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

本研究的目的是确定rho激酶抑制剂法舒地尔是否能预防大鼠短暂局灶性脑缺血后神经元细胞死亡，以及超轻度低温（35℃）是否能增强rho激酶抑制剂的神经保护作用。使用管腔内缝合技术（Nito C等人，Brain Res 1008：179-185，2004）使Sprague-Dawley大鼠经受MCAo 2小时。将大鼠再灌注24小时并断头用于梗塞和水肿分析。Rho激酶抑制剂（法舒地尔）治疗的动物在缺血发作后接受法舒地尔（3.0或10.0mg/kg）连续注射1小时，而载体治疗组接受相同剂量的载体。依达拉奉治疗组动物在再循环开始后即刻和30分钟后接受依达拉奉3.0mg/kg剂量的两次注射。在缺血期间，监测给药动物的颞肌和直肠温度，并将其维持在37℃。将动物随机分为： ...更多信息 分为以下四组（每组，n=10）：（I）溶剂处理组（对照）;（II）低剂量法舒地尔处理组（3.0 mg/kg）;（III）高剂量法舒地尔处理组（10.0 mg/kg）;（IV）依达拉奉处理组（3.0 mg/kg × 2）。缺血期间，颞肌和直肠温度保持在37 ± 0.2℃。低剂量法舒地尔（II）与对照组（I）相比显著改善皮质和纹状体缺血损伤（p<0.05），而高剂量法舒地尔（III）与I和II组相比没有显著减少皮质和纹状体梗死体积（p<0.05）。此外，低剂量法舒地尔（II）也减少皮质和纹状体水肿体积与对照组（I）相比显着。这些结果表明，rho激酶抑制剂法舒地尔与已在日本临床应用的依达拉奉相比具有较强的神经保护作用，该药物可能是临床领域治疗急性脑卒中的新的治疗性神经保护剂。少

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