کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2532175 1558974 2013 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Valproic acid attenuates ischemia-reperfusion injury in the rat brain through inhibition of oxidative stress and inflammation
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Valproic acid attenuates ischemia-reperfusion injury in the rat brain through inhibition of oxidative stress and inflammation
چکیده انگلیسی

Valproic acid (VPA), widely used in clinical contexts for the treatment of seizures and bipolar mood disorder, has neuroprotective properties in cellular and animal models. However, the precise mechanisms underlying its neuroprotection against stroke remain unknown. In the present study, we explored the effect of VPA on experimental ischemic stroke. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 90 min, followed by reperfusion. The animals received a single injection of VPA (300 mg/kg) immediately, 90, or 270 min after the induction of ischemia. Vehicle-treated animals underwent the same procedure with physiological saline. Infarct volume and neurological symptoms were evaluated 24 h after reperfusion. Immunohistochemical staining for myeloperoxidase (MPO), microglia (Iba1), 4-hydroxy-2-nonenal (4-HNE), or 8-hydroxy-deoxyguanosine (8-OHdG) was performed. Ischemic boundary zone cell death was determined by TUNEL staining. VPA injected immediately or 90 min after ischemia induction significantly reduced infarct volume and improved neurological deficit compared with vehicle (P<0.05). VPA was ineffective when given 270 min after ischemia induction. VPA significantly reduced TUNEL-positive cells, MPO-positive cells, Iba1-positive cells, 4-HNE-positive cells, and 8-OHdG-positive cells compared with vehicle in the ischemic boundary zone (P<0.05). The therapeutic time window for single injection of VPA is between 0 and 90 min in this model. Our results demonstrate that single injection of VPA may have anti-inflammatory as well as antioxidative effects, leading to reduced cell death in ischemia-reperfusion injury.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 707, Issues 1–3, 5 May 2013, Pages 26–31
نویسندگان
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