The effect of hypothermia on gene expression in the ischemic hippocampal CAI

低温对缺血海马CAI基因表达的影响

• 批准号: 12557117
• 负责人: MITANI Akira
• 金额: $ 8.45万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557117/
• 关键词: hypothermia; ischemia; neuronal death; gene; hippocambal CA1; 低温; 脳虚血; 保護機構; 海馬CA1; ニューロン死防御

It has been known that mild hypothermia prevents neuronal damage against ischemia, however, the mechanism has not been established. In the present study, we assembled a telemeter-based brain temperature control system that allows continuous monitoring and regulating of brain temperature to investigate the neuroprotective effects of hypothermia. A brain temperature transmitter was attached to the gerbil skull and 5-min transient ischemia was induced. The brain temperature was lowered from 1 hour after recirculation and kept at 32℃ for 24 hours. The result showed that this system regulated gerbil brain temperature continuously, and proved that the post-ischemic hypothermia provided effective and long lasting neuroprotection in the hippocampal CA1. Then, we attempted to examine changes of gene expression in gerbil hippocampal CA1 subjected to ischemia and/or hypothermia. Besides numerous ischemia induced gene products such as interferon induced gene 2, GTPase, and Ca<^2+> pump, hypothermia induced specific up regulation or down regulation of several genes including tyrosine phosphatase-receptor type. This result suggests that these genes induced by hypothermia may be used to present a novel strategy for development of preventives/therapeutics of brain stroke.

已知亚低温可预防缺血对神经元的损伤，但其机制尚不明确。在本研究中，我们组装了一个基于遥测仪的大脑温度控制系统，该系统可以连续监测和调节大脑温度，以研究低温的神经保护作用。在沙土鼠颅骨上安装脑温传输器，造成短暂性脑缺血5min。再灌流后1h开始降温，维持在32℃持续24小时。结果表明，该系统连续调节沙土鼠脑温度，证明缺血后亚低温对海马区CA1区具有有效而持久的神经保护作用。然后，我们试图检测缺血和/或低温对沙土鼠海马CA1区基因表达的影响。除了大量的缺血诱导基因产物如干扰素诱导基因2、GTPase和Ca&lt；^2+&gt；泵外，低温还诱导包括酪氨酸磷酸酶受体类型在内的几个基因的特异性上调或下调。这一结果表明，低温诱导的这些基因可能为开发脑中风的预防/治疗提供了一种新的策略。

项目成果

Suguyama, T.: "Inhibition of glutamate transporter by theanine enhances the therapeutic efficacy of doxorubicin"Toxicology Letters. 121・2. 89-96 (2001)

Suguyama, T.：“茶氨酸对谷氨酸转运蛋白的抑制增强了阿霉素的治疗效果”毒理学快报 121・2 (2001)。

Gray, C.: "Glutamate does not play a major role in controlling bone growth"Journal of Bone Mineral Research. 16・4. 742-749 (2001)

Gray, C.：“谷氨酸在控制骨骼生长方面不起主要作用”《骨矿物质研究杂志》16・4 (2001)。

Kataoka, Y.: "Neovascularization with blood-brain barrier breakdown in delayed neuronal death"Biochemical and Biophysical Research Communication. 273・2. 637-641 (2000)

Kataoka，Y.：“迟发性神经元死亡中的血脑屏障破坏的新生血管”生物化学和生物物理研究通讯273·2（2000）。

Katagiri, H.: "Requirement of appropriate glutamate concentrations in the synaptic cleft for hippocampal LTP induction"European Journal of Neuroscience. 14・3. 547-553 (2001)

Katagiri, H.：“海马 LTP 诱导的突触间隙中适当的谷氨酸浓度的要求”欧洲神经科学杂志 14・3 (2001)。

Hakuba,N. et al.: "Hearing loss and glutamate efflux in the perilymph following transient hindbrain ischemia in gerbils"Journal of Comparative Neurology. 418・2. 217-226 (2000)

Hakuba, N. 等人：“沙鼠短暂后脑缺血后的听力损失和外淋巴液中的谷氨酸流出”，比较神经学杂志 418・2（2000 年）。