Effect of cerebral hypothermia and asphyxia on the subventricular zone and white matter tracts in preterm fetal sheep
Effect of cerebral hypothermia and asphyxia on the subventricular zone and white matter tracts in preterm fetal sheep
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DOI：
10.1016/j.brainres.2012.06.018
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发表时间：
2012-08-21
期刊：
影响因子：
2.9
通讯作者：
Gunn, Alistair Jan
中科院分区：
文献类型：
--
作者：
Barrett, Robert Daniel;Bennet, Laura;Gunn, Alistair Jan
实验性缺氧缺血后，长时间、中等程度的脑低温始终具有神经保护作用。我们之前已经证明，低温对早产儿大脑严重窒息后也有保护作用。然而，人们担心低温是否会抑制白质或室下区（SVZ）损伤的增殖反应。早产（0.7 妊娠）胎羊接受完全脐带闭塞 25 分钟，然后在闭塞或假冷却结束后 90 分钟至 70 小时进行脑低温（硬膜外温度从 39.4 +/- 0.3 降低至 29.5 +/- 2.6 摄氏度）。与假闭塞相比，正常体温闭塞对 CNPase+ 细胞没有影响，但脑回和脑室周围白质中 O4+ 少突胶质细胞丢失、裂解的 caspase-3 和 IB4+ microgjia (p < 0.05)，并且脑室周围白质中 KI67+ 细胞显着增加 (p < 0.05)。低温与 O4+ 细胞的显着保护有关，并抑制脑室周围白质中的 IB4+ 小胶质细胞和 KI67+ 细胞。窒息后 SVZ 中的星形胶质细胞、小胶质细胞、KI67+ 或 caspase-3+ 细胞没有显着变化。总之，这项研究为未成熟少突胶质细胞对胎羊中高度相关的损伤的选择性脆弱性提供了强有力的支持。尽管脑低温对白质的保护与白质束增殖减少有关，但它并不损害 SVZ 的增殖。 (C) 2012 Elsevier B.V. 保留所有权利。
Prolonged, moderate cerebral hypothermia is consistently neuroprotective after experimental hypoxia-ischemia. We have previously shown that hypothermia is also protective after profound asphyxia in the preterm brain. However, there is a concern whether hypothermia could suppress the proliferative response to injury in the white matter or subventricular zone (SVZ). Preterm (0.7 gestation) fetal sheep received complete umbilical cord occlusion for 25 min followed by cerebral hypothermia (extradural temperature reduced from 39.4 +/- 0.3 to 29.5 +/- 2.6 degrees C) from 90 min to 70 h after the end of occlusion or sham cooling. Occlusion-normothermia was associated with no effect on CNPase+ cells, but loss of O4+ oligodendrocytes, induction of cleaved caspase-3, and IB4+ microgjia in the gyral and periventricular white matter compared to sham-occlusion (p < 0.05), with a significant increase in KI67+ cells in the periventricular white matter (p < 0.05). Hypothermia was associated with significant protection of O4+ cells, with suppression of IB4+ microglia and KI67+ cells in the periventricular white matter. There was no significant change in astrocytes, microglia, KI67+, or caspase-3+ cells in the SVZ after asphyxia. In conclusion, this study provides strong support for the selective vulnerability of immature oligodendrocytes to a highly relevant insult in the fetal sheep. Although white matter protection with cerebral hypothermia was associated with reduced proliferation in the white matter tracts, it did not impair proliferation in the SVZ. (C) 2012 Elsevier B.V. All rights reserved.