Involvement of MAPK cascade in ischemic neuronal damage

MAPK 级联参与缺血性神经元损伤

• 批准号: 17390398
• 负责人: NOZAKI Kazuhiko
• 金额: $ 9.98万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390398/
• 关键词: cerebral ischemia; ischemic tolerance; MAPK; 脳神経疾患; cerebral ischemia; ischemic tolerance

It remains to be shown whether or not the activations of MAPK cascades may affect ischemic neuronal damage and ischemic tolerance induced by sublethal ischemia. We obtained evidence suggesting that p38 was activated in the gerbil hippocampus after 5-minute transient forebrain ischemia in vivo and that the inhibition of the activity of p38 protected against delayed neuronal death in CA1 pyramidal cells. We also confirmed the activation of p38 mitogen-activated protein kinase in the gerbil hippocampus by Western blotting and immunohistochemistry after 2 minutes of global sublethal ischemia, and pretreatment with SB203580,an inhibitor of active p38,30 minutes before the 2-minute ischemia reduced the ischemic tolerance effect in a dose-dependent manner.JNKI also attenuated CA1 ischemic damage.Genetic disruption of STAT1, a targeted molecule of p38,reduced ischemic damage in a mice ischemic model. These findings suggest that p38 may contribute to both ischemic damage and tolerance in CA1 neurons of the hippocampus and that components of the p38 cascade can be target molecules to modify neuronal survival after ischemia.

MAPK级联的激活是否影响亚致死性缺血诱导的缺血性神经元损伤和缺血耐受还有待证实。我们获得的证据表明，p38被激活后5分钟短暂的前脑缺血在体内的沙鼠海马和抑制p38的活性保护对迟发性神经元死亡的CA1锥体细胞。我们还通过Western blotting和免疫组织化学证实了沙土鼠全脑亚致死性缺血2分钟后海马中p38丝裂原活化蛋白激酶的激活，并且在2分钟缺血前30分钟用活性p38抑制剂SB 203580预处理以剂量依赖性方式降低缺血耐受效应。JNKI还减轻了CA 1缺血损伤。p38的靶向分子，减少小鼠缺血模型中的缺血性损伤。这些研究结果表明，p38可能有助于缺血性损伤和耐受性海马CA1神经元和p38级联的组件可以修改缺血后的神经元存活的靶分子。

项目成果

Administratlon of ex vivo-expanded bone marrow-derived endothellalprogenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats.

给予离体扩增的骨髓源性内皮祖细胞可减轻大鼠局灶性脑缺血再灌注损伤。

• 发表时间: 2006
• 期刊: Neurosurgery 59
• 作者: Jun;Takahashi;Takahashi J.;Ohta T et al.
• 通讯作者: Ohta T et al.

Activation of p38 kinase in the gerbil hippocampus showing ischemic tolerance.

沙鼠海马中 p38 激酶的激活显示出缺血耐受性。

• 发表时间: 2003
• 期刊: J CBFMetab 23
• 作者: Nishimura M;Sugino T;Nozaki K;Takagi Y;Hashimoto N;Moriguchi T;Nishida E.
• 通讯作者: Nishida E.

Neuroprotective Role of A Peptide Inhibitor of c-Jun N-terminal Kinase on Global ischemia in Gerbils

c-Jun N 末端激酶肽抑制剂对沙鼠全身缺血的神经保护作用

• 期刊: (In press)
• 作者: Sugino T;Nozaki K;Takagi Y;Hattori I;Hashimoto N;Moriguchi T;Nishida E.;Duysenbi S et al.
• 通讯作者: Duysenbi S et al.

Intravenous administration of thioredoxin decreases brain damage following transient focal cerebral ischemia in mice

• DOI: 10.1089/152308604771978372
• 发表时间: 2004-02-01
• 期刊: ANTIOXIDANTS & REDOX SIGNALING
• 影响因子: 6.6
• 作者: Hattori, I;Takagi, Y;Yodoi, J
• 通讯作者: Yodoi, J

Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain

• DOI: 10.3171/jns.2005.103.2.0304
• 发表时间: 2005-08-01
• 期刊: JOURNAL OF NEUROSURGERY
• 影响因子: 4.1
• 作者: Takagi, Y;Nishimura, M;Hashimoto, N
• 通讯作者: Hashimoto, N