The cellular mechanism of ischemic tolerance in hippocampus

海马缺血耐受的细胞机制

• 批准号: 13680877
• 负责人: SHIMAZAKI Kuniko
• 金额: $ 2.24万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680877/
• 关键词: ischemia; hippocampus; apoptosis; AAV vector; Bcl-2; gene therapy

1) Development of Adeno-assiciated virus: AAV is a potentially useful gene transfer vehicle for neurological gene therapies. Recent findings have shown that recombinant AAV type 5 (rAAV5) can efficiently transduce both neuronal cells and glial cells, while eAAV2 preferentially transduces neuronal cells. Cerebral parenchyaml gene transduction by rAVV5 is more diffuse and widespread compared to transduction by rAAV2.2) Ischemic tolerance in developing brain: By using heterotopic brain graft model, we have made histological and electrophysiological studies of the infant rat brain after prolonged ischemia (90-120min). Our results are consistent with data indicating that deep hypothermia has a notable neuroprotective effect on ischemic injury.

1)腺相关病毒的发展：AAV是一种潜在的用于神经基因治疗的基因转移载体。最近的研究表明，重组AAV5型病毒(RAAV5)可以有效地转导神经细胞和神经胶质细胞，而eAAV2则优先转导神经细胞。与rAAV5基因转导相比，rAVV5转导脑实质蛋白基因更具弥漫性和广泛性。2)脑缺血耐受：采用异位脑移植模型，对新生大鼠长时间脑缺血(90~120min)后的脑组织进行了组织学和电生理研究。我们的结果与深低温对脑缺血损伤有显著神经保护作用的数据相一致。

项目成果

Niu, A., et al.: "Heterotropic graft of infant rat brain as an ischemic model for prolonged whole-brain ischemia"Neurosci Lett. 325(1). 37-41 (2002)

Niu, A. 等人：“婴儿大鼠脑的异向移植物作为长期全脑缺血的缺血模型”Neurosci Lett。

K.Okada, et al.: "Adeno-associated viral vector-mediated gene therapy of ischemia-induced neuronal death"Methods in Enzymology. 346. 378-393 (2002)

K.Okada等人：“腺相关病毒载体介导的缺血诱导的神经元死亡的基因治疗”酶学方法。

島崎久仁子: "別冊・医学のあゆみ 脳血管障害-臨床と研究の最前線"東儀英夫. 6 (2001)

Kuniko Shimazaki：“单独卷：医学史 - 脑血管疾病 - 临床实践和研究的前沿” Hideo Togi 6 (2001)。

Okada T, et al.: "Adeno-associated virus vectors for gene transfer to the brain"Methods. 28(2). 237-247 (2002)

Okada T等人：“用于基因转移至大脑的腺相关病毒载体”方法。

Tanaka, H., et al.: "Disturbance of hippocampal long-term potentiation after transient ischemia in GFAP deficient mice"J Neurosci Res. 67. 11-20 (2002)

Tanaka, H. 等人：“GFAP 缺陷小鼠短暂性缺血后海马长时程增强的紊乱”J Neurosci Res。