Venna V.R.,University of Connecticut Health Center |
Xu Y.,University of Connecticut Health Center |
Doran S.J.,University of Connecticut Health Center |
Patrizz A.,University of Connecticut Health Center |
And 2 more authors.
Translational Psychiatry | Year: 2014
Stroke survivors often experience social isolation. Social interaction improves quality of life and decreases mortality after stroke. Male mice (20-25 g; C57BL/6N), all initially pair housed, were subjected to middle cerebral artery occlusion (MCAO). Mice were subsequently assigned into one of three housing conditions: (1) Isolated (SI); (2) Paired with their original cage mate who was also subjected to stroke (stroke partner (PH-SP)); or (3) Paired with their original cage mate who underwent sham surgery (healthy partner (PH-HP)). Infarct analysis was performed 72 h after stroke and chronic survival was assessed at day 30. Immediate poststroke isolation led to a significant increase in infarct size and mortality. Interestingly, mice paired with a healthy partner had significantly lower mortality than mice paired with a stroke partner, despite equivalent infarct damage. To control for changes in infarct size induced by immediate post-stroke isolation, additional cohorts were assessed that remained pair housed for three days after stroke prior to randomization. Levels of brain-derived neurotrophic factor (BDNF) were assessed at 90 days and cell proliferation (in cohorts injected with 5-bromo-2'- deoxyuridine, BrdU) was evaluated at 8 and 90 days after stroke. All mice in the delayed housing protocol had equivalent infarct volumes (SI, PH-HP and PH-SP). Mice paired with a healthy partner showed enhanced behavioral recovery compared with either isolated mice or mice paired with a stroke partner. Behavioral improvements paralleled changes in BDNF levels and neurogenesis. These findings suggest that the social environment has an important role in recovery after ischemic brain injury. © 2014 Macmillan Publishers Limited.
Lapchak P.A.,Cedars Sinai Medical Center |
Han M.K.,Stroke Center
Brain Research | Year: 2010
Statins have pleiotropic neuroprotective effects in the central nervous system. In this study, we assessed the pharmacological effects of simvastatin on measures of behavior in New Zealand white rabbits embolized using a suspension of small-sized blood clots. For these studies, simvastatin was administered up to 3 hours following embolization, and behavior was measured 48 hours following embolization to calculate the dose of emboli (P50 in mg) that produces neurological deficits in 50% of the rabbits. A treatment is considered neuroprotective if it significantly increases the P50 compared to control. Simvastatin treatment (20 mg/kg, bolus subcutaneous injection) significantly improved clinical function and increased the P50 by 143% when administered 1 hour following embolization but was ineffective at 3 hours. In combination studies with the thrombolytic, tissue plasminogen activator (tPA) using a standard intravenous dose of 3.3 mg/kg (20% bolus, 80% infused), we found that simvastatin could be safely administered with tPA to improve clinical scores; however, the maximum behavioral improvement with the combination treatment was similar to either monotherapy alone, both of which significantly improved behavior (p < 0.05). It has been proposed that Simvastatin neuroprotection may be related to a variety of signaling pathways including Rho-kinase (ROCK). To determine if a ROCK mechanism is involved in simvastatin-induced neuroprotection following embolic strokes, we used pharmacological intervention with the ROCK inhibitor, fasudil. When fasudil was administered 30 minutes before simvastatin (given at 1 hour), there was an additional significant (p = 0.0217) synergistic increase in behavioral function. However, fasudil as a monotherapy did not affect behavioral function in embolized rabbits. The study suggests that there may be an interaction between simvastatin treatment and the ROCK signaling pathway that should be further explored. Our results suggest that simvastatin treatment may have clinical benefit when used alone or in the presence of tPA, but the therapeutic window using a single-dose regimen is narrow. © 2010 Elsevier B.V. All rights reserved.
Iwata T.,Stroke Center
Clinical Neurology | Year: 2014
Recently, remarkable progress has been made in the field of endovascular treatment, and endovascular treatment for acute ischemic stroke due to large vessel occlusion has been an effective and therapeutic option. However, there is no randomized control trial as to superiority of endovascular treatment for acute ischemic stroke compared to the standard treatment including intravenous rt-PA. Inclusion criteria for the performance of endovascular treatment for acute ischemic stroke will need to be defined more precisely, and high rates of fast recanalization will be needed in future. We expect the evidence that endovascular treatment for acute ischemic stroke due to large vessel occlusion is superior to standard treatment by the detailed images of the brain, more strict indications and novel endovascular devices such as percutaneous transluminal mechanical thrombectomy devices.
Haratz S.,Stroke Center |
Haratz S.,University of Sao Paulo |
Tanne D.,University of Sao Paulo |
Tanne D.,Tel Aviv University
Current Opinion in Neurology | Year: 2011
Purpose of review: Hyperglycemia is frequent in patients with cerebrovascular disease. This review article aims to summarize the recent evidence from observational studies that examined the adverse cerebrovascular effects of dysglycemic states as well as interventional studies assessing intensive management strategies for hyperglycemia. Recent findings: In recent years, diabetes, prediabetic states and insulin resistance and their association with cerebrovascular disease were an important focus of research. The cerebrovascular consequences of these metabolic abnormalities were found to extend beyond ischemic stroke to covert brain infarcts, other structural brain changes and to cognitive impairment with and without dementia. Interventional studies did not reveal that more intensive management of chronic hyperglycemia and of hyperglycemia in the setting of acute stroke improves outcome. There is clear evidence, however, that the overall management of multiple risk factors and behavior modification in patients with dysglycemia may reduce the burden of cerebrovascular disease. Summary: Observational studies reveal the growing burden and adverse cerebrovascular effects of dysglycemic states. Currently available interventional studies assessing more intensive strategies for the management of hyperglycemia did not prove, however, to be effective. We discuss the current evidence, pathophysiological considerations and management implications. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Lin C.-M.,Stroke Center |
Liu C.-K.,Chunghua Christian Hospital
Journal of Neuroimaging | Year: 2015
Substance poisoning, such as toluene intoxication, has seldom been reported in the relevant literature. The documented cerebral neuroimaging has mostly described reversible symmetrical white matter changes in both the cerebral and cerebellar hemispheres. This paper presents 2 patients with toluene poisoning, whose brain magnetic resonance imaging studies showed a similar picture that included extra involvement over the corpus callosum; however, such corpus callosum involvement has never been mentioned and is quite rare in the literature. We discussed the underlying neuropathological pathways in this article. Hopefully, these cases will provide first-line clinicians with some valuable information with regard to toluene intoxication and clinical neuroimaging presentations. © 2014 by the American Society of Neuroimaging.