Varathan S, Shibuta S, Shimizu T, Mashimo T
Department of Anesthesiology, Osaka University Medical School, Suita-city, Osaka, Japan.
J Neurosci Res. 2001 Sep 15;65(6):583-90. doi: 10.1002/jnr.1188.
Many experimental and clinical studies have shown that hypothermia confers cerebroprotective benefits against ischemic insults. Because of the many conflicting reports on hypothermic neuroprotection, we undertook this cellular study to identify the optimal temperature or a range of temperatures for maximal neuroprotection at different times (6-24 hr) during ischemic insults. Cultured Wistar rat cortical neurons were exposed to oxygen deprivation at defined times and temperatures (37 degrees C normothermia, 32 degrees C mild hypothermia, 27 degrees C moderate hypothermia, 22 degrees C deep hypothermia, and 17 degrees C profound hypothermia). The survival rate of neurons was evaluated by assessing viable neurons on photomicrographs. The normothermic group demonstrated a significantly lower survival rate of cultured neurons (6 hr, 80.3% +/- 2.7%; 12 hr, 56.1% +/- 2.1%; 18 hr, 34.2% +/- 1%; 24 hr, 18.1% +/- 2.2%) compared to hypothermic groups (P < 0.001). The survival rate for the profound hypothermic group was significantly reduced (P < 0.01) compared to other hypothermic groups (at 17 degrees C: 12 hr, 85.9% +/- 2.5%, 18 hr, 74.7% +/- 3.7%, 24 hr, 58.7% +/- 2.7%). Almost equal survival rates were observed among mild, moderate, and deep hypothermic groups following <18 hr exposure to hypoxia, but the deep hypothermic group showed a significantly higher survival rate (84.1% +/- 1.6%; P < 0.001) when subjected to hypoxia for 24 hr. In conclusion, hypothermia offers marked neuroprotection against hypoxia, but attenuation of neuronal cell death was less with profound hypothermia compared to mild, moderate, and deep hypothermia. Deep hypothermia affords maximal protection of neurons compared to mild and moderate hypothermia during long-lasting hypoxia (>18 hr).
许多实验和临床研究表明，低温对缺血性损伤具有脑保护作用。由于关于低温神经保护存在许多相互矛盾的报道，我们进行了这项细胞研究，以确定在缺血性损伤的不同时间（6 - 24小时）实现最大神经保护的最佳温度或温度范围。将培养的Wistar大鼠皮质神经元在特定时间和温度下（37℃正常体温、32℃轻度低温、27℃中度低温、22℃深度低温和17℃极深度低温）暴露于缺氧环境。通过评估显微照片上的存活神经元来评估神经元的存活率。与低温组相比，正常体温组培养的神经元存活率显著降低（6小时，80.3%±2.7%；12小时，56.1%±2.1%；18小时，34.2%±1%；24小时，18.1%±2.2%）（P < 0.001）。与其他低温组相比，极深度低温组的存活率显著降低（P < 0.01）（在17℃时：12小时，85.9%±2.5%，18小时，74.7%±3.7%，24小时，58.7%±2.7%）。在缺氧暴露<18小时后，轻度、中度和深度低温组的存活率几乎相等，但在缺氧24小时时，深度低温组的存活率显著更高（84.1%±1.6%；P < 0.001）。总之，低温对缺氧具有显著的神经保护作用，但与轻度、中度和深度低温相比，极深度低温时神经元细胞死亡的减轻程度较小。在长时间缺氧（>18小时）期间，与轻度和中度低温相比，深度低温能为神经元提供最大程度的保护。
