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Sample records for experimental stroke severity

  1. 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

  2. Differential effects of sympathetic nervous system and hypothalamic-pituitary-adrenal axis on systemic immune cells after severe experimental stroke.

    PubMed

    Mracsko, Eva; Liesz, Arthur; Karcher, Simone; Zorn, Markus; Bari, Ferenc; Veltkamp, Roland

    2014-10-01

    Infectious complications are the leading cause of death in the post-acute phase of stroke. Post-stroke immunodeficiency is believed to result from neurohormonal dysregulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. However, the differential effects of these neuroendocrine systems on the peripheral immune cells are only partially understood. Here, we determined the impact of the hormones of the SNS and HPA on distinct immune cell populations and characterized their interactions after stroke. At various time points after cortical or extensive hemispheric cerebral ischemia, plasma cortisone, corticosterone, metanephrine and adrenocorticotropic hormone (ACTH) levels were measured in mice. Leukocyte subpopulations were flow cytometrically analyzed in spleen and blood. To investigate their differential sensitivity to stress hormones, splenocytes were incubated in vitro with prednisolone, epinephrine and their respective receptor blockers. Glucocorticoid receptor (GCR) and beta2-adrenergic receptor (β2-AR) on leukocyte subpopulations were quantified by flow cytometry. In vivo effects of GCR and selective β2-AR blockade, respectively, were defined on serum hormone concentrations, lymphopenia and interferon-γ production after severe ischemia. We found elevated cortisone, corticosterone and metanephrine levels and associated lymphocytopenia only after extensive brain infarction. Prednisolone resulted in a 5 times higher cell death rate of splenocytes than epinephrine in vitro. Prednisolone and epinephrine-induced leukocyte cell death was prevented by GCR and β2-AR blockade, respectively. In vivo, only GCR blockade prevented post ischemic lymphopenia whereas β2-AR preserved interferon-γ secretion by lymphocytes. GCR blockade increased metanephrine levels in vivo and prednisolone, in turn, decreased β2-AR expression on lymphocytes. In conclusion, mediators of the SNS and the HPA axis differentially affect the systemic

  3. Multimodal MRI of experimental stroke

    PubMed Central

    Duong, Timothy Q

    2014-01-01

    Stroke is the fourth leading cause of death and the leading cause of long-term disability in the United States. Brain imaging data from experimental stroke models and stroke patients have shown that there is often a gradual progression of potentially reversible ischemic injury toward infarction. Reestablishing tissue perfusion and/or treating with neuroprotective drugs in a timely fashion are expected to salvage some ischemic tissues. Diffusion-weighted imaging based on magnetic resonance imaging (MRI) in which contrast is based on water motion can detect ischemic injury within minutes after onsets, whereas computed tomography and other imaging modalities fail to detect stroke injury for at least a few hours. Along with quantitative perfusion imaging, the perfusion-diffusion mismatch which approximates the ischemic penumbra could be imaged non-invasively. This review describes recent progresses in the development and application of multimodal MRI and image analysis techniques to study ischemic tissue at risk in experimental stroke in rats. PMID:24323751

  4. 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.

  5. IV thrombolysis in very severe and severe ischemic stroke

    PubMed Central

    Lees, Kennedy R.; Collas, David; Rand, Viiu-Marika; Mikulik, Robert; Toni, Danilo; Wahlgren, Nils; Ahmed, Niaz

    2015-01-01

    Objective: To study the safety of off-label IV thrombolysis in patients with very severe stroke (NIH Stroke Scale [NIHSS] scores >25) compared with severe stroke (NIHSS scores 15–25), where treatment is within European regulations. Methods: Data were analyzed from 57,247 patients with acute ischemic stroke receiving IV tissue plasminogen activator in 793 hospitals participating in the Safe Implementation of Thrombolysis in Stroke (SITS) International Stroke Thrombolysis Registry (2002–2013). Eight hundred sixty-eight patients (1.5%) had NIHSS scores >25 and 19,995 (34.9%) had NIHSS scores 15–25. Outcome measures were parenchymal hemorrhage, symptomatic intracerebral hemorrhage, mortality, and functional outcome. Results: Parenchymal hemorrhage occurred in 10.7% vs 11.0% (p = 0.79), symptomatic intracerebral hemorrhage per SITS-MOST (SITS–Monitoring Study) in 1.4% vs 2.5% (p = 0.052), death at 3 months in 50.4% vs 26.9% (p < 0.001), and functional independence at 3 months in 14.0% vs 29.0% (p < 0.001) of patients with NIHSS scores >25 and NIHSS scores 15–25, respectively. Multivariate adjustment did not change findings from univariate comparisons. Posterior circulation stroke was more common in patients with NIHSS scores >25 (36.2% vs 7.4%, p < 0.001), who were also more often obtunded or comatose on presentation (58.4% vs 7.1%, p < 0.001). Of patients with NIHSS scores >25, 26.2% were treated >3 hours from symptom onset vs 14.5% with NIHSS scores of 15–25. Conclusions: Our data show no excess risk of cerebral hemorrhage in patients with NIHSS score >25 compared to score 15–25, suggesting that the European contraindication to IV tissue plasminogen activator treatment at NIHSS levels >25 may be unwarranted. Increased mortality and lower rates of functional independence in patients with NIHSS score >25 are explained by higher stroke severity, impaired consciousness on presentation due to posterior circulation ischemia, and longer treatment delays. PMID

  6. Aspirin resistance is more common in lacunar strokes than embolic strokes and is related to stroke severity.

    PubMed

    Englyst, Nicola A; Horsfield, Gill; Kwan, Joseph; Byrne, Christopher D

    2008-06-01

    The aim of this study was to investigate the relationship between aspirin resistance, ischaemic stroke subtype, stroke severity, and inflammatory cytokines. Aspirin resistance was assessed by thrombelastography in 45 people with ischaemic stroke and 25 controls. Plasma interleukin (IL)-6 was measured. Stroke severity was assessed using the modified Rankin scale and National Institute of Health Stroke Score within 72 h of stroke. Aspirin resistance was more common in the stroke than the control group (67% versus 40%, P=0.028), and within the stroke group the aspirin-resistant group had a higher Rankin score (4.0 versus 2.0, P=0.013). Aspirin resistance was greater in lacunar than embolic strokes (platelet activation 79% versus 59%, P=0.020). The stroke aspirin-resistant group had higher levels of IL-6 than the stroke aspirin-sensitive group (2.4+/-1 versus 1.8+/-0.9 ng/mL, P=0.037). Using multivariate analysis, we examined the interrelationships between aspirin resistance, IL-6, and stroke severity. These analyses showed that IL-6 was independently associated with stroke severity as the outcome (B=3.738, P=0.036), and aspirin resistance was independently associated with IL-6 (B=0.765, P=0.005) as the outcome. In conclusion, aspirin resistance is related to stroke severity and aspirin resistance is more common in lacunar strokes than embolic strokes.

  7. Cortex Integrity Relevance in Muscle Synergies in Severe Chronic Stroke

    PubMed Central

    García-Cossio, Eliana; Broetz, Doris; Birbaumer, Niels; Ramos-Murguialday, Ander

    2014-01-01

    Background: Recent experimental evidence has indicated that the motor system coordinates muscle activations through a linear combination of muscle synergies that are specified at the spinal or brainstem networks level. After stroke upper limb impairment is characterized by abnormal patterns of muscle activations or synergies. Objective: This study aimed at characterizing the muscle synergies in severely affected chronic stroke patients. Furthermore, the influence of integrity of the sensorimotor cortex on synergy modularity and its relation with motor impairment was evaluated. Methods: Surface electromyography from 33 severely impaired chronic stroke patients was recorded during 6 bilateral movements. Muscle synergies were extracted and synergy patterns were correlated with motor impairment scales. Results: Muscle synergies extracted revealed different physiological patterns dependent on the preservation of the sensorimotor cortex. Patients without intact sensorimotor cortex showed a high preservation of muscle synergies. On the contrary, patients with intact sensorimotor cortex showed poorer muscle synergies preservation and an increase in new generated synergies. Furthermore, the preservation of muscle synergies correlated positively with hand functionality in patients with intact sensorimotor cortex and subcortical lesions only. Conclusion: Our results indicate that severely paralyzed chronic stroke patient with intact sensorimotor cortex might sculpt new synergy patterns as a response to maladaptive compensatory strategies. PMID:25294998

  8. Do Women With Atrial Fibrillation Experience More Severe Strokes? Results From the Austrian Stroke Unit Registry.

    PubMed

    Lang, Clemens; Seyfang, Leonhard; Ferrari, Julia; Gattringer, Thomas; Greisenegger, Stefan; Willeit, Karin; Toell, Thomas; Krebs, Stefan; Brainin, Michael; Kiechl, Stefan; Willeit, Johann; Lang, Wilfried; Knoflach, Michael

    2017-03-01

    Ischemic strokes associated with atrial fibrillation (AF) are more severe than those of other cause. We aim to study potential sex effects in this context. In this cross-sectional study, 74 425 adults with acute ischemic stroke from the Austrian Stroke Unit Registry were included between March 2003 and January 2016. In 63 563 patients, data on the National Institutes of Health Stroke Scale on admission to the stroke unit, presence of AF, vascular risk factors, and comorbidities were complete. Analysis was done by a multivariate regression model. Stroke severity in general increased with age. AF-related strokes were more severe than strokes of other causes. Sex-related differences in stroke severity were only seen in stroke patients with AF. Median (Q25,75) National Institutes of Health Stroke Scale score points were 9 (4,17) in women and 6 (3,13) in men (P<0.001). The interaction between AF and sex on stroke severity was independent of age, previous functional status, vascular risk factors, and vascular comorbidities and remained significant in various subgroups. Women with AF do not only have an increased risk of stroke when compared with men but also experience more severe strokes. © 2017 American Heart Association, Inc.

  9. 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

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

    PubMed

    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

  11. Outcomes in severe middle cerebral artery ischemic stroke.

    PubMed

    Walcott, Brian P; Miller, Jennifer C; Kwon, Churl-Su; Sheth, Sameer A; Hiller, Marc; Cronin, Carolyn A; Schwamm, Lee H; Simard, J Marc; Kahle, Kristopher T; Kimberly, W Taylor; Sheth, Kevin N

    2014-08-01

    Severe middle cerebral artery stroke (MCA) is associated with a high rate of morbidity and mortality. We assessed the hypothesis that patient-specific variables may be associated with outcomes. We also sought to describe under-recognized patient-centered outcomes. A consecutive, multi-institution, retrospective cohort of adult patients (≤70 years) was established from 2009 to 2011. We included patients with NIHSS score ≥15 and infarct volume ≥60 mL measured within 48 h of symptom onset. Malignant edema was defined as the development of midline brain shift of ≥5 mm in the first 5 days. Exclusion criterion was enrollment in any experimental trial. A univariate and multivariate logistic regression analysis was performed to model and predict the factors related to outcomes. 46 patients (29 female, 17 male; mean age 57.3 ± 1.5 years) met study criteria. The mortality rate was 28% (n = 13). In a multivariate analysis, only concurrent anterior cerebral artery (ACA) involvement was associated with mortality (OR 9.78, 95% CI 1.15, 82.8, p = 0.04). In the malignant edema subgroup (n = 23, 58%), 4 died (17%), 7 underwent decompressive craniectomy (30%), 7 underwent tracheostomy (30%), and 15 underwent gastrostomy (65%). Adverse outcomes after severe stroke are common. Concurrent ACA involvement predicts mortality in severe MCA stroke. It is useful to understand the incidence of life-sustaining procedures, such as tracheostomy and gastrostomy, as well as factors that contribute to their necessity.

  12. Patients living in impoverished areas have more severe ischemic strokes.

    PubMed

    Kleindorfer, Dawn; Lindsell, Christopher; Alwell, Kathleen A; Moomaw, Charles J; Woo, Daniel; Flaherty, Matthew L; Khatri, Pooja; Adeoye, Opeolu; Ferioli, Simona; Kissela, Brett M

    2012-08-01

    Initial stroke severity is one of the strongest predictors of eventual stroke outcome. However, predictors of initial stroke severity have not been well-described within a population. We hypothesized that poorer patients would have a higher initial stroke severity on presentation to medical attention. We identified all cases of hospital-ascertained ischemic stroke occurring in 2005 within a biracial population of 1.3 million. "Community" socioecomic status was determined for each patient based on the percentage below poverty in the census tract in which the patient resided. Linear regression was used to model the effect of socioeconomic status on stroke severity. Models were adjusted for race, gender, age, prestroke disability, and history of medical comorbidities. There were 1895 ischemic stroke events detected in 2005 included in this analysis; 22% were black, 52% were female, and the mean age was 71 years (range, 19-104). The median National Institutes of Health Stroke Scale was 3 (range, 0-40). The poorest community socioeconomic status was associated with a significantly increased initial National Institutes of Health Stroke Scale by 1.5 points (95% confidence interval, 0.5-2.6; P<0.001) compared with the richest category in the univariate analysis, which increased to 2.2 points after adjustment for demographics and comorbidities. We found that increasing community poverty was associated with worse stroke severity at presentation, independent of other known factors associated with stroke outcomes. Socioeconomic status may impact stroke severity via medication compliance, access to care, and cultural factors, or may be a proxy measure for undiagnosed disease states.

  13. Elevated admission blood pressure and stroke severity in acute ischemic stroke: the Bergen NORSTROKE Study.

    PubMed

    Kvistad, Christopher Elnan; Logallo, Nicola; Oygarden, Halvor; Thomassen, Lars; Waje-Andreassen, Ulrike; Naess, Halvor

    2013-01-01

    Transient elevated blood pressure (BP) is frequent in patients presenting with acute ischemic stroke. The pathophysiology of this response is not clear and its effect on clinical outcome has shown contradictory results. Some studies have suggested that BP elevation may represent a protective response to enhance perfusion in ischemic brain tissue. In this study, we aimed to explore the association between elevated admission BP and stroke severity in the acute phase of ischemic stroke. If it is true that elevated BP represents a protective response in acute ischemia, we expected an inverse association between elevated BP and admission stroke severity, and a positive association between elevated BP and complete neurological recovery within 24 h and/or favorable short-term outcome. Patients with ischemic stroke with hospital admission <6 h after symptom onset were prospectively included in a stroke registry (Bergen NORSTROKE Registry). BP was measured immediately after admission in all patients. Elevated BP was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg. The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity upon admission. Mild stroke was defined as NIHSS score <8, moderate stroke as NIHSS score 8-14, and severe stroke as NIHSS score ≥15. Complete neurological recovery (CNR) was defined as no persistent ischemic stroke symptoms at 24 h after admission. Favorable short-term outcome was defined as a modified Rankin Scale score of 0 or 1 at day 7. A total of 749 patients with ischemic stroke were included, of which 621 patients (82.9%) presented with elevated BP. Elevated BP was independently associated with mild stroke (odds ratio, OR: 2.12; 95% CI: 1.39-3.24; p < 0.001), whereas lack of elevated BP was independently associated with severe stroke (OR: 0.41; 95% CI: 0.25-0.68; p < 0.001). There was a nonsignificant association between elevated BP and CNR (OR: 2.11; 95% CI: 0.96-4.68; p = 0.063), yet no association

  14. Targeting neutrophils in ischemic stroke: translational insights from experimental studies

    PubMed Central

    Jickling, Glen C; Liu, DaZhi; Ander, Bradley P; Stamova, Boryana; Zhan, Xinhua; Sharp, Frank R

    2015-01-01

    Neutrophils have key roles in ischemic brain injury, thrombosis, and atherosclerosis. As such, neutrophils are of great interest as targets to treat and prevent ischemic stroke. After stroke, neutrophils respond rapidly promoting blood–brain barrier disruption, cerebral edema, and brain injury. A surge of neutrophil-derived reactive oxygen species, proteases, and cytokines are released as neutrophils interact with cerebral endothelium. Neutrophils also are linked to the major processes that cause ischemic stroke, thrombosis, and atherosclerosis. Thrombosis is promoted through interactions with platelets, clotting factors, and release of prothrombotic molecules. In atherosclerosis, neutrophils promote plaque formation and rupture by generating oxidized-low density lipoprotein, enhancing monocyte infiltration, and degrading the fibrous cap. In experimental studies targeting neutrophils can improve stroke. However, early human studies have been met with challenges, and suggest that selective targeting of neutrophils may be required. Several properties of neutrophil are beneficial and thus may important to preserve in patients with stroke including antimicrobial, antiinflammatory, and neuroprotective functions. PMID:25806703

  15. The asparaginyl endopeptidase legumain after experimental stroke.

    PubMed

    Ishizaki, Taku; Erickson, Agnes; Kuric, Enida; Shamloo, Mehrdad; Hara-Nishimura, Ikuko; Inácio, Ana Rita Lourenço; Wieloch, Tadeusz; Ruscher, Karsten

    2010-10-01

    Various proteases in the brain contribute to ischemic brain injury. We investigated the involvement of the asparaginyl endopeptidase legumain after experimental stroke. On the basis of gene array studies and in situ hybridizations, we observed an increase of legumain expression in the peri-infarct area of rats after transient occlusion of the middle cerebral artery (MCAO) for 120 mins with a maximum expression at 24 and 48 h. Immunohistochemical analyses revealed the expression of legumain in Iba1(+) microglial cells and glial fibrillary acidic protein-positive astrocytes of the peri-infarct area in mice after MCAO. Post-stroke recovery was also studied in aged legumain-deficient mice (45 to 58 weeks old). Legumain-deficient mice did not show any differences in physiologic parameters compared with respective littermates before, during MCAO (45 mins), and the subsequent recovery period of 8 days. Moreover, legumain deficiency had no effect on mortality, infarct volume, and the neurologic deficit determined by the rotating pole test, a standardized grip strength test, and the pole test. However, a reduced number of invading CD74(+) cells in the ischemic hemisphere indicates an involvement in post-stroke inflammation. We conclude that legumain is not essential for the functional deficit after MCAO but may be involved in mechanisms of immune cell invasion.

  16. Temporal profile of body temperature in acute ischemic stroke: relation to stroke severity and outcome

    PubMed Central

    2012-01-01

    Background Pyrexia after stroke (temperature ≥37.5°C) is associated with poor prognosis, but information on timing of body temperature changes and relationship to stroke severity and subtypes varies. Methods We recruited patients with acute ischemic stroke, measured stroke severity, stroke subtype and recorded four-hourly tympanic (body) temperature readings from admission to 120 hours after stroke. We sought causes of pyrexia and measured functional outcome at 90 days. We systematically summarised all relevant previous studies. Results Amongst 44 patients (21 males, mean age 72 years SD 11) with median National Institute of Health Stroke Score (NIHSS) 7 (range 0–28), 14 had total anterior circulation strokes (TACS). On admission all patients, both TACS and non-TACS, were normothermic (median 36.3°C vs 36.5°C, p=0.382 respectively) at median 4 hours (interquartile range, IQR, 2–8) after stroke; admission temperature and NIHSS were not associated (r2=0.0, p=0.353). Peak temperature, occurring at 35.5 (IQR 19.0 to 53.8) hours after stroke, was higher in TACS (37.7°C) than non-TACS (37.1°C, p<0.001) and was associated with admission NIHSS (r2=0.20, p=0.002). Poor outcome (modified Rankin Scale ≥3) at 90 days was associated with higher admission (36.6°C vs. 36.2°C p=0.031) and peak (37.4°C vs. 37.0°C, p=0.016) temperatures. Sixteen (36%) patients became pyrexial, in seven (44%) of whom we found no cause other than the stroke. Conclusions Normothermia is usual within the first 4 hours of stroke. Peak temperature occurs at 1.5 to 2 days after stroke, and is related to stroke severity/subtype and more closely associated with poor outcome than admission temperature. Temperature-outcome associations after stroke are complex, but normothermia on admission should not preclude randomisation of patients into trials of therapeutic hypothermia. PMID:23075282

  17. 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.

  18. Successfully Climbing the "STAIRs": Surmounting Failed Translation of Experimental Ischemic Stroke Treatments.

    PubMed

    Kahle, Michael P; Bix, Gregory J

    2012-01-01

    The Stroke Therapy Academic Industry Roundtable (STAIR) provided initial (in 1999) and updated (in 2009) recommendations with the goal of improving preclinical stroke therapy assessment and to increase the translational potential of experimental stroke treatments. It is important for preclinical stroke researchers to frequently consider and revisit these concepts, especially since promising experimental stroke treatments continue to fail in human clinical trials. Therefore, this paper will focus on considerations for several key aspects of preclinical stroke studies including the selection and execution of the animal stroke model, drug/experimental treatment administration, and outcome measures to improve experimental validity and translation potential. Specific points of interest discussed include the incorporation of human comorbid conditions and drugs, the benefits of defining a proposed mechanism of action, replication of results using multiple methods, using clinically relevant routes of administration and treatment time windows, and performing and reporting good experimental methods to reduce bias such as, as suggested by the updated STAIR recommendations, sample size calculations, randomization, allocation concealment, blinding, and appropriate inclusion/exclusion criteria. It is our hope that reviewing and revisiting these considerations will benefit researchers in their investigations of stroke therapies and increase the likelihood of translational success in the battle against stroke.

  19. Interactions between Age, Sex, and Hormones in Experimental Ischemic Stroke

    PubMed Central

    Liu, Fudong; McCullough, Louise D.

    2012-01-01

    Age, sex, and gonadal hormones have profound effects on ischemic stroke outcomes, although how these factors impact basic stroke pathophysiology remains unclear. There is a plethora of inconsistent data reported throughout the literature, primarily due to differences in the species examined, the timing and methods used to evaluate injury, the models used, and confusion regarding differences in stroke incidence as seen in clinical populations versus effects on acute neuroprotection or neurorepair in experimental stroke models. Sex and gonadal hormone exposure have considerable independent impact on stroke outcome, but these factors also interact with each other, and the contribution of each differs throughout the lifespan. The contribution of sex and hormones to experimental stroke will be the focus of this review. Recent advances and our current understanding of age, sex, and hormone interactions in ischemic stroke with a focus on inflammation will be discussed. PMID:23068990

  20. Tracheostomy after severe ischemic stroke: a population-based study.

    PubMed

    Walcott, Brian P; Kamel, Hooman; Castro, Brandyn; Kimberly, W Taylor; Sheth, Kevin N

    2014-01-01

    Stroke can result in varying degrees of respiratory failure. Some patients require tracheostomy in order to facilitate weaning from mechanical ventilation, long-term airway protection, or a combination of the two. Little is known about the rate and predictors of this outcome in patients with severe stroke. We aim to determine the rate of tracheostomy after severe ischemic stroke. Using the Nationwide Inpatient Sample database from 2007 to 2009, patients hospitalized with ischemic stroke were identified based on validated International Classification of Diseases, 9th revision, Clinical Modification codes. Next, patients with stroke were stratified based on whether they were treated with or without decompressive craniectomy, and the rate of tracheostomy for each group was determined. A logistic regression analysis was used to identify predictors of tracheostomy after decompressive craniectomy. Survey weights were used to obtain nationally representative estimates. In 1,550,000 patients discharged with ischemic stroke nationwide, the rate of tracheostomy was 1.3% (95% confidence interval [CI], 1.2-1.4%), with a 1.3% (95% CI, 1.1-1.4%) rate in patients without decompressive craniectomy and a 33% (95% CI, 26-39%) rate in the surgical treatment group. Logistic regression analysis identified pneumonia as being significantly associated with tracheostomy after decompressive craniectomy (odds ratio, 3.95; 95% CI, 1.95-6.91). Tracheostomy is common after decompressive craniectomy and is strongly associated with the development of pneumonia. Given its impact on patient function and potentially modifiable associated factors, tracheostomy may warrant further study as an important patient-centered outcome among patients with stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Tracheostomy following severe ischemic stroke: a population based study

    PubMed Central

    Walcott, Brian P.; Kamel, Hooman; Castro, Brandyn; Kimberly, W. Taylor; Sheth, Kevin N.

    2013-01-01

    Goal Stroke can result in varying degrees of respiratory failure. Some patients require tracheostomy in order to facilitate weaning from mechanical ventilation, long-term airway protection, or a combination of the two. Little is known about the rate and predictors of this outcome in patients with severe stroke. We aim to determine the rate of tracheostomy after severe ischemic stroke. Materials & Methods Using the Nationwide Inpatient Sample database from 2007–2009, patients hospitalized with ischemic stroke were identified based on validated International Classification of Diseases, 9th Revision, Clinical Modification codes. Next, patients with stroke were stratified based on whether they were treated with or without decompressive craniectomy, and the rate of tracheostomy for each group was determined. A logistic regression analysis was used to identify predictors of tracheostomy after decompressive craniectomy. Survey weights were used to obtain nationally representative estimates. Findings In 1,550,000 patients discharged with ischemic stroke nationwide, the rate of tracheostomy was 1.3% (95% CI, 1.2–1.4%), with a 1.3% (95% CI, 1.1–1.4%) rate in patients without decompressive craniectomy and a 33% (95% CI, 26–39%) rate in the surgical-treatment group. Logistic regression analysis identified pneumonia as being significantly associated with tracheostomy after decompressive craniectomy (OR 3.95; 95% CI 1.95–6.91). Conclusion Tracheostomy is common following decompressive craniectomy and is strongly associated with the development of pneumonia. Given its impact on patient function and potentially modifiable associated factors, tracheostomy may warrant further study as an important patient-centered outcome among patients with stroke. PMID:24103666

  2. 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

  3. Neuroanatomical correlates of severe cardiac arrhythmias in acute ischemic stroke.

    PubMed

    Seifert, Frank; Kallmünzer, Bernd; Gutjahr, Isabell; Breuer, Lorenz; Winder, Klemens; Kaschka, Iris; Kloska, Stephan; Doerfler, Arnd; Hilz, Max-Josef; Schwab, Stefan; Köhrmann, Martin

    2015-05-01

    Neurocardiological interactions can cause severe cardiac arrhythmias in patients with acute ischemic stroke. The relationship between the lesion location in the brain and the occurrence of cardiac arrhythmias is still discussed controversially. The aim of the present study was to correlate the lesion location with the occurrence of cardiac arrhythmias in patients with acute ischemic stroke. Cardiac arrhythmias were systematically assessed in patients with acute ischemic stroke during the first 72 h after admission to a monitored stroke unit. Voxel-based lesion-symptom mapping (VLSM) was used to correlate the lesion location with the occurrence of clinically relevant severe arrhythmias. Overall 150 patients, 56 with right-hemispheric and 94 patients with a left-hemispheric lesion, were eligible to be included in the VLSM study. Severe cardiac arrhythmias were present in 49 of these 150 patients (32.7%). We found a significant association (FDR correction, q < 0.05) between lesions in the right insular, right frontal and right parietal cortex as well as the right amygdala, basal ganglia and thalamus and the occurrence of cardiac arrhythmias. Because left- and right-hemispheric lesions were analyzed separately, the significant findings rely on the 56 patients with right-hemispheric lesions. The data indicate that these areas are involved in central autonomic processing and that right-hemispheric lesions located to these areas are associated with an elevated risk for severe cardiac arrhythmias.

  4. Neuroprotection in experimental stroke with targeted neurotrophins.

    PubMed

    Wu, Dafang

    2005-01-01

    More than 30 neurotrophins have been identified, and many of them have neuroprotective effects in brain ischemia or injury. However, all the clinical trials with several neurotrophins for the treatment of acute ischemic stroke or neurodegenerative diseases have failed so far, primarily because of their poor blood-brain barrier (BBB) permeability. This article is an overview of recent progress in the research focused on BBB targeted neurotrophins using a chimeric peptide approach, in which antitransferrin receptor antibody was used as a BBB delivery vector, and neurotrophin peptide was conjugated to the antibody via the avidin/biotin technology. Vasoactive intestinal peptide was the first model chimeric peptide to show an enhanced CNS effect after noninvasive peripheral administration. Brain-derived neurotrophic factor (BDNF) chimeric peptide was neuroprotective in rats subjected to transient forebrain ischemia, permanent focal ischemia, or transient focal ischemia. Delayed treatments with the BDNF chimeric peptide showed an effective time window of 1-2 h after ischemia. Basic FGF chimeric peptide was highly effective in the reduction of infarct volume in the rat model of permanent focal ischemia, with lowest effective dose of 1 mug per rat. Future studies in this exciting area include genetically engineered fusion proteins or humanized antibodies for BBB drug targeting with less immunogenicity and reduced working burden in the chemical conjugation, the use of antihuman insulin receptor antibody for higher BBB delivery efficiency, and combination therapies using chimeric neurotrophins plus other neuroprotectants to achieve additive or synergistic effects.

  5. 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.

  6. 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

  7. The Role of Arginase 1 in Post-Stroke Immunosuppression and Ischemic Stroke Severity.

    PubMed

    Petrone, Ashley B; O'Connell, Grant C; Regier, Michael D; Chantler, Paul D; Simpkins, James W; Barr, Taura L

    2016-04-01

    A balanced immune system response plays an important role in acute ischemic stroke (AIS) recovery. Our laboratory has previously identified several immune-related genes, including arginase 1 (ARG1), with altered expression in human AIS patients. The neutrophil-lymphocyte ratio (NLR) may be a marker of the degree of immune dysregulation following AIS; however, the molecular mechanisms that may mediate the NLR are unknown. The purpose of this study was to (1) examine the relationship between ARG1, NLR, and AIS severity and (2) to utilize principal component analysis (PCA) to statistically model multiple gene expression changes following AIS. AIS patients and stroke-free control subjects were recruited, and blood samples were collected from AIS patients within 24 h of stroke symptom onset. White blood cell differentials were obtained at this time to calculate the NLR. Gene expression was measured using real-time PCR. PCA with varimax rotation was used to develop composite variables consisting of a five-gene profile. ARG1 was positively correlated with NLR (r = 0.57, p = 0.003), neutrophil count (r = 0.526, p = 0.007), NIHSS (r = 0.607, p = 0.001), and infarct volume (r = 0.27, p = 0.051). PCA identified three principal components that explain 84.4 % of variation in the original patient gene dataset comprised of ARG1, LY96, MMP9, s100a12, and PC1 was a significant explanatory variable for NIHSS (p < 0.001) and NLR (p = 0.005). Our study suggests a novel relationship between ARG1, NLR, and stroke severity, and the NLR is an underutilized clinically available biomarker to monitor the post-stroke immune response.

  8. Experimental neuroprotection in ischemic stroke: a concise review.

    PubMed

    Rajah, Gary B; Ding, Yuchuan

    2017-04-01

    Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide. To date, intravenous tissue plasminogen activator and mechanical thrombectomy have been standards of care for AIS. There have been many advances in diagnostic imaging and endovascular devices for AIS; however, most neuroprotective therapies seem to remain largely in the preclinical phase. While many neuroprotective therapies have been identified in experimental models, none are currently used routinely to treat stroke patients. This review seeks to summarize clinical studies pertaining to neuroprotection, as well as the different preclinical neuroprotective therapies, their presumed mechanisms of action, and their future applications in stroke patients.

  9. 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

  10. [Sequential enteral nutrition support for patients with severe cerebral stroke].

    PubMed

    Chen, Jiefang; He, Xudong; Zhang, Lisan; Hu, Xingyue

    2013-11-01

    To evaluate the efficacy of sequential enteral nutrition support in patients with severe cerebral stroke. Forty-nine patients with severe cerebral stroke met the inclusion criteria were randomly divided into sequential enteral nutrition group (Group A, n=24) and conventional enteral nutrition group (Group B, n=25). Patients in Group A received short-peptide-based enteral nutrition support first, then gradually transferred to intact protein enteral nutrition. Meanwhile, patients in Group B constantly received intact protein enteral nutrition support. The nutritional indexes and the rate of complications were compared between two groups. The nutritional indexes were decreased in both groups within 4 weeks after admission, but the decreasing levels of hemoglobin and albumin in Group A were significantly lower than those in Group B (P<0.05), and the incidence of infections and gastrointestinal hemorrhage in Group A was also lower than that in Group B (P<0.05). However, there were no significant differences in body weight, BMI, triceps skinfold thickness, biceps circumference, arm muscle circumference between two groups (P>0.05). Sequential enteral nutritional support can improve the nutritional status and decrease the incidence of complications in critical patients with cerebral stroke.

  11. Sex Differences in Stroke Subtypes, Severity, Risk Factors, and Outcomes among Elderly Patients with Acute Ischemic Stroke.

    PubMed

    Yu, Changshen; An, Zhongping; Zhao, Wenjuan; Wang, Wanjun; Gao, Chunlin; Liu, Shoufeng; Wang, Jinghua; Wu, Jialing

    2015-01-01

    Although the age-specific incidence and mortality of stroke is higher among men, stroke has a greater clinical effect on women. However, the sex differences in stroke among elderly patients are unknown. Therefore, we aimed to assess the sex differences in stroke among elderly stroke patients. Between 2005 and 2013, we recruited 1484 consecutive acute ischemic stroke (AIS) patients (≥75 years old) from a specialized neurology hospital in Tianjin, China. Information regarding their stroke subtypes, severity, risk factors, and outcomes at 3 and 12 months after stroke were recorded. Comparing with men, women had a significantly higher prevalence of severe stroke (17.20 vs. 12.54%), hypertension (76.42 vs. 66.39%), dyslipidemias (30.35 vs. 22.76%), and obesity (18.40 vs. 9.32%), P < 0.05. Comparing with women, men had a significantly higher prevalence of intracranial artery stenosis (23.11 vs. 17.45%), current smoking (29.60 vs. 13.05%), and alcohol consumption (12.15 vs. 0.47%), P < 0.05. Moreover, dependency was more common among women at 3 and 12 months after stroke, although the sex difference disappeared after adjusting for stroke subtypes, severity, and risk factors. Elderly women with AIS had more severe stroke status and worse outcomes at 3 and 12 months after stroke. Thus, elderly female post-AIS patients are a crucial population that should be assisted with controlling their risk factors for stroke and changing their lifestyle.

  12. 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

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

    PubMed

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

    2015-02-01

    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.

  14. Stroke

    MedlinePlus

    ... version of this page please turn Javascript on. Stroke About Stroke Stroke -- A Serious Event A stroke is serious, just ... lifestyle can help you prevent stroke. What Is Stroke? A stroke is sometimes called a "brain attack." ...

  15. Dissociation of severity of stroke and aphasia recovery early after intravenous recombinant tissue plasminogen activator thrombolysis.

    PubMed

    Kremer, Christine; Kappelin, Johan; Perren, Fabienne

    2014-10-01

    Clinical observation suggested to us that aphasia recovers relatively better than other deficits early after intravenous recombinant tissue plasminogen activator (IV-rtPA) treatment in stroke patients with minor deficits, while the reverse seemed the case in those with severe deficits. Retrospective analysis of acute ischemic stroke patients with aphasia admitted within 3 hours from symptom onset and treated with IV-rtPA was carried out. Stroke severity, aphasia and global neurological impairment were assessed at admission and 24 hours after thrombolysis. Improvement of aphasia (gain of ⩾ 1 point on the National Institutes of Health Stroke Scale [NIHSS] aphasia score) and global neurological improvement (gain of ⩾ 4 points on the NIHSS) were compared in minor strokes (NIHSS ⩽ 7), moderate strokes (NIHSS 8-15), and major strokes (NIH ⩾ 16). Sixty-nine of 243 stroke patients suffered from aphasia. Improvement of aphasia occurred in 7/16 minor strokes, 11/25 moderate strokes, and 7/28 severe strokes. Improvement of ⩾ 4 points on the NIHSS occurred in 3/16 minor strokes, 17/25 moderate strokes and 15/28 severe strokes. There is a significant (X(2)=4.073, p<0.05) dissociation of recovery of aphasia and that of other neurological deficits between minor versus severe strokes. This confirms the clinically suspected dissociation between a good early recovery from aphasia in minor strokes relative to recovery of other neurological deficits, as opposed to a better recovery from other neurological deficits than from aphasia in patients with severe strokes.

  16. Stroke neuroprotection revisited: Intra-arterial verapamil is profoundly neuroprotective in experimental acute ischemic stroke.

    PubMed

    Maniskas, Michael E; Roberts, Jill M; Aron, Ishi; Fraser, Justin F; Bix, Gregory J

    2016-04-01

    While clinical trials have now solidified the role of thrombectomy in emergent large vessel occlusive stroke, additional therapies are needed to optimize patient outcome. Using our previously described experimental ischemic stroke model for evaluating adjunctive intra-arterial drug therapy after vessel recanalization, we studied the potential neuroprotective effects of verapamil. A calcium channel blocker, verapamil is often infused intra-arterially by neurointerventionalists to treat cerebral vasospasm. Such a direct route of administration allows for both focused targeting of stroke-impacted brain tissue and minimizes potential systemic side effects. Intra-arterial administration of verapamil at a flow rate of 2.5 µl/min and injection volume of 10 µl immediately after middle cerebral artery recanalization in C57/Bl6 mice was shown to be profoundly neuroprotective as compared to intra-arterial vehicle-treated stroke controls. Specifically, we noted a significant (P ≤ 0.05) decrease in infarct volume, astrogliosis, and cellular apoptosis as well as a significant increase in neuronal survival and functional outcome over seven days. Furthermore, intra-arterial administration of verapamil was well tolerated with no hemorrhage, systemic side effects, or increased mortality. Thus, verapamil administered intra-arterially immediately following recanalization in experimental ischemic stroke is both safe and neuroprotective and merits further study as a potential therapeutic adjunct to thrombectomy.

  17. Mediterranean Diet in patients with acute ischemic stroke: Relationships between Mediterranean Diet score, diagnostic subtype, and stroke severity index.

    PubMed

    Tuttolomondo, Antonino; Casuccio, Alessandra; Buttà, Carmelo; Pecoraro, Rosaria; Di Raimondo, Domenico; Della Corte, Vittoriano; Arnao, Valentina; Clemente, Giuseppe; Maida, Carlo; Simonetta, Irene; Miceli, Giuseppe; Lucifora, Benedetto; Cirrincione, Anna; Di Bona, Danilo; Corpora, Francesca; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

    2015-11-01

    Adherence to a Mediterranean Diet appears to reduce the risk of cardiovascular disease, cancer, Alzheimer's disease, and Parkinson's disease, as well as the risk of death due to cardiovascular disease. No study has addressed the association between diagnostic subtype of stroke and its severity and adherence to a Mediterranean Diet in subjects with acute ischemic stroke. To evaluate the association between Mediterranean Diet adherence, TOAST subtype, and stroke severity by means of a retrospective study. The type of acute ischemic stroke was classified according to the TOAST criteria. All patients admitted to our ward with acute ischemic stroke completed a 137-item validated food-frequency questionnaire adapted to the Sicilian population. A scale indicating the degree of adherence to the traditional Mediterranean Diet was used (Me-Di score: range 0-9). 198 subjects with acute ischemic stroke and 100 control subjects without stroke. Stroke subjects had a lower mean Mediterranean Diet score compared to 100 controls without stroke. We observed a significant positive correlation between Me-Di score and SSS score, whereas we observed a negative relationship between Me-Di score and NIHSS and Rankin scores. Subjects with atherosclerotic (LAAS) stroke subtype had a lower mean Me-Di score compared to subjects with other subtypes. Multinomial logistic regression analysis in a simple model showed a negative relationship between MeDi score and LAAS subtype vs. lacunar subtype (and LAAS vs. cardio-embolic subtype). Patients with lower adherence to a Mediterranean Diet are more likely to have an atherosclerotic (LAAS) stroke, a worse clinical presentation of ischemic stroke at admission and a higher Rankin score at discharge. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Effects of Chronic and Acute Oestrogen Replacement Therapy in Aged Animals after Experimental Stroke

    PubMed Central

    Liu, F.; Benashski, S. E.; Xu, Y.; Siegel, M.; McCullough, L. D.

    2013-01-01

    The effect of oestrogen replacement therapy (ERT) on stroke incidence and severity has been extensively debated. Clinical trials of ERT have demonstrated an increased risk of stroke in treated women, although the study participants were well past menopause when therapy was initiated. It has been suggested that detrimental effects of ERT may be unmasked after prolonged periods of hypoestrogenicity. To date, very few studies have examined the effect of ERT in aged animals, although the timing of replacement may be critical to the neuroprotective effects of ERT. We hypothesised that chronic ERT initiated in late middle age would decrease infarct size in the brain after an induced stroke, whereas acute ERT would have no beneficial effects in aged females. To test this hypothesis, two paradigms of ERT were administered to aged mice of both sexes aiming to determine the effects on stroke outcome and to explore the possible mechanisms by which ERT interacts with age. Female mice that received chronic ERT from 17–20 months of age showed improved stroke outcomes after experimental stroke, whereas females that had acute ERT initiated at 20 months of age did not. Chronic ERT females exhibited diminished levels of nuclear factor kappa B (NF-κB) translocation compared to acute ERT females after stroke. Acute ERT females demonstrated both an increase in nuclear NF-κB and enhanced expression of pro-inflammatory cytokines. In addition, a sexual dimorphic effect of ERT was seen because males benefited from ERT, regardless of the timing of initiation. Aged males had significantly reduced expression of pro-inflammatory markers after stroke compared to age-matched females, suggesting a pro-inflammatory milieu emerges with age in females. These results are consistent with the emerging clinical literature suggesting that ERT should be initiated at the time of menopause to achieve beneficial effects. The present study demonstrates the importance of using appropriate animal models in

  19. Sex differences in regulatory cells in experimental stroke.

    PubMed

    Seifert, Hilary A; Benedek, Gil; Liang, Jian; Nguyen, Ha; Kent, Gail; Vandenbark, Arthur A; Saugstad, Julie A; Offner, Halina

    2017-08-01

    Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19(+)CD5(+)CD1d(hi) B10 cells as well as anti-inflammatory CD11b(+)CD206(+) microglia/macrophages in the ipsilateral vs. contralateral hemisphere of female but not male mice undergoing 60min middle cerebral artery occlusion followed by 96h of reperfusion. Moreover, female mice with MCAO had increased total spleen cell numbers but lower B10 levels in spleens. These results elucidate differing sex-dependent regulatory mechanisms that account for diminished stroke severity in females and underscore the need to test immune-modulating therapies for stroke in both males and females. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Chronic metformin treatment improves post-stroke angiogenesis and recovery after experimental stroke

    PubMed Central

    Venna, Venugopal Reddy; Li, Jun; Hammond, Matthew D.; Mancini, Nickolas S.; McCullough, Louise D.

    2014-01-01

    Metformin is currently the first-line treatment drug for type 2 diabetes. Metformin is a well-known activator of AMP-activated protein kinase (AMPK). In experimental studies, metformin has been shown to exert direct vascular effects by increasing vascular endothelial growth factor expression and improving microvascular density. As stroke is the leading cause of long-term disability and angiogenesis is implicated as an important mechanism in functional recovery, we hypothesized that chronic metformin treatment would improve post-stroke functional recovery by enhancing functional microvascular density. For this study, C57BL/6N male mice were subjected to a 60-min middle cerebral artery occlusion, and were given 50 mg/kg/day metformin beginning 24 h post-stroke for 3 weeks. Behavioral recovery was assessed using adhesive-tape removal and the apomorphine-induced turning test. The role of angiogenesis was assessed by counting vessel branch points from fluorescein-conjugated lectin-perfused brain sections. Importantly even if metformin treatment was initiated 24 h after injury it enhanced recovery and significantly improved stroke-induced behavioral deficits. This recovery occurred in parallel with enhanced angiogenesis and with restoration of endogenous cerebral dopaminergic tone and revascularization of ischemic tissue. We assessed if the effects on recovery and angiogenesis were mediated by AMPK. When tested in AMPK α-2 knockout mice, we found that metformin treatment did not have the same beneficial effects on recovery and angiogenesis, suggesting that metformin-induced angiogenic effects are mediated by AMPK. The results from this study suggest that metformin mediates post-stroke recovery by enhancing angiogenesis, and these effects are mediated by AMPK signaling. PMID:24649970

  1. Cortisol levels and the severity and outcomes of acute stroke: a systematic review.

    PubMed

    Barugh, Amanda Jayne; Gray, Paul; Shenkin, Susan Deborah; MacLullich, Alasdair Maurice Joseph; Mead, Gillian Elizabeth

    2014-03-01

    Studies in non-stroke patients have shown an association between dysregulation of the hypothalamic-pituitary-adrenal axis and morbidity and mortality. We conducted a systematic review to evaluate cortisol levels in acute stroke and their associations with outcome. We searched MEDLINE and EMBASE for articles up to April 2013 and PsychINFO for articles up to July 2013, using the keywords "cortisol" and "stroke" and associated terms or synonyms. We included studies published in peer-reviewed journals that recruited 10 or more participants and measured cortisol at least once in the first year following stroke. Data were extracted regarding cortisol levels, including changes over time and their relationship to stroke severity, and outcome. Of 11,240 abstracts, 101 full texts were obtained and 48 fulfilled our inclusion criteria. Cortisol levels were high in the first week after stroke in the majority of studies (26 studies, n = 1,340). Higher cortisol was associated with dependency (8/11 studies, n = 822), delirium (5/6 studies, n = 269) depression (3/5 studies n = 117) and mortality (8/10 studies, n = 856). Five studies adjusted for stroke severity; one found an association between higher cortisol and dependency, and three found an association between higher cortisol and mortality. Cortisol levels are high for at least 7 days after stroke. Elevated cortisol after stroke is associated with dependency, morbidity, and mortality; however, there is insufficient evidence to conclude that these relationships are independent of stroke severity.

  2. Stress as necessary component of realistic recovery in animal models of experimental stroke.

    PubMed

    Walker, Frederick R; Jones, Kimberley A; Patience, Madeleine J; Zhao, Zidan; Nilsson, Michael

    2014-02-01

    Over the last decade there has been a considerable effort directed toward reformulating the standard approach taken to preclinically model stroke and stroke recovery. The principal objective of this undertaking has been to improve the success with which preclinical findings can be translated. Although several advancements have already been introduced, one potentially critical feature that appears to have been overlooked is psychological stress. Stroke is well recognized to produce high levels of stress in patients, and ongoing exposure to stress is recognized to deleteriously interfere with recovery. The presence of high levels of stress (distress) in stroke patients is also relevant because nearly all clinically deployed neurorestorative interventions occur against this background. Somewhat perplexingly, however, we could find no preclinical stroke studies concerned with investigating the efficacy of putative neurorestorative compounds that did so in the presence of stress. The following article will make the case that failure to recognize or compensate for the effects of ongoing stress in standard preclinical experimental models of recovery is likely to result in overestimation of the effectiveness of pharmacological or behavioral neurorestorative interventions.

  3. Cortisol levels and the severity and outcomes of acute stroke: a systematic review

    PubMed Central

    Gray, Paul; Shenkin, Susan Deborah; MacLullich, Alasdair Maurice Joseph; Mead, Gillian Elizabeth

    2016-01-01

    Studies in non-stroke patients have shown an association between dysregulation of the hypothalamic–pituitary–adrenal axis and morbidity and mortality. We conducted a systematic review to evaluate cortisol levels in acute stroke and their associations with outcome. We searched MEDLINE and EMBASE for articles up to April 2013 and PsychINFO for articles up to July 2013, using the keywords “cortisol” and “stroke” and associated terms or synonyms. We included studies published in peer-reviewed journals that recruited 10 or more participants and measured cortisol at least once in the first year following stroke. Data were extracted regarding cortisol levels, including changes over time and their relationship to stroke severity, and outcome. Of 11,240 abstracts, 101 full texts were obtained and 48 fulfilled our inclusion criteria. Cortisol levels were high in the first week after stroke in the majority of studies (26 studies, n = 1,340). Higher cortisol was associated with dependency (8/11 studies, n = 822), delirium (5/6 studies, n = 269) depression (3/5 studies n = 117) and mortality (8/10 studies, n = 856). Five studies adjusted for stroke severity; one found an association between higher cortisol and dependency, and three found an association between higher cortisol and mortality. Cortisol levels are high for at least 7 days after stroke. Elevated cortisol after stroke is associated with dependency, morbidity, and mortality; however, there is insufficient evidence to conclude that these relationships are independent of stroke severity. PMID:24477489

  4. Synergism of Short-Term Air Pollution Exposures and Neighborhood Disadvantage on Initial Stroke Severity.

    PubMed

    Wing, Jeffrey J; Sánchez, Brisa N; Adar, Sara D; Meurer, William J; Morgenstern, Lewis B; Smith, Melinda A; Lisabeth, Lynda D

    2017-09-27

    Little is known about the relation between environment and stroke severity. We investigated associations between environmental exposures, including neighborhood socioeconomic disadvantage and short-term exposure to airborne particulate matter <2.5 μm and ozone, and their interactions with initial stroke severity. First-ever ischemic stroke cases were identified from the Brain Attack Surveillance in Corpus Christi project (2000-2012). Associations between pollutants, disadvantage, and National Institutes of Health Stroke Scale were modeled using linear and logistic regression with adjustment for demographics and risk factors. Pollutants and disadvantage were modeled individually, jointly, and with interactions. Higher disadvantage scores and previous-day ozone concentrations were associated with higher odds of severe stroke. Higher levels of particulate matter <2.5 μm were associated with higher odds of severe stroke among those in higher disadvantage areas (odds ratio, 1.24; 95% confidence interval, 1.00-1.55) but not in lower disadvantage areas (odds ratio, 0.82; 95% confidence interval, 0.56-1.22; P interaction =0.097). Air pollution exposures and neighborhood socioeconomic status may be important in understanding stroke severity. Future work should consider the multiple levels of influence on this important stroke outcome. © 2017 American Heart Association, Inc.

  5. Test repositioning for functional assessment of neurological outcome after experimental stroke in mice

    PubMed Central

    Godino, María del Carmen; Díaz-Guzmán, Jaime; Moro, María Ángeles; Lizasoain, Ignacio

    2017-01-01

    Stroke is a cerebrovascular pathology for which the only approved treatment is fibrinolysis. Several studies have focused on the development of new drugs but none has led to effective therapies to date, due, among others, to the difficulty to evaluate clinical deficits in experimental animal models. The present study aims to explore the applicability of known behavioral tests not commonly used in ischemia for the neurological assessment of mice after experimental stroke in different brain areas. A total of 225 CD1 male mice were randomly assigned to permanent middle cerebral artery occlusion by ligature (pMCAO) or permanent anterior cerebral artery occlusion by photothrombosis (pACAO) models. Modified neuroseverity score, footprint test, forced swim test and elevated plus maze were performed. Under these experimental conditions, modified neuroseverity score showed neurological impairment early after experimental stroke in both models. By contrast, the footprint test and the elevated plus maze detected short-term neurological deterioration in the pMCAO model but not in the pACAO model. Furthermore, the forced swim test identified depression-like behavior in mice after ischemia only when the left hemisphere was affected. In conclusion, we propose the repositioning of known neurobehavioral tests, but not commonly used in the stroke field, for the fast detection of neurological impairments early after ischemia, and even specific to discriminate the territory affected by arterial occlusion as well as the hemisphere where brain damage occurs. All these findings may prove useful to improve the experimental design of neuroprotective drugs in order to bridge the gap between experimental studies and clinical trials. PMID:28472090

  6. Test repositioning for functional assessment of neurological outcome after experimental stroke in mice.

    PubMed

    Hernández-Jiménez, Macarena; Peña-Martínez, Carolina; Godino, María Del Carmen; Díaz-Guzmán, Jaime; Moro, María Ángeles; Lizasoain, Ignacio

    2017-01-01

    Stroke is a cerebrovascular pathology for which the only approved treatment is fibrinolysis. Several studies have focused on the development of new drugs but none has led to effective therapies to date, due, among others, to the difficulty to evaluate clinical deficits in experimental animal models. The present study aims to explore the applicability of known behavioral tests not commonly used in ischemia for the neurological assessment of mice after experimental stroke in different brain areas. A total of 225 CD1 male mice were randomly assigned to permanent middle cerebral artery occlusion by ligature (pMCAO) or permanent anterior cerebral artery occlusion by photothrombosis (pACAO) models. Modified neuroseverity score, footprint test, forced swim test and elevated plus maze were performed. Under these experimental conditions, modified neuroseverity score showed neurological impairment early after experimental stroke in both models. By contrast, the footprint test and the elevated plus maze detected short-term neurological deterioration in the pMCAO model but not in the pACAO model. Furthermore, the forced swim test identified depression-like behavior in mice after ischemia only when the left hemisphere was affected. In conclusion, we propose the repositioning of known neurobehavioral tests, but not commonly used in the stroke field, for the fast detection of neurological impairments early after ischemia, and even specific to discriminate the territory affected by arterial occlusion as well as the hemisphere where brain damage occurs. All these findings may prove useful to improve the experimental design of neuroprotective drugs in order to bridge the gap between experimental studies and clinical trials.

  7. A longitudinal study investigating how stroke severity, disability, and physical function the first week post-stroke are associated with walking speed six months post-stroke.

    PubMed

    Aaslund, Mona Kristin; Moe-Nilssen, Rolf; Gjelsvik, Bente Bassøe; Bogen, Bård; Næss, Halvor; Hofstad, Håkon; Skouen, Jan Sture

    2017-08-17

    To investigate to which degree stroke severity, disability, and physical function the first week post-stroke are associated with preferred walking speed (PWS) at 6 months. Longitudinal observational study. Participants were recruited from a stroke unit and tested within the first week (baseline) and at 6 months post-stroke. Outcome measures were the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index (BI), modified Rankin Scale (mRS), PWS, Postural Assessment Scale for Stroke (PASS), and the Trunk Impairment Scale modified-Norwegian version. Multiple regression models were used to explore which variables best predict PWS at 6 months, and the Receiver Operating Characteristics (ROC) curves to determine the cutoffs. A total of 132 participants post-stroke were included and subdivided into two groups based on the ability to produce PWS at baseline. For the participants that could produce PWS at baseline (WSB group), PASS, PWS, and age at baseline predicted PWS at 6 months with an explained variance of 0.77. For the participants that could not produce a PWS at baseline (NoWSB group), only PASS predicted PWS at 6 months with an explained variance of 0.49. For the Walking speed at baseline (WSB) group, cutoffs at baseline for walking faster than 0.8 m/s at 6 months were 30.5 points on the PASS, PWS 0.75 m/s, and age 73.5 years. For the NoWSB group, the cutoff for PASS was 20.5 points. PASS, PWS, and age the first week predicted PWS at 6 months post-stroke for participants with the best walking ability, and PASS alone predicted PWS at 6 months post-stroke for participants with the poorest walking ability.

  8. Role of Acute Lesion Topography in Initial Ischemic Stroke Severity and Long-Term Functional Outcomes.

    PubMed

    Wu, Ona; Cloonan, Lisa; Mocking, Steven J T; Bouts, Mark J R J; Copen, William A; Cougo-Pinto, Pedro T; Fitzpatrick, Kaitlin; Kanakis, Allison; Schaefer, Pamela W; Rosand, Jonathan; Furie, Karen L; Rost, Natalia S

    2015-09-01

    Acute infarct volume, often proposed as a biomarker for evaluating novel interventions for acute ischemic stroke, correlates only moderately with traditional clinical end points, such as the modified Rankin Scale. We hypothesized that the topography of acute stroke lesions on diffusion-weighted magnetic resonance imaging may provide further information with regard to presenting stroke severity and long-term functional outcomes. Data from a prospective stroke repository were limited to acute ischemic stroke subjects with magnetic resonance imaging completed within 48 hours from last known well, admission NIH Stroke Scale (NIHSS), and 3-to-6 months modified Rankin Scale scores. Using voxel-based lesion symptom mapping techniques, including age, sex, and diffusion-weighted magnetic resonance imaging lesion volume as covariates, statistical maps were calculated to determine the significance of lesion location for clinical outcome and admission stroke severity. Four hundred ninety subjects were analyzed. Acute stroke lesions in the left hemisphere were associated with more severe NIHSS at admission and poor modified Rankin Scale at 3 to 6 months. Specifically, injury to white matter (corona radiata, internal and external capsules, superior longitudinal fasciculus, and uncinate fasciculus), postcentral gyrus, putamen, and operculum were implicated in poor modified Rankin Scale. More severe NIHSS involved these regions, as well as the amygdala, caudate, pallidum, inferior frontal gyrus, insula, and precentral gyrus. Acute lesion topography provides important insights into anatomic correlates of admission stroke severity and poststroke outcomes. Future models that account for infarct location in addition to diffusion-weighted magnetic resonance imaging volume may improve stroke outcome prediction and identify patients likely to benefit from aggressive acute intervention and personalized rehabilitation strategies. © 2015 American Heart Association, Inc.

  9. Wolf Motor Function Test for Characterizing Moderate to Severe Hemiparesis in Stroke Patients

    PubMed Central

    Hodics, Timea M.; Nakatsuka, Kyle; Upreti, Bhim; Alex, Arun; Smith, Patricia S.; Pezzullo, John C.

    2012-01-01

    Objective To extend the applicability of the Wolf Motor Function test (WMFT) to describe the residual functional abilities of moderate-to-severely affected stroke patients. The WMFT is a motor function test for mild to moderate upper extremity weakness in stroke patients, but it has not been routinely used for evaluation of more severe hemiparetic stroke patients due to its numerical characteristics. Design Data was collected as part of two double-blind sham controlled randomized interventional studies, the Transcranial Direct Current Stimulation (tDCS) in Chronic Stroke Recovery and tDCS Enhanced Stroke Recovery and Cortical Reorganization. Stroke patients were evaluated with the upper-extremity Fugl-Meyer (UFM) and the WMFT in the same setting prior to treatment. Setting University inpatient rehabilitation and outpatient clinic. Participants 32 stroke patients with moderate-to-severe hemiparesis enrolled in the tDCS in Chronic Stroke Recovery and tDCS Enhanced Stroke Recovery and Cortical Reorganization studies. Intervention Not applicable. Main Outcome Measures WMFT scores were calculated using 1) median performance times, 2) new calculation using the mean rate of performance. We compared the distribution of values from the two methods and examined the WMFT-UFM correlation for the traditional and the new calculation. Results WMFT rate values were more evenly distributed across their range than median WMFT time scores. The association between the WMFT rate and UFM was as good as the association between the median WMFT time scores and UFM (Spearman rs 0.84 vs −0.79). Conclusions The new WMFT mean rate of performance is valid and a more sensitive measure in describing the functional activities of the moderate to severely affected upper extremity of stroke subjects and avoids the pitfalls of the median WMFT time calculations. PMID:22579647

  10. Use of Antihypertensive Drugs and Ischemic Stroke Severity - Is There a Role for Angiotensin-II?

    PubMed

    Hwong, Wen Yea; Bots, Michiel L; Selvarajah, Sharmini; Abdul Aziz, Zariah; Sidek, Norsima Nazifah; Spiering, Wilko; Kappelle, L Jaap; Vaartjes, Ilonca

    2016-01-01

    The increase in angiotensin II (Ang II) formation by selected antihypertensive drugs is said to exhibit neuroprotective properties, but this translation into improvement in clinical outcomes has been inconclusive. We undertook a study to investigate the relationship between types of antihypertensive drugs used prior to a stroke event and ischemic stroke severity. We hypothesized that use of antihypertensive drugs that increase Ang II formation (Ang II increasers) would reduce ischemic stroke severity when compared to antihypertensive drugs that suppress Ang II formation (Ang II suppressors). From the Malaysian National Neurology Registry, we included hypertensive patients with first ischemic stroke who presented within 48 hours from ictus. Antihypertensive drugs were divided into Ang II increasers (angiotensin-I receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics) and Ang II suppressors (angiotensin-converting-enzyme inhibitors (ACEIs) and beta blockers). We evaluated stroke severity during admission with the National Institute of Health Stroke Scale (NIHSS). We performed a multivariable logistic regression with the score being dichotomized at 15. Scores of less than 15 were categorized as less severe stroke. A total of 710 patients were included. ACEIs was the most commonly prescribed antihypertensive drug in patients using Ang II suppressors (74%) and CCBs, in patients prescribed with Ang II increasers at 77%. There was no significant difference in the severity of ischemic stroke between patients who were using Ang II increasers in comparison to patients with Ang II suppressors (OR: 1.32, 95%CI: 0.83-2.10, p = 0.24). In our study, we found that use of antihypertensive drugs that increase Ang II formation was not associated with less severe ischemic stroke as compared to use of antihypertensive drugs that suppress Ang II formation.

  11. [Disability after stroke: a longitudinal study in moderate and severe stroke patients included in a multidisciplinary rehabilitation program].

    PubMed

    Noe-Sebastian, E; Balasch-Bernat, M; Colomer-Font, C; Moliner-Munoz, B; Rodriguez Sanchez-Leiva, C; Ugart, P; Llorens, R; Ferri-Campos, J

    2017-05-01

    Stroke is a recognized cause of disability among adults. However the impact that the deficits that occur after a moderate/severe stroke have on long-term disability, as well as the response of the resultant deficits to rehabilitation, are not completely understood. A total of 396 patients with a modified Rankin score >= 3 after an ischemic (n = 221) or hemorrhagic (n = 175) stroke were included in this study. All patients were assessed with cognitive, behavior, emotional, motor and functional domains. All patients were assessed at baseline and six months after inclusion in a multidisciplinary rehabilitation program. Risk of falling (Berg Balance Scale < 45 in 83.1% of the sample at baseline and 49.5% at follow-up) and functional problems (82.8% with a Barthel Index < 75 at baseline and 53% at follow-up) were the most prevalent deficits. Emotional disturbances were those that most improved while behavioral problems were those that did less. Although global disability improved during treatment among most patients, only 11% of our patients, especially those with preserved cognitive function at baseline, could be classified as patients with mild disability at follow-up. Stroke consequences are multidimensional. The symptoms that the stroke can cause in multiple domains, as well as the pattern of recovery are widely diverse, with prevalence of behavioral long-term disturbances.

  12. Developing a stroke severity index based on administrative data was feasible using data mining techniques.

    PubMed

    Sung, Sheng-Feng; Hsieh, Cheng-Yang; Kao Yang, Yea-Huei; Lin, Huey-Juan; Chen, Chih-Hung; Chen, Yu-Wei; Hu, Ya-Han

    2015-11-01

    Case-mix adjustment is difficult for stroke outcome studies using administrative data. However, relevant prescription, laboratory, procedure, and service claims might be surrogates for stroke severity. This study proposes a method for developing a stroke severity index (SSI) by using administrative data. We identified 3,577 patients with acute ischemic stroke from a hospital-based registry and analyzed claims data with plenty of features. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). We used two data mining methods and conventional multiple linear regression (MLR) to develop prediction models, comparing the model performance according to the Pearson correlation coefficient between the SSI and the NIHSS. We validated these models in four independent cohorts by using hospital-based registry data linked to a nationwide administrative database. We identified seven predictive features and developed three models. The k-nearest neighbor model (correlation coefficient, 0.743; 95% confidence interval: 0.737, 0.749) performed slightly better than the MLR model (0.742; 0.736, 0.747), followed by the regression tree model (0.737; 0.731, 0.742). In the validation cohorts, the correlation coefficients were between 0.677 and 0.725 for all three models. The claims-based SSI enables adjusting for disease severity in stroke studies using administrative data. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Social deprivation and stroke severity on admission: a French cohort study in Burgundy and the West Indies - Guyana region.

    PubMed

    Béjot, Y; Guilloteau, A; Joux, J; Lannuzel, A; Mimeau, E; Mislin-Tritsch, C; Fournel, I; Bonithon-Kopp, C

    2017-05-01

    Although there is growing and convincing evidence that socially deprived patients are at higher risk of stroke and worse outcomes, it remains controversial whether or not they suffer more severe stroke. This study aimed to evaluate the influence of social deprivation on initial clinical severity in patients with stroke. A total of 1536 consecutive patients with an acute first-ever stroke (both ischaemic stroke and intracerebral hemorrhage) were prospectively enrolled from six French study centers. Stroke severity on admission was measured by the National Institutes of Health Stroke Scale score. Social deprivation was assessed at the individual level by the Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé (EPICES) score, a validated multidimensional questionnaire, and several additional single socioeconomic indicators. Polytomous logistic regression analyses were performed to evaluate the association between social deprivation and stroke severity. In univariate analysis, the EPICES score (P = 0.039) and level of education (P = 0.018) were the only two socioeconomic variables associated with stroke severity. Multivariate analysis of the association between EPICES and National Institutes of Health Stroke Scale scores showed that more deprived patients presented a significantly higher risk of both mild and moderate/severe stroke (odds ratio for mild versus minor stroke, 1.39; 95% confidence interval, 1.06-1.84; odds ratio for moderate/severe versus minor stroke, 1.44; 95% confidence interval, 1.09-1.92). A non-significant trend towards a higher risk of both mild and moderate/severe stroke in less educated patients was observed. Social deprivation was associated with a more severe clinical presentation in patients with stroke. These findings may contribute to the worse outcome after stroke in deprived patients, and underline the need for strategies to reduce social inequalities for stroke. © 2017 EAN.

  14. Characterization of ICP Behavior in an Experimental Model of Hemorrhagic Stroke in Rats.

    PubMed

    Cardim, Danilo Augusto; do Val da Silva, Raquel Araújo; Cardim, Ana Carolina; Cabella, Brenno Caetano Troca; Frigieri, Gustavo Henrique; de Sousa Torres, Cecília Vidal; Wang, Charles Chenwei; de Pacheco Andrade, Rodrigo Albuquerque; Scandiuzzi, Renata Caldo; Rizzatti, Ana Carolina Segato; Mascarenhas, Yvonne Maria; Leite, João Pereira; Mascarenhas, Sérgio

    2016-01-01

    Intracranial pressure (ICP) monitoring is sometimes required in clinical pictures of stroke, as extensive intraparenchymal hematomas and intracranial bleeding may severely increase ICP, which can lead to irreversible conditions, such as dementia and cognitive derangement. ICP monitoring has been accepted as a procedure for the safe diagnosis of increased ICP, and for the treatment of intracranial hypertension in some diseases. In this work, we evaluated ICP behavior during the induction of an experimental model of autologous blood injection in rats, simulating a hemorrhagic stroke. Rats were subjected to stereotactic surgery for the implantation of a unilateral cannula into the left striatal region of the brain. Autologous blood was infused into the left striatal region with an automatic microinfusion pump. ICP monitoring was performed throughout the procedure of hemorrhagic stroke induction. Analyses consisted of short-time Fourier transform for ICP before and after stroke induction and the histological processing of the animals' brains. Short-time Fourier transform analysis demonstrated oscillations in the ICP frequency components throughout time after the microinjections compared with data before them. Histological analysis revealed neuropathological changes in the striatum in all microinjected animals.

  15. Stroke Severity and Comorbidity Index for Prediction of Mortality after Ischemic Stroke from the Virtual International Stroke Trials Archive-Acute Collaboration.

    PubMed

    Phan, Thanh G; Clissold, Benjamin; Ly, John; Ma, Henry; Moran, Chris; Srikanth, Velandai

    2016-04-01

    There is increasing interest in the use of administrative data (incorporating comorbidity index) and stroke severity score to predict ischemic stroke mortality. The aim of this study was to determine the optimal timing for the collection of stroke severity data and the minimum clinical dataset to be included in models of stroke mortality. To address these issues, we chose the Virtual International Stroke Trials Archive (VISTA), which contains National Institutes of Health Stroke Scale (NIHSS) on admission and at 24 hours, as well as outcome at 90 days. VISTA was searched for patients who had baseline and 24-hour NIHSS. Improvement in regression models was performed by the net reclassification improvement (NRI) method. The clinical data among 5206 patients were mean age, 69 ± 13; comorbidity index, 3.3 ± .9; median NIHSS at baseline, 12 (interquartile range [IQR] 8-17); NIHSS at 24 hours, 9 (IQR 8-15); and death at 90 days in 15%. The baseline model consists of age, gender, and comorbidity index. Adding the baseline NIHSS to model 1 improved the NRI by 0.671 (95% confidence interval [CI] 0.595-0.747) [or 67.1% correct reclassification between model 1 and model 2]. Adding the 24 hour NIHSS term to model 1 (model 3) improved the NRI by 0.929 (95% CI 0.857-1.000) for model 3 versus model 1. Adding the variable thrombolysis to model 3 (model 4) improve NRI by 0.1 (95% CI 0.023-0.178) [model 4 versus model 3]. The optimal model for the prediction of mortality was achieved by adding the 24-hour NIHSS and thrombolysis to the baseline model. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Severe edentulism is a major risk factor influencing stroke incidence in rural Ecuador (The Atahualpa Project).

    PubMed

    Del Brutto, Oscar H; Mera, Robertino M; Zambrano, Mauricio; Del Brutto, Victor J

    2017-02-01

    Background There is no information on stroke incidence in rural areas of Latin America, where living conditions and cardiovascular risk factors are different from urban centers. Aim Using a population-based prospective cohort study design, we aimed to assess risk factors influencing stroke incidence in community-dwelling adults living in rural Ecuador. Methods First-ever strokes occurring from 1 June 2012 to 31 May 2016, in Atahualpa residents aged ≥40 years, were identified from yearly door-to-door surveys and other overlapping sources. Poisson regression models adjusted for demographics, cardiovascular risk factors, edentulism and the length of observation time per subject were used to estimate stroke incidence rate ratio as well as factors influencing such incidence. Results Of 807 stroke-free individuals prospectively enrolled in the Atahualpa Project, follow-up was achieved in 718 (89%), contributing 2,499 years of follow-up (average 3.48 ± 0.95 years). Overall stroke incidence rate was 2.97 per 100 person-years of follow-up (95% CI: 1.73-4.2), which increased to 4.77 (95% CI: 1.61-14.1) when only persons aged ≥57 years were considered. Poisson regression models, adjusted for relevant confounders, showed that high blood pressure (IRR: 5.24; 95% CI: 2.55-7.93) and severe edentulism (IRR: 5.06; 95% CI: 2.28-7.85) were the factors independently increasing stroke incidence. Conclusions Stroke incidence in this rural setting is comparable to that reported from the developed world. Besides age and high blood pressure, severe edentulism is a major factor independently predicting incident strokes. Public awareness of the consequences of poor dental care might reduce stroke incidence in rural settings.

  17. The association between OPG rs3102735 gene polymorphism, microembolic signal and stroke severity in acute ischemic stroke patients.

    PubMed

    Zhao, Hongqin; Cao, Yanyan; Chen, Honghua; Xu, Wanqun; Sun, Ximei; Pan, Xudong

    2017-05-20

    Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and is involved in the progress of atherosclerosis. We chose a gene polymorphism locus, OPG rs3102735, to explore how OPG gene polymorphisms relate to the occurrence of ischemic stroke and microembolic signals and to evaluate their relationship with the severity of neurologic deficits at admission and the degree of vascular stenosis. We studied 251 patients diagnosed with large artery atherosclerosis (LAA) stroke and 121 controls. The LAA stroke patients were divided into clinical subgroups according to the presence of microembolic signals, severity of neurologic deficits at admission, and the degree of vascular stenosis. The OPG rs3102735 gene polymorphism was examined by polymerase chain reaction and restriction fragment length polymorphism. The microembolic signals (MES) were monitored by transcranial Doppler (TCD) for 60min within 72h of stroke onset. The severity of neurologic deficits at admission was evaluated by the National Institutes of Health Stroke Scale (NIHSS). The CC+CT genotypes and allele C frequencies of the rs3102735 gene polymorphism were significantly higher in the LAA group than in the control group (39% vs. 25.6%, P=0.026; 21.7% vs.13.2%, P=0.006), higher in MES-positive compared to MES-negative patients (58.7% vs. 32.4%, P<0.01; 34.1% vs.17.6%, P<0.01), and higher in patients with an NIHSS Score (≥6) than in those with an NIHSS Score (<6) (46.9% vs.33.3%, P=0.031; 43.4% vs.18.3%, P=0.04). However, the genotypes and allele frequencies of SNPs in rs3102735 did not show significant differences in the degree of vascular stenosis (P>0.05). Our findings suggest that the OPG rs3102735 gene polymorphism might be related to the occurrence of LAA ischemic stroke, microembolic signals and stroke severity and not the degree of vascular stenosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Validation of a novel claims-based stroke severity index in patients with intracerebral hemorrhage

    PubMed Central

    Hung, Ling-Chien; Sung, Sheng-Feng; Hsieh, Cheng-Yang; Hu, Ya-Han; Lin, Huey-Juan; Chen, Yu-Wei; Yang, Yea-Huei Kao; Lin, Sue-Jane

    2016-01-01

    Background Stroke severity is an important outcome predictor for intracerebral hemorrhage (ICH) but is typically unavailable in administrative claims data. We validated a claims-based stroke severity index (SSI) in patients with ICH in Taiwan. Methods Consecutive ICH patients from hospital-based stroke registries were linked with a nationwide claims database. Stroke severity, assessed using the National Institutes of Health Stroke Scale (NIHSS), and functional outcomes, assessed using the modified Rankin Scale (mRS), were obtained from the registries. The SSI was calculated based on billing codes in each patient's claims. We assessed two types of criterion-related validity (concurrent validity and predictive validity) by correlating the SSI with the NIHSS and the mRS. Logistic regression models with or without stroke severity as a continuous covariate were fitted to predict mortality at 3, 6, and 12 months. Results The concurrent validity of the SSI was established by its significant correlation with the admission NIHSS (r = 0.731; 95% confidence interval [CI], 0.705–0.755), and the predictive validity was verified by its significant correlations with the 3-month (r = 0.696; 95% CI, 0.665–0.724), 6-month (r = 0.685; 95% CI, 0.653–0.715) and 1-year (r = 0.664; 95% CI, 0.622–0.702) mRS. Mortality models with NIHSS had the highest area under the receiver operating characteristic curve, followed by models with SSI and models without any marker of stroke severity. Conclusions The SSI appears to be a valid proxy for the NIHSS and an effective adjustment for stroke severity in studies of ICH outcome with administrative claims data. PMID:28135194

  19. The real estate factor: quantifying the impact of infarct location on stroke severity.

    PubMed

    Menezes, Nina M; Ay, Hakan; Wang Zhu, Ming; Lopez, Chloe J; Singhal, Aneesh B; Karonen, Jari O; Aronen, Hannu J; Liu, Yawu; Nuutinen, Juho; Koroshetz, Walter J; Sorensen, A Gregory

    2007-01-01

    The severity of the neurological deficit after ischemic stroke is moderately correlated with infarct volume. In the current study, we sought to quantify the impact of location on neurological deficit severity and to delineate this impact from that of volume. We developed atlases consisting of location-weighted values indicating the relative importance in terms of neurological deficit severity for every voxel of the brain. These atlases were applied to 80 first-ever ischemic stroke patients to produce estimates of clinical deficit severity. Each patient had an MRI and National Institutes of Health Stroke Scale (NIHSS) examination just before or soon after hospital discharge. The correlation between the location-based deficit predictions and measured neurological deficit (NIHSS) scores were compared with the correlation obtained using volume alone to predict the neurological deficit. Volume-based estimates of neurological deficit severity were only moderately correlated with measured NIHSS scores (r=0.62). The combination of volume and location resulted in a significantly better correlation with clinical deficit severity (r=0.79, P=0.032). The atlas methodology is a feasible way of integrating infarct size and location to predict stroke severity. It can estimate stroke severity better than volume alone.

  20. Effect of prior medical treatments on ischemic stroke severity and outcome

    PubMed Central

    Sacco, Simona; Toni, Danilo; Bignamini, Angelo A.; Zaninelli, Augusto; Gensini, Gian Franco; Carolei, Antonio

    Summary Antiplatelets, antihypertensives, and statins might reduce the severity of the event or improve outcome in patients who, despite prior medical treatment, have a stroke. We evaluated, in patients who had an ischemic stroke, the effect, on stroke severity and outcome, of prior treatment with antiplatelets, antihypertensives, and statins, used either alone or in a three-drug combination. Stroke in Italy and Related Impact on Outcome (SIRIO) was a prospective, nationwide, multicenter, hospital-based, observational study that included patients aged ≥18 years with acute ischemic stroke. We studied 2,529 acute ischemic stroke patients from the SIRIO population: 887 were antiplatelet users, 1,497 antihypertensive users, 231 statin users, and 138 three-drug combination users prior to the index event. The adjusted logistic regression analysis showed an association between prior treatment with statins and good functional outcome at discharge, while prior treatment with antiplatelets, antihypertensives or the three-drug combination did not influence severity or outcome. The absolute probability of a good functional outcome was 46.3% (95% CI: 40.3%–53.2%) in statin users and 36.7% (95% CI: 34.7%–38.7%) in non-users of statins; the absolute risk difference was 9.6% (95% CI: 2.9%–16.4%; p=0.004). Prior treatment with antiplatelets, antihypertensives, or the three-drug combination did not influence stroke severity or outcome, while prior treatment with statins did not influence stroke severity but was associated with a better functional outcome. PMID:22152434

  1. Duration of paroxysmal atrial fibrillation in cryptogenic stroke is not associated with stroke severity and early outcomes.

    PubMed

    Liantinioti, Chrissoula; Tympas, Konstantinos; Katsanos, Aristeidis H; Parissis, John; Chondrogianni, Maria; Zompola, Christina; Papadimitropoulos, Georgios; Ioakeimidis, Michael; Triantafyllou, Sokratis; Roussopoulou, Andromaxi; Voumvourakis, Konstantinos; Lekakis, John; Filippatos, Gerasimos; Stefanis, Leonidas; Tsivgoulis, Georgios

    2017-05-15

    The current definition of paroxysmal atrial fibrillation (PAF) requires an arbitrary cut-off of >30s, but in clinical practice cryptogenic stroke (CS) patients with PAF duration of ≤30s are not usually excluded from anticoagulation therapy. We sought to evaluate the clinical relevance of short-duration (≤30s) PAF in CS. Consecutive CS patients with no prior AF history and sinus-rhythm on baseline electrocardiography (ECG) were prospectively evaluated over a three-year period. Baseline stroke severity was assessed by NIHSS-scores. All patients underwent 24-hour Holter-ECG during hospitalization. ECG recordings were analyzed by two blinded investigators using dedicated analysis software. Total time in AF was calculated as the sum of each individual AF episode for patients with multiple episodes during monitoring. Patients were dichotomized in two groups using PAF total duration (≤30s & >30s). Early recurrent stroke and favorable functional outcome (FFO, defined as mRS-grades of 0-1) were evaluated during a three-month follow-up period. A total of 184 patients (66% men, mean age 57±11years) with CS (median NIHSS-score 4, IQR: 2-7) were evaluated. PAF of any duration was detected in 23 individuals (13%; 95%CI: 8%-18%). Among these patients the prevalence of brief PAF was 57% (n=13). The two groups did not differ (p>0.2) in terms of demographics, vascular risk factors and NIHSS-scores. Early recurrent stroke and FFO rates were similar (p>0.4) in the two groups. Duration of PAF is not associated with baseline stroke severity and early outcomes in patients with CS and should not influence anticoagulation decision in these patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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

  3. Severity and outcome of acute stroke in women: relation to adrenal sex steroid levels.

    PubMed

    Pappa, Theodora; Vemmos, Konstantinos; Saltiki, Katerina; Mantzou, Emilia; Stamatelopoulos, Kimon; Alevizaki, Maria

    2012-01-01

    Adrenal sex steroids exert diverse metabolic and neurobiological actions. Their levels have been associated with cardiovascular disease, but data concerning cerebrovascular disease are lacking. The objective of our study was to investigate the role of adrenal sex steroids in a female population suffering an acute stroke. We addressed the question of whether their levels are associated with disease severity and prognosis. A 2-year cohort study was performed in 2 tertiary hospitals, where we prospectively studied 302 consecutive postmenopausal female patients hospitalized for an acute stroke. Neurological severity on admission was assessed by the National Institutes of Health Stroke Scale; and handicap 1 month after stroke, with the modified Rankin Scale. Δ4-androstenedione levels were positively and dehydroepiandrosterone sulfate was inversely associated with stroke severity (r = 0.142, P = .014 and r = -0.153, P = .008, respectively), and both parameters remained as significant determinants even after entering other confounders in the multivariate model (r = 0.118, P = .039 and r = -0.150, P = .011, respectively). Levels of Δ4-androstenedione were significantly associated with 1-month mortality in the multivariate analysis (odds ratio with 95% confidence intervals: 1.540 [1.107-2.138)], P = .010). Δ4-androstenedione and dehydroepiandrosterone sulfate levels were associated with poor outcome in the univariate analysis, that is, combined severe handicap (modified Rankin Scale ≥4) and death, 1 month poststroke, although this was not significant in the multivariate analysis. Adrenal sex steroids, and especially Δ4-androstenedione, are significantly associated with stroke severity on admission and short-term prognosis among female stroke subjects. Well-designed prospective studies will further clarify their role in cerebrovascular disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Predicting recovery of voluntary upper extremity movement in subacute stroke patients with severe upper extremity paresis.

    PubMed

    Koh, Chia-Lin; Pan, Shin-Liang; Jeng, Jiann-Shing; Chen, Bang-Bin; Wang, Yen-Ho; Hsueh, I-Ping; Hsieh, Ching-Lin

    2015-01-01

    Prediction of voluntary upper extremity (UE) movement recovery is largely unknown in patients with little voluntary UE movement at admission. The present study aimed to investigate (1) the extent and variation of voluntary UE movement recovery, and (2) the best predictive model of the recovery of voluntary UE movement by clinical variables in patients with severe UE paresis. Prospective cohort study. 140 (out of 590) stroke patients with severe UE paresis completed all assessments. Voluntary UE movement was assessed using the UE subscale of the Stroke Rehabilitation Assessment of Movement (STREAM-UE). Two outcome measures, STREAM-UE scores at discharge (DC(STREAM-UE)) and changes between admission and discharge (Δ(STREAM-UE)), were investigated to represent the final states and improvement of the recovery of voluntary UE movement. Stepwise regression analyses were used to investigate 19 clinical variables and to find the best predictive models of the two outcome measures. The participants showed wide variation in both DC(STREAM-UE) and Δ(STREAM-UE). 3.6% of the participants almost fully recovered at discharge (DC(STREAM-UE) > 15). A large improvement (Δ(STREAM-UE) >= 10) occurred in 16.4% of the participants, while 32.9% of the participants did not have any improvement. The four predictors for the DC(STREAM-UE) (R(2) = 35.0%) were 'baseline STREAM-UE score', 'hemorrhagic stroke', 'baseline National Institutes of Health Stroke Scale (NIHSS) score', and 'cortical lesion excluding primary motor cortex'. The three predictors for the Δ(STREAM-UE) (R(2) = 22.0%) were 'hemorrhagic stroke', 'baseline NIHSS score', and 'cortical lesion excluding primary motor cortex'. Recovery of voluntary UE movement varied widely in patients with severe UE paresis after stroke. The predictive power of clinical variables was poor. Both results indicate the complex nature of voluntary UE movement recovery in patients with severe UE paresis after stroke.

  5. Safety and efficacy of transcranial direct current stimulation in acute experimental ischemic stroke.

    PubMed

    Peruzzotti-Jametti, Luca; Cambiaghi, Marco; Bacigaluppi, Marco; Gallizioli, Mattia; Gaude, Edoardo; Mari, Silvia; Sandrone, Stefano; Cursi, Marco; Teneud, Luis; Comi, Giancarlo; Musco, Giovanna; Martino, Gianvito; Leocani, Letizia

    2013-11-01

    Transcranial direct current stimulation is emerging as a promising tool for the treatment of several neurological conditions, including cerebral ischemia. The therapeutic role of this noninvasive treatment is, however, limited to chronic phases of stroke. We thus ought to investigate whether different stimulation protocols could also be beneficial in the acute phase of experimental brain ischemia. The influence of both cathodal and anodal transcranial direct current stimulation in modifying brain metabolism of healthy mice was first tested by nuclear magnetic resonance spectroscopy. Then, mice undergoing transient proximal middle cerebral artery occlusion were randomized and treated acutely with anodal, cathodal, or sham transcranial direct current stimulation. Brain metabolism, functional outcomes, and ischemic lesion volume, as well as the inflammatory reaction and blood brain barrier functionality, were analyzed. Cathodal stimulation was able, if applied in the acute phase of stroke, to preserve cortical neurons from the ischemic damage, to reduce inflammation, and to promote a better clinical recovery compared with sham and anodal treatments. This finding was attributable to the significant decrease of cortical glutamate, as indicated by nuclear magnetic resonance spectroscopy. Conversely, anodal stimulation induced an increase in the postischemic lesion volume and augmented blood brain barrier derangement. Our data indicate that transcranial direct current stimulation exerts a measurable neuroprotective effect in the acute phase of stroke. However, its timing and polarity should be carefully identified on the base of the pathophysiological context to avoid potential harmful side effects.

  6. Antiretroviral Treatment with Efavirenz Disrupts the Blood-Brain Barrier Integrity and Increases Stroke Severity

    PubMed Central

    Bertrand, Luc; Dygert, Levi; Toborek, Michal

    2016-01-01

    The introduction of antiretroviral drugs (ARVd) changed the prognosis of HIV infection from a deadly disease to a chronic disease. However, even with undetectable viral loads, patients still develop a wide range of pathologies, including cerebrovascular complications and stroke. It is hypothesized that toxic side effects of ARVd may contribute to these effects. To address this notion, we evaluated the impact of several non-nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine) on the integrity of the blood-brain barrier, and their impact on severity of stroke. Among studied drugs, Efavirenz, but not other NNRTIs, altered claudin-5 expression, increased endothelial permeability, and disrupted the blood-brain barrier integrity. Importantly, Efavirenz exposure increased the severity of stroke in a model of middle cerebral artery occlusion in mice. Taken together, these results indicate that selected ARVd can exacerbate HIV-associated cerebrovascular pathology. Therefore, careful consideration should be taken when choosing an anti-retroviral therapy regimen. PMID:28008980

  7. Functional recovery in aging mice after experimental stroke.

    PubMed

    Manwani, Bharti; Liu, Fudong; Xu, Yan; Persky, Rebecca; Li, Jun; McCullough, Louise D

    2011-11-01

    Aging is a non-modifiable risk factor for stroke. Since not all strokes can be prevented, a major emerging area of research is the development of effective strategies to enhance functional recovery after stroke. However, in the vast majority of pre-clinical stroke studies, the behavioral tests used to assess functional recovery have only been validated for use in young animals, or are designed for rats. Mice are increasingly utilized in stroke models but well validated behavioral tests designed for rats are not necessarily reproducible in mice. We examined a battery of behavioral tests to evaluate functional recovery in an aging murine model of stroke. We found that the vertical pole, hanging wire and open field can accurately assess acute behavioral impairments after stroke in both young and aging male mice, but animals recover rapidly on these tasks. The corner test can accurately and repeatedly differentiate stroke from sham animals up to 30 days post stroke and can be performed reliably in aging mice. Aging male mice had significantly worse behavioral impairment compared to young male mice in the first two weeks after stroke but eventually recovered to the same degree as young mice. In contrast, chronic infarct size, as measured by ipsilateral cerebral atrophy, was significantly lower in aging male mice compared to young male mice. Reactive gliosis, formation of glial scar, and an enhanced innate immune response was seen in the aging brain and may contribute to the delayed behavioral recovery seen in the aging animals. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. 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

  9. A rapid and transient peripheral inflammatory response precedes brain inflammation after experimental stroke.

    PubMed

    Chapman, Katie Z; Dale, Verity Q; Dénes, Adám; Bennett, Gavin; Rothwell, Nancy J; Allan, Stuart M; McColl, Barry W

    2009-11-01

    Increasing evidence suggests that peripheral inflammatory responses to stroke and other brain injuries have an important role in determining neurological outcome. The mediators of this response and the temporal relationships between peripheral and central inflammatory alterations are poorly understood. In this study, we show that experimental stroke in mice induces a peripheral inflammatory response that peaks 4 h after stroke, and precedes the peak in brain inflammation 24 h after stroke. This peripheral response is dominated by the induction of the chemokine CXCL-1 and the proinflammatory cytokine interleukin-6 and could serve as an accessible target for therapy and as a source of biomarkers predictive of prognosis.

  10. Subacute default mode network dysfunction in the prediction of post-stroke depression severity.

    PubMed

    Lassalle-Lagadec, Saioa; Sibon, Igor; Dilharreguy, Bixente; Renou, Pauline; Fleury, Olivier; Allard, Michèle

    2012-07-01

    To identify patterns of rest functional connectivity (FC) in the whole brain with the default mode network (DMN) soon after stroke and to explore the predictive accuracy of the strength of rest FC in specific areas on poststroke severity of depression and anxiety symptoms. The protocol was accepted by the local ethics board, and all patients provided informed consent to participate. Resting-state functional magnetic resonance (MR) images were acquired 10 days after a first stroke in 24 patients without a history of psychiatric illness. Independent component analysis was used to isolate the DMN in each subject. Hamilton Depression Rating Scale (HDRS) 17 and Hamilton Anxiety Rating Scale (HARS) were recorded 10 days and 3 months after the stroke. Associations between severity of anxiety or depression symptoms and DMN functional connectivity were investigated with whole-brain analyses by using statistical parametric mapping software and were adjusted for age, sex, manual laterality, and National Institutes of Health Stroke Severity scores. Correlations were considered significant if P<.001, with a cluster size of more than 50 voxels. Ten days after stroke, anxiety severity was correlated with functional connectivity in the middle temporal cortex and the anterior midcingulate cortex, while at 3 months after stroke, a correlation was observed with the middle temporal cortex and the posterior cingulate cortex. Poststroke depressive symptom severity did not correlate with functional connectivity changes at 10-day follow-up, while the HDRS 17 score was correlated with functional connectivity in the left middle temporal cortex and precuneus at 3-month follow-up. These results suggest that a dysfunction of DMN functional connectivity involved in emotional control is associated with the severity of poststroke depression. Further studies are necessary to determine the mechanisms of this functional impairment. © RSNA, 2012.

  11. 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

  12. 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 ...

  13. Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke.

    PubMed

    Chang, Won Hyuk; Park, Chang-hyun; Kim, Deog Young; Shin, Yong-Il; Ko, Myoung-Hwan; Lee, Ahee; Jang, Shin Yi; Kim, Yun-Hee

    2016-03-02

    Cerebrolysin is a neuropeptide preparation with neuroprotective and neurorestorative effects. Combining Cerebrolysin treatment with a standardized rehabilitation program may have a potential synergistic effect in the subacute stage of stroke. This study aims to evaluate whether Cerebrolysin provides additional motor recovery on top of rehabilitation therapy in the subacute stroke patients with moderate to severe motor impairment. This phase IV trial was designed as a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. A total of 70 patients (Cerebrolysin n = 35, placebo n = 35) with moderate to severe motor function impairment were included within 7 days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo, given in addition to standardized rehabilitation therapy. Assessments were performed at baseline, immediately after treatment as well as 2 and 3 months after stroke onset. The plasticity of motor system was assessed by diffusion tensor imaging and with resting state functional magnetic resonance imaging. Both groups demonstrated significant improvement in motor function (p < 0.05); however, no significant difference was found between the two groups. In the stroke patients with severe motor impairment, the Cerebrolysin group exhibited significantly more improvement in motor function compared with the placebo group (p < 0.05). Effects of Cerebrolysin were demonstrated as restricted increments of corticospinal diffusivity and as recovery of the sensorimotor connectivity. The combination of standard rehabilitation therapy with Cerebrolysin treatment in the subacute stroke has shown additional benefit on motor recovery and plastic changes of the corticospinal tract in patients with severe motor impairment. NCT01996761 (November 5, 2013).

  14. Design and validation of a clinical scale for prehospital stroke recognition, severity grading and prediction of large vessel occlusion: the shortened NIH Stroke Scale for emergency medical services.

    PubMed

    Purrucker, Jan Christoph; Härtig, Florian; Richter, Hardy; Engelbrecht, Andreas; Hartmann, Johannes; Auer, Jonas; Hametner, Christian; Popp, Erik; Ringleb, Peter Arthur; Nagel, Simon; Poli, Sven

    2017-09-01

    To develop an NIH Stroke Scale (NIHSS)-compatible, all-in-one scale for rapid and comprehensive prehospital stroke assessment including stroke recognition, severity grading and progression monitoring as well as prediction of large vessel occlusion (LVO). Emergency medical services (EMS) personnel and stroke physicians (n=326) rated each item of the NIHSS regarding suitability for prehospital use; best rated items were included. Stroke recognition was evaluated retrospectively in 689 consecutive patients with acute stroke or stroke mimics, prediction of LVO in 741 consecutive patients with ischaemic stroke with acute vessel imaging independent of admission NIHSS score. Nine of the NIHSS items were rated as 'suitable for prehospital use.' After excluding two items in order to increase specificity, the final scale (termed shortened NIHSS for EMS, sNIHSS-EMS) consists of 'level of consciousness', 'facial palsy', 'motor arm/leg', 'sensory', 'language' and 'dysarthria'. Sensitivity for stroke recognition of the sNIHSS-EMS is 91% (95% CI 86 to 94), specificity 52% (95% CI 47 to 56). Receiver operating curve analysis revealed an optimal cut-off point for LVO prediction of ≥6 (sensitivity 70% (95% CI 65 to 76), specificity 81% (95% CI 76 to 84), positive predictive value 70 (95% CI 65 to 75), area under the curve 0.81 (95% CI 0.78 to 0.84)). Test characteristics were non-inferior to non-comprehensive scales. The sNIHSS-EMS may overcome the sequential use of multiple emergency stroke scales by permitting parallel stroke recognition, severity grading and LVO prediction. Full NIHSS-item compatibility allows for evaluation of stroke progression starting at the prehospital phase. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Design and validation of a clinical scale for prehospital stroke recognition, severity grading and prediction of large vessel occlusion: the shortened NIH Stroke Scale for emergency medical services

    PubMed Central

    Purrucker, Jan Christoph; Härtig, Florian; Richter, Hardy; Engelbrecht, Andreas; Hartmann, Johannes; Auer, Jonas; Hametner, Christian; Popp, Erik; Ringleb, Peter Arthur; Nagel, Simon; Poli, Sven

    2017-01-01

    Objective To develop an NIH Stroke Scale (NIHSS)-compatible, all-in-one scale for rapid and comprehensive prehospital stroke assessment including stroke recognition, severity grading and progression monitoring as well as prediction of large vessel occlusion (LVO). Methods Emergency medical services (EMS) personnel and stroke physicians (n=326) rated each item of the NIHSS regarding suitability for prehospital use; best rated items were included. Stroke recognition was evaluated retrospectively in 689 consecutive patients with acute stroke or stroke mimics, prediction of LVO in 741 consecutive patients with ischaemic stroke with acute vessel imaging independent of admission NIHSS score. Results Nine of the NIHSS items were rated as ‘suitable for prehospital use.’ After excluding two items in order to increase specificity, the final scale (termed shortened NIHSS for EMS, sNIHSS-EMS) consists of ‘level of consciousness’, ‘facial palsy’, ‘motor arm/leg’, ‘sensory’, ‘language’ and ‘dysarthria’. Sensitivity for stroke recognition of the sNIHSS-EMS is 91% (95% CI 86 to 94), specificity 52% (95% CI 47 to 56). Receiver operating curve analysis revealed an optimal cut-off point for LVO prediction of ≥6 (sensitivity 70% (95% CI 65 to 76), specificity 81% (95% CI 76 to 84), positive predictive value 70 (95% CI 65 to 75), area under the curve 0.81 (95% CI 0.78 to 0.84)). Test characteristics were non-inferior to non-comprehensive scales. Conclusions The sNIHSS-EMS may overcome the sequential use of multiple emergency stroke scales by permitting parallel stroke recognition, severity grading and LVO prediction. Full NIHSS-item compatibility allows for evaluation of stroke progression starting at the prehospital phase. PMID:28864702

  16. Severity of Post-stroke Aphasia According to Aphasia Type and Lesion Location in Koreans

    PubMed Central

    Kang, Eun Kyoung; Sohn, Hae Min; Han, Moon-Ku; Kim, Won; Han, Tai Ryoon

    2010-01-01

    To determine the relations between post-stroke aphasia severity and aphasia type and lesion location, a retrospective review was undertaken using the medical records of 97 Korean patients, treated within 90 days of onset, for aphasia caused by unilateral left hemispheric stroke. Types of aphasia were classified according to the validated Korean version of the Western Aphasia Battery (K-WAB), and severities of aphasia were quantified using WAB Aphasia Quotients (AQ). Lesion locations were classified as cortical or subcortical, and were determined by magnetic resonance imaging. Two-step cluster analysis was performed using AQ values to classify aphasia severity by aphasia type and lesion location. Cluster analysis resulted in four severity clusters: 1) mild; anomic type, 2) moderate; Wernicke's, transcortical motor, transcortical sensory, conduction, and mixed transcortical types, 3) moderately severe; Broca's aphasia, and 4) severe; global aphasia, and also in three lesion location clusters: 1) mild; subcortical 2) moderate; cortical lesions involving Broca's and/or Wernicke's areas, and 3) severe; insular and cortical lesions not in Broca's or Wernicke's areas. These results revealed that within 3 months of stroke, global aphasia was the more severely affected type and cortical lesions were more likely to affect language function than subcortical lesions. PMID:20052357

  17. Severity of post-stroke aphasia according to aphasia type and lesion location in Koreans.

    PubMed

    Kang, Eun Kyoung; Sohn, Hae Min; Han, Moon-Ku; Kim, Won; Han, Tai Ryoon; Paik, Nam-Jong

    2010-01-01

    To determine the relations between post-stroke aphasia severity and aphasia type and lesion location, a retrospective review was undertaken using the medical records of 97 Korean patients, treated within 90 days of onset, for aphasia caused by unilateral left hemispheric stroke. Types of aphasia were classified according to the validated Korean version of the Western Aphasia Battery (K-WAB), and severities of aphasia were quantified using WAB Aphasia Quotients (AQ). Lesion locations were classified as cortical or subcortical, and were determined by magnetic resonance imaging. Two-step cluster analysis was performed using AQ values to classify aphasia severity by aphasia type and lesion location. Cluster analysis resulted in four severity clusters: 1) mild; anomic type, 2) moderate; Wernicke's, transcortical motor, transcortical sensory, conduction, and mixed transcortical types, 3) moderately severe; Broca's aphasia, and 4) severe; global aphasia, and also in three lesion location clusters: 1) mild; subcortical 2) moderate; cortical lesions involving Broca's and/or Wernicke's areas, and 3) severe; insular and cortical lesions not in Broca's or Wernicke's areas. These results revealed that within 3 months of stroke, global aphasia was the more severely affected type and cortical lesions were more likely to affect language function than subcortical lesions.

  18. 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.

  19. Tert-butylhydroquinone compromises survival in murine experimental stroke.

    PubMed

    Sun, Jiahong; Hu, Heng; Ren, Xuefang; Simpkins, James W

    2016-01-01

    Tert-butylhydroquinone (tBHQ), an Nrf2 signaling pathway inducer that is widely used as a food additive in the U.S., prevents oxidative stress-induced cytotoxicity in neurons. This study assesses the effects of tBHQ on ischemic stroke outcomes in mice. We measured infarct size, neurological deficits, and brain volume after tBHQ treatments in murine permanent middle cerebral artery occlusion (pMCAO) model in vivo. Further, we evaluated the regulation of tBHQ on mitochondrial function in cerebrovascular endothelial cells in vitro, which is critical to the blood-brain barrier (BBB) permeability. Our results demonstrated that tBHQ increased post-stroke mortality and worsened stroke outcomes. Mitochondrial function was suppressed by tBHQ treatment of cerebrovascular endothelial cells, and this suppression was potentiated by co-treatment with lipopolysaccharide (LPS), the bacterial mimic. These data indicate that tBHQ-exacerbated stroke damage might due to the compromised BBB permeability in permanent stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Tert-butylhydroquinone Compromises Survival in Murine Experimental Stroke

    PubMed Central

    Sun, Jiahong; Hu, Heng; Ren, Xuefang; Simpkins, James W.

    2016-01-01

    tert-butylhydroquinone (tBHQ), an Nrf2 signaling pathway inducer that is widely used as a food additive in the U.S., prevents oxidative stress-induced cytotoxicity in neurons. This study assesses the effects of tBHQ on ischemic stroke outcomes in mice. We measured infarct size, neurological deficits, and brain volume after tBHQ treatments in murine permanent middle cerebral artery occlusion (pMCAO) model in vivo. Further, we evaluated the regulation of tBHQ on mitochondrial function in cerebrovascular endothelial cells in vitro, which is critical to the blood–brain barrier (BBB) permeability. Our results demonstrated that tBHQ increased post-stroke mortality and worsened stroke outcomes. Mitochondrial function was suppressed by tBHQ treatment of cerebrovascular endothelial cells, and this suppression was potentiated by co-treatment with lipopolysaccharide (LPS), the bacterial mimic. These data indicate that tBHQ-exacerbated stroke damage might due to the compromised BBB permeability in permanent stroke. PMID:26827673

  1. NLRP3 deficiency ameliorates neurovascular damage in experimental ischemic stroke.

    PubMed

    Yang, Fan; Wang, Ziying; Wei, Xinbing; Han, Huirong; Meng, Xianfang; Zhang, Yan; Shi, Weichen; Li, Fengli; Xin, Tao; Pang, Qi; Yi, Fan

    2014-04-01

    Although the innate immune response to induce postischemic inflammation is considered as an essential step in the progression of cerebral ischemia injury, the role of innate immunity mediator NLRP3 in the pathogenesis of ischemic stroke is unknown. In this study, focal ischemia was induced by middle cerebral artery occlusion in NLRP3(-/-), NOX2(-/-), or wild-type (WT) mice. By magnetic resonance imaging (MRI), Evans blue permeability, and electron microscopic analyses, we found that NLRP3 deficiency ameliorated cerebral injury in mice after ischemic stroke by reducing infarcts and blood-brain barrier (BBB) damage. We further showed that the contribution of NLRP3 to neurovascular damage was associated with an autocrine/paracrine pattern of NLRP3-mediated interleukin-1β (IL-1β) release as evidenced by increased brain microvessel endothelial cell permeability and microglia-mediated neurotoxicity. Finally, we found that NOX2 deficiency improved outcomes after ischemic stroke by mediating NLRP3 signaling. This study for the first time shows the contribution of NLRP3 to neurovascular damage and provides direct evidence that NLRP3 as an important target molecule links NOX2-mediated oxidative stress to neurovascular damage in ischemic stroke. Pharmacological targeting of NLRP3-mediated inflammatory response at multiple levels may help design a new approach to develop therapeutic strategies for prevention of deterioration of cerebral function and for the treatment of stroke.

  2. Red cell distribution width does not predict stroke severity or functional outcome.

    PubMed

    Ntaios, George; Gurer, Ozgur; Faouzi, Mohamed; Aubert, Carole; Michel, Patrik

    2012-01-01

    Red cell distribution width was recently identified as a predictor of cardiovascular and all-cause mortality in patients with previous stroke. Red cell distribution width is also higher in patients with stroke compared with those without. However, there are no data on the association of red cell distribution width, assessed during the acute phase of ischemic stroke, with stroke severity and functional outcome. In the present study, we sought to investigate this relationship and ascertain the main determinants of red cell distribution width in this population. We used data from the Acute Stroke Registry and Analysis of Lausanne for patients between January 2003 and December 2008. Red cell distribution width was generated at admission by the Sysmex XE-2100 automated cell counter from ethylene diamine tetraacetic acid blood samples stored at room temperature until measurement. An χ(2) -test was performed to compare frequencies of categorical variables between different red cell distribution width quartiles, and one-way analysis of variance for continuous variables. The effect of red cell distribution width on severity and functional outcome was investigated in univariate and multivariate robust regression analysis. Level of significance was set at 95%. There were 1504 patients (72±15·76 years, 43·9% females) included in the analysis. Red cell distribution width was significantly associated to NIHSS (β-value=0·24, P=0·01) and functional outcome (odds ratio=10·73 for poor outcome, P<0·001) at univariate analysis but not multivariate. Prehospital Rankin score (β=0·19, P<0·001), serum creatinine (β=0·008, P<0·001), hemoglobin (β=-0·009, P<0·001), mean platelet volume (β=0·09, P<0·05), age (β=0·02, P<0·001), low ejection fraction (β=0·66, P<0·001) and antihypertensive treatment (β=0·32, P<0·001) were independent determinants of red cell distribution width. Red cell distribution width, assessed during the early phase of acute ischemic stroke

  3. Melatonin reduces the severity of experimental amoebiasis

    PubMed Central

    2011-01-01

    Background Melatonin has immunomodulatory effects but very little is known about its influence in protozoan infections, such as Entamoeba histolytica, which causes amoebiasis, a disease with significant morbidity and mortality. In this study, we evaluated the effects of exogenous melatonin interference in experimental amoebiasis and on interactions between human blood cells and E. histolytica trophozoites. Methods The effect of melatonin was investigated in models of experimental amoebiasis in hamsters and rats by evaluating the area of necrosis induced by E. histolytica. The activity of melatonin on the interactions between leukocytes and amoebae was determined by examining leukophagocytosis. For in vitro tests, polymorphonuclear and mononuclear human blood leucocytes were incubated with E. histolytica trophozoites. Results The areas of amoebic necrosis were significantly reduced in animals treated with melatonin. Melatonin treatment increased leukophagocytosis but was associated with a greater number of dead amoebae. Conclusions These results suggest that melatonin may play a beneficial role in the control of amoebic lesions, raising the possibility that this drug may be used as an adjuvant in anti-amoebic therapy. PMID:21501501

  4. 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

  5. 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, José 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.

  6. Endovascular Treatment of a Severe Stroke Occurring in a Commercial Airplane Over the Sahara.

    PubMed

    Foerch, Christian; Mayer, Christoph A; Berkefeld, Joachim; You, Se-Jong

    2016-09-01

    The occurrence of an acute stroke syndrome during a long-distance flight demands critical decisions from the crew and attendant physicians. One in particular is whether the flight should be continued or be detoured to a nearby airport. We describe a 42-yr-old woman who suffered from a severe stroke in a commercial airplane over the Sahara. The captain, together with a physician aboard and the next of kin, decided not to detour to north African or south European airports, but to continue flying to Frankfurt, Germany (final destination; remaining flight time 4 h), where an efficient transfer infrastructure and an advanced medical standard were presumed. At the hospital, the patient was successfully treated by means of catheter-based mechanical thrombus extraction. The patient was free of neurological deficits at discharge. The geographically unbalanced availability of complex but highly effective therapies such as mechanical recanalization in acute stroke challenges decision making in aviation medicine. In selected cases it might be beneficial to continue flying to cities with advanced medical standards instead of deviating to nearby airports. Foerch C, Mayer CA, Berkefeld J, You S-J. Endovascular treatment of a severe stroke occurring in a commercial airplane over the Sahara. Aerosp Med Hum Perform. 2016; 87(9):825-829.

  7. Prediction of Independent Walking Ability for Severely Hemiplegic Stroke Patients at Discharge from a Rehabilitation Hospital.

    PubMed

    Hirano, Yoshitake; Hayashi, Takeshi; Nitta, Osamu; Takahashi, Hidetoshi; Nishio, Daisuke; Minakawa, Tomoya; Kigawa, Hiroshi

    2016-08-01

    It is important to predict walking ability for stroke patients, because rehabilitation programs are planned on such predictions. We therefore examined predictive factors that are available before discharge from a rehabilitation hospital. Seventy-two consecutive patients with a first attack of stroke with severe hemiplegia were included in this study. We retrospectively evaluated background factors (age, gender, time from stroke onset, paresis side, and stroke type). Other neurological and physical parameters were collected by means of the modified National Institutes of Health Stroke Scale, the Mini-Mental State Examination, the Trunk Control Test (TCT), and the knee extension strength/body weight ratio on the unaffected side (KES/BW-US) at the time of admission. We divided the patients into 2 groups, the independent group (n = 49) and the dependent group (n = 23), on the basis of the Barthel Index of mobility at the time of discharge. We then compared the 2 groups with respect to the aforementioned parameters. We also performed stepwise discriminant analyses to ascertain which parameters are the best predictors of walking ability at the time of discharge. Age, TCT score, and the KES/BW-US ratio were significantly different between the groups. Discriminant analysis revealed that younger age and a higher KES/BW-US ratio were significantly associated with walking ability at discharge, which could be precisely predicted using the following formula: Y = .093 × (age) - 4.316 × (KES/BW-US) - 4.984. At the time of admission, age and the KES/BW-US ratio permit the prediction of independent walking ability at the time of discharge. Our formula predicts walking ability with an accuracy of more than 91%. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  8. Mirror therapy for patients with severe arm paresis after stroke--a randomized controlled trial.

    PubMed

    Thieme, Holm; Bayn, Maria; Wurg, Marco; Zange, Christian; Pohl, Marcus; Behrens, Johann

    2013-04-01

    To evaluate the effects of individual or group mirror therapy on sensorimotor function, activities of daily living, quality of life and visuospatial neglect in patients with a severe arm paresis after stroke. Randomized controlled trial. Inpatient rehabilitation centre. Sixty patients with a severe paresis of the arm within three months after stroke. Three groups: (1) individual mirror therapy, (2) group mirror therapy and (3) control intervention with restricted view on the affected arm. Motor function on impairment (Fugl-Meyer Test) and activity level (Action Research Arm Test), independence in activities of daily living (Barthel Index), quality of life (Stroke Impact Scale) and visuospatial neglect (Star Cancellation Test). After five weeks, no significant group differences for motor function were found (P > 0.05). Pre-post differences for the Action Research Arm Test and Fugl-Meyer Test: individual mirror therapy: 3.4 (7.1) and 3.2 (3.8), group mirror therapy: 1.1 (3.1) and 5.1 (10.0) and control therapy: 2.8 (6.7) and 5.2 (8.7). However, a significant effect on visuospatial neglect for patients in the individual mirror therapy compared to control group could be shown (P < 0.01). Furthermore, it was possible to integrate a mirror therapy group intervention for severely affected patients after stroke. This study showed no effect on sensorimotor function of the arm, activities of daily living and quality of life of mirror therapy compared to a control intervention after stroke. However, a positive effect on visuospatial neglect was indicated.

  9. Stroke

    MedlinePlus

    ... Is a Stroke? A stroke occurs if the flow of oxygen-rich blood to a portion of the brain ... pressure from the leaked blood damages brain cells. High blood pressure and ... A TIA occurs if blood flow to a portion of the brain is blocked ...

  10. Histopathology of motor cortex in an experimental focal ischemic stroke in mouse model.

    PubMed

    de Oliveira, Juçara Loli; Crispin, Pedro di Tárique Barreto; Duarte, Elisa Cristiana Winkelmann; Marloch, Gilberto Domingos; Gargioni, Rogério; Trentin, Andréa Gonçalves; Alvarez-Silva, Marcio

    2014-05-01

    Experimental ischemia results in cortical brain lesion followed by ischemic stroke. In this study, focal cerebral ischemia was induced in mice by occlusion of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm motor cortex, significant differences were observed in the numbers of neurons, astrocytes and microglia in the superficial II/III and deep V cortical layers. Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis, chromatin fragmentation, necrosis and degeneration, as well as, morphological evidence of apoptosis, mainly in neurons. As result, the CFA was more severely impaired than the AGm in this focal cerebral ischemic model, as evidenced by the proliferation of astrocytes, potentially resulting in neuroinflammation by microglia-like cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Movement related slow cortical potentials in severely paralyzed chronic stroke patients

    PubMed Central

    Yilmaz, Ozge; Birbaumer, Niels; Ramos-Murguialday, Ander

    2015-01-01

    Movement-related slow cortical potentials (SCPs) are proposed as reliable and immediate indicators of cortical reorganization in motor learning. SCP amplitude and latency have been reported as markers for the brain's computational effort, attention and movement planning. SCPs have been used as an EEG signature of motor control and as a main feature in Brain-Machine-Interfaces (BMIs). Some reports suggest SCPs are modified following stroke. In this study, we investigated movement-related SCPs in severe chronic stroke patients with no residual paretic hand movements preceding and during paretic (when they try to move) and healthy hand movements. The aim was to identify SCP signatures related to cortex integrity and complete paralysis due to stroke in the chronic stage. Twenty severely impaired (no residual finger extension) chronic stoke patients, of whom ten presented subcortical and ten cortical and subcortical lesions, underwent EEG and EMG recordings during a cue triggered hand movement (open/close) paradigm. SCP onset appeared and peaked significantly earlier during paretic hand movements than during healthy hand movements. Amplitudes were significantly larger over the midline (Cz, Fz) for paretic hand movements while contralateral (C4, F4) and midline (Cz, Fz) amplitudes were significantly larger than ipsilateral activity for healthy hand movements. Dividing the participants into subcortical only and mixed lesioned patient groups, no significant differences observed in SCP amplitude and latency between groups. This suggests lesions in the thalamocortical loop as the main factor in SCP changes after stroke. Furthermore, we demonstrated how, after long-term complete paralysis, post-stroke intention to move a paralyzed hand resulted in longer and larger SCPs originating in the frontal areas. These results suggest SCP are a valuable feature that should be incorporated in the design of new neurofeedback strategies for motor neurorehabilitation. PMID:25642177

  12. Severe hemiparesis as a prehospital tool to triage stroke severity: a pilot study to assess diagnostic accuracy and treatment times.

    PubMed

    Gupta, Rishi; Manuel, Marissa; Owada, Kumiko; Dhungana, Samish; Busby, Leslie; Glenn, Brenda A; Brown, Debbie; Zimmermann, Susan A; Horn, Christopher; Rochestie, Dustin; Hormes, Joseph T; Johnson, Andrew K; Khaldi, Ahmad

    2016-08-01

    With the publication of the recent trials showing the tremendous benefits of mechanical thrombectomy, opportunities exist to refine prehospital processes to identify patients with larger stroke syndromes. We retrospectively reviewed consecutive patients who were brought via scene flight from rural parts of the region to our institution, from December 1, 2014 to June 5, 2015, with severe hemiparesis or hemiplegia. We assessed the accuracy of the diagnosis of stroke and the number of patients requiring endovascular therapy. Moreover, we reviewed the times along the pathway of patients who were treated with endovascular therapy. 45 patients were brought via helicopter from the field to our institution. 27 (60%) patients were diagnosed with an ischemic stroke. Of these, 12 (26.7%) were treated with mechanical thrombectomy and 6 (13.3%) with intravenous tissue plasminogen activator alone. An additional three patients required embolization procedures for either a dural arteriovenous fistula or cerebral aneurysm. Thus a total of 15 (33%) patients received an endovascular procedure and 21/45 (46.7%) received an acute treatment. For patients treated with thrombectomy, the median time from first medical contact to groin puncture was 101 min, with 8 of the 12 patients (66.7%) being discharged to home. We have presented a pilot study showing that severe hemiparesis or hemiplegia may be a reasonable prehospital tool in recognizing patients requiring endovascular treatment. Patients being identified earlier may be treated faster and potentially improve outcomes. Further prospective controlled studies are required to assess the impact on outcomes and cost effectiveness using this methodology. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Preservation of structural brain network hubs is associated with less severe post-stroke aphasia.

    PubMed

    Gleichgerrcht, Ezequiel; Kocher, Madison; Nesland, Travis; Rorden, Chris; Fridriksson, Julius; Bonilha, Leonardo

    2015-01-01

    Post-stroke aphasia is typically associated with ischemic damage to cortical areas or with loss of connectivity among spared brain regions. It remains unclear whether the participation of spared brain regions as networks hubs affects the severity of aphasia. We evaluated language performance and magnetic resonance imaging from 44 participants with chronic aphasia post-stroke. The individual structural brain connectomes were constructed from diffusion tensor. Hub regions were defined in accordance with the rich club classification and studied in relation with language performance. Number of remaining left hemisphere rich club nodes was associated with aphasia, including comprehension, repetition and naming sub-scores. Importantly, among participants with relative preservation of regions of interest for language, aphasia severity was lessened if the region was not only spared, but also participated in the remaining network as a rich club node: Brodmann area (BA) 44/45 - repetition (p = 0.009), BA 39 - repetition (p = 0.045) and naming (p <  0.01), BA 37 - fluency (p <  0.001), comprehension (p = 0.025), repetition (p <  0.001) and naming (p <  0.001). Disruption of language network structural hubs is directly associated with aphasia severity after stroke.

  14. Resting Energy Expenditure in Patients with Stroke during the Subacute Phases - Relationships with Stroke Types, Location, Severity of Paresis, and Activities of Daily Living.

    PubMed

    Kawakami, Michiyuki; Liu, Meigen; Wada, Ayako; Otsuka, Tomoyoshi; Nishimura, Atsuko

    2015-01-01

    The energy demands in patients with stroke during the subacute phases are unclear. However, this information is essential for appropriate clinical and nutritional management. The aims of this study were to determine the resting energy expenditure (REE) during the subacute phases, examine its relationships with stroke types, location, severity of hemiparesis, and activities of daily living (ADL), and evaluate whether estimation of REE from the Harris-Benedict equation (HB) requires the addition of a 'stress factor' to capture possible additional REE imposed by stroke. We measured REE in 95 patients with subacute stroke (53.5 ± 16.6 days post-stroke) with indirect calorimetry, and compared it with predicted values of energy expenditure estimated from the HB (expressed as percentage). Patients were admitted for rehabilitation of their first ischemic or nonsurgical hemorrhagic stroke. The severity of hemiparesis was assessed with the motor items of the Stroke Impairment Assessment Set (SIAS). The ADL was assessed with the Functional Independence Measure (FIM). We compared REE and %HB of the two groups divided by hemiparesis severity and ADL limitation using the Student's t-test, and those of the five groups divided by stroke location. The correlations between REE and the motor items of the SIAS and the FIM score were assessed with the Spearman rank correlation test. A multiple regression analysis for REE was conducted. The average body weight (BW) was 57.1 ± 11.3 kg. The average body mass index (BMI) was 22.5 ± 4.0. The mean REE (%HB) was 1,271 ± 284 kcal/day (106.0 ± 17.3%). REE and %HB of the low ADL group was less than that of the high ADL group (p < 0.05). The REE had a positive correlation with the FIM score (rs = 0.51, p < 0.01). The motor items of the SIAS were not significantly correlated with REE. BW, FIM, and stroke location were independent predictors of REE. Analysis of energy expenditure suggests that stroke patients are not hypermetabolic during the

  15. Brain regions important for recovery after severe post-stroke upper limb paresis.

    PubMed

    Rondina, Jane M; Park, Chang-Hyun; Ward, Nick S

    2017-09-01

    Background The ability to predict outcome after stroke is clinically important for planning treatment and for stratification in restorative clinical trials. In relation to the upper limbs, the main predictor of outcome is initial severity, with patients who present with mild to moderate impairment regaining about 70% of their initial impairment by 3 months post-stroke. However, in those with severe presentations, this proportional recovery applies in only about half, with the other half experiencing poor recovery. The reasons for this failure to recover are not established although the extent of corticospinal tract damage is suggested to be a contributory factor. In this study, we investigated 30 patients with chronic stroke who had presented with severe upper limb impairment and asked whether it was possible to differentiate those with a subsequent good or poor recovery of the upper limb based solely on a T1-weighted structural brain scan. Methods A support vector machine approach using voxel-wise lesion likelihood values was used to show that it was possible to classify patients as good or poor recoverers with variable accuracy depending on which brain regions were used to perform the classification. Results While considering damage within a corticospinal tract mask resulted in 73% classification accuracy, using other (non-corticospinal tract) motor areas provided 87% accuracy, and combining both resulted in 90% accuracy. Conclusion This proof of concept approach highlights the relative importance of different anatomical structures in supporting post-stroke upper limb motor recovery and points towards methodologies that might be used to stratify patients in future restorative clinical trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Delayed Varenicline Administration Reduces Inflammation and Improves Forelimb Use Following Experimental Stroke.

    PubMed

    Chen, Siyi; Bennet, Laura; McGregor, Ailsa L

    2017-08-07

    Pharmacological activation of the cholinergic anti-inflammatory pathway (CAP), specifically by activating α7 nicotinic acetylcholine receptors, has been shown to confer short-term improvements in outcome. Most studies have investigated administration within 24 hours of stroke, and few have investigated drugs approved for use in human patients. We investigated whether delayed administration of varenicline, a high-affinity agonist at α7 nicotinic receptors and an established therapy for nicotine addiction, decreased brain inflammation and improved functional performance in a mouse model of experimental stroke. CSF-1R-EGFP (MacGreen) mice were subjected to transient middle cerebral artery occlusion and administered varenicline (2.5 mg/kg/d for 7 days) or saline (n = 10 per group) 3 days after stroke. Forelimb asymmetry was assessed in the Cylinder test every 2 days after surgery, and structural lesions were quantified at day 10. Enhanced green fluorescent protein (EGFP) and growth associated protein 43 (GAP43) immunohistochemistry were used to evaluate the effect of varenicline on inflammation and axonal regeneration, respectively. Varenicline-treated animals showed a significant increase in impaired forelimb use compared with saline-treated animals 10 days after stroke. Varenicline treatment was associated with reduced EGFP expression and increased GAP43 expression in the striatum of MacGreen mice. Our results show that delayed administration of varenicline promotes recovery of function following experimental stroke. Motor function improvements were accompanied by decreased brain inflammation and increased axonal regeneration in nonpenumbral areas. These results suggest that the administration of an exogenous nicotinic agonist in the subacute phase following stroke may be a viable therapeutic strategy for stroke patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  17. The role of acute lesion topography in initial ischemic stroke severity and long-term functional outcomes

    PubMed Central

    Wu, Ona; Cloonan, Lisa; Mocking, Steven JT.; Bouts, Mark JRJ.; Copen, William A.; Cougo-Pinto, Pedro; Fitzpatrick, Kaitlin; Kanakis, Allison; Schaefer, Pamela W.; Rosand, Jonathan; Furie, Karen L.; Rost, Natalia S.

    2015-01-01

    Background and Purpose Acute infarct volume, often proposed as a biomarker for evaluating novel interventions for acute ischemic stroke (AIS), correlates only moderately with traditional clinical endpoints such as the modified Rankin Scale (mRS). We hypothesized that the topography of acute stroke lesions on diffusion-weighted MRI (DWI) may provide further information with regard to presenting stroke severity and long-term functional outcomes. Methods Data from a prospective stroke repository were limited to AIS subjects with MRI completed within 48 hours from last known well, admission NIH Stroke Scale (NIHSS), and 3-to-6 months mRS scores. Using voxel-based lesion symptom mapping techniques including age, sex and DWI lesion volume as covariates, statistical maps were calculated to determine the significance of lesion location for clinical outcome and admission stroke severity. Results 490 subjects were analyzed. Acute stroke lesions in the left hemisphere were associated with more severe NIHSS at admission and poor mRS at 3 to 6 months. Specifically, injury to white matter (corona radiata, internal and external capsules, superior longitudinal fasciculus, and uncinate fasciculus), post-central gyrus, putamen, and operculum were implicated in poor mRS. More severe NIHSS involved these regions as well as the amygdala, caudate, pallidum, inferior frontal gyrus, insula, and pre-central gyrus. Conclusions Acute lesion topography provides important insights into anatomical correlates of admission stroke severity and post-stroke outcomes. Future models that account for infarct location in addition to DWI volume may improve stroke outcome prediction and identify patients likely to benefit from aggressive acute intervention and personalized rehabilitation strategies. PMID:26199314

  18. Hemodynamic comparison of mild and severe preeclampsia: concept of stroke systemic vascular resistance index.

    PubMed

    Scardo, J; Kiser, R; Dillon, A; Brost, B; Newman, R

    1996-01-01

    Our purpose was to compare baseline hemodynamic parameters of mild and severe preeclampsia. Patients admitted to the Medical University Labor and Delivery Unit with the diagnosis of preeclampsia who had not received prior antihypertensive or magnesium sulfate therapy were recruited for noninvasive hemodynamic monitoring with thoracic electrical bioimpedance. After stabilization in the lateral recumbent position, hemodynamic monitoring was begun. Baseline hemodynamic parameters, mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance index (SVRI), cardiac index (CI), and stroke index (SI) were recorded. Stroke systemic vascular resistance index (SSVRI), the resistance imposed by vasculature on each beat of the heart, was calculated for each patient by multiplying SVRI by HR. For statistical analysis, unpaired Student's t-tests (two-tailed) were utilized (P < 0.01). Forty-one preeclamptic patients (20 mild, 21 severe) were enrolled. Mean gestational age of severe patients was 32.2 +/- 4.0 and of mild patients was 37.0 +/- 3.5. MAP, SBP, diastolic blood pressure, HR, and SSVRI were higher in the severe group. SVRI, CI, cardiac output, and SI did not differ significantly between groups. Severe preclampsia appears to be a more intensely vasoconstricted state than mild preeclampsia. Although CI is inversely proportional to SVRI, increased HR in severe preeclampsia prevents this expected decrease in cardiac output.

  19. Risk Factors for Multiple Organ Dysfunction Syndrome in Severe Stroke Patients

    PubMed Central

    Yang, Shuna; Li, Yue; Yuan, Junliang; Yang, Lei; Li, Shujuan; Hu, Wenli

    2016-01-01

    Background Severe stroke patients have poor clinical outcome which may be associated with development of multiple organ dysfunction syndrome (MODS). Therefore, the aim of our study was to investigate independent risk factors for development of MODS in severe stroke patients. Methods Ninety seven severe stroke patients were prospective recruited from Jan 2011 to Jun 2015. The development of MODS was identified by Sequential Organ Failure Assessment (SOFA) score (score ≥ 3, at least two organs), which was assessed on day 1, 4, 7, 10 and 14 after admission. Baseline characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow coma score (GCS) and cerebral imaging parameters were collected at admission. Cox regression was performed to determine predictors for the development of MODS. Medical complications after admission and in-hospital mortality were also investigated. Results 33 (34%) patients were in MODS group and 64 (66%) were in non-MODS group within 14 days after admission. Patients in MODS group had more smoker (51.5% vs 28.1%, p = 0.023), higher NIHSS score (23.48 ± 6.12 vs 19.81 ± 4.83, p = 0.004), higher APACHE II score (18.70 ± 5.18 vs 15.64 ± 4.36, p = 0.003) and lower GCS score (6.33 ± 2.48 vs 8.14 ± 2.73, p = 0.002). They also had higher rate of infarction in multi vascular territories (36.4% vs 10.9%, p = 0.003). The most common complication in all patients was pulmonary infection, while complication scores were comparable between two groups. Patients with MODS had higher in-hospital mortality (69.7% vs 9.4%, p = 0.000). In Cox regression, NIHSS score (RR = 1.084, 95% CI 1.019–1.153) and infarction in multi vascular territories (RR = 2.345 95% CI 1.105–4.978) were independent risk factors for development of MODS. Conclusions In acute phase of stroke, NIHSS score and infarction in multi vascular territories predicted MODS in severe stroke patients. Moreover, patients with MODS had higher in-hospital mortality

  20. Risk Factors for Multiple Organ Dysfunction Syndrome in Severe Stroke Patients.

    PubMed

    Qin, Wei; Zhang, Xiaoyu; Yang, Shuna; Li, Yue; Yuan, Junliang; Yang, Lei; Li, Shujuan; Hu, Wenli

    2016-01-01

    Severe stroke patients have poor clinical outcome which may be associated with development of multiple organ dysfunction syndrome (MODS). Therefore, the aim of our study was to investigate independent risk factors for development of MODS in severe stroke patients. Ninety seven severe stroke patients were prospective recruited from Jan 2011 to Jun 2015. The development of MODS was identified by Sequential Organ Failure Assessment (SOFA) score (score ≥ 3, at least two organs), which was assessed on day 1, 4, 7, 10 and 14 after admission. Baseline characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow coma score (GCS) and cerebral imaging parameters were collected at admission. Cox regression was performed to determine predictors for the development of MODS. Medical complications after admission and in-hospital mortality were also investigated. 33 (34%) patients were in MODS group and 64 (66%) were in non-MODS group within 14 days after admission. Patients in MODS group had more smoker (51.5% vs 28.1%, p = 0.023), higher NIHSS score (23.48 ± 6.12 vs 19.81 ± 4.83, p = 0.004), higher APACHE II score (18.70 ± 5.18 vs 15.64 ± 4.36, p = 0.003) and lower GCS score (6.33 ± 2.48 vs 8.14 ± 2.73, p = 0.002). They also had higher rate of infarction in multi vascular territories (36.4% vs 10.9%, p = 0.003). The most common complication in all patients was pulmonary infection, while complication scores were comparable between two groups. Patients with MODS had higher in-hospital mortality (69.7% vs 9.4%, p = 0.000). In Cox regression, NIHSS score (RR = 1.084, 95% CI 1.019-1.153) and infarction in multi vascular territories (RR = 2.345 95% CI 1.105-4.978) were independent risk factors for development of MODS. In acute phase of stroke, NIHSS score and infarction in multi vascular territories predicted MODS in severe stroke patients. Moreover, patients with MODS had higher in-hospital mortality, suggesting that early identification of MODS

  1. Predicting Recovery of Voluntary Upper Extremity Movement in Subacute Stroke Patients with Severe Upper Extremity Paresis

    PubMed Central

    Koh, Chia-Lin; Pan, Shin-Liang; Jeng, Jiann-Shing; Chen, Bang-Bin; Wang, Yen-Ho; Hsueh, I-Ping; Hsieh, Ching-Lin

    2015-01-01

    Background and Objective Prediction of voluntary upper extremity (UE) movement recovery is largely unknown in patients with little voluntary UE movement at admission. The present study aimed to investigate (1) the extent and variation of voluntary UE movement recovery, and (2) the best predictive model of the recovery of voluntary UE movement by clinical variables in patients with severe UE paresis. Design Prospective cohort study. Methods 140 (out of 590) stroke patients with severe UE paresis completed all assessments. Voluntary UE movement was assessed using the UE subscale of the Stroke Rehabilitation Assessment of Movement (STREAM-UE). Two outcome measures, STREAM-UE scores at discharge (DCSTREAM-UE) and changes between admission and discharge (ΔSTREAM-UE), were investigated to represent the final states and improvement of the recovery of voluntary UE movement. Stepwise regression analyses were used to investigate 19 clinical variables and to find the best predictive models of the two outcome measures. Results The participants showed wide variation in both DCSTREAM-UE and ΔSTREAM-UE. 3.6% of the participants almost fully recovered at discharge (DCSTREAM-UE > 15). A large improvement (ΔSTREAM-UE >= 10) occurred in 16.4% of the participants, while 32.9% of the participants did not have any improvement. The four predictors for the DCSTREAM-UE (R2 = 35.0%) were ‘baseline STREAM-UE score’, ‘hemorrhagic stroke’, ‘baseline National Institutes of Health Stroke Scale (NIHSS) score’, and ‘cortical lesion excluding primary motor cortex’. The three predictors for the ΔSTREAM-UE (R2 = 22.0%) were ‘hemorrhagic stroke’, ‘baseline NIHSS score’, and ‘cortical lesion excluding primary motor cortex’. Conclusions Recovery of voluntary UE movement varied widely in patients with severe UE paresis after stroke. The predictive power of clinical variables was poor. Both results indicate the complex nature of voluntary UE movement recovery in patients

  2. Stem cell transplantation enhances endogenous brain repair after experimental stroke.

    PubMed

    Horie, Nobutaka; Hiu, Takeshi; Nagata, Izumi

    2015-01-01

    Stem cell transplantation for stroke treatment has been a promising therapy in small and large animal models, and many clinical trials are ongoing to establish this strategy in a clinical setting. However, the mechanism underlying functional recovery after stem cell transplantation has not been fully established and there is still a need to determine the ideal subset of stem cells for such therapy. We herein reviewed the recent evidences showing the underlying mechanism of functional recovery after cell transplantation, focusing on endogenous brain repair. First, angiogenesis/neovascularization is promoted by trophic factors including vascular endothelial growth factor secreted from stem cells, and stem cells migrated to the lesion along with the vessels. Second, axonal sprouting, dendritic branching, and synaptogenesis were enhanced altogether in the both ipsilateral and contralateral hemisphere remapping the pyramidal tract across the board. Finally, endogenous neurogenesis was also enhanced although little is known how much these neurogenesis contribute to the functional recovery. Taken together, it is clear that stem cell transplantation provides functional recovery via endogenous repair enhancement from multiple ways. This is important to maximize the effect of stem cell therapy after stroke, although it is still undetermined which repair mechanism is mostly contributed.

  3. The relationship of patent foramen ovale location with severity of stroke: A new risk factor for paradoxical embolism.

    PubMed

    Erkoç, Mustafa Fatih; Öztoprak, Bilge; Okur, Aylin; Ede, Hüseyin; Örsçelik, Özcan; Kantarcı, Mecit; Kızrak, Yeşim

    2016-06-01

    Patent foramen ovale (PFO) is a common developmental anomaly and is well associated with paradoxical embolism and cryptogenic stroke. The aim of this study was to investigate the relationship of PFO location with severity of cryptogenic stroke. Fifty patients with cryptogenic stroke and echocardiographically proven PFO were classified according to the severity of stroke. In order to define the location of PFOs, an imaginary line dividing the length of interatrial septum vertically into two equal parts was drawn manually at axial plane on cardiac multidetector computed tomography. PFOs located at superior part of this imaginary line was defined as superiorly located PFO, while PFOs located at inferior part of this imaginary line was defined as inferiorly located PFO. Fourteen patients (28%) revealed mild, 20 patients (40%) revealed moderate and 16 patients (32%) had severe stroke. Based on PFO location, there were 34 patients (68%) with superiorly (group 1), and 16 patients (32%) with inferiorly (group 2) located PFO. It was found that patients of group 1 had significantly higher frequency of moderate or severe stroke compared to those of group 2 (p < 0.005) CONCLUSION: In conclusion, the patients with superiorly located PFO had higher frequency of severe stroke compared to the patients with inferiorly located PFO. Since this is a preliminary study, clinical application and importance of this finding necessitates further large-scale interventional studies.

  4. Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke

    PubMed Central

    Inácio, Ana R; Ruscher, Karsten; Leng, Lin; Bucala, Richard; Deierborg, Tomas

    2011-01-01

    Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo). In mice subjected to tMCAo, we found that MIF accumulates in neurons of the peri-infarct region, particularly in cortical parvalbumin-positive interneurons. Likewise, in cultured cortical neurons exposed to oxygen and glucose deprivation, MIF levels increase, and inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) protects against cell death. Deletion of MIF in Mif−/− mice does not affect interleukin-1β protein levels in the brain and serum after tMCAo. Furthermore, disruption of the Mif gene in mice does not affect CD68, but it is associated with higher galectin-3 immunoreactivity in the brain after tMCAo, suggesting that MIF affects the molecular/cellular composition of the macrophages/microglia response after experimental stroke. We conclude that MIF promotes neuronal death and aggravates neurologic deficits after experimental stroke, which implicates MIF in the pathogenesis of neuronal injury after stroke. PMID:21063426

  5. Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke.

    PubMed

    Inácio, Ana R; Ruscher, Karsten; Leng, Lin; Bucala, Richard; Deierborg, Tomas

    2011-04-01

    Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo). In mice subjected to tMCAo, we found that MIF accumulates in neurons of the peri-infarct region, particularly in cortical parvalbumin-positive interneurons. Likewise, in cultured cortical neurons exposed to oxygen and glucose deprivation, MIF levels increase, and inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) protects against cell death. Deletion of MIF in Mif(-/-) mice does not affect interleukin-1β protein levels in the brain and serum after tMCAo. Furthermore, disruption of the Mif gene in mice does not affect CD68, but it is associated with higher galectin-3 immunoreactivity in the brain after tMCAo, suggesting that MIF affects the molecular/cellular composition of the macrophages/microglia response after experimental stroke. We conclude that MIF promotes neuronal death and aggravates neurologic deficits after experimental stroke, which implicates MIF in the pathogenesis of neuronal injury after stroke.

  6. Pretreatment with indomethacin results in increased heat stroke severity during recovery in a rodent model of heat stroke.

    PubMed

    Audet, Gerald N; Dineen, Shauna M; Stewart, Delisha A; Plamper, Mark L; Pathmasiri, Wimal W; McRitchie, Susan L; Sumner, Susan J; Leon, Lisa R

    2017-09-01

    It has been suggested that medications can increase heat stroke (HS) susceptibility/severity. We investigated whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) increases HS severity in a rodent model. Core temperature (Tc) of male, C57BL/6J mice (n = 45) was monitored continuously, and mice were given a dose of INDO [low dose (LO) 1 mg/kg or high dose (HI) 5 mg/kg in flavored treat] or vehicle (flavored treat) before heating. HS animals were heated to 42.4°C and euthanized at three time points for histological, molecular, and metabolic analysis: onset of HS [maximal core temperature (Tc,Max)], 3 h of recovery [minimal core temperature or hypothermia depth (HYPO)], and 24 h of recovery (24 h). Nonheated (control) animals underwent identical treatment in the absence of heat. INDO (LO or HI) had no effect on physiological indicators of performance (e.g., time to Tc,Max, thermal area, or cooling time) during heating or recovery. HI INDO resulted in 45% mortality rate by 24 h (HI INDO + HS group). The gut showed dramatic increases in gross morphological hemorrhage in HI INDO + HS in both survivors and nonsurvivors. HI INDO + HS survivors had significantly lower red blood cell counts and hematocrit suggesting significant hemorrhage. In the liver, HS induced cell death at HYPO and increased inflammation at Tc,Max, HYPO, and 24 h; however, there was additional effect with INDO + HS group. Furthermore, the metabolic profile of the liver was disturbed by heat, but there was no additive effect of INDO + HS. This suggests that there is an increase in morbidity risk with INDO + HS, likely resulting from significant gut injury.NEW & NOTEWORTHY This paper suggests that in a translational mouse model, NSAIDs may be counterindicated in situations that put an individual at risk of heat injury. We show here that a small, single dose of the NSAID indomethacin before heat stroke has a dramatic and highly damaging effect on the gut, which ultimately leads to

  7. Use of Antihypertensive Drugs and Ischemic Stroke Severity – Is There a Role for Angiotensin-II?

    PubMed Central

    Bots, Michiel L.; Selvarajah, Sharmini; Abdul Aziz, Zariah; Sidek, Norsima Nazifah; Spiering, Wilko; Kappelle, L. Jaap; Vaartjes, Ilonca

    2016-01-01

    Background The increase in angiotensin II (Ang II) formation by selected antihypertensive drugs is said to exhibit neuroprotective properties, but this translation into improvement in clinical outcomes has been inconclusive. We undertook a study to investigate the relationship between types of antihypertensive drugs used prior to a stroke event and ischemic stroke severity. We hypothesized that use of antihypertensive drugs that increase Ang II formation (Ang II increasers) would reduce ischemic stroke severity when compared to antihypertensive drugs that suppress Ang II formation (Ang II suppressors). Methods From the Malaysian National Neurology Registry, we included hypertensive patients with first ischemic stroke who presented within 48 hours from ictus. Antihypertensive drugs were divided into Ang II increasers (angiotensin-I receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics) and Ang II suppressors (angiotensin-converting-enzyme inhibitors (ACEIs) and beta blockers). We evaluated stroke severity during admission with the National Institute of Health Stroke Scale (NIHSS). We performed a multivariable logistic regression with the score being dichotomized at 15. Scores of less than 15 were categorized as less severe stroke. Results A total of 710 patients were included. ACEIs was the most commonly prescribed antihypertensive drug in patients using Ang II suppressors (74%) and CCBs, in patients prescribed with Ang II increasers at 77%. There was no significant difference in the severity of ischemic stroke between patients who were using Ang II increasers in comparison to patients with Ang II suppressors (OR: 1.32, 95%CI: 0.83–2.10, p = 0.24). Conclusion In our study, we found that use of antihypertensive drugs that increase Ang II formation was not associated with less severe ischemic stroke as compared to use of antihypertensive drugs that suppress Ang II formation. PMID:27846309

  8. Low body temperature associated with severe ischemic stroke within 6 hours of onset: The Bergen NORSTROKE Study.

    PubMed

    Kvistad, Christopher E; Thomassen, Lars; Waje-Andreassen, Ulrike; Naess, Halvor

    2012-01-01

    Hypothermia is considered neuroprotective and a potential treatment in cerebral ischemia. Some studies suggest that hyperthermia may promote clot lysis. We hypothesized that low body temperature would prolong time to spontaneous clot lysis resulting in an association between low body temperature and severe neurological deficits in the early phase of ischemic stroke. In this prospective study, patients (n = 516) exhibiting ischemic stroke with symptom onset within 6 hours were included. Body temperature and National Institute of Health Stroke Scale (NIHSS) score were registered on admission. Because low body temperature on admission may be secondary to immobilization due to large stroke, separate analyses were performed on patients with cerebral hemorrhage admitted within 6 hours (n = 85). Linear regression showed that low body temperature on admission was independently associated with a high NIHSS score within 6 hours of stroke onset in patients with ischemic stroke (P < 0.001). The association persisted when NIHSS was measured at 24 hours after admission. No such associations were found in patients with cerebral hemorrhage admitted within 6 hours of stroke onset. Our study suggests that low body temperature within 6 hours of symptom onset is associated with severe ischemic stroke. This is in support of our hypothesis, although other contributing mechanisms cannot be excluded.

  9. Experimental evidence and early translational steps using bone marrow derived stem cells after human stroke.

    PubMed

    Kasahara, Yukiko; Ihara, Masafumi; Taguchi, Akihiko

    2013-01-01

    Neurogenesis is principally restricted to the subventricular zone of the lateral ventricle wall and the subgranular zone of the hippocampal dentate gyrus in physiological situations. However, neuronal stem cells are known to be mobilized into the post- and peristroke area and we have demonstrated that appropriate support of these stem cells, achieved by therapeutic angiogenesis, enhances neuroregeneration followed by neuronal functional recovery in an experimental stroke model. We also found that neural stem cells are mobilized in patients after stroke, as well as in animal models. Based on these observations, we have started cell-based therapy using autologous bone marrow-derived stem/progenitor cells in patients after stroke. This review summarizes the findings of recent experimental and clinical studies that have focused on neurogenesis in the injured brain after cerebral infarction. We also refer to the challenges for future cell-based therapy, including regeneration of the aged brain. Copyright © 2013 S. Karger AG, Basel.

  10. Functional MRI and diffusion tensor imaging of brain reorganization after experimental stroke.

    PubMed

    Dijkhuizen, Rick M; van der Marel, Kajo; Otte, Willem M; Hoff, Erik I; van der Zijden, Jet P; van der Toorn, Annette; van Meer, Maurits P A

    2012-03-01

    The potential of the adult brain to reorganize after ischemic injury is critical for functional recovery and provides a significant target for therapeutic strategies to promote brain repair. Despite the accumulating evidence of brain plasticity, the interaction and significance of morphological and physiological modifications in post-stroke brain tissue remain mostly unclear. Neuroimaging techniques such as functional MRI (fMRI) and diffusion tensor imaging (DTI) enable in vivo assessment of the spatial and temporal pattern of functional and structural changes inside and outside ischemic lesion areas. This can contribute to the elucidation of critical aspects in post-stroke brain remodeling. Task/stimulus-related fMRI, resting-state fMRI, or pharmacological MRI enables direct or indirect measurement of neuronal activation, functional connectivity, or neurotransmitter system responses, respectively. DTI allows estimation of the structural integrity and connectivity of white matter tracts. Together, these MRI methods provide an unprecedented means to (a) measure longitudinal changes in tissue structure and function close by and remote from ischemic lesion areas, (b) evaluate the organizational profile of neural networks after stroke, and (c) identify degenerative and restorative processes that affect post-stroke functional outcome. Besides, the availability of MRI in clinical institutions as well as research laboratories provides an optimal basis for translational research on stroke recovery. This review gives an overview of the current status and perspectives of fMRI and DTI applications to study brain reorganization in experimental stroke models.

  11. 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.

  12. 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

  13. Multiparametric, longitudinal optical coherence tomography imaging reveals acute injury and chronic recovery in experimental ischemic stroke.

    PubMed

    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.

  14. Changes in auditory feedback connections determine the severity of speech processing deficits after stroke

    PubMed Central

    Schofield, T.M.; Penny, W.D.; Stephan, K.E.; Crinion, J.T.; Thompson, A.J.; Price, C.J.; Leff, A.P.

    2012-01-01

    We compared brain structure and function in two sub-groups of 21 stroke patients with either moderate or severe chronic speech comprehension impairment. Both groups had damage to the supra-temporal plane; however, the severe group suffered greater damage to two unimodal auditory areas: primary auditory cortex and the planum temporale. The effects of this damage were investigated using fMRI while patients listened to speech and speech-like sounds. Pronounced changes in connectivity were found in both groups, in undamaged parts of the auditory hierarchy. Compared to controls, moderate patients had significantly stronger feedback connections from planum temporale to primary auditory cortex bilaterally, while in severe patients this connection was significantly weaker in the undamaged right hemisphere. This suggests that predictive feedback mechanisms compensate in moderately affected patients but not in severely affected patients. The key pathomechanism in humans with persistent speech comprehension impairments may be impaired feedback connectivity to unimodal auditory areas. PMID:22442088

  15. Vitamin D Deficiency Exacerbates Experimental Stroke Injury and Dysregulates Ischemia-Induced Inflammation in Adult Rats

    PubMed Central

    Balden, Robyn; Selvamani, Amutha

    2012-01-01

    Vitamin D deficiency (VDD) is widespread and considered a risk factor for cardiovascular disease and stroke. Low vitamin D levels are predictive for stroke and more fatal strokes in humans, whereas vitamin D supplements are associated with decreased risk of all-cause mortality. Because VDD occurs with other comorbid conditions that are also independent risk factors for stroke, this study examined the specific effect of VDD on stroke severity in rats. Adult female rats were fed control or VDD diet for 8 wk and were subject to middle cerebral artery occlusion thereafter. The VDD diet reduced circulating vitamin D levels to one fifth (22%) of that observed in rats fed control chow. Cortical and striatal infarct volumes in animals fed VDD diet were significantly larger, and sensorimotor behavioral testing indicated that VDD animals had more severe poststroke behavioral impairment than controls. VDD animals were also found to have significantly lower levels of the neuroprotective hormone IGF-I in plasma and the ischemic hemisphere. Cytokine analysis indicated that VDD significantly reduced IL-1α, IL-1β, IL-2, IL-4, IFN-γ, and IL-10 expression in ischemic brain tissue. However, ischemia-induced IL-6 up-regulation was significantly higher in VDD animals. In a separate experiment, the therapeutic potential of acute vitamin D treatments was evaluated, where animals received vitamin D injections 4 h after stroke and every 24 h thereafter. Acute vitamin D treatment did not improve infarct volume or behavioral performance. Our data indicate that VDD exacerbates stroke severity, involving both a dysregulation of the inflammatory response as well as suppression of known neuroprotectants such as IGF-I. PMID:22408173

  16. Enhanced estimations of post-stroke aphasia severity using stacked multimodal predictions.

    PubMed

    Pustina, Dorian; Coslett, Harry Branch; Ungar, Lyle; Faseyitan, Olufunsho K; Medaglia, John D; Avants, Brian; Schwartz, Myrna F

    2017-08-07

    The severity of post-stroke aphasia and the potential for recovery are highly variable and difficult to predict. Evidence suggests that optimal estimation of aphasia severity requires the integration of multiple neuroimaging modalities and the adoption of new methods that can detect multivariate brain-behavior relationships. We created and tested a multimodal framework that relies on three information sources (lesion maps, structural connectivity, and functional connectivity) to create an array of unimodal predictions which are then fed into a final model that creates "stacked multimodal predictions" (STAMP). Crossvalidated predictions of four aphasia scores (picture naming, sentence repetition, sentence comprehension, and overall aphasia severity) were obtained from 53 left hemispheric chronic stroke patients (age: 57.1 ± 12.3 yrs, post-stroke interval: 20 months, 25 female). Results showed accurate predictions for all four aphasia scores (correlation true vs. predicted: r = 0.79-0.88). The accuracy was slightly smaller but yet significant (r = 0.66) in a full split crossvalidation with each patient considered as new. Critically, multimodal predictions produced more accurate results that any single modality alone. Topological maps of the brain regions involved in the prediction were recovered and compared with traditional voxel-based lesion-to-symptom maps, revealing high spatial congruency. These results suggest that neuroimaging modalities carry complementary information potentially useful for the prediction of aphasia scores. More broadly, this study shows that the translation of neuroimaging findings into clinically useful tools calls for a shift in perspective from unimodal to multimodal neuroimaging, from univariate to multivariate methods, from linear to nonlinear models, and, conceptually, from inferential to predictive brain mapping. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Recovery-related indicators of motor network plasticity according to impairment severity after stroke.

    PubMed

    Lee, J; Park, E; Lee, A; Chang, W H; Kim, D-S; Kim, Y-H

    2017-10-01

    Brain connectivity analysis has been widely used to investigate brain plasticity and recovery-related indicators of patients with stroke. However, results remain controversial because of interindividual variability of initial impairment and subsequent recovery of function. In this study, we aimed to investigate the differences in network plasticity and motor recovery-related indicators according to initial severity. We divided participants (16 males and 14 females, aged 54.2 ± 12.0 years) into groups of different severity by Fugl-Mayer Assessment score, i.e. moderate (50-84), severe (20-49) and extremely severe (<20) impairment groups. Longitudinal resting-state functional magnetic resonance imaging data were acquired at 2 weeks and 3 months after onset. The differences in network plasticity and recovery-related indicators between groups were investigated using network distance and graph measurements. As the level of impairment increased, the network balance was more disrupted. Network balance, interhemispheric connectivity and network efficiency were recovered at 3 months only in the moderate impairment group. However, this was not the case in the extremely severe impairment group. A single connection strength between the ipsilesional primary motor cortex and ventral premotor cortex was implicated in the recovery of motor function for the extremely severe impairment group. The connections of the ipsilesional primary motor cortex-ventral premotor cortex were positively associated with motor recovery as the patients were more severely impaired. Differences in plasticity and recovery-related indicators of motor networks were noted according to impairment severity. Our results may suggest meaningful implications for recovery prediction and treatment strategies in future stroke research. © 2017 EAN.

  18. Psychoneuroimmunology of stroke.

    PubMed

    Skinner, Robert; Georgiou, Rachel; Thornton, Peter; Rothwell, Nancy

    2006-08-01

    There is now considerable evidence from both experimental and clinical studies that immune and inflammatory processes can contribute to the onset of stroke and the neurologic and psychologic outcomes. Several specific therapeutic targets have been identified that may significantly improve the devastating impact of stroke.

  19. Katanin spiral and ring structures shed light on power stroke for microtubule severing.

    PubMed

    Zehr, Elena; Szyk, Agnieszka; Piszczek, Grzegorz; Szczesna, Ewa; Zuo, Xiaobing; Roll-Mecak, Antonina

    2017-09-01

    Microtubule-severing enzymes katanin, spastin and fidgetin are AAA ATPases important for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. Because of a lack of known 3D structures for these enzymes, their mechanism of action has remained poorly understood. Here we report the X-ray crystal structure of the monomeric AAA katanin module from Caenorhabditis elegans and cryo-EM reconstructions of the hexamer in two conformations. The structures reveal an unexpected asymmetric arrangement of the AAA domains mediated by structural elements unique to microtubule-severing enzymes and critical for their function. The reconstructions show that katanin cycles between open spiral and closed ring conformations, depending on the ATP occupancy of a gating protomer that tenses or relaxes interprotomer interfaces. Cycling of the hexamer between these conformations would provide the power stroke for microtubule severing.

  20. Communication impairment and activity limitation in stroke patients with severe aphasia.

    PubMed

    Darrigrand, Benedicte; Dutheil, Sabine; Michelet, Valerie; Rereau, Stephanie; Rousseaux, Marc; Mazaux, Jean-Michel

    2011-01-01

    This study investigated how patients with severe aphasia communicated in daily living, which verbal and non-verbal communication skills were spared and which were impaired, and whether activity limitations in communication are related to verbal impairments. Twenty-seven patients with severe aphasia and 9 with moderate aphasia originating from a sample of 102 aphasic persons followed up in a French regional survey were assessed with a communication test and a communication activity limitation questionnaire 12-18 months after a first stroke. Patients with severe aphasia suffered severe activity limitations in communication, with performance 3-fold lower than that of patients with moderate aphasia, and 4-fold lower than scores attained by normals. Both aphasia severity and communication disability at follow-up were related to the initial severity of aphasia. Using a phone, credit card and a chequebook, reading and filling in administrative documents, and communication behaviours involved in social life were the most severely impaired. Non-verbal communication performance was not related to aphasia severity. We conclude that there is a great need for speech therapy research to develop new compensatory or alternative strategies for patients with severe aphasia.

  1. No evidence that severity of stroke in internal carotid occlusion is related to collateral arteries

    PubMed Central

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

    2006-01-01

    Background/Aim The neurological effects of internal carotid artery (ICA) occlusion vary between patients. The authors investigated whether the severity of symptoms in a large group of patients with ipsilateral or/and contralateral ICA occlusion at presentation with ocular or cerebral ischaemic symptoms could be explained by patency of other extra or intracranial arteries to act as collateral pathways. Methods The authors prospectively identified all patients (n = 2881) with stroke, cerebral transient ischaemic attack (TIA), retinal artery occlusion (RAO), and amaurosis fugax (AFx) presenting to our hospital over five years, obtained detailed history and examination, and examined the intra and extracranial arteries with carotid and colour‐power transcranial Doppler ultrasound. For this analysis, all those with intracranial haemorrhage on brain imaging and cerebral events without brain imaging were excluded. Results Among 2228/2397 patients with brain imaging (1713 ischaemic strokes, 401 cerebral TIAs, 193 AFx, and 90 RAO) who underwent carotid Doppler, 195 (9%) had ICA occlusion. Among those patients with cortical events, disease in potential collateral arteries (contralateral ICA, external carotid, ipsilateral or contralateral vertebral or intracranial arteries) was equally distributed among patients with severe and mild ischaemic presenting symptoms. Conclusion The authors found no evidence that the clinical presentation associated with an ICA occlusion was related to patency of other extra or intracranial arteries to act as collateral pathways. Further work is required to investigate what determines the clinical effects of ICA occlusion. PMID:16488923

  2. [Percutaneous transluminal angioplasty for progressing stroke caused by severe basilar artery stenosis: case report].

    PubMed

    Yamamura, A; Takamura, Y; Yamaki, T; Nakagawa, T; Hashi, K

    1994-03-01

    We encountered one case of progressing stroke caused by severe basilar artery stenosis. The patient was treated with emergent percutaneous transluminal angioplasty (PTA) with satisfactory results. A 54 year-old woman was admitted 15 minutes after the sudden onset of rt. hemiparesis, rt. hemidysesthesia, dysarthria and consciousness disturbance. CT scan on admission showed no abnormal findings. The consciousness level of the patient deteriorated rapidly from JCS 1 to JCS 20 within 30 minutes from the ictus. An emergent angiogram revealed severe basilar artery stenosis at its middle portion and poorly developed collateral circulation. One hour after the stroke occurred, PTA was performed. Using a 3mm diameter balloon catheter, we introduced the balloon into the stenotic lesion and inflated it 6 times from 4 atm to 8 atm pressure. The patient recovered immediately on the operating table improving from JCS 20 to JCS 1. Rt. hemiparesis also improved. Follow-up MRI showed a small area of ischemic change in the brain stem, but no large infarction appeared. The patient was discharged with no neurosurgical deficits after 30 days of PTA. PTA for basilar artery stenosis is still a controversial subject. One reason is the risk of basilar artery perforating branches occlusion by balloon catheter and the other is the difficulty of introducing a flexible balloon catheter into the basilar artery beyond the acute angulation of the vertebral artery. If those two problems were solved, PTA would be the first-choice therapy for basilar artery stenosis in both acute and chronic stages.

  3. 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

  4. Lack of sex-linked differences in cerebral edema and aquaporin-4 expression after experimental stroke

    PubMed Central

    Liu, Xiaoqin; Zhang, Wenri; Alkayed, Nabil J; Froehner, Stanley C; Adams, Marvin E; Amiry-Moghaddam, Mahmood; Ottersen, Ole Petter; Hurn, Patricia D; Bhardwaj, Anish

    2009-01-01

    Aquaporin-4 (AQP4) has been shown to be important in the evolution of stroke-associated cerebral edema. However, the role of AQP4 in stroke-associated cerebral edema as it pertains to sex has not been previously studied. The perivascular pool of AQP4 is important in the influx and efflux of water during focal cerebral ischemia. We used mice with targeted disruption of the gene encoding α-syntrophin (α-Syn−/−) that lack the perivascular AQP4 pool but retain the endothelial pool of this protein. Infarct volume at 72h after transient focal ischemia (90 mins) in isoflurane-anesthetized mice was attenuated in both sexes with α-Syn deletion as compared with their wild-type (WT) counterparts. There were no sex differences in hemispheric water content in WT and α-Syn−/− mice or regional AQP4 expression in WT mice. In neither sex did α-Syn deletion lead to alterations in end-ischemic regional cerebral blood flow (rCBF). These data suggest that after experimental stroke: (1) there is no difference in stroke-associated cerebral edema based on sex, (2) AQP4 does not involve in sex-based differences in stroke volume, and (3) perivascular pool of AQP4 has no significant role in end-ischemic rCBF. PMID:18648381

  5. Epidermal growth factor and growth hormone-releasing peptide-6: combined therapeutic approach in experimental stroke.

    PubMed

    García Del Barco-Herrera, Diana; Martínez, Nelvys Subirós; Coro-Antich, Rosa María; Machado, Jorge Martín; Alba, José Suárez; Salgueiro, Sandra Rodríguez; Acosta, Jorge Berlanga

    2013-01-01

    Stroke is the second cause of mortality worldwide, with a high incidence of disability in survivors. Promising candidate drugs have failed in stroke trials. Combined therapies are attractive strategies that simultaneously target different points of stroke pathophysiology. The aim of this work is to determine whether the combined effects of epidermal growth factor (EGF) and growth hormone-releasing peptide-6 (GHRP6) can attenuate clinical signs and pathology in an experimental stroke model. Brain global ischemia was generated in Mongolian gerbils by 15 minutes of carotid occlusion. After reperfusion, EGF, GHRP6 or EGF+GHRP6 were intraperitoneally administered. Clinical manifestations were monitored daily. Three days after reperfusion, animals were anesthetized and perfused with an ink solution. The anatomy of the Circle of Willis was characterized. Infarct volume and neuronal density were analyzed. EGF+GHRP6 co-administration reduced clinical manifestations and infarct volume and preserved neuronal density. No correlation was observed between the grade of anastomosis of the Circle of Willis and clinical manifestations in the animals receiving EGF+GHRP6, as opposed to the vehicle-treated gerbils. Co-treatment with EGF and GHRP6 affects both the clinical and pathological outcomes in a global brain ischemia model, suggesting a suitable therapeutic approach for the acute management of stroke.

  6. Aggressive surgical interventions for severe stroke: Impact on quality of life, caregiver burden and family outcomes.

    PubMed

    Green, Theresa; Demchuk, Andrew; Newcommon, Nancy

    2015-01-01

    Decompressive hemicraniectomy, clot evacuation, and aneurysmal interventions are considered aggressive surgical therapeutic options for treatment of massive cerebral artery infarction (MCA), intracerebral hemorrhage (ICH), and severe subarachnoid hemorrhage (SAH) respectively. Although these procedures are saving lives, little is actually known about the impact on outcomes other than short-term survival and functional status. The purpose of this study was to gain a better understanding of personal and social consequences of surviving these aggressive surgical interventions in order to aid acute care clinicians in helping family members make difficult decisions about undertaking such interventions. An exploratory mixed method study using a convergent parallel design was conducted to examine functional recovery (NIHSS, mRS & BI), cognitive status (Montreal Cognitive Assessment Scale, MoCA), quality of life (Euroqol 5-D), and caregiver outcomes (Bakas Caregiver Outcome Scale, BCOS) in a cohort of patients and families who had undergone aggressive surgical intervention for severe stroke between the years 2000-2007 Data were analyzed using descriptive statistics, univariate and multivariate analysis of variance, and multivariate logistic regression. Content analysis was used to analyze the qualitative interviews conducted with stroke survivors and family members. Twenty-seven patients and 13 spouses participated in this study. Based on patient MOCA scores, overall cognitive status was 25.18 (range 23.4-26.9); current functional outcomes scores: NIHSS 2.22, mRS 1.74, and BI 88.5. EQ-5D scores revealed no significant differences between patients and caregivers (p = 0.585) and caregiver outcomes revealed no significant diferences between male/female caregivers or patient diagnostic group (MCA, SAH, ICH; p = 0.103). Overall, patients and families were satisfied with quality of life and decisions made at the time of the initial stroke. There was consensus among study

  7. Open Heart Surgery Does Not Increase the Incidence of Ipsilateral Ischemic Stroke in Patients with Asymptomatic Severe Carotid Stenosis.

    PubMed

    Castaldo, John E; Yacoub, Hussam A; Li, Yuebing; Kincaid, Hope; Jenny, Donna

    2017-06-13

    We evaluated the incidence of perioperative stroke following the institution's 2007 practice change of discontinuing combined carotid endarterectomy and open heart surgery (OHS) for patients with severe carotid stenosis. In this retrospective cohort study, we compared 113 patients undergoing coronary artery bypass grafting, aortic valve replacement, or both from 2007 to 2011 with data collected from 2001 to 2006 from a similar group of patients. Our aim was to assess whether the practice change led to a greater incidence of stroke. A total of 7350 consecutive patients undergoing OHS during the specified time period were screened. Of these, 3030 had OHS between 2007 and 2011 but none were combined with carotid artery surgery (new cohort). The remaining 4320 had OHS before 2007 and 44 had combined procedures (old cohort). Of patients undergoing OHS during the 10-year period of observation, 230 had severe (>80%) carotid stenosis. In the old cohort (before 2007), carotid stenosis was associated with perioperative stroke in 2.5% of cases. None of the 113 patients having cardiac procedures after 2007 received combined carotid artery surgery; only 1 of these patients harboring severe carotid stenosis had an ischemic stroke (.9%) during the perioperative period. The difference in stroke incidence between the 2 cohorts was statistically significant (P = .002). The incidence of stroke in patients with severe carotid artery stenosis undergoing OHS was lower after combined surgery was discontinued. Combined carotid and OHS itself seems to be an important risk factor for stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  8. Validating imaging biomarkers of cerebral edema in patients with severe ischemic stroke.

    PubMed

    Yoo, Albert J; Sheth, Kevin N; Kimberly, W Taylor; Chaudhry, Zeshan A; Elm, Jordan J; Jacobson, Sven; Davis, Stephen M; Donnan, Geoffrey A; Albers, Gregory W; Stern, Barney J; González, R Gilberto

    2013-08-01

    There is no validated neuroimaging marker for quantifying brain edema. We sought to test whether magnetic resonance imaging (MRI)-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints. Serial MRI studies from patients in the Echoplanar Imaging Thrombolytic Evaluation Trial with initial diffusion-weighted imaging (DWI) lesion volume >82 cm(3) were analyzed. Two independent readers outlined the hemisphere and lateral ventricle on the involved side and calculated respective volumes at baseline and days 3 to 5. We assessed interrater agreement, volume change between scans, and the association of volume change with early neurologic deterioration (National Institutes of Health Stroke Scale score worsening of ≥ 4 points), a 90-day modified Rankin scale (mRS) score of 0 to 4, and mortality. Of 12 patients who met study criteria, average baseline and follow-up DWI lesion size was 138 cm(3) and 234 cm(3), respectively. The mean time to follow-up MRI was 62 hours. Concordance correlation coefficients between readers were >0.90 for both hemisphere and ventricle volume assessment. Mean percent hemisphere volume increase was 16.2 ± 8.3% (P < .0001), and the mean percent ventricle volume decrease was 45.6 ± 16.9% (P < .001). Percent hemisphere growth predicted early neurologic deterioration (area under the curve [AUC] 0.92; P = .0005) and 90-day mRS 0 to 4 (AUC 0.80; P = .02). In this exploratory analysis of severe ischemic stroke patients, statistically significant changes in hemisphere and ventricular volumes within the first week are consistent with expected changes of cerebral edema. MRI-based analysis of hemisphere growth appears to be a suitable biomarker for edema formation. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  9. Use of calcitonin to prevent complex regional pain syndrome type I in severe hemiplegic patients after stroke.

    PubMed

    Matayoshi, Satoru; Shimodozono, Megumi; Hirata, Yoshifumi; Ueda, Toshie; Horio, Shinya; Kawahira, Kazumi

    2009-01-01

    To evaluate the effects of calcitonin in preventing complex regional pain syndrome type I (CRPS) in patients with severe hemiplegia following stroke. In this observer-blinded, controlled study comparison with historical controls between April 2003 and May 2004, subjects comprised consecutive patients with post-stroke hemiplegia admitted between June 2004 and September 2005, with any upper limb or finger graded as Brunnstrom stage (BrST) III or below. One group was administered intramuscular injection of 20 units of elcatonin (EL) (Asu(1-7) eel calcitonin) weekly from immediately after admission to discharge, together with rehabilitation therapy. The control group received rehabilitation therapy alone. Patients were observed during the in-hospital rehabilitation period. The main outcome measure was onset of CRPS. Incidence of CRPS in all patients with post-stroke hemiplegia during the control period was about 8.2%, similar to recent studies. Limited to serious hemiplegic patients graded as BrST III or below, incidence of CRPS was significantly lower in the EL group (12.5%) than in controls (57.1%). No significant differences in patient background were seen between groups. CRPS was completely prevented when EL injection was started stroke, but prophylactic effects were weak when EL was started >6 weeks after stroke. Intramuscular calcitonin appears to suppress onset of CRPS after stroke, particularly when started early after stroke.

  10. A comparison of stroke severity proxy measures for claims data research: a population-based cohort study.

    PubMed

    Sung, Sheng-Feng; Chen, Solomon Chih-Cheng; Hsieh, Cheng-Yang; Li, Chung-Yi; Lai, Edward Chia-Cheng; Hu, Ya-Han

    2016-04-01

    Confounding by disease severity has been viewed as an intractable problem in claims-based studies. A novel 7-variable stroke severity index (SSI) was designed for estimating stroke severity by using claims data. This study compared the performance of mortality models with various proxy measures of stroke severity, including the SSI, in patients hospitalized for acute ischemic stroke (AIS). Data from the Taiwan National Health Insurance Research Database (NHIRD) were analyzed. Three proxy measures of stroke severity were evaluated: Measure 1, the SSI; Measure 2, intensive care unit admission and length of stay; and Measure 3, surgical operation, mechanical ventilation, hemiplegia or hemiparesis, and residual neurological deficits. We performed logistic regression by including age, sex, vascular risk factors, Charlson comorbidity index, and one of the proxy measures as covariates to predict 30-day and 1-year mortality after AIS. Model discrimination was evaluated using the area under the receiver-operating characteristic curve (AUC). We identified 7551 adult patients with AIS. Models using the SSI (Measure 1) outperformed models using the other proxy measures in predicting 30-day mortality (AUC 0.892 vs 0.851, p < 0.001 for Measure 2; 0.892 vs 0.853, p < 0.001 for Measure 3) and 1-year mortality (AUC 0.816 vs 0.784, p < 0.001 for Measure 2; 0.816 vs 0.782, p < 0.001 for Measure 3). Using the SSI facilitated risk adjustment for stroke severity in mortality models for patients with AIS. The SSI is a viable methodological tool for stroke outcome studies using the NHIRD. Copyright © 2015 John Wiley & Sons, Ltd.

  11. [Emotional stress in the development of experimental hemorrhagic stroke in rats with different resistance to stress].

    PubMed

    Ivannikova, N O; Koplik, E V; Popova, E N; Sudakov, K V

    2009-01-01

    Individual behavioral characteristics of rats in the open-field test reflect their resistance to emotional stress and determine the severity of neurological disorders during intracerebral hemorrhage. Stress-resistant rats are characterized by a more rapid restoration of neurological status and disappearance of locomotor and coordination disturbances on day 7 after unilateral hemorrhage stroke in the caudate nucleus as compared to stress-predisposed animals. After hemorrhage stroke in the caudate nucleus, changes in vessels and neurons of the contralateral sensorimotor cortex were more pronounced in stress-predisposed passive rats than in stress-resistant active animals. The newly formed capillaries were not seen in stress-predisposed specimens. To day 7 of post stress hemorrhage stroke in the caudate nucleus, signs of the involvement of compensatory mechanisms in the contralateral sensorimotor cortex appeared in stress-resistant but not in stress-predisposed rats. This finding suggests the possibility of restoration of structure and normal functioning of neurons.

  12. Endovascular Therapy Is Effective and Safe for Patients With Severe Ischemic Stroke: Pooled Analysis of Interventional Management of Stroke III and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands Data.

    PubMed

    Broderick, Joseph P; Berkhemer, Olvert A; Palesch, Yuko Y; Dippel, Diederik W J; Foster, Lydia D; Roos, Yvo B W E M; van der Lugt, Aad; Tomsick, Thomas A; Majoie, Charles B L M; van Zwam, Wim H; Demchuk, Andrew M; van Oostenbrugge, Robert J; Khatri, Pooja; Lingsma, Hester F; Hill, Michael D; Roozenbeek, Bob; Jauch, Edward C; Jovin, Tudor G; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A; Goyal, Mayank; Schonewille, Wouter J; Mazighi, Mikael; Engelter, Stefan T; Anderson, Craig S; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J; Janis, L Scott; Simpson, Kit N

    2015-12-01

    We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (National Institutes of Health Stroke Scale score, ≥20) after a prespecified analysis plan. The pooled analysis of the Interventional Management of Stroke III (IMS III) and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trials included participants with an National Institutes of Health Stroke Scale score of ≥20 before intravenous tissue-type plasminogen activator (tPA) treatment (IMS III) or randomization (MR CLEAN) who were treated with intravenous tPA ≤3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy after intravenous tPA would have improved 90-day outcome (distribution of modified Rankin Scale scores), when compared with those who received intravenous tPA alone. Among 342 participants in the pooled analysis (194 from IMS III and 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared with the intravenous tPA group (adjusted odds ratio, 1.78; 95% confidence interval, 1.20-2.66). In the logistic regression model of the dichotomous outcome (modified Rankin Scale score, 0-2, or functional independence), the endovascular group had superior outcomes (adjusted odds ratio, 1.97; 95% confidence interval, 1.09-3.56). Functional independence (modified Rankin Scale score, ≤2) at 90 days was 25% in the endovascular group when compared with 14% in the intravenous tPA group. Endovascular therapy after intravenous tPA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424 (IMS III) and ISRCTN10888758 (MR CLEAN). © 2015 American Heart Association, Inc.

  13. Improved status following behavioural intervention in a case of severe dysarthria with stroke aetiology.

    PubMed

    Mackenzie, Catherine; Lowit, Anja

    2012-08-01

    There is little published intervention outcome literature concerning dysarthria acquired from stroke. Single case studies have potential for more detailed specification and interpretation than is generally possible in larger studies so are informative for clinicians dealing with similar cases. Such research also contributes to planning of larger scale investigations. Behavioural intervention is described which was carried out between 7-9 months after stroke with a 69-year-old man with severe dysarthria. Pre-intervention stability between 5-7 months contrasted with post-intervention gains. Significant improvement was demonstrated using randomized, blinded assessment by 10 judges on measures of word and reading intelligibility and communication effectiveness in conversation. A range of speech analyses were undertaken (rate, pause, and intonation characteristics in connected speech and single word phonetic transcription), with the aim of identifying speech components which might explain the listeners' perceptions of improvement. Changes were detected mainly in parameters related to utterance segmentation and intonation. The basis of post-intervention improvement in dysarthria is complex, both in terms of the active therapeutic dimensions and also the specific speech alterations which account for changes to intelligibility and effectiveness.

  14. Prediction of the survival and functional ability of severe stroke patients after ICU therapeutic intervention

    PubMed Central

    Riachy, Moussa; Sfeir, Frida; Sleilaty, Ghassan; Hage-Chahine, Samer; Dabar, Georges; Bazerbachi, Taha; Aoun-Bacha, Zeina; Khayat, Georges; Koussa, Salam

    2008-01-01

    Background This study evaluated the benefits and impact of ICU therapeutic interventions on the survival and functional ability of severe cerebrovascular accident (CVA) patients. Methods Sixty-two ICU patients suffering from severe ischemic/haemorrhagic stroke were evaluated for CVA severity using APACHE II and the Glasgow coma scale (GCS). Survival was determined using Kaplan-Meier survival tables and survival prediction factors were determined by Cox multivariate analysis. Functional ability was assessed using the stroke impact scale (SIS-16) and Karnofsky score. Risk factors, life support techniques and neurosurgical interventions were recorded. One year post-CVA dependency was investigated using multivariate analysis based on linear regression. Results The study cohort constituted 6% of all CVA (37.8% haemorrhagic/62.2% ischemic) admissions. Patient mean(SD) age was 65.8(12.3) years with a 1:1 male: female ratio. During the study period 16 patients had died within the ICU and seven in the year following hospital release. The mean(SD) APACHE II score at hospital admission was 14.9(6.0) and ICU mean duration of stay was 11.2(15.4) days. Mechanical ventilation was required in 37.1% of cases. Risk ratios were; GCS at admission 0.8(0.14), (p = 0.024), APACHE II 1.11(0.11), (p = 0.05) and duration of mechanical ventilation 1.07(0.07), (p = 0.046). Linear coefficients were: type of CVA – haemorrhagic versus ischemic: -18.95(4.58) (p = 0.007), GCS at hospital admission: -6.83(1.08), (p = 0.001), and duration of hospital stay -0.38(0.14), (p = 0.40). Conclusion To ensure a better prognosis CVA patients require ICU therapeutic interventions. However, as we have shown, where tests can determine the worst affected patients with a poor vital and functional outcome should treatment be withheld? PMID:18582387

  15. Evaluation of exercise capacity after severe stroke using robotics-assisted treadmill exercise: a proof-of-concept study.

    PubMed

    Stoller, O; de Bruin, E D; Schindelholz, M; Schuster, C; de Bie, R A; Hunt, K J

    2013-01-01

    Robotics-assisted treadmill exercise (RATE) with focus on motor recovery has become popular in early post-stroke rehabilitation but low endurance for exercise is highly prevalent in these individuals. This study aimed to develop an exercise testing method using robotics-assisted treadmill exercise to evaluate aerobic capacity after severe stroke. Constant load testing (CLT) based on body weight support (BWS) control, and incremental exercise testing (IET) based on guidance force (GF) control were implemented during RATE. Analyses focussed on step change, step response kinetics, and peak performance parameters of oxygen uptake. Three subjects with severe motor impairment 16-23 days post-stroke were included. CLT yielded reasonable step change values in oxygen uptake, whereas response kinetics of oxygen uptake showed low goodness of fit. Peak performance parameters were not obtained during IET. Exercise testing in post-stroke individuals with severe motor impairments using a BWS control strategy for CLT is deemed feasible and safe. Our approach yielded reasonable results regarding cardiovascular performance parameters. IET based on GF control does not provoke peak cardiovascular performance due to uncoordinated walking patterns. GF control needs further development to optimally demand active participation during RATE. The findings warrant further research regarding the evaluation of exercise capacity after severe stroke.

  16. Severe Spastic Trismus without Generalized Spasticity after Unilateral Brain Stem Stroke

    PubMed Central

    Seo, Jong-Hyun; Kang, Si Hyun; Seo, Kyung-Mook; Seok, Ju Won

    2012-01-01

    A 62-year-old female patient diagnosed with left brain stem stroke 2 months ago was admitted to our clinic for rehabilitation. She had no generalized spasticity on both extremities, but could open her mouth only approximately 2 mm between her upper and lower teeth due to severe trismus. On needle electromyography, the left masseter muscle showed paradoxically increased muscle activity during mouth opening. We injected 50 units of type A botulinum toxin (Botox®) into the left masseter muscle, and 20 units into the left temporalis muscle with guidance of ultrasonography. The interincisal distance increased to 8 mm on the 3rd day after injection, and 9 mm on the 4th day. One month later, the interincisal distance increased to 14 mm. The increased interincisal distance was maintained for 13 months after injection, and the quality of hygienic care and compliance of oral stimulation therapy also improved. PMID:22506250

  17. Neuroprotective effect of a cell-free extract derived from human adipose stem cells in experimental stroke models.

    PubMed

    Jeon, Daejong; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Ban, Jae-Jun; Park, Dong-Kyu; Yoon, Hye-Jin; Jung, Seungmoon; Yang, Hyunwoo; Kim, Byung Sun; Choi, Ji Ye; Kim, So Hee; Kim, Jeong-Min; Won, Chong-Hyun; Kim, Manho; Lee, Sang Kun; Roh, Jae-Kyu

    2013-06-01

    A recent study suggested that a cell-free extract of human adipose stem cells (hASCs-E) has beneficial effects on neurological diseases by modulating the host environment. Here, we investigated the effects of hASCs-E in several experimental models of stroke in vitro (oxygen and glucose deprivation, OGD) and in vivo (transient or permanent focal cerebral ischemia and intracerebral hemorrhage, ICH). Ischemia was induced in vitro in Neuro2A cells, and the hASCs-E was applied 24h before the OGD or concurrently. Focal cerebral ischemia was induced by unilateral intraluminal thread occlusion of the middle cerebral artery (MCA) in rats for 90min or permanently, or by unilateral MCA microsurgical direct electrocoagulation in mice. The ICH model was induced with an intracerebral injection of collagenase in rats. The hASCs-E was intraperitoneally administered 1h after the stroke insults. Treatment of the hASCs-E led to a substantially high viability in the lactate dehydrogenase and WST-1 assays in the in vitro ischemic model. The cerebral ischemic and ICH model treated with hASCs-E showed decreased ischemic volume and reduced brain water content and hemorrhage volume. The ICH model treated with hASCs-E exhibited better performance on the modified limb placing test. The expression of many genes related to inflammation, immune response, and cell-death was changed substantially in the ischemic rats or neuronal cells treated with the hASCs-E. These results reveal a neuroprotective role of hASCs-E in animal models of stroke, and suggest the feasible application of stem cell-based, noninvasive therapy for treating stroke.

  18. Slow Versus Fast Robot-Assisted Locomotor Training After Severe Stroke: A Randomized Controlled Trial.

    PubMed

    Rodrigues, Thais Amanda; Goroso, Daniel Gustavo; Westgate, Philip M; Carrico, Cheryl; Batistella, Linamara R; Sawaki, Lumy

    2017-10-01

    Robot-assisted locomotor training on a bodyweight-supported treadmill is a rehabilitation intervention that compels repetitive practice of gait movements. Standard treadmill speed may elicit rhythmic movements generated primarily by spinal circuits. Slower-than-standard treadmill speed may elicit discrete movements, which are more complex than rhythmic movements and involve cortical areas. Compare effects of fast (i.e., rhythmic) versus slow (i.e., discrete) robot-assisted locomotor training on a bodyweight-supported treadmill in subjects with chronic, severe gait deficit after stroke. Subjects (N = 18) were randomized to receive 30 sessions (5 d/wk) of either fast or slow robot-assisted locomotor training on a bodyweight-supported treadmill in an inpatient setting. Functional ambulation category, time up and go, 6-min walk test, 10-m walk test, Berg Balance Scale, and Fugl-Meyer Assessment were administered at baseline and postintervention. The slow group had statistically significant improvement on functional ambulation category (first quartile-third quartile, P = 0.004), 6-min walk test (95% confidence interval [CI] = 1.8 to 49.0, P = 0.040), Berg Balance Scale (95% CI = 7.4 to 14.8, P < 0.0001), time up and go (95% CI = -79.1 to 5.0, P < 0.0030), and Fugl-Meyer Assessment (95% CI = 24.1 to 45.1, P < 0.0001). The fast group had statistically significant improvement on Berg Balance Scale (95% CI = 1.5 to 10.5, P = 0.02). In initial stages of robot-assisted locomotor training on a bodyweight-supported treadmill after severe stroke, slow training targeting discrete movement may yield greater benefit than fast training.

  19. Acute Ischemic Stroke After Moderate to Severe Traumatic Brain Injury: Incidence and Impact on Outcome.

    PubMed

    Kowalski, Robert G; Haarbauer-Krupa, Juliet K; Bell, Jeneita M; Corrigan, John D; Hammond, Flora M; Torbey, Michel T; Hofmann, Melissa C; Dams-O'Connor, Kristen; Miller, A Cate; Whiteneck, Gale G

    2017-07-01

    Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, -16.8 to -9.7; P<0.001), a 1.9-point increase in Disability Rating Scale (95% confidence interval, 1.3-2.5; P<0.001), and an 18.3-day increase in posttraumatic amnesia duration (95% confidence interval, 13.1-23.4; P<0.001). Ischemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events. © 2017 American Heart Association, Inc.

  20. Neuroprotective Properties and Mechanisms of Resveratrol in in Vitro and in Vivo Experimental Cerebral Stroke Models

    PubMed Central

    2013-01-01

    Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and seeds and red wine, is known for its purported antioxidant activity in the vascular and nervous systems. In contrast to its direct antioxidant role within the central nervous system, recent research supports a protective mechanism through increasing endogenous cellular antioxidant defenses, which triggers a cascade of parallel neuroprotective pathways. A growing body of in vitro and in vivo evidence indicates that resveratrol acts through multiple pathways and reduces ischemic damage in vital organs, such as the heart and the brain, in various rodent models. Most of the protective biological actions of resveratrol have been associated with its antioxidative, anti-inflammatory, and antiapoptotic properties and other indirect pathways. Continued public interest and increasing resveratrol supplements on the market warrant a review of the available in vitro and in vivo science reported in the stroke-related literature. Rigorous clinical trials evaluating the effects of resveratrol in stroke are absent, though the general population consumption appears to be relatively safe. Resveratrol has shown potential for treating stroke in laboratory animals and in vitro human cell studies, yet there is still a need for human research in preclinical settings. This review summarizes many of the findings on the neuroprotective potential of resveratrol in cerebral stroke, focusing on both the in vitro and in vivo experimental models and some proposed mechanisms of action. PMID:23758534

  1. Early sitting, standing, and walking in conjunction with contemporary Bobath approach for stroke patients with severe motor deficit.

    PubMed

    Tang, Qingping; Tan, Lihong; Li, Baojun; Huang, Xiaosong; Ouyang, Chunhong; Zhan, Hailan; Pu, Qinqin; Wu, Lixiang

    2014-01-01

    The commonly used therapeutic approach, the contemporary Bobath approach (CBA), is not sufficient to restore independent locomotion for individuals with severe motor deficit (SMD) after stroke. Therefore, we propose that the early sitting, standing, and walking in conjunction with the CBA (ECBA) be used to treat individuals with SMD after stroke. To investigate whether ECBA may enhance mobility and balance in subjects with SMD after stroke. Thirty-three men and 15 women, aged 60 to 74 years, with SMD after stroke were recruited for the study. CBA or ECBA was performed with the subjects 5 times per week in 50-minute sessions for 8 weeks. The Stroke Rehabilitation Assessment of Movement (STREAM) and the Berg Balance Scale were implemented before treatment and at 4 and 8 weeks after treatment, respectively. The STREAM scores indicated that ECBA was more efficient than the CBA intervention for lower extremity mobility, F(1, 46) = 24.0, P < .001, and basic mobility, F(1, 46) = 102.6, P < .001. Overall STREAM scores were higher in the ECBA group, F(1, 46) =24.1, P < .001, after 8 weeks of therapy. Balance scores of the ECBA subjects were higher than those of the CBA subjects after 8 weeks of therapy, F(1, 46) = 73.1, P < .001. However, there was no difference in upper extremity mobility between the 2 groups. ECBA is a valuable intervention to improve lower extremity mobility, basic mobility, and balance ability for individuals with SMD after stroke.

  2. Neuroinflammatory response to experimental stroke is inhibited by boldine.

    PubMed

    de Lima, Neila Maria R; Ferreira, Emerson de O; Fernandes, Mara Yone S D; Lima, Francisco Arnaldo V; Neves, Kelly Rose T; do Carmo, Marta Regina S; de Andrade, Geanne M

    2017-04-01

    Inflammation plays a pivotal role in the development of ischemic brain damage. Astrocyte activation promotes the production of several proinflammatory mediators, such as TNF-α and iNOS. Eventually, neuronal death occurs, leading to the development of motor and memory deficits in patients. Boldine is the main alkaloid in the leaves and bark of the Peumus boldus Molina, and has anti-inflammatory and antioxidant properties. The aim of this work was to investigate the neuroprotective effect of boldine on neuroinflammation and memory deficits induced by permanent middle cerebral artery occlusion (pMCAO) in mice. Thirty minutes before pMCAO and during the next 5 days, animals received vehicle (0.025 µmol/l HCl) or boldine (8, 16 and 25 mg/kg, intraperitoneally). The extension of the infarct area, neurological scores, and myeloperoxidase activity were evaluated 24 h after pMCAO. Locomotor activity, working, and aversive memory were evaluated 72 h after pMCAO, object recognition memory was tested 96 h after pMCAO, and spatial memory was tested 120 h after pMCAO. Cresyl violet, Fluoro-Jade C staining, and immunohistochemical for GFAP, TNF-α, and iNOS were also carried out. The treatment with boldine significantly decreased the infarct area, improved the neurological scores, and increased cell viability. The vertical exploratory activity and aversive, spatial, object recognition, and working memory deficits induced by pMCAO were prevented by boldine. Moreover, myeloperoxidase activity and GFAP, TNF-α, and iNOS immunoreactivity were decreased significantly by boldine. Although various mechanisms such as its antioxidant activity should be considered, these results suggest that the neuroprotective effect of boldine might be related in part to its anti-inflammatory properties.

  3. Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke.

    PubMed

    Hurtado, Olivia; Hernández-Jiménez, Macarena; Zarruk, Juan G; Cuartero, María I; Ballesteros, Iván; Camarero, Guadalupe; Moraga, Ana; Pradillo, Jesús M; Moro, María A; Lizasoain, Ignacio

    2013-09-01

    CDP-choline has shown neuroprotective effects in cerebral ischemia. In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA. Several mechanisms have been proposed to explain the beneficial actions of CDP-choline. We have now studied the participation of Sirtuin1 (SIRT1) in the neuroprotective actions of CDP-choline. Fischer rats and Sirt1⁻/⁻ mice were subjected to permanent focal ischemia. CDP-choline (0.2 or 2 g/kg), sirtinol (a SIRT1 inhibitor; 10 mg/kg), and resveratrol (a SIRT1 activator; 2.5 mg/kg) were administered intraperitoneally. Brains were removed 24 and 48 h after ischemia for western blot analysis and infarct volume determination. Treatment with CDP-choline increased SIRT1 protein levels in brain concomitantly to neuroprotection. Treatment with sirtinol blocked the reduction in infarct volume caused by CDP-choline, whereas resveratrol elicited a strong synergistic neuroprotective effect with CDP-choline. CDP-choline failed to reduce infarct volume in Sirt1⁻/⁻ mice. Our present results demonstrate a robust effect of CDP-choline like SIRT1 activator by up-regulating its expression. Our findings suggest that therapeutic strategies to activate SIRT1 may be useful in the treatment of stroke. Sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions. Regarding stroke, there is no direct evidence. We have demonstrated that citicoline increases SIRT1 protein levels in brain concomitantly to neuroprotection. Citicoline fails to reduce infarct volume in Sirt1⁻/⁻ mice. Our findings suggest that therapeutic strategies acting on SIRT1 may be useful in the treatment of stroke.

  4. Following experimental stroke, the recovering brain is vulnerable to lipoxygenase-dependent semaphorin signaling

    PubMed Central

    Pekcec, Anton; Yigitkanli, Kazim; Jung, Joo Eun; Pallast, Stefanie; Xing, Changhong; Antipenko, Alexander; Minchenko, Maria; Nikolov, Dimitar B.; Holman, Theodore R.; Lo, Eng H.; van Leyen, Klaus

    2013-01-01

    Recovery from stroke is limited, in part, by an inhibitory environment in the postischemic brain, but factors preventing successful remodeling are not well known. Using cultured cortical neurons from mice, brain endothelial cells, and a mouse model of ischemic stroke, we show that signaling from the axon guidance molecule Sema3A via eicosanoid second messengers can contribute to this inhibitory environment. Either 90 nM recombinant Sema3A, or the 12/15-lipoxygenase (12/15-LOX) metabolites 12-HETE and 12-HPETE at 300 nM, block axon extension in neurons compared to solvent controls, and decrease tube formation in endothelial cells. The Sema3A effect is reversed by inhibiting 12/15-LOX, and neurons derived from 12/15-LOX-knockout mice are insensitive to Sema3A. Following middle cerebral artery occlusion to induce stroke in mice, immunohistochemistry shows both Sema3A and 12/15-LOX are increased in the cortex up to 2 wk. To determine whether a Sema3A-dependent damage pathway is activated following ischemia, we injected recombinant Sema3A into the striatum. Sema3A alone did not cause injury in normal brains. But when injected into postischemic brains, Sema3A increased cortical damage by 79%, and again, this effect was reversed by 12/15-LOX inhibition. Our findings suggest that blocking the semaphorin pathway should be investigated as a therapeutic strategy to improve stroke recovery.—Pekcec, A., Yigitkanli, K., Jung, J. E., Pallast, S., Xing, C., Antipenko, A., Minchenko, M., Nikolov, D. B., Holman, T. R., Lo, E. H.,van Leyen, K. Following experimental stroke, the recovering brain is vulnerable to lipoxygenase-dependent semaphorin signaling. PMID:23070608

  5. Significance of marrow-derived nicotinamide adenine dinucleotide phosphate oxidase in experimental ischemic stroke.

    PubMed

    Tang, Xian N; Zheng, Zhen; Giffard, Rona G; Yenari, Midori A

    2011-10-01

    Reperfusion after stroke leads to infiltration of inflammatory cells into the ischemic brain. Nicotinamide adenine dinucleotide phosphate oxidase (NOX2) is a major enzyme system that generates superoxide in immune cells. We studied the effect of NOX2 derived from the immune cells in the brain and in blood cells in experimental stroke. To establish whether NOX2 plays a role in brain ischemia, strokes were created in mice, then mice were treated with the NOX2 inhibitor apocynin or vehicle and compared to mice deficient in NOX2's gp91 subunit and their wild-type littermates. To determine whether NOX2 in circulating cells versus brain resident cells contribute to ischemic injury, bone marrow chimeras were generated by transplanting bone marrow from wild-type or NOX2-deficient mice into NOX2 or wild-type hosts, respectively. Apocynin and NOX2 deletion both significantly reduced infarct size, blood-brain barrier disruption, and hemorrhagic transformation of the infarcts, compared to untreated wild-type controls. This was associated with decreased matrix metalloproteinase 9 expression and reduced loss of tight junction proteins. NOX2-deficient mice receiving wild-type marrow had better outcomes compared to the wild-type mice receiving wild-type marrow. Interestingly, wild-type mice receiving NOX2-deficient marrow had even smaller infarct sizes and less hemorrhage than NOX2-deficient mice receiving wild-type marrow. This indicates that NOX2, whether present in circulating cells or brain resident cells, contributes to ischemic brain injury and hemorrhage. However, NOX2 from the circulating cells contributed more to the exacerbation of stroke than that from brain resident cells. These data suggest the importance of targeting the peripheral immune system for treatment of stroke. Copyright © 2011 American Neurological Association.

  6. Point-of-care cardiac troponin test accurately predicts heat stroke severity in rats.

    PubMed

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

    2015-11-15

    Heat stroke (HS) remains a significant public health concern. Despite the substantial threat posed by HS, there is still no field or clinical test of HS severity. We suggested previously that circulating cardiac troponin (cTnI) could serve as a robust biomarker of HS severity after heating. In the present study, we hypothesized that (cTnI) point-of-care test (ctPOC) could be used to predict severity and organ damage at the onset of HS. Conscious male Fischer 344 rats (n = 16) continuously monitored for heart rate (HR), blood pressure (BP), and core temperature (Tc) (radiotelemetry) were heated to maximum Tc (Tc,Max) of 41.9 ± 0.1°C and recovered undisturbed for 24 h at an ambient temperature of 20°C. Blood samples were taken at Tc,Max and 24 h after heat via submandibular bleed and analyzed on ctPOC test. POC cTnI band intensity was ranked using a simple four-point scale via two blinded observers and compared with cTnI levels measured by a clinical blood analyzer. Blood was also analyzed for biomarkers of systemic organ damage. HS severity, as previously defined using HR, BP, and recovery Tc profile during heat exposure, correlated strongly with cTnI (R(2) = 0.69) at Tc,Max. POC cTnI band intensity ranking accurately predicted cTnI levels (R(2) = 0.64) and HS severity (R(2) = 0.83). Five markers of systemic organ damage also correlated with ctPOC score (albumin, alanine aminotransferase, blood urea nitrogen, cholesterol, and total bilirubin; R(2) > 0.4). This suggests that cTnI POC tests can accurately determine HS severity and could serve as simple, portable, cost-effective HS field tests.

  7. Percutaneous Recanalization of Acute Internal Carotid Artery Occlusions in Patients with Severe Stroke

    SciTech Connect

    Dabitz, Rainer; Triebe, Stefan; Leppmeier, Ullrich; Ochs, Guenther; Vorwerk, Dierk

    2007-02-15

    Background. Sudden symptomatic occlusions of the proximal internal carotid artery (ICA) resulting in severe middle cerebral artery (MCA) ischemia and stroke are usually not accessible by rt-PA thrombolysis and the prognosis is usually very poor. Mechanical recanalization of the proximal ICA combined with intravenous and intra-arterial thrombolysis was therefore used as a rescue procedure. Methods. Ten patients (9 men, 1 woman; mean age 56.1 years) were treated with emergency recanalization of the proximal carotid artery by using stents and/or balloon angioplasty as a rescue procedure. Three patients showed dissection, and 7 had atherothrombotic occlusions. Nine of 10 presented with an initial modified Rankin Scale (mRS) of 5, the remaining patient with mRS 4 (average NIHSS 21.4). After sonographic confirmation of ICA with associated MCA/distal ICA occlusion and bridging with rt-PA (without abciximab) an emergency angiography was performed with subsequent mechanical recanalization by percutaneous transluminal angioplasty (PTA) (n = 1) or primary stenting (n = 9) using self-expanding stents. Distal protection was used in 1 of 10 patients. Results. Recanalization of the proximal ICA was achieved in all. At least partial recanalization of the intracerebral arteries was achieved in all, and complete recanalization in 5. In 4 of 10 patients limited hemorrhage was detected during CT controls. Major complications included 2 patients who had to undergo hemicraniectomy. One patient died from malignant infarction. At the time of discharge from the stroke unit 9 of 10 patients had improved markedly, 5 patients having an mRS of {<=}2, and 3 patients a mRS of 3. At control after a mean of 20 weeks, 7 of 8 (88%) patients had a mRS {<=}2, and 1 a mRS of 3. Conclusions. Primary mechanical recanalization of ICA occlusions by stent and PTA combined with fibrinolysis and/or GPIIb/IIIa-receptor antagonists seems to be feasible to improve patient outcome significantly.

  8. Cortical activation during robotic therapy for a severely affected arm in a chronic stroke patient: a case report.

    PubMed

    Saeki, Satoru; Matsushima, Yasuyuki; Hachisuka, Kenji

    2008-06-01

    The use of robotic-aided therapy in a patient with residual damage from a previous stroke was an attempt to improve function in a moderate to severe hemiparetic arm. Cortical activities associated with motor recovery are not well documented and require investigation. A chronic stroke patient with a severely affected arm underwent a robotic-training program for 12 weeks. The robotic-aided therapy improved motor control and spasticity in the proximal upper-limb. An increased oxygenated hemoglobin level was observed at the motor-related area in the affected hemisphere. A 12-week robotic-aided training program used in a chronic stroke patient demonstrated elements of motor recovery, and was also associated with direct activation of the affected hemisphere.

  9. 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

  10. Genetic variation in retinal vascular patterning predicts variation in pial collateral extent and stroke severity

    PubMed Central

    Prabhakar, Pranay; Zhang, Hua; Chen, De; Faber, James E.

    2015-01-01

    The presence of a native collateral circulation in tissues lessens injury in occlusive vascular diseases. However, differences in genetic background cause wide variation in collateral number and diameter in mice, resulting in large variation in protection. Indirect estimates of collateral perfusion suggest wide variation also exists in humans. Unfortunately, methods used to obtain these estimates are invasive and not widely available. We sought to determine if differences in genetic background in mice result in variation in branch-patterning of the retinal arterial circulation, and if these differences predict strain-dependent differences in pial collateral extent and severity of ischemic stroke. Retinal patterning metrics, collateral extent, and infarct volume were obtained for 10 strains known to differ widely in collateral extent. Multivariate regression was conducted and model performance assessed using K-fold cross-validation. Twenty-one metrics varied with strain (p<0.01). Ten metrics (eg, bifurcation angle, lacunarity, optimality) predicted collateral number and diameter across 7 regression models, with the best model closely predicting (p<0.0001) number (± 1.2-3.4 collaterals, K-fold R2=0.83-0.98), diameter (± 1.2-1.9μm, R2=0.73-0.88) and infarct volume (± 5.1 mm3, R2=0.85-0.87). These metrics obtained for the middle cerebral artery tree in a subset of the above strains also predicted (p<0.0001) collateral number and diameter and diameter, although with less strength (K-fold R2=0.61-0.78) and 0.60-0.86, respectively). Thus, differences in arterial branch-patterning in the retina and the MCA trees are specified by genetic background and predict variation in collateral extent and stroke severity. If also true in human retina, and since genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar “retinal predictor index” could serve as a non-or minimally invasive biomarker for collateral extent in brain and other

  11. Plasticity of premotor cortico-muscular coherence in severely impaired stroke patients with hand paralysis.

    PubMed

    Belardinelli, Paolo; Laer, Leonard; Ortiz, Erick; Braun, Christoph; Gharabaghi, Alireza

    2017-01-01

    Motor recovery in severely impaired stroke patients is often very limited. To refine therapeutic interventions for regaining motor control in this patient group, the functionally relevant mechanisms of neuronal plasticity need to be detected. Cortico-muscular coherence (CMC) may provide physiological and topographic insights to achieve this goal. Synchronizing limb movements to motor-related brain activation is hypothesized to reestablish cortico-motor control indexed by CMC. In the present study, right-handed, chronic stroke patients with right-hemispheric lesions and left hand paralysis participated in a four-week training for their left upper extremity. A brain-robot interface turned event-related beta-band desynchronization of the lesioned sensorimotor cortex during kinesthetic motor-imagery into the opening of the paralyzed hand by a robotic orthosis. Simultaneous MEG/EMG recordings and individual models from MRIs were used for CMC detection and source reconstruction of cortico-muscular connectivity to the affected finger extensors before and after the training program. The upper extremity-FMA of the patients improved significantly from 16.23 ± 6.79 to 19.52 ± 7.91 (p = 0.0015). All patients showed significantly increased CMC in the beta frequency-band, with a distributed, bi-hemispheric pattern and considerable inter-individual variability. The location of CMC changes was not correlated to the severity of the motor impairment, the motor improvement or the lesion volume. Group analysis of the cortical overlap revealed a common feature in all patients following the intervention: a significantly increased level of ipsilesional premotor CMC that extended from the superior to the middle and inferior frontal gyrus, along with a confined area of increased CMC in the contralesional premotor cortex. In conclusion, functionally relevant modulations of CMC can be detected in patients with long-term, severe motor deficits after a brain-robot assisted

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

    PubMed Central

    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

  13. [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.

  14. Severe Cerebral Vasospasm and Childhood Arterial Ischemic Stroke After Intrathecal Cytarabine.

    PubMed

    Tibussek, Daniel; Natesirinilkul, Rungrote; Sun, Lisa R; Wasserman, Bruce A; Brandão, Leonardo R; deVeber, Gabrielle

    2016-02-01

    We report on 2 patients who developed widespread cerebral vasospasm and arterial ischemic strokes (AIS) after application of intrathecal (IT) cytarabine. In a 3-year-old child with acute lymphoblastic leukemia (ALL), left leg weakness, hyperreflexia, and clonus were noted 4 days after her first dose of IT cytarabine during the induction phase of her chemotherapy. Cerebral MRI revealed multiple acute cerebral ischemic infarcts and widespread cerebral vasospasm. A 5-year-old girl complained of right arm and leg pain and began limping 11 days after IT cytarabine. Symptoms progressed to right dense hemiplegia, left gaze deviation, headache, and speech arrest. MRI revealed 2 large cortical areas of diffusion restriction in the right frontal and left parietal lobes. Cerebral magnetic resonance angiography (MRA) showed irregular narrowing affecting much of the intracranial arterial circulation. Although the first child fully recovered from her neurologic symptoms, the second patient had persistent hemiplegia on follow-up. Including this report, there are now 4 pediatric ALL cases of severe cerebral vasospasm and AIS in the context of IT cytarabine administration, strongly suggesting a true association. Differential diagnosis and management issues are discussed. Along with the more widespread use of MRI and MRA, the true frequency of this severe adverse effect will become clearer in future. For any child with neurologic symptoms within hours or days of receiving IT cytarabine, a low threshold for cerebral imaging with MRI and MRA is recommended.

  15. [Effects of different intakes of protein on nutritional status in severe stroke patients].

    PubMed

    Zhang, Li; Li, Zebin; Luo, Bin; Li, Zengning; Lei Min; Jing, Yongmin

    2014-11-01

    To investigate the effects of different intake of protein on nutritional indicators in severe stroke patients. 89 patients with severe stroke and NRS-2002 scores not less than 3 were enrolled. The patients were divided into group A, group B and group C by random, and 28 cases were in group A with protein intake at 0.9 g/kg, 30 cases were in group B with protein intake at 1.2 g/kg and 31 cases were in group C with protein intake at 1.6 g/kg, all patients were given the same calories support (25 kcal/kg). On the day of pre-intervention, the 7th and 14th day of post-intervention, fasting blood samples were collected from every subjects. The total protein (TP), albumin (ALB), hemoglobin (Hb), creatinine (Cr), blood urea nitrogen (BUN), midarm circumference (MAC) and calf circumference (CC) were recorded. (1) The MAC and CC of health side body decreased on the 14th day post-intervention in group A and group B, the differences were significant compared with pre-intervention and on the 7th day post-intervention (P < 0.05), but there were no statistical differences between group A and group B. The index of group C had no significant changes from pre-intervention to the 14th day post-intervention. The differences among the three groups were statistically significant on the 14th day post-intervention (P < 0.05). (2) TP, ALB and Hb in group A were decreased from pre-intervention to the 14th day post-intervention, the differences were statistically significant. The levels of TP and Hb decreased in group B during the observation period, the differences were statistically significant. ALB in group B was decreased on the 7th day post-intervention, but it was increased on the 14th day post-intervention, there was no statistical difference compared with pre-intervention. The levels of TP, ALB and Hb in group C had no significant differences on the 7th day post-intervention, but they all increased on the 14th day post-intervention. The differences of ALB and Hb in group C were

  16. 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

  17. Oxygen uptake response to cycle ergometry in post-acute stroke patients with different severity of hemiparesis.

    PubMed

    Chen, Chun-Kai; Weng, Ming-Cheng; Chen, Tien-Wen; Huang, Mao-Hsiung

    2013-11-01

    This study evaluated the impact of severity of hemiparesis on oxygen uptake (VO2) response in post-acute stroke patients. Sixty-four patients with a mean poststroke interval of 8.6 ± 3.8 days underwent a ramp cardiopulmonary exercise test on a cycling ergometer to volitional termination. Mean peak VO2 (VO2peak) and work efficiency (ΔVO2/ΔWR) were measured by open-circuit spirometry during standard upright ergometer cycling. Severity of the hemiparetic lower limb was assessed by Brunnstrom's motor recovery stages lower extremity (BMRSL). VO2peak was 10% lower in hemiparetic leg with BMRSL V than in that with BMRSL VI, 20% lower in BMRSL IV, and 50% lower in BMRSL III. ΔVO2/ΔWR was higher for the group with increased BMRSL. The relations were consistent after adjustment for age, sex, body mass index, stroke type, hemiparetic side, modified Ashworth Scale, time poststroke, comorbidities, and medications. Our findings revealed that O2peak is dependent on the severity of hemiparesis in leg, and along with ΔO2/ΔWR closely related to the severity of hemiparesis in post-acute stroke patients, regardless of the types and locations of lesion after stroke, as well as the differences in comorbidities and medications. Copyright © 2013. Published by Elsevier B.V.

  18. Synergy effects of combined multichannel EMG-triggered electrical stimulation and mirror therapy in subacute stroke patients with severe or very severe arm/hand paresis.

    PubMed

    Schick, Thomas; Schlake, Hans-Peter; Kallusky, Juliane; Hohlfeld, Günter; Steinmetz, Maria; Tripp, Florian; Krakow, Karsten; Pinter, Michaela; Dohle, Christian

    2017-01-01

    Neurorehabilitation requires the development of severity-dependent and successful therapies for arm/hand rehabilitation in stroke patients. To evaluate the effectiveness of adding mirror therapy to bilateral EMG-triggered multi-channel electrostimulation for the treatment of severe arm/hand paresis in stroke patients. The subjects of this randomized, controlled, multicentre study were stroke patients who had suffered their first insult between 1 and 6 months before study start and had severe or very severe arm/hand paresis, as classified by Fugl-Meyer-Assessment. Subjects were randomly allocated to an intervention group (n = 16) or control group (n = 17). Both groups were treated for 3 weeks (5x week, 30 minutes) with bilateral EMG-triggered multi-channel electrostimulation. The intervention group additionally received mirror feedback of the unaffected limb. The primary outcome measure was motor recovery of the upper extremities, as measured by the Fugl-Meyer Assessment. The Intervention Group with very severe paresis had significantly better motor recovery in total Fugl-Meyer Assessment (p = 0.017) at a medium effect size (Cohen) of d = 0.7, due to a significant recovery of shoulder and elbow function (p = 0.003) in the Fugl-Meyer Assessment Part A subtest. For subjects with severe paresis, additional mirror therapy did not significantly influence outcome. Additional mirror therapy in combination with EMG-triggered multi-channel electrostimulation is therapeutically beneficial for post-acute stroke patients with very severe arm/hand paresis.

  19. Enriched housing enhances recovery of limb placement ability and reduces aggrecan-containing perineuronal nets in the rat somatosensory cortex after experimental stroke.

    PubMed

    Madinier, Alexandre; Quattromani, Miriana Jlenia; Sjölund, Carin; Ruscher, Karsten; Wieloch, Tadeusz

    2014-01-01

    Stroke causes life long disabilities where few therapeutic options are available. Using electrical and magnetic stimulation of the brain and physical rehabilitation, recovery of brain function can be enhanced even late after stroke. Animal models support this notion, and housing rodents in an enriched environment (EE) several days after experimental stroke stimulates lost brain function by multisensory mechanisms. We studied the dynamics of functional recovery of rats with a lesion to the fore and hind limb motor areas induced by photothrombosis (PT), and with subsequent housing in either standard (STD) or EE. In this model, skilled motor function is not significantly enhanced by enriched housing, while the speed of recovery of sensori-motor function substantially improves over the 9-week study period. In particular, this stroke lesion completely obliterates the fore and hind limb placing ability when visual and whisker guidance is prevented, a deficit that persists for up to 9 weeks of recovery, but that is markedly restored within 2 weeks by enriched housing. Enriched housing after stroke also leads to a significant loss of perineuronal net (PNN) immunoreactivity; detection of aggrecan protein backbone with AB1031 antibody was decreased by 13-22%, and labelling of a glycan moiety of aggrecan with Cat-315 antibody was reduced by 25-30% in the peri-infarct area and in the somatosensory cortex, respectively. The majority of these cells are parvalbumin/GABA inhibitory interneurons that are important in sensori-information processing. We conclude that damage to the fore and hind limb motor areas provides a model of loss of limb placing response without visual guidance, a deficit also seen in more than 50% of stroke patients. This loss is amenable to recovery induced by multiple sensory stimulation and correlates with a decrease in aggrecan-containing PNNs around inhibitory interneurons. Modulating the PNN structure after ischemic damage may provide new therapies

  20. Multiparametric magnetic resonance imaging including oxygenation mapping of experimental ischaemic stroke.

    PubMed

    Boisserand, Ligia Simões Braga; Lemasson, Benjamin; Hirschler, Lydiane; Moisan, Anaïck; Hubert, Violaine; Barbier, Emmanuel L; Rémy, Chantal; Detante, Olivier

    2017-06-01

    Recent advances in MRI methodology, such as microvascular and brain oxygenation (StO2) imaging, may prove useful in obtaining information about the severity of the acute stroke. We assessed the potential of StO2 to detect the ischaemic core in the acute phase compared to apparent diffusion coefficient and to predict the final necrosis. Sprague-Dawley rats (n = 38) were imaged during acute stroke (D0) and 21 days after (D21). A multiparametric MRI protocol was performed at 4.7T to characterize brain damage within three region of interest: 'LesionD0' (diffusion), 'Mismatch' representing penumbra (perfusion/diffusion) and 'Hypoxia' (voxels < 40% of StO2 within the region of interest LesionD0). Voxel-based analysis of stroke revealed heterogeneity of the region of interest LesionD0, which included voxels with different degrees of oxygenation decrease. This finding was supported by a dramatic decrease of vascular and perfusion parameters within the region of interest hypoxia. This zone presented the lowest values of almost all parameters analysed, indicating a higher severity. Our study demonstrates the potential of StO2 magnetic resonance imaging to more accurately detect the ischaemic core without the inclusion of any reversible ischaemic damage. Our follow-up study indicates that apparent diffusion coefficient imaging overestimated the final necrosis while StO2 imaging did not.

  1. Experimental analysis of precursors to severe problem behavior.

    PubMed

    Fritz, Jennifer N; Iwata, Brian A; Hammond, Jennifer L; Bloom, Sarah E

    2013-01-01

    Some individuals engage in both mild and severe forms of problem behavior. Research has shown that when mild behaviors precede severe behaviors (i.e., the mild behaviors serve as precursors), they can (a) be maintained by the same source of reinforcement as severe behavior and (b) reduce rates of severe behavior observed during assessment. In Study 1, we developed an objective checklist to identify precursors via videotaped trials for 16 subjects who engaged in problem behavior and identified at least 1 precursor for every subject. In Study 2, we conducted separate functional analyses of precursor and severe problem behaviors for 8 subjects, and obtained correspondence between outcomes in 7 cases. In Study 3, we evaluated noncontingent reinforcement schedule thinning plus differential reinforcement of alternative behavior to reduce precursors, increase appropriate behavior, and maintain low rates of severe behavior during 3 treatment analyses for 2 subjects. Results showed that this treatment strategy was effective for behaviors maintained by positive and negative reinforcement. © Society for the Experimental Analysis of Behavior.

  2. White Matter Repair After Extracellular Vesicles Administration in an Experimental Animal Model of Subcortical Stroke

    PubMed Central

    Otero-Ortega, Laura; Laso-García, Fernando; Gómez-de Frutos, María del Carmen; Rodríguez-Frutos, Berta; Pascual-Guerra, Jorge; Fuentes, Blanca; Díez-Tejedor, Exuperio; Gutiérrez-Fernández, María

    2017-01-01

    Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50–100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers. We found that a single administration of EVs improved functional recovery, fiber tract integrity, axonal sprouting and white matter repair markers in an experimental animal model of subcortical stroke. EVs were found in the animals’ brain and peripheral organs after euthanasia. White matter integrity was in part restored by EVs administration mediated by molecular repair factors implicated in axonal sprouting, tract connectivity, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery. This novel role for EVs presents a new perspective in the development of biologics for brain repair. PMID:28300134

  3. 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.

  4. Changes in Quadriceps Muscle Thickness, Disease Severity, Nutritional Status, and C-Reactive Protein after Acute Stroke.

    PubMed

    Nozoe, Masafumi; Kanai, Masashi; Kubo, Hiroki; Kitamura, Yuka; Yamamoto, Miho; Furuichi, Asami; Takashima, Sachie; Mase, Kyoshi; Shimada, Shinichi

    2016-10-01

    Lower leg muscle wasting is common in stroke patients; however, patient characteristics in the acute phase are rarely studied. This study aimed to examine the relationship between changes in quadriceps muscle thickness and disease severity, nutritional status, and C-reactive protein (CRP) levels after acute stroke. Thirty-one consecutive patients with acute intracerebral hemorrhage or ischemic stroke had quadriceps muscle thickness measured in the paretic and nonparetic limbs within 1 week after admission (first week) and 2 weeks after the first examination (last week) using ultrasonography. We also determined the relationship between the percentage change in muscle thickness and disease severity, nutritional status, and CRP levels on admission. There was a significant correlation between changes in muscle thickness for both paretic and nonparetic sides and National Institutes of Health Stroke Scale (NIHSS) scores (paretic limb: r = -.46, P = .01; nonparetic limb: r = -.54, P = .002, respectively); however, there was no significant correlation with nutritional status on admission. Quadriceps muscle thickness was reduced more in the CRP-positive (≥.3 mg/dL) patients than in the CRP-negative (<.3 mg/dL) patients in the nonparetic limb (positive: -21.4 ± 12.1, negative: -11.4 ± 16.4%; P = .039), but not in the paretic limb (positive: -23.4 ± 9.0, negative: -19.1 ± 15.7; P = .27). A high NIHSS score and a positive CRP on admission were both significantly correlated with decreased quadriceps muscle thickness after acute stroke. Nutritional status on admission was not correlated with changes in quadriceps muscle thickness for these patients. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. 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.

  6. Osmolality of enteral formula and severity of experimental necrotizing enterocolitis.

    PubMed

    Miyake, Hiromu; Chen, Yong; Koike, Yuhki; Hock, Alison; Li, Bo; Lee, Carol; Zani, Augusto; Pierro, Agostino

    2016-12-01

    Administration of hyperosmolar formula is regarded as a risk factor for the development of necrotizing enterocolitis (NEC). However, there are limited number of reports about the relationship between formula osmolality and NEC. The aim of this study is to evaluate the effects of formula concentration in an experimental model of NEC. We studied experimental NEC in C57BL/6 mice. NEC was induced by giving hypoxia, gavage administration of lipopolysaccharide and gavage formula feeding from postnatal day 5-9. We used two types of formula: (1) hyperosmolar formula (HF): 15 g Similac + 75 ml Esbilac (849 mOsm/kg); (2) diluted formula (DF): dilute hyperosmolar formula with an equal amount of water (325 mOsm/kg). Controls were fed by the mother. On postnatal day 9, the ileum was harvested and evaluated for severity of mucosal injury (hematoxylin/eosin staining) and inflammation (PCR for IL6 and TNFα mRNA expression). The incidence of NEC was same in both HF and DF (80%). The intestinal inflammatory response was similar between HF and DF (IL6: p = 0.26, TNFα: p = 0.69). This study indicates the osmolality of enteral formula does not affect incidence of experimental NEC. This experimental study provides new insights into the relationship between formula feeding and NEC.

  7. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Prophylactic antibiotic treatment in severe acute ischemic stroke: the Antimicrobial chemopRrophylaxis for Ischemic STrokE In MaceDonIa-Thrace Study (ARISTEIDIS).

    PubMed

    Tziomalos, Konstantinos; Ntaios, George; Miyakis, Spiros; Papanas, Nikolaos; Xanthis, Andreas; Agapakis, Dimitrios; Milionis, Haralampos; Savopoulos, Christos; Maltezos, Efstratios; Hatzitolios, Apostolos I

    2016-10-01

    Infections represent a leading cause of mortality in patients with acute ischemic stroke, but it is unclear whether prophylactic antibiotic treatment improves the outcome. We aimed to evaluate the effects of this treatment on infection incidence and short-term mortality. This was a pragmatic, prospective multicenter real-world analysis of previously independent consecutive patients with acute ischemic stroke who were >18 years, and who had at admission National Institutes of Health Stroke Scale (NIHSS) >11. Patients with infection at admission or during the preceding month, with axillary temperature at admission >37 °C, with chronic inflammatory diseases or under treatment with corticosteroids were excluded from the study. Among 110 patients (44.5 % males, 80.2 ± 6.8 years), 31 (28.2 %) received prophylactic antibiotic treatment, mostly cefuroxime (n = 21). Prophylactic antibiotic treatment was administered to 51.4 % of patients who developed infection, and to 16.4 % of patients who did not (p < 0.001). Independent predictors of infection were NIHSS at admission [relative risk (RR) 1.16, 95 % confidence interval (CI) 1.08-1.26, p < 0.001] and prophylactic antibiotic treatment (RR 5.84, 95 % CI 2.03-16.79, p < 0.001). The proportion of patients who received prophylactic antibiotic treatment did not differ between patients who died during hospitalization and those discharged, or between patients who died during hospitalization or during follow-up and those who were alive 3 months after discharge. Prophylactic administration of antibiotics in patients with severe acute ischemic stroke is associated with an increased risk of infection during hospitalization, and does not affect short-term mortality risk.

  9. Role of corpus callosum integrity in arm function differs based on motor severity after stroke.

    PubMed

    Stewart, Jill Campbell; Dewanjee, Pritha; Tran, George; Quinlan, Erin Burke; Dodakian, Lucy; McKenzie, Alison; See, Jill; Cramer, Steven C

    2017-01-01

    While the corpus callosum (CC) is important to normal sensorimotor function, its role in motor function after stroke is less well understood. This study examined the relationship between structural integrity of the motor and sensory sections of the CC, as reflected by fractional anisotropy (FA), and motor function in individuals with a range of motor impairment level due to stroke. Fifty-five individuals with chronic stroke (Fugl-Meyer motor score range 14 to 61) and 18 healthy controls underwent diffusion tensor imaging and a set of motor behavior tests. Mean FA from the motor and sensory regions of the CC and from corticospinal tract (CST) were extracted and relationships with behavioral measures evaluated. Across all participants, FA in both CC regions was significantly decreased after stroke (p < 0.001) and showed a significant, positive correlation with level of motor function. However, these relationships varied based on degree of motor impairment: in individuals with relatively less motor impairment (Fugl-Meyer motor score > 39), motor status correlated with FA in the CC but not the CST, while in individuals with relatively greater motor impairment (Fugl-Meyer motor score ≤ 39), motor status correlated with FA in the CST but not the CC. The role interhemispheric motor connections play in motor function after stroke may differ based on level of motor impairment. These findings emphasize the heterogeneity of stroke, and suggest that biomarkers and treatment approaches targeting separate subgroups may be warranted.

  10. [Nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients].

    PubMed

    Hong, Qing; Zhang, Li-San; Chen, Yin; He, Xu-Dong; Hu, Xing-Yue

    2015-01-01

    To investigate the nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients. Fifty patients with ischemic stroke were admitted in hospital within 48 h after onset. National Institute of Health stroke scale (NIHSS) was used to assess the severity of stroke. Physical index and laboratory index were measured on d1, d7 and d14 after admission. Physical index included body weight, body mass index, triceps skin folds, upper arm circumference and arm muscle circumference. Laboratory index included prealbumin, high sensitivity C-reactive protein (hs-CRP), complement C3 and cortisol. The severity of metabolic disturbance was expressed as the difference of biochemical indexes between the d7 and d1. All cases were followed up for 6 months. The prognosis of stroke was evaluated with modified Rankin (mRankin) scores. No significant changes of physical indexes were found between d7 and d1. The levels of prealbumin and complement C3 on d7 after admission were significantly decreased compared to d1 (198.8 mg/L±20.3 mg/L vs 286.7 mg/L±23.8 mg/L and 0.6 g/L±0.1 g/L vs 1.0 g/L±0.1 g/L, respectively, both P<0.05). The levels of hs-CRP and cortisol at d7 were significantly increased compared to d1 (495.2 nmol/L±39.5 nmol/L vs 24.1 mg/L±5.2 mg/L and 396.4 nmol/L±41.3 nmol/L vs 5.1 mg/L±1.2 mg/L, respectively, both P<0.05). On d14 after admission hs-CRP (13.2 mg/L±4.5 mg/L) and cortisol levels (463.4 nmol/L±32.1 nmol/L) were still significantly higher than d1 (both P<0.05). However, there were no difference in prealbumin (259.2 mg/L±22.8 mg/L) and complement C3 (0.8 g/L±0.2 g/L) levels between d1 and d14 after admission. Correlation analysis revealed that the NIHSS scores and mRankin scores were correlated with nutrition metabolism disturbances (P<0.05). Nutrition metabolism disturbances in patients with acute ischemic stroke are related to the disease duration, the severity and prognosis of stroke.

  11. 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.

  12. Early prediction of functional outcome using dynamic contrast enhanced magnetic resonance imaging in experimental stroke.

    PubMed

    Huang, Wei-Yuan; Wu, Gang; Li, Jian-Jun; Geng, Dao-Ying; Tan, Wen-Li; Yu, Xiang-Rong

    2016-09-01

    Early prediction of functional outcome in cerebral ischemia stroke using MRI remains a challenge. The aim of this study was to evaluate the predictive value of dynamic contrast-enhanced (DCE) MRI in terms of functional outcome of ischemia stroke. Right middle cerebral artery occlusion (MCAO) was performed in male SD rats (n=50), followed by withdrawal of the occluding filament after 3 (n = 10), 4 (n = 10), 5 (n = 10), 6 (n = 10) or 7 (n = 10) h to establish ischemia and reperfusion stroke. DCE and conventional MRI were performed in each animal 60 ± 15 min before and after reperfusion. The outcome was assessed by the modified Neurological Severity Scores (mNSS) (before reperfusion and at 72 h after reperfusion) and the infarct volume. Comparisons of functional prognosis and DCE parameters (K(trans), Ve and Kep) were performed using binary logistic regression and operating characteristic (ROC) analysis. DCE parameters results indicated that blood brain barrier (BBB) permeability increased with prolonged reperfusion timing. Using binary logistic regression analysis on stroke characteristics (reperfusion timing, infarct volume) and BBB permeability parameters (drK(trans)subcortex, drK(trans)cortex, drVesubcortex, drVecortex, drKepsubcortex and drKepcortex) as covariates , the results demonstrated that reperfusion timing, infarct volume, drK(trans)subcortex and drKepsubcortex were independent factors that were associated with prognosis (OR=0.01, OR=0.23, OR=245.23, OR=1.29). ROC analysis indicated that a drK(trans)subcortex threshold of 0.88 with a sensitivity of 95.7% and a specificity of 85.2% and a drKepsubcortex threshold of -0.25 with a sensitivity of 69.6% and a specificity of 70.4% for differentiation between favourable and unfavourable prognosis. Quantitative DCE-MRI can be used to predict the functional outcomes of cerebral ischemia injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Field Validation of the Los Angeles Motor Scale as a Tool for Paramedic Assessment of Stroke Severity.

    PubMed

    Kim, Joon-Tae; Chung, Pil-Wook; Starkman, Sidney; Sanossian, Nerses; Stratton, Samuel J; Eckstein, Marc; Pratt, Frank D; Conwit, Robin; Liebeskind, David S; Sharma, Latisha; Restrepo, Lucas; Tenser, May-Kim; Valdes-Sueiras, Miguel; Gornbein, Jeffrey; Hamilton, Scott; Saver, Jeffrey L

    2017-02-01

    The Los Angeles Motor Scale (LAMS) is a 3-item, 0- to 10-point motor stroke-deficit scale developed for prehospital use. We assessed the convergent, divergent, and predictive validity of the LAMS when performed by paramedics in the field at multiple sites in a large and diverse geographic region. We analyzed early assessment and outcome data prospectively gathered in the FAST-MAG trial (Field Administration of Stroke Therapy-Magnesium phase 3) among patients with acute cerebrovascular disease (cerebral ischemia and intracranial hemorrhage) within 2 hours of onset, transported by 315 ambulances to 60 receiving hospitals. Among 1632 acute cerebrovascular disease patients (age 70±13 years, male 57.5%), time from onset to prehospital LAMS was median 30 minutes (interquartile range 20-50), onset to early postarrival (EPA) LAMS was 145 minutes (interquartile range 119-180), and onset to EPA National Institutes of Health Stroke Scale was 150 minutes (interquartile range 120-180). Between the prehospital and EPA assessments, LAMS scores were stable in 40.5%, improved in 37.6%, and worsened in 21.9%. In tests of convergent validity, against the EPA National Institutes of Health Stroke Scale, correlations were r=0.49 for the prehospital LAMS and r=0.89 for the EPA LAMS. Prehospital LAMS scores did diverge from the prehospital Glasgow Coma Scale, r=-0.22. Predictive accuracy (adjusted C statistics) for nondisabled 3-month outcome was as follows: prehospital LAMS, 0.76 (95% confidence interval 0.74-0.78); EPA LAMS, 0.85 (95% confidence interval 0.83-0.87); and EPA National Institutes of Health Stroke Scale, 0.87 (95% confidence interval 0.85-0.88). In this multicenter, prospective, prehospital study, the LAMS showed good to excellent convergent, divergent, and predictive validity, further establishing it as a validated instrument to characterize stroke severity in the field. © 2017 American Heart Association, Inc.

  14. Differences in initial stroke severity between Mexican Americans and non-Hispanic whites vary by age: the Brain Attack Surveillance in Corpus Christi (BASIC) project

    PubMed Central

    Wing, Jeffrey J.; Baek, Jonggyu; Sánchez, Brisa N.; Lisabeth, Lynda D.; Smith, Melinda A.; Morgenstern, Lewis B.; Zahuranec, Darin B.

    2014-01-01

    Background A wide variety of racial and ethnic disparities in stroke epidemiology and treatment have been reported. Race-ethnic differences in initial stroke severity may be one important determinant of differences in outcome after stroke. The overall goal of this study was to move beyond ethnic comparisons in the mean or median severity, and instead investigate ethnic differences in the entire distribution of initial stroke severity. Additionally, we investigated whether age modifies the relationship between ethnicity and initial stroke severity as this may be an important determinant of racial differences in outcome after stroke. Methods Ischemic stroke cases were identified from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project. National Institutes of Health Stroke Scale (NIHSS) was determined from the medical record or abstracted from the chart. Ethnicity was reported as Mexican American (MA) or non-Hispanic white (NHW). Quantile regression was used to model the distribution of NIHSS score by age category (45–59, 60–74, 75+) to test whether ethnic differences exist over different quantiles of NIHSS (5 percentile increments). Crude models examined the interaction between age category and ethnicity; models were then adjusted for history of stroke/transient ischemic attack, hypertension, atrial fibrillation, coronary artery disease, and diabetes. Results were adjusted for multiple comparisons. Results There were 4,366 ischemic strokes, with median age 72 years (IQR: 61–81), 55% MA and median NIHSS of 4 (IQR: 2–8). MAs were younger, more likely to have a history of hypertension and diabetes, but less likely to have atrial fibrillation compared to NHWs. In the crude model, the ethnicity-age interaction was not statistically significant. After adjustment, the ethnicity-age interaction became significant at the 85th and 95th percentiles of NIHSS distribution. MAs in the younger age category (45–59) were significantly less

  15. Long-term behavioral assessment of function in an experimental model for ischemic stroke.

    PubMed

    Encarnacion, Angelo; Horie, Nobutaka; Keren-Gill, Hadar; Bliss, Tonya M; Steinberg, Gary K; Shamloo, Mehrdad

    2011-03-30

    Middle cerebral artery occlusion (MCAO) in rats is a well-studied experimental model for ischemic stroke leading to brain infarction and functional deficits. Many preclinical studies have focused on a small time window after the ischemic episode to evaluate functional outcome for screening therapeutic candidates. Short evaluation periods following injury have led to significant setbacks due to lack of information on the delayed effects of treatments, as well as short-lived and reversible neuroprotection, so called false-positive results. In this report, we evaluated long-term functional deficit for 90 days after MCAO in two rat strains with two durations of ischemic insult, in order to identify the best experimental paradigm to assess injury and subsequent recovery. Behavioral outcomes were measured pre-MCAO followed by weekly assessment post-stroke. Behavioral tests included the 18-point composite neurological score, 28-point neuroscore, rearing test, vibrissae-evoked forelimb placing test, foot fault test and the CatWalk. Brain lesions were assessed to correlate injury to behavior outcomes at the end of study. Our results indicate that infarction volume in Sprague-Dawley rats was dependent on occlusion duration. In contrast, the infarction volume in Wistar rats did not correlate with the duration of ischemic episode. Functional outcomes were not dependent on occlusion time in either strain; however, measurable deficits were detectable long-term in limb asymmetry, 18- and 28-point neuroscores, forelimb placing, paw swing speed, and gait coordination. In conclusion, these behavioral assays, in combination with an extended long-term assessment period, can be used for evaluating therapeutic candidates in preclinical models of ischemic stroke. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. The efficacy of SMART Arm training early after stroke for stroke survivors with severe upper limb disability: a protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Recovery of upper limb function after stroke is poor. The acute to subacute phase after stroke is the optimal time window to promote the recovery of upper limb function. The dose and content of training provided conventionally during this phase is however, unlikely to be adequate to drive functional recovery, especially in the presence of severe motor disability. The current study concerns an approach to address this shortcoming, through evaluation of the SMART Arm, a non-robotic device that enables intensive and repetitive practice of reaching by stroke survivors with severe upper limb disability, with the aim of improving upper limb function. The outcomes of SMART Arm training with or without outcome-triggered electrical stimulation (OT-stim) to augment movement and usual therapy will be compared to usual therapy alone. Methods/Design A prospective, assessor-blinded parallel, three-group randomised controlled trial is being conducted. Seventy-five participants with a first-ever unilateral stroke less than 4 months previously, who present with severe arm disability (three or fewer out of a possible six points on the Motor Assessment Scale [MAS] Item 6), will be recruited from inpatient rehabilitation facilities. Participants will be randomly allocated to one of three dose-matched groups: SMART Arm training with OT-stim and usual therapy; SMART Arm training without OT-stim and usual therapy; or usual therapy alone. All participants will receive 20 hours of upper limb training over four weeks. Blinded assessors will conduct four assessments: pre intervention (0-weeks), post intervention (4-weeks), 26 weeks and 52 weeks follow-up. The primary outcome measure is MAS item 6. All analyses will be based on an intention-to-treat principle. Discussion By enabling intensive and repetitive practice of a functional upper limb task during inpatient rehabilitation, SMART Arm training with or without OT-stim in combination with usual therapy, has the potential to

  17. The efficacy of SMART Arm training early after stroke for stroke survivors with severe upper limb disability: a protocol for a randomised controlled trial.

    PubMed

    Brauer, Sandra G; Hayward, Kathryn S; Carson, Richard G; Cresswell, Andrew G; Barker, Ruth N

    2013-07-02

    Recovery of upper limb function after stroke is poor. The acute to subacute phase after stroke is the optimal time window to promote the recovery of upper limb function. The dose and content of training provided conventionally during this phase is however, unlikely to be adequate to drive functional recovery, especially in the presence of severe motor disability. The current study concerns an approach to address this shortcoming, through evaluation of the SMART Arm, a non-robotic device that enables intensive and repetitive practice of reaching by stroke survivors with severe upper limb disability, with the aim of improving upper limb function. The outcomes of SMART Arm training with or without outcome-triggered electrical stimulation (OT-stim) to augment movement and usual therapy will be compared to usual therapy alone. A prospective, assessor-blinded parallel, three-group randomised controlled trial is being conducted. Seventy-five participants with a first-ever unilateral stroke less than 4 months previously, who present with severe arm disability (three or fewer out of a possible six points on the Motor Assessment Scale [MAS] Item 6), will be recruited from inpatient rehabilitation facilities. Participants will be randomly allocated to one of three dose-matched groups: SMART Arm training with OT-stim and usual therapy; SMART Arm training without OT-stim and usual therapy; or usual therapy alone. All participants will receive 20 hours of upper limb training over four weeks. Blinded assessors will conduct four assessments: pre intervention (0-weeks), post intervention (4-weeks), 26 weeks and 52 weeks follow-up. The primary outcome measure is MAS item 6. All analyses will be based on an intention-to-treat principle. By enabling intensive and repetitive practice of a functional upper limb task during inpatient rehabilitation, SMART Arm training with or without OT-stim in combination with usual therapy, has the potential to improve recovery of upper limb function

  18. Initial Body Temperature in Ischemic Stroke: Non-Potentiation of TPA Benefit and Inverse Association with Severity

    PubMed Central

    Kim, Seo Hyun; Saver, Jeffrey L.

    2014-01-01

    Background and Purpose Body temperature (BT) is an important physiologic factor in acute ischemic stroke. However, the relation of initial BT to stroke severity and degree of benefit from thrombolytic therapy has been incompletely delineated. Methods We analyzed the public data set of the two National Institute of Neurological Disorders and Stroke tissue plaminogen activator (TPA) stroke trials, comparing patients with lower (<37.0°C) and higher (≥37.0°C) presenting BT. Results Among 595 patients (297 placebo- and 298 tPA-treated) with documented initial BT, 77.1% had initial BT <37.0°C and 22.9% ≥37.0°C. Patients with higher initial BT had lower baseline stroke severity in both tPA-treated patients (the National Institute of Health Stroke Scale median, 11 versus 15; p = 0.05) and placebo-treated patients (median, 13 versus 16; p <0.01). Patients with higher initial BT also had lower infarction volume on CT at 3 months in both tPA-treated patients (median, 9.6 versus 16.7 cm3; p = 0.08) and placebo-treated patients (median, 13.1 versus 28.1 cm3; p = 0.02), but no clinical outcome differences. Analysis of lytic treatment effect found no heterogeneity in the degree of tPA benefit in both higher and lower BT groups (≥37.0°C: odds ratio [OR] for the modified Rankin Scale 0-1 outcome 2.55, 95% confidence interval [CI] 1.05-6.21; <37.0°C: OR 2.30, 95% CI 1.38-3.84; heterogeneity p = 0.83). Conclusions In hyperacute stroke patients, higher presenting temperatures are associated with less severe neurological deficits and reduced final infarct volumes. Presenting temperature does not modify the benefit of tPA on 3-month favorable outcome. Clinical Trial Registration This trial was not registered because enrollment began prior to July 1, 2005. PMID:25424482

  19. Validating Imaging Biomarkers of Cerebral Edema in Patients with Severe Ischemic Stroke

    PubMed Central

    Yoo, Albert J.; Sheth, Kevin N.; Kimberly, W. Taylor; Chaudhry, Zeshan A.; Elm, Jordan J.; Jacobson, Sven; Davis, Stephen M.; Donnan, Geoffrey A.; Albers, Gregory W.; Stern, Barney J.; González, R. Gilberto

    2012-01-01

    Background and Purpose There is no validated neuroimaging marker for quantifying brain edema. We sought to test whether MRI-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints. Methods Serial MRI studies from patients in the EPITHET trial with initial diffusion weighted imaging (DWI) lesion volume >82 cm3 were analyzed. Two independent readers outlined the hemisphere and lateral ventricle on the involved side and calculated respective volumes at baseline and day 3 to 5. We assessed inter-rater agreement, volume change between scans and the association of volume change with early neurological deterioration (END: NIHSS score worsening ≥4 points), 90-day modified Rankin Scale (mRS) score 0–4 and mortality. Results Of 12 patients who met study criteria, average baseline and follow-up DWI lesion size was 138 cm3 and 234 cm3, respectively. Mean time to follow-up MRI was 62 hours. Concordance correlation coefficients between readers were >0.90 for both hemisphere and ventricle volume assessment. Mean percent hemisphere volume increase was 16.2±8.3% (p<.0001), and mean percent ventricle volume decrease was 45.6±16.9% (p<0.001). Percent hemisphere growth predicted END (area under the curve [AUC]=0.92, p=0.0005) and 90-day mRS 0–4 (AUC 0.80, p=0.02). Conclusions In this exploratory analysis of severe ischemic stroke patients, statistically significant changes in hemisphere and ventricular volumes within the first week are consistent with expected changes of cerebral edema. MRI-based analysis of hemisphere growth appears to be a suitable biomarker for edema formation. PMID:22325573

  20. 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

  1. Progress in the experimental therapy of severe arenaviral infections.

    PubMed

    Gowen, Brian B; Bray, Mike

    2011-12-01

    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 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 hemorrhagic fever, but it is not an approved treatment for either disease. Human immune convalescent plasma was proven to be effective for Argentine hemorrhagic fever 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.

  2. 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

  3. Preventing increased blood pressure in the obese Zucker rat improves severity of stroke

    PubMed Central

    Osmond, Jessica M.; Mintz, James D.

    2010-01-01

    Obesity is a risk factor for stroke, but the determinants of increased stroke risk in obesity are unknown. We have previously reported that obese Zucker rats (OZRs) have a worse stroke outcome and display evidence of remodeling of the middle cerebral artery (MCA), in parallel with hypertension, compared with lean controls. This study tested the hypothesis that hypertension is an essential determinant of cerebral vascular remodeling and increased stroke damage in OZRs. Blood pressure was measured by telemetery in lean and obese rats with and without hydrochlorthiazide (HCT; 2 mg·kg−1·day−1) from 8 to 15 wk of age. A separate group of rats was also chronically fed a low-sodium (LS) diet. Vessel structure was assessed in isolated, pressurized MCAs. Cerebral ischemia was induced for 60 min using an intralumenal suture technique, followed by 24 h of reperfusion. HCT treatment effectively prevented the increase in blood pressure in obese rats; however, the LS diet did not lower pressure. Importantly, infarct size was normalized by HCT after ischemia-reperfusion injury. Additionally, HCT improved the changes in MCA structure observed in untreated OZRs. There were no benefits of the LS diet on stroke injury or vessel structure. These results indicate that increased pressure is essential for driving the changes in infarct size in OZRs. PMID:20418477

  4. 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

  5. Relationship between plasma metalloproteinase-9 levels and volume and severity of infarct in patients with acute ischemic stroke.

    PubMed

    Demir, Recep; Ulvi, Hızır; Özel, Lütfi; Özdemir, Gökhan; Güzelcik, Metin; Aygül, Recep

    2012-12-01

    Matrix metalloproteinases (MMP) constitute an endopeptidase family involved in various physiological and pathological processes. It was demonstrated that plasma MMP-9 level was increased in patients with acute ischemic stroke. In this study, it was investigated whether there was a relationship between the levels of plasma MMP-9 and the severity of stroke and infarct volume in patients with acute ischemic stroke. A total of 32 patients with acute ischemic stroke, (16 males and 16 females) and 30 healthy controls were included in the study. Plasma MMP-9 levels were measured using ELISA method. Computed tomography was performed at 48th hour and infarct volume was calculated using the Cavalieri method. The National Institute of Health Stroke Scale (NIHSS) was checked at baseline, 12, 24, and 48th hour. Plasma MMP-9 levels of the patient group at baseline, 12, 24, and 48th hour were found significantly higher compared to the control group (p < 0.05). An important correlation between MMP-9 levels and the infarct volume was observed at baseline, 12, 24, and 48th hour (p < 0.001). Furthermore, a positive correlation was recorded between plasma MMP-9 levels and NIHSS scores at baseline, 12, 24, and 48th hour (p < 0.001). Plasma MMP-9 levels of those of suffering medium and heavy damages were found significantly higher when compared to those of having slight damage (p < 0.05). A significant relationship was also observed between infarct volumes and neurological deficits (p < 0.05). Plasma MMP-9 levels of the patients at 48th hour were found to be significantly lower in recovered patients compared to those who did not improved or worsened (p < 0.05). A positive correlation was recorded between the infarct volume and infarct progression (p < 0.05). In conclusion, this study showed that plasma MMP-9 level substantially increased during the acute period of ischemic cerebrovascular disease and correlated with the severity of the disease and infarct volume. The

  6. Effectiveness of finger-equipped electrode (FEE)-triggered electrical stimulation improving chronic stroke patients with severe hemiplegia

    PubMed Central

    Inobe, Jun-ichi; Kato, Takashi

    2013-01-01

    Background: Electric stimulation (ES) has been recognized as an effective method to improve motor function to paralysed patients with stroke. It is important for ES to synchronize with voluntary movement. To enhance this co-ordination, the finger-equipped electrode (FEE) was developed. The purpose of this study was to evaluate FEE in improving motor function of upper extremities (UEs) in patients with chronic stroke. Methods and subjects: The study participants included four patients with chronic stroke who received FEE electronic stimulation (FEE-ES) plus passive and active training and three control patients who underwent training without FEE-ES. The patients were treated five times weekly for 4 weeks. UE motor function was evaluated before and after treatment using Fugl-Meyer Assessment (FMA) and Brunnstrom recovery staging. Results: The mean age of patients in each group was 60-years and there was a mean of 49 months since the onset of symptoms. All patients had severe UE weakness. The patients receiving FEE-ES had greater improvement in UE function than control patients (total, proximal and distal FMA, p < 0.05; Brunnstrom staging of UE, p < 0.05). Discussion: The results indicate that FEE-ES may be an effective treatment for patients with chronic stroke. PMID:23252442

  7. Effectiveness of finger-equipped electrode (FEE)-triggered electrical stimulation improving chronic stroke patients with severe hemiplegia.

    PubMed

    Inobe, Jun-ichi; Kato, Takashi

    2013-01-01

    Electric stimulation (ES) has been recognized as an effective method to improve motor function to paralysed patients with stroke. It is important for ES to synchronize with voluntary movement. To enhance this co-ordination, the finger-equipped electrode (FEE) was developed. The purpose of this study was to evaluate FEE in improving motor function of upper extremities (UEs) in patients with chronic stroke. The study participants included four patients with chronic stroke who received FEE electronic stimulation (FEE-ES) plus passive and active training and three control patients who underwent training without FEE-ES. The patients were treated five times weekly for 4 weeks. UE motor function was evaluated before and after treatment using Fugl-Meyer Assessment (FMA) and Brunnstrom recovery staging. The mean age of patients in each group was 60-years and there was a mean of 49 months since the onset of symptoms. All patients had severe UE weakness. The patients receiving FEE-ES had greater improvement in UE function than control patients (total, proximal and distal FMA, p < 0.05; Brunnstrom staging of UE, p < 0.05). The results indicate that FEE-ES may be an effective treatment for patients with chronic stroke.

  8. 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. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  9. Use of magnetic resonance imaging to predict outcome after stroke: a review of experimental and clinical evidence.

    PubMed

    Farr, Tracy D; Wegener, Susanne

    2010-04-01

    Despite promising results in preclinical stroke research, translation of experimental data into clinical therapy has been difficult. One reason is the heterogeneity of the disease with outcomes ranging from complete recovery to continued decline. A successful treatment in one situation may be ineffective, or even harmful, in another. To overcome this, treatment must be tailored according to the individual based on identification of the risk of damage and estimation of potential recovery. Neuroimaging, particularly magnetic resonance imaging (MRI), could be the tool for a rapid comprehensive assessment in acute stroke with the potential to guide treatment decisions for a better clinical outcome. This review describes current MRI techniques used to characterize stroke in a preclinical research setting, as well as in the clinic. Furthermore, we will discuss current developments and the future potential of neuroimaging for stroke outcome prediction.

  10. Use of magnetic resonance imaging to predict outcome after stroke: a review of experimental and clinical evidence

    PubMed Central

    Farr, Tracy D; Wegener, Susanne

    2010-01-01

    Despite promising results in preclinical stroke research, translation of experimental data into clinical therapy has been difficult. One reason is the heterogeneity of the disease with outcomes ranging from complete recovery to continued decline. A successful treatment in one situation may be ineffective, or even harmful, in another. To overcome this, treatment must be tailored according to the individual based on identification of the risk of damage and estimation of potential recovery. Neuroimaging, particularly magnetic resonance imaging (MRI), could be the tool for a rapid comprehensive assessment in acute stroke with the potential to guide treatment decisions for a better clinical outcome. This review describes current MRI techniques used to characterize stroke in a preclinical research setting, as well as in the clinic. Furthermore, we will discuss current developments and the future potential of neuroimaging for stroke outcome prediction. PMID:20087362

  11. Life-and-death decision-making in the acute phase after a severe stroke: Interviews with relatives.

    PubMed

    de Boer, Marike E; Depla, Marja; Wojtkowiak, Joanna; Visser, Marieke C; Widdershoven, Guy A M; Francke, Anneke L; Hertogh, Cees M P M

    2015-05-01

    Decision-making in the acute phase after a severe stroke is complex and may involve life-and-death decisions. Apart from the medical condition and prognosis, quality of life and the deliberation of palliative care should be part of the decision-making process. Relatives play an important role by informing physicians about the patient's values and preferences. However, little is known about how the patients' relatives experience the decision-making process. To elicit the perspective of relatives of severe stroke patients with regard to the decision-making process in the acute phase in order to understand how they participate in treatment decisions. An exploratory qualitative interview approach guided by the principles of grounded theory. Relatives of severe stroke patients (n = 15) were interviewed about their experiences in the decision-making process in the acute phase. Four categories reflecting relatives' experiences were identified: (1) making decisions under time pressure, (2) the feeling of 'who am I' to decide, (3) reluctance in saying 'let her die' and (4) coping with unexpected changes. Following the treatment proposal of the physician was found to be the prevailing tendency of relatives in the decision-making process. A better understanding of the latent world of experiences of relatives that influence the decision-making process may help physicians and other health-care providers to better involve relatives in decision-making and enhance the care, including palliative care, for patients with severe stroke in line with their values and preferences. Communication between physician and relatives seems vital in this process. © The Author(s) 2015.

  12. Human Urinary Kallidinogenase Promotes Angiogenesis and Cerebral Perfusion in Experimental Stroke.

    PubMed

    Han, Lijuan; Li, Jie; Chen, Yanting; Zhang, Meijuan; Qian, Lai; Chen, Yan; Wu, Zhengzheng; Xu, Yun; Li, Jingwei

    2015-01-01

    Angiogenesisis a key restorative mechanism in response to ischemia, and pro-angiogenic therapy could be beneficial in stroke. Accumulating experimental and clinical evidence suggest that human urinary kallidinogenase (HUK) improves stroke outcome, but the underlying mechanisms are not clear. The aim of current study was to verify roles of HUK in post-ischemic angiogenesis and identify relevant mediators. In rat middle cerebral artery occlusion (MCAO) model, we confirmed that HUK treatment could improve stroke outcome, indicated by reduced infarct size and improved neurological function. Notably, the 18F-FDG micro-PET scan indicated that HUK enhanced cerebral perfusion in rats after MCAO treatment. In addition, HUK promotespost-ischemic angiogenesis, with increased vessel density as well as up-regulated VEGF andapelin/APJ expression in HUK-treated MCAO mice. In endothelial cell cultures, induction of VEGF and apelin/APJ expression, and ERK1/2 phosphorylation by HUK was further confirmed. These changes were abrogated by U0126, a selective ERK1/2 inhibitor. Moreover, F13A, a competitive antagonist of APJ receptor, significantly suppressed HUK-induced VEGF expression. Furthermore, angiogenic functions of HUK were inhibited in the presence of selective bradykinin B1 or B2 receptor antagonist both in vitro and in vivo. Our findings indicate that HUK treatment promotes post-ischemic angiogenesis and cerebral perfusion via activation of bradykinin B1 and B2 receptors, which is potentially due to enhancement expression of VEGF and apelin/APJ in ERK1/2 dependent way.

  13. Human Urinary Kallidinogenase Promotes Angiogenesis and Cerebral Perfusion in Experimental Stroke

    PubMed Central

    Chen, Yanting; Zhang, Meijuan; Qian, Lai; Chen, Yan; Wu, Zhengzheng; Xu, Yun; Li, Jingwei

    2015-01-01

    Angiogenesisis a key restorative mechanism in response to ischemia, and pro-angiogenic therapy could be beneficial in stroke. Accumulating experimental and clinical evidence suggest that human urinary kallidinogenase (HUK) improves stroke outcome, but the underlying mechanisms are not clear. The aim of current study was to verify roles of HUK in post-ischemic angiogenesis and identify relevant mediators. In rat middle cerebral artery occlusion (MCAO) model, we confirmed that HUK treatment could improve stroke outcome, indicated by reduced infarct size and improved neurological function. Notably, the 18F-FDG micro-PET scan indicated that HUK enhanced cerebral perfusion in rats after MCAO treatment. In addition, HUK promotespost-ischemic angiogenesis, with increased vessel density as well as up-regulated VEGF andapelin/APJ expression in HUK-treated MCAO mice. In endothelial cell cultures, induction of VEGF and apelin/APJ expression, and ERK1/2 phosphorylation by HUK was further confirmed. These changes were abrogated by U0126, a selective ERK1/2 inhibitor. Moreover, F13A, a competitive antagonist of APJ receptor, significantly suppressed HUK-induced VEGF expression. Furthermore, angiogenic functions of HUK were inhibited in the presence of selective bradykinin B1 or B2 receptor antagonist both in vitro and in vivo. Our findings indicate that HUK treatment promotes post-ischemic angiogenesis and cerebral perfusion via activation of bradykinin B1 and B2 receptors, which is potentially due to enhancement expression of VEGF and apelin/APJ in ERK1/2 dependent way. PMID:26222055

  14. Effect of Transcranial Direct Current Stimulation on Severely Affected Arm-Hand Motor Function in Patients After an Acute Ischemic Stroke: A Pilot Randomized Control Trial.

    PubMed

    Rabadi, Meheroz H; Aston, Christopher E

    2017-10-01

    The aim of this article was to determine whether cathodal transcranial direct current stimulation (c-tDCS) to unaffected primary motor cortex (PMC) plus conventional occupational therapy (OT) improves functional motor recovery of the affected arm hand in patients after an acute ischemic stroke compared with sham transcranial direct current stimulation plus conventional OT. In this prospective, randomized, double-blinded, sham-controlled trial of 16 severe, acute ischemic stroke patients with severe arm-hand weakness were randomly assigned to either experimental (c-tDCS plus OT; n = 8) or control (sham transcranial direct current stimulation plus OT; n = 8) groups. All patients received a standard 3-hr in-patient rehabilitation therapy, plus an additional ten 30-min sessions of tDCS. During each session, 1 mA of cathodal stimulation to the unaffected PMC is performed followed by the patient's scheduled OT. The primary outcome measure was change in Action Research Arm Test (ARAT) total and subscores on discharge. Application of c-tDCS to unaffected PMC resulted in a clinically relevant 10-point improvement in the affected arm-hand function based on ARAT total score compared with a 2-point improvement in the control group. Application of 30-min of c-tDCS to the unaffected PMC showed a 10-point improvement in the ARAT score. This corresponds to a large effect size in improvement of affected arm-hand function in patients with severe, acute ischemic stroke. Although not statistically significant, this suggests that larger studies, enrolling at least 25 patients in each group, and with a longer follow-up are warranted.

  15. Changes at the focus of experimental ischemic stroke treated with neuroprotective agents.

    PubMed

    Onishchenko, L S; Gaikova, O N; Yanishevskii, S N

    2008-01-01

    The aim of the present work was to compare the morphological changes occurring at the focus of experimental ischemic stroke treated with agents of the neurotrophic group (alpha-GPC, cerebrolysin), an agent with nootropic properties (piracetam), and a mixed-action agent (vinpocetine). Experiments were performed on 18 rats. Transient cerebral circulatory lesions (acute ischemia) were produced in the right hemisphere by clipping the stem of the innominate artery for 40 min. Light microscopic and electron microscopic studies were performed on fragments of cerebral cortex, brainstem, and cerebellum. Use of alpha-GPC and cerebrolysin increased the tolerance of neurons to ischemic damage and slowed the execution of the cell death program. Intracellular changes were seen and were interpreted as adaptive and reparative: these included folding of the nuclear membrane, abundance of polyribosomes, and endoplasmic reticulum and Golgi complex hypertrophy. These agents preserved the structures of the nuclear membranes and major cellular organelles. When piracetam and vinpocetine were used, all morphological measures indicated inadequate energy provision for repair processes in the acute stage of ischemic stroke. Morphological signs of functional tension of cerebral cortex neurons were seen, with gliocytes in different stages of apoptosis, along with the phenomenon of incomplete separation of gliocytes during proliferation, pathological changes to myelin and non-myelinated fibers, and abnormalities in synapse structure.

  16. 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.

  17. [The effect of nitrates on the outcome of acute experimental ischemic stroke].

    PubMed

    Kuzenkov, V S; Krushinskiĭ, A L; Reutov, V P

    2012-01-01

    Effects of nitrates NaNO(3), KNO(3), Mg(NO(3)) 2 on animals (Wistar rats) were studied on the basis of the experimental model of ischemic stroke induced by the occlusion of two carotid arteries. The animals were divided into two groups: the main group (n=60) and the control group (n=30). Three series of experiments were conducted. In each experiment, the rats of the main group were treated with one of nitrates and the control group was treated with physiological solution. It has been shown that nitrates exert either positive or negative effect depending on the cation type, nitrate concentration and the duration of their action on the dynamics of neurologic disturbances. Conditions of the development of neuroprotective effect of nitrates are discussed.

  18. Lipoprotein(a), ferritin, and albumin in acute phase reaction predicts severity and mortality of acute ischemic stroke in North Indian Patients.

    PubMed

    Chakraborty, Baidarbhi; Vishnoi, Gaurav; Goswami, Binita; Gowda, Srinivas H; Chowdhury, Debashish; Agarwal, Sarita

    2013-10-01

    Inflammation plays a crucial role in the pathogenesis and prognosis of stroke. We studied the behavior of lipoprotein(a) [Lp(a)], ferritin, and albumin as acute phase reactants and their roles in the severity and mortality of stroke. We recruited 100 consecutive patients with acute ischemic stroke and 120 controls. Blood samples were drawn on days 1 and 7 and at both 3 and 6 months. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment classification. Stroke severity was assessed using the National Institutes of Health Stroke Scale. Prognosis at 6 months was assessed using the modified Rankin Scale, and mortality was assessed using the Kaplan-Meier analysis. Serum levels of interleukin-6 (IL-6), Lp(a), ferritin, and albumin were measured using enzyme-linked immunosorbent assay, immunoturbidimetry, and chemiluminescence commercial kits, respectively. Levels of IL-6, Lp(a), and ferritin were consistently higher among cases than controls (P < .0001). Serum Lp(a) levels peaked at day 7 after stroke and tapered thereafter. Albumin levels were lower than controls on admission day and increased subsequently. In our study, Lp(a) acted as an acute phase reactant while albumin acted as a negative acute phase reactant. There was no association between Trial of Org 10172 in Acute Stroke Treatment subtype and elevated serum levels of Lp(a), albumin, and ferritin. Lp(a) and ferritin were high in patients with severe stroke. Albumin was negatively correlated with stroke severity. Serum levels of Lp(a) ≥ 77 mg/dL, albumin ≤ 3.5 g/dL, and ferritin ≥ 370 ng/dL is associated with a significantly increased risk of having a poorer outcome in stroke. Serum levels of Lp(a) >77 mg/dL and albumin <3.5 g/dL were also associated with increased mortality. High levels of Lp(a) and ferritin and low levels of albumin are associated with increased severity and poorer long term prognosis of stroke. Patients with admission levels of Lp(a) >77 mg/dL and albumin <3.5 g/dL had

  19. 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.

  20. Training-induced changes in the pattern of triceps to biceps activation during reaching tasks after chronic and severe stroke.

    PubMed

    Barker, Ruth Nancy; Brauer, Sandra; Carson, Richard

    2009-07-01

    This exploratory study was undertaken to investigate the mechanisms that contributed to improvements in upper limb function following a novel training program. Surface electromyography (EMG) was used to examine training-induced changes in the pattern of triceps and biceps activation during reaching tasks in stroke survivors with severe paresis in the chronic stage of recovery. The EMG data were obtained in the context of a single blind randomised clinical trial conducted with 42 stroke survivors with minimal upper limb muscle activity and who were more than 6 months post-stroke. Of the 33 participants who completed the study, 10 received training of reaching using a non-robotic upper limb training device, the SMART Arm, with EMG triggered functional electrical stimulation (EMG-stim), 13 received training of reaching using the SMART Arm alone, and 10 received no intervention. Each intervention group engaged in 12 1-h training sessions over a 4-week period. Clinical and laboratory measures of upper limb function were administered prior to training (0 weeks), at completion (4 weeks) and 2 months (12 weeks) after training. The primary outcome measure was 'upper arm function' which is Item 6 of the Motor Assessment Scale (MAS). Laboratory measures consisted of two multijoint reaching tasks to assess 'maximum isometric force' and 'maximum distance reached'. Surface EMG was used to monitor triceps brachii and biceps brachii during the two reaching tasks. To provide a comparison with normal values, seven healthy adults were tested on one of the reaching tasks according to the same procedure. Study findings demonstrated a statistically significant improvement in upper limb function for stroke participants in the two training groups compared to those who received no training however no difference was found between the two training groups. For the reaching tasks, all stroke participants, when compared to normal healthy adults, exhibited lower triceps and biceps activation and

  1. Electrically Assisted Movement Therapy in Chronic Stroke Patients With Severe Upper Limb Paresis: A Pilot, Single-Blind, Randomized Crossover Study.

    PubMed

    Carda, Stefano; Biasiucci, Andrea; Maesani, Andrea; Ionta, Silvio; Moncharmont, Julien; Clarke, Stephanie; Murray, Micah M; Millán, José Del R

    2017-08-01

    To evaluate the effects of electrically assisted movement therapy (EAMT) in which patients use functional electrical stimulation, modulated by a custom device controlled through the patient's unaffected hand, to produce or assist task-specific upper limb movements, which enables them to engage in intensive goal-oriented training. Randomized, crossover, assessor-blinded, 5-week trial with follow-up at 18 weeks. Rehabilitation university hospital. Patients with chronic, severe stroke (N=11; mean age, 47.9y) more than 6 months poststroke (mean time since event, 46.3mo). Both EAMT and the control intervention (dose-matched, goal-oriented standard care) consisted of 10 sessions of 90 minutes per day, 5 sessions per week, for 2 weeks. After the first 10 sessions, group allocation was crossed over, and patients received a 1-week therapy break before receiving the new treatment. Fugl-Meyer Motor Assessment for the Upper Extremity, Wolf Motor Function Test, spasticity, and 28-item Motor Activity Log. Forty-four individuals were recruited, of whom 11 were eligible and participated. Five patients received the experimental treatment before standard care, and 6 received standard care before the experimental treatment. EAMT produced higher improvements in the Fugl-Meyer scale than standard care (P<.05). Median improvements were 6.5 Fugl-Meyer points and 1 Fugl-Meyer point after the experimental treatment and standard care, respectively. The improvement was also significant in subjective reports of quality of movement and amount of use of the affected limb during activities of daily living (P<.05). EAMT produces a clinically important impairment reduction in stroke patients with chronic, severe upper limb paresis. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  2. High-dosage granulocyte colony stimulating factor treatment alters monocyte trafficking to the brain after experimental stroke.

    PubMed

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

    2017-02-01

    Ischemic stroke elicits a prompt inflammatory response that is characterized by a well-timed recruitment of peripheral immune cells to the brain. Among these, monocytes play a particularly important, but multifaceted role and have been increasingly recognized to affect stroke outcome. Granulocyte colony stimulating factor (GCSF) is known for its immunosuppressive actions on mononuclear cells, but previous studies in the stroke field were mainly confined to its neuroprotective actions. Herein, we investigated whether GCSF affects post-stroke inflammation in a mouse model of focal brain ischemia by modulating monocyte responses. Treatment with GCSF was controlled by vehicle injection, sham surgery and naive animals. Despite a significant monocytosis, high-dosage GCSF reduced the number of brain-infiltrating monocytes/macrophages four days after stroke. Lower numbers of mononuclear phagocytes in the brain were associated with smaller cerebral edema and improved motor outcome after stroke. GCSF treatment over 72h, but not 24h diminished integrin expression on circulating Ly6C+ inflammatory monocytes. In vitro experiments further revealed that GCSF strongly promotes interleukin (IL)-10 secretion by activated mononuclear cells. Blockade of the IL-10 receptor partly reversed GCSF-induced downregulation of integrin surface expression. Overall, our results suggest that high-dosage GCSF mitigates monocyte infiltration after stroke, likely by attenuating integrin-mediated adhesion to the brain endothelium in an IL-10-dependent manner. Lower amounts of mononuclear cells in the brain translate to less severe brain edema and functional impairment and thus support a harmful role of Ly6C+ inflammatory monocytes in the acute stage of stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 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.

  4. Higher on-admission serum triglycerides predict less severe disability and lower all-cause mortality after acute ischemic stroke.

    PubMed

    Pikija, Slaven; Trkulja, Vladimir; Juvan, Lucija; Ivanec, Marija; Dukši, Dunja

    2013-10-01

    High(er) on-admission triglyceride (TG) levels have been suggested as an independent predictor of better outcomes of the acute ischemic stroke. Data regarding poststroke physical disabilities have been contradictory. We aimed to investigate the relationship between fasting on-admission TG and development of disability and all-cause mortality over a 2.5-year period. This prospective observational study included 83 acute ischemic stroke patients (29 cardioembolic; 41% men; median age 76 years) followed-up for 28 to 30 months and assessed for physical disability using the Modified Rankin scale (mRS) at 1 week and 3, 12, and 24 months poststroke. TGs were considered as a continuous and a binary variable (≤ 1.27 [n = 43] and >1.27 mmol/L [n = 43]). Higher TGs (continuous or binary) were independently (default adjustments: stroke type, severity at presentation, age, atrial fibrillation, preindex event antiplatelet use, infarct volume, postindex event antiplatelet, statin and angiotensin-converting enzyme inhibitor use, on-admission fasting cholesterol, mean platelet volume, and glomerular filtration rate) were associated with: (1) higher odds of mRS 0 to 2 (none/mild disability) across the assessments (overall odds ratio [OR] 2.73 [95% confidence interval {CI} 1.15-6.38] and OR 3.57 [95% CI 1.04-12.3], respectively); (2) lower odds of mRS worsening between any 2 consecutive assessments (overall OR 0.44 [95% CI 0.20-0.96] and OR 0.35 [95% CI 0.16-0.77], respectively); (3) lower risk of all-cause mortality (hazard ratio 0.47 [95% CI 0.23-0.96] and hazard ratio 0.45 [95% CI 0.21-0.98], respectively). These data suggest that higher fasting TGs on-admission predict less severe disability, reduced disability progression, and all-cause mortality in patients with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Combination therapy with normobaric oxygen (NBO) plus thrombolysis in experimental ischemic stroke

    PubMed Central

    Fujiwara, Norio; Murata, Yoshihiro; Arai, Ken; Egi, Yasuhiro; Lu, Jie; Wu, Ona; Singhal, Aneesh B; Lo, Eng H

    2009-01-01

    Background The widespread use of tissue plasminogen activator (tPA), the only FDA-approved acute stroke treatment, remains limited by its narrow therapeutic time window and related risks of brain hemorrhage. Normobaric oxygen therapy (NBO) may be a useful physiological strategy that slows down the process of cerebral infarction, thus potentially allowing for delayed or more effective thrombolysis. In this study we investigated the effects of NBO started simultaneously with intravenous tPA, in spontaneously hypertensive rats subjected to embolic middle cerebral artery (MCA) stroke. After homologous clot injection, animals were randomized into different treatment groups: saline injected at 1 hour; tPA at 1 hour; saline at 1 hour plus NBO; tPA at 1 hour plus NBO. NBO was maintained for 3 hours. Infarct volume, brain swelling and hemorrhagic transformation were quantified at 24 hours. Outcome assessments were blinded to therapy. Results Upon clot injection, cerebral perfusion in the MCA territory dropped below 20% of pre-ischemic baselines. Both tPA-treated groups showed effective thrombolysis (perfusion restored to nearly 100%) and smaller infarct volumes (379 ± 57 mm3 saline controls; 309 ± 58 mm3 NBO; 201 ± 78 mm3 tPA; 138 ± 30 mm3 tPA plus NBO), showing that tPA-induced reperfusion salvages ischemic tissue and that NBO does not significantly alter this neuroprotective effect. NBO had no significant effect on hemorrhagic conversion, brain swelling, or mortality. Conclusion NBO can be safely co-administered with tPA. The efficacy of tPA thrombolysis is not affected and there is no induction of brain hemorrhage or edema. These experimental results require clinical confirmation. PMID:19604385

  6. Chloride Co-transporter NKCC1 Inhibitor Bumetanide Enhances Neurogenesis and Behavioral Recovery in Rats After Experimental Stroke.

    PubMed

    Xu, Wangshu; Mu, Xiaopeng; Wang, Huibin; Song, Chengguang; Ma, Wenping; Jolkkonen, Jukka; Zhao, Chuansheng

    2017-05-01

    Bumetanide, a selective Na(+)-K(+)-Cl(-)-co-transporter inhibitor, is widely used in clinical practice as a loop diuretic. In addition, bumetanide has been reported to attenuate ischemia-induced cerebral edema and reduce neuronal injury. This study examined whether bumetanide could influence neurogenesis and behavioral recovery in rats after experimentally induced stroke. Adult male Wistar rats were randomly assigned to four groups: sham, sham treated with bumetanide, ischemia, and ischemia treated with bumetanide. Focal cerebral ischemia was induced by injection of endothelin-1. Bumetanide (0.2 mg/kg/day) was infused into the lateral ventricle with drug administration being initiated 1 week after ischemia and continued for 3 weeks. Behavioral impairment and recovery were evaluated by tapered/ledged beam-walking test on post-stroke days 28. Then, the rats were perfused for BrdU/DCX (neuroblast marker), BrdU/NeuN (neuronal marker), BrdU/GFAP (astrocyte marker), and BrdU/Iba-1 (microglia marker) immunohistochemistry. The numbers of neuroblasts in the subventricular zone (SVZ) were significantly increased after the experimentally induced stroke. Bumetanide treatment increased migration of neuroblasts in the SVZ towards the infarct area, enhanced long-term survival of newborn neurons, and improved sensorimotor recovery, but it did not exert any effects on inflammation. In conclusion, our results demonstrated that chronic bumetanide treatment enhances neurogenesis and behavioral recovery after experimentally induced stroke in rats.

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

    PubMed

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

    2015-12-09

    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.

  8. 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

  9. Memantine attenuates cell apoptosis by suppressing the calpain-caspase-3 pathway in an experimental model of ischemic stroke.

    PubMed

    Chen, Bin; Wang, Guoxiang; Li, Weiwei; Liu, Weilin; Lin, Ruhui; Tao, Jing; Jiang, Min; Chen, Lidian; Wang, Yun

    2017-02-15

    Ischemic stroke, the second leading cause of death worldwide, leads to excessive glutamate release, over-activation of N-methyl-D-aspartate receptor (NMDAR), and massive influx of calcium (Ca(2+)), which may activate calpain and caspase-3, resulting in cellular damage and death. Memantine is an uncompetitive NMDAR antagonist with low-affinity/fast off-rate. We investigated the potential mechanisms through which memantine protects against ischemic stroke in vitro and in vivo. Middle cerebral artery occlusion-reperfusion (MCAO) was performed to establish an experimental model of ischemic stroke. The neuroprotective effects of memantine on ischemic rats were evaluated by neurological deficit scores and infarct volumes. The activities of calpain and caspase-3, and expression levels of microtubule-associated protein-2 (MAP2) and postsynaptic density-95 (PSD95) were determined by Western blotting. Additionally, Nissl staining and immunostaining were performed to examine brain damage, cell apoptosis, and neuronal loss induced by ischemia. Our results show that memantine could significantly prevent ischemic stroke-induced neurological deficits and brain infarct, and reduce ATP depletion-induced neuronal death. Moreover, memantine markedly suppressed the activation of the calpain-caspase-3 pathway and cell apoptosis, and consequently, attenuated brain damage and neuronal loss in MCAO rats. These results provide a molecular basis for the role of memantine in reducing neuronal apoptosis and preventing neuronal damage, suggesting that memantine may be a promising therapy for stroke patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 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

  11. Frequency of early remodeling of left ventricle and its comparison between patients with stroke volume ≥97 Ml versus patients with stroke volume <97 Ml after aortic valve replacement for severe aortic regurgitation

    PubMed Central

    Ali Rizvi, Hafiz Muhammad Farhan; Khalid, Zaigham Rasool; Baksh, Allah; Raza Baig, Mirza Ahmad

    2016-01-01

    Objectives: To evaluate the frequency of early remodeling in patients of severe aortic regurgitation after aortic valve replacement and to see the incidence of early remodeling in patients with stroke volume >97 ml versus < 97 ml before aortic valve replacement. Method: This was a prospective comparative study conducted from August 2013 to December 2014 in a tertiary care hospital. Fifty seven (57) patients of isolated chronic aortic regurgitation were included in this study. SPSS v23 was used for data analysis. Independent sample t-test was used for analysis of continuous variables and chi-square test for qualitative variables. Results: Out of fifty seven patients, early remodeling occurred in 34 (59.64%) patients after surgery. The mean pre-operative stroke volume of patient in whom remodeling occurred was 110.3+9.66 ml while mean pre-operative stroke volume of patients who did not undergo remodeling was 86.65+7.63 ml. There were 28 (82.4%) patients with stroke volume >97 ml in whom Remodeling occurred where as in patients with stroke volume <97 ml remodeling occurred only in 6 (17.6%) patients (p value 0.004). There was no in-hospital mortality. Conclusion: There is an association between stroke volume and early LV remodeling after Aortic valve replacement. Stroke volume >97 ml is a good predictor of early LV remodeling. PMID:28083026

  12. Interleukin-6 gene -174 G/C promoter polymorphism predicts severity and outcome in acute ischemic stroke patients from north India.

    PubMed

    Chakraborty, Baidarbhi; Chowdhury, Debashish; Vishnoi, Gaurav; Goswami, Binita; Kishore, Jugal; Agarwal, Sarita

    2013-07-01

    A guanine/cytosine (G/C) substitution occurring in position -174 of the interleukin-6 (IL-6) gene promoter changes the expression of IL-6 circulating proteins. We evaluated the occurrence of IL-6 -174 G/C polymorphism in patients with acute ischemic stroke and studied its association with stroke severity, outcome, and mortality. One hundred patients with acute ischemic stroke and 120 age and sex-matched healthy controls were studied. Genotyping was performed using polymerase chain reaction and restriction enzyme analysis. Serum levels of IL-6 were measured using enzyme-linked immunosorbent assay. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale. Outcome measures included modified Rankin Scale (mRS) and Barthel Index (BI) scores at 7 days and 3 and 6 months. Mortality/survival was assessed using the Kaplan-Meier analysis. The frequency of GG, GC, and CC genotypes did not differ significantly between cases and controls. No association was seen between TOAST subtype and genotype. At the time of admission, stroke was more severe in patients with the GC genotype (P = .03) and less severe in the GG genotype (P = .04). The GC genotype was also associated with higher serum IL-6 levels and poor short-term (BI P = .001; mRS P = .003) and long-term outcomes (BI P = 9 × 10(-5); mRS P = 9 × 10(-5)), while the GG genotype had significantly lower serum IL-6 levels and better short and long-term outcomes (BI P = 3 × 10(-5); mRS P = 2 × 10(-4)). There was significantly lesser mortality in the GG genotype and more in the GC genotype based on the Kaplan-Meier analysis. Patients with the GC genotype had more severe strokes with poorer short and long-term outcomes and increased mortality. The GG genotype was associated with less severe strokes, better short and long-term prognosis, and survival. The GG genotype appears to be protective against stroke severity

  13. 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

    2015-08-06

    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.

  14. Monitoring Non-Invasive Cardiac Output and Stroke Volume during Experimental Human Hypovolaemia and Resuscitation

    DTIC Science & Technology

    2011-01-01

    FloTrac method (Edwards Lifesciences , Irvine, CA, USA) ‘is the physiological premise that PP is pro- portional to stroke volume’,9 whereas the PulseCO...cardiac output and stroke volume BJA 29 9 Edwards Lifesciences . Available from http://www.edwards.com/ sitecollectionimages/products/mininvasive

  15. Longitudinal MRI evaluation of neuroprotective effects of pharmacologically induced hypothermia in experimental ischemic stroke.

    PubMed

    Wang, Silun; Gu, Xiaohuan; Paudyal, Ramesh; Wei, Ling; Dix, Thomas A; Yu, Shan P; Zhang, Xiaodong

    2017-04-01

    Pharmacologically induced hypothermia (PIH) shows promising neuroprotective effects after stroke insult. However, the dynamic evolution of stroke infarct during the hypothermic therapy has not been understood very well. In the present study, MRI was utilized to longitudinally characterize the infarct evolution in a mouse model of ischemic stroke treated by PIH using the neurotensin agonist HPI201. Adult male C57BL/6 mice underwent permanent occlusion of the right middle cerebra artery (MCA). Each animal received a vehicle or HPI201 intraperitoneal injection. The temporal changes of stroke lesion were examined using T2-weighted imaging and diffusion-weighted imaging (DWI) in the acute phase (1-3h) and 24h post stroke. Significantly reduced infarct and edema volumes were observed in PIH treated stroke mice, in agreement with TTC staining findings. Also, the TUNEL staining results indicated apoptotic cells were widely distributed among the ischemic cortex in control group but limited in PIH treated mice. Dramatically reduced growth rate of infarction was seen in PIH treated stroke mice. These results demonstrate HPI201 has strong neuroprotection effects during acute stroke. In particular, MRI with the numerical modelling of temporal infarct evolution could provide a unique means to examine and predict the dynamic response of the PIH treatment on infarct evolution.

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

    PubMed

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

    2014-03-01

    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.

  17. Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

    PubMed Central

    Waller, Amanda P.; Sharma, Ruchika; Chanley, Melinda A.; Nieman, Marvin T.; Smoyer, William E.

    2015-01-01

    Thrombotic disease, a major life–threatening complication of nephrotic syndrome, has been associated with proteinuria and hypoalbuminemia severity. However, it is not fully understood how disease severity correlates with severity of the acquired hypercoagulopathy of nephrotic syndrome. Without this knowledge, the utility of proteinuria and/or hypoalbuminemia as biomarkers of thrombotic risk remains limited. Here, we show that two well established ex vivo hypercoagulopathy assays, thrombin generation and rotational thromboelastometry, are highly correlated with proteinuria and hypoalbuminemia in the puromycin aminonucleoside and adriamycin rat models of nephrotic syndrome. Notably, in the puromycin aminonucleoside model, hyperfibrinogenemia and antithrombin deficiency were also correlated with proteinuria severity, consistent with reports in human nephrotic syndrome. Importantly, although coagulation was not spontaneously activated in vivo with increasing proteinuria, vascular injury induced a more robust thrombotic response in nephrotic animals. In conclusion, hypercoagulopathy is highly correlated with nephrotic disease severity, but overt thrombosis may require an initiating insult, such as vascular injury. Our results suggest that proteinuria and/or hypoalbuminemia could be developed as clinically meaningful surrogate biomarkers of hypercoagulopathy to identify patients with nephrotic syndrome at highest risk for thrombotic disease and potentially target them for anticoagulant pharmacoprophylaxis. PMID:25855774

  18. 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

  19. 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

  20. Therapeutic potential of human induced pluripotent stem cells in experimental stroke.

    PubMed

    Chang, Da-Jeong; Lee, Nayeon; Park, In-Hyun; Choi, Chunggab; Jeon, Iksoo; Kwon, Jihye; Oh, Seung-Hun; Shin, Dong Ah; Do, Jeong Tae; Lee, Dong Ryul; Lee, Hyunseung; Moon, Hyeyoung; Hong, Kwan Soo; Daley, George Q; Song, Jihwan

    2013-01-01

    Ischemic stroke mainly caused by middle cerebral artery occlusion (MCAo) is a major type of stroke, but there are currently very limited therapeutic options for its cure. Neural stem cells (NSCs) or neural precursor cells (NPCs) derived from various sources are known to survive and improve neurological functions when they are engrafted in animal models of stroke. Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients are novel cells that promise the autologous cell therapy for stroke. In this study, we successfully differentiated iPSCs derived from human fibroblasts into NPCs and found their robust therapeutic potential in a rodent MCAo stroke model. We observed the significant graft-induced behavioral recovery, as well as extensive neural tissue formation. Animal MRI results indicated that the majority of contralaterally transplanted iPSC-derived NPCs migrated to the peri-infarct area, showing a pathotropism critical for tissue recovery. The transplanted animals exhibited the significant reduction of stroke-induced inflammatory response, gliosis and apoptosis, and the contribution to the endogenous neurogenesis. Our results demonstrate that iPSC-derived NPCs are effective cells for the treatment of stroke.

  1. Speed of motor re-learning after experimental stroke depends on prior skill.

    PubMed

    Schubring-Giese, Maximilian; Molina-Luna, Katiuska; Hertler, Benjamin; Buitrago, Manuel M; Hanley, Daniel F; Luft, Andreas R

    2007-08-01

    Many motor rehabilitation therapies are based on principles of motor learning. Motor learning depends on preliminary knowledge of the trained and other (similar) skills. This study sought to investigate the influence of prior skill knowledge on re-learning of a precision reaching skill after a cortical lesion in rat. One group of animals recovered a previously known skill (skill training, followed by stroke and re-learning training, TST, n = 8). A second group learned the skill for the first time after stroke (ST, n = 6). A control group received prolonged training without stroke (n = 6). Unilateral partial motor cortex lesions were induced photothrombotically after identifying the forelimb representation using epidural stimulation mapping. In TST animals, re-learning after stroke was slower than learning before stroke (post hoc repeated measures ANOVA P = 0.039) and learning in the control group (P = 0.033). De novo learning after stroke (ST group) was not different from healthy learning. These findings show that skill learning can be performed if the motor cortex is partially lesioned; re-learning of a skill after stroke is slowed by prior knowledge of the skill. It remains to be tested in humans whether task novelty positively influences rehabilitation therapy.

  2. Sex Differences in Stroke Therapies

    PubMed Central

    Sohrabji, Farida; Park, Min Jung; Mahnke, Amanda H

    2016-01-01

    Stroke is the 5th leading cause of death and acquired disability in aged populations. Women are disproportionally affected by stroke, having a higher incidence and worse outcomes than men. Numerous preclinical studies have discovered novel therapies for the treatment of stroke, but almost all of these were found to be unsuccessful in clinical trials. Despite known sex differences in occurrence and severity of stroke, few therapeutics, both preclinically and clinically, take into account possible sex differences in treatment. Reanalysis of data from the only currently FDA-approved stroke therapy, tPA, has shown to not only improve stroke outcomes for both sexes, but to also show sexual dimorphism by more robust improvement in stroke outcome in females. Experimental evidence supports the inclusion of sex as a variable in the study of a number of novel stroke drugs and therapies, including preclinical studies of anti-inflammatory drugs (minocycline), stimulators of cell survival (IGF-1), and inhibitors of cell death pathways (pharmacological inhibition of PARP-1, NO production, and caspase activation), as well as in current clinical trials of stem cell therapy and cortical stimulation. Overall, study design and analyses in clinical trials, as well as in preclinical studies, must include both sexes equally, consider possible sex differences in the analyses, and report the differences/similarities in more systemized/structured way to translate promising therapies to both sexes and increase stroke recovery. PMID:27870437

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

    PubMed Central

    Wali, Bushra; Ishrat, Tauheed; Won, Soonmi; Stein, Donald G.

    2014-01-01

    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

  4. Kinematic measures for upper limb motor assessment during robot-mediated training in patients with severe sub-acute stroke.

    PubMed

    Duret, Christophe; Courtial, Ophélie; Grosmaire, Anne Gaelle

    2016-01-01

    Kinematic assessments are increasingly used as motor outcome measures during upper limb robot-assisted training, in addition to clinical scales. However, their relevance has not been evaluated much. Thirty-eight patients with severe sub-acute stroke (age 56 ± 17 [19-87] years; time since stroke, 55 ± 22 days) carried out 16 sessions (average 3/week, 35 ± 15 days) of upper limb robot-assisted training combined with standard therapy. Pre/post motor performance was evaluated using the Fugl-Meyer Assessment scale, Motor Status Scale (MSS) and kinematic measures. Motor outcomes were compared and relationships between clinical and kinematic outcomes were analyzed. All clinical and kinematic outcomes improved after training (p <  0.01). FM score increased from 17.7 ± 10.0 to 28.6 ± 15.4. All baseline kinematic measures were strongly correlated with clinical scores. Correlations between clinical and kinematic changes were moderate (r = -0.65 for change in FM Proximal score and change in accuracy measure). However, smoothness and accuracy indicators were shown to be responsive measures. This study demonstrated that baseline kinematic measures and their pre/post training changes were significantly correlated with clinical motor outcome measures. However, even if kinematic measures are valid for the evaluation of motor impairment we cannot propose to substitute common clinical measures of motor function which also evaluate functional abilities of the upper limb.

  5. Translational MR Neuroimaging of Stroke and Recovery.

    PubMed

    Mandeville, Emiri T; Ayata, Cenk; Zheng, Yi; Mandeville, Joseph B

    2017-02-01

    Multiparametric magnetic resonance imaging (MRI) has become a critical clinical tool for diagnosing focal ischemic stroke severity, staging treatment, and predicting outcome. Imaging during the acute phase focuses on tissue viability in the stroke vicinity, while imaging during recovery requires the evaluation of distributed structural and functional connectivity. Preclinical MRI of experimental stroke models provides validation of non-invasive biomarkers in terms of cellular and molecular mechanisms, while also providing a translational platform for evaluation of prospective therapies. This brief review of translational stroke imaging discusses the acute to chronic imaging transition, the principles underlying common MRI methods employed in stroke research, and the experimental results obtained by clinical and preclinical imaging to determine tissue viability, vascular remodeling, structural connectivity of major white matter tracts, and functional connectivity using task-based and resting-state fMRI during the stroke recovery process.

  6. Neural Substrates of Motor Recovery in Severely Impaired Stroke Patients With Hand Paralysis.

    PubMed

    Harris-Love, Michelle L; Chan, Evan; Dromerick, Alexander W; Cohen, Leonardo G

    2016-05-01

    In well-recovered stroke patients with preserved hand movement, motor dysfunction relates to interhemispheric and intracortical inhibition in affected hand muscles. In less fully recovered patients unable to move their hand, the neural substrates of recovered arm movements, crucial for performance of daily living tasks, are not well understood. Here, we evaluated interhemispheric and intracortical inhibition in paretic arm muscles of patients with no recovery of hand movement (n = 16, upper extremity Fugl-Meyer Assessment = 27.0 ± 8.6). We recorded silent periods (contralateral and ipsilateral) induced by transcranial magnetic stimulation during voluntary isometric contraction of the paretic biceps and triceps brachii muscles (correlates of intracortical and interhemispheric inhibition, respectively) and investigated links between the silent periods and motor recovery, an issue that has not been previously explored. We report that interhemispheric inhibition, stronger in the paretic triceps than biceps brachii muscles, significantly correlated with the magnitude of residual impairment (lower Fugl-Meyer scores). In contrast, intracortical inhibition in the paretic biceps brachii, but not in the triceps, correlated positively with motor recovery (Fugl-Meyer scores) and negatively with spasticity (lower Modified Ashworth scores). Our results suggest that interhemispheric inhibition and intracortical inhibition of paretic upper arm muscles relate to motor recovery in different ways. While interhemispheric inhibition may contribute to poorer recovery, muscle-specific intracortical inhibition may relate to successful motor recovery and lesser spasticity.

  7. Flexion synergy overshadows flexor spasticity during reaching in chronic moderate to severe hemiparetic stroke.

    PubMed

    Ellis, Michael D; Schut, Ingrid; Dewald, Julius P A

    2017-07-01

    Pharmaceutical intervention targets arm flexor spasticity with an often-unsuccessful goal of improving function. Flexion synergy is a related motor impairment that may be inadvertently neglected. Here, flexor spasticity and flexion synergy are disentangled to determine their contributions to reaching dysfunction. Twenty-six individuals participated. A robotic device systematically modulated shoulder abduction loading during ballistic reaching. Elbow muscle electromyography data were partitioned into windows delineated by elbow joint velocity allowing for the separation of synergy- and spasticity-related activation. Reaching velocity decreased with abduction loading (p<0.001) such that velocity was 30% slower when lifting the arm at 50% of abduction strength compared to when arm weight was supported. Abnormal flexion synergy increased with abduction loading (p<0.001) such that normalized activation ranged from a median (interquartile range) of 0.07 (0.03-0.12) when arm weight was supported to 0.19 (0.12-0.40) when actively lifting (large effect size, d=0.59). Flexor spasticity was detected during reaching (p=0.016) but only when arm weight was supported (intermediate effect size, d=0.33). Flexion synergy is the predominant contributor to reaching dysfunction while flexor spasticity appears only relevant during unnaturally occurring passively supported movement. Interventions targeting flexion synergy should be leveraged in future stroke recovery trials. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  8. Are we armed with the right data? Pooled individual data review of biomarkers in people with severe upper limb impairment after stroke.

    PubMed

    Hayward, Kathryn S; Schmidt, Julia; Lohse, Keith R; Peters, Sue; Bernhardt, Julie; Lannin, Natasha A; Boyd, Lara A

    2017-01-01

    To build an understanding of the neurobiology underpinning arm recovery in people with severe arm impairment due to stroke, we conducted a pooled individual data systematic review to: 1) characterize brain biomarkers; 2) determine relationship(s) between biomarkers and motor outcome; and 3) establish relationship(s) between biomarkers and motor recovery. Three electronic databases were searched up to October 2, 2015. Eligible studies included adults with severe arm impairment after stroke. Descriptive statistics were calculated to characterize brain biomarkers, and pooling of individual patient data was performed using mixed-effects linear regression to examine relationships between brain biomarkers and motor outcome and recovery. Thirty-eight articles including individual data from 372 people with severe arm impairment were analysed. The majority of individuals were in the chronic (> 6 months) phase post stroke (51%) and had a subcortical stroke (49%). The presence of a motor evoked potential (indexed by transcranial magnetic stimulation) was the only biomarker related to better motor outcome (p = 0.02). There was no relationship between motor outcome and stroke volume (cm(3)), location (cortical, subcortical, mixed) or side (left vs. right), and corticospinal tract asymmetry index (extracted from diffusion weighted imaging). Only one study had longitudinal data, thus no data pooling was possible to address change over time (preventing our third objective). Based on the available evidence, motor evoked potentials at rest were the only biomarker that predicted motor outcome in individuals with severe arm impairment following stroke. Given that few biomarkers emerged, this review highlights the need to move beyond currently known biomarkers and identify new indices with sufficient variability and sensitivity to guide recovery models in individuals with severe motor impairments following stroke.

  9. A systematic review and meta-analysis of the efficacy of piracetam and piracetam-like compounds in experimental stroke.

    PubMed

    Wheble, Philippa C R; Sena, Emily S; Macleod, Malcolm R

    2008-01-01

    Piracetam was a candidate neuroprotective drug for acute stroke ineffective in clinical trial. Here we use systematic review and meta-analysis to describe the evidence supporting a protective effect of piracetam and its derivatives in animal models of stroke. We present a systematic review of reports describing the use of piracetam and its derivatives in animal models of focal ischaemia, where the outcome was measured as an infarct size or neurological score (Der Simonian and Laird random effects meta-analysis). Only 2 studies, published 10 years after the first clinical trial of piracetam had been initiated, described its efficacy in animal models of stroke. A further 4 studies described the efficacy of related compounds. Piracetam and its derivatives improved the outcome by 30.2% (95% CI = 16.1-44.4). The median study quality was 4/10 (inter-quartile range = 4-6). Piracetam and its derivatives demonstrate neuroprotective efficacy in experimental stroke, but our findings raise concerns about the amount of available data, the quality of the studies and publication bias. (c) 2007 S. Karger AG, Basel.

  10. 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

  11. Nerve Stimulation Enhances Task-Oriented Training in Chronic, Severe Motor Deficit After Stroke: A Randomized Trial.

    PubMed

    Carrico, Cheryl; Chelette, Kenneth C; Westgate, Philip M; Powell, Elizabeth; Nichols, Laurie; Fleischer, Anne; Sawaki, Lumy

    2016-07-01

    A sensory-based intervention called peripheral nerve stimulation can enhance outcomes of motor training for stroke survivors with mild-to-moderate hemiparesis. Further research is needed to establish whether this paired intervention can have benefit in cases of severe impairment (almost no active movement). Subjects with chronic, severe poststroke hemiparesis (n=36) were randomized to receive 10 daily sessions of either active or sham stimulation (2 hours) immediately preceding intensive task-oriented training (4 hours). Upper extremity movement function was assessed using Fugl-Meyer Assessment (primary outcome measure), Wolf Motor Function Test, and Action Research Arm Test at baseline, immediately post intervention and at 1-month follow-up. Statistically significant difference between groups favored the active stimulation group on Fugl-Meyer at postintervention (95% confidence interval [CI], 1.1-6.9; P=0.008) and 1-month follow-up (95% CI, 0.6-8.3; P=0.025), Wolf Motor Function Test at postintervention (95% CI, -0.21 to -0.02; P=0.020), and Action Research Arm Test at postintervention (95% CI, 0.8-7.3; P=0.015) and 1-month follow-up (95% CI, 0.6-8.4; P=0.025). Only the active stimulation condition was associated with (1) statistically significant within-group benefit on all outcomes at 1-month follow-up and (2) improvement exceeding minimal detectable change, as well as minimal clinically significant difference, on ≥1 outcomes at ≥1 time points after intervention. After stroke, active peripheral nerve stimulation paired with intensive task-oriented training can effect significant improvement in severely impaired upper extremity movement function. Further confirmatory studies that consider a larger group, as well as longer follow-up, are needed. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02633215. © 2016 American Heart Association, Inc.

  12. Protective effects of rhubarb on experimental severe acute pancreatitis

    PubMed Central

    Zhao, Yu-Qing; Liu, Xiao-Hong; Ito, Tetsuhide; Qian, Jia-Ming

    2004-01-01

    AIM: To investigate the effects of rhubarb on severe acute pancreatitis (SAP) in rats. METHODS: Severe acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 μg/kg body weight) plus 5-h restraint water-immersion stress. Rhubarb (75-150 mg/kg) was orally fed before the first cerulein injection. The degree of pancreatic edema, serum amylase level, local pancreatic blood flow (PBF), and histological alterations were investigated. The effects of rhubarb on pancreatic exocrine secretion in this model were evaluated by comparing with those of somatostatin. RESULTS: In the Cerulein + Stress group, severe edema and diffuse hemorrhage in the pancreas were observed, the pancreatic wet weight (11.60 ± 0.61 g/Kg) and serum amylase (458 490 ± 43 100 U/L) were markedly increased (P < 0.01 vs control). In the rhubarb (150 mg/kg) treated rats, necrosis and polymorphonuclear neutrophil (PMN) infiltration in the pancreas were significantly reduced (P < 0.01), and a marked decrease (50%) in serum amylase levels was also observed (P < 0.01). PBF dropped to 38% (93 ± 5 mL/min per 100 g) of the control in the Cerulein + Stress group and partly recovered in the Cerulein + Stress + Rhubarb 150 mg group (135 ± 12 mL/min per 100 g) (P < 0.01). The pancreatic exocrine function was impaired in the SAP rats. The amylase levels of pancreatic juice were reduced in the rats treated with rhubarb or somatostatin, comparing with that of untreated SAP group. The bicarbonate concentration of pancreatic juice was markedly elevated only in the rhubarb-treated group (P < 0.01). CONCLUSION: Rhubarb can exert protective effects on SAP, probably by inhibiting the inflammation of pancreas, improving pancreatic microcirculation, and altering exocrine secretion. PMID:15052683

  13. 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

  14. Main experimental results of the Phebus Severe Fuel Damage Program

    SciTech Connect

    Gonnier, C. )

    1993-01-01

    The main objective of this program is to improve our knowledge about the early phase of a pressurized water reactor in-vessel core melt degradation in a temperature range up to 2800 K. The experimental program performed from December 1986 to June 1989 consists of six in-pile experiments with 21 fresh fuel rod bundles of 0.8 m active length. It is divided into two series of tests: (1) The first one (B9, B9R, B9+) is mainly devoted to the oxidation phenomenon and its consequences for fuel degradation. This series is characterized by high oxidation rates. (2) The second series [C3, C3+, Ag-In-CD (AIC)] is characterized by low oxidation rates of the cladding in order to study the interaction between the remaining Zircaloy and the other materials: interactions with Inconel and UO[sub 2] for C3 and C3+ tests and interactions with the Ag-In-Cd alloy and stainless steel of the control rod for the AIC test.

  15. Prediction of regional functional impairment following experimental stroke via connectome analysis.

    PubMed

    Schmitt, O; Badurek, S; Liu, W; Wang, Y; Rabiller, G; Kanoke, A; Eipert, P; Liu, J

    2017-04-13

    Recent advances in functional connectivity suggest that shared neuronal activation patterns define brain networks linking anatomically separate brain regions. We sought to investigate how cortical stroke disrupts multiple brain regions in processing spatial information. We conducted a connectome investigation at the mesoscale-level using the neuroVIISAS-framework, enabling the analysis of directed and weighted connectivity in bilateral hemispheres of cortical and subcortical brain regions. We found that spatial-exploration induced brain activation mapped by Fos, a proxy of neuronal activity, was differentially affected by stroke in a region-specific manner. The extent of hypoactivation following spatial exploration is inversely correlated with the spatial distance between the region of interest and region damaged by stroke, in particular within the parietal association and the primary somatosensory cortex, suggesting that the closer a region is to a stroke lesion, the more it would be affected during functional activation. Connectome modelling with 43 network parameters failed to reliably predict regions of hypoactivation in stroke rats exploring a novel environment, despite a modest correlation found for the centrality and hubness parameters in the home-caged animals. Further investigation in the inhibitory versus excitatory neuronal networks and microcircuit connectivity is warranted to improve the accuracy of predictability in post-stroke functional impairment.

  16. Astrocyte morphology after ischemic and hemorrhagic experimental stroke has no influence on the different recovery patterns.

    PubMed

    Mestriner, Régis Gemerasca; Saur, Lisiani; Bagatini, Pamela Brambilla; Baptista, Pedro Porto Alegre; Vaz, Sabrina Pereira; Ferreira, Kelly; Machado, Susane Alves; Xavier, Léder Leal; Netto, Carlos Alexandre

    2015-02-01

    Stroke, broadly subdivided into ischemic and hemorrhagic subtypes, is a serious health-care problem worldwide. Previous studies have suggested ischemic and hemorrhagic stroke could present different functional recovery patterns. However, little attention has been given to this neurobiological finding. Coincidently, astrocyte morphology could be related to improved sensorimotor recovery after skilled reaching training and modulated by physical exercise and environmental enrichment. Therefore, it is possible that astrocyte morphology might be linked to differential recovery patterns between ischemic and hemorrhagic stroke. Thus, we decided to compare long-term GFAP-positive astrocyte morphology after ischemic (IS, n=5), hemorrhagic (HS, n=5) and sham (S, n=5) stroke groups (induced by endothelin-1, collagenase type IV-S and salina, respectively). Our results showed ischemic and hemorrhagic stroke subtypes induced similar long-term GFAP-positive astrocyte plasticity (P>0.05) for all evaluated measures (regional and cellular optical density; astrocytic primary processes ramification and length; density of GFAP positive astrocytes) in perilesional sensorimotor cortex and striatum. These interesting negative results discourage similar studies focused on long-term plasticity of GFAP-positive astrocyte morphology and recovery comparison of stroke subtypes.

  17. High-Intensity, Unilateral Resistance Training of a Non-Paretic Muscle Group Increases Active Range of Motion in a Severely Paretic Upper Extremity Muscle Group after Stroke

    PubMed Central

    Urbin, M. A.; Harris-Love, Michelle L.; Carter, Alex R.; Lang, Catherine E.

    2015-01-01

    Limited rehabilitation strategies are available for movement restoration when paresis is too severe following stroke. Previous research has shown that high-intensity resistance training of one muscle group enhances strength of the homologous, contralateral muscle group in neurologically intact adults. How this “cross education” phenomenon might be exploited to moderate severe weakness in an upper extremity muscle group after stroke is not well understood. The primary aim of this study was to examine adaptations in force-generating capacity of severely paretic wrist extensors resulting from high intensity, dynamic contractions of the non-paretic wrist extensors. A secondary, exploratory aim was to probe neural adaptations in a subset of participants from each sample using a single-pulse, transcranial magnetic stimulation (TMS) protocol. Separate samples of neurologically intact controls (n = 7) and individuals ≥4 months post stroke (n = 6) underwent 16 sessions of training. Following training, one-repetition maximum of the untrained wrist extensors in the control group and active range of motion of the untrained, paretic wrist extensors in the stroke group were significantly increased. No changes in corticospinal excitability, intracortical inhibition, or interhemispheric inhibition were observed in control participants. Both stroke participants who underwent TMS testing, however, exhibited increased voluntary muscle activation following the intervention. In addition, motor-evoked potentials that were unobtainable prior to the intervention were readily elicited afterwards in a stroke participant. Results of this study demonstrate that high-intensity resistance training of a non-paretic upper extremity muscle group can enhance voluntary muscle activation and force-generating capacity of a severely paretic muscle group after stroke. There is also preliminary evidence that corticospinal adaptations may accompany these gains. PMID:26074871

  18. Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage.

    PubMed

    Sheng, Siyuan P; Lei, Beilei; James, Michael L; Lascola, Christopher D; Venkatraman, Talaignair N; Jung, Jin Yong; Maze, Mervyn; Franks, Nicholas P; Pearlstein, Robert D; Sheng, Huaxin; Warner, David S

    2012-12-01

    Xenon has been proven to be neuroprotective in experimental brain injury. The authors hypothesized that xenon would improve outcome from focal cerebral ischemia with a delayed treatment onset and prolonged recovery interval. Rats were subjected to 70 min temporary focal ischemia. Ninety minutes later, rats were treated with 0, 15, 30, or 45% Xe for 20 h or 0 or 30% Xe for 8, 20, or 44 h. Outcome was measured after 7 days. In another experiment, after ischemia, rats were maintained at 37.5° or 36.0°C for 20 h with or without 30% Xe. Outcome was assessed 28 days later. Finally, mice were subjected to intracerebral hemorrhage with or without 30% Xe for 20 h. Brain water content, hematoma volume, rotarod function, and microglial activation were measured. Cerebral infarct sizes (mean±SD) for 0, 15, 30, and 45% Xe were 212±27, 176±55, 160±32, and 198±54 mm, respectively (P=0.023). Neurologic scores (median±interquartile range) followed a similar pattern (P=0.002). Infarct size did not vary with treatment duration, but neurologic score improved (P=0.002) at all xenon exposure durations (8, 20, and 44 h). Postischemic treatment with either 30% Xe or subtherapeutic hypothermia (36°C) had no effect on 28-day outcome. Combination of these interventions provided long-term benefit. Xenon improved intracerebral hemorrhage outcome measures. Xenon improved focal ischemic outcome at 7, but not 28 days postischemia. Xenon combined with subtherapeutic hypothermia produced sustained recovery benefit. Xenon improved intracerebral hemorrhage outcome. Xenon may have potential for clinical stroke therapy under carefully defined conditions.

  19. 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

  20. 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

  1. GSK249320, A Monoclonal Antibody Against the Axon Outgrowth Inhibition Molecule Myelin-Associated Glycoprotein, Improves Outcome of Rodents with Experimental Stroke

    PubMed Central

    Cash, Diana; Easton, Alanna C.; Mesquita, Michel; Beech, John; Williams, Steve; Lloyd, Andrew; Irving, Elaine; Cramer, Steven C.

    2016-01-01

    Myelin-associated glycoprotein (MAG) is an inhibitor of axon growth. MAG levels increase after stroke. GSK249320 is a monoclonal antibody that neutralizes MAG-mediated inhibition and so may promote axon outgrowth and improve post-stroke outcomes. The current study tested the hypothesis that GSK249320 initiated 24 hours or 7 days after experimental stroke improves behavioural outcomes. Rats with right middle cerebral artery occlusion for 90 minutes were randomized to receive 6 weeks of intravenous (a) GSK249320 starting 24 hours post-stroke, (b) GSK249320 starting 7 days post-stroke, or (c) vehicle. Behavioral testing was performed over 7 weeks. Serial MRI demonstrated no differences in infarct volume across groups. Animals treated with GSK249320 24 hours post-stroke showed larger increases in Neuroscore (time X group, p = 0.0008) and staircase test (main effect of group, p = 0.0214) as compared to controls, but animals treated 7 days post-stroke showed no significant behavioral benefit. No significant results were found for the sticky tape or cylinder tests. A separate set of animals with experimental stroke received a single intravenous dose of GSK249320 or vehicle at 1 hour, 24 hours, 48 hours or 1 week post-stroke, and immunohistochemistry methods were used to measure GSK249320 distribution; GSK249320 was found in the ipsilesional hemisphere only, the extent of which increased with later times of injection. These data suggest that intravenous GSK249320 penetrates the lesion site and is associated with a small effect on functional outcomes when initiated 24 hours post-stroke and so support the translational potential of this monoclonal antibody as a restorative therapy for patients with stroke. PMID:28018988

  2. 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

  3. Aphasia severity in chronic stroke patients: a combined disconnection in the dorsal and ventral language pathways.

    PubMed

    Rosso, Charlotte; Vargas, Patricia; Valabregue, Romain; Arbizu, Céline; Henry-Amar, François; Leger, Anne; Lehéricy, Stéphane; Samson, Yves

    2015-01-01

    The contribution of lesion size and location in poststroke aphasia is debated, especially the extent to which aphasia severity is affected by damage to specific white matter areas. To identify specific white matter areas critical for poststroke aphasia global severity and to determine whether injury to these areas had more impact on aphasia severity than the infarct volume. Twenty-three chronic poststroke aphasic patients were assessed with the Aphasia Rapid Test (ART) and the Boston Diagnosis Aphasia Examination (BDAE) global severity scales and underwent diffusion tensor and structural imaging. Voxel-based diffusion tensor imaging regression analysis was used to determine in which areas fractional anisotropy (FA) abnormalities were correlated with ART and BDAE severity scales. The relationships between aphasia severity, FA values, and infarct volumes were investigated using global and partial correlations. We found a critical area associated with aphasia severity overlapping with the arcuate and the inferior fronto-occipital fasciculi, resulting in a combined disconnection of the dorsal and ventral pathways. ART scores were inversely correlated with FA values in this region, with greater severity present with lower FA values (correlation coefficient = -0.833, P < .0001). The proportion of variance explained by the FA value was higher than the proportion of variance explained by the infarct volume (R (2) = 68% vs 27%, P = .01). The impact of infarct volume on aphasia severity disappeared when damage to this critical white matter area was taken into account (P = .38). The assessment of the integrity of this region may potentially have a clinical impact in neurorehabilitation and acute decision making. © The Author(s) 2014.

  4. Early prediction of functional recovery after experimental stroke: functional magnetic resonance imaging, electrophysiology, and behavioral testing in rats.

    PubMed

    Weber, Ralph; Ramos-Cabrer, Pedro; Justicia, Carlos; Wiedermann, Dirk; Strecker, Cordula; Sprenger, Christiane; Hoehn, Mathias

    2008-01-30

    Therapeutic success of treatment of cerebral diseases must be assessed in terms of functional outcome. In experimental stroke studies, this has been limited to behavioral studies combined with morphological evaluations and single time point functional magnetic resonance imaging (fMRI) measurements but lacking the access to understanding underlying mechanisms for alterations in brain activation. Using a recently developed blood oxygenation level-dependent fMRI protocol to study longitudinal and intraindividual profiles of functional brain activation in the somatosensory system, we have demonstrated activation reemergence in the original representation field as the basic principle of functional recovery from experimental stroke. No plastic reorganization has been observed at any time point during 7 weeks after stroke induction. Applying combined recording of fMRI and somatosensory evoked potentials, we observed a tight coupling of electrical brain activity and hemodynamic response at all times, indicating persistent preservation of neurovascular coupling. Identification of functional brain recovery mechanisms has important implications for the understanding of brain plasticity after cerebral lesions, whereas preservation of neurovascular coupling is important for the clinical translation of fMRI.

  5. Early Trajectory of Stroke Severity Predicts Long-Term Functional Outcomes in Ischemic Stroke Subjects: Results From the ESCAPE Trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times).

    PubMed

    Sajobi, Tolulope T; Menon, Bijoy K; Wang, Meng; Lawal, Oluwaseyi; Shuaib, Ashfaq; Williams, David; Poppe, Alexandre Y; Jovin, Tudor G; Casaubon, Leanne K; Devlin, Thomas; Dowlatshahi, Dar; Fanale, Chris; Lowerison, Mark W; Demchuk, Andrew M; Goyal, Mayank; Hill, Michael D

    2017-01-01

    The trajectory of neurological improvement after stroke treatment is clinically likely to be an important prognostic signal. We compared the accuracy of early longitudinal National Institutes of Health Stroke Scale (NIHSS) measurement versus other early markers of stroke severity post treatment in predicting subjects' 90-day stroke outcome. Data are from the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). Stroke severity was assessed at baseline, 1, 2, 5, 30, and 90 days. Subjects' functional outcome was assessed using the modified Rankin Scale at baseline, 30 days, and 90 days. Group-based trajectory model was used to identify distinct subgroups of longitudinal trajectories of NIHSS measured over the first 2, 5, and 30 days. The accuracy of baseline NIHSS, infarct volume, 24-hour change in NIHSS, infarct volume, and disease severity trajectory subgroups in predicting 90-day stroke outcome were assessed using logistic regression analysis. Group-based trajectory model of the 2-day longitudinal NIHSS data revealed 3 distinct subgroups of NIHSS trajectories-large improvement (41.6%), minimal improvement (31.1%), and no improvement (27.3%) subgroups. Individuals in the large improvement group were more likely were more likely to exhibit good outcomes after 90 days than those in the minimal improvement or no improvement subgroup. Among candidate predictors, the 2-day trajectory subgroup variable was the most accurate in predicting 90-day modified Rankin Scale at 84.5%. Early trajectory of neurological improvement defined by 2-day longitudinal NIHSS data predicts functional outcomes with greater accuracy than other common variables. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335. © 2016 American Heart Association, Inc.

  6. [Japan stroke scales and its application for stroke].

    PubMed

    Amano, Takahiro

    2002-11-01

    There are many stroke scales currently available for estimating the severity and outcome of stroke. However, none of the stroke scales have been able to objectively quantify the severity of stroke. The Japan Stroke Society formed a subcommittee to task force the development of an innovative, quantifiable stroke scale. Conjoint analysis was utilized to compile this data. Finally, they developed a novel, and quantifiable Japan Stroke for the acute phase of stroke (JSS) (Stroke 32: 1800-1807, 2001). In addition to standard JSS, the Japan Stroke Scale Motor Function and Japan Stroke scale--Higher Cortical Function were finalized. These stroke scales are all parametric stroke scales. We utilize the stroke scales to monitor stroke patients, to start clinical pathway on patients with lacunas infarction after deciding whether severity of stroke is suitable for the clinical pathway by JSS. We use the JSS for the clinical studies of stroke patients. Furthermore, the JSS was utilized in the phase 2 trial of a new treatment in stroke patients which had significant statistical power. The scales were also introduced to the stroke databank. Therefore, these scales are useful to monitoring the neurological damage of stroke patients in the acute and chronic phase and to estimating the severity of stroke symptoms and predicting stroke outcome in clinical studies. They also have a potential to prove the efficacy of treatments through parametric analysis.

  7. IL-20 is regulated by hypoxia-inducible factor and up-regulated after experimental ischemic stroke.

    PubMed

    Chen, Wei-Yu; Chang, Ming-Shi

    2009-04-15

    IL-20, an IL-10 family member, is involved in various inflammatory diseases, such as psoriasis, rheumatoid arthritis, and atherosclerosis. We investigated whether hypoxia in vitro and an in vivo model of ischemic stroke would up-regulate IL-20 expression. In vitro, IL-20 expression increased in hypoxic HaCaT, HEK293 cells, chondrocytes, monocytes, and glioblastoma cells. Inhibition of hypoxia-inducible factor 1alpha inhibited CoCl(2)-induced IL-20 expression. We identified two putative hypoxia response elements in the human il20 gene promoter. Promoter activity assays showed that CoCl(2) mimicked hypoxia-activated luciferase reporter gene expression. In vivo, experimental ischemic stroke up-regulated IL-20 in the sera and brain tissue of rats. IL-20 stained positively in glia-like cells in peri-infarcted lesions, but not in contralateral tissue. Administration of IL-20 mAb ameliorated ischemia-induced brain infarction of rats after experimental ischemic stroke. In vitro, RT-PCR analysis showed that glioblastoma cells, GBM8901, expressed IL-20 and its receptor subunits IL-20R1, IL-20R2, and IL-22R1. IL-20 induced cell proliferation in GBM8901 cells by activating the JAK2/STAT3 and ERK1/2 pathways. IL-20 also induced production of IL-1beta, IL-8, and MCP-1 in GBM8901 cells. We conclude that IL-20 was responsive to hypoxia in vitro and in the ischemic stroke model and that up-regulation of IL-20 in the ischemic brain may contribute to brain injury.

  8. Acupuncture for neurogenesis in experimental ischemic stroke: a systematic review and meta-analysis.

    PubMed

    Lu, Lin; Zhang, Xiao-guang; Zhong, Linda L D; Chen, Zi-xian; Li, Yan; Zheng, Guo-qing; Bian, Zhao-xiang

    2016-01-20

    Acupuncture has been used for patients with stroke and post-stroke rehabilitation for thousands of years. Previous studies reported that acupuncture enhanced stroke recovery through neurogenesis. Hence, we conducted a systematic review and meta-analysis for preclinical studies to assess the current evidence for acupuncture effect on neurogenesis in treating ischaemic stroke. Studies were obtained from six databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, and Chinese Biomedical Literature Database, Ultimately, 34 studies containing 1617 animals were identified. Neurogenesis markers of Brdu, Nestin, PSA-NCAM, NeuN and GFAP were selected as major outcomes. The pooled results of 15 studies marked with Brdu showed significant effects of acupuncture for improving proliferation when compared with control groups (P < 0.01); 13 studies marked with Nestin showed significant effects of acupuncture for increasing proliferation when compared with control groups (P < 0.01); 4 studies marked with PSA-NCAM showed significant effects of acupuncture for enhancing migration when compared with control groups (P < 0.01); 4 studies marked with NeuN showed significant effects of acupuncture for stimulating differentiation when compared with control groups (P < 0.01). The findings suggest that acupuncture is a prospective therapy targeting neurogenesis for ischemic stroke.

  9. Acupuncture for neurogenesis in experimental ischemic stroke: a systematic review and meta-analysis

    PubMed Central

    Lu, Lin; Zhang, Xiao-guang; Zhong, Linda L.D.; Chen, Zi-xian; Li, Yan; Zheng, Guo-qing; Bian, Zhao-xiang

    2016-01-01

    Acupuncture has been used for patients with stroke and post-stroke rehabilitation for thousands of years. Previous studies reported that acupuncture enhanced stroke recovery through neurogenesis. Hence, we conducted a systematic review and meta-analysis for preclinical studies to assess the current evidence for acupuncture effect on neurogenesis in treating ischaemic stroke. Studies were obtained from six databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, and Chinese Biomedical Literature Database, Ultimately, 34 studies containing 1617 animals were identified. Neurogenesis markers of Brdu, Nestin, PSA-NCAM, NeuN and GFAP were selected as major outcomes. The pooled results of 15 studies marked with Brdu showed significant effects of acupuncture for improving proliferation when compared with control groups (P < 0.01); 13 studies marked with Nestin showed significant effects of acupuncture for increasing proliferation when compared with control groups (P < 0.01); 4 studies marked with PSA-NCAM showed significant effects of acupuncture for enhancing migration when compared with control groups (P < 0.01); 4 studies marked with NeuN showed significant effects of acupuncture for stimulating differentiation when compared with control groups (P < 0.01). The findings suggest that acupuncture is a prospective therapy targeting neurogenesis for ischemic stroke. PMID:26786869

  10. ACTION OF VITAMIN E ON EXPERIMENTAL SEVERE ACUTE LIVER FAILURE.

    PubMed

    Miguel, Fabiano Moraes; Schemitt, Elizângela Gonçalves; Colares, Josieli Raskopf; Hartmann, Renata Minuzzo; Morgan-Martins, Maria Isabel; Marroni, Norma Possa

    2017-01-01

    Severe Acute Liver Failure (ALF) is a life-threatening clinical syndrome characterized by hepatocyte necrosis, loss of hepatic architecture, and impairment of liver functions. One of the main causes of ALF is hepatotoxicity from chemical agents, which damage hepatocytes and result in increase of reactive oxygen species. The vitamin E isoform is the one with the strongest biological antioxidant activity. To evaluate the antioxidant effect of vitamin E in this ALF model. We used 56 rats (mean weight of 300 g) divided into eight groups, four groups assessed at 24 hours and 4 assessed at 48 hours after induction: control group (CO); Vitamin E (Vit. E); Thioacetamide (TAA) and Thioacetamide + Vitamina E (TAA+Vit.E). Rats were submitted to injections of thioacetamide (400 mg/kg i.p.) at baseline and 8 hours later. Vitamin E (100 mg/kg ip) was administered 30 minutes after the second dose of thioacetamide. The 48-hour group rats received two additional doses of vitamin E (24h and 36h). At 24h or 48 hours after the administration of the first dose of TAA, rats were weighed and anesthetized and their blood sampled for evaluation of liver integrity through enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver tissue was sampled for assessment of lipid peroxidation (LPO) by the technique TBARS, antioxidant enzymes SOD, CAT, GPx and GST activity, levels of the NO 2 /NO 3 and histology by H&E in two times. The results were expressed as mean ± standard deviation and statistically analyzed by ANOVA followed by Student-Newman-Keuls, with P <0.05 considered as significant. After treatment with vitamin E, we observed a reduction in liver enzymes AST (U/L) (101.32±19.45 in 24 hours and 97.85±29.65 in 48 hours) related to the TAA group (469.56± 0.69 in 24 hours and 598.23±55.45 in 48 hours) and ALT (U/L) (76.59±8.56 in 24 hours and 68.47±6.49 in 48 hours) compared to the TAA group (312.21±10.23 in 24 hours and 359.15±17.58 in 48 hours). There was

  11. Role of the Sympathetic Nervous System and Spleen in Experimental Stroke-Induced Immunodepression

    PubMed Central

    Yan, Fu-Ling; Zhang, Jin-Hua

    2014-01-01

    Background The mechanism of stroke-induced immunodepression syndrome (SIDS) remains uncertain. Some studies suggest that hyperactivation of the sympathetic nervous system (SNS) may be the key factor underlying SIDS. Catecholamines impair early lymphocyte response, which can increase the risk of stroke-associated infection (SAI). Material/Methods Our study focused on dynamic changes of metanephrine (MN), normetanephrine (NMN), cytokines, and spleen volume in the rat middle cerebral artery occlusion (MCAO) model. Results After MCAO, there is hyperactivation of SNS and pro-/anti-inflammatory imbalance, indicating systemic immunodepression. In addition, rat spleen size was reduced. Correlation analysis indicated that MCAO-induced spleen size reduction correlated with the changes in MN, NMN, and cytokines. Blocking SNS with propranolol can partly reverse the immunodepression and the reduction in spleen volume. Conclusions Taken together, these findings suggest that acute ischemic stroke induces over-activation of the SNS, which lowers the threshold of infection and increases the risk of infection. PMID:25434807

  12. 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

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

    PubMed

    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.

  14. Possible pathophysiologic mechanisms supporting the superior stroke protection of angiotensin receptor blockers compared to angiotensin-converting enzyme inhibitors: clinical and experimental evidence.

    PubMed

    Chrysant, S G

    2005-12-01

    Stroke is a major cause of death and disability and its incidence increases linearly with age and the level of systolic and diastolic blood pressure. Stroke, besides being a cause of long-term disability for the affected person, also imposes a significant burden on society and healthcare costs. Although good blood pressure control is very critical for stroke prevention, angiotensin receptor blockers (ARBs) may be superior to angiotensin-converting enzyme inhibitors (ACEIs) for the same degree of blood pressure control. This hypothesis has clinical and experimental support. ARBs prevent stroke incidence by blocking the angiotensin II (AII), AT1 receptors preventing brain ischaemia and allowing AII to stimulate the unoccupied AT2 receptors, which improve brain ischaemia. ACEIs, by reducing AII generation, are less effective in preventing stroke. This hypothesis provides evidence that AII plays an important role in the prevention of stroke. Certain ARBs like losartan, and telmisartan, irbesartan and candesartan possess additional properties which may play a role in stroke prevention, which is independent of AII. These include antiplatelet aggregating, hypouricemic, antidiabetic and atrial antifibrillatory effects. However, the most critical factor in stroke prevention is good blood pressure control irrespective of drug used.

  15. Isolation and purification of self-renewable human neural stem cells for cell therapy in experimental model of ischemic stroke.

    PubMed

    Azevedo-Pereira, Ricardo L; Daadi, Marcel M

    2013-01-01

    Human embryonic stem cells (hESCs) are pluripotent with a strong self-renewable ability making them a virtually unlimited source of neural cells for structural repair in neurological disorders. Currently, hESCs are one of the most promising cell sources amenable for commercialization of off-shelf cell therapy products. However, along with this strong proliferative capacity of hESCs comes the tumorigenic potential of these cells after transplantation. Thus, the isolation and purification of a homogeneous, population of neural stem cells (hNSCs) are of paramount importance to avoid tumor formation in the host brain. This chapter describes the isolation, neuralization, and long-term perpetuation of hNSCs derived from hESCs through use of specific mitogenic growth factors and the preparation of hNSCs for transplantation in an experimental model of stroke. Additionally, we describe methods to analyze the stroke and size of grafts using magnetic resonance imaging and Osirix software, and neuroanatomical tracing procedures to study axonal remodeling after stroke and cell transplantation.

  16. Neurogenin 2 converts mesenchymal stem cells into a neural precursor fate and improves functional recovery after experimental stroke.

    PubMed

    Cheng, Feng; Lu, Xiao Cheng; Hao, Huai Yong; Dai, Xue Liang; Qian, Teng Da; Huang, Bao Sheng; Tang, Lin Jun; Yu, Wan; Li, Li Xin

    2014-01-01

    Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. Here, we investigated whether Ngn2 can reprogram MSCs to adopt a neural precursor fate and enhance the therapeutic effects of MSCs after experimental stroke. In vitro, MSCs were transfected with lenti-GFP or lenti-Ngn2. Following neuronal induction, cells were identified by immunocytochemistry, Western blot and electrophysiological analyses. In a stroke model induced by transient right middle cerebral artery occlusion (MCAO), PBS, GFP-MSCs or Ngn2-MSCs were injected 1 day after MCAO. Behavioral tests, neurological and immunohistochemical assessments were performed. In vitro, Ngn2-MSCs expressed neural stem cells markers (Pax6 and nestin) and lost the potential to differentiate into mesodermal cell types. Following neural induction, Ngn2-MSCs expressed higher levels of neuron-specific proteins MAP2, Tuj1 and NeuN, and also expressed voltage-gated Na+ channel, which was absent in GFP-MSCs. In vivo, after transplantation, Ngn2-MSCs significantly reduced apoptotic cells, decreased infarct volume, and increased the expression of VEGF and BDNF. Finally, Ngn2-MSCs treated animals showed the highest functional recovery among the three groups. Ngn2 was sufficient to convert MSCs into a neural precursor fate and transplantation of Ngn2-MSCs was advantageous for the treatment of stroke rats. © 2014 S. Karger AG, Basel.

  17. 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

  18. EEG-Triggered Functional Electrical Stimulation Therapy for Restoring Upper Limb Function in Chronic Stroke with Severe Hemiplegia

    PubMed Central

    Marquis, Aaron; Popovic, Milos R.

    2016-01-01

    We report the therapeutic effects of integrating brain-computer interfacing technology and functional electrical stimulation therapy to restore upper limb reaching movements in a 64-year-old man with severe left hemiplegia following a hemorrhagic stroke he sustained six years prior to this study. He completed 40 90-minute sessions of functional electrical stimulation therapy using a custom-made neuroprosthesis that facilitated 5 different reaching movements. During each session, the participant attempted to reach with his paralyzed arm repeatedly. Stimulation for each of the movement phases (e.g., extending and retrieving the arm) was triggered when the power in the 18 Hz–28 Hz range (beta frequency range) of the participant's EEG activity, recorded with a single electrode, decreased below a predefined threshold. The function of the participant's arm showed a clinically significant improvement in the Fugl-Meyer Assessment Upper Extremity (FMA-UE) subscore (6 points) as well as moderate improvement in Functional Independence Measure Self-Care subscore (7 points). The changes in arm's function suggest that the combination of BCI technology and functional electrical stimulation therapy may restore voluntary motor function in individuals with chronic hemiplegia which results in severe upper limb deficit (FMA-UE ≤ 15), a population that does not benefit from current best-practice rehabilitation interventions. PMID:27882256

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

    PubMed

    Ruscher, Karsten; Shamloo, Mehrdad; Rickhag, Mattias; Ladunga, Istvan; Soriano, Liza; Gisselsson, Lennart; Toresson, Håkan; Ruslim-Litrus, Lily; Oksenberg, Donna; Urfer, Roman; Johansson, Barbro B; Nikolich, Karoly; Wieloch, Tadeusz

    2011-03-01

    Stroke leads to brain damage with subsequent slow and incomplete recovery of lost brain functions. Enriched housing of stroke-injured rats provides multi-modal sensorimotor stimulation, which improves recovery, although the specific mechanisms involved have not been identified. In rats housed in an enriched environment for two weeks after permanent middle cerebral artery occlusion, we found increased sigma-1 receptor expression in peri-infarct areas. Treatment of rats subjected to permanent or transient middle cerebral artery occlusion with 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride, an agonist of the sigma-1 receptor, starting two days after injury, enhanced the recovery of lost sensorimotor function without decreasing infarct size. The sigma-1 receptor was found in the galactocerebroside enriched membrane microdomains of reactive astrocytes and in neurons. Sigma-1 receptor activation increased the levels of the synaptic protein neurabin and neurexin in membrane rafts in the peri-infarct area, while sigma-1 receptor silencing prevented sigma-1 receptor-mediated neurite outgrowth in primary cortical neuronal cultures. In astrocytic cultures, oxygen and glucose deprivation induced sigma-1 receptor expression and actin dependent membrane raft formation, the latter blocked by sigma-1 receptor small interfering RNA silencing and pharmacological inhibition. We conclude that sigma-1 receptor activation stimulates recovery after stroke by enhancing cellular transport of biomolecules required for brain repair, thereby stimulating brain plasticity. Pharmacological targeting of the sigma-1 receptor provides new opportunities for stroke treatment beyond the therapeutic window of neuroprotection.

  20. 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.

  1. [Amantadine sulfate (PK-Merz) in the treatment of ischemic stroke: a clinical-experimental study].

    PubMed

    Khasanova, D R; Saĭkhunov, M V; Kitaeva, E A; Khafiz'ianova, R Kh; Islaamov, R R; Demin, T V

    2009-01-01

    A rat model of big brain ischemia with the middle brain artery occlusion was used for the study of amantadine sulfate (PK-Merz) effect on the expression of Hsp70 measured with immunohistochemical method and Western blot 12 h and 4 days after surgery. The neuroprotective effect of PK-Merz associated with the enhancement of Hsp70 expression in ischemic stroke in rats. To confirm the multivector neuroprotective action of the drug, a comparative study of clinical effectiveness of PK-Merz and magnesium sulfate was carried out in 40 patients (20 patients in each group) in the most acute period of atherothrombotic and cardioembolic strokes. Patients treated with PK-Merz exhibited the more significant restoration of consciousness and better dynamics (regress) of neurological deficit with the most intensive restoration of neurological deficit in the first day that allows to recommend the use of amantadine sulfate in the first hours of ischemic stroke and for the prevention of reperfusion damage in recanalisation therapy of ischemic stroke.

  2. CDP-choline at high doses is as effective as i.v. thrombolysis in experimental animal stroke.

    PubMed

    Gutiérrez-Fernández, María; Leciñana, María Alonso de; Rodríguez-Frutos, Berta; Ramos-Cejudo, Jaime; Roda, José María; Díez-Tejedor, Exuperio

    2012-09-01

    Use of thrombolysis in acute ischaemic stroke may be limited by a narrow benefit/risk ratio. Pharmacological inhibition of the ischaemic cascade may constitute an effective and safer approach to stroke treatment. This study compared the effects of high doses of cytidine diphosphate-choline (CDP-choline; 1000 mg/kg) with recombinant tissue plasminogen activator (rt-PA; 5 mg/kg) in an experimental animal model of embolic stroke. Fifteen rats were embolized in the right internal carotid artery with an autologous clot and were divided into three groups: (1) infarct; (2) intravenous rt-PA 5 mg/kg 30 minutes post-embolization; and (3) CDP-choline 1000 mg/kg, intraperitoneal, three doses, 30 minutes, 24 hours, and 48 hours post-embolization. Functional evaluation scores were evaluated using Rogers test, lesion volume by haematoxylin and eosin staining, cell death with transferase-mediated dUTP nick-end labelling, and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha with enzyme-linked immunosorbent assay. In this study, CDP-choline and rt-PA produced a significant reduction in brain damage considering infarct volume, cell death, and inflammatory cytokines (tumour necrosis factor-alpha and IL-6) compared with the infarct group. Additionally, CDP-choline significantly decreased infarct volume, cell death, and IL-6 levels with respect to the rt-PA group. From these results, we conclude that high-dose CDP-choline may be an effective treatment for acute ischaemic stroke even in absence of thrombolysis.

  3. 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…

  4. 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…

  5. [Clinical severity and functionality of acute stroke patients attended at the physiotherapy public services of Natal, Rio Grande do Norte State, Brazil].

    PubMed

    da Costa, Fabrícia Azevêdo; da Silva, Diana Lídice Araújo; da Rocha, Vera Maria

    2011-01-01

    This article investigates the severity and functional independence of hemiplegics patients' post-acute stroke by means of a multidisciplinary clinical staff. It is a descriptive study composed by 40 hemiplegics attended at the four largest physiotherapy public services in Natal, Rio Grande do Norte State. The methods used were an evaluation form, Functional Independence Measure and NIHSS. The results showed a sample predominantly female (55%), stroke ischemic (90%), right brain hemisphere (52.5%) and Hypertension Risk Factor (90%). The mean of clinical severity and functional independence was 13.32±4.7 and 54.6±17.15 respectively. There was no significant difference between the mean of functionality about stroke side (pvalue = 0.66). There is a significant relation between clinical severity and functional independence (r = -0.45 pvalue=0.003). It can be concluded that the level of clinical severity and functional dependence of stroke patients that make use of public physiotherapy services is significant and show the necessity, beyond the classic treatment, to be encouraged preventive educational actions to improve knowledge of this population.

  6. Transplantation of Unique Subpopulation of Fibroblasts, Muse Cells, Ameliorates Experimental Stroke Possibly via Robust Neuronal Differentiation.

    PubMed

    Uchida, Hiroki; Morita, Takahiro; Niizuma, Kuniyasu; Kushida, Yoshihiro; Kuroda, Yasumasa; Wakao, Shohei; Sakata, Hiroyuki; Matsuzaka, Yoshiya; Mushiake, Hajime; Tominaga, Teiji; Borlongan, Cesario V; Dezawa, Mari

    2016-01-01

    Muse cells reside as pre-existing pluripotent-like stem cells within the fibroblasts, are nontumorigenic, exhibit differentiation capacity into triploblastic-lineage cells, and replenish lost cells when transplanted in injury models. Cell fate and function of human skin fibroblast-derived Muse cells were evaluated in a rat stroke model. Muse cells (30,000), collected by pluripotent surface marker stage-specific embryonic antigen-3, were injected stereotaxically into three deposits within the rat ischemic cortex at 2 days after transient middle cerebral artery occlusion, and the cells' biological effects were examined for more than 84 days. Muse cells spontaneously and promptly committed to neural/neuronal-lineage cells when cocultured with stroke brain slices. Muse-transplanted stroke rats exhibited significant improvements in neurological and motor functions compared to control groups at chronic days 70 and 84, without a reduction in the infarct size. Muse cells survived in the host brain for up to 84 days and differentiated into NeuN (∼ 65%), MAP-2 (∼ 32%), calbindin (∼ 28%), and GST-π (∼ 25%)-positive cells in the cortex, but glial fibrillary acidic protein-positive cells were rare. Tumor formation was not observed. Muse cells integrated into the sensory-motor cortex, extended their neurites into cervical spinal cord, and displayed normalized hind limb somatosensory evoked potentials. Muse cells are unique from other stem cells in that they differentiate with high ratio into neuronal cells after integration with host brain microenvironment, possibly reconstructing the neuronal circuit to mitigate stroke symptoms. Human fibroblast-derived Muse cells pose as a novel source of transplantable stem cells, circumventing the need for gene manipulations, especially when contemplating autologous cell therapy for stroke. © 2015 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  7. Magnetic resonance imaging in experimental stroke and comparison with histology: systematic review and meta-analysis.

    PubMed

    Milidonis, Xenios; Marshall, Ian; Macleod, Malcolm R; Sena, Emily S

    2015-03-01

    Because the new era of preclinical stroke research demands improvements in validity and generalizability of findings, moving from single site to multicenter studies could be pivotal. However, the conduct of magnetic resonance imaging (MRI) in stroke remains ill-defined. We sought to assess the variability in the use of MRI for evaluating lesions post stroke and to examine the possibility as an alternative to gold standard histology for measuring the infarct size. We identified animal studies of ischemic stroke reporting lesion sizes using MRI. We assessed the degree of heterogeneity and reporting of scanning protocols, postprocessing methods, study design characteristics, and study quality. Studies performing histological evaluation of infarct size were further selected to compare with corresponding MRI using meta-regression. Fifty-four articles undertaking a total of 78 different MRI scanning protocols met the inclusion criteria. T2-weighted imaging was most frequently used (83% of the studies), followed by diffusion-weighted imaging (43%). Reporting of the imaging parameters was adequate, but heterogeneity between studies was high. Twelve studies assessed the infarct size using both MRI and histology at corresponding time points, with T2-weighted imaging-based treatment effect having a significant positive correlation with histology (; P<0.001). Guidelines for standardized use and reporting of MRI in preclinical stroke are urgently needed. T2-weighted imaging could be used as an effective in vivo alternative to histology for estimating treatment effects based on the extent of infarction; however, additional studies are needed to explore the effect of individual parameters. © 2015 American Heart Association, Inc.

  8. Quasi-experimental evaluation of a home care model for patients with stroke in China.

    PubMed

    Chen, Lu; Sit, Janet Wing-Hung; Shen, Xiaofang

    2016-11-01

    To evaluate the effectiveness of a modified home care model in China. First-time stroke survivors were recruited from a comprehensive teaching hospital in China. Subjects in the intervention group (n = 168) received modified home care involving detailed pre-discharge preparation and post-discharge follow-up lasting one month. The following outcomes were assessed at the end of follow-up: length of hospital stay, satisfaction with acute hospitalisation, medication compliance, complications and stroke-related re-hospitalisation. The outcomes were compared for the intervention group and a historical control group (n = 173) who received routine care. Modified home care was associated with shorter acute hospitalisation (11.29 ± 2.18 vs. 12.36 ± 4.33 d, p = 0.03), higher compliance [161 (95.83%) vs. 92 (53.18%), p = 0.004] and ability to perform daily activities (38.25 ± 10.22 vs. 32.08 ± 10.32, p = 0.03), and a lower rate of re-hospitalisation [2 (1.19%) vs. 11 (6.36%), p = 0.02]. Home care may be associated with higher quality of life and reduced dependency among stroke patients in China. Implications for Rehabilitation Home care can be effective method at improving the physical and psychological well-being of stroke survivors in China. The home care model in this study can improve health outcomes as well as reduce healthcare resources utilisation. Home care models for stroke survivors should be adapted to local healthcare policies and resources.

  9. Prediction of hemorrhagic transformation after experimental ischemic stroke using MRI-based algorithms.

    PubMed

    Bouts, Mark Jrj; Tiebosch, Ivo Acw; Rudrapatna, Umesh S; van der Toorn, Annette; Wu, Ona; Dijkhuizen, Rick M

    2017-08-01

    Estimation of hemorrhagic transformation (HT) risk is crucial for treatment decision-making after acute ischemic stroke. We aimed to determine the accuracy of multiparametric MRI-based predictive algorithms in calculating probability of HT after stroke. Spontaneously, hypertensive rats were subjected to embolic stroke and, after 3 h treated with tissue plasminogen activator (Group I: n = 6) or vehicle (Group II: n = 7). Brain MRI measurements of T2, T2*, diffusion, perfusion, and blood-brain barrier permeability were obtained at 2, 24, and 168 h post-stroke. Generalized linear model and random forest (RF) predictive algorithms were developed to calculate the probability of HT and infarction from acute MRI data. Validation against seven-day outcome on MRI and histology revealed that highest accuracy of hemorrhage prediction was achieved with a RF-based model that included spatial brain features (Group I: area under the receiver-operating characteristic curve (AUC) = 0.85 ± 0.14; Group II: AUC = 0.89 ± 0.09), with significant improvement over perfusion- or permeability-based thresholding methods. However, overlap between predicted and actual tissue outcome was significantly lower for hemorrhage prediction models (maximum Dice's Similarity Index (DSI) = 0.20 ± 0.06) than for infarct prediction models (maximum DSI = 0.81 ± 0.06). Multiparametric MRI-based predictive algorithms enable early identification of post-ischemic tissue at risk of HT and may contribute to improved treatment decision-making after acute ischemic stroke.

  10. Eprosartan reduces cardiac hypertrophy, protects heart and kidney, and prevents early mortality in severely hypertensive stroke-prone rats.

    PubMed

    Barone, F C; Coatney, R W; Chandra, S; Sarkar, S K; Nelson, A H; Contino, L C; Brooks, D P; Campbell, W G; Ohlstein, E H; Willette, R N

    2001-06-01

    Eprosartan is a selective angiotensin II type I receptor antagonist approved for the treatment of hypertension. In the present studies, eprosartan's ability to provide end-organ protection was evaluated in a model of cardiomyopathy and renal failure in stroke-prone rats (SP). SP were fed a high fat (24.5% in food) and high salt (1% in water) diet (SFD). Eprosartan (60 mg/kg/day) or vehicle (saline control) (n = 25/group) was administered by intraperitoneally-implanted minipumps to these SP on the SFD for 12 weeks. Normal diet fed SP and WKY rats (n = 25/group) were also included for comparison (i.e. served as normal controls). Mortality, hemodynamics, and both renal and cardiac function and histopathology were monitored in all treatment groups. Eprosartan decreased the severely elevated arterial pressure (-12%; P < 0.05) produced by SFD but did not affect heart rate. Vehicle-treated SP-SFD control rats exhibited significant weight loss (-13%; P < 0.05) and marked mortality (50% by week 6 and 95% by week 9; P < 0.01). Eprosartan-treated SP-SFD rats maintained normal weight, and exhibited zero mortality at week 12 and beyond. Eprosartan prevented the increased urinary protein excretion (P < 0.05) that was observed in vehicle-treated SP-SFD rats. Echocardiographic (i.e. 2-D guided M-mode) evaluation indicated that SP-SFD vehicle control rats exhibited increased septal (+22.2%) and posterior left ventricular wall (+30.0%) thickness, and decreased left ventricular chamber diameter (-15.9%), chamber volume (-32.7%), stroke volume (-48.7%) and ejection fraction (-22.3%), and a remarkable decrease in cardiac output (-59.3%) compared to controls (all P < 0.05). These same parameters in eprosartan-treated SP-SFD rats were normal and differed markedly and consistently from vehicle-treated SP-SFD rats (i.e. treatment prevented pathology; all P < 0.05). Cardiac-gated MRI data confirmed the ability of eprosartan to prevent cardiac pathology/remodeling (P < 0

  11. Neuropharmacological Actions of Metformin in Stroke

    PubMed Central

    Jia, Jia; Cheng, Jian; Ni, Jingshu; Zhen, Xuechu

    2015-01-01

    Increasing epidemiologic evidence suggests that metformin, a well-established AMPK activator and the most favorable first-line anti-diabetic drug, reduces stroke incidence and severity. However, the mechanism for this remains unclear. Moreover, previous experimental studies have reported controversial results about the effects of metformin on stroke outcomes during the acute phase. However, recent studies have consistently suggested that AMPK-mediated microglia/macrophage polarization and angioneurogenesis may play essential roles in metformin-promoted, long-term functional recovery following stroke. The present review summarizes the neuropharmacological actions of metformin in experimental stroke with an emphasis on the recent findings that the cell-specific effects and duration of AMPK activation are critical to the effects of metformin on stroke outcomes. PMID:26411966

  12. Menstrual Blood Cells Display Stem Cell–Like Phenotypic Markers and Exert Neuroprotection Following Transplantation in Experimental Stroke

    PubMed Central

    Kaneko, Yuji; Maki, Mina; Yu, Seong-Jin; Ali, Mohammed; Allickson, Julie G.; Sanberg, Cyndy D.; Kuzmin-Nichols, Nicole; Sanberg, Paul R.

    2010-01-01

    Cell therapy remains an experimental treatment for neurological disorders. A major obstacle in pursuing the clinical application of this therapy is finding the optimal cell type that will allow benefit to a large patient population with minimal complications. A cell type that is a complete match of the transplant recipient appears as an optimal scenario. Here, we report that menstrual blood may be an important source of autologous stem cells. Immunocytochemical assays of cultured menstrual blood reveal that they express embryonic-like stem cell phenotypic markers (Oct4, SSEA, Nanog), and when grown in appropriate conditioned media, express neuronal phenotypic markers (Nestin, MAP2). In order to test the therapeutic potential of these cells, we used the in vitro stroke model of oxygen glucose deprivation (OGD) and found that OGD-exposed primary rat neurons that were co-cultured with menstrual blood-derived stem cells or exposed to the media collected from cultured menstrual blood exhibited significantly reduced cell death. Trophic factors, such as VEGF, BDNF, and NT-3, were up-regulated in the media of OGD-exposed cultured menstrual blood-derived stem cells. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously and without immunosuppression, after experimentally induced ischemic stroke in adult rats also significantly reduced behavioral and histological impairments compared to vehicle-infused rats. Menstrual blood-derived cells exemplify a source of “individually tailored” donor cells that completely match the transplant recipient, at least in women. The present neurostructural and behavioral benefits afforded by transplanted menstrual blood-derived cells support their use as a stem cell source for cell therapy in stroke. PMID:19860544

  13. Menstrual blood cells display stem cell-like phenotypic markers and exert neuroprotection following transplantation in experimental stroke.

    PubMed

    Borlongan, Cesar V; Kaneko, Yuji; Maki, Mina; Yu, Seong-Jin; Ali, Mohammed; Allickson, Julie G; Sanberg, Cyndy D; Kuzmin-Nichols, Nicole; Sanberg, Paul R

    2010-04-01

    Cell therapy remains an experimental treatment for neurological disorders. A major obstacle in pursuing the clinical application of this therapy is finding the optimal cell type that will allow benefit to a large patient population with minimal complications. A cell type that is a complete match of the transplant recipient appears as an optimal scenario. Here, we report that menstrual blood may be an important source of autologous stem cells. Immunocytochemical assays of cultured menstrual blood reveal that they express embryonic-like stem cell phenotypic markers (Oct4, SSEA, Nanog), and when grown in appropriate conditioned media, express neuronal phenotypic markers (Nestin, MAP2). In order to test the therapeutic potential of these cells, we used the in vitro stroke model of oxygen glucose deprivation (OGD) and found that OGD-exposed primary rat neurons that were co-cultured with menstrual blood-derived stem cells or exposed to the media collected from cultured menstrual blood exhibited significantly reduced cell death. Trophic factors, such as VEGF, BDNF, and NT-3, were up-regulated in the media of OGD-exposed cultured menstrual blood-derived stem cells. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously and without immunosuppression, after experimentally induced ischemic stroke in adult rats also significantly reduced behavioral and histological impairments compared to vehicle-infused rats. Menstrual blood-derived cells exemplify a source of "individually tailored" donor cells that completely match the transplant recipient, at least in women. The present neurostructural and behavioral benefits afforded by transplanted menstrual blood-derived cells support their use as a stem cell source for cell therapy in stroke.

  14. Thioredoxin interacting protein: A novel target for neuroprotection in experimental thromboembolic stroke in mice

    PubMed Central

    Ishrat, Tauheed; Mohamed, Islam N.; Pharm, B.; Pillai, Bindu; Soliman, Sahar; Fouda, Abdelrahman Y; Ergul, Adviye; El-Remessy, Azza B; Fagan, Susan C

    2015-01-01

    Redox imbalance in the brain significantly contributes to ischemic stroke pathogenesis but antioxidant therapies have failed in clinical trials. Activation of endogenous defense mechanisms may provide better protection against stroke-induced oxidative injury. TXNIP (thioredoxin-interacting protein) is an endogenous inhibitor of thioredoxin (TRX), a key antioxidant system. We hypothesize that TXNIP inhibition attenuates redox imbalance and inflammation and provide protection against a clinically relevant model of embolic stroke. Male TXNIP-knockout (TKO), wild-type (WT) and WT mice treated with a pharmacological inhibitor of TXNIP, resveratrol (RES; 5mg/kg body weight) were subjected to embolic middle cerebral artery occlusion (eMCAO). Behavior outcomes were monitored using neurological deficits score and grip strength meter at 24 h after eMCAO. Expression of oxidative, inflammatory and apoptotic markers were analyzed by Western blot, immunohistochemistry and slot blot at 24h post-eMCAO. Our result showed that ischemic injury increases TXNIP in WT mice and that RES inhibits TXNIP expression and protects brain against ischemic damage. TKO and RES-treated mice exhibited 39.26% and 41.11% decrease in infarct size and improved neurological score and grip strength compared to WT mice after eMCAO. Furthermore, the levels of TRX, nitrotyrosine, NOD-like receptor protein (NLRP3), interleukin-1β (IL-1β), tumor necrosis factor- α (TNF-α), and activations of caspase-1, caspase-3 and poly ADP ribose polymerase (PARP) were significantly (P<0.05) attenuated in TKO and RES-treated mice. The present study suggests that TXNIP is contributing to acute ischemic stroke through redox-imbalance and inflammasome activation, and inhibition of TXNIP may provide a new target for therapeutic interventions. This study also affirms the importance of the antioxidant effect of RES on the TRX/TXNIP system. PMID:24939693

  15. CORPUS CALLOSUM AND EXPERIMENTAL STROKE: STUDIES IN CALLOSOTOMIZED RATS AND ACALLOSAL MICE

    PubMed Central

    Jin, Kunlin; Xie, Lin; Sun, Fen; Mao, XiaoOu; Greenberg, David A.

    2011-01-01

    Background and Purpose Interhemispheric inhibition via the corpus callosum has been proposed as an exacerbating factor in outcome from stroke. Methods We measured infarct volume and behavioral outcome following middle cerebral artery occlusion in callosotomized rats and acallosal mice. Results Neither callosotomy in rats nor callosal agenesis in mice improved infarct volume or behavioral outcome after middle cerebral artery occlusion. Conclusions These findings argue against a role for transcallosal projections in exacerbating focal cerebral ischemia. PMID:21737800

  16. Brain metabolic pattern analysis using a magnetic resonance spectra classification software in experimental stroke.

    PubMed

    Jiménez-Xarrié, Elena; Davila, Myriam; Candiota, Ana Paula; Delgado-Mederos, Raquel; Ortega-Martorell, Sandra; Julià-Sapé, Margarida; Arús, Carles; Martí-Fàbregas, Joan

    2017-01-13

    Magnetic resonance spectroscopy (MRS) provides non-invasive information about the metabolic pattern of the brain parenchyma in vivo. The SpectraClassifier software performs MRS pattern-recognition by determining the spectral features (metabolites) which can be used objectively to classify spectra. Our aim was to develop an Infarct Evolution Classifier and a Brain Regions Classifier in a rat model of focal ischemic stroke using SpectraClassifier. A total of 164 single-voxel proton spectra obtained with a 7 Tesla magnet at an echo time of 12 ms from non-infarcted parenchyma, subventricular zones and infarcted parenchyma were analyzed with SpectraClassifier ( http://gabrmn.uab.es/?q=sc ). The spectra corresponded to Sprague-Dawley rats (healthy rats, n = 7) and stroke rats at day 1 post-stroke (acute phase, n = 6 rats) and at days 7 ± 1 post-stroke (subacute phase, n = 14). In the Infarct Evolution Classifier, spectral features contributed by lactate + mobile lipids (1.33 ppm), total creatine (3.05 ppm) and mobile lipids (0.85 ppm) distinguished among non-infarcted parenchyma (100% sensitivity and 100% specificity), acute phase of infarct (100% sensitivity and 95% specificity) and subacute phase of infarct (78% sensitivity and 100% specificity). In the Brain Regions Classifier, spectral features contributed by myoinositol (3.62 ppm) and total creatine (3.04/3.05 ppm) distinguished among infarcted parenchyma (100% sensitivity and 98% specificity), non-infarcted parenchyma (84% sensitivity and 84% specificity) and subventricular zones (76% sensitivity and 93% specificity). SpectraClassifier identified candidate biomarkers for infarct evolution (mobile lipids accumulation) and different brain regions (myoinositol content).

  17. 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

  18. 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

  19. Stroke Treatments

    MedlinePlus

    ... Association.org About Stroke for Stroke Association.org Life After Stroke for Stroke Association.org Stroke Connection Magazine ... that may be treatable during recovery. Visit our Life After Stroke section for support and to learn more. ...

  20. Variants of Rab GTPase-Effector Binding Protein-2 Cause Variation in the Collateral Circulation and Severity of Stroke.

    PubMed

    Lucitti, Jennifer L; Sealock, Robert; Buckley, Brian K; Zhang, Hua; Xiao, Lin; Dudley, Andrew C; Faber, James E

    2016-12-01

    The extent (number and diameter) of collateral vessels varies widely and is a major determinant, along with arteriogenesis (collateral remodeling), of variation in severity of tissue injury after large artery occlusion. Differences in genetic background underlie the majority of the variation in collateral extent in mice, through alterations in collaterogenesis (embryonic collateral formation). In brain and other tissues, ≈80% of the variation in collateral extent among different mouse strains has been linked to a region on chromosome 7. We recently used congenic (CNG) fine mapping of C57BL/6 (B6, high extent) and BALB/cByJ (BC, low extent) mice to narrow the region to a 737 Kb locus, Dce1. Herein, we report the causal gene. We used additional CNG mapping and knockout mice to narrow the number of candidate genes. Subsequent inspection identified a nonsynonymous single nucleotide polymorphism between B6 and BC within Rabep2 (rs33080487). We then created B6 mice with the BC single nucleotide polymorphism at this locus plus 3 other lines for predicted alteration or knockout of Rabep2 using gene editing. The single amino acid change caused by rs33080487 accounted for the difference in collateral extent and infarct volume between B6 and BC mice attributable to Dce1. Mechanistically, variants of Rabep2 altered collaterogenesis during embryogenesis but had no effect on angiogenesis examined in vivo and in vitro. Rabep2 deficiency altered endosome trafficking known to be involved in VEGF-A→VEGFR2 signaling required for collaterogenesis. Naturally occurring variants of Rabep2 are major determinants of variation in collateral extent and stroke severity in mice. © 2016 American Heart Association, Inc.

  1. Intravenous Administration of Achyranthes Bidentata Polypeptides Supports Recovery from Experimental Ischemic Stroke in Vivo

    PubMed Central

    Sun, Hualing

    2013-01-01

    Background Achyranthes bidentata Blume (A. bidentata) is a commonly prescribed Chinese medicinal herb. A. bidentata polypeptides (ABPP) is an active composite constituent, separated from the aqueous extract of A. bidentata. Our previous studies have found that ABPP have the neuroprotective function in vitro and in rat middle cerebral artery occlusion (MCAO) model in attenuating the brain infract area induced by focal ischemia-reperfusion. However, the ultimate goal of the stroke treatment is the restoration of behavioral function. Identifying behavioral deficits and therapeutic treatments in animal models of ischemic stroke is essential for potential translational applications. Methodology and Principal Findings The effect of ABPP on motor, sensory, and cognitive function in an ischemic stroke model with MCAO was investigated up to day 30. The function recovery monitored by the neurological deficit score, grip test, body asymmetry, beam-balancing task, and the Morris Water Maze. In this study, systemic administration of ABPP by i.v after MCAO decreased the neurological deficit score, ameliorated the forepaw muscle strength, and diminished the motor and sensory asymmetry on 7th and 30th day after MCAO. MCAO has been observed to cause prolonged disturbance of spatial learning and memory in rats using the MWM, and ABPP treatment could improve the spatial learning and memory function, which is impaired by MCAO in rats, on 30th day after MCAO. Then, the viable cells in CA1 region of hippocampus were counted by Nissl staining, and the neuronal cell death were significantly suppressed in the ABPP treated group. Conclusion ABPP could improve the recovery of sensory, motor and coordination, and cognitive function in MCAO-induced ischemic rats. And this recovery had a good correlation to the less of neuronal injury in brain. PMID:23468912

  2. Magnetic resonance imaging of local and remote vascular remodelling after experimental stroke.

    PubMed

    Yanev, Pavel; Seevinck, Peter R; Rudrapatna, Umesh S; Bouts, Mark Jrj; van der Toorn, Annette; Gertz, Karen; Kronenberg, Golo; Endres, Matthias; van Tilborg, Geralda A; Dijkhuizen, Rick M

    2017-08-01

    The pattern of vascular remodelling in relation to recovery after stroke remains largely unclear. We used steady-state contrast-enhanced magnetic resonance imaging to assess the development of cerebral blood volume and microvascular density in perilesional and exofocal areas from (sub)acutely to chronically after transient stroke in rats. Microvascular density was verified histologically after infusion with Evans Blue dye. At day 1, microvascular cerebral blood volume and microvascular density were reduced in and around the ischemic lesion (intralesional borderzone: microvascular cerebral blood volume = 72 ± 8%; microvascular density = 76 ± 8%) (P < 0.05), while total cerebral blood volume remained relatively unchanged. Perilesional microvascular cerebral blood volume and microvascular density subsequently normalized (day 7) and remained relatively stable (day 70). In remote ipsilateral areas in the thalamus and substantia nigra - not part of the ischemic lesion - microvascular density gradually increased between days 1 and 70 (thalamic ventral posterior nucleus: microvascular density = 119 ± 9%; substantia nigra: microvascular density = 122 ± 8% (P < 0.05)), which was confirmed histologically. Our data indicate that initial microvascular collapse, with maintained collateral flow in larger vessels, is followed by dynamic revascularization in perilesional tissue. Furthermore, progressive neovascularization in non-ischemic connected areas may offset secondary neuronal degeneration and/or contribute to non-neuronal tissue remodelling. The complex spatiotemporal pattern of vascular remodelling, involving regions outside the lesion territory, may be a critical endogenous process to promote post-stroke brain reorganization.

  3. 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.

  4. MicroRNA-15a/16-1 Antagomir Ameliorates Ischemic Brain Injury in Experimental Stroke.

    PubMed

    Yang, Xinxin; Tang, Xuelian; Sun, Ping; Shi, Yejie; Liu, Kai; Hassan, Sulaiman H; Stetler, R Anne; Chen, Jun; Yin, Ke-Jie

    2017-07-01

    Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. This study is aimed at investigating the regulatory role of the miR-15a/16-1 cluster in ischemic brain injury and insight mechanisms. Adult male miR-15a/16-1 knockout and wild-type mice, or adult male C57 BL/6J mice injected via tail vein with the miR-15a/16-1-specific inhibitor (antagomir, 30 pmol/g), were subjected to 1 hour of middle cerebral artery occlusion and 72 hours of reperfusion. The neurological scores, brain infarct volume, brain water content, and neurobehavioral tests were then evaluated and analyzed. To explore underlying signaling pathways associated with alteration of miR-15a/16-1 activity, major proinflammatory cytokines were measured by quantitative polymerase chain reaction or ELISA and antiapoptotic proteins were examined by Western blotting. Genetic deletion of the miR-15a/16-1 cluster or intravenous delivery of miR-15a/16-1 antagomir significantly reduced cerebral infarct size, decreased brain water content, and improved neurological outcomes in stroke mice. Inhibition of miR-15a/16-1 significantly decreased the expression of the proinflammatory cytokines interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule 1, tumor necrosis factor alpha, and increased Bcl-2 and Bcl-w levels in the ischemic brain regions. Our data indicate that pharmacological inhibition of the miR-15a/16-1 cluster reduces ischemic brain injury via both upregulation of antiapoptotic proteins and suppression of proinflammatory molecules. These results suggest that the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke. © 2017 American Heart Association, Inc.

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

    PubMed Central

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

    2012-01-01

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

  6. Training of reaching in stroke survivors with severe and chronic upper limb paresis using a novel nonrobotic device: a randomized clinical trial.

    PubMed

    Barker, Ruth N; Brauer, Sandra G; Carson, Richard G

    2008-06-01

    Severe upper limb paresis is a major contributor to disability after stroke. This study investigated the efficacy of a new nonrobotic training device, the Sensorimotor Active Rehabilitation Training (SMART) Arm, that was used with or without electromyography-triggered electrical stimulation of triceps brachii to augment elbow extension, permitting stroke survivors with severe paresis to practice a constrained reaching task. A single-blind, randomized clinical trial was conducted with 42 stroke survivors with severe and chronic paresis. Thirty-three participants completed the study, of whom 10 received training using the SMART Arm with electromyography-triggered electrical stimulation, 13 received training using the SMART Arm alone, and 10 received no intervention (control). Training consisted of 12 1-hour sessions over 4 weeks. The primary outcome measure was "upper arm function," item 6 of the Motor Assessment Scale. Secondary outcome measures included impairment measures; triceps muscle strength, reaching force, modified Ashworth scale; and activity measures: reaching distance and Motor Assessment Scale. Assessments were administered before (0 weeks) and after training (4 weeks) and at 2 months follow-up (12 weeks). Both SMART Arm groups demonstrated significant improvements in all impairment and activity measures after training and at follow-up. There was no significant difference between these 2 groups. There was no change in the control group. Our findings indicate that training of reaching using the SMART Arm can reduce impairment and improve activity in stroke survivors with severe and chronic upper limb paresis, highlighting the benefits of intensive task-oriented practice, even in the context of severe paresis.

  7. Stroke vision, aphasia, neglect (VAN) assessment—a novel emergent large vessel occlusion screening tool: pilot study and comparison with current clinical severity indices

    PubMed Central

    Teleb, Mohamed S; Ver Hage, Anna; Carter, Jaqueline; Jayaraman, Mahesh V; McTaggart, Ryan A

    2017-01-01

    Background Identification of emergent large vessel occlusion (ELVO) stroke has become increasingly important with the recent publications of favorable acute stroke thrombectomy trials. Multiple screening tools exist but the length of the examination and the false positive rate range from good to adequate. A screening tool was designed and tested in the emergency department using nurse responders without a scoring system. Methods The vision, aphasia, and neglect (VAN) screening tool was designed to quickly assess functional neurovascular anatomy. While objective, there is no need to calculate or score with VAN. After training participating nurses to use it, VAN was used as an ELVO screen for all stroke patients on arrival to our emergency room before physician evaluation and CT scan. Results There were 62 consecutive code stroke activations during the pilot study. 19 (31%) of the patients were VAN positive and 24 (39%) had a National Institutes of Health Stroke Scale (NIHSS) score of ≥6. All 14 patients with ELVO were either VAN positive or assigned a NIHSS score ≥6. While both clinical severity thresholds had 100% sensitivity, VAN was more specific (90% vs 74% for NIHSS ≥6). Similarly, while VAN and NIHSS ≥6 had 100% negative predictive value, VAN had a 74% positive predictive value while NIHSS ≥6 had only a 58% positive predictive value. Conclusions The VAN screening tool accurately identified ELVO patients and outperformed a NIHSS ≥6 severity threshold and may best allow clinical teams to expedite care and mobilize resources for ELVO patients. A larger study to both validate this screening tool and compare with others is warranted. PMID:26891627

  8. [The influence of inhibitors of neuronal and inducible NO-synthases on experimental hemorrhagic stroke].

    PubMed

    Krushinskiĭ, A L; Kuzenkov, V S; D'iakonova, V E; Reutov, V P

    2014-01-01

    Objectives. To study the effect of inhibitors of neuronal and inducible NO-synthase on the development of hemorrhagic stroke in rats Krushinsky-Molodkina (KM) without adaptation to hypoxia and with short-term adaptation to hypobaric hypoxia. Material and methods. Ninety rats were included in the study. Experiments with short-term adaptation to hypobaric hypoxia were performed on 48 rats. The inhibitor of inducible NO-synthase (aminoguanidine, "Sigma") or the inhibitor of neuronal NO-synthase (7-nitroindasol, "Sigma") were injected in dosage 2.5 mg/100g intraperitoneally. Results. Selective inhibitors of neuronal and inducible NO-synthase had a protective effect on stress injuries in KM rats. The inhibitor of neuronal NO-synthase was more effective than the inhibitor of inducible NO-synthase in the experiments without adaptation to hypoxia. Markedly greater protective effect was achieved by the simultaneous introduction of inhibitors of neuronal and inducible NO-synthase. The greatest protective effect in the development of stress damage in rats of KM was observed in short-term adaptation to hypobaric hypoxia with simultaneous introduction of both inhibitors. Conclusions. It can be assumed that an excessive amount of NO produced by neuronal and inducible NO-synthases during the acoustic exposure in KM rats leads to stress damage. Use of selective inhibitors reduce the excess NO synthesis and the development of audiogenic stress damage caused by hemorrhagic stroke.

  9. [Changes in the focus of experimental ischemic stroke under the influence of neuroprotective drugs].

    PubMed

    Onishchenko, L S; Gaĭkova, O N; Ianishevskiĭ, S N

    2006-01-01

    The purpose of this study was to compare the morphological changes in the focus of ischemic stroke under the influence of the drugs of neurotrophic group (alpha-GPC, cerebrolysin), drugs possessing the nootropic properties (piracetam) and those with combined effect (vinpocetin). The experiments were performed in 18 rats. Temporary disturbance of cerebral circulation (acute ischemia) in right cerebral hemisphere was induced by clipping the trunk of innominate artery for 40 minutes. Areas of cerebral cortex, brainstem and cerebellar cortex were studied using light and electron microscopy. Treatment with alpha-GPC or cerebrolysin resulted in an increased tolerance of neurons to ischemic damage and in delayed realization of the program of cell death. Some intracellular changes were detected that could be regarded as the signs of adaptation and repair (indentation of nuclear envelope, increased number of ribosomes, hypertrophy of endoplasmic reticulum and Golgi complex). These drugs preserved the structure of the membranes in the nucleus and major organelles. In animals treated with piracetam and vinpocetin, all morphological signs were indicative of insufficient supply of energy-consuming processes of repair in the acute phase of ischemic stroke. This was accompanied by morphological features of functional stress of the neurons of the cerebral cortex, different stages of gliocyte apoptosis, phenomenon of incomplete separation of gliocytes during their proliferation, myelin and unmyelinated nerve fiber pathology, as well as by changes in synapse structure.

  10. Brain-Derived Neurotrophic Factor Knockdown Blocks the Angiogenic and Protective Effects of Angiotensin Modulation After Experimental Stroke.

    PubMed

    Fouda, Abdelrahman Y; Alhusban, Ahmed; Ishrat, Tauheed; Pillai, Bindu; Eldahshan, Wael; Waller, Jennifer L; Ergul, Adviye; Fagan, Susan C

    2017-01-01

    Angiotensin type 1 receptor blockers (ARBs) have been shown to be neuroprotective and neurorestorative in experimental stroke. The mechanisms proposed include anti-inflammatory, antiapoptotic effects, as well as stimulation of endogenous trophic factors leading to angiogenesis and neuroplasticity. We aimed to investigate the involvement of the neurotrophin, brain-derived neurotrophic factor (BDNF), in ARB-mediated functional recovery after stroke. To achieve this aim, Wistar rats received bilateral intracerebroventricular (ICV) injections of short hairpin RNA (shRNA) lentiviral particles or nontargeting control (NTC) vector, to knock down BDNF in both hemispheres. After 14 days, rats were subjected to 90-min middle cerebral artery occlusion (MCAO) and received the ARB, candesartan, 1 mg/kg, or saline IV at reperfusion (one dose), then followed for another 14 days using a battery of behavioral tests. BDNF protein expression was successfully reduced by about 70 % in both hemispheres at 14 days after bilateral shRNA lentiviral particle injection. The NTC group that received candesartan showed better functional outcome as well as increased vascular density and synaptogenesis as compared to saline treatment. BDNF knockdown abrogated the beneficial effects of candesartan on neurobehavioral outcome, vascular density, and synaptogenesis. In conclusion, BDNF is directly involved in candesartan-mediated functional recovery, angiogenesis, and synaptogenesis.

  11. Neuroprotective Effect of a New Synthetic Aspirin-decursinol Adduct in Experimental Animal Models of Ischemic Stroke

    PubMed Central

    Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

    2013-01-01

    Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants. PMID:24073226

  12. A systematic review and meta-analysis of Baihui (GV20)-based scalp acupuncture in experimental ischemic stroke

    PubMed Central

    Wang, Wen-wen; Xie, Cheng-long; Lu, Lin; Zheng, Guo-qing

    2014-01-01

    Acupuncture for stroke has been used in China for over 2,000 years and nowadays is increasingly practiced elsewhere in the world. However, previous studies had conflicting findings on the results of acupuncture. Here, we conducted a systematic review and meta-analysis to assess the current evidence for the effect of Baihui (GV20)-based scalp acupuncture in animal models of focal cerebral ischemia. Six databases from the inception of each database up to June 2013 were electronically searched. Primary outcomes were infarct size and neurobehavioral outcome. Ultimately, 54 studies involving 1816 animals were identified describing procedures. Meta-analysis results showed that twelve studies reported significant effects of Baihui (GV20)-based scalp acupuncture for improving infarct volume compared with middle cerebral artery occlusion group (P < 0.01), and thirty-two studies reported significant effects of Baihui (GV20)-based scalp acupuncture for improving the neurological function score when compared with the control group (P < 0.01). In conclusion, Baihui (GV20)-based scalp acupuncture could improve infarct volume and neurological function score and exert potential neuroprotective role in experimental ischemic stroke. PMID:24496233

  13. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials

    PubMed Central

    Emberson, Jonathan; Lees, Kennedy R; Lyden, Patrick; Blackwell, Lisa; Albers, Gregory; Bluhmki, Erich; Brott, Thomas; Cohen, Geoff; Davis, Stephen; Donnan, Geoffrey; Grotta, James; Howard, George; Kaste, Markku; Koga, Masatoshi; von Kummer, Ruediger; Lansberg, Maarten; Lindley, Richard I; Murray, Gordon; Olivot, Jean Marc; Parsons, Mark; Tilley, Barbara; Toni, Danilo; Toyoda, Kazunori; Wahlgren, Nils; Wardlaw, Joanna; Whiteley, William; del Zoppo, Gregory J; Baigent, Colin; Sandercock, Peter; Hacke, Werner

    2014-01-01

    Summary Background Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase. Methods We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3–6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality. Findings Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35–2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05–1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95–1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3

  14. Role of sleep-disordered breathing and sleep-wake disturbances for stroke and stroke recovery.

    PubMed

    Hermann, Dirk M; Bassetti, Claudio L

    2016-09-27

    Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) are highly prevalent in stroke patients. Recent studies suggest that they represent both a risk factor and a consequence of stroke and affect stroke recovery, outcome, and recurrence. Review of literature. Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in TIA and stroke patients are recommended in view of the very high prevalence (>50%) of SDB (Class IIb, level of evidence B). Treatment of obstructive SDB with continuous positive airway pressure is recommended given the strength of the increasing evidence in support of a positive effect on outcome (Class IIb, level of evidence B). Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB. Recently, both reduced and increased sleep duration, as well as hypersomnia, insomnia, and restless legs syndrome (RLS), were also suggested to increase stroke risk. Mainly experimental studies found that SWD may in addition impair neuroplasticity processes and functional stroke recovery. Treatment of SWD with hypnotics and sedative antidepressants (insomnia), activating antidepressants or stimulants (hypersomnia), dopaminergic drugs (RLS), and clonazepam (parasomnias) are based on single case observations and should be used with caution. SDB and SWD increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome. Current knowledge supports the systematic implementation of clinical procedures for the diagnosis and treatment of poststroke SDB and SWD on stroke units. © 2016 American Academy of Neurology.

  15. Role of sleep-disordered breathing and sleep-wake disturbances for stroke and stroke recovery

    PubMed Central

    2016-01-01

    Background: Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) are highly prevalent in stroke patients. Recent studies suggest that they represent both a risk factor and a consequence of stroke and affect stroke recovery, outcome, and recurrence. Methods: Review of literature. Results: Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in TIA and stroke patients are recommended in view of the very high prevalence (>50%) of SDB (Class IIb, level of evidence B). Treatment of obstructive SDB with continuous positive airway pressure is recommended given the strength of the increasing evidence in support of a positive effect on outcome (Class IIb, level of evidence B). Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB. Recently, both reduced and increased sleep duration, as well as hypersomnia, insomnia, and restless legs syndrome (RLS), were also suggested to increase stroke risk. Mainly experimental studies found that SWD may in addition impair neuroplasticity processes and functional stroke recovery. Treatment of SWD with hypnotics and sedative antidepressants (insomnia), activating antidepressants or stimulants (hypersomnia), dopaminergic drugs (RLS), and clonazepam (parasomnias) are based on single case observations and should be used with caution. Conclusions: SDB and SWD increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome. Current knowledge supports the systematic implementation of clinical procedures for the diagnosis and treatment of poststroke SDB and SWD on stroke units. PMID:27488603

  16. Neuroprotective effect of epidermal growth factor plus growth hormone-releasing peptide-6 resembles hypothermia in experimental stroke.

    PubMed

    Subirós, N; Pérez-Saad, H; Aldana, L; Gibson, C L; Borgnakke, W S; Garcia-Del-Barco, D

    2016-11-01

    Combined therapy with epidermal growth factor (EGF) and growth hormone-releasing peptide 6 (GHRP-6) in stroke models has accumulated evidence of neuroprotective effects from several studies, but needs further support before clinical translation. Comparing EGF + GHRP-6 to hypothermia, a gold neuroprotection standard, may contribute to this purpose. The aims of this study were to compare the neuroprotective effects of a combined therapy based on EGF + GHRP-6 with hypothermia in animal models of (a) global ischemia representing myocardial infarction and (b) focal brain ischemia representing ischemic stroke. (a) Global ischemia was induced in Mongolian gerbils by a 15-min occlusion of both carotid arteries, followed by reperfusion. (b) Focal brain ischemia was achieved by intracerebral injection of endothelin 1 in Wistar rats. In each experiment, three ischemic treatment groups - vehicle, EGF + GHRP-6, and hypothermia - were compared to each other and to a sham-operated control group. End points were survival, neurological scores, and infarct volume. (a) In global ischemia, neurological score at 48-72 h, infarct volume, and neuronal density of hippocampal CA1 zone in gerbils treated with EGF + GHRP-6 were similar to the hypothermia-treated group. (b) In focal ischemia, the neurologic score and infarct volume of rats receiving EGF + GHRP-6 were also similar to animals in the hypothermia group. With hypothermia being a good standard neuroprotectant reference, these results provide additional proof of principle for EGF and GHRP-6 co-administration as a potentially neuroprotective stroke therapy.

  17. Sex differences in stroke therapies.

    PubMed

    Sohrabji, Farida; Park, Min Jung; Mahnke, Amanda H

    2017-01-02

    Stroke is the fifth leading cause of death and acquired disability in aged populations. Women are disproportionally affected by stroke, having a higher incidence and worse outcomes than men. Numerous preclinical studies have discovered novel therapies for the treatment of stroke, but almost all of these have been shown to be unsuccessful in clinical trials. Despite known sex differences in occurrence and severity of stroke, few preclinical or clinical therapeutics take into account possible sex differences in treatment. Reanalysis of data from studies of tissue plasminogen activator (tPA), the only currently FDA-approved stroke therapy, has shown that tPA improves stroke outcomes for both sexes and also shows sexual dimorphism by more robust improvement in stroke outcome in females. Experimental evidence supports the inclusion of sex as a variable in the study of a number of novel stroke drugs and therapies, including preclinical studies of anti-inflammatory drugs (minocycline), stimulators of cell survival (insulin-like growth factor-1), and inhibitors of cell death pathways (pharmacological inhibition of poly[ADP-ribose] polymerase-1, nitric oxide production, and caspase activation) as well as in current clinical trials of stem cell therapy and cortical stimulation. Overall, study design and analysis in clinical trials as well as in preclinical studies must include both sexes equally, consider possible sex differences in the analyses, and report the differences/similarities in more systematic/structured ways to allow promising therapies for both sexes and increase stroke recovery. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies.

    PubMed

    Chapman, J; Rand, J H; Brey, R L; Levine, S R; Blatt, I; Khamashta, M A; Shoenfeld, Y

    2003-01-01

    Although many types of neurological disorders and events have been described in association with antiphospholipid antibodies (aPL) and the antiphospholipid syndrome (APS), only ischaemic stroke is reasonably well established and accepted as a diagnostic criterion for the syndrome. We propose to evaluate, classify and rank the association of other neurological manifestations as possible, probable, or definite according to the data available from clinical studies and animal models. By these criteria, none of the neurological disorders or events such as epilepsy, psychiatric disease, dementia, transverse myelitis, multiple sclerosis-like disease, chorea, migraine, Guillian-Barrè syndrome, and sensory-neural hearing loss, can be definitely associated with aPL or APS.

  19. Age-related differences in experimental stroke: possible involvement of mitochondrial dysfunction and oxidative damage.

    PubMed

    Li, Nanlin; Kong, Xiangwei; Ye, Ruidong; Yang, Qianzi; Han, Junliang; Xiong, Lize

    2011-06-01

    Age is the single most important risk factor for cerebral stroke. Unfortunately, the effect of age on ischemic brain damage is less clear. In this study, we sought to examine the potential influence of aging on the histologic and functional outcomes after ischemia. Juvenile (4 weeks of age), young adult (4 months of age), mid-aged (11-12 months of age), and aged (18-19 months of age) mice were subjected to transient middle cerebral artery occlusion. There was no remarkable difference of infarct volume on postoperative days 1 and 3. However, on postoperative day 7, aged mice exhibited significantly worsened infarct volume compared with juvenile and young mice. Intriguingly, the increase of infarct volume was most prominent in the striatal area rather than in cortex. Accordingly, aged mice displayed a slower and incomplete functional recovery after stroke. We further evaluated the effects of aging on the oxidative damage and mitochondrial dysfunction following ischemia. Brain tissues were assayed for lipid, DNA, and protein peroxidation products, mitochondrial enzyme activities, mitochondrial membrane potential, production of reactive oxygen species, and antioxidant activities. Aging was associated with declined mitochondrial function and antioxidant detoxification following ischemia, thereby inducing a deteriorated oxidative damage. Regional subanalyses demonstrated that, in accordance with infarct area, the pro-oxidant/antioxidant imbalance occurred more prominently in subcortical areas. Collectively, these findings suggest mitochondria-mediated oxidative damage may be involved in the age-related aggravated injury in subcortical areas. Mitochondrial protection could be a promising target for neuroprotective therapy, especially in the aged population.

  20. Endovascular Therapy is Effective and Safe for Patients with Severe Ischemic Stroke: Pooled Analysis of IMS III and MR CLEAN Data

    PubMed Central

    Broderick, Joseph P.; Berkhemer, Olvert A.; Palesch, Yuko Y.; Dippel, Diederik W.J.; Foster, Lydia D.; Roos, Yvo B.W.E.M.; van der Lugt, Aad; Tomsick, Thomas A.; Majoie, Charles B.L.M.; van Zwam, Wim H.; Demchuk, Andrew M.; van Oostenbrugge, Robert J.; Khatri, Pooja; Lingsma, Hester F.; Hill, Michael D.; Roozenbeek, Bob; Jauch, Edward C.; Jovin, Tudor G.; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A.; Goyal, Mayank; Schonewille, Wouter J.; Mazighi, Mikael; Engelter, Stefan T.; Anderson, Craig S.; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J.; Janis, L. Scott; Simpson, Kit

    2015-01-01

    Background and Purpose We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (NIHSS ≥20) following a pre-specified analysis plan. Methods The pooled analysis of the IMS III and MR CLEAN trial included participants with an NIHSS ≥20 prior to intravenous (IV) t-PA treatment (IMS III) or randomization (MR CLEAN) who were treated with IV t-PA ≤ 3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy following IV t-PA would have improved 90-day outcome (distribution of modified Rankin scale [mRS] scores), as compared to those who received IV t-PA alone. Results Among 342 participants in the pooled analysis (194 from IMS III, 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared to the IV t-PA group (adjusted odds ratio [aOR] 1.78; 95% confidence interval [CI] 1.20-2.66). In the logistic regression model of the dichotomous outcome (mRS 0-2, or ‘functional independence’), the endovascular group had superior outcomes (aOR 1.97; 95% CI 1.09-3.56). Functional independence (mRS ≤2) at 90 days was 25% in the endovascular group as compared to 14% in the IV t-PA group. Conclusions Endovascular therapy following IV t-PA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke. PMID:26486865

  1. Stroke in Minorities

    PubMed Central

    Trimble, Brian; Morgenstern, Lewis B.

    2009-01-01

    Synopsis Minorities in the United States have higher stroke risks, stroke occurrence at an earlier age, and for some groups, more severe strokes than non-Hispanic whites. Factors contributing to this disparity are explored. Characteristics of African American, Hispanic, and Native American stroke risk and incidence are reviewed. We mention recent interventions to raise the awareness of stroke risk factors and symptoms in minorities. The importance of the problem is discussed, and we suggest ways stroke in minorities may be reduced. PMID:19026907

  2. Stroke in centenarians.

    PubMed

    Olsen, Tom Skyhøj; Andersen, Klaus Kaae

    2014-01-01

    Reports on centenarians with stroke have thus far been casuistic. We present clinical characteristics and 1-month mortality in 39 centenarians admitted to Danish hospitals with acute stroke within 2000-2010. A Danish stroke registry (2000-2010) contains information about 61 935 acute stroke patients among which 39 patients were centenarians. Data included age, sex, civil and housing status, stroke severity (Scandinavian Stroke Scale [SSS], 0 worst to 58 best), computed tomography scan, cardiovascular risk factors and death within 1 month after stroke. Data in centenarians were compared with similar data in stroke patients aged 40-69 years (n = 25 023), 70-79 years (n = 16 048), 80-89 years (n = 16 274) and 90-99 years (n = 3379). Of the 39 centenarians, 87% were women, 82% were living alone and 64% were living in their own home before the stroke. In general, the prevalence of cardiovascular risk factors was lower in centenarians, particularly with regard to previous myocardial infarction, previous stroke and diabetes mellitus. Strokes were significantly more severe (SSS 25.4), and 1-month mortality (38.5%) was significantly higher in centenarians when compared with other age groups. Centenarians with stroke are from a cardiovascular standpoint healthier than their younger counterparts. Yet, strokes in centenarians are more severe and associated with very high mortality. © 2013 Japan Geriatrics Society.

  3. Shared decision making after severe stroke-How can we improve patient and family involvement in treatment decisions?

    PubMed

    Visvanathan, Akila; Dennis, Martin; Mead, Gillian; Whiteley, William N; Lawton, Julia; Doubal, Fergus Neil

    2017-01-01

    People who are well may regard survival with disability as being worse than death. However, this is often not the case when those surviving with disability (e.g. stroke survivors) are asked the same question. Many routine treatments provided after an acute stroke (e.g. feeding via a tube) increase survival, but with disability. Therefore, clinicians need to support patients and families in making informed decisions about the use of these treatments, in a process termed shared decision making. This is challenging after acute stroke: there is prognostic uncertainty, patients are often too unwell to participate in decision making, and proxies may not know the patients' expressed wishes (i.e. values). Patients' values also change over time and in different situations. There is limited evidence on successful methods to facilitate this process. Changes targeted at components of shared decision making (e.g. decision aids to provide information and discussing patient values) increase patient satisfaction. How this influences decision making is unclear. Presumably, a "shared decision-making tool" that introduces effective changes at various stages in this process might be helpful after acute stroke. For example, by complementing professional judgement with predictions from prognostic models, clinicians could provide information that is more accurate. Decision aids that are personalized may be helpful. Further qualitative research can provide clinicians with a better understanding of patient values and factors influencing this at different time points after a stroke. The evaluation of this tool in its success to achieve outcomes consistent with patients' values may require more than one clinical trial.

  4. Modeling the inflammatory response in the hypothalamus ensuing heat stroke: iterative cycle of model calibration, identifiability analysis, experimental design and data collection.

    PubMed

    Klett, Hagen; Rodriguez-Fernandez, Maria; Dineen, Shauna; Leon, Lisa R; Timmer, Jens; Doyle, Francis J

    2015-02-01

    Heat Stroke (HS) is a life-threatening illness caused by prolonged exposure to heat that causes severe hyperthermia and nervous system abnormalities. The long term consequences of HS are poorly understood and deeper insight is required to find possible treatment strategies. Elevated pro- and anti-inflammatory cytokines during HS recovery suggest to play a major role in the immune response. In this study, we developed a mathematical model to understand the interactions and dynamics of cytokines in the hypothalamus, the main thermoregulatory center in the brain. Uncertainty and identifiability analysis of the calibrated model parameters revealed non-identifiable parameters due to the limited amount of data. To overcome the lack of identifiability of the parameters, an iterative cycle of optimal experimental design, data collection, re-calibration and model reduction was applied and further informative experiments were suggested. Additionally, a new method of approximating the prior distribution of the parameters for Bayesian optimal experimental design based on the profile likelihood is presented.

  5. [Experimental model of severe local radiation injuries of the skin after X-rays].

    PubMed

    Kotenko, K V; Moroz, B B; Nasonova, T A; Dobrynina, O A; LIpengolz, A A; Gimadova, T I; Deshevoy, Yu B; Lebedev, V G; Lyrschikova, A V; Eremin, I I

    2013-01-01

    The experimental model of severe local radiation injuries skin under the influence of a relatively soft X-rays on a modified device RAP 100-10 produced by "Diagnostica-M" (Russia) was proposed. The model can be used as pre-clinical studies in small experimental animals in order to improve the treatment of local radiation injuries, especially in the conditions of application of cellular therapy.

  6. Percutaneous transluminal angioplasty and stenting for severe stenosis of the intracranial extradural internal carotid artery causing transient ischemic attack or minor stroke

    PubMed Central

    Ko, Jun Kyeung; Choi, Chang Hwa; Cha, Seung Heon; Choi, Byung Kwan; Cho, Won Ho; Kang, Tae Ho; Sung, Sang Min; Cho, Han Jin

    2015-01-01

    The purpose of this study is to assess the technical feasibility and clinical efficacy of percutaneous transluminal angioplasty and stenting (PTAS) for symptomatic stenosis of the intracranial extradural (petrous and cavernous) internal carotid artery (ICA). Review of medical records identified 26 consecutive patients who underwent PTAS using a balloon-expandable coronary stent (n = 15, 57.7%) or a Wingspan self-expandable stent (n = 11, 42.3%) for treatment of severe stenosis (>70%) involving the intracranial extradural ICA. The inclusion criteria were transient ischemic attack with an ABCD2 score of ≥3 (n = 12, 46.2%) or minor stroke with an NIHSS score of ≤4 (n = 14, 53.8%). Technical success rates, complications, and angiographic and clinical outcomes were analyzed retrospectively. PTAS was technically successful in all patients. The mean stenosis ratio decreased from 77.1% to 10.0% immediately after PTAS. The overall incidence of procedural complications was 23.1%, and the postoperative permanent morbidity/mortality rate was 7.7%. A total of 22 patients were tracked over an average period of 29.9 months. During the observation period, 20 patients (90.9%) had no further cerebrovascular events and stroke recurrence occurred in two patients (9.1%), resulting in an annual stroke risk of 3.7%. Two cases (11.1%) of significant in-stent restenosis (>50%) were found on follow-up angiography (n = 18). PTAS for severe stenosis (>70%) involving the intracranial extradural ICA showed a good technical feasibility and favorable clinical outcome in patients with transient ischemic attack or minor stroke. PMID:26063697

  7. 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.

  8. Effects of brain-derived neurotrophic factor on local inflammation in experimental stroke of rat.

    PubMed

    Jiang, Yongjun; Wei, Ning; Zhu, Juehua; Lu, Tingting; Chen, Zhaoyao; Xu, Gelin; Liu, Xinfeng

    2010-01-01

    This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF) can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO) for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobility shift assay, respectively. Exogenous BDNF significantly improved motor-sensory, sensorimotor function, and vestibulomotor function, while BDNF did not decrease the infarct volume. Exogenous BDNF increased the number of both activated and phagocytotic microglia in brain. BDNF upregulated interleukin10 and its mRNA expression, while downregulated tumor necrosis factor α and its mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B. BDNF antibody, which blocked the activity of endogenous BDNF, showed the opposite effect of exogenous BDNF. Our data indicated that BDNF may modulate local inflammation in ischemic brain tissues on the cellular, cytokine, and transcription factor levels.

  9. Malibatol A protects against brain injury through reversing mitochondrial dysfunction in experimental stroke.

    PubMed

    Yang, Wenjie; Chen, Xiang; Pan, Jie; Ge, Huiming; Yin, Kailin; Wu, Zhengzheng; Li, Xiaoxi; Sha, Dujuan; Xu, Yun

    2015-01-01

    Ischemic stroke is particularly susceptible to free radicals mediated secondary neuronal damage, especially mitochondrial dysfunction. Malibatol A (MA), a novel resveratrol oligomer, has shown potential antioxidant property in vitro. But little is known about its effect on central nervous system (CNS) in vivo. In the present study, the effect of MA was evaluated in focal cerebral ischemia induced by right middle cerebral artery occlusion (MCAO) in mice. MA at the dose of 20 mg/kg was administered by caudal-vein injection within 15 min after reperfusion. At 24 h after cerebral ischemia/reperfusion (I/R) injury, ameliorated neurological scores and reduced infarct volume was observed in MA treated group. Also, MA treatment restored the increased levels of reactive oxygen species (ROS), 3-Nitrotyrosine (3-NT), and 4-Hydroxynonenal (4-HNE) induced by MCAO. The activities of respiratory enzyme complex I, III and mitochondrial transmembrane potential (Δm) were effectively preserved compared with MCAO group through MA treatment. Western blot analysis showed a marked increase in Bcl-2 and decrease in Bax expression after MA treatment as compared with MCAO group. Moreover, MA treatment prevented release of cytochrome c from mitochondria into cytoplasm and blunted activities of caspase-9 and caspase-3. Collectively, the present study indicates that MA can ameliorate MCAO-induced mitochondrial dysfunction, and this might partially contribute to its protective effect on brain damage after 24 h of I/R injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

  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. Experimental study on the lethal threshold value of multiple successive voltage impulses to rabbits simulating multi-stroke lightning flash

    NASA Astrophysics Data System (ADS)

    Ishikawa, T.; Ohashi, M.; Kitagawa, N.; Nagai, Y.; Miyazawa, T.

    1985-06-01

    It is well known that about three-quarters of a lightning discharge to the ground consists of multi-stroke flashes among which 3- or 4-stroke flashes are the most frequent. A new type of impulse-generator was developed which can produce 3-successive impulse voltages to simulate multi-stroke lightning flashes. Experiments were conducted to investigate the effects of multi-stroke flash on the living body and the results were compared with those for the well-known effects of a single-stroke discharge. The results demonstrated that in the case of the multi-stroke discharge, the animal died when of the energy of one of the individual impulses reached the lethal threshold value established for a single-stroke discharge. It was found that the effect of the individual impulses did not last longer than the stroke interval and did not exert an additive effect on the living body. In natural lightning discharges, the multi-stroke flash should be regarded as more dangerous than the single-stroke flash, since it is liable to an energy that exceeds the lethal threshold value and to be associated with a higher probability of a continuing current (known to be the most fatal of discharge components).

  12. Therapeutic interventions in acute stroke.

    PubMed Central

    Lees, K R

    1992-01-01

    1. Potential therapies for ischaemic stroke include agents to reduce oedema, to improve cerebral perfusion, to reduce excitotoxic damage, to minimise free-radical induced injury and to reduce complications such as deep venous thrombosis. 2. Of the anti-oedema drugs, steroids are ineffective and possibly dangerous; intravenous glycerol is unproven. 3. Haemodilution to reduce whole blood viscosity and improve perfusion is ineffective. Thrombolytic drugs have not been adequately tested but several randomised multicentre trials are now commencing. Early treatment and CT scanning are essential. 4. Anticoagulants and antiplatelet drugs may have wide applicability but have not been tested in the acute phase of stroke. A multi-centre trial will address this issue. 5. Neuronal cytoprotection offers exciting prospects for acute stroke treatment. Antagonists of glutamate at the NMDA receptor, calcium and sodium channel blocking agents and free radical scavenging drugs have potent effects experimentally. Several agents are now reaching clinical trials. The calcium antagonist nimodipine has been disappointing in large scale trials but some studies were flawed by late treatment. 6. Successful treatment of acute stroke is likely to combine several approaches. 7. Therapeutic trials in stroke must include CT scanning, early treatment and a multicentre approach to achieve large numbers of patients. PMID:1493080

  13. Seladin-1/DHCR24 Is Neuroprotective by Associating EAAT2 Glutamate Transporter to Lipid Rafts in Experimental Stroke.

    PubMed

    Hernández-Jiménez, Macarena; Martínez-López, Diego; Gabandé-Rodríguez, Enrique; Martín-Segura, Adrian; Lizasoain, Ignacio; Ledesma, María D; Dotti, Carlos G; Moro, María A

    2016-01-01

    3β-Hydroxysteroid-Δ24 reductase (DHCR24) or selective alzheimer disease indicator 1 (seladin-1), an enzyme of cholesterol biosynthetic pathway, has been implicated in neuroprotection, oxidative stress, and inflammation. However, its role in ischemic stroke remains unexplored. The aim of this study was to characterize the effect of seladin-1/DHCR24 using an experimental stroke model in mice. Dhcr24(+/-) and wild-type (WT) mice were subjected to permanent middle cerebral artery occlusion. In another set of experiments, WT mice were treated intraperitoneally either with vehicle or U18666A (seladin-1/DHCR24 inhibitor, 10 mg/kg) 30 minutes after middle cerebral artery occlusion. Brains were removed 48 h after middle cerebral artery occlusion for infarct volume determination. For protein expression determination, peri-infarct region was obtained 24 h after ischemia, and Western blot or cytometric bead array was performed. Dhcr24(+/-) mice displayed larger infarct volumes after middle cerebral artery occlusion than their WT littermates. Treatment of WT mice with the seladin-1/DHCR24 inhibitor U18666A also increased ischemic lesion. Inflammation-related mediators were increased after ischemia in Dhcr24(+/-) mice compared with WT counterparts. Consistent with a role of cholesterol in proper function of glutamate transporter EAAT2 in membrane lipid rafts, we found a decreased association of EAAT2 with lipid rafts after ischemia when DHCR24 is genetically deleted or pharmacologically inhibited. Accordingly, treatment with U18666A decreases [(3)H]-glutamate uptake in cultured astrocytes. These results support the idea that lipid raft integrity, ensured by seladin-1/DHCR24, plays a crucial protective role in the ischemic brain by guaranteeing EAAT2-mediated uptake of glutamate excess. © 2015 American Heart Association, Inc.

  14. 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

  15. Examining a participation-focused stroke self-management intervention in a day rehabilitation setting: a quasi-experimental pilot study.

    PubMed

    Lee, Danbi; Fischer, Heidi; Zera, Sarah; Robertson, Rosetta; Hammel, Joy

    2017-09-28

    Background People with stroke often find discharge from rehabilitation distressing because they do not feel prepared to participate in life roles as they want. A self-management approach can facilitate improvement in confidence and ability to manage post-stroke community living and participation after transitioning into the community. Objective To evaluate the feasibility and effectiveness of the Improving Participation After Stroke Self-management program - Rehab version (IPASS-R) in a day rehabilitation setting. Methods We used a mixed-method non-randomized quasi-experimental design. The IPASS-R program is a six-session group-based intervention led by a trained occupational therapist and lay person with stroke. The program uses an efficacy building approach to support aging adults to maintain active participation in home and community activities post-stroke. Primary outcome measures were the Reintegration to Normal Living Index (RNLI), Stroke Impact Scale (SIS), and Participation Strategies Self-Efficacy Scale. Qualitative feedback was collected post-treatment. Results Seventeen participants with stroke (intervention n = 9; control n = 8) were enrolled across two sites. Non-parametric effect sizes calculated using the Wilcoxon Signed-Rank test revealed larger effects on RNLI and SIS outcomes in the intervention group. The Mann-Whitney U test showed significant differences between the two groups' changes in scores on perceived recovery and strength. Conclusions The result shows that IPASS-R has the potential to be integrated into a day rehabilitation setting with a positive impact on community integration and perceived recovery outcomes. Future study is needed to investigate the IPASS-R with a larger sample size and more rigorous study design.

  16. Novel aspirin-triggered neuroprotectin D1 attenuates cerebral ischemic injury after experimental stroke.

    PubMed

    Bazan, Nicolas G; Eady, Tiffany N; Khoutorova, Larissa; Atkins, Kristal D; Hong, Song; Lu, Yan; Zhang, Changde; Jun, Bokkyoo; Obenaus, Andre; Fredman, Gabrielle; Zhu, Min; Winkler, Jeremy W; Petasis, Nicos A; Serhan, Charles N; Belayev, Ludmila

    2012-07-01

    Acute ischemic stroke triggers complex neurovascular, neuroinflammatory and synaptic alterations. Aspirin and docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member, have beneficial effects on cerebrovascular diseases. DHA is the precursor of neuroprotectin D1 (NPD1), which downregulates apoptosis and, in turn, promotes cell survival. Here we have tested the effect of aspirin plus DHA administration and discovered the synthesis of aspirin-triggered NPD1 (AT-NPD1) in the brain. Then we performed the total chemical synthesis of this molecule and tested in the setting of 2h middle cerebral artery occlusion (MCAo) in Sprague-Dawley rats. Neurological status was evaluated at 24h, 48 h, 72 h, and 7 days. At 3h post-stroke onset, an intravenous administration of 333 μg/kg of AT-NPD1 sodium salt (AT-NPD1-SS) or methyl-ester (AT-NPD1-ME) or vehicle (saline) as treatment was given. On day 7, ex vivo magnetic resonance imaging (MRI) of the brains was conducted on 11.7 T MRI. T2WI, 3D volumes, and apparent diffusion coefficient (ADC) maps were generated. In addition, infarct volumes and number of GFAP (reactive astrocytes), ED-1 (activated microglia/macrophages) and SMI-71-positive vessels were counted in the cortex and striatum at the level of the central lesion. All animals showed similar values for rectal and cranial temperatures, arterial blood gases, and plasma glucose during and after MCAo. Treatment with both AT-NPD1-SS and AT-NPD1-ME significantly improved neurological scores compared to saline treatment at 24h, 48 h, 72 h and 7 days. Total lesion volumes computed from T2WI images were significantly reduced by both AT-NPD1-SS and AT-NPD1-ME treatment in the cortex (by 44% and 81%), striatum (by 61% and 77%) and total infarct (by 48% and 78%, respectively). Brain edema, computed from T2WI in the cortex (penumbra) and striatum (core), was elevated in the saline group. In contrast, both AT-NPD1 decreased water content in the striatum on day 7. 3D

  17. 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.

  18. 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

  19. Hippocampal stroke.

    PubMed

    Szabo, Kristina

    2014-01-01

    The first to link disturbance of memory and lesions of the medial temporal lobe was the Russian neurologist von Bechterew, who in 1989 presented the brain of a 60-year-old man who had suffered from severe amnesia. Autopsy showed bilateral damage of the medial temporal lobe. Several following postmortem case studies confirmed the association between permanent amnesia and bitemporal stroke. Reports of transient memory deficits in unilateral stroke in combination with other neurological and neuropsychological deficits followed. With the advent of brain imaging, persistent or transient amnesia as the sole or primary manifestation of acute - mostly left-sided - hippocampal stroke was described. With the use of modern MRI techniques the identification of typical ischemic stroke lesion patterns affecting the hippocampus has become possible. Although overt cognitive deficits in unilateral hippocampal stroke seem to be rare, a careful neuropsychological examination might be necessary to detect resulting neuropsychological deficits including disturbances of verbal and nonverbal episodic long-term memory and spatial orientation.

  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. 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.

  2. 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

  3. 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.

  4. Pre-admission CHADS2, CHA2DS2-VASc, and R2CHADS2 Scores on Severity and Functional Outcome in Acute Ischemic Stroke with Atrial Fibrillation.

    PubMed

    Tanaka, Koji; Yamada, Takeshi; Torii, Takako; Furuta, Konosuke; Matsumoto, Shoji; Yoshimura, Takeo; Takase, Kei-ichiro; Wakata, Yoshifumi; Nakashima, Naoki; Kira, Jun-ichi; Murai, Hiroyuki

    2015-07-01

    We examined the association between pre-admission risk scores and severity on admission and functional outcome in acute ischemic stroke with atrial fibrillation (AF). Between September 2011 and April 2014, we retrospectively extracted consecutive ischemic stroke patients with AF whose pre-admission modified Rankin Scale (mRS) score was 2 or less from our prospective database. Pre-admission CHADS2, CHA2DS2-VASc, and R2CHADS2 scores were calculated in each patient, and their association with the National Institutes of Health Stroke Scale (NIHSS) score on admission or unfavorable outcome (mRS ≥ 3 at 3 months from the onset) was assessed. A total of 344 patients (189 were men; age, 77.7 ± 10.0 years) were included in the analysis. The median pre-admission CHADS2, CHA2DS2-VASc, and R2CHADS2 scores were 2, 4, and 4, respectively. NIHSS score on admission was positively correlated with pre-admission CHADS2 (ρ = .116, P = .031), CHA2DS2-VASc (ρ = .166, P = .020), and R2CHADS2 scores (ρ = .106, P = .049). Receiver operating characteristic (ROC) curve analysis revealed that pre-admission CHADS2 score of 2 or more (sensitivity, 80%; specificity, 45%; area under the ROC curve [AUC], .654), CHA2DS2-VASc score of 3 or more (sensitivity, 86%; specificity, 44%; AUC, .683), and R2CHADS2 score of 4 or more (sensitivity, 61%; specificity, 62%; AUC, .657) were associated with unfavorable outcome. The pre-admission CHA2DS2-VASc score was better than the pre-admission CHADS2 score in estimating unfavorable outcome (P = .017). In multivariate analysis, cutoffs of these scores, female sex, higher NIHSS score, and internal carotid artery occlusion were associated with unfavorable outcome. Pre-admission CHADS2, CHA2DS2-VASc, and R2CHADS2 scores were associated with onset severity and functional outcome in acute ischemic stroke with AF. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Sonographic stroke templates.

    PubMed

    Govaert, Paul

    2009-10-01

    This chapter provides arterial and venous stroke templates, designed with neonatal brain ultrasound as the viewpoint and adult stroke templates as the basis. Images change with maturation of the stages of infarction: swelling, necrosis, organisation and tissue loss. Adult templates permit recognition of well-delineated stroke types observed in the newborn brain. All circle of Willis arteries can be involved, as can their perforator branches. Middle cerebral artery (MCA) truncal stroke (anterior or posterior) is an important entity, with different prognosis than complete MCA stroke. Knowledge of these templates also aids in the definition of combinations of infarction (e.g. internal carotid artery stroke or pial plus perforator stroke) and of interarterial watershed injury. Venous templates, even if still under development around the time of birth, permit us to understand brain injury associated with sinus or deep vein thrombosis, especially several types of intracranial haemorrhage. Hindbrain stroke templates are scarcely applied to perinatal lesions.

  6. Analytical and Experimental Investigation of Process Loads on Incremental Severe Plastic Deformation

    NASA Astrophysics Data System (ADS)

    Okan Görtan, Mehmet

    2017-05-01

    From the processing point of view, friction is a major problem in the severe plastic deformation (SPD) using equal channel angular pressing (ECAP) process. Incremental ECAP can be used in order to optimize frictional effects during SPD. A new incremental ECAP has been proposed recently. This new process called as equal channel angular swaging (ECAS) combines the conventional ECAP and the incremental bulk metal forming method rotary swaging. ECAS tool system consists of two dies with an angled channel that contains two shear zones. During ECAS process, two forming tool halves, which are concentrically arranged around the workpiece, perform high frequency radial movements with short strokes, while samples are pushed through these. The oscillation direction nearly coincides with the shearing direction in the workpiece. The most important advantages in comparison to conventional ECAP are a significant reduction in the forces in material feeding direction plus the potential to be extended to continuous processing. In the current study, the mechanics of the ECAS process is investigated using slip line field approach. An analytical model is developed to predict process loads. The proposed model is validated using experiments and FE simulations.

  7. Transcranial magnetic stimulation in mild to severe hemiparesis early after stroke: a proof of principle and novel approach to improve motor function

    PubMed Central

    Anjos, Sarah M.; Saposnik, Gustavo; Mello, Eduardo A.; Nagaya, Erina M.; Santos, Waldyr; Ferreiro, Karina N.; Melo, Eduardo S.; Reis, Felipe I.; Scaff, Milberto; Cohen, Leonardo G.

    2016-01-01

    Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can enhance function of the paretic hand in patients with mild motor impairment. Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown. In this pilot, randomized, double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpatient customary rehabilitation, in 30 patients within 5–45 days after ischemic stroke, and mild to severe hand paresis. The primary feasibility outcome was compliance with the interventions. The primary safety outcome was the proportion of intervention-related adverse events. Performance of the paretic hand in the Jebsen–Taylor test and pinch strength were secondary outcomes. Outcomes were assessed at baseline, after ten sessions of treatment administered over 2 weeks and at 1 month after end of treatment. Baseline clinical features were comparable across groups. For the primary feasibility outcome, compliance with treatment was 100% in the active group and 94% in the sham group. There were no serious intervention-related adverse events. There were significant improvements in performance in the Jebsen–Taylor test (mean, 12.3% 1 month after treatment) and pinch force (mean, 0.5 Newtons) in the active group, but not in the sham group. Low-frequency rTMS to the contralesional motor cortex early after stroke is feasible, safe and potentially effective to improve function of the paretic hand, in patients with mild to severe hemiparesis. These promising results will be valuable to design larger randomized clinical trials. PMID:22173953

  8. 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

  9. Motor unit rate coding is severely impaired during forceful and fast muscular contractions in individuals post stroke.

    PubMed

    Chou, Li-Wei; Palmer, Jacqueline A; Binder-Macleod, Stuart; Knight, Christopher A

    2013-06-01

    Information regarding how motor units are controlled to produce forces in individuals with stroke and the mechanisms behind muscle weakness and movement slowness can potentially inform rehabilitation strategies. The purpose of this study was to describe the rate coding mechanism in individuals poststroke during both constant (n = 8) and rapid (n = 4) force production tasks. Isometric ankle dorsiflexion force, motor unit action potentials, and surface electromyography were recorded from the paretic and nonparetic tibialis anterior. In the paretic limb, strength was 38% less and the rate of force development was 63% slower. Linear regression was used to describe and compare the relationships between motor unit and electromyogram (EMG) measures and force. During constant force contractions up to 80% maximal voluntary contraction (MVC), rate coding was compressed and discharge rates were lower in the paretic limb. During rapid muscle contractions up to 90% MVC, the first interspike interval was prolonged and the rate of EMG rise was less in the paretic limb. Future rehabilitation strategies for individuals with stroke could focus on regaining these specific aspects of motor unit rate coding and neuromuscular activation.

  10. 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.

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

    PubMed

    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.

  12. 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. PMID:27346996

  13. 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 © 1997-2017 - The Internet Stroke Center. All rights reserved. The information contained ...

  14. 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.

  15. Content of conventional therapy for the severely affected arm during subacute rehabilitation after stroke: An analysis of physiotherapy and occupational therapy practice.

    PubMed

    de Jong, Lex D; van Wijck, Frederike; Stewart, Roy E; Geurts, Alexander C H; Dijkstra, Pieter U

    2017-01-16

    Physiotherapy (PT) and occupational therapy (OT) are key professions providing treatment for the arm after stroke; however, knowledge about the content of these treatments is scant. Detailed data are needed to replicate interventions, evaluate their effective components, and evaluate PT and OT practice. This paper describes PT and OT treatment for the severely affected arm in terms of duration, content according to components and categories of the International Classification of Human Functioning, Disability and Health, and to analyze differences between professions. Design: This is a retrospective analysis of randomized trial data. 46 patients after stroke with poor arm motor control recruited from inpatient neurological units from three rehabilitation centers in the Netherlands. PTs and OTs recorded duration and content of arm treatment interventions for 8 weeks using a bespoke treatment schedule with 15 International Classification of Human Functioning, Disability and Health categories. PTs and OTs spent on average 4-7 min per treatment session (30 min) on arm treatment. OTs spent significantly more time providing arm treatment and treatment at the activities level than PTs. PTs spent 79% of their arm treatment time on body functions, OTs 41%. OTs spent significantly more time on "moving around using transportation," "self care," and "household tasks" categories. Patients after stroke with a severely affected arm and an unfavorable prognosis for arm motor recovery receive little arm-oriented PT and OT. Therapists spent most arm treatment time on body functions. There was a considerable overlap in the content of PT and OT in 12 of the 15 categories. Results can be generalized only to patients with poor arm motor control and may not represent practice in other countries. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Effect on arm function and cost of robot-assisted group therapy in subacute patients with stroke and a moderately to severely affected arm: a randomized controlled trial.

    PubMed

    Hesse, Stefan; Heß, Anke; Werner C, Cordula; Kabbert, Nadine; Buschfort, Rüdiger

    2014-07-01

    To evaluate the effectiveness and efficiency of robot-assisted arm group therapy (RAGT) versus individual arm therapy (IAT) to restore motor function in the moderately to severely affected patient after stroke. Single blind randomized controlled trial. Two in-patient neurological rehabilitation centers. Fifty first time subacute patients with stroke and a non-functional hand. The patients practiced either 30 minutes of RAGT + 30 minutes of IAT (group A) or 2x30 minutes of IAT (group B), per workday for four weeks. The RAGT consisted of six workstations enabling repetitive practice of finger, wrist, forearm and shoulder movements. Patients practiced according to their impairment level on at least two workstations per session. The IAT followed the Motor Relearning Programme, enriched by elements of the impairment-oriented training. Changes of the Fugl Meyer Score (FM, 0-66) between baseline and after 4 weeks, incremental cost effectiveness. Patients were homogeneous at study onset. All patients improved their upper limb motor function over time, but there were no between group differences. The initial (terminal) FM scores were 14.6±9.4 (25.7±16.5) in group A and 16.5±9.8 (31.1±19.1) in group B. The treatment of a single patient with RAGT cost 4.15 €, compared to 10.00 € for a patient to receive IAT. RAGT in combination with IAT was equally effective as a double session of IAT regarding the restoration of upper limb motor functions in moderate to severely affected subacute patients with stroke. The treatment costs for RAGT were less. © The Author(s) 2014.

  17. Psychoneuroimmunology of stroke.

    PubMed

    Skinner, Robert; Georgiou, Rachel; Thornton, Peter; Rothwell, Nancy

    2009-05-01

    Stroke is the major cause of disability in the Western world and is the third greatest cause of death, but there are no widely effective treatments to prevent the devastating effects of stroke. Extensive and growing evidence implicates inflammatory and immune processes in the occurrence of stroke and particularly in the subsequent injury. Several inflammatory mediators have been identified in the pathogenesis of stroke including specific cytokines, adhesion molecules, matrix metalloproteinases, and eicosanoids. An early clinical trial suggests that inhibiting interleukin-1 may be of benefit in the treatment of acute stroke.

  18. 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

  19. New thrombolytic strategy providing neuroprotection in experimental ischemic stroke: MMP10 alone or in combination with tissue-type plasminogen activator.

    PubMed

    Roncal, Carmen; Martinez de Lizarrondo, Sara; Salicio, Agustina; Chevilley, Arnaud; Rodriguez, Jose A; Rosell, Anna; Couraud, Pierre-Olivier; Weksler, Babette; Montaner, Joan; Vivien, Denis; Páramo, Jose A; Orbe, Josune

    2017-08-01

    Early reperfusion with tissue-type plasminogen activator (tPA) is an effective therapeutic strategy to treat acute ischemic stroke, but only 1/3 of tPA-treated patients recover and are free from disability. tPA has also shown neurotoxicity in experimental models of cerebral ischemia. Considering that MMP-10 improves stroke injury, we have examined the therapeutic and protective effect of MMP10 and tPA/MMP10 as clot-dissolving and neuroprotective agent in an experimental model of ischemic stroke and studied in vitro the molecular pathways involved in MMP10-mediated effects. Cerebral ischemia was induced by the local injection of thrombin into the middle cerebral artery followed by reperfusion with MMP10 (6.5 µg/kg) and tPA (10 mg/kg) alone or in combination with MMP10. Cell cultures were also performed to determine the effect of MMP10 and tPA/MMP10 on brain endothelial cells and neurons. tPA/MMP10 significantly reduced the infarct size in the ischemic stroke model compared with tPA alone (P < 0.05). In vitro, MMP10 reduced the tPA-promoted endothelial ionic permeability, preserved the expression of claudin-5 and decreased ERK1/2 activation. Moreover, combination of tPA/MMP10 prevented tPA-mediated neuronal excitotoxicity and calcium influx. These effects were reversed by blocking MMP10 activity with a monoclonal antibody. These results show that MMP10, either alone or in combination with tPA, might represent a new strategy for thrombolysis in ischemic stroke, providing higher protection against cerebrovascular damage.

  20. Embolic Stroke due to a Common Carotid Artery Thrombus in a Young Patient with Severe Iron-Deficiency Anemia without Thrombocytosis

    PubMed Central

    2016-01-01

    This case report describes a 41-year-old previously healthy male who presented with stuttering transient ischemic symptoms and radiographic evidence of a left common carotid artery thrombus as well as acute and subacute ischemic infarcts in the left middle cerebral artery territory. An exhaustive stroke work-up did not provide a plausible etiology for his symptoms. His complete blood count and iron studies, however, revealed evidence of severe iron-deficiency anemia without reactive thrombocytosis. His stool guaiac test was positive. He was discharged home on oral antithrombotic agents and aggressive iron replacement therapy with a plan for repeat vascular imaging in 3 months and a colonoscopy. This case report suggests that severe iron-deficiency anemia with or without reactive thrombocytosis should be viewed as a possible hematologic condition associated with thrombotic tendencies and a risk factor for ischemic stroke, especially in young adults. Aggressive iron supplementation and short-term antithrombotic therapy with follow-up vascular imaging are a reasonable treatment for these patients. PMID:27752375

  1. Decreased expression of brain-derived neurotrophic factor in BDNF(+/-) mice is associated with enhanced recovery of motor performance and increased neuroblast number following experimental stroke.

    PubMed

    Nygren, Josefine; Kokaia, Merab; Wieloch, Tadeusz

    2006-08-15

    Brain-derived neurotrophic factor (BDNF) is involved in brain plasticity and neuronal survival. Generally, BDNF enhances synaptic activity and neurite growth, although the effect of BDNF on neuronal survival and brain plasticity following injury is equivocal. Housing rats in an enriched environment after experimental stroke enhances recovery of sensory-motor function, which is associated with a decrease in the BDNF mRNA and protein levels. We used BDNF(+/-) mice and wild-type littermate mice to investigate whether the decrease in the brain levels of BDNF affected motor function or infarct volume following transient occlusion of the middle cerebral artery (tMCAO) for 40 min. We found that the BDNF(+/-) mice had a significantly improved motor function on the rotating pole test 2 weeks after tMCAO compared with wild-type mice. When intermittently exposed to an enriched environment following tMCAO, the wild-type mice improved motor function to the same degree as BDNF(+/-) mice. There was no effect of BDNF reduction on infarct volume. Neurogenesis is induced following experimental stroke, and in the striatum of BDNF(+/-) mice significantly increased numbers of neuroblasts compared with wild-type mice were seen, both in standard and in enriched conditions. We conclude that decreasing brain levels of BDNF enhances the recovery of function following experimental stroke.

  2. The severity of experimental arthritis is independent of IL-36 receptor signaling.

    PubMed

    Lamacchia, Céline; Palmer, Gaby; Rodriguez, Emiliana; Martin, Praxedis; Vigne, Solenne; Seemayer, Christian A; Talabot-Ayer, Dominique; Towne, Jennifer E; Gabay, Cem

    2013-03-01

    Interleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36α, IL-36β, and IL-36γ, that bind to the IL-36 receptor (IL-36R). IL-36 exerts proinflammatory effects in skin and lung and stimulates T cell responses. In the present study, we examined the expression and function of IL-36R and its ligands in experimental arthritis. Collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and K/BxN serum transfer-induced arthritis were induced according to standard protocols. Messenger RNA levels for IL-36R and its ligands in the joints of mice with CIA were determined by RT-qPCR. Mice with CIA were injected with a blocking monoclonal anti-IL-36R, a blocking anti-IL-1RI, or their isotype-matched control antibodies at the time of arthritis onset. Anti-IL-36R or control antibodies were also injected at the time of AIA induction. Finally, IL-36R-deficient mice were examined in AIA and serum transfer-induced arthritis. The development and severity of arthritis were assessed by clinical and histological scoring. IL-36R, IL-36Ra and IL-36γ mRNA were detected in the joints of mice with CIA, but their levels did not correlate with arthritis severity. As opposed to anti-IL-1RI antibody treatment, the injection of an anti-IL-36R antibody was devoid of effect on the development and severity of CIA. The severity of joint inflammation and structural damage in AIA was also unaltered by anti-IL-36R antibody treatment. Finally, the severity of AIA and K/BxN serum transfer-induced arthritis was similar in IL-36R-deficient and wild-type mice. The development and severity of experimental arthritis are independent of IL-36R signaling.

  3. The severity of experimental arthritis is independent of IL-36 receptor signaling

    PubMed Central

    2013-01-01

    Introduction Interleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36α, IL-36β, and IL-36γ, that bind to the IL-36 receptor (IL-36R). IL-36 exerts proinflammatory effects in skin and lung and stimulates T cell responses. In the present study, we examined the expression and function of IL-36R and its ligands in experimental arthritis. Methods Collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and K/BxN serum transfer-induced arthritis were induced according to standard protocols. Messenger RNA levels for IL-36R and its ligands in the joints of mice with CIA were determined by RT-qPCR. Mice with CIA were injected with a blocking monoclonal anti-IL-36R, a blocking anti-IL-1RI, or their isotype-matched control antibodies at the time of arthritis onset. Anti-IL-36R or control antibodies were also injected at the time of AIA induction. Finally, IL-36R-deficient mice were examined in AIA and serum transfer-induced arthritis. The development and severity of arthritis were assessed by clinical and histological scoring. Results IL-36R, IL-36Ra and IL-36γ mRNA were detected in the joints of mice with CIA, but their levels did not correlate with arthritis severity. As opposed to anti-IL-1RI antibody treatment, the injection of an anti-IL-36R antibody was devoid of effect on the development and severity of CIA. The severity of joint inflammation and structural damage in AIA was also unaltered by anti-IL-36R antibody treatment. Finally, the severity of AIA and K/BxN serum transfer-induced arthritis was similar in IL-36R-deficient and wild-type mice. Conclusions The development and severity of experimental arthritis are independent of IL-36R signaling. PMID:23452551

  4. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Incidence and severity of shoulder pain does not increase with the use of circuit class therapy during inpatient stroke rehabilitation: a controlled trial.

    PubMed

    English, Coralie; Hillier, Susan; Stiller, Kathy

    2008-01-01

    Does circuit class therapy result in a greater incidence or severity of shoulder pain compared with individual therapy? Is the incidence influenced by the degree of active shoulder control? Controlled trial with intention-to-treat analysis. Sixty-eight people (6 drop-outs) undergoing inpatient rehabilitation after stroke. Participants received either individual therapy or group circuit class therapy. Incidence of shoulder pain over the previous 24 hours was measured as a yes/no response while severity of shoulder pain was measured using a visual analogue scale at admission, Week 4, and discharge. There was no greater chance of participants receiving circuit class therapy having shoulder pain at Week 4 (OR 0.95, 95% CI 0.32 to 2.80) or discharge (OR 0.38, 95% CI 0.11 to 1.45) than participants receiving individual therapy. Of those participants who reported pain, there was no difference between groups in the severity of pain at Week 4 (mean difference -0.2 cm, 95% CI -3.2 to 2.7) or discharge (mean difference -2.1 cm, 95% CI -4.8 to 0.6). There was a greater chance of participants who had no active shoulder control having shoulder pain at Week 4 (OR 5.8, 95% CI 1.6 to 20.4) and at discharge (OR 3.8, 95% CI 1.0 to 13.9) than participants who had active shoulder control. The incidence and severity of shoulder pain was influenced by degree of active shoulder control but not by type of physiotherapy service delivery. Concerns regarding shoulder pain should not be a barrier to the implementation of circuit class therapy during inpatient stroke rehabilitation.

  6. Secondary stroke prevention.

    PubMed

    Hankey, Graeme J

    2014-02-01

    Survivors of stroke and transient ischaemic attacks are at risk of a recurrent stroke, which is often more severe and disabling than the index event. Optimum secondary prevention of recurrent stroke needs rapid diagnosis and treatment and prompt identification of the underlying cardiovascular cause. Effective treatments include organised acute assessment and intervention with antithrombotic therapy, carotid revascularisation, and control of causal risk factors, as appropriate. However, effective treatments are not implemented optimally in clinical practice. Recurrent strokes continue to account for 25-30% of all strokes and represent unsuccessful secondary prevention. Immediate and sustained implementation of effective and appropriate secondary prevention strategies in patients with first-ever stroke or transient ischaemic attack has the potential to reduce the burden of stroke by up to a quarter.

  7. 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.

  8. Comparison of joint space and end point space robotic training modalities for rehabilitation of interjoint coordination in individuals with moderate to severe impairment from chronic stroke.

    PubMed

    Brokaw, Elizabeth B; Holley, Rahsaan J; Lum, Peter S

    2013-09-01

    We have developed a novel robotic modality called Time Independent Functional Training (TIFT) that provides focused retraining of interjoint coordination after stroke. TIFT was implemented on the ARMin III exoskeleton and provides joint space walls that resist movement patterns that are inconsistent with the targeted interjoint coordination pattern. In a single test session, ten moderate to severely impaired individuals with chronic stroke practiced synchronous shoulder abduction and elbow extension in TIFT and also in a comparison mode commonly used in robotic therapy called end point tunnel training (EPTT). In EPTT, error is limited by forces applied to the hand that are normal to the targeted end point trajectory. The completion percentage of the movements was comparable between modes, but the coordination patterns used by subjects differed between modes. In TIFT, subjects performed the targeted pattern of synchronous shoulder abduction and elbow extension, while in EPTT, movements were completed with compensatory strategies that incorporated the flexor synergy (shoulder abduction with elbow flexion) or the extensor synergy (shoulder adduction with elbow extension). There were immediate effects on free movements, with TIFT resulting in larger improvements in interjoint coordination than EPTT. TIFT's ability to elicit normal coordination patterns merits further investigation into the effects of longer duration training.

  9. Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial.

    PubMed

    Andrade, Suellen M; Batista, Larissa M; Nogueira, Lídia L R F; de Oliveira, Eliane A; de Carvalho, Antonio G C; Lima, Soriano S; Santana, Jordânia R M; de Lima, Emerson C C; Fernández-Calvo, Bernardino

    2017-01-01

    Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex) combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence) after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561).

  10. Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial

    PubMed Central

    Batista, Larissa M.; Nogueira, Lídia L. R. F.; de Oliveira, Eliane A.; de Carvalho, Antonio G. C.; Lima, Soriano S.; Santana, Jordânia R. M.; de Lima, Emerson C. C.; Fernández-Calvo, Bernardino

    2017-01-01

    Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex) combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence) after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561). PMID:28250992

  11. Transplantation of post-mitotic human neuroteratocarcinoma-overexpressing Nurr1 cells provides therapeutic benefits in experimental stroke: in vitro evidence of expedited neuronal differentiation and GDNF secretion.

    PubMed

    Hara, Koichi; Matsukawa, Noriyuki; Yasuhara, Takao; Xu, Lin; Yu, Guolong; Maki, Mina; Kawase, Takeshi; Hess, David C; Kim, Seung U; Borlongan, Cesar V

    2007-05-01

    Nurr1 has been implicated as a transcription factor mediating the endogenous neuroprotective mechanism against stroke. We examined the in vivo and in vitro properties of a new human embryonic carcinoma Ntera-2 cell line carrying the human Nurr1 gene (NT2N.Nurr1). Adult Sprague-Dawley rats underwent experimental stroke initially and 14 days later were assigned randomly to receive stereotaxic transplantation of NT2N.Nurr1 cells or infusion of vehicle into their ischemic striatum. Transplantation of NT2N.Nurr1 cells promoted significant attenuation of behavioral impairments over a 56-day period after stroke, characterized by decreased hyperactivity, biased swing activity, and neurologic deficits, as well as significant reduction in ischemic striatal cell loss compared to vehicle-infused stroke animals. Transplanted NT2N.Nurr1 cells survived and expressed neuronal phenotypic markers in the ischemic striatum. In vitro results showed that cultured NT2.Nurr1 cells were already negative for nestin even before retinoic acid treatment, despite strong nestin immunoreactivity in NT2 cells. This indicates Nurr1 triggered a rapid commitment of NT2 cells into a neuronal lineage. Indeed, NT2.Nurr1 cells, at 4 weeks into RA treatment, displayed more abundant tyrosine hydroxylase positive cells than NT2 cells. Parallel ELISA studies showed further that cultured NT2N.Nurr1, but not NT2N cells, secreted glial cell derived neurotrophic factor. The present study shows efficacy of NT2N.Nurr1 cell grafts in ischemic stroke, with in vitro evidence suggesting the cells' excellent neuronal differentiation capability and ability to secrete GDNF as likely mechanisms mediating the observed therapeutic benefits. (c) 2007 Wiley-Liss, Inc.

  12. 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.

  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. Burden of stroke in Estonia.

    PubMed

    Kõrv, Janika; Vibo, Riina

    2013-07-01

    Estonia is the smallest of the three Baltic countries. The decline in incidence of first-ever stroke during the 1990s has left Tartu, Estonia with a relatively low stroke incidence. However, the incidence rates for younger age groups, and the 28-day case fatality rate are higher compared with several other studies. Developments in the national health care system in recent years have been positive: the decline of mortality rate of stroke in Estonia is greater than the European Union average. However, the mortality of cardiovascular diseases is higher compared with several European countries. The prevalence of most stroke risk factors is comparable with European Union countries, while atrial fibrillation is somewhat more frequent (30%) among the patients having suffered from ischemic stroke. The management of stroke in Estonia has been in accordance with European and national stroke guidelines. Stroke units are organized in regional and central hospitals in bigger cities. A well-developed and free ambulance service, and a high priority of stroke code, enable a quick transportation of patients to the nearest hospital providing thrombolytic therapy. The number of thrombolyzed stroke cases has increased since 2003. The Estonian Stroke Initiative was founded in 2008 to improve stroke care, promote regional networks, and increase stroke knowledge among the general population and medical professionals. Since then, several activities regarding stroke awareness have been organized.

  15. Gonadotropin-releasing hormone reduces the severity of experimental autoimmune encephalomyelitis, a model of multiple sclerosis.

    PubMed

    Quintanar, J Luis; Salinas, Eva; Quintanar-Stephano, Andrés

    2011-02-01

    It has been reported that the spinal cord possesses Gonadotropin-releasing hormone (GnRH) receptor and that GnRH has neurotrophic properties. Experimental autoimmune encephalomyelitis (EAE) causes neurodegeneration in spinal cord. Thus, the present study was designed to determine whether administration of GnRH reduces the severity of EAE. The clinical signs of locomotion, axonal morphometry and neurofilaments (NFs) expression were evaluated. Clinical signs remained significantly lower in EAE rats with GnRH administration compared to animals without treatment. Morphometric analysis, there were more axons of larger areas in the spinal cord of EAE+GnRH group compared to EAE animals. Western blot analysis demonstrated that GnRH administration significantly increased the expression of NFs of 68, 160 and 200kDa in the spinal cord of EAE animals. Our results indicate that GnRH administration reduces the severity of EAE in the rat.

  16. 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

  17. 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

  18. 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

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

    2012-05-09

    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

  19. [Effects of essential periodontal treatment on serum level of sCD40L and periodontal clinical parameters in patients with moderate to severe periodontitis at high risk of stroke].

    PubMed

    Gao, Lei; Sun, Xiao-Ju; Xie, Hong; Nan, Shun-Hua; Xie, Hui-Xin

    2016-10-01

    To investigate the effect of periodontal treatment on patients with moderate to severe periodontitis at high risk of stroke, by detecting the level of serum soluble cell differentiation antigen 40 ligand (sCD40L) before and after periodontal non-surgical treatment. Seventy-six patients with moderate to severe periodontitis at high risk of stroke were collected and randomly divided into 2 groups, 40 patients in group A received essential periodontal treatment + routine maintenance therapy, 36 cases in group B only received routine maintenance therapy. Another 36 patients with moderate and severe periodontitis were selected as group C, and received essential periodontal treatment. Bleeding on probing (BOP), periodontal probing depth (PD) and attachment loss (AL) in 6 loci were examined by the same dentists, and enzyme linked immunosorbent assay (ELISA) was used to detect the level of serum sCD40L before treatment and 3 months after treatment. The data were analyzed by SPSS 17.0 software package. Compared with pre-treatment, serum level of sCD40L and periodontal clinical indexes of the three groups decreased. Compared with group B, serum SCD40L in group A significantly decreased(P<0.05). Periodontal treatment can reduce the serum level of sCD40L in patients with moderate to severe periodontitis at high risk of stroke, and improve the patient's inflammatory state. To a certain extent, periodontal treatment may reduce the risk of high-risk stroke population to develop stroke.

  20. High phosphate serum levels correlate with the severity of experimental severe acute pancreatitis: insight into the purinergic system.

    PubMed

    Mazzini, Guilherme S; Jost, Daniel T; Ramos, Denise B; Oses, Jean P; Zeni, Mateus A; Machoseki, Rafael; Kist, Luiza W; Bogo, Mauricio R; Bonan, Carla D; Edelweiss, Maria I; Duarte, Marta M; Portela, Luis V; Souza, Diogo O; Osvaldt, Alessandro B

    2015-05-01

    Extracellular purines are a component of the systemic inflammatory response, and their levels are modulated by ectonucleotidases. In addition, nucleotide hydrolysis releases phosphate. We studied serum phosphate levels as a predictor of severity in acute pancreatitis (AP) and their correlation with extracellular purinergic metabolism. Acute pancreatitis was induced by the retrograde injection of sodium taurocholate. The AP group was compared with animals submitted to a model of sepsis by cecal ligation and puncture. The sham group was submitted to laparotomy and closure. We measured the phosphate and purine levels in serum and the expression of 5'-nucleotidase (CD73) and the adenosine A2a receptor in pancreatic tissue by quantitative real-time polymerase chain reaction. Serum phosphate levels were higher in severe AP and correlated with severity. Severe AP led to increased serum levels of adenosine diphosphate, adenosine monophosphate, and adenosine. In addition, adenosine monophosphate conversion to adenosine in serum was accelerated in the AP groups. We found a positive correlation between serum adenosine and phosphate in the AP groups. The expression levels of CD73 and the adenosine A2a receptor in the pancreas were not altered. Our study suggests that serum phosphate correlates with severity in AP and implicates extracellular purines in the systemic response to severe AP.

  1. N-acetylaspartate decrease in acute stage of ischemic stroke: a perspective from experimental and clinical studies.

    PubMed

    Igarashi, Hironaka; Suzuki, Yuji; Huber, Vincent J; Ida, Masahiro; Nakada, Tsutomu

    2015-01-01

    N-acetylaspartate (NAA) appears in a prominent peak in proton magnetic resonance spectroscopy ((1)H-MRS) of the brain. Exhibition by NAA of time-dependent attenuation that reflects energy metabolism during the acute stage of cerebral ischemia makes this metabolite a unique biomarker for assessing ischemic stroke. Although magnetic resonance (MR) imaging is a powerful technique for inspecting the pathological changes that occur during ischemic stroke, biomarkers that directly reflect the drastic metabolic changes associated with acute-stage ischemia are strongly warranted for appropriate therapeutic decision-making in daily clinical settings. In this review, we provide a brief overview of NAA metabolism and focus on the use of attenuation in NAA as a means for assessing the pathophysiological changes that occur during the acute stage of ischemic stroke.

  2. Influences of stand structure and fuel treatments on wildfire severity at Blacks Mountain Experimental Forest, northeastern California

    Treesearch

    Julie N. Symons; Dean H. K. Fairbanks; Carl N. Skinner

    2008-01-01

    This study utilizes forest stand structures and fuel profiles to evaluate the influence of different types of silvicultural treatments on fire severity in the Blacks Mountain Experimental Forest (BMEF), located within Lassen National Forest of northeastern California. We compare the severity of fire, assessed based on tree crown and bole scorch on 100 ha experimental...

  3. 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 ...

  4. Stroke Rehabilitation

    MedlinePlus

    A stroke can cause lasting brain damage. People who survive a stroke need to relearn skills they lost because of ... them relearn those skills. The effects of a stroke depend on which area of the brain was ...

  5. 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, ...

  6. Improving public education about stroke.

    PubMed

    Alberts, Mark J

    2012-09-01

    Stroke is a common and serious disease. Most studies have shown that basic public knowledge about what a stroke is, symptoms of a stroke, and the proper reaction to a stroke is quite deficient. The fact that a stroke affects cognitive, communicative, and motor functions may partially explain the poor reaction to acute stroke symptoms. Several educational studies, using diverse formats and messaging paradigms, have been shown to positively affect public knowledge of stroke symptoms. Such efforts have often used mass media public education campaigns with an emphasis on recognizing symptoms of an acute stroke. Some have been able to demonstrate an increase in the chance of patients (or by-standers) calling 911 and seeking emergency care. However, many programs were of brief duration, and their long-term benefits are uncertain. Continual educational efforts will be needed to improve stroke knowledge and increase the percentage of patients who seek emergency care. © 2012 New York Academy of Sciences.

  7. Thiamet G mediates neuroprotection in experimental stroke by modulating microglia/macrophage polarization and inhibiting NF-κB p65 signaling.

    PubMed

    He, Yating; Ma, Xiaofeng; Li, Daojing; Hao, Junwei

    2016-01-01

    Inflammatory responses are accountable for secondary injury induced by acute ischemic stroke (AIS). Previous studies indicated that O-GlcNAc modification (O-GlcNAcylation) is involved in the pathology of AIS, and increase of O-GlcNAcylation by glucosamine attenuated the brain damage after ischemia/reperfusion. Inhibition of β-N-acetylglucosaminidase (OGA) with thiamet G (TMG) is an alternative option for accumulating O-GlcNAcylated proteins. In this study, we investigate the neuroprotective effect of TMG in a mouse model of experimental stroke. Our results indicate that TMG administration either before or after middle cerebral artery occlusion (MCAO) surgery dramatically reduced infarct volume compared with that in untreated controls. TMG treatment ameliorated the neurological deficits and improved clinical outcomes in neurobehavioral tests by modulating the expression of pro-inflammatory and anti-inflammatory cytokines. Additionally, TMG administration reduced the number of Iba1(+) cells in MCAO mice, decreased expression of the M1 markers, and increased expression of the M2 markers in vivo. In vitro, M1 polarization of BV2 cells was inhibited by TMG treatment. Moreover, TMG decreased the expression of iNOS and COX2 mainly by suppressing NF-κB p65 signaling. These results suggest that TMG exerts a neuroprotective effect and could be useful as an anti-inflammatory agent for ischemic stroke therapy.

  8. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. 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.

  10. Hypercoagulable states and strokes.

    PubMed

    Matijevic, Nena; Wu, Kenneth K

    2006-07-01

    Several hematologic disorders and hemostatic defects increase risk of ischemic stroke. A common feature of these disorders is the creation of a prothrombotic state, now commonly referred to as "hypercoagulable state." Hematologic diseases such as essential thrombocythemia, polycythemia vera, and thrombotic thrombocytopenic purpura clearly cause stroke. Effective treatment is now available for these disorders. Association of hemostatic defects with stroke risk is still at the investigational stage. Although a number of factors such as soluble thrombomodulin, fibrinogen, factor VIII, von Willebrand factor, and plasminogen activator inhibitor-1 are associated with stroke risk, their predictive values remain unknown. Furthermore, causal relationship has not been established.

  11. 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…

  12. 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…

  13. The effect of a haptic biofeedback system on postural control in patients with stroke: An experimental pilot study.

    PubMed

    Yasuda, Kazuhiro; Kaibuki, Naomi; Harashima, Hiroaki; Iwata, Hiroyasu

    2017-06-01

    Impaired balance in patients with hemiparesis caused by stroke is frequently related to deficits in the central integration of afferent inputs, and traditional rehabilitation reinforces excessive visual reliance by focusing on visual compensation. The present study investigated whether a balance task involving a haptic biofeedback (BF) system, which provided supplementary vibrotactile sensory cues associated with center-of-foot-pressure displacement, improved postural control in patients with stroke. Seventeen stroke patients were assigned to two groups: the Vibrotactile BF and Control groups. During the balance task (i.e., standing on a foam mat), participants in the Vibrotactile BF group tried to stabilize their postural sway while wearing the BF system around the pelvic girdle. In the Control group, participants performed an identical postural task without the BF system. Pre- and post-test measurements of postural control using a force plate revealed that the stability of bipedal posture in the Vibrotactile BF group was markedly improved compared with that in the Control group. A balance task involving a vibrotactile BF system improved postural stability in patients with stroke immediately. This confirms the potential of a haptic-based BF system for balance training, both in routine clinical practice and in everyday life.

  14. Chloroquine Treatment Enhances Regulatory T Cells and Reduces the Severity of Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Thomé, Rodolfo; Moraes, Adriel S.; Bombeiro, André Luis; Farias, Alessandro dos Santos; Francelin, Carolina; da Costa, Thiago Alves; Di Gangi, Rosária; dos Santos, Leonilda Maria Barbosa; de Oliveira, Alexandre Leite Rodrigues; Verinaud, Liana

    2013-01-01

    Background The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg) cells and suppressive Dendritic Cells (DCs), to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ), an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE), an experimental model for human Multiple Sclerosis, was investigated as well. Methodology/Principal Findings EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35–55) peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS) and increased frequency of Treg cells. Also, proliferation of MOG35–55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. Conclusion We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of EAE

  15. Dose-response relationship for exercise on severity of experimental osteoarthritis in rats: a pilot study.

    PubMed

    Galois, Laurent; Etienne, Stéphanie; Grossin, Laurent; Watrin-Pinzano, Astrid; Cournil-Henrionnet, Christel; Loeuille, Damien; Netter, Patrick; Mainard, Didier; Gillet, Pierre

    2004-10-01

    To investigate the influence of a calibrated exercise on the progression of structural lesions in an experimental model of osteoarthritis (OA) in the rat, and to explore the effect of exercise on the level of chondrocyte caspase-dependent apoptosis and of Hsp70. The OA model was induced by anterior cruciate ligament transection (ACLT). Rats were placed in 4 experimental groups: operated (ACLT) free moving rats, and 3 exercise groups (slight, moderate and intense) subjected to running training. Rats were killed 14 and 28 days after surgery. On D14 histological assessment demonstrated a beneficial influence of a slight and a moderate exercise vs control ACLT group. Hsp70 increased significantly in the moderate group vs controls. On D28, histological lesions strongly decreased in the slight and moderate exercise groups vs ACLT group, while an intense effort abolished this beneficial trend. Interestingly, the concomitant course of apoptotic events (caspase 3-positive cells) and the co-expression of Hsp70 in the various groups varied, when significant, in an inverse manner. In the intense group this overexpression was not noted, as a "burn out" appeared, thus leading to a loss of this protective effect. This study shows that a calibrated slight or moderate exercise exerts a beneficial influence on the severity of chondral lesions in ACLT rats. Conversely, a strong effort abolishes this chondroprotective effect. This effect could be related to a reduced level of chondrocyte apoptosis through anti-apoptotic capacities of stress-induced Hsp70 overexpression.

  16. Impairment-oriented training or Bobath therapy for severe arm paresis after stroke: a single-blind, multicentre randomized controlled trial.

    PubMed

    Platz, T; Eickhof, C; van Kaick, S; Engel, U; Pinkowski, C; Kalok, S; Pause, M

    2005-10-01

    To study the effects of augmented exercise therapy time for arm rehabilitation as either Bobath therapy or the impairment-oriented training (Arm BASIS training) in stroke patients with arm severe paresis. Single blind, multicentre randomized control trial. Three inpatient neurorehabilitation centres. Sixty-two anterior circulation ischaemic stroke patients. Random assignment to three group: (A) no augmented exercise therapy time, (B) augmented exercise therapy time as Bobath therapy and (C) augmented exercise therapy time as Arm BASIS training. Fugl-Meyer arm motor score. Secondary measure: Action Research Arm Test (ARA). Ancillary measures: Fugl-Meyer arm sensation and joint motion/pain scores and the Ashworth Scale (elbow flexors). An overall effect of augmented exercise therapy time on Fugl-Meyer scores after four weeks was not corroborated (mean and 95% confidence interval (CI) of change scores: no augmented exercise therapy time (n=20) 8.8, 5.2-12.3; augmented exercise therapy time (n=40) 9.9, 6.8-13.9; p = 0.2657). The group who received the augmented exercise therapy time as Arm BASIS training (n=20) had, however, higher gains than the group receiving the augmented exercise therapy time as Bobath therapy (n=20) (mean and 95% CI of change scores: Bobath 7.2, 2.6-11.8; BASIS 12.6, 8.4-16.8; p = 0.0432). Passive joint motion/pain deteriorated less in the group who received BASIS training (mean and 95% CI of change scores: Bobath -3.2, -5.2 to -1.1; BASIS 0.1, -1.8-2.0; p = 0.0090). ARA, Fugl-Meyer arm sensation, and Ashworth Scale scores were not differentially affected. The augmented exercise therapy time as Arm BASIS training enhanced selective motor control. Type of training was more relevant for recovery of motor control than therapeutic time spent.

  17. 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. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. 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.

  19. Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis

    PubMed Central

    Alves da Costa, Thiago; Di Gangi, Rosária; Thomé, Rodolfo; Barreto Felisbino, Marina; Pires Bonfanti, Amanda; Lumi Watanabe Ishikawa, Larissa; Sartori, Alexandrina; Burger, Eva; Verinaud, Liana

    2016-01-01

    T cell maturation takes place within the thymus, a primary lymphoid organ that is commonly targeted during infections. Previous studies showed that acute infection with Paracoccidioides brasiliensis (Pb), the causative agent of paracoccidioidomycosis (PCM), promotes thymic atrophy that is associated with the presence of yeast cells in the organ. However, as human PCM is a chronic infection, it is imperative to investigate the consequences of Pb infection over the thymic structure and function in chronic infection. In this sense, we developed a new experimental model where Pb yeast cells are injected through the intraperitoneal route and mice are evaluated over 120 days of infection. Thymuses were analyzed in chronically infected mice and we found that the thymus underwent extensive morphological alterations and severe infiltration of P. brasiliensis yeast cells. Further analyses showed an altered phenotype and function of thymocytes that are commonly found in peripheral mature T lymphocytes. We also observed activation of the NLRP3 inflammasome in the thymus. Our data provide new information on the severe changes observed in the thymic microenvironment in a model of PCM that more closely mimics the human infection. PMID:27736987

  20. Experimental colitis delays and reduces the severity of collagen-induced arthritis in mice.

    PubMed

    Hablot, Julie; Peyrin-Biroulet, Laurent; Kokten, Tunay; El Omar, Reine; Netter, Patrick; Bastien, Claire; Jouzeau, Jean-Yves; Sokol, Harry; Moulin, David

    2017-01-01

    Amongst extraintestinal manifestations (EIM) occurring in IBD patients, rheumatologic manifestations are the most frequent. Understanding the relationships between arthritis and colitis is a prerequisite to improving the management of these patients. Microbiota of patients with IBD or rheumatologic diseases, like spondyloarthritis (SpA) is modified compared to healthy individual. Thus, we have evaluated the impact of colitis in the development of arthritis in mice and we have analyzed microbiota changes. Collagen-induced arthritis (CIA) was induced at day 0 in DBA1 mice exposed or not to Dextran Sodium Sulfate (DSS) to induce colitis between day 14 and day 21. Animals were monitored regularly for arthritis and colitis severity (clinical score, hindpaw edema). Fecal microbiota was studied by 16S rRNA deep sequencing at critical time points (D14, D14, D21 & D41). At day 41, histological scoring of the intestines and ankles were performed at the end of experiment. Induction of colitis slightly delayed arthritis onset (2 ± 1 days of delay) and reduced its severity (5.75 ± 1.62 in arthritis only group vs 4.00 ± 1.48 in arthritis + colitis group (p = 0.02 at day 28) macroscopically and histologically. In contrast, colitis severity was not influenced by arthritis development. Induction of colitis promoted a modification of microbiota composition and a decrease of α-diversity. Fecal microbiota composition was different between "colitis" and "arthritis+colitis" groups during colitis development. Interestingly a milder decrease of bacterial diversity in the "arthritis+colitis" group was observed. Concomitant experimental colitis protects mice against collagen-induced arthritis and this is associated with changes in gut microbiome composition.

  1. Experimental nowcasting and short-range forecasting of severe storms at the ESSL Testbed

    NASA Astrophysics Data System (ADS)

    Groenemeijer, Pieter; Holzer, Alois M.; Pistotnik, Georg; Riemann-Campe, Kathrin

    2013-04-01

    From 4 June to 6 July 2012, the first ESSL Testbed has taken place at the Research and Training Centre of the European Severe Storms Laboratory in Wiener Neustadt, Austria. During this time, researchers and forecasters worked closely together putting new forecast supporting products to the test. The Testbed's main activity is to prepare experimental forecasts for severe weather, of which short-range forecasts and nowcasts for the following 2 hours form an important part. These nowcasts are made using new tools based on NWP, radar and satellite, as well as surface and upper-air observations. Subsequently, a verification of the forecasts is performed using the European Severe Weather Database, followed by an evaluation of forecasting tools and techniques. Inspired by the annual Spring Program at NOAA's Hazardous Weather Testbed (HWT), the ESSL Testbed has a stronger focus on forecaster training than the HWT. Given the various backgrounds of the participants, an important Testbed goal is to acquaint its participants with severe weather forecasting methods and techniques that work universally. Among the tools that were evaluated at the 2012 Testbed were visualizations of high-resolution ensemble NWP (DWD's COSMO-DE-EPS), satellite-based cloud top cooling and overshooting top detection algorithms, lightning detection, and satellite and radar-based cell-tracking algorithms (DLR's Cb-TRAM and RadTRAM, and DWD's NowcastMix). In daily "Expert Lectures", that were broadcast online to remote participants, researchers provided background information on their products and internationally renowned experts in forecasting presented their viewpoints on storm forecasting and its scientific roots. Organized by ESSL in close cooperation with the Austrian Central Institute for Meteorology and Geodynamics (ZAMG), the Testbed was supported - among others - by the German Weather Service (DWD), EUMETSAT, WMO, ECMWF, VAISALA, and the GOES-R programme, providing products for evaluation and

  2. A pilot study of sensory feedback by transcutaneous electrical nerve stimulation to improve manipulation deficit caused by severe sensory loss after stroke

    PubMed Central

    2013-01-01

    Background Sensory disturbance is common following stroke and can exacerbate functional deficits, even in patients with relatively good motor function. In particular, loss of appropriate sensory feedback in severe sensory loss impairs manipulation capability. We hypothesized that task-oriented training with sensory feedback assistance would improve manipulation capability even without sensory pathway recovery. Methods We developed a system that provides sensory feedback by transcutaneous electrical nerve stimulation (SENS) for patients with sensory loss, and investigated the feasibility of the system in a stroke patient with severe sensory impairment and mild motor deficit. The electrical current was modulated by the force exerted by the fingertips so as to allow the patient to identify the intensity. The patient had severe sensory loss due to a right thalamic hemorrhage suffered 27 months prior to participation in the study. The patient first practiced a cylindrical grasp task with SENS for 1 hour daily over 29 days. Pressure information from the affected thumb was fed back to the unaffected shoulder. The same patient practiced a tip pinch task with SENS for 1 hour daily over 4 days. Pressure information from the affected thumb and index finger was fed back to the unaffected and affected shoulders, respectively. We assessed the feasibility of SENS and examined the improvement of manipulation capability after training with SENS. Results The fluctuation in fingertip force during the cylindrical grasp task gradually decreased as the training progressed. The patient was able to maintain a stable grip force after training, even without SENS. Pressure exerted by the tip pinch of the affected hand was unstable before intervention with SENS compared with that of the unaffected hand. However, they were similar to each other immediately after SENS was initiated, suggesting that the somatosensory information improved tip pinch performance. The patient’s manipulation

  3. Mechanisms of perinatal arterial ischemic stroke

    PubMed Central

    Fernández-López, David; Natarajan, Niranjana; Ashwal, Stephen; Vexler, Zinaida S

    2014-01-01

    The incidence of perinatal stroke is high, similar to that in the elderly, and produces a significant morbidity and severe long-term neurologic and cognitive deficits, including cerebral palsy, epilepsy, neuropsychological impairments, and behavioral disorders. Emerging clinical data and data from experimental models of cerebral ischemia in neonatal rodents have shown that the pathophysiology of perinatal brain damage is multifactorial. These studies have revealed that, far from just being a smaller version of the adult brain, the neonatal brain is unique with a very particular and age-dependent responsiveness to hypoxia–ischemia and focal arterial stroke. In this review, we discuss fundamental clinical aspects of perinatal stroke as well as some of the most recent and relevant findings regarding the susceptibility of specific brain cell populations to injury, the dynamics and the mechanisms of neuronal cell death in injured neonates, the responses of neonatal blood–brain barrier to stroke in relation to systemic and local inflammation, and the long-term effects of stroke on angiogenesis and neurogenesis. Finally, we address translational strategies currently being considered for neonatal stroke as well as treatments that might effectively enhance repair later after injury. PMID:24667913

  4. Intercellular adhesion molecule-1 (ICAM-1) deficiency protects mice against severe forms of experimentally induced colitis

    PubMed Central

    Bendjelloul, F; Malý, P; Mandys, V; Jirkovská, M; Prokešová, L; Tučková, L; Tlaskalová-Hogenová, H

    2000-01-01

    ICAM-1 (CD54), the ligand for LFA-1 and Mac-1, is up-regulated during inflammatory reaction on the activated vascular endothelium. To determine its role in intestinal inflammation, we induced acute experimental colitis in mice with a deleted ICAM-1 gene, by feeding them with 3% dextran sodium sulphate (DSS) in drinking water for 7 days. Chronic colitis was elicited by DSS similarly, followed by 2 weeks with water. In the acute phase of inflammation, ICAM-1-deficient mice exhibited a significantly lower mortality rate (5%) than control C57Bl/6J mice (35%). Control animals, but not the ICAM-1-deficient mice, exhibited diarrhoea and rectal bleeding. Histological examination of large-bowel samples evaluated the intensity of inflammatory changes, and type and extent of mucosal lesions. In the acute phase, 33.3% of samples from ICAM-1-deficient mice exhibited mucosal defects (flat and fissural ulcers), predominantly mild to moderate inflammatory infiltrate within the lamina propria mucosae and lower grades of mucosal lesions. Much stronger inflammatory changes were present in control animals, flat ulcers (sometimes multiple) and fissural ulcers being observed in 62.5% of samples. Mucosal inflammatory infiltrate was moderate to severe, typically with higher grades of mucosal lesions. In chronic colitis, smaller inflammatory changes were found in the large bowel. The two mouse strains differed, the chronic colitis being accompanied by an increased serum level of anti-epithelial IgA autoantibodies in C57Bl/6 control mice but not in ICAM-1-deficient mice. These findings provide direct evidence of the participation of ICAM-1 molecule in the development of experimentally induced intestinal inflammation. PMID:10606964

  5. Recovery of sensorimotor function after experimental stroke correlates with restoration of resting-state interhemispheric functional connectivity.

    PubMed

    van Meer, Maurits P A; van der Marel, Kajo; Wang, Kun; Otte, Willem M; El Bouazati, Soufian; Roeling, Tom A P; Viergever, Max A; Berkelbach van der Sprenkel, Jan Willem; Dijkhuizen, Rick M

    2010-03-17

    Despite the success of functional imaging to map changes in brain activation patterns after stroke, spatiotemporal dynamics of cerebral reorganization in correlation with behavioral recovery remain incompletely characterized. Here, we applied resting-state functional magnetic resonance imaging (rs-fMRI) together with behavioral testing to longitudinally assess functional connectivity within neuronal networks, in relation to changes in associated function after unilateral stroke in rats. Our specific goals were (1) to identify temporal alterations in functional connectivity within the bilateral cortical sensorimotor system and (2) to elucidate the relationship between those alterations and changes in sensorimotor function. Our study revealed considerable loss of functional connectivity between ipsilesional and contralesional primary sensorimotor cortex regions, alongside significant sensorimotor function deficits in the first days after stroke. The interhemispheric functional connectivity restored in the following weeks, but remained significantly reduced up to 10 weeks after stroke in animals with lesions that comprised subcortical and cortical tissue, whereas transcallosal neuroanatomical connections were preserved. Intrahemispheric functional connectivity between primary somatosensory and motor cortex areas was preserved in the lesion border zone and moderately enhanced contralesionally. The temporal pattern of changes in functional connectivity between bilateral primary motor and somatosensory cortices correlated significantly with the evolution of sensorimotor function scores. Our study (1) demonstrates that poststroke loss and recovery of sensorimotor function is associated with acute deterioration and subsequent retrieval of interhemispheric functional connectivity within the sensorimotor system and (2) underscores the potential of rs-fMRI to assess spatiotemporal characteristics of functional brain reorganization that may underlie behavioral recovery after

  6. Proteomic Analysis of the Peri-Infarct Area after Human Umbilical Cord Mesenchymal Stem Cell Transplantation in Experimental Stroke

    PubMed Central

    He, Dongsheng; Zhang, Zhuo; Lao, Jiamin; Meng, Hailan; Han, Lijuan; Chen, Fan; Ye, Dan; Zhang, He; Xu, Yun

    2016-01-01

    Among various therapeutic approaches for stroke, treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs) has acquired some promising results. However, the underlying mechanisms remain unclear. We analyzed the protein expression spectrum of the cortical peri-infarction region after ischemic stroke followed by treatment with hUC-MSCs, and found 16 proteins expressed differentially between groups treated with or without hUC-MSCs. These proteins were further determined by Gene Ontology term analysis and network with CD200-CD200R1, CCL21-CXCR3 and transcription factors. Three of them: Abca13, Grb2 and Ptgds were verified by qPCR and ELISA. We found the protein level of Abca13 and the mRNA level of Grb2 consistent with results from the proteomic analysis. Finally, the function of these proteins was described and the potential proteins that deserve to be further studied was also highlighted. Our data may provide possible underlying mechanisms for the treatment of stroke using hUC-MSCs. PMID:27699085

  7. Low-level light emitting diode (LED) therapy suppresses inflammasome-mediated brain damage in experimental ischemic stroke.

    PubMed

    Lee, Hae In; Lee, Sae-Won; Kim, Nam Gyun; Park, Kyoung-Jun; Choi, Byung Tae; Shin, Yong-Il; Shin, Hwa Kyoung

    2017-02-06

    Use of photostimulation including low-level light emitting diode (LED) therapy has broadened greatly in recent years because it is compact, portable, and easy to use. Here, the effects of photostimulation by LED (610 nm) therapy on ischemic brain damage was investigated in mice in which treatment started after a stroke in a clinically relevant setting. The mice underwent LED therapy (20 min) twice a day for 3 days, commencing at 4 hours post-ischemia. LED therapy group generated a significantly smaller infarct size and improvements in neurological function based on neurologic test score. LED therapy profoundly reduced neuroinflammatory responses including neutrophil infiltration and microglia activation in the ischemic cortex. LED therapy also decreased cell death and attenuated the NLRP3 inflammasome, in accordance with down-regulation of pro-inflammatory cytokines IL-1β and IL-18 in the ischemic brain. Moreover, the mice with post-ischemic LED therapy showed suppressed TLR-2 levels, MAPK signaling and NF-kB activation. These findings suggest that by suppressing the inflammasome, LED therapy can attenuate neuroinflammatory responses and tissue damage following ischemic stroke. Therapeutic interventions targeting the inflammasome via photostimulation with LED may be a novel approach to ameliorate brain injury following ischemic stroke. Effect of post-ischemic low-level light emitting diode therapy (LED-T) on infarct reduction was mediated by inflammasome suppression.

  8. Strokes are possible complications of cannabinoids use.

    PubMed

    Wolff, Valérie; Jouanjus, Emilie

    2017-02-23

    cannabinoids, the low frequency of neurovascular complications after their use may be due to a genetic predisposition to their neurovascular toxicity in some individuals. Further studies should focus on this point. More importantly however, this low frequency may be underestimated because the drug consumption may not be systematically researched, neither by questioning nor by laboratory screening. Besides this vascular role of cannabinoids in the occurrence of stroke, a cellular effect of cannabis on brain mitochondria was recently suggested in an experimental study. One of the mechanisms involved in young cannabis users with stroke may be the generation of reactive oxygen species leading to an oxidative stress, which is a known mechanism in stroke in humans. It is useful to inform the young population about the real potential risk of using cannabinoids. We suggest to systematically ask all young adults with stroke about their drug consumption including cannabinoids, to screen urine for cannabis or to include a specific diagnostic test to detect synthetic cannabinoids, and to obtain non-invasive intracranial arterial investigations (i.e. CT-angiography or cerebral MRA) in order to search for cerebral vasoconstriction. However, several questions remained unresolved and further research is still needed to assess the pathophysiological mechanisms involved in young cannabinoids users with stroke. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".

  9. Digoxin Inhibits Induction of Experimental Autoimmune Uveitis in Mice, but Causes Severe Retinal Degeneration

    PubMed Central

    Hinshaw, Samuel J. H.; Ogbeifun, Osato; Wandu, Wambui S.; Lyu, Cancan; Shi, Guangpu; Li, Yichao; Qian, Haohua; Gery, Igal

    2016-01-01

    Purpose Digoxin, a major medication for heart disease, was recently reported to have immunosuppressive capacity. Here, we determined the immunosuppressive capacity of digoxin on the development of experimental autoimmune uveitis (EAU) and on related immune responses. Methods The B10.A mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) and were treated daily with digoxin or vehicle control. On postimmunization day 14, the mouse eyes were examined histologically, while spleen cells were tested for cytokine production in response to IRBP and purified protein derivative. The immunosuppressive activity of digoxin was also tested in vitro, by its capacity to inhibit development of Th1 or Th17 cells. To investigate the degenerative effect of digoxin on the retina, naïve (FVB/N × B10.BR)F1 mice were similarly treated with digoxin and tested histologically and by ERG. Results Treatment with digoxin inhibited the development of EAU, as well as the cellular response to IRBP. Unexpectedly, treatment with digoxin suppressed the production of interferon-γ to a larger extent than the production of interleukin 17. Importantly, digoxin treatment induced severe retinal degeneration, determined by histologic analysis with thinning across all layers of the retina. Digoxin treatment also induced dose-dependent vision loss monitored by ERG on naïve mice without induction of EAU. Conclusions Treatment of mice with digoxin inhibited the development of EAU and cellular immune response to IRBP. However, the treatment induced severe damage to the retina. Thus, the use of digoxin in humans should be avoided due to its toxicity to the retina. PMID:27028065

  10. Digoxin Inhibits Induction of Experimental Autoimmune Uveitis in Mice, but Causes Severe Retinal Degeneration.

    PubMed

    Hinshaw, Samuel J H; Ogbeifun, Osato; Wandu, Wambui S; Lyu, Cancan; Shi, Guangpu; Li, Yichao; Qian, Haohua; Gery, Igal

    2016-03-01

    Digoxin, a major medication for heart disease, was recently reported to have immunosuppressive capacity. Here, we determined the immunosuppressive capacity of digoxin on the development of experimental autoimmune uveitis (EAU) and on related immune responses. The B10.A mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) and were treated daily with digoxin or vehicle control. On postimmunization day 14, the mouse eyes were examined histologically, while spleen cells were tested for cytokine production in response to IRBP and purified protein derivative. The immunosuppressive activity of digoxin was also tested in vitro, by its capacity to inhibit development of Th1 or Th17 cells. To investigate the degenerative effect of digoxin on the retina, naïve (FVB/N × B10.BR)F1 mice were similarly treated with digoxin and tested histologically and by ERG. Treatment with digoxin inhibited the development of EAU, as well as the cellular response to IRBP. Unexpectedly, treatment with digoxin suppressed the production of interferon-γ to a larger extent than the production of interleukin 17. Importantly, digoxin treatment induced severe retinal degeneration, determined by histologic analysis with thinning across all layers of the retina. Digoxin treatment also induced dose-dependent vision loss monitored by ERG on naïve mice without induction of EAU. Treatment of mice with digoxin inhibited the development of EAU and cellular immune response to IRBP. However, the treatment induced severe damage to the retina. Thus, the use of digoxin in humans should be avoided due to its toxicity to the retina.

  11. Multi-site laser Doppler flowmetry for assessing collateral flow in experimental ischemic stroke: Validation of outcome prediction with acute MRI.

    PubMed

    Cuccione, Elisa; Versace, Alessandro; Cho, Tae-Hee; Carone, Davide; Berner, Lise-Prune; Ong, Elodie; Rousseau, David; Cai, Ruiyao; Monza, Laura; Ferrarese, Carlo; Sganzerla, Erik P; Berthezène, Yves; Nighoghossian, Norbert; Wiart, Marlène; Beretta, Simone; Chauveau, Fabien

    2017-06-01

    High variability in infarct size is common in experimental stroke models and affects statistical power and validity of neuroprotection trials. The aim of this study was to explore cerebral collateral flow as a stratification factor for the prediction of ischemic outcome. Transient intraluminal occlusion of the middle cerebral artery was induced for 90 min in 18 Wistar rats. Cerebral collateral flow was assessed intra-procedurally using multi-site laser Doppler flowmetry monitoring in both the lateral middle cerebral artery territory and the borderzone territory between middle cerebral artery and anterior cerebral artery. Multi-modal magnetic resonance imaging was used to assess acute ischemic lesion (diffusion-weighted imaging, DWI), acute perfusion deficit (time-to-peak, TTP), and final ischemic lesion at 24 h. Infarct volumes and typology at 24 h (large hemispheric versus basal ganglia infarcts) were predicted by both intra-ischemic collateral perfusion and acute DWI lesion volume. Collateral flow assessed by multi-site laser Doppler flowmetry correlated with the corresponding acute perfusion deficit using TTP maps. Multi-site laser Doppler flowmetry monitoring was able to predict ischemic outcome and perfusion deficit in good agreement with acute MRI. Our results support the additional value of cerebral collateral flow monitoring for outcome prediction in experimental ischemic stroke, especially when acute MRI facilities are not available.

  12. Google Calendar: A single case experimental design study of a man with severe memory problems.

    PubMed

    Baldwin, Victoria N; Powell, Theresa

    2015-01-01

    A single case experimental design across behaviours was utilised to explore the effectiveness of Google Calendar text alerts delivered to a mobile phone as a memory aid. The participant was a 43-year-old man (JA) with severe memory problems and executive difficulties caused by a traumatic brain injury (TBI). JA was initially very unwilling to use any memory aid and so a detailed assessment of his beliefs about memory aids, his cognitive difficulties and his social context was performed and a set of specifications for an aid was produced collaboratively. Six weeks of baseline data and six weeks of intervention data were collected for three target memory behaviours and three control memory behaviours. Results were analysed using nonoverlap of all pairs (NAP) analysis which showed a reduction in forgetting in the three target behaviours and no change in two of the three control behaviours. A subjective measure (the revised Everyday Memory Questionnaire) also suggested improvement. This study illustrates that Google Calendar is a highly effective memory aid and emphasises the importance of choosing a memory aid to suit the person's lifestyle and beliefs.

  13. Treatment with the antipsychotic agent, risperidone, reduces disease severity in experimental autoimmune encephalomyelitis.

    PubMed

    O'Sullivan, David; Green, Laura; Stone, Sarrabeth; Zareie, Pirooz; Kharkrang, Marie; Fong, Dahna; Connor, Bronwen; La Flamme, Anne Camille

    2014-01-01

    Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-γ production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naïve T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS.

  14. Treatment with the Antipsychotic Agent, Risperidone, Reduces Disease Severity in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Stone, Sarrabeth; Zareie, Pirooz; Kharkrang, Marie; Fong, Dahna; Connor, Bronwen; La Flamme, Anne Camille

    2014-01-01

    Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-γ production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naïve T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS. PMID:25116424

  15. Experimental densities of binary mixtures: Acetic acid with benzene at several temperatures

    NASA Astrophysics Data System (ADS)

    Bolat, Georgiana; Sutiman, Daniel; Lisa, Gabriela

    2011-03-01

    Hydrocarbons are the most commonly used chemicals in the hydrocarbon processing industries. The knowledge of thermodynamic properties of various binary organic or inorganic mixtures is essential in many practical aspects concerning the mass transport and fluid flow. Such properties are important from the fundamental point of view to understand their mixing behaviour (molecular interactions), as well for practical applications (e.g. in the petrochemical industry). The density of acetic acid-benzene mixtures at several temperatures (T = 296.15, 302.15, 308.15, 314.15 and 319.15 K) were measured over the whole composition range and atmospheric pressure, along with the physical-chemical properties of the pure components (e.g. density, viscosity, refractive index at 298.15 K). The excess molar volumes at the above-mentioned temperatures were calculated from experimental data and fitted by using a new polynomial equation comparing the results with the known equation of Redlich-Kister. The excess volumes for acetic acid with benzene were positive and increase with the temperature. Results were analyzed in terms of molecular interactions. This research was financed by the postdoc grant PERFORM-ERA-ID 57649.

  16. Contribution to modeling of the reflooding of a severely damaged reactor core using PRELUDE experimental results

    SciTech Connect

    Bachrata, A.; Fichot, F.; Repetto, G.; Quintard, M.; Fleurot, J.

    2012-07-01

    In case of accident at a nuclear power plant, water sources may not be available for a long period of time and the core heats up due to the residual power. The reflooding (injection of water into core) may be applied if the availability of safety injection is recovered during accident. If the injection becomes available only in the late phase of accident, water will enter a core configuration that will differ significantly from original rod-bundle geometry. Any attempt to inject water after significant core degradation can lead to further fragmentation of core material. The fragmentation of fuel rods may result in the formation of a 'debris bed'. The typical particle size in a debris bed might reach few millimeters (characteristic length-scale: 1 to 5 mm), i.e., a high permeability porous medium. The French 'Institut de Radioprotection et de Surete Nucleaire' is developing experimental programs (PEARL and PRELUDE) and simulation tools (ICARE-CATHARE and ASTEC) to study and optimize the severe accident management strategy and to assess the probabilities to stop the progress of in-vessel core degradation. It is shown that the quench front exhibits either a ID behaviour or a 2D one, depending on injection rate or bed characteristics. The PRELUDE experiment covers a rather large range of variation of parameters, for which the developed model appears to be quite predictive. (authors)

  17. An Experimental Investigation of Several Low-Drag Wing-Nacelle Combinations with Internal Air Flow

    NASA Technical Reports Server (NTRS)

    Allen, H. Julian; Frick, Charles W.; Erickson, Myles D.

    1945-01-01

    The results of an experimental investigation of several low-drag wing-nacelle combinations, incorporating internal air-flow systems, are presented. The external-drag increments due to these nacelles are between one-half and two-thirds of those of conventional nacelle forms. This improvement is accomplished with only minor effects on the lift and moment characteristics of the wing. The procedure employed to determine the external shape of such low-drag nacelles is considered in detail. The design of an efficient internal-flow system with or without a blower or throttle, presents no serious problems. The energy losses in the expansion before the engine and the contraction thereafter can be kept small. It is believed that these nacelles have a wide application in housing engine pusher-propeller units and, with some alteration, jet-propulsion devices. It is probable that the low external drags may not be realized if such nacelles are used with a tractor propeller because of the high level of turbulence in the propeller slipstream.

  18. Google Calendar: A single case experimental design study of a man with severe memory problems

    PubMed Central

    Baldwin, Victoria N.; Powell, Theresa

    2015-01-01

    A single case experimental design across behaviours was utilised to explore the effectiveness of Google Calendar text alerts delivered to a mobile phone as a memory aid. The participant was a 43-year-old man (JA) with severe memory problems and executive difficulties caused by a traumatic brain injury (TBI). JA was initially very unwilling to use any memory aid and so a detailed assessment of his beliefs about memory aids, his cognitive difficulties and his social context was performed and a set of specifications for an aid was produced collaboratively. Six weeks of baseline data and six weeks of intervention data were collected for three target memory behaviours and three control memory behaviours. Results were analysed using nonoverlap of all pairs (NAP) analysis which showed a reduction in forgetting in the three target behaviours and no change in two of the three control behaviours. A subjective measure (the revised Everyday Memory Questionnaire) also suggested improvement. This study illustrates that Google Calendar is a highly effective memory aid and emphasises the importance of choosing a memory aid to suit the person's lifestyle and beliefs. PMID:25263266

  19. An Experimental and Computational Study of Windborne Debris in Severe Storms

    NASA Astrophysics Data System (ADS)

    Karimpour, Arash

    This research focuses on an experimental and theoretical investigation of windborne debris emanating from loose gravel on built-up roofs. During severe storms, windborne debris can cause considerable physical harm and property damage. One of the major sources of flying debris in large commercial areas is loose gravel on built-up roofs. Such loose gravel can be responsible loss of life and significant property damage. Despite the high risk of windborne debris, their flight mechanics are poorly understood. To better understand windborne debris flight, a series of experiments were conducted in the Clemson University Boundary Layer Wind Tunnel. These experiments were designed to quantify the conditions under which gravel became airborne, the rate at which it was removed, and the resulting flight distance of the debris. In order to conduct experiments in the Boundary Layer Wind Tunnel it is important to understand how to model the atmospheric boundary layer (ABL). A new curve fitting method is presented for calculating the ABL logarithmic velocity profile parameters i.e. shear velocity, surface roughness and zero plane displacement. The new method uses only the time averaged velocity profile and requires no iteration. Comparison with existing methods shows that the new approach has equal or better accuracy than existing curve fitting and geometric approaches with fewer calculation steps. Debris flight is a highly stochastic process with uncertainty and variability in the debris particle the turbulent wind field. However, current models are almost entirely deterministic. A series of Monte Carlo simulations based on existing debris flight equations were run to quantify the impact if input uncertainty on flight outcome (flight distance and impact kinetic energy). Results indicate that failure to account for parameter variability will result in under predicting the mean flight distance and kinetic energy, and ignoring outcome variability / uncertainty. A full quantification

  20. Ischemic stroke and depression.

    PubMed

    Desmond, David W; Remien, Robert H; Moroney, Joan T; Stern, Yaakov; Sano, Mary; Williams, Janet B W

    2003-03-01

    Previous studies of depression after stroke have reported widely variable findings, possibly due to differences between studies in patient characteristics and methods for the assessment of depression, small sample sizes, and the failure to examine stroke-free reference groups to determine the base rate of depression in the general population. In an effort to address certain of those methodologic issues and further investigate the frequency and clinical determinants of depression after stroke, we administered the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) and neurological, neuropsychological, and functional assessments to 421 patients (age = 71.5 +/- 8.0 years) 3 months after ischemic stroke and 249 stroke-free control subjects (age = 70.8 +/- 6.7 years). We required a SIGH-D total score > 11 for the identification of depression. We found that depression was less frequent (47/421 patients, or 11.2%, and 13/249 control subjects, or 5.2%), less severe, and less persistent in our stroke cohort than previously reported, possibly due to the underrepresentation of patients with a premorbid history of affective illness. Depression was associated with more severe stroke, particularly in vascular territories that supply limbic structures; dementia; and female sex. SIGH-D item analyses suggested that a reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnoses of depression after ischemic stroke.

  1. Proteinase inhibitors in severe inflammatory processes (septic shock and experimental endotoxaemia): biochemical, pathophysiological and therapeutic aspects.

    PubMed

    Fritz, H

    1979-01-01

    Plasma levels of antithrombin III, alpha 2-macroglobulin and inter-alpha-trypsin inhibitor, as well as those of various clotting, complement and other plasma factors, were significantly decreased in 18 patients suffering from hyperdynamic septic shock. A similar statistically significant reduction of the concentrations of several plasma factors (prothrombin and antithrombin III, plasminogen and alpha 2-plasmin inhibitor, complement factor C3 and clotting factor XIII) was observed in experimental endotoxaemia. In this model the reduction in the plasma levels of these factors was considerably diminished by the intravenous injection of a granulocytic elastase--cathepsin G inhibitor of lower molecular weight from soybeans. The results of both studies indicate that consumption of plasma factors in the course of Gram-negative sepsis proceeds not only via the classical routes (by activation of the clotting, fibrinolytic and complement cascades by system-specific proteinases such as thrombokinase or the plasminogen activator) but also to an appreciable degree of unspecific degradation of plasma factors by neutral proteinases such as elastase and cathepsin G. The endotoxin-induced release of both sorts of proteinases, the system-specific ones and the unspecific lysosomal proteinases from leucocytes and other cells, is likely to be mainly responsible for the consumption of antithrombin III and alpha-2-macroglobulin via complex formation (followed by elimination of the complexes) and the increased turnover of the inter-alpha-trypsin inhibitor as observed in the clinical study. The therapeutic use of an exogenous elastase--cathepsin G inhibitor in the experimental model was stimulated by the observation that human mucous secretions contain and acid-stable inhibitor of the neutral granulocytic proteinases, called HUSI-I or antileucoproteinase. This inhibitor protects mucous membranes and soluble proteins against proteolytic attack by leucocytic proteinases released in the

  2. Anatomical and technical factors associated with stroke or death during carotid angioplasty and stenting: results from the endarterectomy versus angioplasty in patients with symptomatic severe carotid stenosis (EVA-3S) trial and systematic review.

    PubMed

    Naggara, Olivier; Touzé, Emmanuel; Beyssen, Bernard; Trinquart, Ludovic; Chatellier, Gilles; Meder, Jean-François; Mas, Jean-Louis

    2011-02-01

    The purposes of this study were to assess the relationships between anatomic and technical factors and the 30-day risk of stroke or death after carotid angioplasty and stenting in the Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial and to perform a systematic review of the literature. We included patients from EVA-3S in whom carotid stenting was attempted irrespective of allocated treatment. Two radiologists blinded to clinical data independently assessed the aortic arch and carotid arteries on procedural angiograms. In addition, we performed a systematic review of studies that reported 30-day risk of stroke or death in relation with arterial anatomy and technique. Outcomes were stroke or death and stroke occurring within 30 days of the carotid angioplasty and stenting procedure. Two hundred sixty-two patients from EVA-3S fulfilled the inclusion criteria (including 1 initially allocated to surgery and 13 in whom stent insertion failed).Within 30 days after the procedure, 25 (9.5%) patients had a stroke or had died. The risk of stroke or death was higher in patients with internal carotid artery-common carotid artery angulation ≥60° (relative risk, 4.96; 2.29 to 10.74) and lower in those treated with cerebral protection devices (relative risk [RR], 0.38; 0.17 to 0.85). In the systematic review (56 studies; 34 398 patients), the risk of stroke or death was higher in patients with left-sided carotid angioplasty and stenting (RR, 1.29; 1.05 to 1.58), increased internal carotid artery-common carotid artery angulation (RR, 3.41; 1.52 to 7.63), and when the target internal carotid artery stenosis was >10 mm (RR, 2.36; 1.28 to 3.38). There was no significant increase in risk of stroke or death in patients with Type III aortic arch, aortic arch calcification, or with ostial involvement, calcification, ulceration or degree of stenosis of the target internal carotid artery stenosis. The use of a cerebral protection device

  3. Strokes in Thai children : etiology and outcome.

    PubMed

    Visudhiphan, P; Chiemchanya, S; Wattanasirichaigoon, D

    1996-12-01

    In Asian countries, specific etiology and outcome of stroke in children are rarely reported. During January 1979 to December 1997, 68 children with stroke, admitted to the Department of Pediatrics, Ramathibodi Hospital, Bangkok were reviewed for etiology and outcome; 38 patients (22 males) had ischemic stroke and 30 (20 males) had hemorrhagic stroke. Severe headache, vomiting, disturbance of consciousness and papilledema were prominent presentations of hemorrhagic stroke. Bleeding from vascular anomalies of the brain (AVM) was the most common etiology of hemorrhagic stroke while septic and non-septic emboli from congenital and acquired heart diseases were the most common cause of ischemic stroke. The mortality rate was 7% and 9% in hemorrhagic and ischemic strokes, respectively. Complete recovery was observed in 52% of cases of hemorrhagic stroke but in only 26% of ischemic stroke. Hemiparesis was the most common residual neurological deficit with higher occurrence in ischemic stroke.

  4. Neuroprotection conferred by post-ischemia ethanol therapy in experimental stroke: an inhibitory effect on hyperglycolysis and NADPH oxidase activation.

    PubMed

    Kochanski, Ryan; Peng, Changya; Higashida, Tetsuhiro; Geng, Xiaokun; Hüttemann, Maik; Guthikonda, Murali; Ding, Yuchuan

    2013-07-01

    Ethanol provides neuroprotection following ischemia/reperfusion. This study assessed ethanol's effect on hyperglycolysis and NADPH oxidase (NOX) activation. Adult, male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Three sets of experiments were conducted to determine ethanol's effect on (i) conferring neuroprotection by measuring infarct volume and neurological deficits 24 h post reperfusion; (ii) cerebral glucose metabolism and lactic acidosis by measuring brain and blood glucose concentrations and protein expression of glucose transporter 1 and 3 (GLUT1, GLUT3), phosphofructokinase (PFK), as well as lactic acidosis by measuring lactate dehydrogenase (LDH), and lactate; and (iii) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation by detecting enzymatic activity and subunit expression at 3 h after reperfusion. When administered upon reperfusion, ethanol (1.5 g/kg) reduced infarct volume by 40% (p < 0.01) and neurological deficits by 48% at 24 h post reperfusion while reducing (p < 0.01) elevations in glycolytic protein expression and lactate levels during early reperfusion (3 h). Ethanol increased the reductions in cerebral glucose concentration at 3 h post reperfusion by 64% (p < 0.01) while enhancing (p < 0.01) post stroke blood glucose concentration, suggesting a reduced cellular glucose uptake and utilization. Ethanol decreased (p < 0.01) stroke-induced NOX activation by reducing enzymatic activity and gp91(phox) expression by 45% and 38%, respectively. Post-ischemia ethanol treatment exerts neuroprotection through attenuation of hyperglycolysis and associated NOX activation. Because of the lack of associated hypoglycemia and selectivity toward decreasing cerebral metabolism, further investigation of ethanol's use as a post-stroke therapy, especially in the context of hyperglycemia, seems warranted. © 2013 International Society for Neurochemistry.

  5. Stroke in childhood.

    PubMed

    Pearce, Lynne

    2017-07-19

    Essential facts About 400 children a year have a stroke in the UK. Many are left with severe disability. While there have been improvements in diagnosis and treatment in recent years, the condition is still not as well recognised as stroke in adults. Experts believe that greater awareness among parents and healthcare professionals could lead to speedier diagnosis and minimise risk of severe long-term health problems.

  6. Prebiotic and synbiotic fructooligosaccharide administration fails to reduce the severity of experimental colitis in rats.

    PubMed

    Geier, Mark S; Butler, Ross N; Giffard, Philip M; Howarth, Gordon S

    2007-07-01

    Opposing effects of the prebiotic, fructooligosaccharide, have been reported in experimental colitis. We compared the effects of the prebiotic, fructooligosaccharide, alone and in synbiotic combination with Lactobacillus fermentum BR11, on the development of dextran sulfate sodium-induced colitis in rats. Rats consumed an 18 percent casein-based diet or diet supplemented with 6 percent fructooligosaccharide or maltodextrin for 14 days. The synbiotic group was gavaged 1 ml of L. fermentum BR11 (1x10(9) cfu/ml) twice daily. From Days 7 to 14, colitis was induced via 3 percent dextran sulfate sodium in drinking water. Disease activity was assessed daily, and at killing, gastrointestinal organs were measured, weighed, and examined by quantitative histology, proliferating cell nuclear antigen immunohistochemistry, and colonic myeloperoxidase activity. Administration of dextran sulfate sodium resulted in an increased colitic disease activity, and an increased colon and cecum weight compared with normal controls. Colon and cecum weights were further increased in dextran sulfate sodium+fructooligosaccharide (colon: 19 percent; cecum: 48 percent) and dextran sulfate sodium+fructooligosaccharide/L. fermentum BR11-treated rats (16 and 62 percent) compared with dextran sulfate sodium+vehicle-treatment. Dextran sulfate sodium+fructooligosaccharide-treated rats displayed an 81 percent increase in colonic myeloperoxidase activity compared with dextran sulfate sodium-treated controls. Histologic damage severity scores increased in dextran sulfate sodium+vehicle, dextran sulfate sodium+fructooligosaccharide, and dextran sulfate sodium+fructooligosaccharide/L. fermentum BR11-treated rats compared with normal controls (P<0.05). Crypt depth increased in all treatments compared with normal controls (P<0.01). No protection from dextran sulfate sodium-colitis was accorded by fructooligosaccharide alone or in synbiotic combination with L. fermentum BR11, whereas fructooligosaccharide

  7. 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.

  8. 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.

  9. Propofol Protects Against Focal Cerebral Ischemia via Inhibition of Microglia-Mediated Proinflammatory Cytokines in a Rat Model of Experimental Stroke

    PubMed Central

    Zhou, Rong; Yang, Zailiang; Tang, Xurong; Tan, Yan; Wu, Xiaofeng; Liu, Feng

    2013-01-01

    Ischemic stroke induces microglial activation and release of proinflammatory cytokines, contributing to the expansion of brain injury and poor clinical outcome. Propofol has been shown to ameliorate neuronal injury in a number of experimental studies, but the precise mechanisms involved in its neuroprotective effects remain unclear. We tested the hypothesis that propofol confers neuroprotection against focal ischemia by inhibiting microglia-mediated inflammatory response in a rat model of ischemic stroke. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by 24 h of reperfusion. Propofol (50 mg/kg/h) or vehicle was infused intravenously at the onset of reperfusion for 30 minutes. In vehicle-treated rats, MCAO resulted in significant cerebral infarction, higher neurological deficit scores and decreased time on the rotarod compared with sham-operated rats. Propofol treatment reduced infarct volume and improved the neurological functions. In addition, molecular studies demonstrated that mRNA expression of microglial marker Cd68 and Emr1 was significantly increased, and mRNA and protein expressions of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β and interleukin-6 were augmented in the peri-infarct cortical regions of vehicle-treated rats 24 h after MCAO. Immunohistochemical study revealed that number of total microglia and proportion of activated microglia in the peri-infarct cortical regions were markedly elevated. All of these findings were ameliorated in propofol-treated rats. Furthermore, vehicle-treated rats had higher plasma levels of interleukin-6 and C-reactive protein 24 h after MCAO, which were decreased after treatment with propofol. These results suggest that propofol protects against focal cerebral ischemia via inhibition of microglia-mediated proinflammatory cytokines. Propofol may be a promising therapeutic agent for the treatment of ischemic stroke and other neurodegenerative diseases

  10. Stroke rehabilitation

    PubMed Central

    Bindawas, Saad M.; Vennu, Vishal S.

    2016-01-01

    Stroke is a major cause of death and other complications worldwide. In Saudi Arabia, stroke has become an emerging health issue leading to disability and death. However, stroke care including rehabilitation services, in Saudi Arabia lags behind developed countries. Stroke rehabilitation is an essential recovery option after stroke and should start as early as possible to avoid potential complications. The growing evidence on stroke rehabilitation effectiveness in different health care settings and outcome measures used widely are reviewed in this call to action paper. PMID:27744457

  11. Correlated sodium and potassium imbalances within the ischemic core in experimental stroke: a 23Na MRI and histochemical imaging study

    PubMed Central

    Yushmanov, Victor E.; Kharlamov, Alexander; Yanovski, Boris; LaVerde, George; Boada, Fernando E.; Jones, Stephen C.

    2013-01-01

    This study addresses the spatial relation between local Na+ and K+ imbalances in the ischemic core in a rat model of focal ischemic stroke. Quantitative [Na+] and [K+] brain maps were obtained by 23Na MRI and histochemical K+ staining, respectively, and calibrated by emission flame photometry of the micropunch brain samples. Stroke location was verified by diffusion MRI, by changes in tissue surface reflectivity and by immunohistochemistry with microtubule-associated protein 2 antibody. Na+ and K+ distribution within the ischemic core was inhomogeneous, with the maximum [Na+] increase and [K+] decrease typically observed in peripheral regions of the ischemic core. The pattern of the [K+] decrease matched the maximum rate of [Na+] increase (‘slope’). Some residual mismatch between the sites of maximum Na+ and K+ imbalances was attributed to the different channels and pathways involved in transport of the two ions. A linear regression of the [Na+]br vs. [K+]br in the samples of ischemic brain indicates that for each K+ equivalent leaving ischemic tissue, 0.8 ± 0.1 Eq, on average, of Na+ enter the tissue. Better understanding of the mechanistic link between the Na+ influx and K+ egress would validate the 23Na MRI slope as a candidate biomarker and a complementary tool for assessing ischemic damage and treatment planning. PMID:23792152

  12. Pathophysiology, treatment, and animal and cellular models of human ischemic stroke.

    PubMed

    Woodruff, Trent M; Thundyil, John; Tang, Sung-Chun; Sobey, Christopher G; Taylor, Stephen M; Arumugam, Thiruma V

    2011-01-25

    Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to

  13. [Antioxidant therapy in ischemic stroke].

    PubMed

    Suslina, Z A; Federova, T N; Maksimova, M Iu; Riasina, T V; Stvolinskiĭ, S L; Khrapova, E V; Boldyrev, A A

    2000-01-01

    The paper presents the results of investigation of emoxipin, an antioxidant synthetic drug, for treatment of patients with ischemic disorders of cerebral circulation. The drug produced a beneficial clinical effect in patients with lacunar and cardioembolic strokes of moderate severity. Therapy with emoxipin increased endogenic antioxidant activity and improved a clinical status of the patients. The protective effect of carnosine was demonstrated in experimental acute hypobaric hypoxia and cerebral ischemia in rats. The results obtained permit to recommend an inclusion of both emoxipin and carnosine in a combined treatment of ischemic disorders of cerebral circulation.

  14. 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 ...

  15. 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 ...

  16. Experimental Stark widths, shifts, and transition probabilities of several ArII lines

    SciTech Connect

    Aparicio, J. A.; Gigosos, M. A.; Mar, S.; Gonzalez, V. R.

    1997-01-05

    This paper is an extensive experimental contribution to the knowledge of ArII atomic parameters. This specie, which is very important for many astrophysical and industrial plasma diagnostics, has been extensively studied. However, there are still great differences in the experimental Stark widths and shifts coefficients, as well as a great lack of transition probability data, especially for lines coming from the very highly excited energy levels.

  17. Experimental Stark widths, shifts, and transition probabilities of several ArII lines

    SciTech Connect

    Aparicio, J.A.; Gigosos, M.A.; Mar, S.; Gonzalez, V.R.

    1997-01-01

    This paper is an extensive experimental contribution to the knowledge of ArII atomic parameters. This specie, which is very important for many astrophysical and industrial plasma diagnostics, has been extensively studied. However, there are still great differences in the experimental Stark widths and shifts coefficients, as well as a great lack of transition probability data, especially for lines coming from the very highly excited energy levels. {copyright} {ital 1997 American Institute of Physics.}

  18. Ischemic Strokes (Clots)

    MedlinePlus

    ... Infographic Stroke Hero F.A.S.T. Quiz Ischemic Strokes (Clots) Updated:Apr 26,2017 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  19. [Mobile stroke unit for prehospital stroke treatment].

    PubMed

    Walter, S; Grunwald, I Q; Fassbender, K

    2016-01-01

    The management of acute stroke patients suffers from several major problems in the daily clinical routine. In order to achieve optimal treatment a complex diagnostic work-up and rapid initiation of therapy are necessary; however, most patients arrive at hospital too late for any type of acute stroke treatment, although all forms of treatment are highly time-dependent according to the generally accepted "time is brain" concept. Recently, two randomized clinical trials demonstrated the feasibility of prehospital stroke diagnostic work-up and treatment. This was accomplished by use of a specialized ambulance, equipped with computed tomography for multimodal imaging and a point-of-care laboratory system. In both trials the results demonstrated a clear superiority of the prehospital treatment group with a significant reduction of treatment times, significantly increased number of patients treated within the first 60 min after symptom onset and an optimized triage to the correct target hospital. Currently, mobile stroke units are in operation in various countries and should lead to an improvement in stroke treatment; nevertheless, intensive research is still needed to analyze the best framework settings for prehospital stroke management.

  20. [Experimental hemorrhagic stroke: the effect of the peptide preparation cortexin in the formation of Hb-NO-complexes and other blood paramagnetic centers].

    PubMed

    Reutov, V P; Baĭder, L M; Kuropteva, Z V; Krushinskiĭ, A L; Kuzenkov, V S; Moldaliev, Zh T; Granstrem, O K

    2011-01-01

    Using electronic paramagnetic resonance (EPR), we studied the effect of the peptide cortexin on the content of hemoglobin nitrozyl complexes (Hb-NO-complexes) and other paramagnetic centers (transferrin, methemoglobin) in the blood of rats of Krushynsky-Molodkina line in the experimental hemorrhagic stroke induced by acoustic stress. After the acoustic exposure, the level of Hb-NO-complexes have increased by more than 6 times. The intensity of the EPR signal of the plasma peptide transferrin increased by 1,5 times. The level of blood methemoglobin was also elevated, though not significantly, after the acoustic stress. Cortexin substantially reduces the formation of Hb-NO-complexes and, therefore, the level of nitride oxide while the contents of transferrin and methemoglobin remain intact.