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.

亚蛛网膜下腔出血（SAH）诱导的早期脑损伤（EBI）可能导致不良结果，其关键病理表现之一是血脑屏障（BBB）的崩溃。我们确定了骨桥蛋白（OPN），一种多效性细胞外基质基质糖蛋白（基质蛋白[MCP]），在大鼠后SAH BBB破坏中的作用。在EBI的恢复阶段，在SAH后72小时后，大脑中的OPN水平显着诱导并达到峰值。 SAH后72小时，OPN siRNA显着阻止了内源性OPN诱导和汇总的神经系统障碍和BBB破坏。与对照大鼠相比，SAH前施用重组OPN（R-OPN）显着阻止了体重损失，神经系统障碍，脑水肿和BBB破坏。用R-OPN处理NF-κB活性，抑制MMP-9诱导以及随之而来的脑微血管碱性层层蛋白和紧密连接蛋白有关。这些发现表明，SAH后，OPN对BBB破坏的保护作用。此外，我们获得了新的发现，表明Tenascin-C是另一位MCP，在SAH后造成脑损伤。

项目成果

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.

アルファ７ニコチン性受容体作動薬PNU-282987のくも膜下出血後early brain injury抑制効果（シンポジウム）

α7烟碱受体激动剂PNU-282987对蛛网膜下腔出血后早期脑损伤的影响（研讨会）

• 作者: 鈴木秀謙;他
• 通讯作者: 他

Tenascin-Cの脳動脈収縮効果

Tenascin-C 的脑动脉收缩作用

• 发表时间: 2012
• 作者: 藤本昌志;鈴木秀謙
• 通讯作者: 鈴木秀謙

テネイシンCとearly brain injuryおよび脳血管攣縮との関連

Tenascin-C与早期脑损伤及脑血管痉挛的关系

• 发表时间: 2012
• 期刊: 脳血管攣縮
• 作者: Yan Zhan;Chunhua Chen;Hidenori Suzuki;et al;鈴木秀謙;鈴木秀謙
• 通讯作者: 鈴木秀謙

Role of Platelet-Derived Growth Factor in Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats

• DOI: 10.1007/978-3-7091-1192-5_40
• 发表时间: 2013-01-01
• 期刊: CEREBRAL VASOSPASM: NEUROVASCULAR EVENTS AFTER SUBARACHNOID HEMORRHAGE
• 作者: Shiba, Masato;Suzuki, Hidenori;Taki, Waro
• 通讯作者: Taki, Waro