Shintani Yasushi, Terao Yasuko, Ohta Hiroyuki
Pharmacology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 2-17-85, Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan.
Stroke Res Treat. 2010 Dec 1;2011:809874. doi: 10.4061/2011/809874.
Stroke is a dynamic event in the brain involving heterogeneous cells. There is now compelling clinical evidence that prolonged, moderate cerebral hypothermia initiated within a few hours after severe ischemia can reduce subsequent neuronal death and improve behavioral recovery. The neuroprotective role of hypothermia is also well established in experimental animals. However, the mechanism of hypothermic neuroprotection remains unclear, although, presumably involves the ability of hypothermia to suppress a broad range of injurious factors. In this paper, we addressed this issue by utilizing comprehensive gene and protein expression analyses of ischemic rat brains. To predict precise target molecules, we took advantage of the therapeutic time window and duration of hypothermia necessary to exert neuroprotective effects. We proposed that hypothermia contributes to protect neuroinflammation, and identified candidate molecules such as MIP-3α and Hsp70 that warrant further investigation as targets for therapeutic drugs acting as "hypothermia-like neuroprotectants."
中风是大脑中涉及多种细胞的动态事件。目前有令人信服的临床证据表明，在严重缺血后数小时内开始的长时间、适度的脑部低温可以减少随后的神经元死亡并改善行为恢复。低温的神经保护作用在实验动物中也已得到充分证实。然而，低温神经保护的机制仍不清楚，尽管推测它涉及低温抑制多种损伤因素的能力。在本文中，我们通过对缺血大鼠大脑进行全面的基因和蛋白质表达分析来解决这个问题。为了预测精确的靶分子，我们利用了发挥神经保护作用所需的治疗时间窗和低温持续时间。我们提出低温有助于保护神经炎症，并鉴定出了如MIP-3α和Hsp70等候选分子，它们作为“类低温神经保护剂”的治疗药物靶点值得进一步研究。
