Elucidation of pathogenesis and new treatment for brain injury after subarachnoid hemorrhage

蛛网膜下腔出血后脑损伤发病机制的阐明和新的治疗方法

• 批准号: 22591584
• 负责人: SUZUKI Hidenori
• 金额: $ 2.83万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591584/
• 关键词: 脳血管障害学; くも膜下出血; 脳損傷; 細胞外基質蛋白; 脳血管攣縮; 細胞外基質; オステオポンチン; マトリックス細胞蛋白; 血液脳関門障害; 脳浮腫; ラット; siRNA

Subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) potentially contributes to poor outcome, one of whose key pathologic manifestation is the breakdown of the blood-brain barrier (BBB). We determined the role of osteopontin (OPN), a pleiotropic extracellular matrix glycoprotein (matricellular protein [MCP]), in the post-SAH BBB disruption in rats. The OPN levels in the brain were significantly induced and peaked at 72 hours after SAH, in the recovery phase of EBI. OPN siRNA significantly blocked the endogenous OPN induction and aggravated neurological impairment and BBB disruption at 72 hours after SAH. Pre-SAH administration of recombinant OPN (r-OPN)significantly prevented a loss in body weight, neurological impairment, brain edema and BBB disruption compared with the control rats. Treatment with r-OPN was associated with the deactivation of NF-κB activity, inhibition of MMP-9 induction, and the consequent preservation of cerebral microvessel basal lamina proteins and tight junction proteins.These findings suggest the protective effects of OPN against BBB disruption after SAH.In addition, we obtained new findings, suggesting that tenascin-C, another MCP, causes brain injury after SAH.

蛛网膜下腔出血（Subarachnoid hemorrhage，SAH）导致的早期脑损伤（early brain injury，EBI）是预后不良的重要原因之一，其主要病理表现是血脑屏障（blood-brain barrier，BBB）的破坏。我们确定了骨桥蛋白（OPN），一种多效性细胞外基质糖蛋白（基质细胞蛋白[MCP]），在大鼠SAH后血脑屏障破坏中的作用。脑内OPN水平在SAH后72小时达到高峰，处于EBI恢复期。SAH后72小时，OPN siRNA明显阻断内源性OPN诱导，并加重神经功能损害和BBB破坏。与对照组相比，SAH前给予重组OPN（r-OPN）显著防止体重减轻、神经功能缺损、脑水肿和BBB破坏。r-OPN可抑制NF-κB活性，抑制MMP-9的诱导，保护脑微血管基底膜蛋白和紧密连接蛋白，提示OPN对SAH后BB B的破坏具有保护作用。

项目成果

くも膜下出血後脳損傷および脳血管攣縮におけるマトリックス細胞蛋白質の役割

基质细胞蛋白在蛛网膜下腔出血后脑损伤及脑血管痉挛中的作用

• 发表时间: 2011
• 作者: 芝 真人;鈴木秀謙;鈴木秀謙;鈴木秀謙
• 通讯作者: 鈴木秀謙

ラットくも膜下出血モデルにおけるImatinib の抗脳血管攣縮効果(シンポジウム)

伊马替尼对大鼠蛛网膜下腔出血模型的抗脑血管痉挛作用（研讨会）

• 发表时间: 2011
• 作者: 芝 真人;鈴木秀謙
• 通讯作者: 鈴木秀謙

ラットくも膜下出血後early brain injuryにおけるテネイシンCの役割（シンポジウム）

Tenascin-C 在大鼠蛛网膜下腔出血后早期脑损伤中的作用（研讨会）

• 作者: 芝 真人;鈴木秀謙;他
• 通讯作者: 他

Tenascin-C induces prolonged constriction of cerebral arteries in rats

• DOI: 10.1016/j.nbd.2013.01.007
• 发表时间: 2013-07-01
• 期刊: NEUROBIOLOGY OF DISEASE
• 影响因子: 6.1
• 作者: Fujimoto, Masashi;Suzuki, Hidenori;Taki, Waro
• 通讯作者: Taki, Waro

Treatment with sodium orthovanadate reduces blood-brain barrier disruption via phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphorylation in experimental subarachnoid hemorrhage.

• DOI: 10.1002/jnr.22801
• 发表时间: 2012-03
• 期刊: JOURNAL OF NEUROSCIENCE RESEARCH
• 影响因子: 4.2
• 作者: Hasegawa, Yu;Suzuki, Hidenori;Altay, Orhan;Chen, Hank;Zhang, John H.
• 通讯作者: Zhang, John H.