Window of opportunity of cerebral hypothermia for postischemic white matter injury in the near-term fetal sheep
Window of opportunity of cerebral hypothermia for postischemic white matter injury in the near-term fetal sheep
复制标题
DOI：
10.1097/01.wcb.0000123904.17746.92
复制
发表时间：
2004-08-01
影响因子：
6.3
通讯作者：
Gunn, TJ
中科院分区：
文献类型：
--
作者：
Roelfsema, V;Bennet, L;Gunn, TJ
复苏后脑低温在实验制剂中始终具有神经保护作用；然而，它对白质损伤的影响尚不清楚。近期未麻醉胎羊可逆性脑缺血模型的建立。我们研究了脑低温（胎儿硬膜外温度从39.4 +/- 0.1℃降至30 ~ 33℃）在缺血后不同时间诱导并持续72小时对缺血后矢状旁白质5层损伤的影响。再灌注90分钟内开始冷却与假性冷却相比，脑回内白质中生物活性少突胶质细胞显著增加（每场41 +/- 20 vs 18 +/- 11， P < 0.05），髓鞘碱性蛋白密度增加，活化caspase-3表达减少（14 +/- 12 vs 91 +/- 51）。P < 0.05)。与假性冷却相比，反应性小胶质细胞被严重抑制（4 +/- 6 vs 38 +/- 18, P < 0.05），对星形胶质细胞数量没有影响。当冷却延迟到再灌注后5.5小时时，对少突胶质细胞的损失没有显著影响（每场24 +/- 12）。总之，低温可以有效地保护缺血后的白质，但只有在损伤后早期开始。保护作用与激活caspase-3和反应性小胶质细胞的表达减少密切相关。
Postresuscitation cerebral hypothermia is consistently neuroprotective in experimental preparations; however, its effects on white matter injury are poorly understood. Using a model of reversible cerebral ischemia in unanesthetized near-term fetal sheep. we examined the effects of cerebral hypothermia (fetal extradural temperature reduced from 39.4 +/- 0.1degreesC to between 30 and 33degreesC), induced at different times after reperfusion and continued for 72 hours after ischemia, on injury in the parasagittal White matter 5 clays after ischemia. Cooling started Within 90 minutes of reperfusion was associated with a significant increase in bioactive oligodendrocytes in the intra-gyral White matter compared With sham cooling (41 +/- 20 vs 18 +/- 11 per field, P < 0.05), increased myelin basic protein density and reduced expression of activated caspase-3 (14 +/- 12 vs 91 +/- 51. P < 0.05). Reactive microglia were profoundly suppressed compared with sham cooling (4 +/- 6 vs 38 +/- 18 per field, P < 0.05) with no effect on numbers of astrocytes. When cooling was delayed until 5.5 hours after reperfusion there was no significant effect on loss of oligodendrocytes (24 +/- 12 per field). In conclusion, hypothermia can effectively protect white matter after ischemia, but only if initiated early after the insult. Protection was closely associated with reduced expression of both activated caspase-3 and of reactive microglia.