A study on the novel therapeutic drugs to protect delayed neuronal death after stroke

保护脑卒中后迟发性神经元死亡的新型治疗药物的研究

• 批准号: 22659109
• 负责人: SOKABE Masahiro
• 金额: $ 1.96万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659109/
• 关键词: 脳卒中治療薬; 神経ステロイド; 脳虚血; 神経細胞死; 神経保護作用; DHEA; プロゲステロン; 脳卒中; 治療薬; progesterone; 新規治療法; アストロサイト; GLT-1

Once a stroke happens, there is virtually no effective treatment except for thrombolysis within 5 hrs after the crisis, but its application ratio is less than 5%. We noticed that most of serious after effects of stroke are caused by the ischemic delayed neuron death starting from 2 days after the crisis, and aimed to develop therapeutic drugs that can protect neurons from ischemic damages. By using animal models with transient brain ischemia, we found that certain neurosteroids, when administered within 48-72 hrs after the crisis, could largely inhibit the ischemic delayed neuron death and learinig/motility impairment. Furthermore we revealed the underlying molecular mechanisms of the neuroprotective effects of the neurosteroids.

一旦发生中风，危象发生后5小时内除了溶栓外，几乎没有有效的治疗方法，但其应用比例不足5%。我们注意到大多数严重的中风后遗症是由中风后两天开始的缺血性迟发性神经元死亡引起的，因此旨在开发可以保护神经元免受缺血性损伤的治疗药物。通过使用短暂性脑缺血的动物模型，我们发现在危机发生后 48-72 小时内给予某些神经类固醇，可以在很大程度上抑制缺血性迟发性神经元死亡和学习/运动障碍。此外，我们揭示了神经类固醇神经保护作用的潜在分子机制。

项目成果

Microtubule dynamics regulate cyclic stretch-induced cellreorientation in human airway smooth muscle cells

微管动力学调节人气道平滑肌细胞循环拉伸诱导的细胞重新定向

• 发表时间: 2011
• 期刊: PLoS One
• 影响因子: 3.7
• 作者: Morioka M;Parameswarane H;Naruse K;Kondo M;Sokabe M;Hasegawa Y;Suki B;Ito S. Hasegawa Y;Suki B;Ito S.
• 通讯作者: Ito S.

Treatment with progesterone after focal cerebral ischemia attenuates progenitor cell proliferation but improves newborn neuron survival in adult male mice

局灶性脑缺血后用黄体酮治疗可减弱成年雄性小鼠的祖细胞增殖，但可提高新生神经元的存活率

• 发表时间: 2010
• 期刊: Neuropharmacol
• 作者: Zhang Z;Yang R;Cai W;Bai Y;Sokabe M;Chen L.
• 通讯作者: Chen L.

Localization of NK1 receptors and roles of substance-P in subepithelial fibroblasts of rat intestinal villi

NK1受体定位及P物质在大鼠肠绒毛上皮下成纤维细胞中的作用

• 发表时间: 2010
• 期刊: Cell Tissue Res
• 影响因子: 3.6
• 作者: Furuya S;Furuya K;Shigemoto R;Sokabe M.
• 通讯作者: Sokabe M.

Application of optical recording technique with voltage sensitive dyes to the study of synaptic transmission and plasticity in the brain

电压敏感染料光学记录技术在大脑突触传递和可塑性研究中的应用

• 发表时间: 2011
• 作者: Sokabe M;Furuya K;Sokabe M;Sokabe M;曽我部正博;曽我部正博;曽我部正博;Sokabe M;Sokabe M;Sokabe M;Sokabe M;Sokabe M;Sokabe M
• 通讯作者: Sokabe M

Advan Time-Window of Progesterone Neuroprotection After Stroke and Its Underlying Molecular Mechanisms. In"Advances in the Preclinical Study of Ischemic Stroke"

中风后黄体酮神经保护的Advan时间窗及其潜在分子机制。

• 发表时间: 2012
• 作者: Cai W;Sokabe M;Chen L
• 通讯作者: Chen L