Yamashita K, Eguchi Y, Kajiwara K, Ito H
Department of Neurosurgery, Yamaguchi University School of Medicine, Japan.
Stroke. 1991 Dec;22(12):1574-81. doi: 10.1161/01.str.22.12.1574.
The purpose of the present study is to determine the effect of mild hypothermia on the synthesis of ubiquitin, an important protein for maintenance of cell viability, in the hippocampal neurons following transient cerebral ischemia.
Transient ischemia was induced by occluding both common carotid arteries for 5 minutes. In experiment 1, the animals were divided into four groups according to the rectal and scalp temperatures during ischemia: the normothermia group and the graded hypothermia A, B, and C groups (n = 9 per group). CA1 neuronal density was assessed at 7 days after ischemia. In experiment 2, the animals were divided into two groups designated the normothermia and the hypothermia groups (n = 6 per group). The presence of ubiquitin was examined by immunohistochemistry at 6, 24, and 48 hours after transient ischemia in various regions of the hippocampus.
In experiment 1, the mean +/- SEM neuronal density per millimeter was 12 +/- 1 in the normothermia group and 126 +/- 25, 225 +/- 10, and 214 +/- 9 in hypothermia groups A, B, and C, respectively. Mild hypothermia in groups B and C, in which the brain temperature was below 33 degrees C, ameliorated markedly the extent of ischemic neuronal damage in the CA1 sector (p less than 0.01). In experiment 2, ubiquitin immunoreactivity had disappeared in all regions of the hippocampus at 6 hours after ischemia and showed no subsequent recovery in the CA1 pyramidal neurons under normothermic conditions. Under hypothermic conditions, however, it had recovered significantly in the CA1 pyramidal neurons at 24 and 48 hours after ischemia (p less than 0.01).
We conclude that mild hypothermia, in which the brain temperature is below 33 degrees C, markedly improves the ischemic delayed neuronal damage in the CA1 sector, and that increased ubiquitin synthesis and protein ubiquitination could be one essential part of the protective mechanism afforded by mild hypothermia against delayed neuronal death.
本研究旨在确定轻度低温对短暂性脑缺血后海马神经元中泛素合成的影响，泛素是维持细胞活力的一种重要蛋白质。
通过夹闭双侧颈总动脉5分钟诱导短暂性缺血。在实验1中，根据缺血期间的直肠和头皮温度将动物分为四组：正常体温组以及分级低温A、B、C组（每组n = 9）。在缺血7天后评估CA1神经元密度。在实验2中，将动物分为两组，即正常体温组和低温组（每组n = 6）。在短暂性缺血后6、24和48小时，通过免疫组织化学检查海马不同区域泛素的存在情况。
在实验1中，正常体温组每毫米的平均±标准误神经元密度为12±1，低温组A、B、C分别为126±25、225±10和214±9。B组和C组的轻度低温（脑温低于33℃）显著改善了CA1区缺血性神经元损伤的程度（p < 0.01）。在实验2中，缺血6小时后海马所有区域的泛素免疫反应性均消失，在正常体温条件下，CA1锥体神经元中泛素免疫反应性随后未恢复。然而，在低温条件下，缺血后24和48小时，CA1锥体神经元中的泛素免疫反应性显著恢复（p < 0.01）。
我们得出结论，脑温低于33℃的轻度低温可显著改善CA1区缺血性延迟神经元损伤，并且泛素合成增加和蛋白质泛素化可能是轻度低温对延迟性神经元死亡提供保护机制的一个重要部分。
