Science.gov

Sample records for experimental stroke severity

  1. 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

  2. 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

  3. Severe stroke: which medicine for which results?

    PubMed

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

    2014-02-01

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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

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

    PubMed Central

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

    2016-01-01

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

  12. 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.

  13. 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.

  14. 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

  15. 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." ...

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  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. 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

  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. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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 ...

  10. 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

  11. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials

    PubMed Central

    Rothwell, Peter M; Algra, Ale; Chen, Zhengming; Diener, Hans-Christoph; Norrving, Bo; Mehta, Ziyah

    2017-01-01

    Background Aspirin is recommended for secondary prevention after transient ischaemic attack (TIA) and ischaemic stroke based on trials showing about a 13% reduction in long-term risk of recurrent stroke. However, the risk of major stroke is very high for only the first few days after TIA and minor ischaemic stroke and observational studies show substantially greater benefits of early medical treatment in the acute phase. We hypothesised that the short-term benefits of early aspirin have been underestimated. Methods Using individual patient data from all randomised trials of aspirin vs placebo in secondary prevention after TIA or ischaemic stroke, we studied the time-course of effects on risk and severity (modified Rankin score - mRS) of recurrent stroke and myocardial infarction. To more reliably determine the very early time-course of effect of aspirin on risk of recurrent ischaemic stroke, we also studied trials in treatment of acute stroke stratified by severity of baseline neurological deficit. To understand possible mechanisms of action, we also studied the time-course of the interaction between effects of aspirin and dipyridamole in secondary prevention of stroke. Results Among 15,778 patients in 12 trials of aspirin vs. control in secondary prevention, aspirin reduced the 6-week risk of major ischaemic vascular events by 70-80% (disabling or fatal ischaemic stroke - HR=0.29,0.20-0.43, p<0.0001; acute myocardial infarction - HR=0.22, 0.09-0.53, p=0.0008), with greatest benefit in patients with TIA or minor stroke (disabling or fatal ischaemic stroke: 0-2 weeks-HR=0.07,0.02-0.31,p=0.0004; 0-6 weeks-HR=0.19,0.11-0.34,p<0.0001). The effect of aspirin on early recurrent ischaemic stroke was due partly to a substantial reduction in severity (mRS shift analysis: OR=0.43,0.26-0.72,p=0.001). These effects were independent of dose, patient characteristics or aetiology of TIA or stroke. Some further reduction in risk of ischaemic stroke on aspirin only vs control

  12. 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

  13. 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

  14. 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 ...

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. [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.

  13. 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.

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

    PubMed Central

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

    2009-01-01

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

  15. 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.

  16. 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.

  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. 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

  19. 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.

  20. [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.

  1. 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.

  2. 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

  3. 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.

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

    PubMed Central

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

    2015-01-01

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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

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

    NASA Astrophysics Data System (ADS)

    Buchman, Michael; Winter, Amos

    2015-11-01

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

  12. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. [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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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

  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. 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.

  8. Constraint-Induced Movement Therapy for Severe Upper-Extremity Impairment after Stroke in an Outpatient Rehabilitation Setting: A Case Report

    PubMed Central

    Shears, Jennifer; Hutchings, Lisa; Osmond, Michelle

    2008-01-01

    Purpose: Laboratory studies confirm that constraint-induced movement therapy (CIMT) improves upper-extremity (UE) function after stroke. Due to strict patient criteria and the intensive resources required, CIMT has been slow to become part of rehabilitation practice. Our purpose was to determine the feasibility and effectiveness of an adapted experimental protocol within an outpatient clinical setting for a patient with moderate to severe UE impairment who did not meet traditional CIMT criteria. Patient Description: AJ, a 16-year-old male, experienced a left middle cerebral artery ischemic stroke due to carotid artery dissection one year before beginning CIMT. He demonstrated some proximal movement but no wrist or finger extension. He had received intensive rehabilitation for 12 months prior to beginning CIMT. Intervention: Two occupational therapists and two physiotherapists collaborated to provide CIMT task training for 6 hours daily for 2 weeks. A knitted mitten extending to the elbow restrained the less-involved UE during 90% of waking hours. Tasks were tailored to AJ's interests, with the goal of integrating his affected UE into his behavioural repertoire. Measures and Outcomes: After 2 weeks of CIMT, AJ improved in all measures (grip and lateral pinch strength, Action Research Arm Test [ARAT], and Box and Block Test) except the Chedoke McMaster Impairment Inventory. Greatest gains were seen at 6 months in the ARAT and Box and Block Test, which coincided with patient and family reports of AJ's using his arm in everyday functional tasks. Implications: Shared workload, emphasis on relevant functional tasks, and complete family participation likely influenced the success of CIMT. Our findings suggest that the strict CIMT criteria used in previous studies may exclude patients who might benefit from the treatment. Controlled trials should be undertaken to examine the effects of CIMT in patients with moderate to severe UE impairment. PMID:20145779

  9. [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.

  10. 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.

  11. 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

  12. 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.

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

    PubMed Central

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

    2015-01-01

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

  14. 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

  15. 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

  16. Stroke: First Aid

    MedlinePlus

    First aid Stroke: First aid Stroke: First aid By Mayo Clinic Staff A stroke occurs when there's bleeding into your brain or when normal blood flow to ... next several hours. Seek immediate medical assistance. A stroke is a true emergency. The sooner treatment is ...

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Pediatric Stroke

    MedlinePlus

    ... News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis Stroke ... communicate with your child’s doctor. Symptoms of a Stroke Stroke is an injury to part of the ...

  6. 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…

  7. [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.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. [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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  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. 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.

  7. [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.

  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. 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

  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. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

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

    PubMed

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

    2015-01-01

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

  19. 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

  20. 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

  1. Ischemic Stroke

    MedlinePlus

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

  2. 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.

  3. 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.

  4. 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.

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

    PubMed Central

    2016-01-01

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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

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

    DTIC Science & Technology

    2011-01-01

    Methods. Healthy human subjects (n¼21) underwent central hypovolaemia through progressive lower body negative pressure (LBNP) until the onset of presyncope...lower body negative pressure (LBNP), a well-established experimental model of central hypovolaemia.15 We assessed how well the investiga- tional methods...JJ, Schreuder JJ. Computation of aortic flow from pressure in humans using a nonlinear, three-element model. J Appl Physiol 1993; 74: 2566–73 8

  15. 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.

  16. [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.

  17. 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

  18. 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.

  19. 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).

  20. 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.

  1. 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 ...

  2. 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 ...

  3. 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, ...

  4. 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.

  5. 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.

  6. 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.

  7. 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…

  8. 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.

  9. 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.

  10. 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".

  11. 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.

  12. 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.

  13. 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

  14. 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.

  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. 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 ...

  18. 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

  19. 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.

  20. Ischemic Strokes (Clots)

    MedlinePlus

    ... Quiz 5 Things to Know About Stroke Ischemic Strokes (Clots) Updated:Nov 9,2016 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  1. Recovering after stroke

    MedlinePlus

    Stroke rehabilitation; Cerebrovascular accident - rehabilitation; Recovery from stroke; Stroke - recovery; CVA - recovery ... WHERE TO LIVE AFTER A STROKE Most people will need stroke ... after they leave the hospital. Stroke rehab will help you ...

  2. Acute ischemic stroke update.

    PubMed

    Baldwin, Kathleen; Orr, Sean; Briand, Mary; Piazza, Carolyn; Veydt, Annita; McCoy, Stacey

    2010-05-01

    Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for

  3. [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.

  4. 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

  5. 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.

  6. 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

  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. 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

  9. Nrf2 Weaves an Elaborate Network of Neuroprotection Against Stroke.

    PubMed

    Jiang, Shuai; Deng, Chao; Lv, Jianjun; Fan, Chongxi; Hu, Wei; Di, Shouyin; Yan, Xiaolong; Ma, Zhiqiang; Liang, Zhenxing; Yang, Yang

    2017-03-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a neuroprotective transcription factor that has recently attracted increased attention. Stroke, a common and serious neurological disease, is currently a leading cause of death in the USA so far. It is therefore of vital importance to explore how Nrf2 behaves in stroke. In this review, we first introduce the structural features of Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) and briefly depict the activation, inactivation, and regulation processes of the Nrf2 pathway. Next, we discuss the physiopathological mechanisms, upstream modulators, and downstream targets of the Nrf2 pathway. Following this background, we expand our discussion to the roles of Nrf2 in ischemic and hemorrhagic stroke and provide several potential future directions. The information presented here may be useful in the design of future experimental research and increase the likelihood of using Nrf2 as a therapeutic target for stroke in the future.

  10. 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

  11. 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.

  12. Prehospital stroke care

    PubMed Central

    Saver, Jeffrey L.; Starkman, Sidney; Lees, Kennedy R.; Endres, Matthias

    2013-01-01

    Brain cells die rapidly after stroke and any effective treatment must start as early as possible. In clinical routine, the tight time–outcome relationship continues to be the major limitation of therapeutic approaches: thrombolysis rates remain low across many countries, with most patients being treated at the late end of the therapeutic window. In addition, there is no neuroprotective therapy available, but some maintain that this concept may be valid if administered very early after stroke. Recent innovations have opened new perspectives for stroke diagnosis and treatment before the patient arrives at the hospital. These include stroke recognition by dispatchers and paramedics, mobile telemedicine for remote clinical examination and imaging, and integration of CT scanners and point-of-care laboratories in ambulances. Several clinical trials are now being performed in the prehospital setting testing prehospital delivery of neuroprotective, antihypertensive, and thrombolytic therapy. We hypothesize that these new approaches in prehospital stroke care will not only shorten time to treatment and improve outcome but will also facilitate hyperacute stroke research by increasing the number of study participants within an ultra-early time window. The potentials, pitfalls, and promises of advanced prehospital stroke care and research are discussed in this review. PMID:23897876

  13. 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

  14. Promoting recovery from ischemic stroke.

    PubMed

    Schmidt, Antje; Minnerup, Jens

    2016-01-01

    Over recent decades, experimental and clinical stroke studies have identified a number of neurorestorative treatments that stimulate neural plasticity and promote functional recovery. In contrast to the acute stroke treatments thrombolysis and endovascular thrombectomy, neurorestorative treatments are still effective when initiated days after stroke onset, which makes them applicable to virtually all stroke patients. In this article, selected physical, pharmacological and cell-based neurorestorative therapies are discussed, with special emphasis on interventions that have already been transferred from the laboratory to the clinical setting. We explain molecular and structural processes that promote neural plasticity, discuss potential limitations of neurorestorative treatments, and offer a speculative viewpoint on how neurorestorative treatments will evolve.

  15. [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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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)

  1. 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

  2. Stroke Rehabilitation

    MedlinePlus

    ... how to subscribe to the Stroke Connection Magazine. Community Resources Home health services, available from the Visiting Nurses Association, public health departments, hospital home care departments ...

  3. 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

  4. Atherosclerosis and Stroke

    MedlinePlus

    ... After Stroke Inspirational Stories Stroke Heroes Among Us Atherosclerosis and Stroke Updated:Oct 24,2016 Excerpted and ... cause difficulty walking and eventually gangrene. Stroke and atherosclerosis There are two types of ischemic stroke caused ...

  5. Effect of a Caregiver's Education Program on Stroke Rehabilitation

    PubMed Central

    2017-01-01

    Objective To evaluate effects of caregiver's education program on their satisfaction, as well as patient functional recovery, performed in addition to daily conventional rehabilitation treatment. Methods Three hundred eleven subjects diagnosed with first-onset stroke and transferred to the Department of Physical Medicine and Rehabilitation of Inha University Hospital were surveyed. In 2015, caregivers attended an education program for acute and subacute stroke patients. Patients who received an additional rehabilitation therapy were assigned to the experimental group (n=81), whereas the control group (n=100) consisted of transfer cases in 2014 with only conventional treatment. The experimental group was classified by severity using the Korean version of the National Institutes of Health Stroke Scale (K-NIHSS), which was administered to all 181 subjects, in addition to, the Korean version of the Mini Mental Status Examination (K-MMSE), a Modified Barthel Index (K-MBI), and the Berg Balance Scale (K-BBS). Caregiver satisfaction and burden before and after education programs were assessed using the Canadian Occupational Performance Measure (COPM), as well as family burden and caregiver burnout scales. Results No significant intergroup difference was observed between initial K-NIHSS, K-MMSE, K-BBS, K-MBI scores, and times from admission to transfer. Those with moderate or severe strokes under the experimental condition showed a more significant improvement than the control group as determined by the K-NIHSS and K-BBS, as well as tendential K-MMSE and K-MBI score increases. Satisfaction was significantly greater for family members and formal caregivers of patients with strokes of moderate severity in the experimental group. Conclusion The caregiver's education program for stroke subjects had a positive outcome on patients' functional improvement and caregiver satisfaction. The authors believe that the additional rehabilitation therapy with the education program aids

  6. 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

  7. 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

  8. Fetal stroke.

    PubMed

    Ozduman, Koray; Pober, Barbara R; Barnes, Patrick; Copel, Joshua A; Ogle, Eileen A; Duncan, Charles C; Ment, Laura R

    2004-03-01

    Fetal stroke, or that which occurs between 14 weeks of gestation and the onset of labor resulting in delivery, has been associated with postnatal epilepsy, mental retardation, and cerebral palsy. The entity is caused by antenatal ischemic, thrombotic, or hemorrhagic injury. We present seven new cases of fetal stroke diagnosed in utero and review the 47 cases reported in the literature. Although risk factors could not be assigned to 50% of the fetuses with stroke, the most common maternal conditions associated with fetal stroke were alloimmune thrombocytopenia and trauma. Magnetic resonance imaging was optimal for identifying fetal stroke, and prenatal imaging revealed hemorrhagic lesions in over 90% of studies; porencephalies were identified in just 13%. Seventy-eight percent of cases with reported outcome resulted in either death or adverse neurodevelopmental outcome at ages 3 months to 6 years. Fetal stroke appears to have different risk factors, clinical characteristics, and outcomes than other perinatal or childhood stroke syndromes. A better understanding of those risk factors predisposing a fetus to cerebral infarction may provide a basis for future therapeutic intervention trials. Ozduman K, Pober BR, Barnes P, Copel JA, Ogle EA, Duncan CC, Ment LR. Fetal stroke.

  9. Autopsy approach to stroke.

    PubMed

    Love, Seth

    2011-02-01

    Stroke is a major cause of morbidity and mortality but the brain and other relevant tissues are often examined only cursorily when stroke patients come to autopsy. The pathological findings and clinical implications vary according to the type of stroke and its location and cause. Large ischaemic strokes are usually associated with atherosclerosis of extracranial or major intracranial arteries but can be caused by dissection. Most small cerebral infarcts are caused by arteriosclerosis or, in the elderly, cerebral amyloid angiopathy (CAA). However, vasculitides and coagulopathies can cause a range of different patterns of ischaemic (and, occasionally, haemorrhagic) stroke. Global brain ischaemia, caused by severe hypotension or raised intracranial pressure, produces damage that is accentuated in certain regions and neuronal populations and may be confused with hypoglycaemic injury. The main cause of subarachnoid haemorrhage is a ruptured berry aneurysm but CAA, arteriovenous malformations and infective aneurysms are occasionally responsible. These can also cause parenchymal brain haemorrhage, although this most often complicates hypertensive small vessel disease. Sometimes the haemorrhage arises from a neoplasm. Performing an adequate autopsy in stroke requires proper preparation, awareness of the likely pathological processes, familiarity with intracranial vascular anatomy, careful gross examination and dissection, and appropriate use of histology.

  10. Ischemic Stroke.

    PubMed

    Capriotti, Teri; Murphy, Teresa

    2016-05-01

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

  11. Improvement of the circulatory function partially accounts for the neuroprotective action of the phytoestrogen genistein in experimental ischemic stroke.

    PubMed

    Cortina, Belén; Torregrosa, Germán; Castelló-Ruiz, María; Burguete, María C; Moscardó, Antonio; Latorre, Ana; Salom, Juan B; Vallés, Juana; Santos, María T; Alborch, Enrique

    2013-05-15

    We tested the hypothesis that the phytoestrogen genistein protects the brain against ischemic stroke by improving the circulatory function in terms of reduced production of thromboxane A2 and leukocyte-platelet aggregates, and of preserved vascular reactivity. Ischemia-reperfusion (90 min-3 days, intraluminal filament) was induced in male Wistar rats, and functional score and cerebral infarct volume were the end points examined. Genistein (10mg/kg/day) or vehicle (β-cyclodextrin) was administered at 30 min after ischemia or sham-operation. Production of thromboxane A2 and leukocyte-platelet aggregates, as well as reactivity of carotid artery to U-46619 (thromboxane A2 analogue) and to platelet releasate was measured. At 3 days post-ischemia, both improvement in the functional examination and reduction in the total infarct volume were shown in the ischemic genistein-treated group. Genistein significantly reverted both the increased thromboxane A2 concentration and the increased leukocyte-platelet aggregates production found in samples from the ischemic vehicle-treated group. Both U-46619 and platelet releasate elicited contractions of the carotid artery, which were significantly lower in the ischemic vehicle-treated group. Genistein significantly restored both the decreased U-46619- and the decreased platelet releasate-elicited contractile responses. In conclusion, genistein protects the brain against an ischemia-reperfusion challenge, at least in part, by its beneficial effects on the circulatory function.

  12. The Neuroprotective Effect of Rosemary (Rosmarinus officinalis L.) Hydro-alcoholic Extract on Cerebral Ischemic Tolerance in Experimental Stroke

    PubMed Central

    Seyedemadi, Parisa; Rahnema, Mehdi; Bigdeli, Mohammad Reza; Oryan, Shahrebano; Rafati, Hassan

    2016-01-01

    The prevention of BBB breakdown and the subsequent vasogenic edema are important parts of the medical management of ischemic stroke. The purpose of this study was to investigate the ischemic tolerance effect of Rosmarinus officinalis leaf hydro-alcoholic extract (RHE). Five groups of animals were designed: sham (underwent surgery without MCAO) and MCAO groups, the MCAO groups were pretreated orally by gavages with RHE (50, 75, and 100 mg/Kg/day), daily for 30 days. Two hours after the last dose, serum lipid levels were determined and then the rats were subjected to 60 min of middle cerebral artery occlusion followed by 24 h of reperfusion. Subsequently, brain infarct size, brain edema and Evans Blue dye extravasations were measured and neurological deficits were scored. Dietary RHE could significantly reduce cortical and sub-cortical infarct volumes (211.55 ± 24.88 mm3 vs. 40.59 ± 10.04 mm3 vs. 29.96 ± 12.19 mm3vs. 6.58 ± 3.2 mm3), neurologic deficit scores, cerebral edema (82.34 ± 0.42% vs. 79.92 ± 0.49% vs. 79.45 ± 0.26% vs. 79.30 ± 0.19%), blood–brain barrier (BBB) permeability (7.73 ± 0.4 μg/g tissue vs. 4.1 ± 0.23 μg/g tissue vs. 3.58 ± 0.3 μg/g tissue vs. 3.38 ± 0.25 μg/g tissue) in doses of 50, 75 and 100 mg/Kg/day as compared with the control group in the transient model of focal cerebral ischemia. Although pretreatment with RHE plays an important role in the generation of tolerance against cerebral I/R injury, further studies are needed to clarify the mechanism of the ischemic tolerance. PMID:28243285

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

    PubMed Central

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

    2009-01-01

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

  14. How a Stroke Is Diagnosed

    MedlinePlus

    ... News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis Stroke ... Diagnosis » How a Stroke is Diagnosed How a Stroke is Diagnosed How a Stroke is Diagnosed Lab ...

  15. Stroke management

    PubMed Central

    2011-01-01

    Introduction Stroke is the third most common cause of death in most developed countries. It is a worldwide problem; about 4.5 million people die from stroke each year. Stroke can occur at any age, but half of all strokes occur in people aged over 70 years. About 80% of all acute strokes are ischaemic, usually resulting from thrombotic or embolic occlusion of a cerebral artery. The remainder are caused either by intracerebral or subarachnoid haemorrhage. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of specialised care in people with acute stroke? What are the effects of medical treatment in people with acute ischaemic stroke? What are the effects of decompressive hemicraniectomy in acute ischaemic stroke? What are the effects of surgical evacuation for intracerebral haematomas? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 41 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acute reduction in blood pressure, aspirin, evacuation (early surgical evacuation, or conservative treatment), decompressive hemicraniectomy, neuroprotective agents (calcium channel blockers, citicoline, gamma-aminobutyric acid agonists, glycine antagonists, lubeluzole, magnesium, N-methyl-D-aspartate antagonists), specialised stroke care, systemic anticoagulation (heparinoids, specific thrombin inhibitors

  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. Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke

    PubMed Central

    2013-01-01

    Introduction Stem cell therapy can promote good recovery from stroke. Several studies have demonstrated that mesenchymal stem cells (MSC) are safe and effective. However, more information regarding appropriate cell type is needed from animal model. This study was targeted at analyzing the effects in ischemic stroke of acute intravenous (i.v.) administration of allogenic bone marrow- (BM-MSC) and adipose-derived-stem cells (AD-MSC) on functional evaluation results and brain repair markers. Methods Allogenic MSC (2 × 106 cells) were administered intravenously 30 minutes after permanent middle cerebral artery occlusion (pMCAO) to rats. Infarct volume and cell migration and implantation were analyzed by magnetic resonance imaging (MRI) and immunohistochemistry. Function was evaluated by the Rogers and rotarod tests, and cell proliferation and cell-death were also determined. Brain repair markers were analyzed by confocal microscopy and confirmed by western blot. Results Compared to infarct group, function had significantly improved at 24 h and continued at 14 d after i.v. administration of either BM-MSC or AD-MSC. No reduction in infarct volume or any migration/implantation of cells into the damaged brain were observed. Nevertheless, cell death was reduced and cellular proliferation significantly increased in both treatment groups with respect to the infarct group. At 14 d after MSC administration vascular endothelial growth factor (VEGF), synaptophysin (SYP), oligodendrocyte (Olig-2) and neurofilament (NF) levels were significantly increased while those of glial fiibrillary acid protein (GFAP) were decreased. Conclusions i.v. administration of allogenic MSC - whether BM-MSC or AD-MSC, in pMCAO infarct was associated with good functional recovery, and reductions in cell death as well as increases in cellular proliferation, neurogenesis, oligodendrogenesis, synaptogenesis and angiogenesis markers at 14 days post-infarct. PMID:23356495

  19. Efficacy of citicoline as an acute stroke treatment.

    PubMed

    Clark, Wayne M

    2009-04-01

    Citicoline (cytidine-5'-diphosphocholine or CDP-choline) is a precursor essential for the synthesis of phosphatidylcholine, one of the cell membrane components that is degraded during cerebral ischemia to free fatty acids and free radicals. Animal studies suggest that citicoline may protect cell membranes by accelerating resynthesis of phospholipids and suppressing the release of free fatty acids, stabilizing cell membranes, and reducing free radical generation. Numerous experimental stroke studies with citicoline have shown improved outcome and reduced infarct size in both ischemic and hemorrhagic stroke models. Citicoline has been studied worldwide in both ischemic and hemorrhagic clinical stroke with excellent safety and possibly efficacy found in several trials. A meta-analysis of four randomized US clinical citicoline trials concluded that treatment with oral citicoline within the first 24 h after a moderate to severe stroke is safe and increases the probability of complete recovery at 3 months. Citicoline clinical efficacy trials are now continuing outside of the US in both ischemic and hemorrhagic stroke. A citicoline supplement is now available from several sources on the internet.

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Aoki, Takashi; Ikezawa, Shunjiro

    1982-09-01

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

  2. Preventing stroke

    MedlinePlus

    ... risk of stroke. Diseases such as cancer, chronic kidney disease , and some autoimmune diseases . Weak areas in an artery wall or abnormal arteries and veins . Pregnancy, both during and in the weeks right after ...

  3. Stroke Prevention in Atrial Fibrillation

    MedlinePlus

    ... Association Cardiology Patient Page Stroke Prevention in Atrial Fibrillation Christian T. Ruff Download PDF https://doi.org/ ... an irregular and fast heartbeat. What Causes Atrial Fibrillation? Several factors and medical conditions make it more ...

  4. Suicide in stroke survivors: epidemiology and prevention.

    PubMed

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

    2015-01-01

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

  5. Post-stroke dyskinesias

    PubMed Central

    Nakawah, Mohammad Obadah; Lai, Eugene C

    2016-01-01

    Strokes, whether ischemic or hemorrhagic, are among the most common causes of secondary movement disorders in elderly patients. Stroke-related (vascular) movement disorders, however, are uncommon complications of this relatively common disease. The spectrum of post-stroke movement disorders is broad and includes both hypo- and hyperkinetic syndromes. Post-stroke dyskinesias are involuntary hyperkinetic movements arising from cerebrovascular insults and often present with mixed phenotypes of hyperkinesia which can sometimes be difficult to classify. Nevertheless, identification of the most relevant motor phenotype, whenever possible, allows for a more specific phenomenological categorization of the dyskinesia and thus helps guide its treatment. Fortunately, post-stroke dyskinesias are usually self-limiting and resolve within 6 to 12 months of onset, but a short-term pharmacotherapy might sometimes be required for symptom control. Functional neurosurgical interventions targeting the motor thalamus or globus pallidus interna might be considered for patients with severe, disabling, and persistent dyskinesias (arbitrarily defined as duration longer than 12 months). PMID:27853372

  6. Recovery After Stroke: Recurrent Stroke

    MedlinePlus

    ... blood pressure  Find out if you have atrial fibrillation (an irregular heartbeat which allows blood to pool ... your stroke risk. One form  known as atrial fibrillation or AF  causes blood to form clots that ...

  7. Stroke (For Kids)

    MedlinePlus

    ... de los dientes Video: Getting an X-ray Stroke KidsHealth > For Kids > Stroke Print A A A ... get help quickly. continue What Happens During a Stroke? A stroke usually happens suddenly, and a person ...

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

    PubMed

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

    2011-03-17

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

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

    PubMed Central

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  11. Does extreme environmental severity promote plant facilitation? An experimental field test in a subtropical coastal dune.

    PubMed

    Castanho, Camila T; Oliveira, Alexandre A; Prado, Paulo Inácio K L

    2015-07-01

    The stress gradient hypothesis (SGH) postulates how the balance between plant competition and facilitation shifts along environmental gradients. Early formulations of the SGH predicted that facilitation should increase monotonically with stress. However, a recent theoretical refinement of the SGH postulates stronger facilitation under moderate stress, followed by a decreasing role of facilitation in the most severe environments. We conducted field experiments along the most severe part of a coastal dune gradient in southeast Brazil to test the effect of stress on the intensity and importance of the net interactions between two tree species. First, we compared the performance of distinct life stages of Ternstroemia brasiliensis in the presence and absence of Guapira opposita adults along a beach-to-inland gradient, a gradient of environmental severity. To test the effect of one stress factor in particular, we also manipulated water availability, a limiting resource due to the sandy soils. At the most severe part of the coastal gradient (i.e. closest to the seashore), both intensity and importance of the interaction between G. opposita and T. brasiliensis were negatively related to stress, with a pattern consistent across distinct life stages of the target species. However, the sign of the net interaction depended on the life stage of the target species. Our results provide empirical evidence that the role of facilitation tends to wane, leading to neutral or even negative net interactions between species as stress reaches its maximum, as predicted by the recent refinements of the SGH.

  12. Brain Edema After Ischaemic Stroke

    PubMed Central

    Dostovic, Zikrija; Dostovic, Ernestina; Smajlovic, Dzevdet; Ibrahimagic, Omer C.; Avdic, Leila

    2016-01-01

    Objectives: To determine the incidence of brain edema after ischaemic stroke and its impact on the outcome of patients in the acute phase of ischaemic stroke. Patients and Methods: We retrospectively analyzed 114 patients. Ischaemic stroke and brain edema are verified by computed tomography. The severity of stroke was determined by National Institutes of Health Stroke Scale. Laboratory findings were made during the first four days of hospitalization, and complications were verified by clinical examination and additional tests. Results: In 9 (7.9%) patients developed brain edema. Pneumonia was the most common complication (12.3%). Brain edema had a higher incidence in women, patients with hypertension and elevated serum creatinine values, and patients who are suffering from diabetes. There was no significant correlation between brain edema and survival in patients after acute ischaemic stroke. Patients with brain edema had a significantly higher degree of neurological deficit as at admission, and at discharge (p = 0.04, p = 0.004). Conclusion: The cerebral edema is common after acute ischaemic stroke and no effect on survival in the acute phase. The existence of brain edema in acute ischaemic stroke significantly influence the degree of neurological deficit. PMID:27994292

  13. Stroke and episodic memory disorders.

    PubMed

    Lim, Chun; Alexander, Michael P

    2009-12-01

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

  14. An experimental comparison of several current viscoplastic constitutive models at elevated temperature

    NASA Technical Reports Server (NTRS)

    James, G. H.; Imbrie, P. K.; Hill, P. S.; Allen, D. H.; Haisler, W. E.

    1988-01-01

    Four current viscoplastic models are compared experimentally for Inconel 718 at 593 C. This material system responds with apparent negative strain rate sensitivity, undergoes cyclic work softening, and is susceptible to low cycle fatigue. A series of tests were performed to create a data base from which to evaluate material constants. A method to evaluate the constants is developed which draws on common assumptions for this type of material, recent advances by other researchers, and iterative techniques. A complex history test, not used in calculating the constants, is then used to compare the predictive capabilities of the models. The combination of exponentially based inelastic strain rate equations and dynamic recovery is shown to model this material system with the greatest success. The method of constant calculation developed was successfully applied to the complex material response encountered. Backstress measuring tests were found to be invaluable and to warrant further development.

  15. Definition and Implications of the Preventable Stroke

    PubMed Central

    Fisher, Mark; Moores, Lisa; Alsharif, Mohamad N.; Paganini-Hill, Annlia

    2016-01-01

    IMPORTANCE Although patients with acute stroke are routinely evaluated for potential treatment (ie, treatability of the stroke), preventability of the presenting stroke is generally not seriously considered. OBJECTIVE To systematically analyze stroke preventability. DESIGN, SETTING, AND PARTICIPANTS We evaluated medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012, at the University of California Irvine Medical Center. Mean (SE) patient age was 67.2 (0.8) years. Data analysis was conducted from July 3, 2014, to August 4, 2015. EXPOSURES Medical records were systematically examined for demographic information, stroke risk factors, stroke severity, and acute stroke treatment. MAIN OUTCOMES AND MEASURES We defined stroke preventability as the degree to which the patient’s presenting stroke was preventable. Using variables easily determined at onset of stroke, we developed a 10-point scale (0, not preventable; 10, most preventable) to classify the degree of stroke preventability. Our focus was effectiveness of treatment of hypertension (0–2 points), hyperlipidemia (0–2 points), and atrial fibrillation (0–4 points), as well as use of antithrombotic treatment for known prior cerebrovascular and cardiovascular disease (0–2 points). RESULTS Total risk scores ranged from 0 to 8 (mean [SE], 2.2 [0.1]), with 207 patients (75.5%) exhibiting some degree of preventability (score of 1 or higher). Seventy-one patients (25.9%) had scores of 4 or higher, indicating that the stroke was highly preventable. Severity of stroke as determined by the National Institutes of Health Stroke Scale score was not related to preventability of stroke. However, 21 of 71 patients (29.6%) whose stroke was highly preventable were treated with intravenous or intra-arterial acute stroke therapy while these treatments were provided for only 13 of 67 patients (19.4%) with scores of 0 (no preventability) and 19 of

  16. Enkephalins and hormonal-metabolic reactions in experimental stress depending on its severity

    SciTech Connect

    Lishmanov, Y.B.; Alekminskaya, L.A.; Lasukova, T.V.

    1985-08-01

    The aim of this investigation was to study the action of enkephalins on changes in hormonal-metabolic constants in stress of varied severity. Catecholamine excretion with the urine was determined fluorometrically, serum cortisol and insulin concentrations were measured radioimmunologically and glucose was determined by the standard orthotoluidine method. The results of the investigation indicate that enkephalins have a modulating effect on various hormonal mechanisms of adaptation stress. The results confirm that the physiological action of the peptide regulator depends on the functional state of the biological systems and it may differ sharply, even to the extent of diametrically opposite effects.

  17. Allopurinol reduces severity of delayed neurologic sequelae in experimental carbon monoxide toxicity in rats.

    PubMed

    Dong, Guangtao; Ren, Ming; Wang, Xiujie; Jiang, Hongquan; Yin, Xiang; Wang, Shuyu; Wang, Xudong; Feng, Honglin

    2015-05-01

    Approximately half of those who survive severe carbon monoxide (CO) poisoning develop delayed neurologic sequelae. Growing evidence supports the crucial role of free radicals in delayed brain injury associated with CO toxicity. Xanthine oxidase (XO) has been reported to play a pivotal role in the generation of reactive oxygen species (ROS) in CO poisoning. A recent report indicates that allopurinol both attenuated oxidative stress and possessed anti-inflammatory properties in an animal model of acute liver failure. In this study, we aimed to explore the potential of allopurinol to reduce the severity of delayed neurologic sequelae. The rats were first exposed to 1000 ppm CO for 40 min and then to 3000 ppm CO for another 20 min. Following CO poisoning, the rats were injected with allopurinol (50 mg/kg, i.p.) six times. Results showed that allopurinol significantly reduced neuronal death and suppressed expression of pro-inflammatory factors, including tumor necrosis factor-α, intercellular adhesion molecule-1, ionized calcium-binding adapter molecule 1, and degraded myelin basic protein. Furthermore, behavioral studies revealed an improved performance in the Morris water maze test. Our findings indicated that allopurinol may have protective effects against delayed neurologic sequelae caused by CO toxicity.

  18. pVAXhsp65 Vaccination Primes for High IL-10 Production and Decreases Experimental Encephalomyelitis Severity.

    PubMed

    Zorzella-Pezavento, Sofia Fernanda Gonçalves; Chiuso-Minicucci, Fernanda; França, Thais Graziela Donegá; Ishikawa, Larissa Lumi Watanabe; da Rosa, Larissa Camargo; Colavite, Priscila Maria; Balbino, Bianca; Marques, Camila; Ikoma, Maura Rosane Valerio; Masson, Ana Paula; Silva, Célio Lopes; Sartori, Alexandrina

    2017-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a demyelinating pathology of the central nervous system (CNS) used as a model to study multiple sclerosis immunopathology. EAE has also been extensively employed to evaluate potentially therapeutic schemes. Considering the presence of an immune response directed to heat shock proteins (hsps) in autoimmune diseases and the immunoregulatory potential of these molecules, we evaluated the effect of a previous immunization with a genetic vaccine containing the mycobacterial hsp65 gene on EAE development. C57BL/6 mice were immunized with 4 pVAXhsp65 doses and 14 days later were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) emulsified in Complete Freund's Adjuvant. Vaccinated mice presented significant lower clinical scores and lost less body weight. MOG35-55 immunization also determined less inflammation in lumbar spinal cord but did not change CD4+CD25+Foxp3+ T cells frequency in spleen and CNS. Infiltrating cells from the CNS stimulated with rhsp65 produced significantly higher levels of IL-10. These results suggest that the ability of pVAXhsp65 vaccination to control EAE development is associated with IL-10 induction.

  19. Experimental study of showerhead cooling on a cylinder comparing several configurations using cylindrical and shaped holes

    SciTech Connect

    Reiss, H.; Boelcs, A.

    2000-01-01

    Film cooling and heat transfer measurements on a cylinder model have been conducted using the transient thermochromic liquid crystal technique. Three showerhead cooling configurations adapted to leading edge film cooling of gas turbine blades were directly compared: classical cylindrical holes versus two types of shaped hole exits. The experiments were carried out in a free jet test facility at two different flow conditions, Mach numbers M = 0.14 and M = 0.26, yielding Reynolds numbers based on the cylinder diameter of 8.6e4 and 1.55e5, respectively, All experiments were done at a mainstream turbulence level of Tu = 7% with an integral length scale of L{sub x} = 9.1 mm (M = 0.14), or L{sub x} = 10.5 mm (M = 0.26), respectively. Foreign gas injection (CO{sub 2}) was used, yielding an engine-near density ratio of 1.6, with blowing ratios ranging from 0.6 to 1.5. Detailed experimental results are shown, including surface distributions of film cooling effectiveness and local heat transfer coefficients. Additionally, heat transfer and heat load augmentation due to injection with respect to the uncooled cylinder are reported. For a given cooling gas consumption, the laid-back shaped hole exits lead to a clear enhancement of the cooling performance compared to cylindrical exits, whereas laterally expanded holes give only slight performance enhancement.

  20. pVAXhsp65 Vaccination Primes for High IL-10 Production and Decreases Experimental Encephalomyelitis Severity

    PubMed Central

    Chiuso-Minicucci, Fernanda; Marques, Camila; Ikoma, Maura Rosane Valerio; Masson, Ana Paula; Silva, Célio Lopes

    2017-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a demyelinating pathology of the central nervous system (CNS) used as a model to study multiple sclerosis immunopathology. EAE has also been extensively employed to evaluate potentially therapeutic schemes. Considering the presence of an immune response directed to heat shock proteins (hsps) in autoimmune diseases and the immunoregulatory potential of these molecules, we evaluated the effect of a previous immunization with a genetic vaccine containing the mycobacterial hsp65 gene on EAE development. C57BL/6 mice were immunized with 4 pVAXhsp65 doses and 14 days later were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein (MOG35–55) emulsified in Complete Freund's Adjuvant. Vaccinated mice presented significant lower clinical scores and lost less body weight. MOG35–55 immunization also determined less inflammation in lumbar spinal cord but did not change CD4+CD25+Foxp3+ T cells frequency in spleen and CNS. Infiltrating cells from the CNS stimulated with rhsp65 produced significantly higher levels of IL-10. These results suggest that the ability of pVAXhsp65 vaccination to control EAE development is associated with IL-10 induction. PMID:28321419

  1. Gestational Hypothyroidism Increases the Severity of Experimental Autoimmune Encephalomyelitis in Adult Offspring

    PubMed Central

    Albornoz, Eduardo A.; Carreño, Leandro J.; Cortes, Claudia M.; Gonzalez, Pablo A.; Cisternas, Pablo A.; Cautivo, Kelly M.; Catalán, Tamara P.; Opazo, M. Cecilia; Eugenin, Eliseo A.; Berman, Joan W.; Bueno, Susan M.; Kalergis, Alexis M.

    2013-01-01

    Background: Maternal thyroid hormones play a fundamental role in appropriate fetal development during gestation. Offspring that have been gestated under maternal hypothyroidism suffer cognitive impairment. Thyroid hormone deficiency during gestation can significantly impact the central nervous system by altering the migration, differentiation, and function of neurons, oligodendrocytes, and astrocytes. Given that gestational hypothyroidism alters the immune cell ratio in offspring, it is possible that this condition could result in higher sensitivity for the development of autoimmune diseases. Methods: Adult mice gestated under hypothyroidism were induced with experimental autoimmune encephalomyelitis (EAE). Twenty-one days after EAE induction, the disease score, myelin content, immune cell infiltration, and oligodendrocyte death were evaluated. Results: We observed that mice gestated under hypothyroidism showed higher EAE scores after disease induction during adulthood compared to mice gestated in euthyroidism. In addition, spinal cord sections of mice gestated under hypothyroidism that suffered EAE in adulthood showed higher demyelination, CD4+ and CD8+ infiltration, and increased oligodendrocyte death. Conclusions: These results show for the first time that a deficiency in maternal thyroid hormones during gestation can influence the outcome of a central nervous system inflammatory disease, such as EAE, in their offspring. These data strongly support evaluating thyroid hormones in pregnant women and treating hypothyroidism during pregnancy to prevent increased susceptibility to inflammatory diseases in the central nervous system of offspring. PMID:23777566

  2. Experimental investigation of fiberglass sandwich composite bending behaviour after severe aging condition

    NASA Astrophysics Data System (ADS)

    Gambaro, Carla; Lertora, Enrico; Mandolfino, Chiara

    2016-10-01

    Fiber Reinforced Polymer (FRP) sandwich panels are increasing their application as structural and non-structural components in all kinds of construction. By varying the material and thickness of core and face sheets, it is possible to obtain sandwich structures with different properties and performance. In particular, their advantages as lightweight and high mechanical properties make them extremely suitable for the transport industry. One of the most critical aspects regarding composite materials for engineering application is their performance after hygrothermal aging. The panels used in this study are composed of low density core, made by thermosetting resin foam with microspheres and glass fibers rolled until obtaining the required thickness, and two face sheets of the same material but realized in high density. In this study, the authors focused on the bending behaviour of this kind of sandwich panel, as received and after severe aging cycles.

  3. Hyperactivity induced by prenatal BrdU exposure across several experimental conditions.

    PubMed

    Kuwagata, Makiko; Ogawa, Tetsuo; Muneoka, Katsumasa; Shioda, Seiji

    2011-12-01

    Behavioral results are sometimes not reproducible even in the positive controls of developmental neurotoxicity (DNT) tests. Effects of several factors on the results should be considered. In the present paper, we examined the effects of strain-, gender-, and test-condition differences on BrdU-induced hyperactivity. The results showed that BrdU-induced hyperactivity was reproducible in two rat strains (SD and F344 rats), rodent species (rat and mouse), and both sexes. When the level of background sound in a test room was increased, the hyperactivity was persistent, resulting in no effect of background sound on BrdU-induced hyperactivity. Thus, we have demonstrated that the BrdU-animal model is a useful positive control via prenatal exposure to validate the entire DNT test process.

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

    PubMed

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

    2014-04-01

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

  5. Stroke at a younger age.

    PubMed

    Delilović-Vranić, Jasminka; Alajbegović, Azra; Tirić-Campara, Merita; Todorović, Ljubica

    2011-06-01

    Stroke is a suddenly developing disorder, caused by focal disturbance of cerebral circulation, followed by neurologic deficits of varying intensity with duration longer than 1 hour; it mostly occurs in old and middle age, and rarely at a younger age. The aim of the study was to analyze the occurrence of stroke at a younger age (18-49 years). We analyzed all stroke patients aged 18-49 treated at University Department of Neurology in Sarajevo during 2009, including analysis of their risk factors. During the one-year period, there were 820 stroke patients in total, 132 (18.5%) of them aged 18-49, male to female ratio 51.35%:48.65%. The majority of strokes were of ischemic type (94.59%), with only 5.41% of hemorrhagic stroke. The following risk factors were confirmed in study patients: hypertension (64.86%), smoking (57.76%), dyslipidemia (48.65%), ischemic heart disease (43.32%), psychological stress (29.73%), diabetes mellitus type 2 (24.43%), previous stroke including transient ischemic attack (21.62%), and others. During the one-month follow-up, 27.03% of patients achieved complete recovery, whereas mild neurologic signs were retained in 54.05%, signs of severe deficit requiring assistance in 13.51%, and 5.41% of patients died. In conclusion, stroke occurs even at a younger age in certain percentage. Along with smoking, diabetes, dyslipidemia and stress, hypertension is one of the leading risk factors for stroke also at a younger age. Timely and appropriate treatment contributes to faster recovery and shorter hospital stay, while reducing overall stroke sequels. The best prevention is primary, i.e. fighting risk factors and healthy lifestyle.

  6. Infusion of Bone Marrow Mesenchymal Stem Cells Attenuates Experimental Severe Acute Pancreatitis in Rats

    PubMed Central

    Huang, Dandan; Gao, Jun; Gong, Yanfang; Wu, Hongyu; Xu, Aifang

    2016-01-01

    Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation. Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection. The survival rate was observed and MSCs were traced after transplantation. The expression of TNF-α and IL-1β mRNA in the transplantation group was also analyzed. Results. The survival rate of the transplantation group was significantly higher compared to the control group (p < 0.05). Infused MSCs were detected in the pancreas and BM 3 days after transplantation. The expression of TNF-α and IL-1β mRNA in the transplantation group was significantly lower than in the control group in both the pancreas and the lungs (p < 0.05). Conclusions. MSC transplantation could improve the prognosis of SAP rats. Engrafted MSCs have the capacity of homing, migration, and planting during the treatment of SAP. PMID:27721836

  7. 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

    PubMed Central

    Guo, Wen-yi; Zhao, Liang; Xiang, Ming-wei; Mei, Fang-chao; Abliz, Ablikim; Hu, Peng; Deng, Wen-hong; Yu, Jia

    2016-01-01

    Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment. PMID:27656209

  8. Experimental functional analysis of severe skin-picking behavior in Prader-Willi syndrome.

    PubMed

    Hall, Scott S; Hustyi, Kristin M; Chui, Clara; Hammond, Jennifer L

    2014-10-01

    Skin picking is an extremely distressing and treatment resistant behavior commonly shown by individuals with Prader-Willi syndrome (PWS). However, with the exception of a limited number of published single-case and survey studies, little is known about the environmental determinants of skin picking in this population. In this study, functional analyses were conducted with thirteen individuals with PWS, aged 6-23 years, who engaged in severe skin-picking behavior. In addition to the conditions typically employed in a functional analysis (i.e., alone, attention, play, demand), we included an ignore condition to examine potential effects of stimulus control by the presence of an adult. Twelve participants engaged in skin picking during the functional analysis, with the highest levels occurring in the alone and ignore conditions for eight participants, suggesting that skin picking in these participants was maintained by automatic reinforcement. For the remaining four participants, an undifferentiated pattern of low-rate skin picking was observed across conditions. These data confirm previous studies indicating that skin picking in PWS may be maintained most often by automatically produced sensory consequences. There were no associations between demographic characteristics of the participants (e.g., sex, age, IQ or BMI) and levels of skin picking observed in the functional analysis. Additional investigations are needed to identify the nature of the sensory consequences produced during episodes of skin picking in PWS. Behavioral interventions designed to extinguish or compete with the potential sensory consequences arising from skin picking in PWS are also warranted.

  9. Biotherapies in stroke.

    PubMed

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

    2014-12-01

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

  10. Severe embryotoxicity of artemisinin derivatives in experimental animals, but possibly safe in pregnant women.

    PubMed

    Li, Qigui; Weina, Peter J

    2009-12-25

    Preclinical studies in rodents have demonstrated that artemisinins, especially injectable artesunate, can induce fetal death and congenital malformations at a low dose range. The embryotoxicity can be induced in those animals only within a narrow window in early embryogenesis. Evidence was presented that the mechanism by which embryotoxicity of artemisinins occurs seems to be limited to fetal erythropoiesis and vasculogenesis/ angiogenesis on the very earliest developing red blood cells, causing severe anemia in the embryos with higher drug peak concentrations. However, this embryotoxicity has not been convincingly observed in clinical trials from 1,837 pregnant women, including 176 patients in the first trimester exposed to an artemisinin agent or artemisinin-based combination therapy (ACT) from 1989 to 2009. In the rodent, the sensitive early red cells are produced synchronously over one day with single or multiple exposures to the drug can result in a high proportion of cell deaths. In contrast, primates required a longer period of treatment of 12 days to induce such embryonic loss. In humans only limited information is available about this stage of red cell development; however, it is known to take place over a longer time period, and it may well be that a limited period of treatment of 2 to 3 days for malaria would not produce serious toxic effects. In addition, current oral intake, the most commonly used route of administration in pregnant women with an ACT, results in lower peak concentration and shorter exposure time of artemisinins that demonstrated that such a concentration-course profile is unlikely to induce the embryotoxicity. When relating the animal and human toxicity of artemisinins, the different drug sensitive period and pharmacokinetic profiles as reviewed in the present report may provide a great margin of safety in the pregnant women.

  11. Severity of experimental traumatic brain injury modulates changes in concentrations of cerebral free amino acids.

    PubMed

    Amorini, Angela Maria; Lazzarino, Giacomo; Di Pietro, Valentina; Signoretti, Stefano; Lazzarino, Giuseppe; Belli, Antonio; Tavazzi, Barbara

    2017-03-01

    In this study, concentrations of free amino acids (FAA) and amino group containing compounds (AGCC) following graded diffuse traumatic brain injury (mild TBI, mTBI; severe TBI, sTBI) were evaluated. After 6, 12, 24, 48 and 120 hr aspartate (Asp), glutamate (Glu), asparagine (Asn), serine (Ser), glutamine (Gln), histidine (His), glycine (Gly), threonine (Thr), citrulline (Cit), arginine (Arg), alanine (Ala), taurine (Tau), γ-aminobutyrate (GABA), tyrosine (Tyr), S-adenosylhomocysteine (SAH), l-cystathionine (l-Cystat), valine (Val), methionine (Met), tryptophane (Trp), phenylalanine (Phe), isoleucine (Ile), leucine (Leu), ornithine (Orn), lysine (Lys), plus N-acetylaspartate (NAA) were determined in whole brain extracts (n = 6 rats at each time for both TBI levels). Sham-operated animals (n = 6) were used as controls. Results demonstrated that mTBI caused modest, transient changes in NAA, Asp, GABA, Gly, Arg. Following sTBI, animals showed profound, long-lasting modifications of Glu, Gln, NAA, Asp, GABA, Ser, Gly, Ala, Arg, Citr, Tau, Met, SAH, l-Cystat, Tyr and Phe. Increase in Glu and Gln, depletion of NAA and Asp increase, suggested a link between NAA hydrolysis and excitotoxicity after sTBI. Additionally, sTBI rats showed net imbalances of the Glu-Gln/GABA cycle between neurons and astrocytes, and of the methyl-cycle (demonstrated by decrease in Met, and increase in SAH and l-Cystat), throughout the post-injury period. Besides evidencing new potential targets for novel pharmacological treatments, these results suggest that the force acting on the brain tissue at the time of the impact is the main determinant of the reactions ignited and involving amino acid metabolism.

  12. Manganese-enhanced MRI Offers Correlation with Severity of Spinal Cord Injury in Experimental Models

    PubMed Central

    Martirosyan, Nikolay L.; Turner, Gregory H.; Kaufman, Jason; Patel, Arpan A.; Belykh, Evgenii; Kalani, M. Yashar S.; Theodore, Nicholas; Preul, Mark C.

    2016-01-01

    Background: Spinal cord injuries (SCI) are clinically challenging, because neural regeneration after cord damage is unknown. In SCI animal models, regeneration is evaluated histologically, requiring animal sacrifice. Noninvasive techniques are needed to detect longitudinal SCI changes. Objective: To compare manganese-enhanced magnetic resonance imaging (MRI [MEMRI]) in hemisection and transection of SCI rat models with diffusion tensor imaging (DTI) and histology. Methods: Rats underwent T9 spinal cord transection (n=6), hemisection (n=6), or laminectomy without SCI (controls, n=6). One-half of each group received lateral ventricle MnCl2 injections 24 hours later. Conventional DTI or T1-weighted MRI was performed 84 hours post-surgery. MEMRI signal intensity ratio above and below the SCI level was calculated. Fractional anisotropy (FA) measurements were taken 1 cm rostral to the SCI. The percentage of FA change was calculated 10 mm rostral to the SCI epicenter, between FA at the dorsal column lesion normalized to a lateral area without FA change. Myelin load (percentage difference) among groups was analyzed by histology. Results: In transection and hemisection groups, mean MEMRI ratios were 0.62 and 0.87, respectively, versus 0.99 in controls (P<0.001 and P<0.001, respectively); mean FA decreases were 67.5% and 40.1%, respectively, compared with a 6.1% increase in controls (P=0.002 and P=0.019, respectively). Mean myelin load decreased by 38.8% (transection) and 51.8% (hemisection) compared to controls (99.1%) (P<0.001 and P<0.001, respectively). Pearson’s correlation coefficients were -0.94 for MEMRI ratio and FA changes and 0.87 for MEMRI and myelin load. Conclusion: MEMERI results correlated to SCI severity measured by FA and myelin load. MEMRI is a useful noninvasive tool to assess neuronal damage after SCI. PMID:28144384

  13. Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation.

    PubMed

    Guidine, Patrícia Alves Maia; Cash, Diana; Drumond, Luciana Estefani; de Souza E Rezende, Gustavo Henrique; Massensini, André Ricardo; Williams, Steve Charles Rees; Moraes-Santos, Tasso; Moraes, Márcio Flávio Dutra; Mesquita, Michel Bernanos Soares

    2014-01-01

    Severe scorpion envenoming (SSE) is more frequent in children and is characterized by systemic dysfunctions with a mortality rate of up to 9%. Recent evidence shows that the central nervous system (CNS) plays a key role in triggering the cascade of symptoms present in SSE. The age-dependent role of the CNS in SSE lethality may be summarized in 3 hypotheses: (1) the shown increased blood brain barrier permeability of infants to the toxins would especially and primarily compromise neurovegetative control areas, (2) the neurons within these areas have high affinity to the toxins, and (3) the neurovascular interaction is such that SSE metabolically compromises proper function of toxin-targeted areas. A pharmacological magnetic resonance imaging paradigm was used to evaluate localized hemodynamic changes in relative cerebral blood volume (rCBV) for 30 min after the injection of TsTX, the most lethal toxin from the venom of the Tityus serrulatus scorpion. The brainstem showed significant rCBV reduction 1 min after TsTX administration, whereas rostral brain areas had delayed increase in rCBV (confirmed by laser Doppler measurements of cortical cerebral blood flow). Moreover, metabolic activity by 14C-2-deoxyglucose autoradiography showed the highest relative increase at the brainstem. To test whether TsTX has high affinity to brainstem neurons, the lateral ventricle was injected with Alexa Fluor 568 TsTX. Although some neurons showed intense fluorescence, the labeling pattern suggests that specific neurons were targeted. Altogether, these results suggest that brainstem areas involved in neurovegetative control are most likely within the primary structures triggering the cascade of symptoms present in SSE.

  14. Estimation of hydrogen sulfide emission rates at several wastewater treatment plants through experimental concentration measurements and dispersion modeling.

    PubMed

    Llavador Colomer, Fernando; Espinós Morató, Héctor; Mantilla Iglesias, Enrique

    2012-07-01

    The management and operation of wastewater treatment plants (WWTP) usually involve the release into the atmosphere of malodorous substances with the potential to reduce the quality of life of people living nearby. In this type of facility, anaerobic degradation processes contribute to the generation of hydrogen sulfide (H2S), often at quite high concentrations; thus, the presence of this chemical compound in the atmosphere can be a good indicator of the occurrence and intensity of the olfactory impact in a specific area. The present paper describes the experimental and modelling work being carried out by CEAM-UMH in the surroundings of several wastewater treatment plants located in the Valencia Autonomous Community (Spain). This work has permitted the estimation of H2S emission rates at different WWTPs under different environmental and operating conditions. Our methodological approach for analyzing and describing the most relevant aspects of the olfactory impact consisted of several experimental campaigns involving intensive field measurements using passive samplers in the vicinity of several WWTPs, in combination with numerical simulation results from a diagnostic dispersion model. A meteorological tower at each WWTP provided the input values for the dispersion code, ensuring a good fit of the advective component and therefore more confidence in the modelled concentration field in response to environmental conditions. Then, comparisons between simulated and experimental H2S concentrations yielded estimates of the global emission rate for this substance at several WWTPs at different time periods. The results obtained show a certain degree of temporal and spatial (between-plant) variability (possibly due to both operational and environmental conditions). Nevertheless, and more importantly, the results show a high degree of uniformity in the estimates, which consistently stay within the same order of magnitude.

  15. Prevalence of electrocardiographic abnormalities based on hypertension severity and blood pressure levels: the Reasons for Geographic and Racial Differences in Stroke study.

    PubMed

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

    2016-09-01

    We evaluated the prevalence of major and minor electrocardiographic (ECG) abnormalities based on blood pressure (BP) control and hypertension (HTN) treatment resistance. We analyzed data from the Reasons for Geographic and Racial Differences in Stroke study of 20,932 participants who were divided into presence of major (n = 3782), only minor (n = 8944), or no (n = 8206) ECG abnormalities. The cohort was stratified into normotension (n = 3373), pre-HTN (n = 4142), controlled HTN (n = 8619), uncontrolled HTN (n = 3544), controlled apparent treatment-resistant HTN (aTRH, n = 400), and uncontrolled aTRH (n = 854) groups, and the prevalence ratios (PRs) of major and minor ECG abnormalities were assessed separately for each BP group. The full multivariable adjustment included demographics, risk factors, and HTN duration. Compared with normotension, the PRs of major ECG abnormalities for pre-HTN, controlled HTN, uncontrolled HTN, controlled aTRH, and uncontrolled aTRH groups were 1.01 (0.90-1.14), 1.30 (1.16-1.45), 1.37 (1.23-1.54), 1.42 (1.22-1.64), and 1.44 (1.26-1.65), respectively (P < .001), whereas the PRs of minor ECG abnormalities among each of the above BP groups were similar. Detection of major ECG abnormalities among hypertensive persons with poor control and treatment resistance may help improve their cardiovascular risk stratification and early intervention.

  16. Experimental testing of total knee replacements with UHMW-PE inserts: impact of severe wear test conditions.

    PubMed

    Zietz, Carmen; Reinders, Joern; Schwiesau, Jens; Paulus, Alexander; Kretzer, Jan Philippe; Grupp, Thomas; Utzschneider, Sandra; Bader, Rainer

    2015-03-01

    Aseptic implant loosening due to inflammatory reactions to wear debris is the main reason for the revision of total knee replacements (TKR). Hence, the decrease in polyethylene wear particle generation from the articulating surfaces is aimed at improving implant design and material. For preclinical testing of new TKR systems standardized wear tests are required. However, these wear tests do not reproduce the entire in vivo situation, since the pattern and amount of wear and subsequent implant failure are underestimated. Therefore, daily activity, kinematics, implant aging and position, third-body-wear and surface properties have to be considered to estimate the wear of implant components in vivo. Hence, severe test conditions are in demand for a better reproduction of the in vivo situation of TKR. In the present article an overview of different experimental wear test scenarios considering clinically relevant polyethylene wear situations using severe test conditions is presented.

  17. Arterial ischemic stroke in HIV

    PubMed Central

    Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J.; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L.; Nath, Avindra; Heyderman, Robert S.; Connor, Myles D.; Solomon, Tom

    2016-01-01

    HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505

  18. Pathophysiology, treatment, and animal and cellular models of human ischemic stroke

    PubMed Central

    2011-01-01

    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

  19. Effects of thoracic epidural anesthesia on survival and microcirculation in severe acute pancreatitis: a randomized experimental trial

    PubMed Central

    2013-01-01

    Introduction Severe acute pancreatitis is still a potentially life threatening disease with high mortality. The aim of this study was to evaluate the therapeutic effect of thoracic epidural anaesthesia (TEA) on survival, microcirculation, tissue oxygenation and histopathologic damage in an experimental animal model of severe acute pancreatitis in a prospective animal study. Methods In this study, 34 pigs were randomly assigned into 2 treatment groups. After severe acute pancreatitis was induced by intraductal injection of glycodesoxycholic acid in Group 1 (n = 17) bupivacaine (0.5%; bolus injection 2 ml, continuous infusion 4 ml/h) was applied via TEA. In Group 2 (n = 17) no TEA was applied. During a period of 6 hours after induction, tissue oxygen tension (tpO2) in the pancreas and pancreatic microcirculation was assessed. Thereafter animals were observed for 7 days followed by sacrification and histopathologic examination. Results Survival rate after 7 days was 82% in Group 1 (TEA) versus 29% in Group 2: (Control) (P <0.05). Group 1 (TEA) also showed a significantly superior microcirculation (1,608 ± 374 AU versus 1,121 ± 510 AU; P <0.05) and tissue oxygenation (215 ± 64 mmHg versus 138 ± 90 mmHG; P <0.05) as compared to Group 2 (Control). Consecutively, tissue damage in Group 1 was reduced in the histopathologic scoring (5.5 (3 to 8) versus 8 (5.5 to 10); P <0.05). Conclusions TEA led to improved survival, enhanced microcirculatory perfusion and tissue oxygenation and resulted in less histopathologic tissue-damage in an experimental animal model of severe acute pancreatitis. PMID:24314012

  20. The "Know Stroke" Campaign

    MedlinePlus

    ... Current Issue Past Issues Special Section The "Know Stroke" Campaign Past Issues / Summer 2007 Table of Contents ... campaign for the U.S. Hispanic community. 1 Know Stroke A stroke occurs when the blood supply to ...

  1. Healthy Living after Stroke

    MedlinePlus

    ... Stories Stroke Heroes Among Us Healthy Living After Stroke Nutrition Good nutrition is one way to reduce ... look to maintain health and wellness. Subscribe to Stroke Connection Get quarterly digital issues plus our monthly ...

  2. CXCR3/CXCL10 Axis Regulates Neutrophil-NK Cell Cross-Talk Determining the Severity of Experimental Osteoarthritis.

    PubMed

    Benigni, Giorgia; Dimitrova, Petya; Antonangeli, Fabrizio; Sanseviero, Emilio; Milanova, Viktoriya; Blom, Arjen; van Lent, Peter; Morrone, Stefania; Santoni, Angela; Bernardini, Giovanni

    2017-03-01

    Several immune cell populations are involved in cartilage damage, bone erosion, and resorption processes during osteoarthritis. The purpose of this study was to investigate the role of NK cells in the pathogenesis of experimental osteoarthritis and whether and how neutrophils can regulate their synovial localization in the disease. Experimental osteoarthritis was elicited by intra-articular injection of collagenase in wild type and Cxcr3(-/-) 8-wk old mice. To follow osteoarthritis progression, cartilage damage, synovial thickening, and osteophyte formation were measured histologically. To characterize the inflammatory cells involved in osteoarthritis, synovial fluid was collected early after disease induction, and the cellular and cytokine content were quantified by flow cytometry and ELISA, respectively. We found that NK cells and neutrophils are among the first cells that accumulate in the synovium during osteoarthritis, both exerting a pathogenic role. Moreover, we uncovered a crucial role of the CXCL10/CXCR3 axis, with CXCL10 increasing in synovial fluids after injury and Cxcr3(-/-) mice being protected from disease development. Finally, in vivo depletion experiments showed that neutrophils are involved in an NK cell increase in the synovium, possibly by expressing CXCL10 in inflamed joints. Thus, neutrophils and NK cells act as important disease-promoting immune cells in experimental osteoarthritis and their functional interaction is promoted by the CXCL10/CXCR3 axis.

  3. Evaluation of the Therapeutic Potential of Anti-TLR4-Antibody MTS510 in Experimental Stroke and Significance of Different Routes of Application

    PubMed Central

    Czech-Zechmeister, Bozena; Könnecke, Birte; Lühder, Fred; Trendelenburg, George

    2016-01-01

    Toll-like receptors (TLRs) are central sensors for the inflammatory response in ischemia-reperfusion injury. We therefore investigated whether TLR4 inhibition could be used to treat stroke in a standard model of focal cerebral ischemia. Anti-TLR4/MD2-antibody (mAb clone MTS510) blocked TLR4-induced cell activation in vitro, as reported previously. Here, different routes of MTS510 application in vivo were used to study the effects on stroke outcome up to 2d after occlusion of the middle cerebral artery (MCAO) for 45min in adult male C57Bl/6 wild-type mice. Improved neurological performance, reduced infarct volumes, and reduced brain swelling showed that intravascular application of MTS510 had a protective effect in the model of 45min MCAO. Evaluation of potential long-term adverse effects of anti-TLR4-mAb-treament revealed no significant deleterious effect on infarct volumes nor neurological deficit after 14d of reperfusion in a mild model of stroke (15min MCAO). Interestingly, inhibition of TLR4 resulted in an altered adaptive immune response at 48 hours after reperfusion. We conclude that blocking TLR4 by the use of specific mAb is a promising strategy for stroke therapy. However, long-term studies with increased functional sensitivity, larger sampling sizes and use of other species are required before a clinical use could be envisaged. PMID:26849209

  4. Evaluation of the Therapeutic Potential of Anti-TLR4-Antibody MTS510 in Experimental Stroke and Significance of Different Routes of Application.

    PubMed

    Andresen, Lena; Theodorou, Konstantina; Grünewald, Sarah; Czech-Zechmeister, Bozena; Könnecke, Birte; Lühder, Fred; Trendelenburg, George

    2016-01-01

    Toll-like receptors (TLRs) are central sensors for the inflammatory response in ischemia-reperfusion injury. We therefore investigated whether TLR4 inhibition could be used to treat stroke in a standard model of focal cerebral ischemia. Anti-TLR4/MD2-antibody (mAb clone MTS510) blocked TLR4-induced cell activation in vitro, as reported previously. Here, different routes of MTS510 application in vivo were used to study the effects on stroke outcome up to 2d after occlusion of the middle cerebral artery (MCAO) for 45 min in adult male C57Bl/6 wild-type mice. Improved neurological performance, reduced infarct volumes, and reduced brain swelling showed that intravascular application of MTS510 had a protective effect in the model of 45 min MCAO. Evaluation of potential long-term adverse effects of anti-TLR4-mAb-treament revealed no significant deleterious effect on infarct volumes nor neurological deficit after 14d of reperfusion in a mild model of stroke (15 min MCAO). Interestingly, inhibition of TLR4 resulted in an altered adaptive immune response at 48 hours after reperfusion. We conclude that blocking TLR4 by the use of specific mAb is a promising strategy for stroke therapy. However, long-term studies with increased functional sensitivity, larger sampling sizes and use of other species are required before a clinical use could be envisaged.

  5. PREDICTORS FOR POST- STROKE DELIRIUM OUTCOME

    PubMed Central

    Dostovic, Zikrija; Dostovic, Ernestina; Smajlovic, Dzevdet; Ibrahimagic, Omer C.; Avdic, Leila; Becirovic, Elvir

    2016-01-01

    Background: There have been only a small number of studies that have evaluated the outcome of post-stroke delirium. Objectives: To evaluate the effects of gender, age, stroke localization, delirium severity, previous illnesses, associated medical complications on delirium outcome as well as, to determine effects of delirium on cognitive functioning one year after stroke. Patients and Methods: Comprehensive neuropsychological assessments were performed within the first week of stroke onset, at hospital discharge, and followed-up for 3, 6 and 12 months after stroke. We used diagnostic tools such as Glazgow Coma Scale, Delirium Rating Scale, National Institutes of Health Stroke Scale and Mini-Mental State. Results: Patients who developed post-stroke delirium had significantly more complications (p = 0.0005). Direct logistic regression was performed to assess the impact of several factors on the likelihood that patients will die. The strongest predictor of outcome was age, mean age ≥ 65 years with a odds ratio (OR) 4.9. Cox’s regression survival was conducted to assess the impact of multiple factors on survival. The accompanying medical complications were the strongest predictor of respondents poore outcome with Hazard-risk 3.3. Cognitive assessments including Mini Mental State score have showen that post-stroke delirium patients had significant cognitive impairment, three (p = 0.0005), six months (p = 0.0005) and one year (p = 0.0005) after stroke, compared to patients without delirium. Conclusion: Patient gender, age, localization of stroke, severity of delirium, chronic diseases and emerging complications significantly affect the outcome of post- stroke delirium. Delirium significantly reduced cognitive functioning of after stroke patients. PMID:27999490

  6. Stroke Knowledge in Spanish-speaking populations

    PubMed Central

    Hawkes, Maximiliano A; Ameriso, Sebastián F; Willey, Joshua Z

    2015-01-01

    Background Spanish is the second most spoken language in the world. Spanish-speaking populations (SSP) have heterogeneous cultural backgrounds, racial and ethnical origins, economic status, and access to health care systems. There are no published reviews about stroke knowledge in SSP. We reviewed the existing literature addressing stroke knowledge among SSP and propose future directions for research. Summary We identified 18 suitable studies by searching PubMed, Lilacs, Scopus, Embase, Cochrane and Scielo databases, and looking at reference lists of eligible articles. We also included 2 conference abstracts. Data related to stroke knowledge from studies of Spanish-speakers was analyzed. Key messages Little is known about stroke knowledge in SSP, especially in Latin America. Information is poor even among subjects at risk, stroke patients, stroke survivors, and health care providers. “Ictus”, the word used for stroke in Spanish, is largely unrecognized among subjects at risk. Furthermore, access to medical care and presence of neurologists are suboptimal in many regions. There are several potential issues to solve regarding stroke knowledge and stroke care in SSP. Programs to educate the general population and non-neurologists medical providers in stroke and telemedicine may be suitable options to improve the present situation. PMID:25871697

  7. Delay time between onset of ischemic stroke and hospital arrival.

    PubMed

    Biller, J; Patrick, J T; Shepard, A; Adams, H P

    1993-01-01

    Some current experimental protocols for acute ischemic stroke require the initiation of treatment within hours of the onset of stroke symptoms. We prospectively evaluated 30 patients with acute ischemic stroke based on clinical and computed tomography findings. The time between the onset of stroke symptoms and arrival in the emergency room and subsequently on the stroke service was determined. Within 3, 6,12, and 24 h of the onset of stroke symptoms, 16 (53%), 19 (63%), 22 (73%), and 25 (83%) patients had arrived at the emergency room and 0 (0%), 4 (13%), 14 (47%), and 22 (73%) of them on the stroke service, respectively. From the onset of stroke symptoms, the mean arrival time to the emergency room was 24 h (range, 30 min to 144 h) and to the stroke service was 61 h (range, 4-150 h). The mean time between arrival in the emergency room and stroke service was 8.6 h (range, 0-47 h). Even though 53% and 63% of our patients arrived at the emergency room within 3 and 6 h of the onset of stroke symptoms, only 0% and 13% of them arrived on the stroke service within the same time period for the initiation of treatment, respectively. Thus, in order for more patients to qualify for current experimental protocols, they must arrive on the stroke service more quickly or treatment must be initiated in the emergency room.

  8. Stroke Code Improves Intravenous Thrombolysis Administration in Acute Ischemic Stroke

    PubMed Central

    Chen, Chih-Hao; Tang, Sung-Chun; Tsai, Li-Kai; Hsieh, Ming-Ju; Yeh, Shin-Joe; Huang, Kuang-Yu; Jeng, Jiann-Shing

    2014-01-01

    Background and Purpose Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with “Stroke Code” (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis. Methods The study period was divided into the “pre-SC era” (January 2006 to July 2010) and “SC era” (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras. Results During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2) at discharge (49.5 vs. 39.6%, P = 0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality. Conclusion The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time. PMID:25111200

  9. The Epidemiology of Atrial Fibrillation and Stroke.

    PubMed

    Pistoia, Francesca; Sacco, Simona; Tiseo, Cindy; Degan, Diana; Ornello, Raffaele; Carolei, Antonio

    2016-05-01

    The burden of stroke is increasing due to aging population and unhealthy lifestyle habits. The considerable rise in atrial fibrillation (AF) is due to greater diffusion of risk factors and screening programs. The link between AF and ischemic stroke is strong. The subtype most commonly associated with AF is cardioembolic stroke, which is particularly severe and shows the highest rates of mortality and permanent disability. A trend toward a higher prevalence of cardioembolic stroke in high-income countries is probably due to the greater diffusion of AF and the control of atherosclerotic of risk factors.

  10. Anesthetic management of patients with acute stroke.

    PubMed

    Flexman, Alana M; Donovan, Anne L; Gelb, Adrian W

    2012-06-01

    Stroke is a major cause of death and disability. Anesthesiologists are likely to encounter patients with stroke and must be aware of the anesthetic considerations for these patients. Intravenous thrombolysis and intra-arterial thrombolysis are effective treatments for acuteischemic stroke as well as evolving endovascular techniques such as mechanical clot retrieval. Recent retrospective studies have found an association between general anesthesia and poor clinical outcome. The results of these studies have several limitations, and current evidence is inadequate to guide the choice of anesthesia in patients with acute stroke. The choice of anesthesia must be based on individual patient factors until further research is completed.

  11. Correlation between Diarrhea Severity and Oocyst Count via Quantitative PCR or Fluorescence Microscopy in Experimental Cryptosporidiosis in Calves

    PubMed Central

    Operario, Darwin J.; Bristol, Lauren S.; Liotta, Janice; Nydam, Daryl V.; Houpt, Eric R.

    2015-01-01

    Cryptosporidium is an important diarrhea-associated pathogen, however the correlation between parasite burden and diarrhea severity remains unclear. We studied this relationship in 10 experimentally infected calves using immunofluorescence microscopy and real-time polymerase chain reaction (qPCR) (N = 124 fecal samples). The qPCR data were corrected for extraction/amplification efficiency and gene copy number to generate parasite counts. The qPCR and microscopic oocyst quantities exhibited significant correlation (R2 = 0.33, P < 0.05), however qPCR had increased sensitivity. Upon comparison with diarrhea severity scores (from 0 to 3), a PCR-based count of ≥ 2.6 × 105 parasites or an immunofluorescence microscopy count of ≥ 4.5 × 104 oocysts were discriminatory predictors of moderate-to-severe diarrhea (versus no-to-mild diarrhea), with accuracies and predictive values of 72–82%. In summary, a quantitative approach for Cryptosporidium can refine predictive power for diarrhea and appears useful for distinguishing clinical cryptosporidiosis versus subclinical infection. PMID:25371182

  12. Neuroprotective Mechanisms of Melatonin in Hemorrhagic Stroke.

    PubMed

    Wu, Hai-Jian; Wu, Cheng; Niu, Huan-Jiang; Wang, Kun; Mo, Lian-Jie; Shao, An-Wen; Dixon, Brandon J; Zhang, Jian-Min; Yang, Shu-Xu; Wang, Yi-Rong

    2017-01-28

    Hemorrhagic stroke which consists of subarachnoid hemorrhage and intracerebral hemorrhage is a dominant cause of death and disability worldwide. Although great efforts have been made, the physiological mechanisms of these diseases are not fully understood and effective pharmacological interventions are still lacking. Melatonin (N-acetyl-5-methoxytryptamine), a neurohormone produced by the pineal gland, is a broad-spectrum antioxidant and potent free radical scavenger. More importantly, there is extensive evidence demonstrating that melatonin confers neuroprotective effects in experimental models of hemorrhagic stroke. Multiple molecular mechanisms such as antioxidant, anti-apoptosis, and anti-inflammation, contribute to melatonin-mediated neuroprotection against brain injury after hemorrhagic stroke. This review article aims to summarize current knowledge regarding the beneficial effects of melatonin in experimental models of hemorrhagic stroke and explores the underlying mechanisms. We propose that melatonin is a promising neuroprotective candidate that is worthy of further evaluation for its potential therapeutic applications in hemorrhagic stroke.

  13. Calorie restriction and stroke

    PubMed Central

    2011-01-01

    Stroke, a major cause of disability and mortality in the elderly, occurs when a cerebral blood vessel is occluded or ruptured, resulting in ischemic damage and death of brain cells. The injury mechanism involves metabolic and oxidative stress, excitotoxicity, apoptosis and inflammatory processes, including activation of glial cells and infiltration of leukocytes. In animal models, dietary energy restriction, by daily calorie reduction (CR) or intermittent fasting (IF), extends lifespan and decreases the development of age-related diseases. Dietary energy restriction may also benefit neurons, as suggested by experimental evidence showing that CR and IF protect neurons against degeneration in animal models. Recent findings by our group and others suggest the possibility that dietary energy restriction may protect against stroke induced brain injury, in part by inducing the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF); protein chaperones, including heat shock protein 70 (Hsp70) and glucose regulated protein 78 (GRP78); antioxidant enzymes, such as superoxide dismutases (SOD) and heme oxygenase-1 (HO-1), silent information regulator T1 (SIRT1), uncoupling proteins and anti-inflammatory cytokines. This article discusses the protective mechanisms activated by dietary energy restriction in ischemic stroke. PMID:21910904

  14. The Christchurch earthquake stroke incidence study.

    PubMed

    Wu, Teddy Y; Cheung, Jeanette; Cole, David; Fink, John N

    2014-03-01

    We examined the impact of major earthquakes on acute stroke admissions by a retrospective review of stroke admissions in the 6 weeks following the 4 September 2010 and 22 February 2011 earthquakes. The control period was the corresponding 6 weeks in the previous year. In the 6 weeks following the September 2010 earthquake there were 97 acute stroke admissions, with 79 (81.4%) ischaemic infarctions. This was similar to the 2009 control period which had 104 acute stroke admissions, of whom 80 (76.9%) had ischaemic infarction. In the 6 weeks following the February 2011 earthquake, there were 71 stroke admissions, and 61 (79.2%) were ischaemic infarction. This was less than the 96 strokes (72 [75%] ischaemic infarction) in the corresponding control period. None of the comparisons were statistically significant. There was also no difference in the rate of cardioembolic infarction from atrial fibrillation between the study periods. Patients admitted during the February 2011 earthquake period were less likely to be discharged directly home when compared to the control period (31.2% versus 46.9%, p=0.036). There was no observable trend in the number of weekly stroke admissions between the 2 weeks leading to and 6 weeks following the earthquakes. Our results suggest that severe psychological stress from earthquakes did not influence the subsequent short term risk of acute stroke, but the severity of the earthquake in February 2011 and associated civil structural damages may have influenced the pattern of discharge for stroke patients.

  15. Role of prediabetes in stroke

    PubMed Central

    Mijajlović, Milija D; Aleksić, Vuk M; Šternić, Nadežda M; Mirković, Mihailo M; Bornstein, Natan M

    2017-01-01

    Stroke is one of the leading causes of death and probably the greatest cause of adult disability worldwide. Diabetes mellitus (DM) is a state of accelerated aging of blood vessels. Patients with diabetes have increased risk of stroke. Hyperglycemia represents a risk factor for poor outcome following stroke, and probably is just a marker of poor outcome rather than a cause. Lowering of blood glucose levels has not been shown to improve prognosis. Also, prevention of stroke risk among patients with DM is not improved with therapy for reduction of glucose levels. On the other hand, prediabetes, a metabolic state between normal glucose metabolism and diabetes, is a risk factor for the development of DM type 2 and subsequently for stroke. Several methods are known to identify prediabetes patients, including fasting plasma glucose levels, 2-hour post load glucose levels, and glycosylated hemoglobin levels. In this text, we tried to summarize known data about diagnosis, epidemiology, risk factors, pathophysiology, and prevention of prediabetes in relation to DM and stroke. PMID:28203079

  16. Using Stroke Removal to Investigate Chinese Character Identification during Reading: Evidence from Eye Movements

    ERIC Educational Resources Information Center

    Yan, Guoli; Bai, Xuejun; Zang, Chuanli; Bian, Qian; Cui, Lei; Qi, Wei; Rayner, Keith; Liversedge, Simon P.

    2012-01-01

    We explored the effect of stroke removal from Chinese characters on eye movements during reading to examine the role of stroke encoding in character identification. Experimental sentences were comprised of characters with different proportions of strokes removed (15, 30, and 50%), and different types of strokes removed (beginning, ending, and…

  17. Protective effect of glucose-insulin-potassium (GIK) on intestinal tissues after severe burn in experimental rats.

    PubMed

    Wang, Zhanke; Liu, Longyan; Hu, Tian; Lei, Wansheng; Wan, Fusheng; Zhang, Ping; Wang, Zhen; Xu, Jinsong; Zhu, Haohao; Zhu, Zhongzhen; Yang, Yang; Hu, Xiaolu; Xu, Linshui; Wang, Shiliang

    2012-09-01

    Intestinal barrier damage after scald and burns, other trauma or major operations result in severe intestinal infections that cause serious consequences. Therefore, it is important to develop methods to protect intestinal barrier after severe burns. This study used rats that had full-thickness burn of approximately 30% of the total body surface area to investigate the effect and mechanism of glucose-insulin-potassium (GIK) and provide experimental evidence for application of GIK in protecting the intestine after burns or other trauma and major surgeries. The results show that the degree of intestinal damage and plasma diamine oxidase (DAO) levels in GIK (the concentrations of glucose, insulin, sodium chloride and potassium chloride were 100 g l(-1), 70 U l(-1), 9 g l(-1) and 5 g l(-1), respectively) and insulin (30 IU l(-1)) treatment groups were significantly lower than that in control group; the status of anti-inflammatory and pro-inflammatory cytokines and the ratio between them in GIK and insulin groups also significantly improved compared to those in control group; intestinal tumour necrosis factor-alpha (TNFα), nuclear factor-kappaB (NF-κB) and interleukin-10 (IL-10) messenger RNA (mRNA) expression and IL10/TNFα in GIK and insulin groups 2 days after the injury were also improved significantly compared to those in control group. All the indices including body weight detected in GIK group were improved to those in insulin group. Taken together, these results show that GIK and insulin show protective effect on intestine after severe burn, which may relate to controlling hyperglycaemia and regulating intestinal expression of NFκB and pro-inflammatory and anti-inflammatory cytokine genes by GIK and insulin; the protective effect of GIK on intestinal tissue after severe burn is superior to that of using insulin alone, which may attribute to improving the nutritional status by glucose supplement and the relatively higher dose of insulin in the GIK group.

  18. Chronic stress exposure following photothrombotic stroke is associated with increased levels of Amyloid beta accumulation and altered oligomerisation at sites of thalamic secondary neurodegeneration in mice.

    PubMed

    Ong, Lin Kooi; Zhao, Zidan; Kluge, Murielle; Walker, Frederick R; Nilsson, Michael

    2017-04-01

    Exposure to severe stress following stroke is recognised to complicate the recovery process. We have identified that stress can exacerbate the severity of post-stroke secondary neurodegeneration in the thalamus. In this study, we investigated whether exposure to stress could influence the accumulation of the neurotoxic protein Amyloid-β. Using an experimental model of focal cortical ischemia in adult mice combined with exposure to chronic restraint stress, we examined changes within the contra- and ipsilateral thalamus at six weeks post-stroke using Western blotting and immunohistochemical approaches. Western blotting analysis indicated that stroke was associated with a significant enhancement of the 25 and 50 kDa oligomers within the ipsilateral hemisphere and the 20 kDa oligomer within the contralateral hemisphere. Stroked animals exposed to stress exhibited an additional increase in multiple forms of Amyloid-beta oligomers. Immunohistochemistry analysis confirmed that stroke was associated with a significant accumulation of Amyloid-beta within the thalami of both hemispheres, an effect that was exacerbated in stroke animals exposed to stress. Given that Amyloid-beta oligomers, most notably the 30-40 and 50 kDa oligomers, are recognised to correlate with accelerated cognitive decline, our results suggest that monitoring stress levels in patients recovering from stroke may merit consideration in the future.

  19. RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection.

    PubMed

    Jozwik, Agnieszka; Habibi, Maximillian S; Paras, Allan; Zhu, Jie; Guvenel, Aleks; Dhariwal, Jaideep; Almond, Mark; Wong, Ernie H C; Sykes, Annemarie; Maybeno, Matthew; Del Rosario, Jerico; Trujillo-Torralbo, Maria-Belen; Mallia, Patrick; Sidney, John; Peters, Bjoern; Kon, Onn Min; Sette, Alessandro; Johnston, Sebastian L; Openshaw, Peter J; Chiu, Christopher

    2015-12-21

    In animal models, resident memory CD8+ T (Trm) cells assist in respiratory virus elimination but their importance in man has not been determined. Here, using experimental human respiratory syncytial virus (RSV) infection, we investigate systemic and local virus-specific CD8+ T-cell responses in adult volunteers. Having defined the immunodominance hierarchy, we analyse phenotype and function longitudinally in blood and by serial bronchoscopy. Despite rapid clinical recovery, we note surprisingly extensive lower airway inflammation with persistent viral antigen and cellular infiltrates. Pulmonary virus-specific CD8+ T cells display a CD69+CD103+ Trm phenotype and accumulate to strikingly high frequencies into convalescence without continued proliferation. While these have a more highly differentiated phenotype, they express fewer cytotoxicity markers than in blood. Nevertheless, their abundance before infection correlates with reduced symptoms and viral load, implying that CD8+ Trm cells in the human lung can confer protection against severe respiratory viral disease when humoral immunity is overcome.

  20. Air pollution and stroke - an overview of the evidence base.

    PubMed

    Maheswaran, Ravi

    2016-08-01

    Air pollution is being increasingly recognized as a significant risk factor for stroke. There are numerous sources of air pollution including industry, road transport and domestic use of biomass and solid fuels. Early reports of the association between air pollution and stroke come from studies investigating health effects of severe pollution episodes. Several daily time series and case-crossover studies have reported associations with stroke. There is also evidence linking chronic air pollution exposure with stroke and with reduced survival after stroke. A conceptual framework linking air pollution exposure and stroke is proposed. It links acute and chronic exposure to air pollution with pathways to acute and chronic effects on stroke risk. Current evidence regarding potential mechanisms mainly relate to particulate air pollution. Whilst further evidence would be useful, there is already sufficient evidence to support consideration of reduction in air pollution as a preventative measure to reduce the stroke burden globally.

  1. Genetic deletion of galectin-3 enhances neuroinflammation, affects microglial activation and contributes to sub-chronic injury in experimental neonatal focal stroke.

    PubMed

    Chip, Sophorn; Fernández-López, David; Li, Fan; Faustino, Joel; Derugin, Nikita; Vexler, Zinaida S

    2017-02-01

    The pathophysiology of neonatal stroke and adult stroke are distinct in many aspects, including the inflammatory response. We previously showed endogenously protective functions of microglial cells in acute neonatal stroke. We asked if galectin-3 (Gal3), a pleotropic molecule that mediates interactions between microglia/macrophages and the extracellular matrix (ECM), plays a role in early injury after transient middle cerebral occlusion (tMCAO) in postnatal day 9-10 mice. Compared to wild type (WT) pups, in Gal3 knockout pups injury was worse and cytokine/chemokine production altered, including further increase of MIP1α and MIP1β levels and reduced IL6 levels 72h after tMCAO. Lack of Gal3 did not affect morphological transformation or proliferation of microglia but markedly attenuated accumulation of CD11b(+)/CD45(med-high) cells after injury, as determined by multi-color flow cytometry. tMCAO increased expression of αV and β3 integrin subunits in CD11b(+)/CD45(low) microglial cells and cells of non-monocyte lineage (CD11b(-)/CD45(-)), but not in CD11b(+)/CD45(med-high) cells within injured regions of WT mice or Gal3-/- mice. αV upregulated in areas occupied and not occupied by CD68(+) cells, most prominently in the ECM, lining blood vessels, with expanded αV coverage in Gal3-/- mice. Cumulatively, these data show that lack of Gal3 worsens subchronic injury after neonatal focal stroke, likely by altering the neuroinflammatory milieu, including an imbalance between pro- and anti-inflammatory molecules, effects on microglial activation, and deregulation of the composition of the ECM.

  2. Inhibition of the NLRP3 inflammasome reduces the severity of experimentally-induced acute pancreatitis in obese mice

    PubMed Central

    York, Jason M; Castellanos, Karla J; Cabay, Robert J; Fantuzzi, Giamila

    2014-01-01

    Acute pancreatitis (AP), while most often a mild and self-limiting inflammatory disease, worsens to a characteristically necrotic severe acute pancreatitis (SAP) in about 20% of cases. Obesity, affecting more than a third of American adults, is a risk factor for the development of SAP, but the exact mechanism of this association has not been identified. Coincidental with chronic low-grade inflammation, activation of the NLRP3 inflammasome increases with obesity. Lean mice genetically deficient for specific components of the NLRP3 inflammasome are protected from experimentally-induced AP, indicating a direct involvement of this pathway in AP pathophysiology. We hypothesized that inhibition of the NLRP3 inflammasome with the sulfonylurea drug glyburide would reduce disease severity in obese mice with cerulein-induced SAP. Treatment with glyburide led to significantly reduced relative pancreatic mass and water content and less pancreatic damage and cell death in genetically obese ob/ob mice with SAP compared to vehicle-treated obese SAP mice. Glyburide administration in ob/ob mice with cerulein induced SAP also resulted in significantly reduced serum levels of interleukin-6, lipase and amylase, and led to lower production of LPS-stimulated IL-1β release in cultured peritoneal cells, compared to vehicle treated ob/ob mice with SAP. Together, these data indicate involvement of the NLRP3 inflammasome in obesity-associated SAP, and expose the possible utility of its inhibition in prevention or treatment of SAP in obese individuals. PMID:25152324

  3. Prenatal Vitamin D Deficiency Induces an Early and More Severe Experimental Autoimmune Encephalomyelitis in the Second Generation

    PubMed Central

    de Abreu, Diana Andrea Fernandes; Landel, Véréna; Barnett, Adrian G.; McGrath, John; Eyles, Darryl; Feron, Francois

    2012-01-01

    In a previous study, we demonstrated that mouse adult F1 offspring, exposed to a vitamin D deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F2 females whose F1 parents (males or females) were vitamin D-deprived when developing in the uterus of F0 females. Unexpectedly, we observed that the vitamin D deficiency affecting the F0 pregnant mice induced a precocious and more severe EAE in the F2 generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents’ dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin D status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding. PMID:23109828

  4. Aerodynamic analysis of several high throat Mach number inlets for the quiet clean short-haul experimental engine

    NASA Technical Reports Server (NTRS)

    Albers, J. A.; Stockman, N. O.; Hirn, J. J.

    1975-01-01

    The results of an analytical study to investigate internal and external surface Mach numbers on several inlet geometries for possible application to the nacelle of the Quiet Clean Short-Haul Experimental Engine (QCSEE) are presented. The effects of external forebody geometry and internal lip geometry were illustrated at both low-speed and cruise conditions. Boundary-layer analyses were performed on several geometries to determine if lip flow separation might exist. The results indicated that inner-surface Mach number level and gradient could be reduced with inlets at a 50 deg incidence angle by blunting the external forebody geometry. The external Mach numbers at cruise conditions indicated that a compromise in the external forebody bluntness might be required to satisfy both low-speed and cruise conditions. For a fixed value of bluntness parameter, no lip flow separation was indicated for the 1.46- and 1.57-area-contraction-ratio inlets at low-speed conditions. However, a lip separation condition was obtained with the 1.37-contraction-ratio inlet. The QCSEE nacelle design takeoff operating condition (incidence angle of 50 deg and free-stream Mach number of 0.12) resulted in higher peak surface Mach numbers than the design crosswind (incidence angle of 90 deg and free-stream Mach number of 0.05) or static condition.

  5. Deletion of both ICAM-1 and C3 Enhances Severity of Experimental Autoimmune Encephalomyelitis Compared to C3-Deficient Mice

    PubMed Central

    Smith, Sherry S.; Ludwig, Michael; Wohler, Jillian E.; Bullard, Daniel C.; Szalai, Alex J.; Barnum, Scott R.

    2008-01-01

    Multiple sclerosis (MS) is an autoimmune disease characterized by central nervous system (CNS) inflammation and leukocyte infiltration, demyelination of neurons, and blood-brain barrier breakdown. The development of experimental autoimmune encephalomyelitis (EAE), the animal model for MS is dependent on a number of components of the immune system including complement and adhesion molecules. Previous studies in our lab have examined the role of C3, the central complement component, and intercellular adhesion molecule-1 (ICAM-1) a key cell adhesion molecule involved in leukocyte trafficking to sites of inflammation including the CNS. In these studies we demonstrated that myelin oligodendrocyte glycoprotein (MOG)-induced EAE is markedly attenuated in both ICAM-1−/− and C3−/− mice. Given the pivotal role that these proteins play in EAE, we hypothesized that EAE in ICAM-1−/− and C3−/− double mutant mice would likely fail to develop. Unexpectedly, EAE in ICAM-1−/− × C3−/− mice was only modestly attenuated compared to wild type mice and significantly worse than C3−/− mice. Leukocyte infiltration was commensurate with disease severity between the three groups of mice. Spinal cord T cells from ICAM-1−/− × C3−/− mice produced the highest levels of IFN-γ and TNF-α, despite reduced disease severity compared to wild type mice. The mechanisms behind the elevated EAE severity in ICAM-1−/− × C3−/− mice may relate to altered homing of leukocytes or processing of self-antigens in the double mutant background. PMID:18634851

  6. The Impact of Cortical Lesions on Thalamo-Cortical Network Dynamics after Acute Ischaemic Stroke: A Combined Experimental and Theoretical Study

    PubMed Central

    van Wijngaarden, Joeri B. G.; Finnigan, Simon

    2016-01-01

    The neocortex and thalamus provide a core substrate for perception, cognition, and action, and are interconnected through different direct and indirect pathways that maintain specific dynamics associated with functional states including wakefulness and sleep. It has been shown that a lack of excitation, or enhanced subcortical inhibition, can disrupt this system and drive thalamic nuclei into an attractor state of low-frequency bursting and further entrainment of thalamo-cortical circuits, also called thalamo-cortical dysrhythmia (TCD). The question remains however whether similar TCD-like phenomena can arise with a cortical origin. For instance, in stroke, a cortical lesion could disrupt thalamo-cortical interactions through an attenuation of the excitatory drive onto the thalamus, creating an imbalance between excitation and inhibition that can lead to a state of TCD. Here we tested this hypothesis by comparing the resting-state EEG recordings of acute ischaemic stroke patients (N = 21) with those of healthy, age-matched control-subjects (N = 17). We observed that these patients displayed the hallmarks of TCD: a characteristic downward shift of dominant α-peaks in the EEG power spectra, together with increased power over the lower frequencies (δ and θ-range). Contrary to general observations in TCD, the patients also displayed a broad reduction in β-band activity. In order to explain the genesis of this stroke-induced TCD, we developed a biologically constrained model of a general thalamo-cortical module, allowing us to identify the specific cellular and network mechanisms involved. Our model showed that a lesion in the cortical component leads to sustained cell membrane hyperpolarization in the corresponding thalamic relay neurons, that in turn leads to the de-inactivation of voltage-gated T-type Ca2+-channels, switching neurons from tonic spiking to a pathological bursting regime. This thalamic bursting synchronises activity on a population level through

  7. Primary and Comprehensive Stroke Centers: History, Value and Certification Criteria

    PubMed Central

    2013-01-01

    In the United States (US) stroke care has undergone a remarkable transformation in the past decades at several levels. At the clinical level, randomized trials have paved the way for many new stroke preventives, and recently, several new mechanical clot retrieval devices for acute stroke treatment have been cleared for use in practice by the US Federal Drug Administration. Furthermore, in the mid 1990s we witnessed regulatory approval of intravenous recombinant tissue plasminogen activator for administration in acute ischemic stroke. In the domain of organization of medical care and delivery of health services, stroke has transitioned from a disease dominated by neurologic consultation services only to one managed by vascular neurologists in geographical stroke units, stroke teams and care pathways, primary stroke center certification according to The Joint Commission, and most recently comprehensive stroke center designation under the aegis of The Joint Commission. Many organizations in the US have been involved to enhance stroke care. To name a few, the American Heart Association/American Stroke Association, Brain Attack Coalition, and National Stroke Association have been on the forefront of this movement. Additionally, governmental initiatives by the US Centers for Disease Control and Prevention and legislative initiatives such as the Paul Coverdell National Acute Stroke Registry program have paved the way to focus on stroke prevention, acute treatment and quality improvement. In this invited review, we discuss a brief history of organized stroke care in the United States, evidence to support the value of primary and comprehensive stroke centers, and the certification criteria and process to become a primary or comprehensive stroke center. PMID:24324943

  8. Galanin's implications for post-stroke improvement

    PubMed Central

    Song, Juhyun

    2016-01-01

    Stroke leads to a variety of pathophysiological conditions such as ischemic infarct, cerebral inflammation, neuronal damage, cognitive decline, and depression. Many endeavors have been tried to find the therapeutic solutions to attenuate severe neuropathogenesis after stroke. Several studies have reported that a decrease in the neuropeptide regulator ‘galanin’ is associated with neuronal loss, learning and memory dysfunctions, and depression following a stroke. The present review summarized recent evidences on the function and the therapeutic potential of galanin in post-ischemic stroke to provide a further understanding of galanin's role. Hence, we suggest that galanin needs to be considered as a therapeutic factor in the alleviation of post-stroke pathologies. PMID:28127496

  9. [Neuroprotective therapy for the treatment of acute ischemic stroke].

    PubMed

    Naritomi, H

    2001-12-01

    Following cerebral ischemia, various biochemical reactions are provoked in a stepwise manner leading neuronal cells to ischemic death. The prevention of these biochemical reactions may exert neuroprotective actions and consequently reduce the magnitude of ischemic cerebral injury. On the basis of such a view, numerous neuroprotective drugs have been developed during the last decade. Quite a few drugs were found effective in reducing the infarct volume in experimental studies, and more than 15 of them were subjected to clinical phase III trials to see a therapeutic effectiveness. However, the results of phase III trials were disappointing in the majority drugs. Only three drugs, nicaravene, ebselen and edaravone, all radical scavengers, were judged effective by small-sized trials with a wide therapeutic window, 48-72 hours after stroke, in Japan. The fact suggests that a one-point prevention of biochemical reactions by single drug is unable to rescue ischemic neuronal cells. Ischemic insult causes damages of vascular wall including the endothelium which play an important role in the development of hemorrhagic changes or cerebral edema. Vascular protection is considered as important as neuroprotection in treatment of clinical stroke. Mild hypothermia has neuroprotective and vascular protective actions and hence may be more effective than neuroprotective drugs for the treatment of stroke. The prevention of fever, which often occurs in severe stroke, may exert the similar effect as hypothermia in neuroprotection. Neuroprotective therapy in the future should proceed toward the simultaneous protections of neurons and vessels using combination of multiple drugs.

  10. [Stroke - lifestyle and environment].

    PubMed

    Gerischer, L M; Flöel, A; Endres, M

    2015-08-01

    Lifestyle modifications and environmental factors are important for stroke prevention and rehabilitation after stroke. The individual stroke risk may be modified by factors like physical activity, body weight and nutrition, special dietary supplements such as vitamins, smoking, consumption of tea, coffee and alcohol, psychological factors and by keeping a pet. The focus of this article lies on measures for stroke prevention. For certain topics, it also comments on factors that are important during rehabilitation after stroke.

  11. Modeling Dynamic Regulatory Processes in Stroke.

    SciTech Connect

    McDermott, Jason E.; Jarman, Kenneth D.; Taylor, Ronald C.; Lancaster, Mary J.; Shankaran, Harish; Vartanian, Keri B.; Stevens, S.L.; Stenzel-Poore, Mary; Sanfilippo, Antonio P.

    2012-10-11

    The ability to examine in silico the behavior of biological systems can greatly accelerate the pace of discovery in disease pathologies, such as stroke, where in vivo experimentation is lengthy and costly. In this paper we describe an approach to in silico examination of blood genomic responses to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs) relating regulators and functional clusters from the data. These ODEs were used to develop dynamic models that simulate the expression of regulated functional clusters using system dynamics as the modeling paradigm. The dynamic model has the considerable advantage of only requiring an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. The manipulation of input model parameters, such as changing the magnitude of gene expression, made it possible to assess the behavior of the networks through time under varying conditions. We report that an optimized dynamic model can provide accurate predictions of overall system behavior under several different preconditioning paradigms.

  12. Anti-vascular endothelial growth factor antibody attenuates inflammation and decreases mortality in an experimental model of severe sepsis

    PubMed Central

    2013-01-01

    Introduction Severe sepsis is associated with an unacceptably high rate of mortality. Recent studies revealed elevated levels of vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, in patients with sepsis. There was also an association between VEGF levels and sepsis severity. Here we investigate the effects of an anti-VEGF antibody (Bevacizumab, Bev) in an experimental model of sepsis. Methods Human umbilical vein endothelial cells (HUVECs), murine cecal ligation and puncture (CLP), and endotoxemia models of sepsis were used. HUVECs were treated with lipopolysaccharide (LPS) and/or Bev, harvested and cytokine mRNA levels determined using a semi-quantitative reverse transcription-polymerase chain reaction assay. The levels of inflammatory cytokine were also determined in HUVECs supernatants. In addition, the effects of Bev on mortality in the CLP and endotoxemia models of sepsis were evaluated. Results Treatment with Bev and LPS significantly decreased the expression and the level of inflammatory cytokines in HUVECs relative to LPS alone. In CLP and endotoxemia models, survival benefits were evident in mice given 0.1 mg/kg of Bev relative to the CLP or LPS alone (P <0.001 and P = 0.028, respectively), and in 6 h post-treated mice relative to the CLP alone for the effect of different time of Bev (P = 0.033). In addition, Bev treatment inhibited LPS-induced vascular leak in the lung, spleen and kidney in the murine endotoxemia model (P <0.05). Conclusions Anti-VEGF antibody may be a promising therapeutic agent due to its beneficial effects on the survival of sepsis by decreasing inflammatory responses and endothelial permeability. PMID:23710641

  13. Stroke rehabilitation in Canada: a work in progress.

    PubMed

    Teasell, Robert; Meyer, Matthew J; Foley, Norine; Salter, Katherine; Willems, Deb

    2009-01-01

    Stroke rehabilitation in Canada continues to function under models and practices that have changed little in the last four decades and struggles to implement new evidence-based or best practices. Ontario, Canada's largest province, has had a coordinated stroke strategy since 2000. The Ontario Stroke System has developed an extensive infrastructure of research syntheses, consensus panel recommendations, practice guidelines, standards of care, and centralized data collection across the continuum of stroke care. This has produced a solid foundation upon which an evidence-based stroke rehabilitation system can be developed. However, failure to invest in stroke rehabilitation or provide incentives to implement change has resulted in the stroke rehabilitation system and critical outcomes remaining largely unchanged. Improvements in time to admission have been countered by rising admission FIM scores such that severe stroke patients often cannot access the stroke rehabilitation system. Many stroke patients are still rehabilitated on general rehabilitation units, therapy intensities remain unacceptably low, and many outpatient programs are being reduced or even closed. Although there are pockets of innovation, the stroke rehabilitation system continues to function more according to traditional ways of practicing. The hope is that with appropriate investments and incentives, Canadians and Ontarians can build upon the existing infrastructure to ensure stroke patients receive optimal rehabilitative care based on best evidence. In the meantime, stroke rehabilitation in Canada remains a work in progress.

  14. Clinical study of 222 patients with pure motor stroke

    PubMed Central

    Arboix, A; Padilla, I; Massons, J; Garcia-Eroles, L; Comes, E; Targa, C

    2001-01-01

    The objective was to assess the frequency of pure motor stroke caused by different stroke subtypes and to compare demographic, clinical, neuroimaging, and outcome data of pure motor stroke with those of patients with other lacunar stroke as well as with those of patients with non-lacunar stroke.
Data from 2000 patients with acute stroke (n=1761) or transient ischaemic attack (n=239) admitted consecutively to the department of neurology of an acute care 350 bed teaching hospital were prospectively collected in the Sagrat Cor Hospital of Barcelona stroke registry over a 10 year period. For the purpose of the study 222 (12.7%) patients with pure motor stroke were selected. The other study groups included 218 (12.3%) patients with other lacunar strokes and 1321 (75%) patients with non-lacunar stroke.
In relation to stroke subtype, lacunar infarcts were found in 189 (85%) patients, whereas ischaemic lacunar syndromes not due to lacunar infarcts occurred in 23 (10.4%) patients (atherothrombotic stroke in 12, cardioembolic stroke in seven, infarction of undetermined origin in three, and infarction of unusual aetiology in one) and haemorrhagic lacunar syndromes in 10 (4.5%). Patients with pure motor stroke showed a better outcome than patients with non-lacunar stroke with a significantly lower number of complications and in hospital mortality rate, shorter duration of hospital stay, and a higher number of symptom free patients at hospital discharge. After multivariate analysis, hypertension, diabetes, obesity, hyperlipidaemia, non-sudden stroke onset, internal capsule involvement, and pons topography seemed to be independent factors of pure motor stroke in patients with acute stroke.
In conclusion, about one of every 10 patients with acute stroke had a pure motor stroke. Pure motor stroke was caused by a lacunar infarct in 85% of patients and by other stroke subtypes in 15%. Several clinical features are more frequent in patients with pure motor stroke than in

  15. Pathophysiology and Treatments of Oxidative Injury in Ischemic Stroke: Focus on the Phagocytic NADPH Oxidase 2

    PubMed Central

    Carbone, Federico; Teixeira, Priscila Camillo; Braunersreuther, Vincent; Mach, François; Vuilleumier, Nicolas

    2015-01-01

    Abstract Significance: Phagocytes play a key role in promoting the oxidative stress after ischemic stroke occurrence. The phagocytic NADPH oxidase (NOX) 2 is a membrane-bound enzyme complex involved in the antimicrobial respiratory burst and free radical production in these cells. Recent Advances: Different oxidants have been shown to induce opposite effects on neuronal homeostasis after a stroke. However, several experimental models support the detrimental effects of NOX activity (especially the phagocytic isoform) on brain recovery after stroke. Therapeutic strategies selectively targeting the neurotoxic ROS and increasing neuroprotective oxidants have recently produced promising results. Critical Issues: NOX2 might promote carotid plaque rupture and stroke occurrence. In addition, NOX2-derived reactive oxygen species (ROS) released by resident and recruited phagocytes enhance cerebral ischemic injury, activating the inflammatory apoptotic pathways. The aim of this review is to update evidence on phagocyte-related oxidative stress, focusing on the role of NOX2 as a potential therapeutic target to reduce ROS-related cerebral injury after stroke. Future Directions: Radical scavenger compounds (such as Ebselen and Edaravone) are under clinical investigation as a therapeutic approach against stroke. On the other hand, NOX inhibition might represent a promising strategy to prevent the stroke-related injury. Although selective NOX inhibitors are not yet available, nonselective compounds (such as apocynin and fasudil) provided encouraging results in preclinical studies. Whereas additional studies are needed to better evaluate this therapeutic potential in human beings, the development of specific NOX inhibitors (such as monoclonal antibodies, small-molecule inhibitors, or aptamers) might further improve brain recovery after stroke. Antioxid. Redox Signal. 23, 460–489. PMID:24635113

  16. RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection

    PubMed Central

    Jozwik, Agnieszka; Habibi, Maximillian S.; Paras, Allan; Zhu, Jie; Guvenel, Aleks; Dhariwal, Jaideep; Almond, Mark; Wong, Ernie H. C.; Sykes, Annemarie; Maybeno, Matthew; Del Rosario, Jerico; Trujillo-Torralbo, Maria-Belen; Mallia, Patrick; Sidney, John; Peters, Bjoern; Kon, Onn Min; Sette, Alessandro; Johnston, Sebastian L.; Openshaw, Peter J.; Chiu, Christopher

    2015-01-01

    In animal models, resident memory CD8+ T (Trm) cells assist in respiratory virus elimination but their importance in man has not been determined. Here, using experimental human respiratory syncytial virus (RSV) infection, we investigate systemic and local virus-specific CD8+ T-cell responses in adult volunteers. Having defined the immunodominance hierarchy, we analyse phenotype and function longitudinally in blood and by serial bronchoscopy. Despite rapid clinical recovery, we note surprisingly extensive lower airway inflammation with persistent viral antigen and cellular infiltrates. Pulmonary virus-specific CD8+ T cells display a CD69+CD103+ Trm phenotype and accumulate to strikingly high frequencies into convalescence without continued proliferation. While these have a more highly differentiated phenotype, they express fewer cytotoxicity markers than in blood. Nevertheless, their abundance before infection correlates with reduced symptoms and viral load, implying that CD8+ Trm cells in the human lung can confer protection against severe respiratory viral disease when humoral immunity is overcome. PMID:26687547

  17. Global Burden of Stroke.

    PubMed

    Feigin, Valery L; Norrving, Bo; Mensah, George A

    2017-02-03

    On the basis of the GBD (Global Burden of Disease) 2013 Study, this article provides an overview of the global, regional, and country-specific burden of stroke by sex and age groups, including trends in stroke burden from 1990 to 2013, and outlines recommended measures to reduce stroke burden. It shows that although stroke incidence, prevalence, mortality, and disability-adjusted life-years rates tend to decline from 1990 to 2013, the overall stroke burden in terms of absolute number of people affected by, or who remained disabled from, stroke has increased across the globe in both men and women of all ages. This provides a strong argument that "business as usual" for primary stroke prevention is not sufficiently effective. Although prevention of stroke is a complex medical and political issue, there is strong evidence that substantial prevention of stroke is feasible in practice. The need to scale-up the primary prevention actions is urgent.

  18. Neurodegeneration and Glial Response after Acute Striatal Stroke: Histological Basis for Neuroprotective Studies

    PubMed Central

    Santana, Luana N. S.; Fernandes, Rafael M.; Nascimento, Elder M.; Oliveira, Ana Carolina A.; Fernandes, Luanna M. P.; dos Santos, Enio Mauricio N.; Tavares, Patrycy Assis N.; dos Santos, Ijair Rogério; Gimarães-Santos, Adriano

    2016-01-01

    Stroke is a leading cause of death and neurological disability worldwide and striatal ischemic stroke is frequent in humans due to obstruction of middle cerebral artery. Several pathological events underlie damage progression and a comprehensive description of the pathological features following experimental stroke in both acute and chronic survival times is a necessary step for further functional studies. Here, we explored the patterns of microglial activation, astrocytosis, oligodendrocyte damage, myelin impairment, and Nogo-A immunoreactivity between 3 and 30 postlesion days (PLDs) after experimental striatal stroke in adult rats induced by microinjections of endothelin-1 (ET-1). The focal ischemia induced tissue loss concomitant with intense microglia activation between 3 and 14 PLDs (maximum at 7 PLDs), decreasing afterward. Astrocytosis was maximum around 7 PLDs. Oligodendrocyte damage and Nogo-A upregulation were higher at 3 PLDs. Myelin impairment was maximum between 7 and 14 PLDs. Nogo-A expression was higher in the first week in comparison to control. The results add important histopathological features of ET-1 induced stroke in subacute and chronic survival times. In addition, the establishment of the temporal evolution of these neuropathological events is an important step for future studies seeking suitable neuroprotective drugs targeting neuroinflammation and white matter damage. PMID:28090244

  19. Neurodegeneration and Glial Response after Acute Striatal Stroke: Histological Basis for Neuroprotective Studies.

    PubMed

    Lima, Rafael R; Santana, Luana N S; Fernandes, Rafael M; Nascimento, Elder M; Oliveira, Ana Carolina A; Fernandes, Luanna M P; Dos Santos, Enio Mauricio N; Tavares, Patrycy Assis N; Dos Santos, Ijair Rogério; Gimarães-Santos, Adriano; Gomes-Leal, Walace

    2016-01-01

    Stroke is a leading cause of death and neurological disability worldwide and striatal ischemic stroke is frequent in humans due to obstruction of middle cerebral artery. Several pathological events underlie damage progression and a comprehensive description of the pathological features following experimental stroke in both acute and chronic survival times is a necessary step for further functional studies. Here, we explored the patterns of microglial activation, astrocytosis, oligodendrocyte damage, myelin impairment, and Nogo-A immunoreactivity between 3 and 30 postlesion days (PLDs) after experimental striatal stroke in adult rats induced by microinjections of endothelin-1 (ET-1). The focal ischemia induced tissue loss concomitant with intense microglia activation between 3 and 14 PLDs (maximum at 7 PLDs), decreasing afterward. Astrocytosis was maximum around 7 PLDs. Oligodendrocyte damage and Nogo-A upregulation were higher at 3 PLDs. Myelin impairment was maximum between 7 and 14 PLDs. Nogo-A expression was higher in the first week in comparison to control. The results add important histopathological features of ET-1 induced stroke in subacute and chronic survival times. In addition, the establishment of the temporal evolution of these neuropathological events is an important step for future studies seeking suitable neuroprotective drugs targeting neuroinflammation and white matter damage.

  20. Towards brain-robot interfaces in stroke rehabilitation.

    PubMed

    Gomez-Rodriguez, M; Grosse-Wentrup, M; Hill, J; Gharabaghi, A; Scholkopf, B; Peters, J

    2011-01-01

    A neurorehabilitation approach that combines robot-assisted active physical therapy and Brain-Computer Interfaces (BCIs) may provide an additional mileage with respect to traditional rehabilitation methods for patients with severe motor impairment due to cerebrovascular brain damage (e.g., stroke) and other neurological conditions. In this paper, we describe the design and modes of operation of a robot-based rehabilitation framework that enables artificial support of the sensorimotor feedback loop. The aim is to increase cortical plasticity by means of Hebbian-type learning rules. A BCI-based shared-control strategy is used to drive a Barret WAM 7-degree-of-freedom arm that guides a subject's arm. Experimental validation of our setup is carried out both with healthy subjects and stroke patients. We review the empirical results which we have obtained to date, and argue that they support the feasibility of future rehabilitative treatments employing this novel approach.

  1. Heart Disease and Stroke Prevention

    MedlinePlus

    ... Heart disease and stroke prevention Heart Health and Stroke Heart disease and stroke prevention Related information Learn more about healthy eating ... to top More information on Heart disease and stroke prevention Read more from womenshealth.gov A Lifetime ...

  2. Difficulty Swallowing After Stroke (Dysphagia)

    MedlinePlus

    ... Stories Stroke Heroes Among Us Difficulty Swallowing After Stroke (Dysphagia) Updated:Nov 15,2016 Excerpted and adapted ... stiffness (spasticity), fatigue and more. Let's Talk About Stroke Fact Sheets Our stroke fact sheets cover treatments, ...

  3. Experimental reproduction of severe hypoglycemia and spiking mortality syndrome using field-derived and embryo-passaged preparations.

    PubMed

    Davis, J F; Castro, A E; de la Torre, J C; Barnes, H J; Doman, J T; Metz, M; Lu, H; Yuen, S; Dunn, P A; Teng, M N

    1996-01-01

    The clinical signs, enteritis, weight depression, and hypoglycemia of spiking mortality syndrome were experimentally reproduced in broiler breeders and broiler chicks. Inocula included 1) virus-like particles from intestines of chicks with spiking mortality syndrome that had been banded in a discontinuous Renograffin gradient, 2) homogenized darkling beetles collected from litter of farms where spiking mortality syndrome had occurred repeatedly, and 3) homogenized embryos which had been inoculated with the Renograffin-banded material. Arkansas variant infectious bronchitis virus and arenavirus-like particles were identified in the inocula. Serology on samples from surviving chicks suggested the presence of an avian encephalomyelitis virus in one of the inocula. One-day-old (n = 172) and 2.5-day-old (n = 30) chicks were inoculated orally, and some were also injected intraperitoneally or subcutaneously, with 0.5 ml of the inocula. Twelve to fourteen days postinoculation, chicks were fasted for 4-6 hours, then briefly stressed with a cool water spray. Within 1.5 hours, inoculated chicks began dying with severe hypoglycemia and clinical signs of spiking mortality syndrome. Body weights were significantly depressed. Uninoculated controls (n = 130) from the same hatches, also fasted and stressed, were unaffected clinically and were not hypoglycemic. One group (n = 52) of inoculated chicks exposed to a controlled lighting program was unaffected clinically, had significantly higher mean plasma glucose levels, and had significantly less body weight depression than chicks exposed to continuous lighting. We concluded that exposure to controlled amounts of light/darkness can ameliorate much of the hypoglycemia, mortality, and runting-stunting associated with spiking mortality syndrome of chickens. The significance of the viruses and virus-like particles detected in the inocula is currently under investigation.

  4. Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

    PubMed Central

    Nighot, Prashant; Al-Sadi, Rana; Guo, Shuhong; Watterson, D. Martin; Ma, Thomas

    2015-01-01

    Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9−/− mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9−/− mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9−/− mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK−/− mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9−/− mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK. PMID:26514773

  5. Promoting endothelial function by S-nitrosoglutathione through the HIF-1α/VEGF pathway stimulates neurorepair and functional recovery following experimental stroke in rats

    PubMed Central

    Khan, Mushfiquddin; Dhammu, Tajinder S; Matsuda, Fumiyo; Baarine, Mauhammad; Dhindsa, Tejbir Singh; Singh, Inderjit; Singh, Avtar K

    2015-01-01

    Background For stroke patients, stimulating neurorepair mechanisms is necessary to reduce morbidity and disability. Our previous studies on brain and spinal cord trauma show that exogenous treatment with the S-nitrosylating agent S-nitrosoglutathione (GSNO) – a nitric oxide and glutathione metabolite of the human body – stimulates neurorepair and aids functional recovery. Using a rat model of cerebral ischemia and reperfusion (IR) in this study, we tested the hypothesis that GSNO invokes the neurorepair process and improves neurobehavioral functions through the angiogenic HIF-1α/VEGF pathway. Methods Stroke was induced by middle cerebral artery occlusion for 60 minutes followed by reperfusion in adult male rats. The injured animals were treated with saline (IR group, n=7), GSNO (0.25 mg/kg, GSNO group, n=7), and GSNO plus the HIF-1α inhibitor 2-methoxyestra-diol (2-ME) (0.25 mg/kg GSNO + 5.0 mg/kg 2-ME, GSNO + 2-ME group, n=7). The groups were studied for either 7 or 14 days to determine neurorepair mediators and functional recovery. Brain capillary endothelial cells were used to show that GSNO promotes angiogenesis and that GSNO-mediated induction of VEGF and the stimulation of angiogenesis are dependent on HIF-1α activity. Results IR injury increased the expression of neurorepair mediators HIF-1α, VEGF, and PECAM-1 and vessel markers to a limited degree that correlate well with significantly compromised neurobehavioral functions compared with sham animals. GSNO treatment of IR not only remarkably enhanced further the expression of HIF-1α, VEGF, and PECAM-1 but also improved functioning compared with IR. The GSNO group also had a higher degree of vessel density than the IR group. Increased expression of VEGF and the degree of tube formation (angiogenesis) by GSNO were reduced after the inhibition of HIF-1α by 2-ME in an endothelial cell culture model. 2-ME treatment of the GSNO group also blocked not only GSNO’s effect of reduced infarct volume

  6. Stroke biomarkers: Can they help us to guide stroke thrombolysis?

    PubMed

    Montaner, Joan

    2006-11-01

    The use of blood biomarkers is getting increasingly popular in the field of cerebrovascular diseases, since biomarkers might aid physicians in several steps of stroke evaluation. We will discuss whether stroke diagnosis might be possible using some specific brain biomarkers and if this approach will permit rapid referral of stroke patients to hospitals with acute treatments such as tissue plasminogen activator (t-PA) available. Although thrombolytic therapy in acute stroke is effective since it accelerates clot lyses and earlier restoration of blood flow, up to 40-50% of treated patients do not recanalize or do it too late, and between 6 and 15% suffer hemorrhagic transformations with high death rates. In the context of the neurovascular unit, t-PA may degrade extracellular matrix integrity and increase risks of neurovascular cell death, blood-brain barrier leakage, edema and hemorrhage. In humans, biomarkers such as matrix metalloproteinase-9 (MMP-9) or fibronectin, which might be used to select patients at higher risk of hemorrhagic transformation, and high plasminogen activator inhibitor-1 (PAI-1) interfering with tPA-induced recanalization, thus predicting clot-lyses resistance and poor outcome, have been recently identified. Moreover, high levels of MMP-9 and MMP-13 are involved in DWI lesion growth in spite of thrombolytic therapy suggesting its ultra-early role in brain injury. Other biomarkers such as C-reactive protein may accurately predict stroke mortality following reperfusion therapies. Finally, we will also show that genetic background of stroke patients may condition plasma levels of some of these biomarkers and influence therapeutic response in t-PA-treated patients.

  7. Stroke Warning Signs

    MedlinePlus

    ... symptoms, call 9-1-1 or emergency medical services immediately. After Calling 911: Receiving timely stroke treatment is important and an important step to recovery. Why Getting Quick Stroke Treatment is Important "Let's ...

  8. Two Kinds of Stroke

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section Two Kinds of Stroke Past Issues / Summer 2007 Table ... minutes, brain cells begin to die. There are two kinds of stroke. The more common kind, called ...

  9. Stroke Connection Magazine

    MedlinePlus

    ... edition or on the Stroke Connection website. The Poetry of Survival Poetry uses words to process emotions, and stroke appears to bring up plenty of emotions. Read the poetry of five survivors as well as guidance from ...

  10. Stroke Trials Registry

    MedlinePlus

    ... News About Neurology Image Library Search The Internet Stroke Center Trials Registry Clinical Trials Interventions Conditions Sponsors ... a clinical trial near you Welcome to the Stroke Trials Registry Our registry of clinical trials in ...

  11. Heart and Stroke Encyclopedia

    MedlinePlus

    ... Venous Thromboembolism Aortic Aneurysm More The Heart and Stroke Encyclopedia Click a letter below to get a ... dozens of cardiovascular terms from our Heart and Stroke Encyclopedia and get links to in-depth information. ...

  12. Geometrical Effects on the Electromagnetic Radiation from Lightning Return Strokes

    NASA Technical Reports Server (NTRS)

    Willett, J. C.; Smith, D. A.; LeVine, D. M.; Zukor, Dorothy J. (Technical Monitor)

    2001-01-01

    The morphological difference between the electromagnetic radiation-field waveforms of "first" and "subsequent" return strokes in cloud-to-ground lightning flashes is well known and can be used to identify the formation of new channels to ground. This difference is generally believed due to the existence of branches on first-stroke channels, whereas subsequent strokes re-illuminate only the main channel of a previous stroke; but experimental evidence for this hypothesis is relatively weak. It has been argued for the influence of channel geometry on the fine structure of radiation from subsequent return strokes by comparing the field-change waveforms recorded at the same station from strokes within the same flash and between different flashes of both natural and triggered lightning. The present paper introduces new evidence for both of these hypotheses from a comparison of waveforms between sensors in different directions from the same stroke.

  13. Stroke care quality in China: Substantial improvement, and a huge challenge and opportunity.

    PubMed

    Wang, Yilong; Li, Zixiao; Zhao, Xingquan; Wang, David; Li, Hao; Xian, Ying; Liu, Liping; Wang, Yongjun

    2017-04-01

    Stroke is The first two authors contributed equally. the leading cause of death and adult disability in China. Although evidence-based clinical interventions have been identified to improve care and outcomes in stroke, significant gaps still exist between guideline recommendations and clinical practice in China. Regional and national stroke registries have been used to assess the benchmark of stroke care quality, provide feedback on compliance with evidence-based performance measures to health care providers, and continuously improve stroke care quality without increasing additional medical costs in the past several decades worldwide. In China, stroke care has become a national priority. A series of stroke care quality assessment and improvement actions was initiated by the Ministry of Health to increase the detection of high-risk populations with stroke, rate of adherence to evidence-based process performance measures of stroke care, and stroke care organization development, aiming to decrease the burden of stroke. China National Stroke Registries have been started in 2007, and they are conducted every 3 to 5 years. A carotid disease screen and intervention project for communities was initiated in 2009. The Chinese Stroke Association, founded in 2015, launched the Chinese Stroke Center Alliance to increase the stroke center design in the near future. In this article, we described these stroke care actions and progression, summarized the benchmark and improvement of stroke care quality, and outlined the future plans in China.

  14. Stroke Fact Sheet

    MedlinePlus

    ... Problems judging distances — The stroke survivor may misjudge distances and fall or be unable to guide her hands to pick something up. Impaired judgment and behavior — The stroke survivor may try to do things that she should not do, such as driving a car. Short-term memory loss — The stroke survivor may ...

  15. Epigenetics in Stroke Recovery

    PubMed Central

    Kassis, Haifa; Shehadah, Amjad; Chopp, Michael; Zhang, Zheng Gang

    2017-01-01

    Abstract: While the death rate from stroke has continually decreased due to interventions in the hyperacute stage of the disease, long-term disability and institutionalization have become common sequelae in the aftermath of stroke. Therefore, identification of new molecular pathways that could be targeted to improve neurological recovery among survivors of stroke is crucial. Epigenetic mechanisms such as post-translational modifications of histone proteins and microRNAs have recently emerged as key regulators of the enhanced plasticity observed during repair processes after stroke. In this review, we highlight the recent advancements in the evolving field of epigenetics in stroke recovery. PMID:28264471

  16. Disturbance of circadian rhythm in heart rate, blood pressure and locomotive activity at the stroke-onset in malignant stroke-prone spontaneously hypertensive rats.

    PubMed

    Tabuchi, M; Umegaki, K; Ito, T; Suzuki, M; Ikeda, M; Tomita, T

    2001-02-01

    Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP), separated from SHRSP, develop severe hypertension and spontaneously develop stroke at early ages. Using this model of cerebrovascular stroke, influence of stroke-onset on the autonomic nervous system was investigated. Heart rate (HR), systolic and diastolic blood pressures (SBP and DBP) and locomotive activity were monitored during development of stroke using a telemetry system. Stroke-onset was assessed by neurologic symptoms, changes in body weight, fluid intake and serum NOx level. The rat displayed a nocturnal pattern of circadian rhythms. At stroke-onset, mean HR over 24 h increased by 20 to 30 bpm and rapidly increased at post stroke, approximately 100 bpm higher than that at pre stroke. Circadian variation in HR, which was normally 50 bpm higher during night than during day, attenuated at stroke-onset, and it was blunted or reversed at post stroke. BP variation, which was approximately 7 mmHg higher at night than at day, decreased one or two days before stroke-onset and reversed at post stroke, especially in DBP. Insufficient falls in HR and BP during the day mainly accounted for the disturbed circadian variations. Variation of locomotive activity also decreased. These changes serve as reliable and accurate markers for stroke-onset in evaluation of drugs for the prevention and outcome predictions of stroke.

  17. Aspiration Pneumonia After Stroke

    PubMed Central

    Armstrong, John R.; Mosher, Benjamin D.

    2011-01-01

    Fifteen million strokes occur worldwide each year with 5 million associated deaths and an additional 5 million people left permanently disabled. In the United States, about 780 000 people suffer a new or recurrent stroke each year. There were an estimated total 5.8 million stroke survivors as of 2008. Mortality from stroke is the third leading cause of death in America following heart disease and cancer. Chest infection may affect up to as many as one-third of stroke patients. This increases the morbidity and mortality of this patient population. Pneumonia causes the highest attributable mortality of all medical complications following stroke. A comprehensive multidisciplinary team approach is required at the hospital level. This requires active administrative commitment and participation. Implementation of evidence-based management strategies can improve outcomes and reduce costs. We sought to review the problem of post-stroke pneumonia and discuss strategies for prevention and intervention. PMID:23983842

  18. Spinal cord stimulation in the treatment of post-stroke patients: current state and future directions.

    PubMed

    Robaina, F; Clavo, B

    2007-01-01

    A decrease in cerebral blood flow (CBF) and brain metabolic activity are well-known complications of stroke. Spinal cord stimulation (SCS) is successfully being used for the treatment of several low-perfusion syndromes. The aim of this chapter is to describe the data that support the effect of SCS on CBF and the use of SCS in the treatment of stroke and cerebral low perfusion syndromes. In addition, we present our relevant studies. Since April 1995, we have assessed 49 non-stroke patients. The following parameters were measured pre- and post-stroke: (1) CBF in healthy contralateral tissue by single photon emission computed tomography (SPECT), (2) systolic and diastolic velocity in the middle cerebral artery (MCA) by transcranial Doppler, (3) blood flow quantification in the common carotid artery (CCA) by color Doppler, and (4) glucose metabolism in healthy contralateral tissue by positron emission tomography (PET). Our results showed that during cervical SCS there was a significant (p < 0.001) increase in systolic (> or =21%) and diastolic (>26%) velocity in the MCA, and CCA blood flow (> or =51%) as well as glucose metabolism (44%). We concluded that cervical SCS (cSCS) can modify CBF and brain metabolism. Its potential role in the management of stroke and low-perfusion syndromes is further investigated by experimental studies and reports describing clinical experience. Appropriate clinical trials are warranted.

  19. Alterations in the corticotropin-releasing hormone (CRH) neurocircuitry: Insights into post stroke functional impairments.

    PubMed

    Barra de la Tremblaye, P; Plamondon, H

    2016-07-01

    Although it is well accepted that changes in the regulation of the hypothalamic-pituitary adrenal (HPA) axis may increase susceptibility to affective disorders in the general population, this link has been less examined in stroke patients. Yet, the bidirectional association between depression and cardiovascular disease is strong, and stress increases vulnerability to stroke. Corticotropin-releasing hormone (CRH) is the central stress hormone of the HPA axis pathway and acts by binding to CRH receptors (CRHR) 1 and 2, which are located in several stress-related brain regions. Evidence from clinical and animal studies suggests a role for CRH in the neurobiological basis of depression and ischemic brain injury. Given its importance in the regulation of the neuroendocrine, autonomic, and behavioral correlates of adaptation and maladaptation to stress, CRH is likely associated in the pathophysiology of post stroke emotional impairments. The goals of this review article are to examine the clinical and experimental data describing (1) that CRH regulates the molecular signaling brain circuit underlying anxiety- and depression-like behaviors, (2) the influence of CRH and other stress markers in the pathophysiology of post stroke emotional and cognitive impairments, and (3) context and site specific interactions of CRH and BDNF as a basis for the development of novel therapeutic targets. This review addresses how the production and release of the neuropeptide CRH within the various regions of the mesocorticolimbic system influences emotional and cognitive behaviors with a look into its role in psychiatric disorders post stroke.

  20. The European Stroke Organisation Guidelines: a standard operating procedure.

    PubMed

    Ntaios, George; Bornstein, Natan M; Caso, Valeria; Christensen, Hanne; De Keyser, Jacques; Diener, Hans-Christoph; Diez-Tejedor, Exuperio; Ferro, Jose M; Ford, Gary A; Grau, Armin; Keller, Emanuella; Leys, Didier; Russell, David; Toni, Danilo; Turc, Guillaume; Van der Worp, Bart; Wahlgren, Nils; Steiner, Thorsten

    2015-10-01

    In 2008, the recently founded European Stroke Organisation published its guidelines for the management of ischemic stroke and transient ischemic attack. This highly cited document was translated in several languages and was updated in 2009. Since then, the European Stroke Organisation has published guidelines for the management of intracranial aneurysms and subarachnoidal hemorrhage, for the establishment of stroke units and stroke centers, and recently for the management of intracerebral hemorrhage. In recent years, the methodology for the development of guidelines has evolved significantly. To keep pace with this progress and driven by the strong determination of the European Stroke Organisation to further promote stroke management, education, and research, the European Stroke Organisation decided to delineate a detailed standard operating procedure for its guidelines. There are two important cornerstones in this standard operating procedure: The first is the implementation of the Grading of Recommendations Assessment, Development, and Evaluation methodology for the development of its Guideline Documents. The second one is the decision of the European Stroke Organisation to move from the classical model of a single Guideline Document about a major topic (e.g. management of ischemic stroke) to focused modules (i.e. subdivisions of a major topic). This will enable the European Stroke Organisation to react faster when new developments in a specific stroke field occur and update its recommendations on the related module rather swiftly; with the previous approach of a single large Guideline Document, its entire revision had to be completed before an updated publication, delaying the production of up-to-date guidelines. After discussion within the European Stroke Organisation Guidelines Committee and significant input from European Stroke Organisation members as well as methodologists and analysts, this document presents the official standard operating procedure for

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

    PubMed Central

    Rabiller, Gratianne; He, Ji-Wei; Nishijima, Yasuo; Wong, Aaron; Liu, Jialing

    2015-01-01

    Brain waves resonate from the generators of electrical current and propagate across brain regions with oscillation frequencies ranging from 0.05 to 500 Hz. The commonly observed oscillatory waves recorded by an electroencephalogram (EEG) in normal adult humans can be grouped into five main categories according to the frequency and amplitude, namely δ (1–4 Hz, 20–200 μV), θ (4–8 Hz, 10 μV), α (8–12 Hz, 20–200 μV), β (12–30 Hz, 5–10 μV), and γ (30–80 Hz, low amplitude). Emerging evidence from experimental and human studies suggests that groups of function and behavior seem to be specifically associated with the presence of each oscillation band, although the complex relationship between oscillation frequency and function, as well as the interaction between brain oscillations, are far from clear. Changes of brain oscillation patterns have long been implicated in the diseases of the central nervous system including ischemic stroke, in which the reduction of cerebral blood flow as well as the progression of tissue damage have direct spatiotemporal effects on the power of several oscillatory bands and their interactions. This review summarizes the current knowledge in behavior and function associated with each brain oscillation, and also in the specific changes in brain electrical activities that correspond to the molecular events and functional alterations observed after experimental and human stroke. We provide the basis of the generations of brain oscillations and potential cellular and molecular mechanisms underlying stroke-induced perturbation. We will also discuss the implications of using brain oscillation patterns as biomarkers for the prediction of stroke outcome and therapeutic efficacy. PMID:26516838

  2. Plant disease severity assessment - How rater bias, assessment method and experimental design affect hypothesis testing and resource use efficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The impact of rater bias and assessment method on hypothesis testing was studied for different experimental designs for plant disease assessment using balanced and unbalanced data sets. Data sets with the same number of replicate estimates for each of two treatments are termed ‘balanced’, and those ...

  3. Evidence for stroke family caregiver and dyad interventions: a statement for healthcare professionals from the American Heart Association and American Stroke Association.

    PubMed

    Bakas, Tamilyn; Clark, Patricia C; Kelly-Hayes, Margaret; King, Rosemarie B; Lutz, Barbara J; Miller, Elaine L

    2014-09-01

    Stroke is a leading cause of severe, long-term disability. Most stroke survivors are cared for in the home by a family caregiver. Caregiver stress is a leading cause of stroke survivor institutionalization, which results in significant costs to the healthcare system. Stroke family caregiver and dyad intervention studies have reported a variety of outcomes. A critical analysis of 17 caregiver intervention studies and 15 caregiver/stroke survivor dyad intervention studies was conducted to provide evidence-based recommendations for the implementation and future design of stroke family caregiver and dyad interventions.

  4. Ischemic stroke selectively inhibits REM sleep of rats.

    PubMed

    Ahmed, Samreen; Meng, He; Liu, Tiecheng; Sutton, Blair C; Opp, Mark R; Borjigin, Jimo; Wang, Michael M

    2011-12-01

    Sleep disorders are important risk factors for stroke; conversely, stroke patients suffer from sleep disturbances including disruptions of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and a decrease in total sleep. This study was performed to characterize the effect of stroke on sleep architecture of rats using continuous electroencephalography (EEG) and activity monitoring. Rats were implanted with transmitters which enabled continuous real time recording of EEG, electromyography (EMG), and locomotor activity. Baseline recordings were performed prior to induction of either transient middle cerebral artery (MCA) occlusion or sham surgery. Sleep recordings were obtained for 60 h after surgery to identify periods of wakefulness, NREM, and REM sleep before and after stroke. Spectral analysis was performed to assess the effects of stroke on state-dependent EEG. Finally, we quantified the time in wake, NREM, and REM sleep before and after stroke. Delta power, a measure of NREM sleep depth, was increased the day following stroke. At the same time, there was a significant shift in theta rhythms to a lower frequency during REM and wake periods. The awake EEG slowed after stroke over both hemispheres. The EEG of the ischemic hemisphere demonstrated diminished theta power specific to REM in excess of the slowing seen over the contralateral hemisphere. In contrast to rats exposed to sham surgery which had slightly increased total sleep, rats undergoing stroke experienced decreased total sleep. The decrease in total sleep after stroke was the result of dramatic reduction in the amount of REM sleep after ischemia. The suppression of REM after stroke was due to a decrease in the number of REM bouts; the length of the average REM bout did not change. We conclude that after stroke in this experimental model, REM sleep of rats is specifically and profoundly suppressed. Further experiments using this experimental model should be performed to investigate the

  5. White matter injury in ischemic stroke.

    PubMed

    Wang, Yuan; Liu, Gang; Hong, Dandan; Chen, Fenghua; Ji, Xunming; Cao, Guodong

    2016-06-01

    Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions.

  6. Therapeutic benefits of nanoparticles in stroke

    PubMed Central

    Panagiotou, Stavros; Saha, Sikha

    2015-01-01

    Stroke represents one of the major causes of death and disability worldwide, for which no effective treatments are available. The thrombolytic drug alteplase (tissue plasminogen activator or tPA) is the only treatment for acute ischemic stroke but its use is limited by several factors including short therapeutic window, selective efficacy, and subsequent haemorrhagic complications. Numerous preclinical studies have reported very promising results using neuroprotective agents but they have failed at clinical trials because of either safety issues or lack of efficacy. The delivery of many potentially therapeutic neuroprotectants and diagnostic compounds to the brain is restricted by the blood-brain barrier (BBB). Nanoparticles (NPs), which can readily cross the BBB without compromising its integrity, have immense applications in the treatment of ischemic stroke. In this review, potential uses of NPs will be summarized for the treatment of ischemic stroke. Additionally, an overview of targeted NPs will be provided, which could be used in the diagnosis of stroke. Finally, the potential limitations of using NPs in medical applications will be mentioned. Since the use of NPs in stroke therapy is now emerging and is still in development, this review is far from comprehensive or conclusive. Instead, examples of NPs and their current use will be provided, as well as the potentials of NPs in an effort to meet the high demand of new therapies in stroke. PMID:26041986

  7. Novel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments

    PubMed Central

    George, Paul M.; Steinberg, Gary K.

    2016-01-01

    Stroke remains a leading cause of death and disability in the world. Over the past few decades our understanding of the pathophysiology of stroke has increased, but greater insight is required to advance the field of stroke recovery. Clinical treatments have improved in the acute time window, but long-term therapeutics remain limited. Complex neural circuits damaged by ischemia make restoration of function after stroke difficult. New therapeutic approaches, including cell transplantation or stimulation, focus on reestablishing these circuits through multiple mechanisms to improve circuit plasticity and remodeling. Other research targets intact networks to compensate for damaged regions. This review highlights several important mechanisms of stroke injury and describes emerging therapies aimed at improving clinical outcomes. PMID:26182415

  8. Protective effect of naringenin in experimental ischemic stroke: down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

    PubMed

    Bai, Xue; Zhang, Xiangjian; Chen, Linyu; Zhang, Jian; Zhang, Lan; Zhao, Xumeng; Zhao, Ting; Zhao, Yuan

    2014-08-01

    Inflammatory damage plays a pivotal, mainly detrimental role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Naringenin (NG) has gained growing appreciation for its beneficial biological effects through its anti-inflammatory property. Whether this protective effect applies to cerebral ischemic injury, we therefore investigate the potential neuroprotective role of NG and the underlying mechanisms. Focal cerebral ischemia in male Sprague-Dawley rats was induced by permanent middle cerebral artery occlusion (pMCAO) and NG was pre-administered intragastrically once daily for four consecutive days before surgery. Neurological deficit, brain water content and infarct volume were measured at 24 h after stroke. Immunohistochemistry, Western blot and RT-qPCR were used to explore the anti-inflammatory potential of NG in the regulation of NOD2, RIP2 and NF-κB in ischemic cerebral cortex. Additionally, the activities of MMP-9 and claudin-5 were analyzed to detect NG's influence on blood-brain barrier. Compared with pMCAO and Vehicle groups, NG noticeably improved neurological deficit, decreased infarct volume and edema at 24 h after ischemic insult. Consistent with these results, our data also indicated that NG significantly downregulated the expression of NOD2, RIP2, NF-κB and MMP-9, and upregulated the expression of claudin-5 (P < 0.05). The results provided a neuroprotective profile of NG in cerebral ischemia, this effect was likely exerted by down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

  9. Literature and art therapy in post-stroke psychological disorders.

    PubMed

    Eum, Yeongcheol; Yim, Jongeun

    2015-01-01

    Stroke is one of the leading causes of morbidity and long-term disability worldwide, and post-stroke depression (PSD) is a common and serious psychiatric complication of stroke. PSD makes patients have more severe deficits in activities of daily living, a worse functional outcome, more severe cognitive deficits and increased mortality as compared to stroke patients without depression. Therefore, to reduce or prevent mental problems of stroke patients, psychological treatment should be recommended. Literature and art therapy are highly effective psychological treatment for stroke patients. Literature therapy divided into poetry and story therapy is an assistive tool that treats neurosis as well as emotional or behavioral disorders. Poetry can add impression to the lethargic life of a patient with PSD, thereby acting as a natural treatment. Story therapy can change the gloomy psychological state of patients into a bright and healthy story, and therefore can help stroke patients to overcome their emotional disabilities. Art therapy is one form of psychological therapy that can treat depression and anxiety in stroke patients. Stroke patients can express their internal conflicts, emotions, and psychological status through art works or processes and it would be a healing process of mental problems. Music therapy can relieve the suppressed emotions of patients and add vitality to the body, while giving them the energy to share their feelings with others. In conclusion, literature and art therapy can identify the emotional status of patients and serve as a useful auxiliary tool to help stroke patients in their rehabilitation process.

  10. Experimental infection of the olive baboon (Paplio anubis) with Plasmodium knowlesi: severe disease accompanied by cerebral involvement.

    PubMed

    Ozwara, Hastings; Langermans, Jan A M; Maamun, Jenneby; Farah, Idle O; Yole, Dorcas S; Mwenda, Jason M; Weiler, Horst; Thomas, Alan W

    2003-08-01

    Experimental systems that model some of the complex interactions between parasite and host can be extremely valuable in identifying and developing new prophylactics and therapeutics against human diseases. Because primates have similar immune systems to humans, we have characterized a baboon model for understanding host response to Plasmodium knowlesi. Ten intact olive baboons (Papio anubis) of either sex were experimentally infected with P. knowlesi H strain erythrocytic parasites. The infection in these baboons was either acute or chronic. Animals with acute infection developed multiple system organ dysfunction and cerebral involvement. In chronically infected animals, only the spleen was moderately enlarged. The P. knowlesi parasitemia profile in baboons and rhesus monkeys was comparable. However, some clinical symptoms of the baboons and P. falciparum-infected humans were similar. These studies demonstrate for the first time that P. anubis is a suitable host for P. knowlesi for studying clinical symptoms and pathology.

  11. Dilemma in the emergency setting: hypomagnesemia mimicking acute stroke

    PubMed Central

    Rico, María; Martinez-Rodriguez, Laura; Larrosa-Campo, Davinia; Calleja, Sergio

    2016-01-01

    Background Stroke mimics may account for up to 30% of all acute stroke consultations. However, in the emergency setting, accurate diagnosis is not always possible. Methods Case report and review of the literature. Results A 73-year-old woman was admitted to the emergency department with acute aphasia and right hemiparesis. The National Institute of Health Stroke Score was 21, compatible with severe stroke, so she received thrombolysis. Laboratory testing demonstrated severe hypomagnesemia. She had been taking proton pump inhibitors for years and neuroimaging did not demonstrate signs of acute ischemic disease. After correcting the metabolic alterations with intravenous and oral supplemental magnesium, the patient was discharged asymptomatic. No further episodes have been registered to date. Conclusion Hypomagnesemia might cause acute neurological symptoms that could be confused with stroke. A careful history is essential for diagnosis but suspicion of stroke mimic should not prevent tPA administration. PMID:27354832

  12. Effect of dexamethasone on brain oedema following acute ischemic stroke.

    PubMed

    Shaikh, A K; Mohammad, Q D; Ullah, M A; Ahsan, M M; Rahman, A; Shakoor, M A

    2011-07-01

    A randomized clinical trial was conducted to asses the effects of dexamethasone on brain oedema following acute ischemic stroke in the departments of Medicine of different hospitals from July, 2003 to December, 2006. A total of 60 patients were included in the study. They were divided into two groups keeping the similarity regarding the age, sex and severity of the stroke between two groups. There were 30 patients in experimental group and 30 in control group. The level of consciousness was compared by Glasgow Coma Scale (GCS) on 3rd, 7th and 10th day of intervention and improvement was found in both the groups, but the improvement of level of consciousness was statistically significant in Dexamethasone treated group. The volume of hypodense area did not differ significantly in two groups in CT scans before and after treatment (p=0.74). The study results demonstrate that Dexamethasone improves the level of consciousness in acute ischemic stroke associated with brain oedema but did not reduce volume of hypodense area.

  13. Stroke risk stratification in acute dizziness presentations

    PubMed Central

    Meurer, William J.; Brown, Devin L.; Burke, James F.; Hofer, Timothy P.; Tsodikov, Alexander; Hoeffner, Ellen G.; Fendrick, A.M.; Adelman, Eric E.; Morgenstern, Lewis B.

    2015-01-01

    Objective: To estimate the ability of bedside information to risk stratify stroke in acute dizziness presentations. Methods: Surveillance methods were used to identify patients with acute dizziness and nystagmus or imbalance, excluding those with benign paroxysmal positional vertigo, medical causes, or moderate to severe neurologic deficits. Stroke was defined as acute infarction or intracerebral hemorrhage on a clinical or research MRI performed within 14 days of dizziness onset. Bedside information comprised history of stroke, the ABCD2 score (age, blood pressure, clinical features, duration, and diabetes), an ocular motor (OM)-based assessment (head impulse test, nystagmus pattern [central vs other], test of skew), and a general neurologic examination for other CNS features. Multivariable logistic regression was used to determine the association of the bedside information with stroke. Model calibration was assessed using low (<5%), intermediate (5% to <10%), and high (≥10%) predicted probability risk categories. Results: Acute stroke was identified in 29 of 272 patients (10.7%). Associations with stroke were as follows: ABCD2 score (continuous) (odds ratio [OR] 1.74; 95% confidence interval [CI] 1.20–2.51), any other CNS features (OR 2.54; 95% CI 1.06–6.08), OM assessment (OR 2.82; 95% CI 0.96–8.30), and prior stroke (OR 0.48; 95% CI 0.05–4.57). No stroke cases were in the model's low-risk probability category (0/86, 0%), whereas 9 were in the moderate-risk category (9/94, 9.6%) and 20 were in the high-risk category (20/92, 21.7%). Conclusion: In acute dizziness presentations, the combination of ABCD2 score, general neurologic examination, and a specialized OM examination has the capacity to risk-stratify acute stroke on MRI. PMID:26511453

  14. Management of depression in elderly stroke patients

    PubMed Central

    Lökk, Johan; Delbari, Ahmad

    2010-01-01

    Poststroke depression (PSD) in elderly patients has been considered the most common neuropsychiatric consequence of stroke up to 6–24 months after stroke onset. When depression appears within days after stroke onset, it is likely to remit, whereas depression at 3 months is likely to be sustained for 1 year. One of the major problems posed by elderly stroke patients is how to identify and optimally manage PSD. This review provides insight to identification and management of depression in elderly stroke patients. Depression following stroke is less likely to include dysphoria and more likely characterized by vegetative signs and symptoms compared with other forms of late-life depression, and clinicians should rely more on nonsomatic symptoms rather than somatic symptoms. Evaluation and diagnosis of depression among elderly stroke patients are more complex due to vague symptoms of depression, overlapping signs and symptoms of stroke and depression, lack of properly trained health care personnel, and insufficient assessment tools for proper diagnosis. Major goals of treatment are to reduce depressive symptoms, improve mood and quality of life, and reduce the risk of medical complications including relapse. Antidepressants (ADs) are generally not indicated in mild forms because the balance of benefit and risk is not satisfactory in elderly stroke patients. Selective serotonin reuptake inhibitors are the first choice of PSD treatment in elderly patients due to their lower potential for drug interaction and side effects, which are more common with tricyclic ADs. Recently, stimulant medications have emerged as promising new therapeutic interventions for PSD and are now the subject of rigorous clinical trials. Cognitive behavioral therapy can also be useful, and electroconvulsive therapy is available for patients with severe refractory PSD. PMID:20856917

  15. Xiaoxuming decoction and stroke: a literature-based study.

    PubMed

    Zhu, Xin-Hong; Chen, Su-Yun; Gao, Tian-Ming

    2002-06-01

    Xiaoxuming decoction, an ancient traditional Chinese medical prescription for treatment of stroke, has somehow lost its clinical application since Tang Dynasty. Based on the historic record of this prescription, mechanisms of composition and clinical and experimental studies, the authors attempt to evaluate the standing of Xiaoxuming decoction as a remedy for stroke.

  16. Projecting the number of patients with first ever strokes and patients newly handicapped by stroke in England and Wales.

    PubMed Central

    Malmgren, R.; Bamford, J.; Warlow, C.; Sandercock, P.; Slattery, J.

    1989-01-01

    The common assumption that future increases in the number of elderly people will result in a parallel increase in the burden of care of long term disabled survivors of stroke was examined. The number of patients with first ever strokes and the net number of people handicapped after these strokes in England and Wales every five years until 2023 have been projected. Between the base year 1983 and the year 2023 an increase in population of about 5% will occur; first ever strokes are projected to increase by about 30% and deaths within six months of first ever strokes by about 40%. The net number of severely handicapped people six months after a first ever stroke is projected to increase by only about 8%, however, and the net number of people who are moderately or severely handicapped by only 4%. This paradox occurs because first ever stroke often kills people who have been handicapped by other causes, particularly if they are elderly. It is concluded that despite the limitations of these data they strongly suggest that the increased burden of health care of patients with first ever strokes in the next 40 years will be primarily that of caring for those in the acute stages of stroke and not with the management of chronic handicap after a stroke. PMID:2523745

  17. [Nutritional support in stroke patients].

    PubMed

    Burgos Peláez, Rosa; Segurola Gurrutxaga, Hegoi; Bretón Lesmes, Irene

    2014-01-01

    Stroke is a public health problem of the first order. In developed countries is one of the leading causes of death, along with cardiovascular disease and cancer. In addition, stroke is the leading cause of permanent disability in adulthood. Many of the patients who survive do so with significant sequelae that limit them in their activities of daily living. Most strokes (80-85%) are due to ischemia, while the rest are hemorrhagic. We have identified many modifiable risk factors, some with an important relationship with dietary factors or comorbidities in wich the diet has a significant impact. The incidence of malnutrition in stroke patients is not well known, but most likely impacts on patient prognosis. Furthermore, the nutritional status of patients admitted for stroke often deteriorates during hospitalization. It is necessary to perform a nutritional assessment of the patient in the early hours of admission, to determine both the nutritional status and the presence of dysphagia. Dysphagia, through alteration of the safety and efficacy of swallowing, is a complication that has an implication for nutritional support, and must be treated to prevent aspiration pneumonia, which is the leading cause of mortality in the stroke patient. Nutritional support should begin in the early hours. In patients with no or mild dysphagia that can be controlled by modifying the texture of the diet, they will start oral diet and oral nutritional supplementation will be used if the patient does not meet their nutritional requirements. There is no evidence to support the use of nutritional supplements routinely. Patients with severe dysphagia, or decreased level of consciousness will require enteral nutrition. Current evidence indicates that early nutrition should be initiated through a nasogastric tube, with any advantages of early feeding gastrostomy. Gastrostomy will be planned when the enteral nutrition support will be expected for long-term (4 weeks). Much evidence points to the

  18. Drug abuse and stroke.

    PubMed

    Fonseca, Ana Catarina; Ferro, José M

    2013-02-01

    Cerebrovascular disorders contribute to the morbidity and disability associated with illicit drug use. Drug abusers have an increased risk of both hemorrhagic and ischemic stroke. In geographic areas with a high prevalence of illicit drug use, drug abuse is a frequent cause of stroke in the young adult. The illicit drugs more commonly associated with stroke are psychomotor stimulants, such as amphetamine and cocaine. Less commonly implicated are opioids and psychotomimetic drugs, including cannabis. Toxicology screening for illicit drugs should be done in young patients with stroke with no obvious cause, or if suggested by history or examination. Although in some patients the mechanism of stroke is identified using neuroimaging and other modern diagnostic tools, in a sizeable fraction of cases the mechanism of stroke remains unclear. Further studies are needed to elucidate the role of hemodynamic and immunologic mechanisms in these cases.

  19. Changes in brain functional network connectivity after stroke

    PubMed Central

    Li, Wei; Li, Yapeng; Zhu, Wenzhen; Chen, Xi

    2014-01-01

    Studies have shown that functional network connection models can be used to study brain network changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlated to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea-lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke. PMID:25206743

  20. Electromagnetic induction holography imaging for stroke detection.

    PubMed

    Wang, Lulu

    2017-02-01

    This paper presents the application of the electromagnetic induction holography (EMIH) approach to imaging the electromagnetic activity of the brain, with a particular focus on stroke detection. An integral equation formulation is presented to describe the scattered magnetic field from the distribution of optically small dielectric and magnetic objects of arbitrary shapes adsorbed onto a planar electromagnetic substrate. A numerical computer model was developed in a MATLAB environment to validate the theory. Several realistic human head models were developed to investigate the detectability of strokes with the multi-channel EMIH system. Small strokes can be clearly identified with the correct location and size in the reconstructed head images. The simulation results demonstrated the feasibility of detecting and imaging small strokes using the approach.

  1. Aspirin resistant patients with recent ischemic stroke.

    PubMed

    Castilla-Guerra, L; Navas-Alcántara, M S; Fernández-Moreno, M C

    2014-04-01

    Some patients with a recent ischemic stroke who are being treated with aspirin as an antiaggregant suffer a new ischemic stroke. These patients (15-25%) have been called unresponsive to aspirin or aspirin resistant. The aspirin-resistant patients have a four-time greater risk of suffering a stroke. Furthermore, these strokes are generally more severe, with increased infarct volume and greater risk of recurrence. There is currently no ideal laboratory test to detect the resistance to the antiaggregant effect of aspirin. The study of resistance to aspirin would only be indicated in selected cases. In these patients, one should first rule out any "pseudo-resistance" to aspirin (lack of compliance, concomitant treatments that interfere with the action of the aspirin).

  2. Emerging Treatments for Motor Rehabilitation After Stroke

    PubMed Central

    Krishnan, Chandramouli; Khot, Sandeep P.

    2015-01-01

    Although numerous treatments are available to improve cerebral perfusion after acute stroke and prevent recurrent stroke, few rehabilitation treatments have been conclusively shown to improve neurologic recovery. The majority of stroke survivors with motor impairment do not recover to their functional baseline, and there remains a need for novel neurorehabilitation treatments to minimize long-term disability, maximize quality of life, and optimize psychosocial outcomes. In recent years, several novel therapies have emerged to restore motor function after stroke, and additional investigational treatments have also shown promise. Here, we familiarize the neurohospitalist with emerging treatments for poststroke motor rehabilitation. The rehabilitation treatments covered in this review will include selective serotonin reuptake inhibitor medications, constraint-induced movement therapy, noninvasive brain stimulation, mirror therapy, and motor imagery or mental practice. PMID:25829989

  3. An experimental study of several wind tunnel wall configurations using two V/STOL model configurations. [low speed wind tunnels

    NASA Technical Reports Server (NTRS)

    Binion, T. W., Jr.

    1975-01-01

    Experiments were conducted in the low speed wind tunnel using two V/STOL models, a jet-flap and a jet-in-fuselage configuration, to search for a wind tunnel wall configuration to minimize wall interference on V/STOL models. Data were also obtained on the jet-flap model with a uniform slotted wall configuration to provide comparisons between theoretical and experimental wall interference. A test section configuration was found which provided some data in reasonable agreement with interference-free results over a wide range of momentum coefficients.

  4. Posterior Circulation Ischemic Stroke.

    PubMed

    Go, Steven

    2015-01-01

    Approximately 20-25% of all acute strokes occur in the posterior circulation. These strokes can be rather difficult to diagnose because they present in such diverse ways, and can easily be mistaken for more benign entities. A fastidious history, physical exam, high clinical suspicion, and appropriate use of imaging are essential for the emergency physician to properly diagnose and treat these patients. Expert stroke neurologist consultation should be utilized liberally.

  5. Improvement of the chromatographic separation of several 1,4-dihydropyridines calcium channel antagonist drugs by experimental design.

    PubMed

    Baranda, Ana B; Etxebarria, Nestor; Jiménez, Rosa M; Alonso, Rosa M

    2005-01-01

    A high-performance liquid chromatographic method with diode array detection has been developed and optimized for the separation of five calcium channel blockers belonging to the 1,4-dihydropyridine subgroup (nifedipine and related drugs). The possibility of the simultaneous drug analysis allows a decrease of time during the assay as well as a saving of reagents and solvents. In this work, the effect of four experimental parameters (organic modifier percentage, pH value, concentration of the buffer in the mobile phase, and column temperature) on the chromatographic resolution are investigated by experimental design in order to optimize the chromatographic separation of five 1,4-dihydropyridines (amlodipine, nitrendipine, felodipine, lacidipine, and lercanidipine). Fractional factorial design, central composite design, and finally the Multisimplex program are used to establish the optimal conditions in terms of resolution and minimum analysis time. Optimal separation of the five compounds under study is achieved in less than 12 min using a Sulpecosil LC-ABZ+Plus C18 column, a composition of mobile phase of acetonitrile-10mM acetic acid acetate buffer pH 5 (72:28, v/v) at a flow rate of 1 mL/min, a column temperature of 30 degrees C +/- 0.1 degrees C, and a detection wavelength of 238 nm.

  6. Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model

    PubMed Central

    Mishra, Vikas; Skotak, Maciej; Schuetz, Heather; Heller, Abi; Haorah, James; Chandra, Namas

    2016-01-01

    Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0–450 kPa (0–800 Pa∙s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146–220 kPa and 221–290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0–145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85–145 kPa. PMID:27270403

  7. Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model

    NASA Astrophysics Data System (ADS)

    Mishra, Vikas; Skotak, Maciej; Schuetz, Heather; Heller, Abi; Haorah, James; Chandra, Namas

    2016-06-01

    Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0–450 kPa (0–800 Pa•s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146–220 kPa and 221–290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0–145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85–145 kPa.

  8. Recovery After Stroke: Healthy Eating

    MedlinePlus

    Recovery After Stroke: Healthy Eating Eating well after stroke is key to your recovery. Choosing healthy foods can help you keep up ... get the nutrition you need for your stroke recovery.  Eat your biggest meal early in the day ...

  9. Stroke Drills for Swimming Instructors.

    ERIC Educational Resources Information Center

    Cahill, Peter J.

    1982-01-01

    Stroke drills to be used by swimming instructors to teach four competitive swim strokes are described. The drills include: one arm swims; (2) alternative kicks; (3) fist swims; and (4) catch-up strokes. (JN)

  10. Current status of endovascular stroke treatment.

    PubMed

    Meyers, Philip M; Schumacher, H Christian; Connolly, E Sander; Heyer, Eric J; Gray, William A; Higashida, Randall T

    2011-06-07

    The management of acute ischemic stroke is rapidly developing.Although acute ischemic stroke is a major cause of adult disability and death, the number of patients requiring emergency endovascular intervention remains unknown, but is a fraction of the overall stroke population. Public health initiatives endeavor to raise public awareness about acute stroke to improve triage for emergency treatment, and the medical community is working to develop stroke services at community and academic medical centers throughout the United States. There is an Accreditation Council for Graduate Medical Education–approved pathway for training in endovascular surgical neuroradiology, the specialty designed to train physicians specifically to treat cerebrovascular diseases. Primary and comprehensive stroke center designations have been defined, yet questions remain about the best delivery model. Telemedicine is available to help community medical centers cope with the complexity of stroke triage and treatment. Should comprehensive care be provided at every community center, or should patients with complex medical needs be triaged to major stroke centers with high-level surgical,intensive care, and endovascular capabilities? Although the answers to these and other questions about stroke care delivery remain unanswered owing to the paucity of empirical data, we are convinced that stroke care regionalization is crucial for delivery of high-quality comprehensive ischemic stroke treatment. A stroke team available 24 hours per day, 7 days per week requires specialty skills in stroke neurology, endovascular surgical neuroradiology, neurosurgery, neurointensive care, anesthesiology, nursing, and technical support for optimal success. Several physician groups with divergent training backgrounds (i.e., interventional neuroradiology, neurosurgery,neurology, peripheral interventional radiology, and cardiology) lay claim to the treatment of stroke patients,particularly the endovascular or

  11. Neurorestoration after stroke

    PubMed Central

    Azad, Tej D.; Veeravagu, Anand; Steinberg, Gary K.

    2016-01-01

    Recent advancements in stem cell biology and neuromodulation have ushered in a battery of new neurorestorative therapies for ischemic stroke. While the understanding of stroke pathophysiology has matured, the ability to restore patients’ quality of life remains inadequate. New therapeutic approaches, including cell transplantation and neurostimulation, focus on reestablishing the circuits disrupted by ischemia through multidimensional mechanisms to improve neuroplasticity and remodeling. The authors provide a broad overview of stroke pathophysiology and existing therapies to highlight the scientifc and clinical implications of neurorestorative therapies for stroke. PMID:27132523

  12. Fecal microbiota transplantation (FMT) could reverse the severity of experimental necrotizing enterocolitis (NEC) via oxidative stress modulation.

    PubMed

    Li, Xiaomei; Li, Xiaowen; Shang, Qingjuan; Gao, Zongwei; Hao, Fabao; Guo, Hongjie; Guo, Chunbao

    2017-03-16

    Fecal microbiota transplantation (FMT) has been used successfully to treat a variety of gastroenterological diseases. The alterations of microbiota in mouse models of necrotizing enterocolitis (NEC) as well as in patients suggested the possibility of treating NEC with FMT. Here we show that FMT caused an improvement in the histopathology and symptoms of NEC in WT mice, but not Grx1-/- mice. FMT eliminated O2(•)- production and promoted NO production in experimental NEC mice though the modulation of S-glutathionylation of eNOS (eNOS-SSG). FMT decreased the extent of TLR4-mediated proinflammatory signaling though TLR9 in the intestinal mucosa tissue. FMT also suppressed intestinal apoptosis and bacterial translocation across the intestinal barrier, which was accompanied by decreased inflammatory cytokine levels, altered bacterial microbiota, and regulated lymphocyte proportions. FMT is effective in a mouse model of NEC through the modulation of oxidative stress and reduced colon inflammation.

  13. Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis.

    PubMed

    Cheng, Ni-Tao; Meng, Hai; Ma, Li-Feng; Zhang, Liang; Yu, Hao-Miao; Wang, Zhen-Zhong; Guo, Ai

    2017-03-23

    Accumulating evidence suggests that autophagy is closely related to the pathogenesis of osteoarthritis (OA). The aim of this study was to determine the changes in autophagy during the progression of OA and to elucidate the specific role of autophagy in OA. For this purpose, a cellular model of OA was generated by stimulating SW1353 cells with interleukin (IL)-1β and a rabbit model of OA was also established by an intra-articular injection of collagenase, followed by treatment with the autophagy specific inhibitor, 3-methyladenine (3-MA). Cell viability was analyzed by MTS assay, and the mRNA expression levels of matrix metalloproteinases (MMP)-13 and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by RT-qPCR. Cartilage degeneration was examined under a light microscope, and autophagosome and chondrocyte degeneration was observed by transmission electron microscopy. The protein expression of Beclin-1 and light chain 3 (LC3)B was evaluated by western blot analysis and immunofluorescence staining. We found that the autophagy was enhanced during the early stages and was weakened during the late stages of experimental OA. The inhibition of autophagy by 3-MA significantly aggravated the degeneration of chondrocytes and cartilage in experimental OA. Our results thus determine the changes in autophagy during different stages of OA, as well as the role of impaired autophagy in the development of OA. Our data suggest that the regulation of autophagy may be a potential therapeutic strategy with which to attenuate OA.

  14. Recovery After Stroke: Dealing with Pain

    MedlinePlus

    Recovery After Stroke: Dealing with Pain Some survivors have to deal with pain caused by their strokes. ... good quality of life.  Get information on stroke recovery from National Stroke Association. Visit www. stroke. org ...

  15. What to Know - and Do! - about Stroke

    MedlinePlus

    ... this page please turn Javascript on. Feature: Stroke Rehabilitation What to Know – and Do! – About Stroke Past ... chances of having a stroke. Read More "Stroke Rehabilitation" Articles What to Know – and Do! – About Stroke / " ...

  16. Stability of muscle synergies for voluntary actions after cortical stroke in humans

    PubMed Central

    Cheung, Vincent C. K.; Piron, Lamberto; Agostini, Michela; Silvoni, Stefano; Turolla, Andrea; Bizzi, Emilio

    2009-01-01

    Production of voluntary movements relies critically on the functional integration of several motor cortical areas, such as the primary motor cortex, and the spinal circuitries. Surprisingly, after almost 40 years of research, how the motor cortices specify descending neural signals destined for the downstream interneurons and motoneurons has remained elusive. In light of the many recent experimental demonstrations that the motor system may coordinate muscle activations through a linear combination of muscle synergies, we hypothesize that the motor cortices may function to select and activate fixed muscle synergies specified by the spinal or brainstem networks. To test this hypothesis, we recorded electromyograms (EMGs) from 12–16 upper arm and shoulder muscles from both the unaffected and the stroke-affected arms of stroke patients having moderate-to-severe unilateral ischemic lesions in the frontal motor cortical areas. Analyses of EMGs using a nonnegative matrix factorization algorithm revealed that in seven of eight patients the muscular compositions of the synergies for both the unaffected and the affected arms were strikingly similar to each other despite differences in motor performance between the arms, and differences in cerebral lesion sizes and locations between patients. This robustness of muscle synergies that we observed supports the notion that descending cortical signals represent neuronal drives that select, activate, and flexibly combine muscle synergies specified by networks in the spinal cord and/or brainstem. Our conclusion also suggests an approach to stroke rehabilitation by focusing on those synergies with altered activations after stroke. PMID:19880747

  17. Vulnerability to Stroke: Implications of Perinatal Programming of the Hypothalamic-Pituitary-Adrenal Axis

    PubMed Central

    Craft, Tara K. S.; DeVries, A. Courtney

    2009-01-01

    Chronic stress is capable of exacerbating each major, modifiable, endogenous risk factor for cerebrovascular and cardiovascular disease. Indeed, exposure to stress can increase both the incidence and severity of stroke, presumably through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Now that characterization of the mechanisms underlying epigenetic programming of the HPA axis is well underway, there has been renewed interest in examining the role of early environment on the evolution of health conditions across the entire lifespan. Indeed, neonatal manipulations in rodents that reduce stress responsivity, and subsequent life-time exposure to glucocorticoids, are associated with a reduction in the development of neuroendocrine, neuroanatomical, and cognitive dysfunctions that typically progress with age. Although improved day to day regulation of the HPA axis also may be accompanied by a decrease in stroke risk, evidence from rodent studies suggest that an associated cost could be increased susceptibility to inflammation and neuronal death in the event that a stroke does occur and the individual is exposed to persistently elevated corticosteroids. Given its importance in regulation of health and disease states, any long-term modulation of the HPA axis is likely to be associated with both benefits and potential risks. The goals of this review article are to examine (1) the clinical and experimental data suggesting that neonatal experiences can shape HPA axis regulation, (2) the influence of stress and the HPA axis on stroke incidence and severity, and (3) the potential for neonatal programming of the HPA axis to impact adult cerebrovascular health. PMID:20057937

  18. Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale

    PubMed Central

    Agis, Daniel; Goggins, Maria B.; Oishi, Kumiko; Oishi, Kenichi; Davis, Cameron; Wright, Amy; Kim, Eun Hye; Sebastian, Rajani; Tippett, Donna C.; Faria, Andreia

    2016-01-01

    Background and Purpose— The National Institutes of Health Stroke Scale (NIHSS) includes minimal assessment of cognitive function, particularly in right hemisphere (RH) stroke. Descriptions of the Cookie Theft picture from the NIHSS allow analyses that (1) correlate with aphasia severity and (2) identify communication deficits in RH stroke. We hypothesized that analysis of the picture description contributes valuable information about volume and location of acute stroke. Methods— We evaluated 67 patients with acute ischemic stroke (34 left hemisphere [LH]; 33 RH) with the NIHSS, analysis of the Cookie Theft picture, and magnetic resonance imaging, compared with 35 sex- and age-matched controls. We evaluated descriptions for total content units (CU), syllables, ratio of left:right CU, CU/minute, and percent interpretive CU, based on previous studies. Lesion volume and percent damage to regions of interest were measured on diffusion-weighted imaging. Multivariable linear regression identified variables associated with infarct volume, independently of NIHSS score, age and sex. Results— Patients with RH and LH stroke differed from controls, but not from each other, on CU, syllables/CU, and CU/minute. Left:right CU was lower in RH compared with LH stroke. CU, syllables/CU, and NIHSS each correlated with lesion volume in LH and RH stroke. Lesion volume was best accounted by a model that included CU, syllables/CU, NIHSS, left:right CU, percent interpretive CU, and age, in LH and RH stroke. Each discourse variable and NIHSS score were associated with percent damage to different regions of interest, independently of lesion volume and age. Conclusions— Brief picture description analysis complements NIHSS scores in predicting stroke volume and location. PMID:27217502

  19. White matter injury and microglia/macrophage polarization are strongly linked with age-related long-term deficits in neurological function after stroke.

    PubMed

    Suenaga, Jun; Hu, Xiaoming; Pu, Hongjian; Shi, Yejie; Hassan, Sulaiman Habib; Xu, Mingyue; Leak, Rehana K; Stetler, R Anne; Gao, Yanqin; Chen, Jun

    2015-10-01

    Most of the successes in experimental models of stroke have not translated well to the clinic. One potential reason for this failure is that stroke mainly afflicts the elderly and the majority of experimental stroke studies rely on data gathered from young adult animals. Therefore, in the present study we established a reliable, reproducible model of stroke with low mortality in aged (18month) male mice and contrasted their pathophysiological changes with those in young (2month) animals. To this end, mice were subjected to permanent tandem occlusion of the left distal middle cerebral artery (dMCAO) with ipsilateral common carotid artery occlusion (CCAO). Cerebral blood flow (CBF) was evaluated repeatedly during and after stroke. Reduction of CBF was more dramatic and sustained in aged mice. Aged mice exhibited more severe long-term sensorimotor deficits, as manifested by deterioration of performance in the Rotarod and hanging wire tests up to 35d after stroke. Aged mice also exhibited significantly worse long-term cognitive deficits after stroke, as measured by the Morris water maze test. Consistent with these behavioral observations, brain infarct size and neuronal tissue loss after dMCAO were significantly larger in aged mice at 2d and 14d, respectively. The young versus aged difference in neuronal tissue loss, however, did not persist until 35d after dMCAO. In contrast to the transient difference in neuronal tissue loss, we found significant and long lasting deterioration of white matter in aged animals, as revealed by the loss of myelin basic protein (MBP) staining in the striatum at 35d after dMCAO. We further examined the expression of M1 (CD16/CD32) and M2 (CD206) markers in Iba-1(+) microglia by double immunofluorescent staining. In both young and aged mice, the expression of M2 markers peaked around 7d after stroke whereas the expression of M1 markers peaked around 14d after stroke, suggesting a progressive M2-to-M1 phenotype shift in both groups. However

  20. A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental model.

    PubMed

    Apitz-Castro, R; Badimon, J J; Badimon, L

    1994-08-01

    Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic. In vitro, ajoene reversibly inhibits platelet aggregation as well as the release reaction induced by all known agonists. We used a well characterized perfusion chamber to study the in vivo effects of ajoene on platelet deposition onto a highly thrombogenic, severely damaged arterial wall, obtained by stripping off the intimal layer and exposing tunica media. Platelet-vessel wall interaction and the effect of ajoene was studied under flow conditions of high and low local shear rate that mimics laminar blood flow in small and medium size arteries (1690 sec-1 and 212 sec-1). Our results indicate that administration of ajoene to heparinized animals, significantly prevents thrombus formation at local low blood shear rate. Ajoene does not inhibit binding of vWF to GPIb, therefore, it does not affect platelet adhesion. In fact, although ajoene impairs fibrinogen and vWF (less efficient) binding to GPlIb/IIIa, it does not totally inhibits platelet deposition to the substrates at any of the shear rates used in this study. Our present results, under in vivo flow conditions and in the presence of physiological calcium levels, suggest that ajoene may be potentially useful for the acute prevention of thrombus formation induced by severe vascular damage, mainly in arterial sites with local low shear rates.

  1. Experimental results from containment piping bellows subjected to severe accident conditions: Results from bellows tested in corroded conditions. Volume 2

    SciTech Connect

    Lambert, L.D.; Parks, M.B.

    1995-10-01

    Bellows are an integral part of the containment pressure boundary in nuclear power plants. They are used at piping penetrations to allow relative movement between piping and the containment wall, while minimizing the load imposed on the piping and wall. Piping bellows are primarily used in steel containments; however, they have received limited use in some concrete (reinforced and prestressed) containments. In a severe accident they may be subjected to pressure and temperature conditions that exceed the design values, along with a combination of axial and lateral deflections. A test program to determine the leak-tight capacity of containment penetration bellows is being conducted at Sandia National Laboratories under the sponsorship of the US Nuclear Regulatory Commission. Several different bellows geometries, representative of actual containment bellows, have been subjected to extreme deflections along with pressure and temperature loads. The bellows geometries and loading conditions are described along with the testing apparatus and procedures. A total of nineteen bellows have been tested. Thirteen bellows were tested in ``like-new`` condition (results reported in Volume 1), and six were tested in a corroded condition. The tests showed that bellows in ``like-new`` condition are capable of withstanding relatively large deformations, up to, or near, the point of full compression or elongation, before developing leakage, while those in a corroded condition did not perform as well, depending on the amount of corrosion. The corroded bellows test program and results are presented in this report.

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

    PubMed

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

    2016-04-01

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

  3. Ipsilateral versus contralateral spontaneous post-stroke neuroplastic changes: involvement of BDNF?

    PubMed

    Madinier, A; Bertrand, N; Rodier, M; Quirié, A; Mossiat, C; Prigent-Tessier, A; Marie, C; Garnier, P

    2013-02-12

    Stroke is a leading cause of death and disability in industrialized countries. Although surviving patients exhibit a certain degree of restoration of function attributable to brain plasticity, the majority of stroke survivors has to struggle with persisting deficits. In order to potentiate post-stroke recovery, several rehabilitation therapies have been undertaken and many experimental studies have reported that brain-derived neurotrophic factor (BDNF) is central to many facets of neuroplastic processes. However, although BDNF role in brain plasticity is well characterized through strategies that manipulate its content, the involvement of this neurotrophin in spontaneous post-stroke recovery remains to be clarified. Besides, while the neuroplastic role of BDNF is restricted to its mature form, most studies investigating the proper effect of ischemia on post-stroke BDNF metabolism focused on mRNA or total protein expressions. In addition, these studies are mainly performed in brain regions collected either at or around the lesion site. Therefore, the objective of the present study was to investigate in both hemispheres, the long-term expression (up to one month) of both pro- and mature BDNF forms in rats subjected to photothrombotic ischemia. These assessments were performed in the cortex and in the hippocampus, two regions known to subserve functional recovery after stroke and were coupled to the study of synaptophysin expression, a marker of synaptogenesis. Our study reports that stroke induces an early and transient increase (4h) in mature BDNF expression in the cortex of both hemispheres that was associated with a delayed rise (30d) in synaptophysin levels ipsilateraly. In both hippocampal territories, the pattern of mature BDNF expression shows a more delayed increase (from 8 to 30d), which coincides with the evolution of synaptophysin expression. Interestingly, in these hippocampal territories, pro-BDNF levels evolve differently suggesting a differential gene

  4. Positive effects of intermittent fasting in ischemic stroke.

    PubMed

    Fann, David Yang-Wei; Ng, Gavin Yong Quan; Poh, Luting; Arumugam, Thiruma V

    2017-03-01

    Intermittent fasting (IF) is a dietary protocol where energy restriction is induced by alternate periods of ad libitum feeding and fasting. Prophylactic intermittent fasting has been shown to extend lifespan and attenuate the progress and severity of age-related diseases such as cardiovascular (e.g. stroke and myocardial infarction), neurodegenerative (e.g. Alzheimer's disease and Parkinson's disease) and cancerous diseases in animal models. Stroke is the second leading cause of death, and lifestyle risk factors such as obesity and physical inactivity have been associated with elevated risks of stroke in humans. Recent studies have shown that prophylactic IF may mitigate tissue damage and neurological deficit following ischemic stroke by a mechanism(s) involving suppression of excitotoxicity, oxidative stress, inflammation and cell death pathways in animal stroke models. This review summarizes data supporting the potential hormesis mechanisms of prophylactic IF in animal models, and with a focus on findings from animal studies of prophylactic IF in stroke in our laboratory.

  5. The Role of Omega-3 Polyunsaturated Fatty Acids in Stroke

    PubMed Central

    Bu, Jiyuan; Dou, Yang; Tian, Xiaodi; Wang, Zhong

    2016-01-01

    Stroke is the third commonest cause of death following cardiovascular diseases and cancer. In particular, in recent years, the morbidity and mortality of stroke keep remarkable growing. However, stroke still captures people attention far less than cardiovascular diseases and cancer. Past studies have shown that oxidative stress and inflammation play crucial roles in the progress of cerebral injury induced by stroke. Evidence is accumulating that the dietary supplementation of fish oil exhibits beneficial effects on several diseases, such as cardiovascular diseases, metabolic diseases, and cancer. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), the major component of fish oil, have been found against oxidative stress and inflammation in cardiovascular diseases. And the potential of n-3 PUFAs in stroke treatment is attracting more and more attention. In this review, we will review the effects of n-3 PUFAs on stroke and mainly focus on the antioxidant and anti-inflammatory effects of n-3 PUFAs. PMID:27433289

  6. Blood pressure control versus atrial fibrillation management in stroke prevention.

    PubMed

    Savoia, Carmine; Sada, Lidia; Volpe, Massimo

    2015-06-01

    Hypertension is one of the major risk factors for atrial fibrillation which in turn is the most prevalent concomitant condition in hypertensive patients. While both these pathological conditions are independent risk factors for stroke, the association of hypertension and atrial fibrillation increases the incidence of disabling strokes. Moreover, documented or silent atrial fibrillation doubles the rate of cardiovascular death. Lowering blood pressure is strongly recommended, particularly for primary stroke prevention. However, a relatively small percentage of hypertensive patients still achieve the recommended blood pressure goals. The management of atrial fibrillation with respect to stroke prevention is changing. New oral anticoagulants represent a major advancement in long-term anticoagulation therapy in non valvular atrial fibrillation. They have several benefits over warfarin, including improved adherence to the anticoagulation therapy. This is an important issue since non-adherence to stroke prevention medications is a risk factor for first and recurrent strokes.

  7. Trypanosomiasis, cardiomyopathy and the risk of ischemic stroke.

    PubMed

    Carod-Artal, Francisco Javier

    2010-05-01

    American (Chagas disease) and African (sleeping sickness) trypanosomiasis are neglected tropical diseases and are a heavy burden in Latin America and Africa, respectively. Chagas disease is an independent risk factor for stroke. Apical aneurysm, heart failure and cardiac arrhythmias are associated with ischemic stroke in chagasic cardiomyopathy. Not all chagasic patients who suffer an ischemic stroke have a severe cardiomyopathy, and stroke may be the first manifestation of Chagas disease. Cardioembolism affecting the middle cerebral artery is the most common stroke subtype. Risk of recurrence is high and careful evaluation of recurrence risk should be addressed. Repolarization changes, low voltage and prolonged QT interval are common electrocardiography alterations in human African trypanosomiasis, and can be found in more than 70% of patients. Epidemiological studies are needed to asses the risk of stroke in African trypanosomiasis perimyocarditis.

  8. National Institutes of Health Stroke Scale in Plain English Is Reliable for Novice Nurse Users with Minimal Training.

    PubMed

    Dancer, Sandy; Brown, Allen J; Yanase, Lisa Rietz

    2017-03-28

    The National Institutes of Health Stroke Scale (NIHSS) is commonly used in Comprehensive Stroke Centers, but it has not been easily implemented in smaller centers. The aim of this study was to assess whether nurse providers who were naive to stroke assessment scales could obtain accurate stroke severity scores using our previously validated NIH Stroke Scale in Plain English (NIHSS-PE) with minimal or no training.

  9. Thrombolysis for acute ischaemic stroke

    PubMed Central

    Wardlaw, Joanna M; Murray, Veronica; Berge, Eivind; del Zoppo, Gregory J

    2014-01-01

    Background Most strokes are due to blockage of an artery in the brain by a blood clot. Prompt treatment with thrombolytic drugs can restore blood flow before major brain damage has occurred and improve recovery after stroke in some people. Thrombolytic drugs, however, can also cause serious bleeding in the brain, which can be fatal. One drug, recombinant tissue plasminogen activator (rt-PA), is licensed for use in selected patients within 4.5 hours of stroke in Europe and within three hours in the USA. There is an upper age limit of 80 years in some countries, and a limitation to mainly non-severe stroke in others. Forty per cent more data are available since this review was last updated in 2009. Objectives To determine whether, and in what circumstances, thrombolytic therapy might be an effective and safe treatment for acute ischaemic stroke. Search methods We searched the Cochrane Stroke Group Trials Register (last searched November 2013), MEDLINE (1966 to November 2013) and EMBASE (1980 to November 2013).We also handsearched conference proceedings and journals, searched reference lists and contacted pharmaceutical companies and trialists. Selection criteria Randomised trials of any thrombolytic agent compared with control in people with definite ischaemic stroke. Data collection and analysis Two review authors applied the inclusion criteria, extracted data and assessed trial quality. We verified the extracted data with investigators of all major trials, obtaining additional unpublished data if available. Main results We included 27 trials, involving 10,187 participants, testing urokinase, streptokinase, rt-PA, recombinant pro-urokinase or desmoteplase. Four trials used intra-arterial administration, while the rest used the intravenous route. Most data come from trials that started treatment up to six hours after stroke. About 44% of the trials (about 70% of the participants) were testing intravenous rt-PA. In earlier studies very few of the participants (0

  10. Stroke (For Kids)

    MedlinePlus

    ... stroke, doctors usually get an MRI or a CAT scan , which take pictures of the brain and how blood is flowing through the brain. This test can show the doctor what part of the brain has been affected and how big the stroke is. How Does a Person Get ...

  11. Immune interventions in stroke

    PubMed Central

    Fu, Ying; Liu, Qiang; Anrather, Josef

    2016-01-01

    Inflammatory and immune responses in the brain can shape the clinical presentation and outcome of stroke. Approaches for effective management of acute stroke are sparse and many measures for brain protection fail, but our ability to modulate the immune system and modify the disease progression of multiple sclerosis is increasing. As a result, immune interventions are currently being explored as therapeutic interventions in acute stroke. In this Review, we compare the immunological features of acute stroke with those of multiple sclerosis, identify unique immunological features of stroke, and consider the evidence for immune interventions. In acute stroke, microglia activation and cell death products trigger an inflammatory cascade that damages vessels and the parenchyma within minutes to hours of the ischaemia or haemorrhage. Immune interventions that restrict brain inflammation, vascular permeability and tissue oedema must be administered rapidly to reduce acute immune-mediated destruction and to avoid subsequent immunosuppression. Preliminary results suggest that the use of drugs that modify disease in multiple sclerosis might accomplish these goals in ischaemic and haemorrhagic stroke. Further elucidation of the immune mechanisms involved in stroke is likely to lead to successful immune interventions. PMID:26303850

  12. The Danish Stroke Registry

    PubMed Central

    Johnsen, Søren Paaske; Ingeman, Annette; Hundborg, Heidi Holmager; Schaarup, Susanne Zielke; Gyllenborg, Jesper

    2016-01-01

    Aim of database The aim of the Danish Stroke Registry is to monitor and improve the quality of care among all patients with acute stroke and transient ischemic attack (TIA) treated at Danish hospitals. Study population All patients with acute stroke (from 2003) or TIA (from 2013) treated at Danish hospitals. Reporting is mandatory by law for all hospital departments treating these patients. The registry included >130,000 events by the end of 2014, including 10,822 strokes and 4,227 TIAs registered in 2014. Main variables The registry holds prospectively collected data on key processes of care, mainly covering the early phase after stroke, including data on time of delivery of the processes and the eligibility of the individual patients for each process. The data are used for assessing 18 process indicators reflecting recommendations in the national clinical guidelines for patients with acute stroke and TIA. Patient outcomes are currently monitored using 30-day mortality, unplanned readmission, and for patients receiving revascularization therapy, also functional level at 3 months poststroke. Descriptive data Sociodemographic, clinical, and lifestyle factors with potential prognostic impact are registered. Conclusion The Danish Stroke Registry is a well-established clinical registry which plays a key role for monitoring and improving stroke and TIA care in Denmark. In addition, the registry is increasingly used for research. PMID:27843349

  13. Relational Processing Following Stroke

    ERIC Educational Resources Information Center

    Andrews, Glenda; Halford, Graeme S.; Shum, David; Maujean, Annick; Chappell, Mark; Birney, Damian

    2013-01-01

    The research examined relational processing following stroke. Stroke patients (14 with frontal, 30 with non-frontal lesions) and 41 matched controls completed four relational processing tasks: sentence comprehension, Latin square matrix completion, modified Dimensional Change Card Sorting, and n-back. Each task included items at two or three…

  14. Effects of early surgical decompression on functional and histological outcomes after severe experimental thoracic spinal cord injury.

    PubMed

    Jalan, Devesh; Saini, Neginder; Zaidi, Mohammad; Pallottie, Alexandra; Elkabes, Stella; Heary, Robert F

    2017-01-01

    OBJECTIVE In acute traumatic brain injury, decompressive craniectomy is a common treatment that involves the removal of bone from the cranium to relieve intracranial pressure. The present study investigated whether neurological function following a severe spinal cord injury improves after utilizing either a durotomy to decompress the intradural space and/or a duraplasty to maintain proper flow of cerebrospinal fluid. METHODS Sixty-four adult female rats (n = 64) were randomly assigned to receive either a 3- or 5-level decompressive laminectomy (Groups A and B), laminectomy + durotomy (Groups C and D), or laminectomy + duraplasty with graft (Group E and F) at 24 hours following a severe thoracic contusion injury (200 kilodynes). Duraplasty involved the use of DuraSeal, a hydrogel dural sealant. Uninjured and injured control groups were included (Groups G, H). Hindlimb locomotor function was assessed by open field locomotor testing (BBB) and CatWalk gait analysis at 35 days postinjury. Bladder function was analyzed and bladder wall thickness was assessed histologically. At 35 days postinjury, mechanical and thermal allodynia were assessed by the Von Frey hair filament and hotplate paw withdrawal tests, respectively. Thereafter, the spinal cords were dissected, examined for gross anomalies at the injury site, and harvested for histological analyses to assess lesion volumes and white matter sparing. ANOVA was used for statistical analyses. RESULTS There was no significant improvement in motor function recovery in any treatment groups compared with injured controls. CatWalk gait analysis indicated a significant decrease in interlimb coordination in Groups B, C, and D (p < 0.05) and swing speed in Groups A, B, and D. Increased mechanical pain sensitivity was observed in Groups A, C, and F (p < 0.05). Rats in Group C also developed thermal pain hypersensitivity. Examination of spinal cords demonstrated increased lesion volumes in Groups C and F and increased white matter

  15. Ischaemic stroke: a thrombo-inflammatory disease?

    PubMed Central

    Nieswandt, Bernhard; Kleinschnitz, Christoph; Stoll, Guido

    2011-01-01

    Abstract Ischaemic stroke is a leading cause of death and disability worldwide. The complex cellular interactions leading from thromboembolic vessel occlusion to infarct development within the brain parenchyma in acute stroke are poorly understood, which translates into only one approved effective treatment, thrombolysis. Importantly, however, patients can develop progressive stroke despite reperfusion of previously occluded major intracranial arteries, a process referred to as ‘reperfusion injury’ which can be reproduced in the mouse model of transient middle cerebral artery occlusion (tMCAO). Although pathological platelet and coagulant activity have long been recognized to be involved in the initiation of ischaemic stroke, their contribution to infarct maturation remained elusive. Experimental evidence now suggests that early platelet adhesion/activation mechanisms involving the von Willebrand factor (vWF) receptor glycoprotein (GP) Ib, its ligand vWF, and the collagen receptor GPVI are critical pathogenic factors in infarct development following tMCAO, whereas platelet aggregation through GPIIb/IIIa is not. Further experimental work indicates that these pathways in conjunction with coagulation factor XII (FXII)-driven processes orchestrate a ‘thrombo-inflammatory’ cascade in acute stroke that results in infarct growth. This review summarizes these recent developments and briefly discusses their potential clinical impact. PMID:21768262

  16. Genetics of ischaemic stroke in young adults

    PubMed Central

    Terni, Eva; Giannini, Nicola; Brondi, Marco; Montano, Vincenzo; Bonuccelli, Ubaldo; Mancuso, Michelangelo

    2014-01-01

    Background Stroke may be a clinical expression of several inherited disorders in humans. Recognition of the underlined genetic disorders causing stroke is important for a correct diagnosis, for genetic counselling and, even if rarely, for a correct therapeutic management. Moreover, the genetics of complex diseases such the stroke, in which multiple genes interact with environmental risk factors to increase risk, has been revolutionized by the Genome-Wide Association Study (GWAS) approach. Scope of review Here we review the single-gene causes of ischemic stroke, bringing the reader from the candidate gene method toward the exciting new horizons of genetic technology. Major conclusions The aetiological diagnosis of ischemic stroke in young adults is more complex than in the elderly. The identification of a genetic cause is important to provide appropriate counseling and to start a correct therapy, when available. The advent of GWAS technology, such as for other complex pathological conditions, has contributed enormously to the understanding of many of these genetic bases. For success large, well phenotyped case cohorts are required, and international collaborations are essential. General significance This review focuses on the main causes of genetically-based ischemic stroke in young adults, often classified as indeterminate, investigating also the recent findings of the GWAS, in order to improve diagnostic and therapeutic management. PMID:26672892

  17. 3-(3-Pyridylmethylidene)-2-indolinone Reduces the Severity of Colonic Injury in a Murine Model of Experimental Colitis

    PubMed Central

    Wang, Kun-Ping; Zhang, Chao; Zhang, Shou-Guo; Liu, En-Dong; Dong, Lan; Kong, Xiang-Zhen; Cao, Peng; Hu, Chun-Ping; Zhao, Ke; Zhan, Yi-Qun; Dong, Xiao-Ming; Ge, Chang-Hui; Yu, Miao; Chen, Hui; Wang, Lin; Yang, Xiao-Ming; Li, Chang-Yan

    2015-01-01

    Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerous in vivo studies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene)-2-indolinone (PMID) is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS-) induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response. PMID:25874026

  18. Assessed and Emerging Biomarkers in Stroke and Training-Mediated Stroke Recovery: State of the Art

    PubMed Central

    Vella, Antonio

    2017-01-01

    Since the increasing update of the biomolecular scientific literature, biomarkers in stroke have reached an outstanding and remarkable revision in the very recent years. Besides the diagnostic and prognostic role of some inflammatory markers, many further molecules and biological factors have been added to the list, including tissue derived cytokines, growth factor-like molecules, hormones, and microRNAs. The literatures on brain derived growth factor and other neuroimmune mediators, bone-skeletal muscle biomarkers, cellular and immunity biomarkers, and the role of microRNAs in stroke recovery were reviewed. To date, biomarkers represent a possible challenge in the diagnostic and prognostic evaluation of stroke onset, pathogenesis, and recovery. Many molecules are still under investigation and may become promising and encouraging biomarkers. Experimental and clinical research should increase this list and promote new discoveries in this field, to improve stroke diagnosis and treatment. PMID:28373915

  19. Ethyl pyruvate therapy attenuates experimental severe arthritis caused by type II collagen (CII) in the mouse (CIA).

    PubMed

    Di Paola, R; Mazzon, E; Galuppo, M; Esposito, E; Bramanti, P; Fink, M P; Cuzzocrea, S

    2010-01-01

    This study tested the hypothesis that ethyl pyruvate (EP), a simple aliphatic ester with anti-inflammatory effects, can reduce type II collagen-induced mouse arthritis (CIA). DBA/1J mice were used for the study, developing erosive hind paw arthritis when immunized with CII in an emulsion in complete Freund?s adjuvant (CFA). The incidence of CIA was 100 percent by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. EP-treatment (40 mg/kg/day i.p.) starting at the onset of arthritis (day 25) ameliorated the clinical signs at days 26-35 and improved histological status in the joint and paw. Immunohistochemical analysis for nitrotyrosine, poly (ADP-ribose) (PAR), inducible nitric oxide synthase (iNOS) revealed a positive staining in inflamed joints from mice subjected to CIA, while no staining was observed for HO-1 and Nrf-2 in the same group. The degree of staining for nitrotyrosine, PAR, iNOS, was significantly reduced in CII-challenged mice treated with the EP. Immuno-positive-staining for HO-1 and Nrf-2 was observed instead, in joints obtained from the EP-treated group. Plasma levels of TNF-α, IL-6 and the joint tissue levels of macrophage inflammatory protein (MIP)-1α and MIP-2 were also significantly reduced by EP treatment. Thirty-five days after immunization, EP-treatment significantly increased plasma levels of IL-10. These data demonstrate that EP treatment exerts an anti-inflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.

  20. Yin-Chen-Hao Tang Attenuates Severe Acute Pancreatitis in Rat: An Experimental Verification of In silico Network Target Prediction

    PubMed Central

    Xiang, Hong; Wang, Guijun; Qu, Jialin; Xia, Shilin; Tao, Xufeng; Qi, Bing; Zhang, Qingkai; Shang, Dong

    2016-01-01

    Yin-Chen-Hao Tang (YCHT) is a classical Chinese medicine compound that has a long history of clinical use in China for the treatment of inflammatory diseases. However, the efficacy and mechanisms of YCHT for the treatment of severe acute pancreatitis (SAP) are not known. The current study investigated the pharmacological properties of YCHT against SAP and its underlying mechanisms. A computational prediction of potential targets of YCHT was initially established based on a network pharmacology simulation. The model suggested that YCHT attenuated SAP progress by apoptosis inducement, anti-inflammation, anti-oxidation and blood lipid regulation. These effects were validated in SAP rats. YCHT administration produced the following results: (1) significantly inhibited the secretion of pancreatic enzymes and protected pancreatic tissue; (2) obviously increased the number of in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells and induced apoptosis; (3) markedly inhibited neutrophil infiltration to the impaired pancreas and reduced the inflammatory reaction; (4) notably enhanced the activities of antioxidant enzymes and decreased the nitric oxide synthase levels; (5) significantly reduced the levels of triglycerides, total cholesterol and low-density lipoprotein and increased high-density lipoprotein; and (6) significantly up-regulated peroxisome proliferator-activated receptor-γ (PPARγ) and down-regulated nuclear factor-kappa B (NF-κB). In summary, these results demonstrated that YCHT attenuated SAP progress by inducing apoptosis, repressing inflammation, alleviating oxidative stress and regulating lipid metabolism partially via regulation of the NF-κB/PPARγ signal pathway. PMID:27790147

  1. Effects of experimental fuel additions on fire intensity and severity: unexpected carbon resilience of a neotropical forest.

    PubMed

    Brando, Paulo M; Oliveria-Santos, Claudinei; Rocha, Wanderley; Cury, Roberta; Coe, Michael T

    2016-07-01

    Global changes and associated droughts, heat waves, logging activities, and forest fragmentation may intensify fires in Amazonia by altering forest microclimate and fuel dynamics. To isolate the effects of fuel loads on fire behavior and fire-induced changes in forest carbon cycling, we manipulated fine fuel loads in a fire experiment located in southeast Amazonia. We predicted that a 50% increase in fine fuel loads would disproportionally increase fire intensity and severity (i.e., tree mortality and losses in carbon stocks) due to multiplicative effects of fine fuel loads on the rate of fire spread, fuel consumption, and burned area. The experiment followed a fully replicated randomized block design (N = 6) comprised of unburned control plots and burned plots that were treated with and without fine fuel additions. The fuel addition treatment significantly increased burned area (+22%) and consequently canopy openness (+10%), fine fuel combustion (+5%), and mortality of individuals ≥5 cm in diameter at breast height (dbh; +37%). Surprisingly, we observed nonsignificant effects of the fuel addition treatment on fireline intensity, and no significant differences among the three treatments for (i) mortality of large trees (≥30 cm dbh), (ii) aboveground forest carbon stocks, and (iii) soil respiration. It was also surprising that postfire tree growth and wood increment were higher in the burned plots treated with fuels than in the unburned control. These results suggest that (i) fine fuel load accumulation increases the likelihood of larger understory fires and (ii) single, low-intensity fires weakly influence carbon cycling of this primary neotropical forest, although delayed postfire mortality of large trees may lower carbon stocks over the long term. Overall, our findings indicate that increased fine fuel loads alone are unlikely to create threshold conditions for high-intensity, catastrophic fires during nondrought years.

  2. Current status of acute stroke management in Korea: a report on a multicenter, comprehensive acute stroke registry.

    PubMed

    Kim, Beom Joon; Han, Moon-Ku; Park, Tai Hwan; Park, Sang-Soon; Lee, Kyung Bok; Lee, Byung-Chul; Yu, Kyung-Ho; Cha, Jae Kwan; Kim, Dae-Hyun; Lee, Jun; Lee, Soo Joo; Ko, Youngchai; Park, Jong-Moo; Kang, Kyusik; Cho, Yong-Jin; Hong, Keun-Sik; Cho, Ki-Hyun; Kim, Joon-Tae; Kim, Dong-Eog; Lee, Juneyoung; Lee, Ji Sung; Jang, Myung Suk; Broderick, Joseph P; Yoon, Byung-Woo; Bae, Hee-Joon

    2014-06-01

    There are limited data on the utilization of diagnostics and the variation of treatments at the national level in acute stroke care. Clinical Research Center for Stroke--5th division stroke registry aimed to describe stroke statistics and quality of care in Korea and to implement quality indicators. Clinical Research Center for Stroke--5th division registry was established in April 2008 and covers pretreatment demographics, medical and stroke severity measures, diagnostic evaluation, hyperacute revascularization, in-hospital management, discharge disposition, quality indicators, and long-term functional outcomes. Consecutive stroke cases from 12 participating centers are registered to a web-based database. Meticulous data management and auditing policy were applied. A total of 14,792 ischemic stroke cases were enrolled from April 2008 to January 2012. The median National Institutes of Health Stroke Scale score was 4 at admission, with median delay of onset to arrival of 14 h. Rate of risk factor management before stroke exceeds more than 80% for hypertension and diabetes. Revascularization procedures were performed in 1736 subjects (12%), and 34% were endovascular (n = 598). Substantial variability was noted in the preferred modality of hyperacute revascularization (range of endovascular recanalization = 6-60%), use of computed tomography (30-93%), and perfusion imaging (2-96%). The Clinical Research Center for Stroke--5th division registry documented that the current practice of acute stroke care in South Korea largely met the standard of guidelines, but variability of practice still remains. The registry would provide an opportunity to evaluate the quality of stroke care across South Korea and compare it with that of other countries.

  3. Intensive Treatment of Dysarthria Secondary to Stroke

    ERIC Educational Resources Information Center

    Mahler, Leslie A.; Ramig, Lorraine O.

    2012-01-01

    This study investigated the impact of a well-defined behavioral dysarthria treatment on acoustic and perceptual measures of speech in four adults with dysarthria secondary to stroke. A single-subject A-B-A experimental design was used to measure the effects of the Lee Silverman Voice Treatment (LSVT[R]LOUD) on the speech of individual…

  4. Trends in the treatment of risk factors for stroke in a Czech stroke unit

    PubMed Central

    Simunek, Libor; Krajickova, Dagmar; Vysata, Oldrich; Valis, Martin

    2015-01-01

    The goal of this study is to evaluate therapeutic trends for several diseases that represent risk factors for stroke. The relative frequency of therapy with compounds that influence the risk factors for stroke was monitored in a group of 3,290 patients who were hospitalised in the Stroke Unit at the University Hospital in Hradec Kralove between 2005 and 2012. For most drugs monitored, the reasons for the significant decrease or increase in use were causes other than the reduction of stroke risk. Despite this finding, the majority of statistically significant changes had, according to review of comparative studies, a positive effect on prevention of stroke. Motivation to change treatment of stroke risk factors, such as hypertension, diabetes mellitus and hypercholesterolemia, was mainly aimed at sufficient disease management with a minimum of adverse effects. On the other hand, optimization of stroke recurrence and economic factors were motivations to treatment changes in prevention with antiplatelets. Antidiabetics were associated with an increase in metformin use and reduction in insulin use. For antihypertensives, the most significant reduction was associated with the use of diuretics, although calcium channel blockers and beta-blockers are also less used. Additionally, the use of the ACE inhibitor ramipril increased PMID:28352720

  5. Risks for Heart Disease & Stroke

    MedlinePlus

    ... for Heart Disease & Stroke Risks for Heart Disease & Stroke About 1.5 million heart attacks and strokes happen every year in the United States. You ... some of your risks for heart disease and stroke, but you can manage many of your risks ...

  6. Heart Failure in Acute Ischemic Stroke

    PubMed Central

    Cuadrado-Godia, Elisa; Ois, Angel; Roquer, Jaume

    2010-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Due to the aging of the population it has become a growing public health problem in recent decades. Diagnosis of HF is clinical and there is no diagnostic test, although some basic complementary testing should be performed in all patients. Depending on the ejection fraction (EF), the syndrome is classified as HF with low EF or HF with normal EF (HFNEF). Although prognosis in HF is poor, HFNEF seems to be more benign. HF and ischemic stroke (IS) share vascular risk factors such as age, hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation. Persons with HF have higher incidence of IS, varying from 1.7% to 10.4% per year across various cohort studies. The stroke rate increases with length of follow-up. Reduced EF, independent of severity, is associated with higher risk of stroke. Left ventricular mass and geometry are also related with stroke incidence, with concentric hypertrophy carrying the greatest risk. In HF with low EF, the stroke mechanism may be embolism, cerebral hypoperfusion or both, whereas in HFNEF the mechanism is more typically associated with chronic endothelial damage of the small vessels. Stroke in patients with HF is more severe and is associated with a higher rate of recurrence, dependency, and short term and long term mortality. Cardiac morbidity and mortality is also high in these patients. Acute stroke treatment in HF includes all the current therapeutic options to more carefully control blood pressure. For secondary prevention, optimal control of all vascular risk factors is essential. Antithrombotic therapy is mandatory, although the choice of a platelet inhibitor or anticoagulant drug depends on the cardiac disease. Trials are ongoing to evaluate anticoagulant therapy for prevention of embolism in patients with low EF who are at

  7. The Migraine–Stroke Connection

    PubMed Central

    Lee, Mi Ji; Lee, Chungbin; Chung, Chin-Sang

    2016-01-01

    Migraine and stroke are common neurovascular disorders which share underlying physiological processes. Increased risks of ischemic stroke, hemorrhagic stroke, and subclinical ischemic lesions have been consistently found in migraineurs. Three possible associations are suggested. One is that underlying pathophysiology of migraine can lead to ischemic stroke. Second, common comorbidities between migraine and stroke can be present. Lastly, some syndromes can manifest with both migraine-like headache and cerebrovascular disease. Future studies should be targeted on bidirectional influence of migraine on different stroke mechanisms and optimal prevention of stroke in migraine patients. PMID:27283278

  8. Sexual function after strokes.

    PubMed

    Boller, François; Agrawal, Kunal; Romano, Alissa

    2015-01-01

    Strokes are the second leading cause of death and the third leading cause of disability worldwide. Thanks in part to better and more available diagnosis, treatment, and rehabilitation, the vast majority of stroke patients tend to survive strokes, particularly in the industrialized world. Motor disability and cognitive changes such as aphasia and visuospatial disorders are most often considered among the major contributors to stroke burden. This chapter discusses disorders of sexual functions as another frequent sequel of strokes. Strokes generally induce hyposexuality, but in some instances they may be followed by hypersexuality. There is some evidence suggesting that lesions of either hemisphere affect sexual activities, but for different reasons: aphasia and depression after left-hemisphere lesions, a deficit in arousal and perhaps visuospatial disorders after right-hemisphere lesions. Psychologic, psychosocial, and physical factors, as well as medications, play an important role. A better understanding of the psychosocial and physiologic mechanisms underlying sexual functioning can provide insight into improving sexual activity and therefore quality of life in patients affected by strokes and other brain lesions.

  9. Interleukin-1β Accelerates the Onset of Stroke in Stroke-Prone Spontaneously Hypertensive Rats

    PubMed Central

    Chiba, Tsuyoshi; Itoh, Tatsuki; Tabuchi, Masaki; Nakazawa, Toru; Satou, Takao

    2012-01-01

    High blood levels of inflammatory biomarkers and immune cells in stroke lesions have been recognized as results of stroke. However, recent studies have suggested that inflammation occurs prior to stroke onset. In this study, we aimed to clarify the role of inflammation in stroke onset among stroke-prone spontaneously hypertensive rats (SHRSP). At 4 weeks of age (before stroke onset), the plasma level of IL-1β was significantly higher in SHRSP (153.0 ± 49.7 pg/ml) than in Wistar Kyoto rats (WKY) (7.7 ± 3.4 pg/ml, P < 0.001 versus SHRSP) or spontaneously hypertensive rats (SHR) (28.0 ± 9.1 pg/ml, P < 0.001 versus SHRSP) (n = 6 per strain). Stimulated IL-1β signal was also observed in cerebrovascular endothelial cells of SHRSP. Gene expressions of IL-1β, IL-1 receptors, caspase-1, and downstream genes (MCP-1 and ICAM-1), which associated with immune cell recruitment, were significantly greater in SHRSP than in WKY or SHR, coincident with greater NFκB protein levels in SHRSP compared to WKY or SHR. In addition, continuous administration of IL-1β (2 μg/day) using an osmotic pump slightly increased the incidence of stroke in SHR (P = 0.046) and significantly accelerated the onset of stroke in SHRSP (P = 0.006) compared to each control (n = 10 per group). These results suggest that a stimulated IL-1β signal might be a cause of stroke onset when concomitant with severe hypertension. PMID:23326018

  10. Assimilation of Web-Based Urgent Stroke Evaluation: A Qualitative Study of Two Networks

    PubMed Central

    Mathiassen, Lars; Switzer, Jeffrey A; Adams, Robert J

    2014-01-01

    Background Stroke is a leading cause of death and serious, long-term disability across the world. Urgent stroke care treatment is time-sensitive and requires a stroke-trained neurologist for clinical diagnosis. Rural areas, where neurologists and stroke specialists are lacking, have a high incidence of stroke-related death and disability. By virtually connecting emergency department physicians in rural hospitals to regional medical centers for consultations, specialized Web-based stroke evaluation systems (telestroke) have helped address the challenge of urgent stroke care in underserved communities. However, many rural hospitals that have deployed telestroke have not fully assimilated this technology. Objective The objective of this study was to explore potential sources of variations in the utilization of a Web-based telestroke system for urgent stroke evaluation and propose a telestroke assimilation model to improve stroke care performance. Methods An exploratory, qualitative case study of two telestroke networks, each comprising an academic stroke center (hub) and connected rural hospitals (spokes), was conducted. Data were collected from 50 semistructured interviews with 40 stakeholders, telestroke usage logs from 32 spokes, site visits, published papers, and reports. Results The two networks used identical technology (called Remote Evaluation of Acute isCHemic stroke, REACH) and were of similar size and complexity, but showed large variations in telestroke assimilation across spokes. Several observed hub- and spoke-related characteristics can explain these variations. The hub-related characteristics included telestroke institutionalization into stroke care, resources for the telestroke program, ongoing support for stroke readiness of spokes, telestroke performance monitoring, and continuous telestroke process improvement. The spoke-related characteristics included managerial telestroke championship, stroke center certification, dedicated telestroke

  11. Potential of the angiotensin receptor blockers (ARBs) telmisartan, irbesartan, and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke.

    PubMed

    Kikuchi, Kiyoshi; Tancharoen, Salunya; Ito, Takashi; Morimoto-Yamashita, Yoko; Miura, Naoki; Kawahara, Ko-ichi; Maruyama, Ikuro; Murai, Yoshinaka; Tanaka, Eiichiro

    2013-09-13

    Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs.

  12. Newer Oral Anticoagulants: Stroke Prevention and Pitfalls

    PubMed Central

    Patel, Anand; Goddeau Jr, Richard P.; Henninger, Nils

    2016-01-01

    Warfarin is very effective in preventing stroke in patients with atrial fibrillation. However, its use is limited due to fear of hemorrhagic complications, unpredictable anticoagulant effects related to multiple drug interactions and dietary restrictions, a narrow therapeutic window, frequent difficulty maintaining the anticoagulant effect within a narrow therapeutic window, and the need for inconvenient monitoring. Several newer oral anticoagulants have been approved for primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation. These agents have several advantages relative to warfarin therapy. As a group, these direct oral anticoagulants (DOAC), which include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), are more effective than dose adjusted warfarin for prevention of all-cause stroke (including both ischemic and hemorrhagic stroke), and have an overall more favorable safety profile. Nevertheless, an increased risk of gastrointestinal bleeding (with the exception of apixaban), increased risk for thrombotic complication with sudden discontinuation, and inability to accurately assess and reverse anticoagulant effect require consideration prior to therapy initiation, and pose a challenge for decision making in acute stroke therapy. PMID:27347226

  13. Sleep and Stroke.

    PubMed

    Mims, Kimberly Nicole; Kirsch, Douglas

    2016-03-01

    Evidence increasingly suggests sleep disorders are associated with higher risk of cardiovascular events, including stroke. Strong data correlate untreated sleep apnea with poorer stroke outcomes and more recent evidence implicates sleep disruption as a possible etiology for increased cerebrovascular events. Also, sleep duration may affect incidence of cardiovascular events. In addition, sleep-disordered breathing, insomnia, restless legs syndrome, and parasomnias can occur as a result of cerebrovascular events. Treatment of sleep disorders improve sleep-related symptoms and may also improve stroke recovery and risk of future events.

  14. Evaluation of stroke disability.

    PubMed Central

    Jimenez, J.; Keltz, E.; Stein, M. C.; White, M. M.

    1976-01-01

    The disabilities resulting from a stroke are not well understood from the epidemiologic or functional point of view. The stroke may impair mental status, perception, sensation, communication and motor ability; the total resulting disability is related to the extent of impairment in each of these areas. A complete evaluation in all these areas has to be done to determine the degree of disability before any rehabilitation program is planned. A comprehensive approach to evaluating stroke disability is presented that includes correlating the degree of impairment in each of the above-mentioned areas with the overall functional ability of the patient. PMID:1260603

  15. GPs have pivotal role in care of stroke patients.

    PubMed

    Best, Catherine; Mead, Gillian

    2010-02-01

    Stroke is a major cause of mortality in the community and the most common cause of disability. At one year, a third of patients who have had a stroke have died, and 37% of survivors are dependent. In the acute phase of ischaemic stroke, patients should receive thrombolysis (within 4.5 hours of stroke onset), aspirin (within 48 hours of onset), and early access to a stroke unit. Care in a stroke unit significantly reduces the risk of death or dependency irrespective of stroke severity. A multidisciplinary team to manage the range of problems after stroke (e.g. swallowing difficulties, communication problems, mobility) is central to rehabilitation. Much rehabilitation is orientated toward physical function whereas returning to their social roles is more important to patients. While the emphasis of rehabilitation is on targeted therapy interventions to improve function and finding compensatory strategies to increase independence--the goal of community exercise is to improve general physical fitness and activity levels. The marked loss of physical fitness evident in stroke survivors can be at least partly reversed by physical fitness training, and leads to improvements in physical function. Group exercise also improves self-confidence and social integration. Pharmacological therapies play a key role in secondary prevention, and must be started as soon as possible to reduce the risk of early recurrence.

  16. Epidemiology and Registry Studies of Stroke in Japan

    PubMed Central

    2013-01-01

    Stroke is the most prevalent cardiovascular disease in Japan. This review introduces two epidemiologic studies and four registry studies of stroke in Japan. The Hisayama Study was begun as a population-based prospective cohort study of cerebrovascular and cardiovascular diseases in 1961 in the town of Hisayama. Most of the deceased subjects of the study underwent autopsy examinations from the beginning of the study. Changes in stroke trends in the last 50 years were clarified by comparison of data from different study cohorts registered every 13 to 14 years. The Suita Study was based on a random sampling of Japanese urban residents. Several reports from this study showed the significance of pre-hypertension, as well as hypertension, as a risk factor for stroke by itself and in combination with other underlying characteristics. In addition, the Japan Multicenter Stroke Investigators' Collaboration (J-MUSIC), the Japan Standard Stroke Registry Study, the Fukuoka Stroke Registry, and the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rt-PA Registry are explained as registry studies involving Japanese stroke patients. PMID:24324936

  17. Epidemiology and registry studies of stroke in Japan.

    PubMed

    Toyoda, Kazunori

    2013-01-01

    Stroke is the most prevalent cardiovascular disease in Japan. This review introduces two epidemiologic studies and four registry studies of stroke in Japan. The Hisayama Study was begun as a population-based prospective cohort study of cerebrovascular and cardiovascular diseases in 1961 in the town of Hisayama. Most of the deceased subjects of the study underwent autopsy examinations from the beginning of the study. Changes in stroke trends in the last 50 years were clarified by comparison of data from different study cohorts registered every 13 to 14 years. The Suita Study was based on a random sampling of Japanese urban residents. Several reports from this study showed the significance of pre-hypertension, as well as hypertension, as a risk factor for stroke by itself and in combination with other underlying characteristics. In addition, the Japan Multicenter Stroke Investigators' Collaboration (J-MUSIC), the Japan Standard Stroke Registry Study, the Fukuoka Stroke Registry, and the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rt-PA Registry are explained as registry studies involving Japanese stroke patients.

  18. Conditional ablation of myeloid TNF increases lesion volume after experimental stroke in mice, possibly via altered ERK1/2 signaling

    PubMed Central

    Clausen, Bettina Hjelm; Degn, Matilda; Sivasaravanaparan, Mithula; Fogtmann, Torben; Andersen, Maria Gammelstrup; Trojanowsky, Michelle D.; Gao, Han; Hvidsten, Svend; Baun, Christina; Deierborg, Tomas; Finsen, Bente; Kristensen, Bjarne Winther; Bak, Sara Thornby; Meyer, Morten; Lee, Jae; Nedospasov, Sergei A.; Brambilla, Roberta; Lambertsen, Kate Lykke

    2016-01-01

    Microglia are activated following cerebral ischemia and increase their production of the neuro- and immunomodulatory cytokine tumor necrosis factor (TNF). To address the function of TNF from this cellular source in focal cerebral ischemia we used TNF conditional knock out mice (LysMcreTNFfl/fl) in which the TNF gene was deleted in cells of the myeloid lineage, including microglia. The deletion reduced secreted TNF levels in lipopolysaccharide-stimulated cultured primary microglia by ~93%. Furthermore, phosphorylated-ERK/ERK ratios were significantly decreased in naïve LysMcreTNFfl/fl mice demonstrating altered ERK signal transduction. Micro-PET using 18[F]-fluorodeoxyglucose immediately after focal cerebral ischemia showed increased glucose uptake in LysMcreTNFfl/fl mice, representing significant metabolic changes, that translated into increased infarct volumes at 24 hours and 5 days compared to littermates (TNFfl/fl). In naïve LysMcreTNFfl/fl mice cytokine levels were low and comparable to littermates. At 6 hours, TNF producing microglia were reduced by 56% in the ischemic cortex in LysMcreTNFfl/fl mice compared to littermate mice, whereas no TNF+ leukocytes were detected. At 24 hours, pro-inflammatory cytokine (TNF, IL-1β, IL-6, IL-5 and CXCL1) levels were significantly lower in LysMcreTNFfl/fl mice, despite comparable infiltrating leukocyte populations. Our results identify microglial TNF as beneficial and neuroprotective in the acute phase and as a modulator of neuroinflammation at later time points after experimental ischemia, which may contribute to regenerative recovery. PMID:27384243

  19. Post-stroke language disorders.

    PubMed

    Sinanović, Osman; Mrkonjić, Zamir; Zukić, Sanela; Vidović, Mirjana; Imamović, Kata

    2011-03-01

    Post-stroke language disorders are frequent and include aphasia, alexia, agraphia and acalculia. There are different definitions of aphasias, but the most widely accepted neurologic and/or neuropsychological definition is that aphasia is a loss or impairment of verbal communication, which occurs as a consequence of brain dysfunction. It manifests as impairment of almost all verbal abilities, e.g., abnormal verbal expression, difficulties in understanding spoken or written language, repetition, naming, reading and writing. During the history, many classifications of aphasia syndromes were established. For practical use, classification of aphasias according to fluency, comprehension and abilities of naming it seems to be most suitable (nonfluent aphasias: Broca's, transcortical motor, global and mixed transcortical aphasia; fluent aphasias: anomic, conduction, Wernicke's, transcortical sensory, subcortical aphasia). Aphasia is a common consequence of left hemispheric lesion and most common neuropsychological consequence of stroke, with a prevalence of one-third of all stroke patients in acute phase, although there are reports on even higher figures. Many speech impairments have a tendency of spontaneous recovery. Spontaneous recovery is most remarkable in the first three months after stroke onset. Recovery of aphasias caused by ischemic stroke occurs earlier and it is most intensive in the first two weeks. In aphasias caused by hemorrhagic stroke, spontaneous recovery is slower and occurs from the fourth to the eighth week after stroke. The course and outcome of aphasia depend greatly on the type of aphasia. Regardless of the fact that a significant number of aphasias spontaneously improve, it is necessary to start treatment as soon as possible. The writing and reading disorders in stroke patients (alexias and agraphias) are more frequent than verified on routine examination, not only in less developed but also in large neurologic departments. Alexia is an acquired

  20. Intensive treatment of dysarthria secondary to stroke.

    PubMed

    Mahler, Leslie A; Ramig, Lorraine O

    2012-08-01

    This study investigated the impact of a well-defined behavioral dysarthria treatment on acoustic and perceptual measures of speech in four adults with dysarthria secondary to stroke. A single-subject A-B-A experimental design was used to measure the effects of the Lee Silverman Voice Treatment (LSVT(®) LOUD) on the speech of individual participants. Dependent measures included vocal sound pressure level, phonatory stability, vowel space area, and listener ratings of speech, voice and intelligibility. Statistically significant improvements (p <  0.05) in vocal dB SPL and phonatory stability as well as larger vowel space area were present for all participants. Listener ratings suggested improved voice quality and more natural speech post-treatment. Speech intelligibility scores improved for one of four participants. These data suggest that people with dysarthria secondary to stroke can respond positively to intensive speech treatments such as LSVT. Further studies are needed to investigate speech treatments specific to stroke.

  1. Stem Cell Therapy and Administration Routes After Stroke.

    PubMed

    Rodríguez-Frutos, Berta; Otero-Ortega, Laura; Gutiérrez-Fernández, María; Fuentes, Blanca; Ramos-Cejudo, Jaime; Díez-Tejedor, Exuperio

    2016-10-01

    Cell-based therapy has demonstrated safety and efficacy in experimental animal models of stroke, as well as safety in stroke patients. However, various questions remain regarding the therapeutic window, dosage, route of administration, and the most appropriate cell type and source, as well as mechanisms of action and immune-modulation to optimize treatment based on stem cell therapy. Various delivery routes have been used in experimental stroke models, including intracerebral, intraventricular, subarachnoid, intra-arterial, intraperitoneal, intravenous, and intranasal routes. From a clinical point of view, it is necessary to demonstrate which is the most feasible, safest, and most effective for use with stroke patients. Therefore, further experimental studies concerning the safety, efficacy, and mechanisms of action involved in these therapeutic effects are required to determine their optimal clinical use.

  2. [Stress effect on the development of hemorrhagic stroke].

    PubMed

    Kalinina, V V; Ivannikova, N O; Koplik, E V; Smolina, N V; Gryzunov, Iu A; Dobretsov, G E

    2012-01-01

    The objective of this work was to study how stress, activity in the open field test, and conformational properties of albumin-binding sites are associated with experimental hemorrhagic stroke in rats. The open-field behavioral pattern in rats was characterized by the previously developed by us activity index. In accordance with this activity index, rats were divided into two groups, i.e., active and passive animals. The animals were subjected to experimental hemorrhagic stroke with or without previous emotional stress. It was shown that the previous stress affected the stroke development. Stress loading before experimental stroke changed albumin conformational properties in rats with active and passive behavioral patterns in different ways. It was associated with different ability of the albumin globule to undergo pH-induced transition N-F and in different accessibility of albumin-bound fluorescent probe CAPIDAN to nitrate-induced fluorescence quenching.

  3. ALTERED PHALANX FORCE DIRECTION DURING POWER GRIP FOLLOWING STROKE

    PubMed Central

    Enders, Leah R.

    2015-01-01

    Many stroke survivors with severe impairment can grasp only with a power grip. Yet, little knowledge is available on altered power grip after stroke, other than reduced power grip strength. This study characterized stroke survivors’ static power grip during 100% and 50% maximum grip. Each phalanx force’s angular deviation from the normal direction and its contribution to total normal force was compared for 11 stroke survivors and 11 age-matched controls. Muscle activities and skin coefficient of friction (COF) were additionally compared for another 20 stroke and 13 age-matched control subjects. The main finding was that stroke survivors gripped with a 34% greater phalanx force angular deviation of 19±2° compared to controls of 14±1° (p<.05). Stroke survivors’ phalanx force angular deviation was closer to the 23° threshold of slippage between the phalanx and grip surface, which may explain increased likelihood of object dropping in stroke survivors. In addition, this altered phalanx force direction decreases normal grip force by tilting the force vector, indicating a partial role of phalanx force angular deviation in reduced grip strength post stroke. Greater phalanx force angular deviation may biomechanically result from more severe underactivation of stroke survivors’ first dorsal interosseous (FDI) and extensor digitorum communis (EDC) muscles compared to their flexor digitorum superficialis (FDS) or somatosensory deficit. While stroke survivors’ maximum power grip strength was approximately half of the controls’, the distribution of their remaining strength over the fingers and phalanges did not differ, indicating evenly distributed grip force reduction over the entire hand. PMID:25795079

  4. Prognosis of stroke in the south of Greece: 1 year mortality, functional outcome and its determinants: the Arcadia Stroke Registry

    PubMed Central

    Vemmos, K; Bots, M; Tsibouris, P; Zis, V; Takis, C; Grobbee, D; Stamatelopoulos, S

    2000-01-01

    OBJECTIVES—For Greece, data on incidence of stroke, type of stroke, and prognosis of stroke is limited. Recently, results on incidence of stroke were published. Here 1 year mortality, functional outcome after a first ever stroke, and determinants of the prognosis are described.
METHODS—A population based registry was established in the Arcadia area, located in eastern central Peloponessos in southern Greece. Between 1 November 1993 and 31 October 1995, 555 patients with a first ever stroke were identified using information from death certificates, hospital records, public health centres and general practitioners. Extensive information on cardiovascular risk factors and stroke characteristics was obtained. After 1 year a modified Rankin score was determined in all surviving patients.
RESULTS—After 1 year of follow up, 204 (36.8%) patients died. The probability of survival 1 year after stroke was higher for cerebral infarction than for intracerebral haemorrhage; 67.8% (95% confidence interval (95% CI) 64-72) and 46.4% (35-57), respectively. Of the survivors, 68.9% had either no symptoms or symptoms that would not interfere with their capacity to look after themselves (Rankin score 0 to 2). Increasing age and low Glasgow coma scale score were the most powerful predictors of death within 1 year (p<0.01), whereas increasing age, atrial fibrillation, and low Glasgow coma scale score were the most important predictors of functional outcome 1 year after a stroke (p<0.01).
CONCLUSIONS—One year mortality from stroke in Greece is similar to that of other industrialised countries. The most important factors that affect the prognosis of a patient with a first ever stroke are increasing age, stroke severity, and atrial fibrillation.

 PMID:11032610

  5. Pediatric Stroke: A Review

    PubMed Central

    Tsze, Daniel S.; Valente, Jonathan H.

    2011-01-01

    Stroke is relatively rare in children, but can lead to significant morbidity and mortality. Understanding that children with strokes present differently than adults and often present with unique risk factors will optimize outcomes in children. Despite an increased incidence of pediatric stroke, there is often a delay in diagnosis, and cases may still remain under- or misdiagnosed. Clinical presentation will vary based on the child's age, and children will have risk factors for stroke that are less common than in adults. Management strategies in children are extrapolated primarily from adult studies, but with different considerations regarding short-term anticoagulation and guarded recommendations regarding thrombolytics. Although most recommendations for management are extrapolated from adult populations, they still remain useful, in conjunction with pediatric-specific considerations. PMID:22254140

  6. Strokes (For Parents)

    MedlinePlus

    ... that could affect a child throughout life, including: cerebral palsy mental retardation paralysis or weakness on one side ... ON THIS TOPIC Meningitis First Aid: Seizures Seizures Cerebral Palsy Brain and Nervous System Stroke Your Brain & Nervous ...

  7. Strokes (For Parents)

    MedlinePlus

    ... in adults, which can include sudden weakness, slurred speech, or blurred vision. These effects vary widely depending ... changes in the child's behavior, concentration, memory, or speech. Common signs of stroke in kids and teens : ...

  8. A Stroke of Language

    ERIC Educational Resources Information Center

    Blaisdell, Bob

    2011-01-01

    The author reflects on foreign-language learning by his EFL students as well as his own foreign-language learning. He concludes by musing on the possible and fantastical devastation on language-ability wrought by strokes.

  9. Stroke: Hope through Research

    MedlinePlus

    ... United States: estimated at about $43 billion / year direct costs for medical care and therapy: estimated at ... days after a stroke: $35,000* percentage of direct cost of care for the first 90 days*: ...

  10. Mitochondrial DNA haplogroups and short-term neurological outcomes of ischemic stroke

    PubMed Central

    Cai, Biyang; Zhang, Zhizhong; Liu, Keting; Fan, Wenping; Zhang, Yumeng; Xie, Xia; Dai, Minhui; Cao, Liping; Bai, Wen; Du, Juan; Dai, Qiliang; Zhou, Shuyu; Zhang, Hao; Zhu, Wusheng; Ma, Minmin; Liu, Wenhua; Liu, Xinfeng; Xu, Gelin

    2015-01-01

    Stroke is one of the leading causes of death and long-term disability worldwide. Mitochondrial DNA (mtDNA) is a potential contributor for the sex differences of ischemic stroke heritability. Although mtDNA haplogroups were associated with stroke onset, their impacts on stroke outcomes remain unclear. This study aimed to evaluate the impacts of mtDNA haplogroups on short-term outcomes of neurological functions in patients with ischemic stroke. A total of 303 patients were included, and their clinical data and mtDNA sequences were analyzed. Based on the changes between baseline and 14-day follow-up stroke severity, our results showed that haplogroup N9 was an independent protective factor against neurological worsening in acute ischemic stroke patients. These findings supported that mtDNA variants play a role in post-stroke neurological recovery, thus providing evidences for future pharmacological intervention in mitochondrial function. PMID:25993529

  11. Coupling of Neurogenesis and Angiogenesis After Ischemic Stroke

    PubMed Central

    Ruan, Linhui; Wang, Brian; ZhuGe, Qichuan; Jin, Kunlin

    2015-01-01

    Stroke is a leading cause of mortality and severe long-term disability worldwide. Development of effective treatment or new therapeutic strategies for ischemic stroke patients is therefore crucial. Ischemic stroke promotes neurogenesis by several growth factors including FGF-2, IGF-1, BDNF, VEGF and chemokines including SDF-1, MCP-1. Stroke-induced angiogenesis is similarly regulated by many factors most notably, eNOS and CSE, VEGF/VEGFR2, and Ang-1/Tie2. Important findings in the last decade have revealed that neurogenesis is not the stand-alone consideration in the fight for full functional recovery from stroke. Angiogenesis has been also shown to be critical in improving post-stroke neurological functional recovery. More than that, recent evidence has shown a highly possible interplay or dependence between stroke-induced neurogenesis and angiogenesis. Moving forward, elucidating the underlying mechanisms of this coupling between stroke-induced neurogenesis and angiogenesis will be of great importance, which will provide the basis for neurorestorative therapy. PMID:25736182

  12. Orthostatic haemodynamic responses in acute stroke

    PubMed Central

    Panayiotou, B; Reid, J; Fotherby, M; Crome, P

    1999-01-01

    Little is known about orthostatic blood pressure regulation in acute stroke. We determined postural haemodynamic responses in 40 patients with acute stroke (mild or moderate severity) and 40 non-stroke control in-patients, at two days (`Day 1') and one week (`Week 1') post-admission. Following a 10-minute supine rest and baseline readings, subjects sat up and blood pressure and heart rate were taken for 5 minutes. The procedure was repeated with subjects moving from supine to the standing posture. Haemodynamic changes from supine data were analysed. On standing up, the control group had a transient significant fall in mean arterial blood pressure on Day 1 but not Week 1. No significant changes were seen on either day when sitting up. In contrast to controls, the stroke group showed increases in mean arterial blood pressure on moving from supine to the sitting and standing positions on both days. Persistent postural hypotension defined as ⩾20 mmHg systolic fall occurred in <10% of either of the study groups on both days. Sitting and standing heart rates in both groups were significantly faster than supine heart rate on both days. The orthostatic blood pressure elevation is consistent with sympathetic nervous system overactivity which has been reported in acute stroke. Upright positioning as part of early rehabilitation and mobilisation following mild-to-moderate stroke would, therefore, not predispose to detrimental postural reductions in blood pressure.


Keywords: stroke; orthostatic hypotension; hypotension PMID:10715760

  13. Telestroke in stroke survivors.

    PubMed

    Joubert, Jacques; Joubert, Lynette B; de Bustos, Elizabeth Medeiros; Ware, Dallas; Jackson, David; Harrison, Terrence; Cadilhac, Dominique

    2009-01-01

    Stroke is a high-frequency disorder placing a significant burden on the health care systems, being the foremost cause of complex chronic disability in adults. Devising systems that can enhance the prevention of stroke recurrence is an important priority and challenge in both the developed and the developing world. The potential for recurrent stroke can be substantially reduced by effective management of vascular risk factors. Telestroke is a tool with potential application to improve risk management of stroke survivors. Lack of acknowledgment of existing practices as well as lack of awareness of potential financial barriers to diffusion of telestroke can lead to limited implementation. Telestroke offers service providers the opportunity to access large numbers of stroke survivors targeting secondary prevention. The ideal 'telestroke model' provides service support, education for the patient and caregiver, as well as integration of specialist and primary care services. Effective use of technological advances, with adequate recognition of the importance of human interaction in the long-term management of a largely elderly population of stroke survivors is challenging but possible. Telestroke should be systems- and not technology-driven. Barriers in the implementation of telestroke have been identified as insufficient planning of IT infrastructure, lack of long-term vision for sustainability, a lack of contextual perspective as well as poor communication across domains. Future telestroke models should provide effective action in an integrated model of care recognizing and involving all existing players and practices.

  14. The Heart and Stroke Foundation of Ontario

    PubMed Central

    Graham, Anthony F.

    1987-01-01

    The Heart and Stroke Foundation of Ontario is a non-profit volunteer-driven organization that is active in supporting research and education programs with the ultimate goal of reducing death and disability from heart disease and stroke. The Foundation has over 65 chapters across the province, a full-time staff of 130, and over 70,000 volunteers involved in various programs and fund-raising activities. Several of the Foundation's programs offer direct assistance to family physicians and their patients. This review summarizes the major programs of the Foundation and specifies how they relate to the physicians of Ontario. PMID:21263913

  15. Clinical presentation and imaging characteristics of occult lung cancer associated ischemic stroke.

    PubMed

    Mai, Hui; Xia, Jun; Wu, Yongjun; Ke, Junlong; Li, Junliang; Pan, Jiangang; Chen, Wubiao; Shao, Yiming; Yang, Zhi; Luo, Saihua; Sun, Yonghua; Zhao, Bin; Li, Longxuan

    2015-02-01

    We investigated the clinical and imaging characteristics of initial and recurrent strokes in patients with occult lung cancer associated ischemic stroke (OLCA-stroke). A retrospective review of all ischemic stroke patients with occult lung cancer in the absence of conventional stroke etiologies between 2005 and 2013 was conducted. We compared the initial and recurrent lesion patterns on diffusion-weighted MRI in patients with OLCA-stroke, with respect to vascular territory involved, number and size of lesions, clinical presentation, cancer subtypes, recurrences and fatalities, and outcome of survivors. Thirteen patients with confirmed OLCA-stroke were identified. All had elevated D-dimer levels, six had central lung cancer and seven had peripheral lung cancer. Eight (62%) had adenocarcinoma, and nine (69%) had metastasis. Ten (77%) patients had multiple lesions in multiple vascular territories. Twelve (92%) patients suffered recurrent strokes. Multiple small and large disseminated lesions in multiple vascular territories were more frequent in recurrent strokes in comparison with initial strokes. The middle cerebral artery was most frequently involved in recurrent strokes, followed by the posterior circulation territory and anterior cerebral artery, which were of similar frequency as initial strokes. Overall, 58% of patients had their first recurrent stroke within the first month, and 69% had a poor outcome, especially for those with multiple recurrent strokes and metastases. Occult cancer should be considered in the setting of multiple and recurrent embolic strokes within the short term in the absence of conventional stroke etiologies. The severity of malignancy and cancer treatments and stroke influenced the recurrences and outcome.

  16. Compensatory Versus Noncompensatory Shoulder Movements Used for Reaching in Stroke.

    PubMed

    Levin, Mindy F; Liebermann, Dario G; Parmet, Yisrael; Berman, Sigal

    2016-08-01

    Background The extent to which the upper-limb flexor synergy constrains or compensates for arm motor impairment during reaching is controversial. This synergy can be quantified with a minimal marker set describing movements of the arm-plane. Objectives To determine whether and how (a) upper-limb flexor synergy in patients with chronic stroke contributes to reaching movements to different arm workspace locations and (b) reaching deficits can be characterized by arm-plane motion. Methods Sixteen post-stroke and 8 healthy control subjects made unrestrained reaching movements to targets located in ipsilateral, central, and contralateral arm workspaces. Arm-plane, arm, and trunk motion, and their temporal and spatial linkages were analyzed. Results Individuals with moderate/severe stroke used greater arm-plane movement and compensatory trunk movement compared to those with mild stroke and control subjects. Arm-plane and trunk movements were more temporally coupled in stroke compared with controls. Reaching accuracy was related to different segment and joint combinations for each target and group: arm-plane movement in controls and mild stroke subjects, and trunk and elbow movements in moderate/severe stroke subjects. Arm-plane movement increased with time since stroke and when combined with trunk rotation, discriminated between different subject groups for reaching the central and contralateral targets. Trunk movement and arm-plane angle during target reaches predicted the subject group. Conclusions The upper-limb flexor synergy was used adaptively for reaching accuracy by patients with mild, but not moderate/severe stroke. The flexor synergy, as parameterized by the amount of arm-plane motion, can be used by clinicians to identify levels of motor recovery in patients with stroke.

  17. Text Detection in Natural Scene Images by Stroke Gabor Words.

    PubMed

    Yi, Chucai; Tian, Yingli

    2011-01-01

    In this paper, we propose a novel algorithm, based on stroke components and descriptive Gabor filters, to detect text regions in natural scene images. Text characters and strings are constructed by stroke components as basic units. Gabor filters are used to describe and analyze the stroke components in text characters or strings. We define a suitability measurement to analyze the confidence of Gabor filters in describing stroke component and the suitability of Gabor filters on an image window. From the training set, we compute a set of Gabor filters that can describe principle stroke components of text by their parameters. Then a K -means algorithm is applied to cluster the descriptive Gabor filters. The clustering centers are defined as Stroke Gabor Words (SGWs) to provide a universal description of stroke components. By suitability evaluation on positive and negative training samples respectively, each SGW generates a pair of characteristic distributions of suitability measurements. On a testing natural scene image, heuristic layout analysis is applied first to extract candidate image windows. Then we compute the principle SGWs for each image window to describe its principle stroke components. Characteristic distributions generated by principle SGWs are used to classify text or nontext windows. Experimental results on benchmark datasets demonstrate that our algorithm can handle complex backgrounds and variant text patterns (font, color, scale, etc.).

  18. Post-stroke depression: mechanisms, translation and therapy

    PubMed Central

    Loubinoux, Isabelle; Kronenberg, Golo; Endres, Matthias; Schumann-Bard, Pascale; Freret, Thomas; Filipkowski, Robert K; Kaczmarek, Leszek; Popa-Wagner, Aurel

    2012-01-01

    The interaction between depression and stroke is highly complex. Post-stroke depression (PSD) is among the most frequent neuropsychiatric consequences of stroke. Depression also negatively impacts stroke outcome with increased morbidity, mortality and poorer functional recovery. Antidepressants such as the commonly prescribed selective serotonin reuptake inhibitors improve stroke outcome, an effect that may extend far beyond depression, e.g., to motor recovery. The main biological theory of PSD is the amine hypothesis. Conceivably, ischaemic lesions interrupt the projections ascending from midbrain and brainstem, leading to a decreased bioavailability of the biogenic amines – serotonin (5HT), dopamine (DA) and norepinephrine (NE). Acetylcholine would also be involved. So far, preclinical and translational research on PSD is largely lacking. The implementation and characterization of suitable animal models is clearly a major prerequisite for deeper insights into the biological basis of post-stroke mood disturbances. Equally importantly, experimental models may also pave the way for the discovery of novel therapeutic targets. If we cannot prevent stroke, we shall try to limit its long-term consequences. This review therefore presents animal models of PSD and summarizes potential underlying mechanisms including genomic signatures, neurotransmitter and neurotrophin signalling, hippocampal neurogenesis, cellular plasticity in the ischaemic lesion, secondary degenerative changes, activation of the hypothalamo-pituitary-adrenal (HPA) axis and neuroinflammation. As stroke is a disease of the elderly, great clinical benefit may especially accrue from deciphering and targeting basic mechanisms underlying PSD in aged animals. PMID:22348642

  19. Citicoline in vascular cognitive impairment and vascular dementia after stroke.

    PubMed

    Alvarez-Sabín, Jose; Román, Gustavo C

    2011-01-01

    Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Neuropathological studies in most cases of dementia in the elderly reveal a large load of vascular ischemic brain lesions mixed with a lesser contribution of neurodegenerative lesions of Alzheimer disease. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment and vascular dementia after stroke. Citicoline has demonstrated neuroprotective effects in acute stroke and has been shown to improve cognition in patients with chronic cerebrovascular disease and in some patients with Alzheimer disease. A recent trial lasting 6 months in patients with first-ever ischemic stroke showed that citicoline prevented cognitive decline after stroke with significant improvement of temporal orientation, attention, and executive function. Experimentally, citicoline exhibits neuroprotective effects and enhances neural repair. Citicoline appears to be a safe and promising alternative to improve stroke recovery and could be indicated in patients with vascular cognitive impairment, vascular dementia, and Alzheimer disease with significant cerebrovascular disease.

  20. Epigenetic Regulation of Oxidative Stress in Ischemic Stroke

    PubMed Central

    Zhao, Haiping; Han, Ziping; Ji, Xunming; Luo, Yumin

    2016-01-01

    The prevalence and incidence of stroke rises with life expectancy. However, except for the use of recombinant tissue-type plasminogen activator, the translation of new therapies for acute stroke from animal models into humans has been relatively unsuccessful. Oxidative DNA and protein damage following stroke is typically associated with cell death. Cause-effect relationships between reactive oxygen species and epigenetic modifications have been established in aging, cancer, acute pancreatitis, and fatty liver disease. In addition, epigenetic regulatory mechanisms during stroke recovery have been reviewed, with focuses mainly on neural apoptosis, necrosis, and neuroplasticity. However, oxidative stress-induced epigenetic regulation in vascular neural networks following stroke has not been sufficiently explored. Improved understanding of the epigenetic regulatory network upon oxidative stress may provide effective antioxidant approaches for treating stroke. In this review, we summarize the epigenetic events, including DNA methylation, histone modification, and microRNAs, that result from oxidative stress following experimental stroke in animal and cell models, and the ways in which epigenetic changes and their crosstalk influence the redox state in neurons, glia, and vascular endothelial cells, helping us to understand the foregone and vicious epigenetic regulation of oxidative stress in the vascular neural network following stroke. PMID:27330844

  1. PTEN degradation after ischemic stroke: a double-edged sword.

    PubMed

    Li, W; Huang, R; Chen, Z; Yan, L-J; Simpkins, J W; Yang, S-H

    2014-08-22

    Tumor suppressor phosphatase and tensin homolog (PTEN) is highly expressed in neurons and PTEN inhibition has been reported to be neuroprotective against ischemic stroke in experimental models. On the other hand, PTEN deletion has been shown to lead to cognitive impairment. In the current study, we examined the expression and functions of PTEN in an ischemic stroke rodent model. We found rapid S-nitrosylation and degradation of PTEN after cerebral ischemia/reperfusion injury. PTEN degradation leads to activation of Akt. PTEN partial deletion or PTEN inhibition increased the expression of GABAA receptor (GABAAR) γ2 subunit and enhanced GABAA receptor current. After cerebral ischemia, increased expression of GABAAR γ2 subunit was observed in the ischemia region and the penumbra area. We also observed PTEN loss in astrocytes after cerebral ischemia. Astrocytic PTEN partial knockout increased astrocyte activation and exacerbated ischemic damage. We speculated that ischemic stroke induced neuronal PTEN degradation, hence enhanced GABAA receptor-medicated neuronal activity inhibition which could attenuate excitotoxicity and provide neuroprotection during the acute phase after stroke, while inhibiting long-term functional recovery and contributing to vascular cognitive impairment after stroke. On the other hand, ischemic stroke induced astrocytic PTEN loss and enhanced ischemic damage and astrogliosis. Taken together, our study indicates that ischemic stroke induces rapid PTEN degradation in both neurons and astrocytes which play both protective and detrimental action in a spatiotemporal- and cell-type-dependent manner. Our study provides critical insight for targeting PTEN signaling pathway for stroke treatment.

  2. Human Data Supporting Glyburide in Ischemic Stroke

    PubMed Central

    Sheth, Kevin N.; Simard, J. Marc; Elm, Jordan; Kronenberg, Golo; Kunte, Hagen; Kimberly, W. Taylor

    2016-01-01

    The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous (IV) formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. Early phase II study of MRI and plasma biomarkers support the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase IIb study and definitive efficacy studies are urgently needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative. PMID:26463916

  3. Potential markers of oxidative stress in stroke.

    PubMed

    Cherubini, Antonio; Ruggiero, Carmelinda; Polidori, M Cristina; Mecocci, Patrizia

    2005-10-01

    Free radical production is increased in ischemic and hemorrhagic stroke, leading to oxidative stress that contributes to brain damage. The measurement of oxidative stress in stroke would be extremely important for a better understanding of its pathophysiology and for identifying subgroups of patients that might receive targeted therapeutic intervention. Since direct measurement of free radicals and oxidized molecules in the brain is difficult in humans, several biological substances have been investigated as potential peripheral markers. Among lipid peroxidation products, malondialdehyde, despite its relevant methodological limitations, is correlated with the size of ischemic stroke and clinical outcome, while F2-isoprostanes appear to be promising, but they have not been adequately evaluated. 8-Hydroxy-2-deoxyguanosine has been extensively investigated as markers of oxidative DNA damage but no study has been done in stroke patients. Also enzymatic and nonenzymatic antioxidants have been proposed as indirect markers. Among them ascorbic acid, alpha-tocopherol, uric acid, and superoxide dismutase are related to brain damage and clinical outcome. After a critical evaluation of the literature, we conclude that, while an ideal biomarker is not yet available, the balance between antioxidants and by-products of oxidative stress in the organism might be the best approach for the evaluation of oxidative stress in stroke patients.

  4. Real-time optoacoustic monitoring of stroke

    NASA Astrophysics Data System (ADS)

    Kneipp, Moritz; Turner, Jake; Hambauer, Sebastian; Krieg, Sandro M.; Lehmberg, Jens; Lindauer, Ute; Razansky, Daniel

    2014-03-01

    Characterizing disease progression and identifying possible therapeutic interventions in stroke is greatly aided by the use of longitudinal function imaging studies. In this study, we investigate the applicability of real-time multispectral optoacoustic tomography (MSOT) as a tool for non-invasive monitoring of the progression of stroke in the whole brain. The middle cerebral artery occlusion (MCAO) method was used to induce stroke. Mice were imaged under isoflurane anesthesia preoperatively and at several time points during and after the 60-minute occlusion. The animals were sacrificed after 24 hours and their excised brains frozen at -80°C for sectioning. The cryosection were stained using H&E staining to identify the ischemic lesion. Major vessels are readily identifiable in the whole mouse head in the in vivo optoacoustic scans. During ischemia, a reduction in cerebral blood volume is detectable in the cortex. Post ischemia, spectral unmixing of the optoacoustic signals shows an asymmetry of the deoxygenated hemoglobin in the hemisphere affected by MCAO. This hypoxic area was mainly located around the boundary of the ischemic lesion and was therefore identified as the ischemic penumbra. Non-invasive functional MSOT imaging is able to visualize the hypoxic penumbra in brains affected by stroke. Stopping the spread of the infarct area and revitalizing the penumbra is central in stroke research, this new imaging technique may therefore prove to be a valuable tool in the monitoring and developing new treatments.

  5. World Stroke Organization global stroke services guidelines and action plan.

    PubMed

    Lindsay, Patrice; Furie, Karen L; Davis, Stephen M; Donnan, Geoffrey A; Norrving, Bo

    2014-10-01

    Every two seconds, someone across the globe suffers a symptomatic stroke. 'Silent' cerebrovascular disease insidiously contributes to worldwide disability by causing cognitive impairment in the elderly. The risk of cerebrovascular disease is disproportionately higher in low to middle income countries where there may be barriers to stroke care. The last two decades have seen a major transformation in the stroke field with the emergence of evidence-based approaches to stroke prevention, acute stroke management, and stroke recovery. The current challenge lies in implementing these interventions, particularly in regions with high incidences of stroke and limited healthcare resources. The Global Stroke Services Action Plan was conceived as a tool to identifying key elements in stroke care across a continuum of health models. At the minimal level of resource availability, stroke care delivery is based at a local clinic staffed predominantly by non-physicians. In this environment, laboratory tests and diagnostic studies are scarce, and much of the emphasis is placed on bedside clinical skills, teaching, and prevention. The essential services level offers access to a CT scan, physicians, and the potential for acute thrombolytic therapy, however stroke expertise may still be difficult to access. At the advanced stroke services level, multidisciplinary stroke expertise, multimodal imaging, and comprehensive therapies are available. A national plan for stroke care should incorporate local and regional strengths and build upon them. This clinical practice guideline is a synopsis of the core recommendations and quality indicators adapted from ten high quality multinational stroke guidelines. It can be used to establish the current level of stroke services, target goals for expanding stroke resources, and ensuring that all stages of stroke care are being adequately addressed, even at the advanced stroke services level. This document is a start, but there is more to be done

  6. Recovery After Stroke: Bladder and Bowel Function

    MedlinePlus

    Recovery After Stroke: Bladder & Bowel Function Problems with bladder and bowel function are common but distressing for ... embarrassed by – these issues.  Get information on stroke recovery from National Stroke Association.  Visit www. stroke. org ...

  7. Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade

    PubMed Central

    Guihaire, Julien; Deuse, Tobias; Wang, Dong; Fadel, Elie; Reichenspurner, Hermann; Schrepfer, Sonja

    2015-01-01

    Background. The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share higher severity of the disease. Objective. To compare the severity of experimental PH between male and female athymic rats. Methods. PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups) using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg). After 28 days, right ventricular (RV) remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed. Results. Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males. Conclusions. Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients. PMID:26421302

  8. Mini-Stroke vs. Regular Stroke: What's the Difference?

    MedlinePlus

    ... How is a ministroke different from a regular stroke? Answers from Jerry W. Swanson, M.D. When ... brain, spinal cord or retina, which may cause stroke-like symptoms but does not damage brain cells ...

  9. MR-angiography allows defining severity grades of cerebral vasospasm in an experimental double blood injection subarachnoid hemorrhage model in rats

    PubMed Central

    Malinova, Vesna; Psychogios, Marios N.; Tsogkas, Ioannis; Koennecke, Birte; Bleuel, Kim; Iliev, Bogdan; Rohde, Veit; Mielke, Dorothee

    2017-01-01

    Objective Magnetic resonance (MR) imaging has been used for the detection of cerebral vasospasm (VSP) related infarction in experimental subarachnoid hemorrhage (eSAH) in rats. Conventional angiography is generally used to visualize VSP, which is an invasive technique with a possible increase in morbidity and mortality. In this study we evaluated the validity of MR-angiography (MRA) in detecting VSP and its feasibility to define VSP severity grades after eSAH in rats. Methods SAH was induced using the double-hemorrhage model in 12 rats. In two rats, saline solution was injected instead of blood (sham group). MR was performed on day 1, 2 and on day 5. T1-, T2-, T2*-weighted and time-of-flight MR sequences were applied, which were analyzed by two blinded neuroradiologists. Vessel narrowing of 25–50% was defined as mild, 50–75% as moderate and >75% as severe VSP. Results We performed a total of 34 MRAs in 14 rats. In 14 rats, MRA was performed on day 2 and day 5. In six rats MRA was additionally performed on day1 before the blood injection. A good visualization of cerebral vessels was possible in all cases. No VSP was seen in the sham group neither on day 2 nor on day 5. We found vasospasm on day 2 in 7 of the 14 rats (50%) whereas all 7 rats had mild and one rat had additionally moderate and severe vasospasm in one vessel, respectively. On day 5 we found vasospasm in 8 of the 14 rats (60%) whereas 4 rats had severe vasospasm, 1 rat had moderate vasospasm and 3 rats demonstrated mild vasospasm. In 4 of the 14 rats (30%) an ischemic lesion was detected on day 5. Three of these rats had severe vasospasm and one rat had mild vasospasm. Severe vasospasm on day 5 was statistically significant correlated with the occurrence of ischemic lesions (Fisher’s Exact test, OR 19.5, p = 0.03). Conclusions MRA is a noninvasive diagnostic tool, which allows a good visualization of the cerebral vasculature and provides reproducible results concerning the detection of VSP and the

  10. Association of Gallbladder Polyp and Stroke

    PubMed Central

    Chen, Chien-Hua; Lin, Cheng-Li; Kao, Chia-Hung

    2015-01-01

    Abstract Gallbladder polyp (GP) and stroke share several metabolic disorders as risk factors. We assessed the association between GP and subsequent stroke risk. From 2000 to 2011, patients with GP aged >20 years were identified from the Longitudinal Health Insurance Database 2000. Of the 15,975 examined patients, 12,780 and 3195 were categorized into the non-GP and GP cohorts, respectively. The relative risks of stroke were estimated using the Cox proportional hazard model after adjusting for age, sex, and comorbidities. The overall incidence of stroke was higher in the GP cohort than in the non-GP cohort (6.66 vs 5.20/1000 person-yr), with an incidence rate ratio (IRR) of 1.28 (95% confidence interval [CI] = 1.15–1.42). The risk of stroke was 1.32-fold (95% CI = 1.06–1.63) in patients with GP compared with patients without GP after adjusting for age, sex, income level, urbanization level, occupation and comorbidities of gallstone, alcohol-related illness, diabetes, hyperlipidemia, hypertension, obesity, COPD, coronary heart disease, and asthma. Furthermore, the stroke risk was higher among elderly patients (with 1-yr intervals; adjusted HR [aHR] = 1.06, 95% CI = 1.05–1.07), the male sex (aHR = 1.62, 95% CI = 1.35–1.96), lower income level (aHR = 1.37, 95% CI = 1.02–1.85 for level I; aHR = 1.62, 95% CI = 1.25–2.10 for level II), living in second urbanized areas (aHR = 1.28, 95% CI = 1.00–1.63), alcohol-related illness (aHR = 1.56, 95% CI = 1.07–2.28), diabetes (aHR = 1.78, 95% CI = 1.41–2.24), and hypertension (aHR = 2.74, 95% CI = 2.19–3.42). GP is associated with stroke; however, GP may be less influential than other risk factors are, such as male sex, lower income level, alcohol-related illness, diabetes, and hypertension, on stroke development. Additional studies are required to clarify whether GP is a risk factor for or an epiphenomenon of stroke development. PMID

  11. Hereditary Connective Tissue Diseases in Young Adult Stroke: A Comprehensive Synthesis

    PubMed Central

    Vanakker, Olivier M.; Hemelsoet, Dimitri; De Paepe, Anne

    2011-01-01

    Though the genetic background of ischaemic and haemorrhagic stroke is often polygenetic or multifactorial, it can in some cases result from a monogenic disease, particularly in young adults. Besides arteriopathies and metabolic disorders, several connective tissue diseases can present with stroke. While some of these diseases have been recognized for decades as causes of stroke, such as the vascular Ehlers-Danlos syndrome, others only recently came to attention as being involved in stroke pathogenesis, such as those related to Type IV collagen. This paper discusses each of these connective tissue disorders and their relation with stroke briefly, emphasizing the main clinical features which can lead to their diagnosis. PMID:21331163

  12. Neurodevelopmental treatment after stroke: a comparative study

    PubMed Central

    Hafsteinsdottir, T; Algra, A; Kappelle, L; Grypdonck, M; on, b

    2005-01-01

    Background: Neurodevelopmental treatment (NDT) is a rehabilitation approach increasingly used in the care of stroke patients, although no evidence has been provided for its efficacy. Objective: To investigate the effects of NDT on the functional status and quality of life (QoL) of patients with stroke during one year after stroke onset. Methods: 324 consecutive patients with stroke from 12 Dutch hospitals were included in a prospective, non-randomised, parallel group study. In the experimental group (n = 223), nurses and physiotherapists from six neurological wards used the NDT approach, while conventional treatment was used in six control wards (n = 101). Functional status was assessed by the Barthel index. Primary outcome was "poor outcome", defined as Barthel index <12 or death after one year. QoL was assessed with the 30 item version of the sickness impact profile (SA-SIP30) and the visual analogue scale. Results: At 12 months, 59 patients (27%) in the NDT group and 24 (24%) in the non-NDT group had poor outcome (corresponding adjusted odds ratio = 1.7 (95% confidence interval, 0.8 to 3.5)). At discharge the adjusted odds ratio was 0.8 (0.4 to 1.5) and after six months it was 1.6 (0.8 to 3.2). Adjusted mean differences in the two QoL measures showed no significant differences between the study groups at six or 12 months after stroke onset. Conclusions: The NDT approach was not found effective in the care of stroke patients in the hospital setting. Health care professionals need to reconsider the use of this approach. PMID:15897499

  13. Oxidative stress in the chronic phase after stroke.

    PubMed

    Alexandrova, Margarita L; Bochev, Petyo G; Markova, Vanya I; Bechev, Blagovest G; Popova, Marina A; Danovska, Maya P; Simeonova, Virginia K

    2003-01-01

    The spontaneous and the stimulated extracellular generation of reactive oxygen species (ROS) by peripheral phagocytes, the blood antioxidant capacity and the degree of oxidative damage were evaluated in patients with severe ischemic and hemorrhagic stroke in the chronic phase of disease. It was found in patients compared to the control group that: (i) the spontaneous phagocyte oxidative activity was enhanced independently of the type of stroke and the time elapsed after stroke onset; (ii) there was no difference in the extracellular ROS generation stimulated by opsonin-dependent and independent receptor mechanisms; (iii) there was no change in the indices of blood antioxidant capacity; (iv) the concentration of plasma lipid peroxides was enhanced regardless of the type of stroke, but it significantly increased over time; and (v) the concentration of blood thiobarbituric acid-reactive material was also enhanced. It was independent of the type of stroke and remained elevated during the whole period studied. We have demonstrated an enhanced spontaneous phagocyte oxidative activity and oxidative damage to lipids in patients in the chronic phase after stroke. The elimination of generated ROS and products of lipid peroxidation from the circulation could prevent the aggravation of chronic vascular injury in patients and could reduce the possibility of a subsequent stroke. This suggests the need for complex therapy, including antioxidant treatment directed to exclude the effects of free radicals, after the oxidative stress of stroke.

  14. Genetic predictors for stroke in children with sickle cell anemia.

    PubMed

    Flanagan, Jonathan M; Frohlich, Denise M; Howard, Thad A; Schultz, William H; Driscoll, Catherine; Nagasubramanian, Ramamoorthy; Mortier, Nicole A; Kimble, Amy C; Aygun, Banu; Adams, Robert J; Helms, Ronald W; Ware, Russell E

    2011-06-16

    Stroke is a devastating complication of sickle cell anemia (SCA), affecting 5% to 10% of patients before adulthood. Several candidate genetic polymorphisms have been proposed to affect stroke risk, but few have been validated, mainly because previous studies were hampered by relatively small sample sizes and the absence of additional patient cohorts for validation testing. To verify the accuracy of proposed genetic modifiers influencing stroke risk in SCA, we performed genotyping for 38 published single nucleotide polymorphisms (SNPs), as well as α-thalassemia, G6PD A(-) variant deficiency, and β-globin haplotype in 2 cohorts of children with well-defined stroke phenotypes (130 stroke, 103 nonstroke). Five polymorphisms had significant influence (P < .05): SNPs in the ANXA2, TGFBR3, and TEK genes were associated with increased stroke risk, whereas α-thalassemia and a SNP in the ADCY9 gene were linked with decreased stroke risk. Further investigation at these genetic regions may help define mutations that confer stroke risk or protection in children with SCA.

  15. Genetics of experimental hypertension.

    PubMed

    Dominiczak, A F; Clark, J S; Jeffs, B; Anderson, N H; Negrin, C D; Lee, W K; Brosnan, M J

    1998-12-01

    Experimental models of genetic hypertension are used to develop paradigms to study human essential hypertension while removing some of the complexity inherent in the study of human subjects. Since 1991 several quantitative trait loci responsible for blood pressure regulation have been identified in various rat crosses. More recently, a series of interesting quantitative trait loci influencing cardiac hypertrophy, stroke, metabolic syndrome and renal damage has also been described. It is recognized that the identification of large chromosomal regions containing a quantitative trait locus is only a first step towards gene identification. The next step is the production of congenic strains and substrains to confirm the existence of the quantitative trait locus and to narrow down the chromosomal region of interest. Several congenic strains have already been produced, with further refinement of the methodology currently in progress. The ultimate goal is to achieve positional cloning of the causal gene, a task which has so far been elusive. There are several areas of cross-fertilization between experimental and human genetics of hypertension, with a successful transfer of two loci directly from rats to humans and with new pharmacogenetic approaches which may be utilized in both experimental and clinical settings.

  16. Impact of stroke on health-related quality of life in diverse cultures: the Berlin-Ibadan multicenter international study

    PubMed Central

    2011-01-01

    Background Various studies have reported discordant profiles of health-related quality of life (HRQOL) after stroke. The aims of this study, the first of its kind, were to determine the real impact of stroke on HRQOL across diverse cultures; and to compare HRQOL between stroke patients and healthy adults, and across stroke severity strata. Methods 100 stroke patients and 100 apparently healthy adults (AHAs) in Nigeria; as well as 103 stroke and 50 AHAs in Germany participated. Stroke severity was measured using the National Institute of Health Stroke Scale, Stroke Levity Scale and modified Rankin scale. HRQOL was evaluated using the HRQOL In Stroke Patients (HRQOLISP) measure, a holistic multiculturally-validated measure with seven therapeutically-relevant domains distributed into two spheres. Results Domains within the spiritual sphere were considered more important by stroke patients. In both countries, stroke patients significantly (0.00001 < p < 0.004) had worse HRQOL than AHAs in all domains within the physical sphere. This was not so for the spiritual sphere. Consistently, stroke severity correlated significantly with all domains in the physical sphere unlike the spiritual sphere. In diverse cultures, the correlation coefficients between HRQOL and all indices of stroke severity revealed a decremental trend from the physical domain (rho = 0.77, p < 0.00001) to the spiritual domain (rho = 0.01, p = 0.893). Conclusions Consistently, stroke elicited a decremental response across domains, with domains in the spiritual sphere being relatively stroke-resilient. The potential utility of the relatively preserved spiritual sphere in facilitating stroke rehabilitation requires evaluation in diverse cultures. PMID:21951379

  17. Education in stroke: strategies to improve stroke patient care.

    PubMed

    Gompertz, Patrick; Slack, Andrew; Vogel, Mira; Burrows, Sharon; Clark, Philippa

    2002-07-01

    'Stroke units save lives', but organized care requires expert staff and regular training to be effective. However, the quality of inpatient care for stroke remains poor, and stroke education is often fragmented between the health-care professions. This review describes some national and local strategies aimed at ensuring that all patients are cared for by expert staff.

  18. Controversies in Cardioembolic Stroke

    PubMed Central

    Wessler, Benjamin S.; Kent, David M

    2015-01-01

    Opinion statement Cardioembolic (CE) stroke mechanisms account for a significant number of ischemic strokes however the true burden is likely underestimated. It is critically important to identify patients with CE strokes since these individuals have high recurrence rates and represent a subgroup of patients who may benefit from targeted therapy in the form of anticoagulation or device based treatments. Current guidelines offer recommendations for diagnosis and treatment of these patients however important questions remain. Appropriate cardiac testing in the setting of CE must be individualized and the optimal duration of electrocardiographic monitoring to rule out atrial fibrillation (AF) is unclear. So too, risk stratification tools for AF remain understudied and there is controversy about which anticoagulant agents are most appropriate. Lastly, important potential CE sources of stroke such as PFO have garnered significant attention recently and debate regarding how to treat these patients remains. In this review we discuss some of the important controversies in diagnosing and treating patients with possible CE stroke, pointing to areas where future research might be particularly valuable. PMID:25398426

  19. Leisure after stroke.

    PubMed

    Sjögren, K

    1982-01-01

    Leisure activities and satisfaction derived from leisure activities were investigated together with feelings of stigma and of depression in 51 first-stroke married/cohabitating hemiplegics (males (n: 39) mean age 54 +/- 9; females (n: 12) mean age 50 +/- 12). Leisure goals appeared to mirror traditional gender roles; males having more outdoor and straining leisure activities. For the majority, number and frequency of active leisure participation decreased after stroke and they became passively discontented. This was the case for outdoor and indoor activities as well as for activities characterized by social interaction and entertainment. Mutual and non-mutual partnership of leisure activities occurred for those investigated within a year after stroke. Dissatisfaction also followed increased, passive, time together with spouse. Stigmatism was common (about 50 per cent) during the first year post-stroke, while depression was most common (65 per cent) between 7 and 12 months after stroke. The findings are discussed in terms of physical (disease-related) resources, geographical circumstances and psychological adaptation in its temporal context.

  20. Fatalism, optimism, spirituality, depressive symptoms and stroke outcome: A population-based analysis

    PubMed Central

    Morgenstern, Lewis B.; Sánchez, Brisa N.; Skolarus, Lesli E.; Garcia, Nelda; Risser, Jan M.H.; Wing, Jeffrey J.; Smith, Melinda A.; Zahuranec, Darin B.; Lisabeth, Lynda D.

    2011-01-01

    Background and Purpose We sought to describe the association of spirituality, optimism, fatalism and depressive symptoms with initial stroke severity, stroke recurrence and post-stroke mortality. Methods Stroke cases June 2004–December 2008 were ascertained in Nueces County, Texas. Patients without aphasia were queried on their recall of depressive symptoms, fatalism, optimism, and non-organizational spirituality before stroke using validated scales. The association between scales and stroke outcomes was studied using multiple linear regression with log-transformed NIHSS and Cox proportional hazards regression for recurrence and mortality. Results 669 patients participated, 48.7% were women. In fully adjusted models, an increase in fatalism from the first to third quartile was associated with all-cause mortality (HR=1.41, 95%CI: 1.06, 1.88), marginally associated with risk of recurrence (HR=1.35, 95%CI: 0.97, 1.88), but not stroke severity. Similarly, an increase in depressive symptoms was associated with increased mortality (HR=1.32, 95%CI: 1.02, 1.72), marginally associated with stroke recurrence (HR=1.22, CI: 0.93, 1.62), and with a 9.0% increase in stroke severity (95%CI: 0.01, 18.0). Depressive symptoms altered the fatalism-mortality association such that the association of fatalism and mortality was more pronounced for patients reporting no depressive symptoms. Neither spirituality nor optimism conferred a significant effect on stroke severity, recurrence or mortality. Conclusions Among patients who have already had a stroke, self-described pre-stroke depressive symptoms and fatalism, but not optimism or spirituality, are associated with increased risk of stroke recurrence and mortality. Unconventional risk factors may explain some of the variability in stroke outcomes observed in populations, and may be novel targets for intervention. PMID:21940963

  1. The Dark Side of the Force – Constraints and Complications of Cell Therapies for Stroke

    PubMed Central

    Boltze, Johannes; Arnold, Antje; Walczak, Piotr; Jolkkonen, Jukka; Cui, Lili; Wagner, Daniel-Christoph

    2015-01-01

    Cell therapies are increasingly recognized as a promising option to augment the limited therapeutic arsenal available to fight ischemic stroke. During the last two decades, cumulating preclinical evidence has indicated a substantial efficacy for most cell treatment paradigms and first clinical trials are currently underway to assess safety and feasibility in patients. However, the strong and still unmet demand for novel stroke treatment options and exciting findings reported from experimental studies may have drawn our attention away from potential side effects related to cell therapies and the ways by which they are commonly applied. This review summarizes common and less frequent adverse events that have been discovered in preclinical and clinical investigations assessing cell therapies for stroke. Such adverse events range from immunological and neoplastic complications over seizures to cell clotting and cell-induced embolism. It also describes potential complications of clinically applicable administration procedures, detrimental interactions between therapeutic cells, and the pathophysiological environment that they are placed into, as well as problems related to cell manufacturing. Virtually each therapeutic intervention comes at a certain risk for complications. Side effects do therefore not generally compromise the value of cell treatments for stroke, but underestimating such complications might severely limit therapeutic safety and efficacy of cell treatment protocols currently under development. On the other hand, a better understanding will provide opportunities to further improve existing therapeutic strategies and might help to define those circumstances, under which an optimal effect can be realized. Hence, the review eventually discusses strategies and recommendations allowing us to prevent or at least balance potential complications in order to ensure the maximum therapeutic benefit at minimum risk for stroke patients. PMID:26257702

  2. A comparison of the experimental subsonic pressure distributions about several bodies of revolution with pressure distributions computed by means of the linearized theory

    NASA Technical Reports Server (NTRS)

    Matthews, Clarence W

    1953-01-01

    An analysis is made of the effects of compressibility on the pressure coefficients about several bodies of revolution by comparing experimentally determined pressure coefficients with corresponding pressure coefficients calculated by the use of the linearized equations of compressible flow. The results show that the theoretical methods predict the subsonic pressure-coefficient changes over the central part of the body but do not predict the pressure-coefficient changes near the nose. Extrapolation of the linearized subsonic theory into the mixed subsonic-supersonic flow region fails to predict a rearward movement of the negative pressure-coefficient peak which occurs after the critical stream Mach number has been attained. Two equations developed from a consideration of the subsonic compressible flow about a prolate spheroid are shown to predict, approximately, the change with Mach number of the subsonic pressure coefficients for regular bodies of revolution of fineness ratio 6 or greater.

  3. Hispanics and Heart Disease, Stroke

    MedlinePlus

    ... Thromboembolism Aortic Aneurysm More Hispanics and Heart Disease, Stroke Updated:Aug 30,2016 Heart disease is the No. 1 killer for all Americans and stroke is the fifth leading cause of death. Hispanics ...

  4. Diabetes, Heart Disease, and Stroke

    MedlinePlus

    ... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Diabetes, Heart Disease, and Stroke Having diabetes means that ... help to stop. What is the link between diabetes, heart disease, and stroke? Over time, high blood ...

  5. When does stroke rehabilitation end?

    PubMed

    Korner-Bitensky, Nicol

    2013-01-01

    This article examines key evidence on intervention effectiveness late poststroke; provides discussion on how this evidence impacts stroke rehabilitation at a clinical and national level; and explores strategies that should improve the way in which chronic stroke is addressed internationally.

  6. Stroke rehabilitation and discharge planning.

    PubMed

    Kerr, Peter

    Nurses play a pivotal role in the rehabilitation and discharge planning process of patients who have had a stroke. The nurse's role in the wider stroke multidisciplinary team is complex and diverse and, as such, stroke nurses may find it hard to describe their role and how it fits into the rehabilitation and discharge planning process. A definition of the stroke nurse role in prominent publications such as those of the Scottish Intercollegiate Guidelines Network and the Royal College of Physicians is lacking. This article emphasises the role of the stroke nurse in the rehabilitation and discharge planning process in the stroke unit, while highlighting the complexity, diversity and importance of this role in providing holistic care and support for patients who have survived a stroke. The author draws on his clinical experience of stroke nursing practice in primary, secondary and tertiary care in west central Scotland.

  7. Blood microRNAs as potential diagnostic markers for hemorrhagic stroke

    PubMed Central

    Martinez, Bridget; Peplow, Philip V.

    2017-01-01

    Proper medical treatment of a stroke victim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke, which in current practice is performed by computerized tomography (CT) or magnetic resonance imaging (MRI) scans. A panel of microRNAs could be an extremely useful clinical tool for distinguishing between hemorrhagic and ischemic stroke. This review has shown that blood miRNA profile can distinguish hemorrhagic from ischemic stroke in patients and in experimental animal models. It also seems likely they can differentiate between intracerebral and subarachnoid hemorrhage stroke. The miRNA profile in cerebrospinal fluid could be a useful diagnostic tool for subarachnoid hemorrhagic stroke. Decreased or increased miRNA levels may be needed either as prevention or treatment of stroke. Administration in vivo of miR-130a inhibitor or miRNA mimic (miR-367, miR-223) in an intracerebral hemorrhage animal model improved neurological outcomes. PMID:28250731

  8. Educational approach on stroke training in Europe.

    PubMed

    Corea, F; Gunther, A; Kwan, J; Petzold, A; Debette, S; Sessa, M; Silvestrelli, G; Parnetti, L; Tambasco, N

    2006-01-01

    According to the European Stroke Initiative (EUSI), stroke care is best delivered within a stroke unit by a specialized multidisciplinary stroke team led by stroke specialists. At present, there is no guideline or consensus regarding training requirements or clinical standards that stroke specialists should achieve. It is envisaged that stroke specialists in training would need to acquire adequate knowledge and competency across three major areas of stroke care: acute stroke, stroke rehabilitation, and stroke prevention. With an EUSI document, the European Association of Young Neurologists and Trainees Stroke Subspeciality Group aims to promote discussion on the many aspects of stroke training and the requirements to be a stroke specialist in the European community. The ultimate purpose is to agree on common standards to promote good clinical care and effective stroke prevention across Europe. In the future, this may be translated into better patient outcome and a reduction in the global burden of this condition.

  9. Recent Epidemiological Trends of Stroke

    PubMed Central

    Park, Hyun-Seok; Kang, Myong-Jin

    2008-01-01

    Objective Rapid increase in aged population and westernization of lifestyle have modified epidemiological status of stroke. The purpose of this study is to analyze changing trends of stroke epidemiology in South Korea. Methods We reviewed retrospectively medical records of 1,124 cases diagnosed as stroke among 54,534 patients who visited the Emergency Medical Center at our hospital from January 1994 to December 1996 (Group A). Also, we evaluated 1,705 cases diagnosed as stroke among 55,381 patients who visited to the same hospital from January 2003 to December 2005 (Group B). The variable features of stroke, such as age, sex, seasonal variation and distribution of stroke subtypes were studied by comparing group A with B. Results In group A, hemorrhagic stroke (67.9%) was more prevalent than ischemic stroke (32.1%). However, group B showed that the ratio of hemorrhagic stroke (40.3%) to ischemic stroke (59.6%) has been reversed. The highest incidence of stroke was noted in their sixties and seventies of age in group B, which was older than that of group A. In group A, male ischemic stroke (IS) patients outnumbered female patients (1.26:1). Moreover, this gender disproportion became higher in group B (1.53:1). In group A, the number of male intracerebral hermorrhage (ICH) patients were similar to that of female patients (0.97:1). However, male ICH patients outnumbered female patients in group B (1.23:1). As for subarachnoid hemorrhage (SAH), female patients outnumbered male patients more than two-fold in both groups. Both groups showed that the occurrence of ischemic stroke was highest in summer, but that of hemorrhagic stroke was the highest in winter. Conclusion This study showed the changing trends of stroke in its distribution of subtypes. Multicenter prospective study using stroke registry would be required for the determination of national epidemiologic trends. PMID:19096539

  10. Plotting Lightning-Stroke Data

    NASA Technical Reports Server (NTRS)

    Tatom, F. B.; Garst, R. A.

    1986-01-01

    Data on lightning-stroke locations become easier to correlate with cloudcover maps with aid of new graphical treatment. Geographic region divided by grid into array of cells. Number of lightning strokes in each cell tabulated, and value representing density of lightning strokes assigned to each cell. With contour-plotting routine, computer draws contours of lightning-stroke density for region. Shapes of contours compared directly with shapes of storm cells.

  11. Microwave hemorrhagic stroke detector

    DOEpatents

    Haddad, Waleed S.; Trebes, James E.

    2002-01-01

    The microwave hemorrhagic stroke detector includes a low power pulsed microwave transmitter with a broad-band antenna for producing a directional beam of microwaves, an index of refraction matching cap placed over the patients head, and an array of broad-band microwave receivers with collection antennae. The system of microwave transmitter and receivers are scanned around, and can also be positioned up and down the axis of the patients head. The microwave hemorrhagic stroke detector is a completely non-invasive device designed to detect and localize blood pooling and clots or to measure blood flow within the head or body. The device is based on low power pulsed microwave technology combined with specialized antennas and tomographic methods. The system can be used for rapid, non-invasive detection of blood pooling such as occurs with hemorrhagic stroke in human or animal patients as well as for the detection of hemorrhage within a patient's body.

  12. [Circadian rhythm and stroke].

    PubMed

    Terayama, Yasuo

    2013-12-01

    Studies on the relationship between stroke incidence and alterations of circadian rhythm are scarce, while pathologically reduced or abolished circadian variation has been described to cause stroke since a long time ago. Although ischemic and hemorrhagic strokes are different entities and are characterized by different pathophysiological mechanisms, they share an identical pattern. A constellation of endogenous circadian rhythms and exogenous cyclic factors are involved. The staging of the circadian rhythms in vascular tone, coagulation balance including platelet function, and blood pressure plus temporal patterns in posture, physical activity, emotional stress, autonomic function, and medication effects play central and/or triggering roles. Features of the circadian rhythm of blood pressure, in terms of their chronic and acute effects on cerebral vessels, and of coagulation are especially important.

  13. Stroke and Episodic Memory Disorders

    ERIC Educational Resources Information Center

    Lim, Chun; Alexander, Michael P.

    2009-01-01

    Memory impairments are common after stroke, and the anatomical basis for impairments may be quite variable. To determine the range of stroke-related memory impairment, we identified all case reports and group studies through the Medline database and the Science Citation Index. There is no hypothesis about memory that is unique to stroke, but there…

  14. Effects on five species of shorebirds of experimental closure of a beach in New Jersey: implications for severe storms and sea-level rise.

    PubMed

    Burger, Joanna; Niles, Larry

    2014-01-01

    For management, it is important to understand the factors that affect foraging efficiency of birds during migration, especially in the face of severe storms and sea-level rise. An experiment was conducted whereby a beach used extensively by migrant shorebirds and people was open and experimentally closed to human activity to examine factors affecting feeding when there was no disturbance, with the beach opened or closed to human activity, and following disturbances. When the beach was closed, the factors affecting the percent of shorebirds foraging varied by species, but involved the number of conspecifics or other shorebirds, location along the beach, and number of raptors. Overall, 30% of flocks were disturbed as a function of type of disturbance, location along the beach, and whether the beach was open or closed. These data suggest that individuals, vehicles, and raptors influence the ability of shorebirds to forage undisturbed, indicating the importance of having some sections of important stopover beaches where shorebirds can feed and roost undisturbed by human activity. A corollary is that other parts of the beach can be freely used by people; environmental health can encompass both protected areas for shorebirds and open areas for fishing and recreation. Severe storms and sea-level rise will limit beach space for both human and avian activities, and understanding mitigation for both is essential to wise adaptive management.

  15. Neuro-fuzzy computing for vibration-based damage localization and severity estimation in an experimental wind turbine blade with superimposed operational effects

    NASA Astrophysics Data System (ADS)

    Hoell, Simon; Omenzetter, Piotr

    2016-04-01

    Fueled by increasing demand for carbon neutral energy, erections of ever larger wind turbines (WTs), with WT blades (WTBs) with higher flexibilities and lower buckling capacities lead to increasing operation and maintenance costs. This can be counteracted with efficient structural health monitoring (SHM), which allows scheduling maintenance actions according to the structural state and preventing dramatic failures. The present study proposes a novel multi-step approach for vibration-based structural damage localization and severity estimation for application in operating WTs. First, partial autocorrelation coefficients (PACCs) are estimated from vibrational responses. Second, principal component analysis is applied to PACCs from the healthy structure in order to calculate scores. Then, the scores are ranked with respect to their ability to differentiate different damage scenarios. This ranking information is used for constructing hierarchical adaptive neuro-fuzzy inference systems (HANFISs), where cross-validation is used to identify optimal numbers of hierarchy levels. Different HANFISs are created for the purposes of structural damage localization and severity estimation. For demonstrating the applicability of the approach, experimental data are superimposed with signals from numerical simulations to account for characteristics of operational noise. For the physical experiments, a small scale WTB is excited with a domestic fan and damage scenarios are introduced non-destructively by attaching small masses. Numerical simulations are also performed for a representative fully functional small WT operating in turbulent wind. The obtained results are promising for future applications of vibration-based SHM to facilitate improved safety and reliability of WTs at lower costs.

  16. A molecular genetic approach to improved animal health. The effect of interferon genotype on the severity of experimental bovine herpesvirus-1 infection.

    PubMed

    Ryan, A M; Womack, J E

    1997-11-01

    In the past decade, biotechnology has brought veterinary medicine an increased understanding of the effects of genetic background on disease resistance and production traits. Specific point mutations have been identified for a number of genetic diseases and genetic testing; selective breeding programs can eliminate these diseases from the population. Complex traits such as disease resistance and production traits are thought to be under the control of multiple genes, making their manipulation more difficult. Because of their antiviral and immune modulating properties, interferons may be a role in the host defense against viral infection. The Type I interferon gene family has been detailed in cattle and consists of approximately 32 genes clustered together on bovine chromosome 8. These genes are very polymorphic in the population, enabling studies on the association between alleles at specific interferon loci and the severity of clinical diseases following experimental Bovine Herpesvirus-1 infection. Associations were observed between specific IFN genotypes and increased severity of clinical disease in a population of unrelated cattle. With a better understanding of IFNs at the genetic level, it may eventually be possible to manipulate the IFN response for the therapeutic benefit of cattle, and lessen the economic impact of specific diseases on cattle producers.

  17. Impact of nutritional status and dietary quality on stroke: do we need specific recommendations?

    PubMed

    Lim, H; Choue, R

    2013-05-01

    Stroke, one of the most prevalent geriatric diseases, is a leading cause of death worldwide that often results in permanent physical disability and decreased quality of life, and can have a negative impact on families both financially and emotionally. Although many previous studies have shown relationships between the risk of stroke and nutritional factors, clear dietary recommendations for the prevention and reduction of stroke recurrence have not been established. Several factors should be considered to control and manage stroke. For example, a considerable number of patients with stroke are poorly nourished, have several comorbidities and undesirable health-related behaviors may be present. Stroke patients are less likely to consume beneficial foods, have poorer eating habits and have impoverished dietary quality. In addition, psychological factors such as depression must also be considered in stroke management. Given these factors, dietary recommendations for stroke patients should be established. In this article, we summarized the nutritional status and dietary quality of stroke patients. We also suggested some nutritional guidelines for stroke patients and for those who are at risk for stroke.

  18. Three Variations in Rabbit Angiographic Stroke Models

    PubMed Central

    Culp, William C.; Woods, Sean D.; Brown, Aliza T.; Lowery, John D.; Hennings, Leah J.; Skinner, Robert D.; Borrelli, Michael J.; Roberson, Paula K.

    2012-01-01

    Purpose To develop angiographic models of embolic stroke in the rabbit using pre-formed clot or microspheres to model clinical situations ranging from transient ischemic events to severe ischemic stroke. Materials and Methods New Zealand White rabbits (N=151) received angiographic access to the internal carotid artery (ICA) from a femoral approach. Variations of emboli type and quantity of emboli were tested by injection into the ICA. These included fresh clots (1.0-mm length, 3–6 h), larger aged clots (4.0-mm length, 3 days), and 2 or 3 insoluble microspheres (700–900 μm). Neurological assessment scores (NAS) were based on motor, sensory, balance, and reflex measures. Rabbits were euthanized at 4, 7, or 24 hours after embolization, and infarct volume was measured as a percent of total brain volume using 2,3,5-triphenyltetrazolium chloride (TTC). Results Infarct volume percent at 24 hours after stroke was lower for rabbits embolized with fresh clot (0.45% ± 0.14%), compared with aged clot (3.52% ± 1.31%) and insoluble microspheres (3.39% ± 1.04%). Overall NAS (including posterior vessel occlusions) were positively correlated to infarct volume percent measurements in the fresh clot (r=0.50), aged clot (r=0.65) and microsphere (r=0.62) models (p<0.001). Conclusion The three basic angiographic stroke models may be similar to human transient ischemic attacks (TIA) (fresh clot), major strokes that can be thrombolysed (aged clot), or major strokes with insoluble emboli such as atheromata (microspheres). Model selection can be tailored to specific research needs. PMID:23142182

  19. Endocarditis and Stroke

    PubMed Central

    GRECU, Nicolae; TIU, Cristina; TERECOASA, Elena; BAJENARU, Ovidiu

    2014-01-01

    Endocarditis is an important, although less common, cause of cerebral embolism. All forms of endocarditis share an initial common pathophysiologic pathway, best illustrated by the non-bacterial thrombotic form, but also a final potential for embolization. Stroke associated with endocarditis has signifficant mortality and morbidity rates, especially due to the frequent concomitant multiple sites of brain embolization. In this article we aim to briefly review endocarditis with a focus on stroke as a complication, while also presenting case correlates from our department. PMID:25705308

  20. Managing severe peripartum hyponatraemia: A case report

    PubMed Central

    Lim, Jerry; Laing, Christopher M; MacCallum, Niall S; Brealey, David A

    2014-01-01

    We present a case of severe peripartum hyponatraemia that occurred following a major obstetric haemorrhage causing both an ischaemic stroke and Sheehan's syndrome and outline the investigations and management strategy required. PMID:27512448

  1. The effects of citicoline on acute ischemic stroke: a review.

    PubMed

    Overgaard, Karsten

    2014-08-01

    Early reopening of the occluded artery is, thus, important in ischemic stroke, and it has been calculated that 2 million neurons die every minute in an ischemic stroke if no effective therapy is given; therefore, "Time is Brain." In massive hemispheric infarction and edema, surgical decompression lowers the risk of death or severe disability defined as a modified Rankin Scale score greater than 4 in selected patients. The majority, around 80%-85% of all ischemic stroke victims, does not fulfill the criteria for revascularization therapy, and also for these patients, there is no effective acute therapy. Also there is no established effective acute treatment of spontaneous intracerebral bleeding. Therefore, an effective therapy applicable to all stroke victims is needed. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11,000 patients with various neurologic disorders, including acute ischemic stroke (AIS). The conclusion is that citicoline is safe to use and may have a beneficial effect in AIS patients and most beneficial in less severe stroke in older patients not treated with recombinant tissue plasminogen activator. No other neuroprotective agent had any beneficial effect in confirmative clinical trials or had any positive effect in the subgroup analysis. Citicoline is the only drug that in a number of different clinical stroke trials continuously had some neuroprotective benefit.

  2. Why are patients with acute stroke admitted to hospital?

    PubMed Central

    Bamford, J; Sandercock, P; Warlow, C; Gray, M

    1986-01-01

    Data on 515 consecutive patients registered with the Oxfordshire Community Stroke Project were used to compare the characteristics of those patients who were admitted to hospital within one month after their first stroke with those who remained in the community during that time. Twenty eight patients had their stroke while in hospital for other conditions, and of the remaining 487, 266 were admitted. Though patients with a severe neurological deficit were significantly more likely to be admitted, 47 out of 202 such patients were managed in the community. In a substudy of 162 consecutive patients the general practitioners' reasons for either arranging admission to hospital or continuing with community care in the first week after the stroke were ascertained. Sixty patients were admitted. The only reason for admission was diagnostic uncertainty in five cases (though this was a contributing factor in 25) and to provide nursing or general, non-medical care in 25. Patients who lived alone were more likely to be admitted. All 12 patients who presented directly to the casualty department were admitted, though only five had had a severe stroke. A stroke service that provides a facility for rapid outpatient and domiciliary diagnosis as well as a rapidly acting domiciliary nursing team might reduce the number of patients with stroke admitted to hospital without adversely affecting the quality of patient care: this should be properly evaluated. PMID:3085852

  3. Global stroke statistics.

    PubMed

    Thrift, Amanda G; Thayabaranathan, Tharshanah; Howard, George; Howard, Virginia J; Rothwell, Peter M; Feigin, Valery L; Norrving, Bo; Donnan, Geoffrey A; Cadilhac, Dominique A

    2017-01-01

    Background Up to date data on incidence, mortality, and case-fatality for stroke are important for setting the agenda for prevention and healthcare. Aims and/or hypothesis We aim to update the most current incidence and mortality data on stroke available by country, and to expand the scope to case-fatality and explore how registry data might be complementary. Methods Data were compiled using two approaches: (1) an updated literature review building from our previous review and (2) direct acquisition and analysis of stroke events in the World Health Organization (WHO) mortality database for each country providing these data. To assess new and/or updated data on incidence, we searched multiple databases to identify new original papers and review articles that met ideal criteria for stroke incidence studies and were published between 15 May 2013 and 31 May 2016. For data on case-fatality, we searched between 1980 and 31 May 2016. We further screened reference lists and citation history of papers to identify other studies not obtained from these sources. Mortality codes for ICD-8, ICD-9, and ICD-10 were extracted. Using population denominators provided for each country, we calculated both the crude mortality from stroke and mortality adjusted to the WHO world population. We used only the most recent year reported to the WHO for which both population and mortality data were available. Results Fifty-one countries had data on stroke incidence, some with data over many time periods, and some with data in more than one region. Since our last review, there were new incidence studies from 12 countries, with four meeting pre-determined quality criteria. In these four studies, the incidence of stroke, adjusted to the WHO World standard population, ranged from 76 per 100,000 population per year in Australia (2009-10) up to 119 per 100,000 population per year in New Zealand (2011-12), with the latter being in those aged at least 15 years. Only in Martinique (2011-12) was the

  4. Mechanisms of action of hyperbaric oxygenation in stroke: a review.

    PubMed

    Sánchez, Ernesto Cuauhtémoc

    2013-01-01

    This article outlines the therapeutic mechanisms of hyperbaric oxygenation in acute stroke, based on information obtained from peer-reviewed medical literature. Hyperbaric oxygen is an approved treatment modality for ischemia-reperfusion injury in several conditions. It maintains the viability of the marginal tissue, reduces the mitochondrial dysfunction, metabolic penumbra, and blocks inflammatory cascades observed in acute stroke. Basic and clinical data suggest that hyperbaric oxygen could be a safe and effective treatment option in the management of acute stroke. Further work is needed to clarify its clinical utility when applied within the treatment window of "gold standard" treatments (<3-5 hours).

  5. Hypernatremia secondary to post-stroke hypodipsia: just add water!

    PubMed

    Ramthun, Maikel; Mocelin, Altair Jacob; Alvares Delfino, Vinicius Daher

    2011-08-01

    Disorders in water metabolism may occur in stroke patients. When hypernatremia arises in this setting, it is usually secondary to the development of central diabetes insipidus or it is the result of neurologic lesions that prevent patients from having free access to water. Much rarer are the cases of post-stroke hypernatremia caused by hypodipsia secondary to lesions of the thirst center. We report the case of a patient with severe hypernatremia, probably secondary to post-hemorrhagic stroke hypodipsia. The hypernatremia seen in this case was corrected by scheduling the patient's water intake.

  6. Diabetes augments in vivo microvascular blood flow dynamics after stroke.

    PubMed

    Tennant, Kelly A; Brown, Craig E

    2013-12-04

    Stroke usually affects people with underlying medical conditions. In particular, diabetics are significantly more likely to have a stroke and the prognosis for recovery is poor. Because diabetes is associated with degenerative changes in the vasculature of many organs, we sought to determine how hyperglycemia affects blood flow dynamics after an ischemic stroke. Longitudinal in vivo two-photon imaging was used to track microvessels before and after photothrombotic stroke in a diabetic mouse model. Chronic hyperglycemia exacerbated acute (3-7 d) ischemia-induced increases in blood flow velocity, vessel lumen diameter, and red blood cell flux in peri-infarct regions. These changes in blood flow dynamics were most evident in superficial blood vessels within 500 μm from the infarct, rather than deeper or more distant cortical regions. Long-term imaging of diabetic mice not subjected to stroke indicated that these acute stroke-related changes in vascular function could not be attributed to complications from hyperglycemia alone. Treating diabetic mice with insulin immediately after stroke resulted in less severe alterations in blood flow within the first 7 d of recovery, but had more variable results at later time points. Analysis of microvessel branching patterns revealed that stroke led to a pruning of microvessels in peri-infarct cortex, with very few instances of sprouting. These results indicate that chronic hyperglycemia significantly affects the vascular response to ischemic stroke and that insulin only partially mitigates these changes. The combination of these acute and chronic alterations in blood flow dynamics could underlie diabetes-related deficits in cortical plasticity and stroke recovery.

  7. Correlates of depressive symptoms in individuals attending outpatient stroke clinics.

    PubMed

    Vermeer, Julianne; Rice, Danielle; McIntyre, Amanda; Viana, Ricardo; Macaluso, Steven; Teasell, Robert

    2017-01-01

    Background and purpose Depressive symptoms are common post-stroke. We examined stroke deficits and lifestyle factors that are independent predictors for depressive symptomology. Methods A retrospective chart review was performed for patients' post-stroke who attended outpatient clinics at a hospital in Southwestern Ontario between 1 January 2014 and 30 September 2014. Demographic variables, stroke deficits, secondary stroke risk factors and disability study measures [Patient Health Questionnaire-9 (PHQ-9) and Montreal Cognitive Assessment (MoCA)] were analyzed. Results Of the 221 outpatients who attended the stroke clinics (53% male; mean age = 65.2 ± 14.9 years; mean time post-stroke 14.6 ± 20.1 months), 202 patients were used in the final analysis. About 36% of patients (mean = 5.17 ± 5.96) reported mild to severe depressive symptoms (PHQ-9 ≥ 5). Cognitive impairment (CI), smoking, pain and therapy enrollment (p < 0.01) were significantly associated with depressive symptoms. Patients reporting CI were 4 times more likely to score highly on the PHQ-9 than those who did not report CI (OR = 4.72). While controlling for age, MoCA scores negatively related to depressive symptoms with higher PHQ-9 scores associated with lower MoCA scores (r= -0.39, p < 0.005). Conclusions High levels of depressive symptoms are common in the chronic phase post-stroke and were partially related to cognition, pain, therapy enrollment and lifestyle factors. Implications for Rehabilitation Stroke patients who report cognitive deficits, pain, tobacco use or being enrolled in therapy may experience increased depressive symptoms. A holistic perspective of disease and lifestyle factors should be considered while assessing risk of depressive symptoms in stroke patients. Patients at risk for depressive symptoms should be monitored at subsequent outpatient visits.

  8. The Importance of Patient Involvement in Stroke Rehabilitation

    PubMed Central

    2016-01-01

    Objective To investigate the perceived needs for health services by persons with stroke within the first year after rehabilitation, and associations between perceived impact of stroke, involvement in decisions regarding care/treatment, and having health services needs met. Method Data was collected, through a mail survey, from patients with stroke who were admitted to a university hospital in 2012 and had received rehabilitation after discharge from the stroke unit. The rehabilitation lasted an average of 2 to 4.6 months. The Stroke Survivor Needs Survey Questionnaire was used to assess the participants' perceptions of involvement in decisions on care or treatment and needs for health services in 11 problem areas: mobility, falls, incontinence, pain, fatigue, emotion, concentration, memory, speaking, reading, and sight. The perceived impact of stroke in eight areas was assessed using the Stroke Impact Scale (SIS) 3.0. Eleven logistic regression models were created to explore associations between having health services needs met in each problem area respectively (dependent variable) and the independent variables. In all models the independent variables were: age, sex, SIS domain corresponding to the dependent variable, or stroke severity in cases when no corresponding SIS domain was identified, and involvement in decisions on care and treatment. Results The 63 participants who returned the questionnaires had a mean age of 72 years, 33 were male and 30 were female. Eighty percent had suffered a mild stroke. The number of participants who reported problems varied between 51 (80%, mobility) and 24 (38%, sight). Involvement in decisions on care and treatment was found to be associated with having health services needs met in six problem areas: falls, fatigue, emotion, memory, speaking, and reading. Conclusions The results highlight the importance of involving patients in making decisions on stroke rehabilitation, as it appears to be associated with meeting their health

  9. Stroke: roles of B vitamins, homocysteine and antioxidants.

    PubMed

    Sánchez-Moreno, Concepción; Jiménez-Escrig, Antonio; Martín, Antonio

    2009-06-01

    In the present review concerning stroke, we evaluate the roles of B vitamins, homocysteine and antioxidant vitamins. Stroke is a leading cause of death in developed countries. However, current therapeutic strategies for stroke have been largely unsuccessful. Several studies have reported important benefits on reducing the risk of stroke and improving the post-stroke-associated functional declines in patients who ate foods rich in micronutrients, including B vitamins and antioxidant vitamins E and C. Folic acid, vitamin B6 and vitamin B12 are all cofactors in homocysteine metabolism. Growing interest has been paid to hyperhomocysteinaemia as a risk factor for CVD. Hyperhomocysteinaemia has been linked to inadequate intake of vitamins, particularly to B-group vitamins and therefore may be amenable to nutritional intervention. Hence, poor dietary intake of folate, vitamin B6 and vitamin B12 are associated with increased risk of stroke. Elevated consumption of fruits and vegetables appears to protect against stroke. Antioxidant nutrients have important roles in cell function and have been implicated in processes associated with ageing, including vascular, inflammatory and neurological damage. Plasma vitamin E and C concentrations may serve as a biological marker of lifestyle or other factors associated with reduced stroke risk and may be useful in identifying those at high risk of stroke. After reviewing the observational and intervention studies, there is an incomplete understanding of mechanisms and some conflicting findings; therefore the available evidence is insufficient to recommend the routine use of B vitamins, vitamin E and vitamin C for the prevention of stroke. A