Hypothermia attenuates apoptosis and protects contact
Hypothermia attenuates apoptosis and protects contact
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低温可减弱细胞凋亡并保护接触
DOI：
10.1002/jnr.23418
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Asou H,
中科院分区：
文献类型：
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作者：
Ichinose M;Kamei Y;Iriyama T;Imada S;Seyama T;Toshimitsu M;Asou H,
脑室周围白质软化症（PVL）是早产儿脑损伤的主要形式，其特征在于由缺氧缺血（HI）诱导的髓鞘前少突胶质细胞（pre-OL）的广泛损失和功能障碍。治疗性低温是足月新生儿HI脑病的标准治疗，不适用于早产儿，因为其安全性和有效性尚未确定。在这里，我们研究了低温抑制PVL中前OLs损伤的有效性和机制。对于体内研究，6日龄大鼠接受左颈动脉结扎，然后在低温或常温条件下暴露于6%氧气1小时。低温可抑制髓鞘碱性蛋白（MBP）的丢失。对于体外研究，在常温或低温条件下对原代前OL培养物进行氧-葡萄糖剥夺（OGD），随后加入背根神经节神经元。低温可抑制前OLs的凋亡，尽管低温可特异性下调21.5-和17-kDa MBP mRNA的表达，但与常温相比，OGD后的表达恢复上级。OGD导致MBP分布紊乱，磷酸化21.5-kDa MBP水平降低，并干扰与神经元接触的能力，所有这些都通过低温恢复。在OGD期间和之后用U0126药理学抑制ERK 1/2磷酸化分别显著降低低温对细胞凋亡和髓鞘形成的保护作用。这些数据表明，磷酸化的外显子2（21.5-和可能的17-kDa）MBP亚型可能在髓鞘形成中发挥关键作用，低温减弱细胞凋亡，并通过ERK 1/2磷酸化保持OL和神经元之间的接触。© 2014 Wiley Periodicals，Inc.
Periventricular leukomalacia (PVL) is a major form of brain injury among preterm infants, which is characterized by extensive loss and dysfunction of premyelinating oligodendrocytes (pre‐OLs) induced by hypoxia–ischemia (HI). Therapeutic hypothermia, which is a standard treatment for term infants with HI encephalopathy, is not indicated for preterm infants because its safety and effect have not been established. Here we investigate the effectiveness and mechanism of hypothermia for the inhibition of pre‐OLs damage in PVL. For in vivo studies, 6‐day‐old rats underwent left carotid artery ligation, followed by exposure to 6% oxygen for 1 hr under hypothermic or normothermic conditions. The loss of myelin basic protein (MBP) was inhibited by hypothermia. For in vitro studies, primary pre‐OLs cultures were subjected to oxygen–glucose deprivation (OGD) under normothermic or hypothermic conditions, and dorsal root ganglion neurons were subsequently added. Hypothermia inhibited apoptosis of pre‐OLs, and, despite specific downregulation of 21.5‐ and 17‐kDa MBP mRNA expression during hypothermia, recovery of the expression after OGD was superior compared with normothermia. OGD caused disarrangement of MBP distribution, decreased the levels of phosphorylated 21.5‐kDa MBP, and disturbed the capacity to contact with neurons, all of which were restored by hypothermia. Pharmacological inhibition of ERK1/2 phosphorylation with U0126 during and after OGD significantly reduced the protective effects of hypothermia on apoptosis and myelination, respectively. These data suggest that phosphorylated exon 2‐containing (21.5‐ and possibly 17‐kDa) MBP isoforms may play critical roles in myelination and that hypothermia attenuates apoptosis and preserves the contact between OLs and neurons via ERK1/2 phosphorylation. © 2014 Wiley Periodicals, Inc.