スダ サトシ   SUDA Satoshi
  須田 智
   所属   埼玉医科大学  医学部 国際医療センター 神経内科・脳卒中内科
   職種   教授
論文種別 学術雑誌(原著)
言語種別 英語
査読の有無 査読あり
表題 Valproic acid ameliorates ischemic brain injury in hyperglycemic rats with permanent middle cerebral occlusion
掲載誌名 正式名:BRAIN RESEARCH
ISSNコード:0006-8993/1872-6240
出版社 ELSEVIER SCIENCE BV
巻・号・頁 1606,1-8頁
著者・共著者 Satoshi Suda,Masayuki Ueda,Chikako Nito,Yasuhiro Nishiyama,Seiji Okubo,Arata Abe,Junya Aoki,Kentaro Suzuki,Yuki Sakamoto,Kazumi Kimura
発行年月 2015/05
概要 Valproic acid (VPA) is widely used for the clinical treatment of epilepsy. Previous studies have demonstrated that VPA ameliorates brain injury following experimental stroke. However, the effect of VPA in stroke models featuring comorbid conditions has not been fully explored. In this study, we investigate the effects of VPA on permanent ischemic stroke with hyperglycemia. Hyperglycemia Was induced by streptozotocin (STZ) injection 3 days before. Test animals received a single injection of VPA immediately after induction of ischemia. Control animals received occlusion and physiological saline injection, or STZ, occlusion, and saline. Magnetic resonance imaging of cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) was performed 60 min after ischemia. Infarct volume, neurological deficits, rotarod test performance, and immunohistological markers were assessed 3 days after ischemia. Hyperglycemia significantly expanded the area of decreased of CBF and ADC, and increased the number of myeloperoxidase-positive cells, ionized calcium binding adapter molecule 1-positive cells, inducible nitric oxide synthase-positive cells, von Willebrand factor-positive cells, and Fluoro-Jade C-positive cells in the ischemic boundary zone, which was accompanied by increased infarct volume and deteriorated neurological deficit and rotarod test compared with normoglycemia (P <0.05). VPA significantly alleviated the aggravation of functional outcome accompanied by suppressing these inflammation, endothelial injury, and neuronal degeneration compared with saline-treated group (P<0.05). A single injection of VPA following permanent ischemia in STZ-induced hyperglycemic rats ameliorates neurological deficits and reduces neuronal degeneration by inhibiting inflammation and endovascular injury. VPA may be promising as a candidate therapy for human stroke. (C) 2015 Elsevier B.V. All rights reserved.
DOI 10.1016/j.brainres.2015.02.013
PMID 25721785