMed

    Michalski, Dominik; Preißler, Hartmut; Hofmann, Sarah; Kacza, Johannes; Härtig, Wolfgang

    2016-08-25

    Stroke therapies are still limited to a minority of patients. Considering time-dependent aspects of stroke, the penumbra concept describes the transition from functional to permanent tissue damage. Thereby, the role of cytoskeletal elements, as for instance microtubules with associated tau remains poorly understood and is therefore not yet considered for therapeutic approaches. This study explored the expression of microtubule-associated protein tau related to neuronal damage in stroke-affected brain regions. Wild-type and triple-transgenic mice of 3, 7 and 12months of age and with an Alzheimer-like background underwent experimental stroke. After 24h, brain sections were used for immunofluorescence labeling of tau and Neuronal Nuclei (NeuN). Potential functional consequences of cellular alterations were explored by statistical relationships to the general health condition, i.e. neurobehavioral deficits and loss of body weight. Immunoreactivity for whole tau decreased significantly in ischemic areas, while the decline at the border zone was more drastic for tau-immunoreactivity compared with the diminished NeuN labeling. Quantitative analyses confirmed pronounced sensitivity for tau-immunoreactivity in the ischemic border zone. Decline of tau- as well as NeuN-immunoreactivity correlated with body weight loss during the 24-h observation period. In conclusion, microtubule-associated protein tau was robustly identified as a highly sensitive cytoskeletal constitute under ischemic conditions, suggesting a pivotal role during the transition process toward long-lasting tissue damage. Consequently, cytoskeletal elements appear as promising targets for novel therapeutic approaches with the objective to impede ischemia-induced irreversible cellular degradation. PMID:27189884

  5. Ischemic Strokes (Clots)

    MedlinePlus

    ... Quiz 5 Things to Know About Stroke Ischemic Strokes (Clots) Updated:Jul 12,2016 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  6. Announcement: National Stroke Awareness Month - May 2016.

    PubMed

    2016-01-01

    May is National Stroke Awareness Month, an observance that raises awareness of the signs and symptoms of stroke and encourages persons to act FAST (Face drooping, Arm weakness, Speech difficulty, Time to call 911) if someone is having a stroke. Stroke is the fifth leading cause of death in the United States and a leading cause of severe disability (1,2). In the United States, one person dies from stroke every 4 minutes (2). PMID:27171846

  7. Relation between stroke volume index to risk of death in patients with low-gradient severe aortic stenosis and preserved left ventricular function.

    PubMed

    Maor, Elad; Beigel, Roy; Grupper, Avishay; Kuperstein, Rafael; Hai, Ilan; Medvedofsky, Diego; Perelstein, Olga; Mazin, Israel; Ziv, Asaf; Goldenberg, Ilan; Feinberg, Micha S; Ben Zekry, Sagit

    2014-08-01

    The aim of the present study was to evaluate whether assessment of stroke volume index (SVI) can be used to improve risk stratification among patients with low-gradient severe aortic stenosis and preserved ejection fraction (EF). Study population comprised 409 patients with aortic valve area ≤1.00 cm(2), mean gradient <40 mm Hg, and a normal EF (≥50%) who were followed up in a tertiary referral center from 2004 to 2012. Echocardiographic parameters and clinical data were collected. Multivariate Cox proportional hazards regression modeling was used to evaluate the association between SVI and the risk of all-cause mortality. Mean age of study patients was 78 ± 11 years, and 42% were men. The mean SVI was 39 ± 7 ml/m(2) (tertile 1 = 32 ± 4 ml/m(2); tertile 2 = 39 ± 1 ml/m(2); tertile 3 = 47 ± 4 ml/m(2)). Multivariate analysis showed that the SVI was the most powerful echocardiographic parameter associated with long-term outcome: each 5 ml/m(2) reduction in SVI was associated with a 20% increase in adjusted mortality risk (p = 0.01). Consistently, Kaplan-Meier analysis showed that the cumulative probability of survival during 3 years of follow-up was 60%, 72%, and 73% among patients in the low-, intermediate-, and high-SVI groups, respectively (p = 0.012). Our findings suggest that in patients with low-gradient severe aortic stenosis and preserved EF, there is a graded inverse relation between SVI and the risk of long-term mortality. PMID:24948491

  8. JAK/STAT pathway regulation of GABAA receptor expression after differing severities of experimental TBI.

    PubMed

    Raible, Daniel J; Frey, Lauren C; Del Angel, Yasmin Cruz; Carlsen, Jessica; Hund, Dana; Russek, Shelley J; Smith, Bret; Brooks-Kayal, Amy R

    2015-09-01

    Synaptic inhibition in the adult brain is primarily mediated by the γ-aminobutyric acid (GABA) type A receptor (GABA(A)R). The distribution, properties, and dynamics of these receptors are largely determined by their subunit composition. Alteration of subunit composition after a traumatic brain injury (TBI) may result in abnormal increased synaptic firing and possibly contribute to injury-related pathology. Several studies have shown that the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathway can alter GABA(A)R subunit expression. The present study investigated changes in JAK/STAT pathway activation after two different severities of experimental TBI in the mouse using the controlled cortical impact (CCI) model. It also investigated whether modulating the activation of the JAK/STAT pathway after severe controlled cortical impact (CCI-S) with a JAK/STAT inhibitor (WP1066) alters post-traumatic epilepsy development and/or neurological recovery after injury. Our results demonstrated differential changes in both the activation of STAT3 and the expression of the GABA(A)R α1 and γ2 subunit levels that were dependent on the severity of the injury. The change in the GABA(A)R α1 subunit levels appeared to be at least partly transcriptionally mediated. We were able to selectively reverse the decrease in GABA(A)R α1 protein levels with WP1066 treatment after CCI injury. WP1066 treatment also improved the degree of recovery of vestibular motor function after injury. These findings suggest that the magnitude of JAK/STAT pathway activation and GABA(A)R α1 subunit level decrease is dependent on injury severity in this mouse model of TBI. In addition, reducing JAK/STAT pathway activation after severe experimental TBI reverses the decrease in the GABA(A)R α1 protein levels and improves vestibular motor recovery. PMID:26172316

  9. Cell therapy for stroke.

    PubMed

    Savitz, Sean I; Dinsmore, Jonathan H; Wechsler, Lawrence R; Rosenbaum, Daniel M; Caplan, Louis R

    2004-10-01

    Increasing experimental evidence suggests that cell transplantation can enhance recovery from stroke in animal models of focal cerebral ischemia. Clinical trials have been investigating the effects of a human immortalized neuronal cell line and porcine fetal neurons in stroke victims with persistent and stable deficits. Preclinical studies are focusing on the effects of human stem cells from various sources including brain, bone marrow, umbilical cord, and adipose tissue. This review presents an overview of preclinical and clinical studies on cell therapy for stroke. We emphasize the current, limited knowledge about the biology of implant sources and discuss special conditions in stroke that will impact the potential success of neurotransplantation in clinical trials. PMID:15717044

  10. Imaging acute ischemic stroke.

    PubMed

    González, R Gilberto; Schwamm, Lee H

    2016-01-01

    Acute ischemic stroke is common and often treatable, but treatment requires reliable information on the state of the brain that may be provided by modern neuroimaging. Critical information includes: the presence of hemorrhage; the site of arterial occlusion; the size of the early infarct "core"; and the size of underperfused, potentially threatened brain parenchyma, commonly referred to as the "penumbra." In this chapter we review the major determinants of outcomes in ischemic stroke patients, and the clinical value of various advanced computed tomography and magnetic resonance imaging methods that may provide key physiologic information in these patients. The focus is on major strokes due to occlusions of large arteries of the anterior circulation, the most common cause of a severe stroke syndrome. The current evidence-based approach to imaging the acute stroke patient at the Massachusetts General Hospital is presented, which is applicable for all stroke types. We conclude with new information on time and stroke evolution that imaging has revealed, and how it may open the possibilities of treating many more patients. PMID:27432672

  11. High severity experimental burns in Siberian larch forests increase permafrost thaw and larch tree regeneration

    NASA Astrophysics Data System (ADS)

    Alexander, H. D.; Davydov, S.; Zimov, N.; Mack, M. C.

    2013-12-01

    Global change models predict increased fire activity in boreal forests as climate warms and dries. We hypothesized that fire-driven decreases in soil organic layer (SOL) depth will (1) increase permafrost thaw by reducing the insulating capacity of the SOL and (2) improve seedbed conditions for tree regeneration. Over time, these changes will lead to altered patterns of above- and belowground carbon (C) accumulation. To test these hypotheses, we conducted plot-level experimental burns in July 2012 in a low-density, mature larch stand near the Northeast Science Station in Cherskii, Siberia. Dried fuels of naturally occurring vegetation were added to plots to achieve four burn severity treatments based on residual SOL depths: control, low (> 8 cm), moderate (5-8 cm), and high severity (2-5 cm). Pre-fire and during two growing seasons post-fire, we measured thaw depth, soil moisture, and soil temperature to determine severity effects on permafrost thaw. We also sowed larch seeds in fall 2012 and quantified germination rates the following growing season. By 1 wk post-fire, thaw depth was 15-25 cm deeper in plots burned at high severity (55 cm) compared to other treatments (30-40 cm). These differences in thaw depth with burn severity were maintained during the subsequent growing season and were associated with increased soil temperature and moisture. Larch regeneration was 10x higher on severely burned plots than those unburned. Our findings highlight the potential for increased fire severity to degrade permafrost and alter successional dynamics and patterns of C accumulation.

  12. Stroke and Stroke-like Episodes in Muscle Disease

    PubMed Central

    Finsterer, Josef

    2012-01-01

    Background: Though not obvious at a first glance, myopathies may be associated with ischemic stroke. Stroke-like episodes resemble ischemic stroke only to some extent but are a unique feature of certain mitochondrial disorders with a pathogenesis at variance from that of ischemic stroke. Only limited data are available about ischemic stroke in pri-mary myopathies and the management of stroke-like episodes in mitochondrial disorders. This review aims to summarize and discuss current knowledge about stroke in myopathies and to delineate stroke-like episodes from ischemic stroke. Methods: Literature review via PubMED using the search terms “stroke”, “cerebrovascular”, “ischemic event”, “stroke-like episode”, “stroke-mimic”, “mitochondrial disorder”. Results: Stroke in myopathies is most frequently cardioembolic due to atrial fibrillation or atrial flutter, dilated cardio-myopathy, or left-ventricular hypertrabeculation (noncompaction). The second most frequent cause of stroke in myopathies is angiopathy from atherosclerosis or vasculitis, which may be a feature of inflammatory myopathies. Athero-sclerosis may either result from classical risk factors, such as diabetes, arterial hypertension, hyperlpidemia, or smoking, associated with muscle disease, or may be an inherent feature of a mitochondrial disorder. In case of severe heart failure from cardiomyopathy as a manifestation of muscle disease low flow infarcts may occur. Thrombophilic stroke has been described in polymyositis and dermatomyositis in association with anti-phospholipid syndrome. Stroke-like episodes occur particularly in mitochondrial encephalopathy, lactacidosis and stroke-likeepisode syndrome but rarely also in Leigh-syndrome and other mitochondrial disorders. Stroke-like episodes are at variance from ischemic stroke, pathogenically, clinically and on imaging. They may be the manifestation of a vascular, metabolic or epileptic process and present with predominantly vasogenic

  13. Experimental investigation of rotor-stator interaction in a centrifugal pump with several vaned diffusers

    NASA Technical Reports Server (NTRS)

    Arndt, N.; Acosta, A. J.; Brennen, C. E.; Caughey, T. K.

    1990-01-01

    Steady and unsteady diffuser vane pressure measurements have been conducted with a two-dimensional test impeller, in an experimental investigation of rotor-stator interaction within a centrifugal pump having several vaned diffusers, under conditions of different flow coefficients and different radial gaps between the impeller blade trailing edge and the diffuser vane leading edge. The largest pressure fluctuations on the diffuser vanes and the impeller blades were found to be of the same order of magnitude as the total pressure rise across the pump. Increasing the number of diffuser vanes was found to result in a significant decrease of impeller blade pressure fluctuations.

  14. First Experimental In Vivo Model of Enhanced Dengue Disease Severity through Maternally Acquired Heterotypic Dengue Antibodies

    PubMed Central

    Ng, Jowin Kai Wei; Zhang, Summer Lixin; Tan, Hwee Cheng; Yan, Benedict; Maria Martinez Gomez, Julia; Tan, Wei Yu; Lam, Jian Hang; Tan, Grace Kai Xin; Ooi, Eng Eong; Alonso, Sylvie

    2014-01-01

    Dengue (DEN) represents the most serious arthropod-borne viral disease. DEN clinical manifestations range from mild febrile illness to life-threatening hemorrhage and vascular leakage. Early epidemiological observations reported that infants born to DEN-immune mothers were at greater risk to develop the severe forms of the disease upon infection with any serotype of dengue virus (DENV). From these observations emerged the hypothesis of antibody-dependent enhancement (ADE) of disease severity, whereby maternally acquired anti-DENV antibodies cross-react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Although in vitro and in vivo experimental set ups have indirectly supported the ADE hypothesis, direct experimental evidence has been missing. Furthermore, a recent epidemiological study has challenged the influence of maternal antibodies in disease outcome. Here we have developed a mouse model of ADE where DENV2 infection of young mice born to DENV1-immune mothers led to earlier death which correlated with higher viremia and increased vascular leakage compared to DENV2-infected mice born to dengue naïve mothers. In this ADE model we demonstrated the role of TNF-α in DEN-induced vascular leakage. Furthermore, upon infection with an attenuated DENV2 mutant strain, mice born to DENV1-immune mothers developed lethal disease accompanied by vascular leakage whereas infected mice born to dengue naïve mothers did no display any clinical manifestation. In vitro ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice born to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice born to DENV1-immune mothers, thus reproducing epidemiological observations. Overall, this work provides direct in vivo demonstration of the role of maternally acquired heterotypic dengue antibodies in the enhancement of dengue

  15. Combined Medication of Lovastatin with Rolipram Suppresses Severity of Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Paintlia, Ajaib S; Paintlia, Manjeet K; Singh, Inderjit; Singh, Avtar K

    2008-01-01

    Combinations of new medications or existing therapies are gaining momentum over monotherapy to treat central nervous system (CNS) demyelinating diseases including multiple sclerosis (MS). Recent studies established that statins (HMG-CoA reductase inhibitors) are effective in experimental autoimmune encephalomyelitis (EAE), an MS model and are promising candidates for future MS medication. Another drug, rolipram (phosphodiesterase-4 inhibitor) ameliorates the clinical severity of EAE via induction of various anti-inflammatory and neuroprotective activities. In this study, we tested whether combining the suboptimal doses of these drugs can suppress the severity of EAE. Prophylactic studies revealed that combined treatment with suboptimal doses of statins perform better than their individually administered optimal doses in EAE as evidenced by delayed clinical scores, reduced disease severity, and rapid recovery. Importantly, combination therapy suppressed the progression of disease in an established EAE case via attenuation of inflammation, axonal loss and demyelination. Combination treatment attenuated inflammatory TH1 and TH17 immune responses and induced TH2-biased immunity in the peripheral and CNS as revealed by serological, quantitative, and immunosorbant assay-based analyses. Moreover, the expansion of T regulatory (CD25+/Foxp3+) cells and self-immune tolerance was apparent in the CNS. These effects of combined drugs were reduced or minimal with either drug alone in this setting. In conclusion, our findings demonstrate that the combination of these drugs suppresses EAE severity and provides neuroprotection thereby suggesting that this pharmacological approach could be a better future therapeutic strategy to treat MS patients. PMID:18775426

  16. Flexures for large stroke electrostatic actuation in MEMS

    NASA Astrophysics Data System (ADS)

    Krijnen, B.; Brouwer, D. M.

    2014-01-01

    The stroke of a microelectromechanical systems (MEMS) stage suspended by a flexure mechanism and actuated by electrostatic comb-drives is limited by pull-in. A method to analyze the electrostatic stability of a flexure mechanism and to optimize the stroke with respect to the footprint of flexure mechanisms is presented. Four flexure mechanisms for large stroke are investigated; the standard folded flexure, the slaved folded flexure, the tilted folded flexure and the Watt flexure. Given a certain stroke and load force, the flexures are optimized to have a minimum wafer footprint. From these optimizations it is concluded that the standard folded flexure mechanism is the best flexure mechanism for relatively small strokes (up to ±40 μm) and for larger strokes it is better to use the tilted folded flexure. Several optimized flexure mechanisms have been fabricated and experimentally tested to reach a stroke of ±100 μm. The displacement of the fabricated stages as a function of the actuation voltage could be predicted with 82% accuracy, limited by the fairly large tolerances of our fabrication process.

  17. Where Have All the Rodents Gone? The Effects of Attrition in Experimental Research on Cancer and Stroke.

    PubMed

    Holman, Constance; Piper, Sophie K; Grittner, Ulrike; Diamantaras, Andreas Antonios; Kimmelman, Jonathan; Siegerink, Bob; Dirnagl, Ulrich

    2016-01-01

    Given small sample sizes, loss of animals in preclinical experiments can dramatically alter results. However, effects of attrition on distortion of results are unknown. We used a simulation study to analyze the effects of random and biased attrition. As expected, random loss of samples decreased statistical power, but biased removal, including that of outliers, dramatically increased probability of false positive results. Next, we performed a meta-analysis of animal reporting and attrition in stroke and cancer. Most papers did not adequately report attrition, and extrapolating from the results of the simulation data, we suggest that their effect sizes were likely overestimated. PMID:26726833

  18. An experimental test of the 'transmission-line model' of electromagnetic radiation from triggered lightning return strokes

    NASA Technical Reports Server (NTRS)

    Willett, J. C.; Idone, V. P.; Orville, R. E.; Leteinturier, C.; Eybert-Berard, A.

    1988-01-01

    Peak currents, two-dimensional average propagation speeds, and electric field waveforms for a number of subsequent return strikes in rocket-triggered lightning flashes were measured in order to test the 'transmission-line model' of return-stroke radiation of Uman and McLain (1970). Reasonable agreement is found between the propagation speeds measured with the streak camera and those deduced from the transmission-line model. A modification of the model is proposed in which two wave fronts travel upward and downward away from a junction point a short distance above the ground.

  19. Growth factors in ischemic stroke

    PubMed Central

    Lanfranconi, S; Locatelli, F; Corti, S; Candelise, L; Comi, G P; Baron, P L; Strazzer, S; Bresolin, N; Bersano, A

    2011-01-01

    Abstract Data from pre-clinical and clinical studies provide evidence that colony-stimulating factors (CSFs) and other growth factors (GFs) can improve stroke outcome by reducing stroke damage through their anti-apoptotic and anti-inflammatory effects, and by promoting angiogenesis and neurogenesis. This review provides a critical and up-to-date literature review on CSF use in stroke. We searched for experimental and clinical studies on haemopoietic GFs such as granulocyte CSF, erythropoietin, granulocyte-macrophage colony-stimulating factor, stem cell factor (SCF), vascular endothelial GF, stromal cell-derived factor-1α and SCF in ischemic stroke. We also considered studies on insulin-like growth factor-1 and neurotrophins. Despite promising results from animal models, the lack of data in human beings hampers efficacy assessments of GFs on stroke outcome. We provide a comprehensive and critical view of the present knowledge about GFs and stroke, and an overview of ongoing and future prospects. PMID:20015202

  20. Apigenin-7-O-β-D-(-6''-p-coumaroyl)-Glucopyranoside Treatment Elicits Neuroprotective Effect against Experimental Ischemic Stroke

    PubMed Central

    Cai, Min; Ma, Yulong; Zhang, Wei; Wang, Shiquan; Wang, Ying; Tian, Li; Peng, Zhengwu; Wang, Huaning; Qingrong, Tan

    2016-01-01

    Stroke is the major cause of permanent disability and mortality in China. Apigenin-7-O-β-D-(-6''-p-coumaroyl)-glucopyranoside (APG) is a glycoside subtype of apigenin and has the antioxidant activity; however, whether and how it plays a neuroprotective role following cerebral ischemia remains unknown. In present study, we adopted the oxygen glucose/reperfusion model in PC12 cells, bilateral common carotid artery occlusion model in C57B6 mice and middle cerebral artery occlusion model in SD rats to observe the therapeutic effects of APG on ischemic stroke. We also discussed the underlying mechanism. Treatment with 0.4 μg/ml or 0.8 μg/ml APG promoted cell viability and proliferation, reduced LDH release and apoptotic cell death levels in PC12 cells. Treatment with 50 mg/kg or 100 mg/kg APG at 30 minutes after reperfusion improved neurological outcomes in vivo, as demonstrated by elevation of neurological scores in both mice and rats. It also increased the number of survival neurons in mice and reduced infarct volume in rats. APG also increased the contents of Mn-SOD and the phosphorylation level of STAT3, elevated the antioxidant activity and reduced oxidative productions. These findings revealed a neuroprotective effect of APG, which possibly induced by the STAT3 phosphorylation-mediated Mn-SOD up-regulation. PMID:26722216

  1. Global specialized stroke care delivery models.

    PubMed

    Theofanidis, Dimitrios; Savopoulos, Christos; Hatzitolios, Apostolos

    2016-03-01

    Stroke services still vary enormously from country to country, with many countries providing no special services at all. The aim of this article is to provide a concise overview of the various types of acute stroke delivery systems at present available and critically describe merits and shortcomings. A systematic literature review was undertaken from 1990 to July 2014. Several models for stroke services have been developed mostly in the past 3 decades, mainly in the Western world. These include state-of-the-art stroke services ranging from highly specialized stroke centers to mobile stroke units for the community. In this light, the recommendations of the structure and organization of stroke units and stroke centers by the European Stroke Organization were recently published. What differentiates the various models of stroke care delivery across the globe is the diversity of services ranging from low key conventional care to highly sophisticated facilities with life saving interventional features via integrated stroke care infrastructure. Effective in-hospital care for stroke should start in the emergency department where a swift and appropriate diagnosis should be made. The role of all brain neuroimaging procedures should have a defined a priori and proper demarcation between actions according to updated stroke care pathways and clinical protocols, which should be followed closely. These essential actions initiated by well-trained staff in the emergency department, should then be carried on in dedicated stroke facilities that is, a stroke unit. PMID:26897346

  2. Stroke Warning Signs

    MedlinePlus

    ... News Advocate Stroke Warning Signs Quiz Stroke Warning Signs and Symptoms THINK YOU ARE HAVING A STROKE? ... Learn more stroke signs and symptoms >>>> Stroke Warning Signs Hip-Hop F.A.S.T. Video Updated Guidelines ...

  3. Covered Stent Membrane Design for Treatment of Atheroembolic Disease at Carotid Artery Bifurcation and Prevention of Thromboembolic Stroke: An In Vitro Experimental Study.

    PubMed

    Kabinejadian, Foad; Nezhadian, Mercedeh Kaabi; Cui, Fangsen; Ho, Pei; Leo, Hwa Liang

    2016-02-01

    In this study, a polymeric membrane has been designed and developed for carotid stents to prevent detachment of emboli from the arterial wall and subsequent stroke, while maintaining side-branch flow. Prototypes of different geometrical design parameters have been fabricated and their performance has been evaluated in vitro under physiological pulsatile flow condition in a life-size silicone anastomotic model of carotid artery bifurcation. These evaluations include both quantitative and qualitative experimental (in vitro) assessments of emboli prevention capability, side-branch flow preservation, and flow visualization. The covered stents with the novel membrane demonstrated significantly higher emboli prevention capability than the corresponding bare nitinol stent as well as some earlier related designs, while preserving more than 93% of the original flow of the external carotid artery (ECA). Flow in the ECA through these covered stents was uniform without evidence of undesirable flow recirculation or retrograde flow that might predispose the vessel wall to intimal thickening and atherosclerotic plaque formation. This study demonstrated the potential of these novel covered stent designs for the treatment of carotid atherosclerotic stenosis and prevention of late embolic stroke. However, further in vivo investigations of biological effects and mechanical performance of this covered stent design (e.g., its thrombogenicity potential and biocompatibility) are warranted. PMID:26147531

  4. A dual-labeled Annexin A5 is not suited for SPECT imaging of brain cell death in experimental murine stroke

    PubMed Central

    Zille, Marietta; Harhausen, Denise; De Saint-Hubert, Marijke; Michel, Roger; Reutelingsperger, Chris P; Dirnagl, Ulrich; Wunder, Andreas

    2014-01-01

    Cell death is one of the pathophysiological hallmarks after stroke. Markers to image cell death pathways in vivo are highly desirable. We previously showed that fluorescently labeled Annexin A5 (AnxA5), which binds specifically to phosphatidylserine (PS) on dead/dying cells, can be used in experimental stroke for monitoring cell death with optical imaging. Here we investigated whether dual-labeled AnxA5 (technetium and fluorescence label) can be used for single-photon emission computed tomography (SPECT) of cell death in the same model. C57Bl6/N mice were subjected to 60-minute middle cerebral artery occlusion (MCAO) and underwent SPECT imaging at 24, 48, and 72 hours afterwards. They were injected intravenously with either PS-binding AnxA5 or the nonfunctional AnxA5 (negative control), labeled with 99mTc and Alexa Fluor 568, respectively. After SPECT imaging, brain sections were cut for autoradiography and fluorescence microscopy. Ethanol-induced cell death in the femur muscle was used as positive control. We detected dual-labeled AnxA5 in the model of ethanol-induced cell death in the femur muscle, but not after MCAO at any time point, either with SPECT or with ex vivo autoradiography or fluorescence microscopy. Dual-labeled AnxA5 appears to be unsuited for visualizing death of brain cells in this MCAO model. PMID:24984896

  5. Recovery of Dysphagia in Lateral Medullary Stroke

    PubMed Central

    Gupta, Hitesh; Banerjee, Alakananda

    2014-01-01

    Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function. PMID:25045555

  6. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    PubMed

    Cousins, Scott W; Espinosa-Heidmann, Diego G; Miller, Daniel M; Pereira-Simon, Simone; Hernandez, Eleut P; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  7. Macrophage Activation Associated with Chronic Murine Cytomegalovirus Infection Results in More Severe Experimental Choroidal Neovascularization

    PubMed Central

    Cousins, Scott W.; Espinosa-Heidmann, Diego G.; Miller, Daniel M.; Pereira-Simon, Simone; Hernandez, Eleut P.; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D.

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  8. Ischemic Stroke.

    PubMed

    Capriotti, Teri; Murphy, Teresa

    2016-05-01

    Each year, more than 795,000 people in the United States suffer a stroke and by 2030, it is estimated that 4% of the U.S. population will have had a stroke. Home healthcare clinicians will be increasingly called upon to assist stroke survivors and their caregivers adjust to disability and assist the survivor during their reintegration into the community. Therapeutic modalities are changing with advanced technology. Great strides are being made in the treatment of acute stroke; particularly endovascular interventions. More patients are surviving the acute stroke event and therefore will need to learn how to live with various degrees of disability. It is important for home healthcare clinicians to understand the process from acute event to medical stabilization, and from rehabilitation to long-term adaptation. PMID:27145407

  9. Probiotics increase T regulatory cells and reduce severity of experimental colitis in mice

    PubMed Central

    Zhao, Hai-Mei; Huang, Xiao-Ying; Zuo, Zhi-Qin; Pan, Qi-Hong; Ao, Mei-Ying; Zhou, Feng; Liu, Hong-Ning; Liu, Zhi-Yong; Liu, Duan-Yong

    2013-01-01

    AIM: To investigate the effect of probiotics on regulating T regulatory cells and reducing the severity of experimental colitis in mice. METHODS: Forty C57/BL mice were randomly divided into four groups. Colitis was induced in the mice using 2,4,6-trinitrobenzene sulfonic acid (TNBS). After 10-d treatment with Bifico capsules (combined bifidobacterium, lactobacillus and enterococcus), body weight, colonic weight, colonic weight index, length of colon, and histological scores were evaluated. CD4+CD25+Foxp3+T cell in mesenteric lymph nodes were measured by flow cytometry, and cytokines in colonic tissue homogenates were analyzed by a cytometric bead array. RESULTS: The colonic weight index and the colonic weight of colitis mice treated with Bifico were lower than that of TNBS-induced mice without treatment. However, colonic length and percent of body weight amplification were higher than in TNBS-induced mice without treatment. Compared with TNBS-induced mice without treatment, the level of CD4+CD25+Foxp3+T cells in mesenteric lymph nodes, the expression of interleukin (IL)-2, IL-4 and IL-10 in colonic tissues from colitis mice treated with Bifico were upregulated, and tumor necrosis factor-α and interferon-γ were downregulated. CONCLUSION: Probiotics effectively treat experimental colitis by increasing CD4+CD25+Foxp3+T cell and regulating the balance of Th1 and Th2 cytokines in the colonic mucosa. PMID:23430765

  10. Stroke genetics: a review and update.

    PubMed

    Lindgren, Arne

    2014-09-01

    Stroke genetics includes several topics of clinical interest, including (1) molecular genetic variations affecting risk of monogenic stroke syndromes; (2) molecular genetic variations affecting risk of common stroke syndromes, sometimes with specific effects on risk of specific main types of stroke or subtypes of ischemic and hemorrhagic stroke; (3) genetics of conditions associated with stroke risk e.g. white matter hyperintensities, atrial fibrillation and hypertension; (4) hereditary causes of familial aggregation of stroke; (5) epigenetic impact on protein expression during acute brain injury; (6) genetic influence on stroke recovery; and (7) pharmacogenetics. Genetic research methods include candidate gene studies; Genome Wide Association Studies; family studies; RNA and protein analyses; and advanced computer-aided analytical methods to detect statistically significant associations. Several methods that could improve our knowledge of stroke genetics are being developed e.g.: Exome content analysis; Next-generation sequencing; Whole genome sequencing; and Epigenetics. During 2012-2014, several Single Nucleotide Polymorphisms (SNPs) have been related to common ischemic stroke risk. Certain SNPs have been associated with risk of specific ischemic stroke subtypes such as large vessel disease and cardiac embolism, particular subtypes of intracerebral hemorrhage (ICH), especially lobar ICH, and with prognosis after ICH. Large international studies on stroke recovery and exome content are ongoing. Advanced mathematical models have been used to study how several SNPs can act together and increase stroke risk burden. Such efforts require large numbers of patients and controls, which is achieved by co-operation in large international consortia such as the International Stroke Genetics Consortium. This overview includes an introduction to genetics, stroke genetics in general, and different genetic variations that may influence stroke risk. It presents some of the latest

  11. Regulatory T Cells in Post-stroke Immune Homeostasis.

    PubMed

    Liesz, Arthur; Kleinschnitz, Christoph

    2016-08-01

    The secondary neuroinflammatory response has come into focus of experimental stroke research. Immunological mechanisms after acute stroke are being investigated in the hope to identify novel and druggable pathways that contribute to secondary infarct growth after stroke. Among a variety of neuroimmunological events after acute brain ischemia, including microglial activation, brain leukocyte invasion, and secretion of pro-inflammatory factors, lymphocytes have been identified as the key leukocyte subpopulation driving the neuroinflammatory response and contributing to stroke outcome. Several studies have shown that pro-inflammatory lymphocyte subpopulations worsen stroke outcome and that inhibiting their invasion to the injured brain is neuroprotective. In contrast to the effector functions of pro-inflammatory lymphocytes, regulatory T cells (Treg) are critically involved in maintaining immune homeostasis and have been characterized as disease-limiting protective cells in several inflammatory conditions, particularly in primary inflammatory diseases of the central nervous system (CNS). However, due to the complex function of regulatory cells in immune homeostasis and disease, divergent findings have been described for the role of Treg in stroke models. Emerging evidence suggests that this discrepancy arises from potentially differing functions of Treg depending on the predominant site of action within the neurovascular unit and the surrounding inflammatory milieu. This article will provide a comprehensive review of current findings on Treg in brain ischemia models and discuss potential reasons for the observed discrepancies. PMID:27030356

  12. The extent of ultrastructural spinal cord pathology reflects disease severity in experimental autoimmune encephalomyelitis.

    PubMed

    Gruppe, Traugott L; Recks, Mascha S; Addicks, Klaus; Kuerten, Stefanie

    2012-09-01

    Experimental autoimmune encephalomyelitis (EAE) has been studied for decades as an animal model for human multiple sclerosis (MS). Here we performed ultrastructural analysis of corticospinal tract (CST) and motor neuron pathology in myelin oligodendrocyte glycoprotein (MOG) peptide 35-55- and MP4-induced EAE of C57BL/6 mice. Both models were clinically characterized by ascending paralysis. Our data show that CST and motor neuron pathology differentially contributed to the disease. In both MOG peptide- and MP4-induced EAE pathological changes in the CST were evident. While the MP4 model also encompassed severe motor neuron degeneration in terms of rough endoplasmic reticulum alterations, the presence of intracytoplasmic vacuoles and nuclear dissolution, both models showed motor neuron atrophy. Features of axonal damage covered mitochondrial swelling, a decrease in nearest neighbor neurofilament distance (NNND) and an increase of the oligodendroglial cytoplasm inner tongue. The extent of CST and motor neuron pathology was reflective of the severity of clinical EAE in MOG peptide- and MP4-elicited EAE. Differential targeting of CNS gray and white matter are typical features of MS pathology. The MOG peptide and MP4 model may thus be valuable tools for downstream studies of the mechanisms underlying these morphological disease correlates. PMID:22806903

  13. Stroke and Native Hawaiians/Pacific Islanders

    MedlinePlus

    ... Other Pacific Islander > Stroke Stroke and Native Hawaiians/Pacific Islanders Native Hawaiians/Pacific Islanders were four times more likely than non- ... a stroke in 2010. In general, Native Hawaiian/Pacific Islander adults have developed several of the high ...

  14. Stroke - risk factors

    MedlinePlus

    Preventing stroke; Stroke - prevention; CVA - prevention; TIA - prevention ... Biology; Council on Hypertension. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from ...

  15. Preventing stroke

    MedlinePlus

    Stroke - prevention; CVA - prevention; cerebral vascular accident - prevention; TIA - prevention, transient ischemic attack - prevention ... Clinical Cardiology; Council on Functional Genomics and ... Council on Hypertension. Guidelines for the primary prevention ...

  16. After Stroke

    MedlinePlus

    ... much function as possible. Learn more about spasticity . Deep Venous Thrombosis – Deep venous thrombosis happens when a clot forms in ... from all RESCUE fact sheets. American Stroke Association Web: www.strokeassociation.org * Phone: 1-888-478-7653 ...

  17. Stroke - discharge

    MedlinePlus

    ... People who have had a stroke may have speech or language problems. Here are some tips for your family and care givers: Keep distractions and noise down. Keep your voice lower. Move to a quieter room. DO NOT ...

  18. Stroke Treatments

    MedlinePlus

    ... weakened blood vessels that also cause hemorrhagic stroke: aneurysms and arteriovenous malformations (AVMs). Treatment differs depending on ... the leg or arm, then guided to the aneurysm or AVM ; it then deposits a mechanical agent, ...

  19. Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin

    PubMed Central

    Yang, Fei; Fu, Han; Lu, Yun-Fei; Wang, Xiao-Liang; Yang, Yan; Yang, Fan; Yu, Yao-Qing; Sun, Wei; Wang, Jia-Shuang; Costigan, Michael; Chen, Jun

    2015-01-01

    Intractable central post-stroke pain (CPSP) is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV (ITC) injection. Then, we evaluated the efficacy of gabapentin (GBP), an anticonvulsant that binds the voltage-gated Ca2+ channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration (1, 10, or 100 mg/kg) on day 7 post-ITC, with significant effects lasting at least 5 h for the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness (drug tolerance) at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system. PMID:25370442

  20. Helicobacter pylori infection reduces disease severity in an experimental model of multiple sclerosis

    PubMed Central

    Cook, Katherine W.; Crooks, James; Hussain, Khiyam; O’Brien, Kate; Braitch, Manjit; Kareem, Huner; Constantinescu, Cris S.; Robinson, Karen; Gran, Bruno

    2015-01-01

    Recent research has demonstrated that infection with the bacterial pathogen Helicobacter pylori is less common amongst patients with multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). We aimed to compare the prevalence of H. pylori amongst MS patients and healthy controls, and also investigated the impact of this infection on an animal model for MS, experimental autoimmune encephalomyelitis (EAE). The H. pylori status of 71 MS patients and 42 healthy controls was determined by serology. Groups of C57BL/6 mice were infected with H. pylori, or given diluent alone as a placebo, prior to inducing EAE. Clinical scores were assessed for all mice, and spleens and spinal cord tissue were harvested. CD4+ T cell subsets were quantified by flow cytometry, and T cell proliferation assays were performed. In MS patients the seroprevalence of H. pylori was half that of healthy controls (p = 0.018). Over three independent experiments, prior H. pylori infection had a moderate effect in reducing the severity of EAE (p = 0.012). In line with this, the antigen-specific T cell proliferative responses of infected animals were significantly reduced (p = 0.001), and there was a fourfold reduction in the number of CD4+ cells in the CNS. CD4+ populations in both the CNS and the spleens of infected mice also contained greatly reduced proportions of IFNγ+, IL-17+, T-bet+, and RORγt+ cells, but the proportions of Foxp3+ cells were equivalent. There were no differences in the frequency of splenic CD4+cells expressing markers of apoptosis between infected and uninfected animals. H. pylori was less prevalent amongst MS patients. In mice, the infection exerted some protection against EAE, inhibiting both Th1 and Th17 responses. This could not be explained by the presence of increased numbers of Foxp3+ regulatory T cells, or T cell apoptosis. This is the first direct experimental evidence showing that H. pylori may provide protection against

  1. Neuroprotective effect of naringenin is mediated through suppression of NF-κB signaling pathway in experimental stroke.

    PubMed

    Raza, S S; Khan, M M; Ahmad, A; Ashafaq, M; Islam, F; Wagner, A P; Safhi, M M; Islam, F

    2013-01-29

    Oxidative stress and inflammation play an integral role in the pathogenesis of cerebral ischemia that leads to a cascade of events culminating in the death of neurons and their supporting structures. The signaling pathways that link these events are not fully understood. Recent studies have demonstrated a close link between the nuclear factor-κB (NF-κB) signaling pathway and cerebral ischemia/reperfusion (I/R)-induced inflammation. Flavonoids have been suggested to exert human health benefits by anti-oxidant and anti-inflammatory mechanisms. In this study we undertook a pharmacological approach to investigate the ability of naringenin, a potent flavonoid, to prevent oxidative stress and NF-κB-mediated inflammatory brain damage in the rat model of focal cerebral I/R injury. To test this hypothesis, male Wistar rats were pretreated with naringenin once daily for 21 days and then subjected to 1h of middle cerebral artery occlusion followed by 23 h of reperfusion. Naringenin treatment successfully upregulates the antioxidant status, decreases the infarct size and lowers the levels of myeloperoxidase, nitric oxide and cytokines, besides functional recovery returned close to the baseline. Moreover, immunohistochemical and Western blot analyses clearly demonstrated that naringenin treatment limits glial activation and downregulates the NF-κB expression level and their target genes. These results show, prophylactic treatment with naringenin improved functional outcomes and abrogated the ischemic brain injury by suppressing NF-κB-mediated neuroinflammation. The present study suggests that naringenin may be used as a potential neuroprotectant in patients at high risk of ischemic stroke. PMID:23103795

  2. A High Soy Diet Reduces Programmed Cell Death and Enhances Bcl-xL Expression In Experimental Stroke

    PubMed Central

    Lovekamp-Swan, Tara; Glendenning, Michele; Schreihofer, Derek A.

    2009-01-01

    Soy phytoestrogens have been proposed as an alternative to estrogen replacement therapy and have demonstrated potential neuroprotective effects in the brain. We have shown that a high soy diet significantly reduces infarct size following permanent middle cerebral artery occlusion (MCAO). Here, we tested the hypothesis that a high soy diet would attenuate programmed cell death after stroke. Adult female Sprague-Dawley rats were ovariectomized and fed either an isoflavone-reduced diet (IFP) or a high soy diet (SP) for 2 weeks before undergoing 90 minutes of transient MCAO (tMCAO) followed by 22.5 hr reperfusion. Infarct size, as assessed by TTC staining, was significantly reduced by a high soy diet (p< 0.05). Apoptosis in the ischemic cortex, measured by TUNEL staining, was significantly reduced by the high soy diet. The number of active caspase-3 positive cells and caspase-mediated α-spectrin cleavage was also significantly decreased in the ischemic cortex of SP rats. Furthermore, nuclear translocation of apoptosis-inducing factor (AIF) was significantly reduced in the ischemic cortex of SP rats. Soy significantly increased bcl-xL mRNA and protein expression in the ischemic cortex compared to IFP rats. Immunohistochemistry revealed increased neuronal expression of bcl-2 and bcl-xL in the ischemic cortex of both IFP and SP rats following tMCAO. These results suggest that a high soy diet decreases both caspase-dependent and caspase-independent programmed cell death following tMCAO. Further, a high soy diet enhances expression of the cell survival factor bcl-xL following tMCAO, contributing to the neuroprotective effects of soy in the ischemic cortex. PMID:17706879

  3. Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling.

    PubMed

    Miao, Yanping; Zhao, Sheng; Gao, Yang; Wang, Ruijun; Wu, Qiong; Wu, Hui; Luo, Tianyou

    2016-03-01

    The effects of curcumin (CCM) on cerebral ischemia/reperfusion injury are not well understood. The aim of this study was to investigate whether CCM attenuates inflammation and mitochondrial dysfunction in a rat model of cerebral ischemia/reperfusion injury and whether Sirt1 is involved in these potential protective effects. Sirtinol, a Sirt1 inhibitor, was used to elucidate the underlying mechanism. Rats were subjected to 2h of transient middle cerebral artery occlusion (MCAO), followed by reperfusion for 24h. Brain magnetic resonance imaging (MRI) was used to detect infarct volumes. Neurological scores and brain water content were also assessed. Levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in the brain were detected using commercial enzyme-linked immunosorbent assay (ELISA) kits. Expression of SIRT1, acetylated p53 (Ac-p53), Bcl-2, and Bax was measured by western blotting. Our results suggested that CCM exerted a neuroprotective effect, as shown by reduced infarct volumes and brain edema and improved neurological scores. CCM also exerted anti-inflammatory effects, as indicated by decreased TNF-α and IL-6 levels in the brain. CCM elevated mitochondrial membrane potential, mitochondrial complex I activity, and mitochondrial cytochrome c levels, but reduced cytosolic cytochrome c levels. Moreover, CCM upregulated SIRT1 and Bcl-2 expression and downregulated Ac-p53 and Bax expression. These effects of CCM were abolished by sirtinol. In conclusion, our results demonstrate that CCM treatment attenuates ischemic stroke-induced brain injury via activation of SIRT1. PMID:26639783

  4. CD28 superagonist-mediated boost of regulatory T cells increases thrombo-inflammation and ischemic neurodegeneration during the acute phase of experimental stroke.

    PubMed

    Schuhmann, Michael K; Kraft, Peter; Stoll, Guido; Lorenz, Kristina; Meuth, Sven G; Wiendl, Heinz; Nieswandt, Bernhard; Sparwasser, Tim; Beyersdorf, Niklas; Kerkau, Thomas; Kleinschnitz, Christoph

    2015-01-01

    While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion. Antibody-mediated expansion of Treg enhanced stroke size and worsened functional outcome. Mechanistically, Treg increased thrombus formation in the cerebral microvasculature. These findings confirm that Treg promote thrombo-inflammatory lesion growth during the acute stage of ischemic stroke. PMID:25315859

  5. [Reducing the burden of stroke in Israel].

    PubMed

    Tanne, David; Goldbourt, Uri

    2008-11-01

    Stroke is the third most common cause of death in Israel. Stroke is a leading cause of severe long-term disability and is associated with staggering economic costs. Ethnic variations observed in stroke mortality rates support that undetermined inherent genetic or sociocultural differences act to increase stroke mortality rates in immigrants from Asia and North Africa over that predicted from their profile of traditional risk factors. In accordance with other Western countries, there has been a decline in mortality rates from stroke, concomitantly with a decline observed in coronary heart disease mortality. With the aging of the population, the burden of stroke is projected to further increase. Moreover, brain infarcts detected by brain imaging are 5-times more common than the clinical syndrome of acute stroke, detected in about 20% of healthy elderly and up to 50% of high risk patients. Estimates of the incidence of stroke, characteristics of patients, management and outcome became available from the tri-annual national acute stroke Israeli survey (NASIS) program, initiated during 2004. The annual incidence of hospitalized acute cerebrovascular events is approximately 13,000 and rates, particularly in women, seem even higher than those observed for acute myocardial infarction. Findings also highlight critical deficiencies in acute stroke units and systems for urgent evaluation and intervention in acute stroke. Action plans are urgently required, in accordance with the experience from other countries, in order to upgrade the stroke infrastructure nationwide for more effective prevention and management of acute stroke. PMID:19264006

  6. Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood

    PubMed Central

    Breivik, Torbjørn; Gundersen, Yngvar; Murison, Robert; Turner, Jonathan D; Muller, Claude P; Gjermo, Per; Opstad, Kristian

    2015-01-01

    Background and Objective: Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. Material and Methods: Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. Results: Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1β in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone. Conclusion: Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis. PMID:25713634

  7. Acute Ischemic Stroke Intervention.

    PubMed

    Khandelwal, Priyank; Yavagal, Dileep R; Sacco, Ralph L

    2016-06-01

    Acute ischemic stroke (AIS) is the leading cause of disability worldwide and among the leading causes of mortality. Although intravenous tissue plasminogen activator (IV-rtPA) was approved nearly 2 decades ago for treatment of AIS, only a minority of patients receive it due to a narrow time window for administration and several contraindications to its use. Endovascular approaches to recanalization in AIS developed in the 1980s, and recently, 5 major randomized trials showed an overwhelming superior benefit of combining endovascular mechanical thrombectomy with IV-rtPA over IV-rtPA alone. In this paper, we discuss the evolution of catheter-based treatment from first-generation thrombectomy devices to the game-changing stent retrievers, results from recent trials, and the evolving stroke systems of care to provide timely access to acute stroke intervention to patients in the United States. PMID:27256835

  8. Stroke in patients with diabetes mellitus.

    PubMed

    Mankovsky, Boris N; Ziegler, Dan

    2004-01-01

    The article's objective is to review the key advances in the scientific literature related to the association of stroke with diabetes mellitus and to summarize the current approaches to stroke prevention in diabetic patients. The key findings from the literature regarding stroke incidence in patients with diabetes, specific and nonspecific risk factors of stroke in the diabetic population, such as arterial hypertension, dyslipidemia, hyperglycemia, diabetes duration, diabetic complications, insulin resistance/hyperinsulinemia, course and outcome of stroke in subjects with diabetes and/or hyperglycemia, and the peculiarities of type, site and size of stroke in diabetic patients are discussed. The results of recent clinical trials aimed at correcting hyperglycemia, hypertension, and dyslipidemia, to prevent stroke in people with diabetes, are reviewed. The medical database Medline along with original articles from peer-reviewed journals were used for analysis. There is convincing evidence suggesting that diabetes mellitus represents a strong independent risk factor of stroke. The contribution of hyperglycemia to increased stroke risk is not proven. Data suggest an association of the full cluster of the insulin resistance syndrome and stroke. Diabetes is a risk factor mainly for ischemic stroke, while its association with hemorrhagic stroke remains controversial. Hyperglycemia is common in stroke patients, but it is not known whether it independently influences the course and outcome of stroke or merely reflects stroke severity and location. Aggressive control of arterial hypertension and dyslipidemia allows to decrease the risk of stroke in diabetic patients substantially, while the importance of glucose control for stroke prevention remains unproven. PMID:15250030

  9. Suicide in stroke survivors: epidemiology and prevention.

    PubMed

    Pompili, Maurizio; Venturini, Paola; Lamis, Dorian A; Giordano, Gloria; Serafini, Gianluca; Belvederi Murri, Martino; Amore, Mario; Girardi, Paolo

    2015-01-01

    Stroke is a dramatic event and is associated with potentially severe consequences, including disability, mortality, and social costs. Stroke may occur at any age; however, most strokes occur in individuals aged 65 years and older. Previous research has found that stroke increases suicide risk, especially among women and younger patients. The aim of the current review is to investigate the relationship between suicide and stroke in order to determine which stroke patients are at elevated risk for suicide. Moreover, we review the literature in order to provide pharmacological treatment strategies for stroke patients at high risk of suicide. We performed a careful search to identify articles and book chapters focused on this issue, selecting only English-language articles published from 1990 to 2014 that addressed the issue of suicide after stroke and its pharmacological management. We found 12 clinical trials that explored the relationship between stroke and suicidal ideation and/or suicidal plans and 11 investigating suicide as the cause of death after stroke. We identified stroke as a significant risk factor for both suicide and suicidal ideation, especially among younger adult depressed patients in all articles, providing further support for the association between post-stroke and suicidality. Suicide risk is particularly high in the first 5 years following stroke. Depression, previous mood disorder, prior history of stroke, and cognitive impairment were found to be the most important risk factors for suicide. Selective serotonin reuptake inhibitors (SSRIs) represent the treatment of choice for stroke survivors with suicide risk, and studies in rats have suggested that carbolithium is a promising treatment in these patients. Early identification and treatment of post-stroke depression may significantly reduce suicide risk in stroke patients. PMID:25491561

  10. Healthy Living after Stroke

    MedlinePlus

    ... After Stroke Weight Training After Stroke Tips for Improving Fine Motor Skills Functional Tone Management Arm Training Program Constraint-Induced Movement Therapy Emotional & Behavioral Challenges Self-Esteem after Stroke Post-Stroke Mood Disorders One-side ...

  11. Stroke and episodic memory disorders.

    PubMed

    Lim, Chun; Alexander, Michael P

    2009-12-01

    Memory impairments are common after stroke, and the anatomical basis for impairments may be quite variable. To determine the range of stroke-related memory impairment, we identified all case reports and group studies through the Medline database and the Science Citation Index. There is no hypothesis about memory that is unique to stroke, but there are several important facets of memory impairment after stroke: (1) Every node of the limbic system implicated in memory may be damaged by stroke but very rarely in isolation and the combination of amnesia with the associated deficits often illuminates additional aspects of memory functions. (2) Stroke produces amnesia by damage to critical convergence white matter connections of the limbic system, and stroke is the only etiology of amnesia that can delineate the entire pathway of memory and critical convergence points. (3) Stroke also impairs memory, without causing classical amnesia, by damaging brain regions responsible for cognitive processes, some modality specific and some more generally strategic, that are essential for normal learning and recall. PMID:19666037

  12. Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

    PubMed Central

    Pereira, Isabela Resende; Vilar-Pereira, Glaucia; da Silva, Andrea Alice; Lannes-Vieira, Joseli

    2014-01-01

    Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease. PMID:24937048

  13. Marginal costing methods highlight the contributing cost of comorbid conditions in Medicare patients: a quasi-experimental case–control study of ischemic stroke costs

    PubMed Central

    2013-01-01

    Background Cost of illness studies are needed to provide estimates for input into cost-effectiveness studies and as information drivers to resource allocation. However, these studies often do not differentiate costs associated with the disease of interest and costs of co-morbidities. The goal of this study was to identify the 1-year cost of ischemic stroke compared to the annual cost of care for a comparable non-stroke group of South Carolina (SC) Medicare beneficiaries resulting in a marginal cost estimate. Methods SC data for 2004 and 2005 were used to estimate the mean 12 month cost of stroke for 2,976 Medicare beneficiaries hospitalized for Ischemic Stroke in 2004. Using nearest neighbor propensity score matching, a control group of non-stroke beneficiaries were matched on age, gender, race, risk factors, and Charlson comorbidity index and their costs were calculated. Marginal cost attributable to ischemic stroke was calculated as the difference between these two adjusted cost estimates. Results The total cost estimated for SC stroke patients for 1 year (2004) was $81.3 million. The cost for the matched comparison group without stroke was $54.4 million. Thus, the 2004 marginal costs to Medicare due to Ischemic stroke in SC are estimated to be $26.9 million. Conclusions Accurate estimates of cost of care for conditions, such as stroke, that are common in older patients with a high rate of comorbid conditions require the use of a marginal costing approach. Over estimation of cost of care for stroke may lead to prediction of larger savings than realizable from important stroke treatment and prevention programs, which may damage the credibility of program advocates, and jeopardize long term funding support. Additionally, correct cost estimates are needed as inputs for valid cost-effectiveness studies. Thus, it is important to use marginal costing for stroke, especially with the increasing public focus on evidence-based economic decision making to be expected with

  14. Stroke and Disorders of Consciousness

    PubMed Central

    Dostović, Zikrija; Smajlović, Dževdet; Dostović, Ernestina; Ibrahimagić, Omer Ć.

    2012-01-01

    Objectives. To determine the severity of stroke and mortality in relation to the type of disturbance of consciousness and outcome of patients with disorders of consciousness. Patients and Methods. We retrospectively analyzed 201 patients. Assessment of disorders of consciousness is performed by Glasgow Coma Scale (Teasdale and Jennet, 1974) and the Diagnostic and Statistical Manual of Mental Disorders (Anonymous, 2000). The severity of stroke was determined by National Institutes of Health Stroke Scale (Lyden et al., 2011). Results. Fifty-four patients had disorders of consciousness (26.9%). Patients with disorders of consciousness on admission (P < 0.001) and discharge (P = 0.003) had a more severe stroke than patients without disturbances of consciousness. Mortality was significantly higher in patients with disorders of consciousness (P = 0.0001), and there was no difference in mortality in relation to the type of disturbance of consciousness. There is no statistically significant effect of specific predictors of survival in patients with disorders of consciousness. Conclusion. Patients with disorders of consciousness have a more severe stroke and higher mortality. There is no difference in mortality and severity of stroke between patients with quantitative and qualitative disorders of consciousness. There is no statistically significant effect of specific predictors of survival in patients with disorders of consciousness. PMID:22973503

  15. Stroke and disorders of consciousness.

    PubMed

    Dostović, Zikrija; Smajlović, Dževdet; Dostović, Ernestina; Ibrahimagić, Omer Ć

    2012-01-01

    Objectives. To determine the severity of stroke and mortality in relation to the type of disturbance of consciousness and outcome of patients with disorders of consciousness. Patients and Methods. We retrospectively analyzed 201 patients. Assessment of disorders of consciousness is performed by Glasgow Coma Scale (Teasdale and Jennet, 1974) and the Diagnostic and Statistical Manual of Mental Disorders (Anonymous, 2000). The severity of stroke was determined by National Institutes of Health Stroke Scale (Lyden et al., 2011). Results. Fifty-four patients had disorders of consciousness (26.9%). Patients with disorders of consciousness on admission (P < 0.001) and discharge (P = 0.003) had a more severe stroke than patients without disturbances of consciousness. Mortality was significantly higher in patients with disorders of consciousness (P = 0.0001), and there was no difference in mortality in relation to the type of disturbance of consciousness. There is no statistically significant effect of specific predictors of survival in patients with disorders of consciousness. Conclusion. Patients with disorders of consciousness have a more severe stroke and higher mortality. There is no difference in mortality and severity of stroke between patients with quantitative and qualitative disorders of consciousness. There is no statistically significant effect of specific predictors of survival in patients with disorders of consciousness. PMID:22973503

  16. Stroke prevention: an update.

    PubMed

    Bousser, Marie-Germaine

    2012-03-01

    Stroke is a personal, familial, and social disaster. It is the third cause of death worldwide, the first cause of acquired disability, the second cause of dementia, and its cost is astronomic. The burden of stroke is likely to increase given the aging of the population and the growing incidence of many vascular risk factors. Prevention of stroke includes--as for all other diseases--a "mass approach" aiming at decreasing the risk at the society level and an individual approach, aiming at reducing the risk in a given subject. The mass approach is primarily based on the identification and treatment of vascular risk factors and, if possible, in the implementation of protective factors. These measures are the basis of primary prevention but most of them have now been shown to be also effective in secondary prevention. The individual approach combines a vascular risk factor modification and various treatments addressing the specific subtypes of stroke, such as antiplatelet drugs for the prevention of cerebral infarction in large and small artery diseases of the brain, carotid endarterectomy or stenting for tight carotid artery stenosis, and oral anticoagulants for the prevention of cardiac emboli. There is a growing awareness of the huge evidence-to-practice gap that exists in stroke prevention largely due to socio-economic factors. Recent approaches include low cost intervention packages to reduce blood pressure and cheap "polypills" combining in a single tablet aspirin and several drugs to lower blood pressure and cholesterol. Polypill intake should however not lead to abandon the healthy life-style measures which remain the mainstay of stroke prevention. PMID:22460445

  17. Experimental study and analysis of lubricants dispersed with nano Cu and TiO2 in a four-stroke two wheeler

    PubMed Central

    2011-01-01

    The present investigation summarizes detailed experimental studies with standard lubricants of commercial quality known as Racer-4 of Hindustan Petroleum Corporation (India) dispersed with different mass concentrations of nanoparticles of Cu and TiO2. The test bench is fabricated with a four-stroke Hero-Honda motorbike hydraulically loaded at the rear wheel with proper instrumentation to record the fuel consumption, the load on the rear wheel, and the linear velocity. The whole range of data obtained on a stationery bike is subjected to regression analysis to arrive at various relationships between fuel consumption as a function of brake power, linear velocity, and percentage mass concentration of nanoparticles in the lubricant. The empirical relation correlates with the observed data with reasonable accuracy. Further, extension of the analysis by developing a mathematical model has revealed a definite improvement in brake thermal efficiency which ultimately affects the fuel economy by diminishing frictional power in the system with the introduction of nanoparticles into the lubricant. The performance of the engine seems to be better with nano Cu-Racer-4 combination than the one with nano TiO2. PMID:21711765

  18. Experimental study and analysis of lubricants dispersed with nano Cu and TiO2 in a four-stroke two wheeler.

    PubMed

    Sarma, Pullela K; Srinivas, Vadapalli; Rao, Vedula Dharma; Kumar, Ayyagari Kiran

    2011-01-01

    The present investigation summarizes detailed experimental studies with standard lubricants of commercial quality known as Racer-4 of Hindustan Petroleum Corporation (India) dispersed with different mass concentrations of nanoparticles of Cu and TiO2. The test bench is fabricated with a four-stroke Hero-Honda motorbike hydraulically loaded at the rear wheel with proper instrumentation to record the fuel consumption, the load on the rear wheel, and the linear velocity. The whole range of data obtained on a stationery bike is subjected to regression analysis to arrive at various relationships between fuel consumption as a function of brake power, linear velocity, and percentage mass concentration of nanoparticles in the lubricant. The empirical relation correlates with the observed data with reasonable accuracy. Further, extension of the analysis by developing a mathematical model has revealed a definite improvement in brake thermal efficiency which ultimately affects the fuel economy by diminishing frictional power in the system with the introduction of nanoparticles into the lubricant. The performance of the engine seems to be better with nano Cu-Racer-4 combination than the one with nano TiO2. PMID:21711765

  19. Stem Cells May Offer New Hope to Stroke Survivors

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159163.html Stem Cells May Offer New Hope to Stroke Survivors Experimental ... HealthDay News) -- Preliminary research suggests that injecting adult stems cells directly into the brain may give stroke patients ...

  20. Germination and Growth of a Vegetable Exposed to Very Severe Environmental Conditions Experimentally Induced by High Voltage

    NASA Astrophysics Data System (ADS)

    Aoki, Takashi; Ikezawa, Shunjiro

    1982-09-01

    Ultra-high-voltage (UHV) transmission power lines are required in order to reduce transmission energy losses, and to transfer more power across long distances. However, the ecological and biological influence of UHV lines has not been documented well. Possible influences of UHV lines are: electro-magnetic field, ozone, NOx, and ion shower. The purpose of this study was to obtain information on the germination and growth of Raphanus sativus L.cv. Kaiware-daikon exposed to an experimental environment in which all the above influences at very severe intensity levels were working simultaneously. Several environmental conditions severer than those predicted for future UHV lines were set up, using a high voltage at 60 Hz. The germination and growth of this plant were suppressed under the experimental conditions used, the suppression being greater the severer the conditions. When the electric field is strong, corona discharge occurs at the tip of the plant.

  1. A comparison of calculated and experimental lift and pressure distributions for several helicopter rotor sections

    NASA Technical Reports Server (NTRS)

    Conlon, J.

    1980-01-01

    The use of computational techniques in predicting lift coefficients and pressure distributions of two dimenstional airfoil sections was studied. The computer code FL06/IBL was used to solve the compressible, two dimensional flow about four different airfoil sections. The lift coefficients of the airfoils were calculated at various angles of attack at subsonic Mach numbers and compared with experimental data.

  2. Rhodococcus equi hyperimmune plasma decreases pneumonia severity after a randomised experimental challenge of neonatal foals.

    PubMed

    Sanz, M G; Loynachan, A; Horohov, D W

    2016-03-12

    Since a vaccine is not available against Rhodococcus equi, R equi-specific hyperimmune plasma (HIP) is commonly used, although its efficacy remains controversial. The objective of this study was to evaluate the ability of a commercially available HIP to prevent clinical rhodococcal pneumonia in neonatal foals after experimental challenge. PMID:26932206

  3. Biotherapies in stroke.

    PubMed

    Detante, O; Jaillard, A; Moisan, A; Barbieux, M; Favre, I M; Garambois, K; Hommel, M; Remy, C

    2014-12-01

    Stroke is the second leading cause of death worldwide and the most common cause of severe disability. Neuroprotection and repair mechanisms supporting endogenous brain plasticity are often insufficient to allow complete recovery. While numerous neuroprotective drugs trials have failed to demonstrate benefits for patients, they have provided interesting translational research lessons related to neurorestorative therapy mechanisms in stroke. Stroke damage is not limited to neurons but involve all brain cell type including the extracellular matrix in a "glio-neurovascular niche". Targeting a range of host brain cells, biotherapies such as growth factors and therapeutic cells, currently hold great promise as a regenerative medical strategy for stroke. These techniques can promote both neuroprotection and delayed neural repair through neuro-synaptogenesis, angiogenesis, oligodendrogliogenesis, axonal sprouting and immunomodulatory effects. Their complex mechanisms of action are interdependent and vary according to the particular growth factor or grafted cell type. For example, while "peripheral" stem or stromal cells can provide paracrine trophic support, neural stem/progenitor cells (NSC) or mature neurons can act as more direct neural replacements. With a wide therapeutic time window after stroke, biotherapies could be used to treat many patients. However, guidelines for selecting the optimal time window, and the best delivery routes and doses are still debated and the answers may depend on the chosen product and its expected mechanism including early neuroprotection, delayed neural repair, trophic systemic transient effects or graft survival and integration. Currently, the great variety of growth factors, cell sources and cell therapy products form a therapeutic arsenal that is available for stroke treatment. Their effective clinical use will require prior careful considerations regarding safety (e.g. tumorgenicity, immunogenicity), potential efficacy, cell

  4. Enhanced recovery from chronic ischemic injury by bone marrow cells in a rat model of ischemic stroke.

    PubMed

    Yoo, Jongman; Seo, Jin-Ju; Eom, Jang-Hyeon; Hwang, Dong-Youn

    2015-01-01

    Even after decades of intensive studies, therapeutic options for patients with stroke are rather limited. Thrombolytic drugs effectively treat the very acute stage of stroke, and several neuroprotectants that are designed to treat secondary injury following stroke are being tested in clinical trials. However, these pharmacological approaches primarily focus on acute stroke recovery, and few options are available for treating chronic stroke patients. In recent years, stem cell-mediated regenerative approaches have emerged as promising therapeutic strategies for treating the chronic stage of stroke. In this study, we examined whether systemically administered bone marrow cells (BMCs) could have beneficial effects in a rat model of chronic ischemia. Our transplantation experiments using BMCs obtained from ischemic donor rats showed functional and structural recovery during the chronic stage of stroke. BMC-mediated neural proliferation was prominent in the brains of rats with chronic stroke, and most of the new cells eventually became neurons instead of astrocytes. BMC-mediated enhanced neural proliferation coincided with a significant reduction (∼50%) in the number of activated microglia, which is consistent with previous reports of enhanced neural proliferation being linked to microglial inactivation. Strikingly, approximately 57% of the BMCs that infiltrated the chronic ischemic brain were CD25(+) cells, suggesting that these cells may exert the beneficial effects associated with BMC transplantation. Based on the reported anti-inflammatory role of CD25(+) regulatory T-cells in acute experimental stroke, we propose a working model delineating the positive effects of BMC transplantation during the chronic phase of stroke; infiltrating BMCs (mostly CD25(+) cells) reduce activated microglia, which leads to enhanced neural proliferation and enhanced recovery from neuronal damage in this rat model of chronic stroke. This study provides valuable insights into the effect

  5. A novel chemically modified curcumin reduces severity of experimental periodontal disease in rats: initial observations.

    PubMed

    Elburki, Muna S; Rossa, Carlos; Guimaraes, Morgana R; Goodenough, Mark; Lee, Hsi-Ming; Curylofo, Fabiana A; Zhang, Yu; Johnson, Francis; Golub, Lorne M

    2014-01-01

    Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar) bone loss was quantified morphometrically and by μ-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1β; ELISA); serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P = 0.003) or μ-CT (P = 0.008) analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations. PMID:25104884

  6. A Novel Chemically Modified Curcumin Reduces Severity of Experimental Periodontal Disease in Rats: Initial Observations

    PubMed Central

    Elburki, Muna S.; Rossa, Carlos; Guimaraes, Morgana R.; Goodenough, Mark; Lee, Hsi-Ming; Curylofo, Fabiana A.; Zhang, Yu; Johnson, Francis; Golub, Lorne M.

    2014-01-01

    Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar) bone loss was quantified morphometrically and by μ-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1β; ELISA); serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P = 0.003) or μ-CT (P = 0.008) analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations. PMID:25104884

  7. Misconduct in the Prosecution of Severe Crimes: Theory and Experimental Test

    ERIC Educational Resources Information Center

    Lucas, Jeffrey W.; Graif, Corina; Lovaglia, Michael J.

    2006-01-01

    Prosecutorial misconduct involves the intentional use of illegal or improper methods for attaining convictions against defendants in criminal trials. Previous research documented extensive errors in the prosecution of severe crimes. A theory formulated to explain this phenomenon proposes that in serious cases, increased pressure to convict…

  8. Life events and difficulties preceding stroke.

    PubMed Central

    House, A; Dennis, M; Mogridge, L; Hawton, K; Warlow, C

    1990-01-01

    Life events and difficulties were recorded for the year before stroke, using a standardised semi-structured interview, in 113 surviving patients seen after their first ever in a lifetime stroke. An age and sex-matched control group (n = 109) was also interviewed about the preceding year. The stroke patients reported fewer non-threatening events and events with only a short-term threat, while difficulties were reported with equal frequency by the two groups. However, events which were severely threatening in the long-term were significantly more common in the stroke patients (in the 52 weeks before stroke 26% versus 13%, odds ratio 2.3, 95% confidence interval 1.1-4.9). The increased rate was apparent throughout the year and not just in the weeks immediately before stroke onset. The number of stroke patients experiencing severe events in the follow up year fell to the level found in the control group. Recognised risk factors for stroke were found equally in those patients with and without severe events before onset, except that hypertension was rather less common in the patients who had experienced a severe event. It therefore appears that severe life events may be one of the determinants of stroke onset. PMID:2292691

  9. Functional up-regulation of endopeptidase neurolysin during post-acute and early recovery phases of experimental stroke in mouse brain.

    PubMed

    Rashid, Mamoon; Wangler, Naomi J; Yang, Li; Shah, Kaushik; Arumugam, Thiruma V; Abbruscato, Thomas J; Karamyan, Vardan T

    2014-04-01

    In this study, we provide evidence for the first time that membrane-bound endopeptidase neurolysin is up-regulated in different parts of mouse brain affected by focal ischemia-reperfusion in a middle cerebral artery occlusion model of stroke. Radioligand binding, enzymatic and immunoblotting experiments in membrane preparations of frontoparietal cortex, striatum, and hippocampus isolated from the ischemic hemisphere of mouse brain 24 h after reperfusion revealed statistically significant increase (≥ twofold) in quantity and activity of neurolysin compared with sham-operated controls. Cerebellar membranes isolated from the ischemic hemisphere served as negative control supporting the observations that up-regulation of neurolysin occurs in post-ischemic brain regions. This study also documents sustained functional up-regulation of neurolysin in frontoparietal cortical membranes for at least 7 days after stroke, which appears not to be transcriptionally or translationally regulated, but rather depends on translocation of cytosolic neurolysin to the membranes and mitochondria. Considering diversity of endogenous neurolysin substrates (neurotensin, bradykinin, angiotensins I/II, substance P, hemopressin, dynorphin A(1-8), metorphamide, somatostatin) and the well-documented role of these peptidergic systems in pathogenesis of stroke, resistance to ischemic injury and/or post-stroke brain recovery, our findings suggest that neurolysin may play a role in processes modulating the brain's response to stroke and its recovery after stroke. PMID:24164478

  10. PROGESTERONE TREATMENT REDUCES DISEASE SEVERITY AND INCREASES IL-10 IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

    PubMed Central

    Yates, M.A; Li, Y.; Chlebeck, P.; Proctor, T.; Vandenbark, A.A.; Offner, H.

    2010-01-01

    Ovarian hormones, including progesterone, are known to have immunomodulatory and neuroprotective effects which may alter the disease course of experimental autoimmune encephalomyelitis (EAE). In the current study, we examined the treatment potential of progesterone beginning at the onset of EAE symptoms. Progesterone treated animals showed reduced peak disease scores and cumulative disease indices, and decreased inflammatory cytokine secretion (IL-2 and IL-17). In addition, increased production of IL-10 was accompanied by increased numbers of CD19+ cells and an increase in CD8+ cells. Decreased chemokine and chemokine receptor expression in the spinal cord also contributed to decreased lesions in the spinal cord. PMID:20153059