Brief exposure to hyperoxia depletes the glial progenitor pool and impairs functional recovery after hypoxic-ischemic brain injury
Brief exposure to hyperoxia depletes the glial progenitor pool and impairs functional recovery after hypoxic-ischemic brain injury
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DOI：
10.1038/jcbfm.2008.15
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发表时间：
2008-07-01
影响因子：
6.3
通讯作者：
Kernie, Steven G.
中科院分区：
文献类型：
--
作者：
Koch, Joshua D.;Miles, Darryl K.;Kernie, Steven G.
婴儿和儿童缺氧缺血性脑损伤的模式提示白色物质发育区域的脆弱性，并且受伤的患者发展导致脑瘫和运动缺陷的髓鞘形成缺陷。再灌注加剧了这种损伤后发生的氧化应激，并可能损害恢复。缺氧缺血性损伤后的复苏通常使用100%氧气进行，这种做法可能会增加再灌注期间发生的氧化应激，并进一步损害已经受损的大脑。我们发现，短暂暴露（30分钟），以100%的氧气在再灌注过程中的组织学损伤的年轻小鼠后，单侧脑缺氧缺血，导致积累的氧化代谢产物硝基酪氨酸，并耗尽前少突胶质细胞胶质祖细胞存在于皮质。这种损伤可以通过抗氧化剂依布硒啉（一种谷胱甘肽过氧化物酶模拟物）的给药来逆转。此外，在100%氧气中恢复的小鼠具有更混乱的髓鞘形成模式，并发展出类似脑瘫的静态运动缺陷，并通过在钢丝悬挂和旋转杆运动测试中的显著更差的表现来表现。我们的结论是，暴露于100%的氧气在缺氧缺血性脑损伤后再灌注增加继发性神经损伤，耗尽发展中的胶质祖细胞，干扰髓鞘形成，并最终损害功能恢复。
Patterns of hypoxic-ischemic brain injury in infants and children suggest vulnerability in regions of white matter development, and injured patients develop defects in myelination resulting in cerebral palsy and motor deficits. Reperfusion exacerbates the oxidative stress that occurs after such injuries and may impair recovery. Resuscitation after hypoxic-ischemic injury is routinely performed using 100% oxygen, and this practice may increase the oxidative stress that occurs during reperfusion and further damage an already compromised brain. We show that brief exposure (30 mins) to 100% oxygen during reperfusion worsens the histologic injury in young mice after unilateral brain hypoxia-ischemia, causes an accumulation of the oxidative metabolite nitrotyrosine, and depletes preoligodendrocyte glial progenitors present in the cortex. This damage can be reversed with administration of the antioxidant ebselen, a glutathione peroxidase mimetic. Moreover, mice recovered in 100% oxygen have a more disrupted pattern of myelination and develop a static motor deficit that mimics cerebral palsy and manifests itself by significantly worse performance on wire hang and rotorod motor testing. We conclude that exposure to 100% oxygen during reperfusion after hypoxic-ischemic brain injury increases secondary neural injury, depletes developing glial progenitors, interferes with myelination, and ultimately impairs functional recovery.