Research on the Mechanism of Extra-mild Hypothermia(35℃) on neuronal cell death

超低温（35℃）对神经细胞死亡的机制研究

• 批准号: 16590851
• 负责人: KATAYAMA Yasuo
• 金额: $ 2.3万
• 依托单位: Nippon 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590851/
• 关键词: Hypothermia; Rat; Focal Ischemia; Apoptosis; Neuronal cell death; Immunocytochemistry; In situ hybridization; Rho-kinase; ERK; JNK

The aim of this study is to determine whether a rho-kinase inhibitor, fasudil, would prevent neuronal cell death and whether a extra-mild hypothermia (35℃) would enhance the neuroprotective effects of the rho-kinase inhibitor, following transient focal ischemia in rats. Sprague-Dawley rats were subjected to MCAo using an intraluminal suture technique (Nito C et al, Brain Res 1008 : 179-185, 2004) for 2hrs. The rats were reperfused for 24hrs and decapitated for infarct and edema analysis. a rho-kinase inhibitor (fasudil)-treated animals received a continuous injection of fasudil (3.0 or 10.0mg/kg) for 1hrs by after the onset of ischemia, while vehicle-treated groups received same dose of vehicle. Edaravone- treated animals received a twice injection of edaravone at the dose of 3.0mg/kg just after the onset of recirculation and 30min after. During ischemia, temporal muscle and rectal temperatures were monitored and maintained at 37℃ in the treated animals. Animals were randomly divided i … More nto the following four groups (each, n=10) : (I) vehicle-treated group (control) ; (II) low dose fasudil-treated group (3.0mg/kg) ; (III) high dose fasudil-treated group (10.0mg/kg) ; (IV) edaravone-treated group (3.0mg/kg x 2). Temporal muscle and rectal temperatures were maintained during ischemia at 37 ± 0.2℃. Low dose fasudil (II) ameliorated the cortical and striatal ischemic damage compared with the control (I) significantly (p<0.05), whereas high dose fasudil (III) did not decreased the cortical and striatal infarct volume significantly compared with those of groups I and II (p<0.05). Furthermore, low dose fasudil (II) also decreased the cortical and striatal edema volume significantly compared with those of control (I). These results suggest that a rho-kinase inhibitor, fasudil, has a strong neuroprotective effect compared with edaravone that has already been applied clinically in Japan, and that this drug may be a new therapeutic neuroprotective agent for the treatment of acute stroke in clinical field. Less

这项研究的目的是确定Rho-激酶抑制剂Fasudil是否会防止神经元细胞死亡，以及在大鼠瞬时局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性局灶性的大鼠中，是否会增强额外的体温过低（35℃）。 Sprague-Dawley大鼠使用内部缝合技术进行MCAO（Nito C等，Brain Res 1008：179-185，2004）进行2小时。将大鼠重新注射24小时，并斩首以进行感染和水肿分析。缺血发作后，经过Rho-激酶抑制剂（FASUDIL）处理的动物接受了1小时的连续注射Fasudil（3.0或10.0mg/kg），而媒介物治疗的组则接受了相同剂量的媒介物。埃达沃内治疗的动物在再循环发作后，以3.0毫克/kg的剂量注射了两次Edaravone，后30分钟后。在缺血期间，在治疗的动物中监测临时肌肉和直肠温度为37℃。将动物随机分割为i…更多到以下四组（每组n = 10）：（i）媒介物处理的组（对照）； （ii）低剂量疲劳治疗组（3.0mg/kg）； （iii）高剂量疲劳治疗组（10.0mg/kg）; （iv）Edaravone处理的组（3.0mg/kg x 2）。在缺血期间，颞肌和直肠温度保持在37±0.2℃。与对照（i）相比，低剂量疲劳（II）可以改善皮质和纹状体缺血性损伤（P <0.05），而与I和II组相比，高剂量疲劳（III）并未显着降低皮质和纹状体梗死体积（P <0.05）。此外，与对照组相比，低剂量疲劳（II）还显着降低了皮质和纹状体水肿的体积。这些结果表明，与已经在日本临床上已应用的Edaravone相比，Rho-激酶抑制剂Fasudil具有很强的神经保护作用，并且该药物可能是一种新的治疗性神经保护剂，用于治疗临床领域的急性中风。较少的