Hypoxic preconditioning improves long-term functional outcomes after neonatal hypoxia-ischemic injury by restoring white matter integrity and brain development
Hypoxic preconditioning improves long-term functional outcomes after neonatal hypoxia-ischemic injury by restoring white matter integrity and brain development
复制标题
缺氧预处理通过恢复白质完整性和大脑发育来改善新生儿缺氧缺血性损伤后的长期功能结果
DOI：
10.1111/cns.13102
复制
发表时间：
2019
影响因子：
5.5
通讯作者：
Zhang Wen-Ting
中科院分区：
文献类型：
--
作者：
Xu Ming-Yue;Wang Yang-Fan;Wei Peng-Ju;Gao Yan-Qin;Zhang Wen-Ting
目的新生儿缺氧缺血（H/I）可导致脑灰质和白色物质损伤，表现为神经元丢失、神经网络形成障碍、髓鞘形成迟缓和少突胶质祖细胞（OPCs）异常聚集。这些变化导致严重的神经功能缺损和死亡。亚致死量低氧预处理（HPC）对发育中的脑组织具有保护作用。然而，有限的证据是关于其对白色物质injuries.MethodsIn这项研究中，P6新生Sprague-道利大鼠进行常氧（21%O2）或HPC（7.8%O2）3小时，随后24小时后，H/I脑损伤。通过步态、翻正反射、足错和Morris水迷宫试验评估神经功能缺损。复合动作电位的胼胝体被记录在手术后35天，轴突髓鞘形成和神经功能之间的相关性determined.ResultsHypoxia预处理显着衰减H/I脑损伤在7天，并显着改善感觉运动和认知功能的表现H/I后35天。HPC提供的长期神经功能结局改善至少部分归因于少突胶质细胞祖细胞分化和成熟能力的恢复，小胶质细胞/巨噬细胞活化和神经炎症的改善，以及H/I后脑发育的持续。结论低氧预处理恢复H/I脑损伤后发育中脑的白色修复、发育和功能完整性。
AimsNeonatal hypoxia–ischemia (H/I) results in gray and white matter injury, characterized by neuronal loss, failure of neural network formation, retarded myelin formation, and abnormal accumulation of oligodendrocyte progenitor cells (OPCs). These changes lead to severe neurological deficits and mortality. Sublethal hypoxic preconditioning (HPC) can protect the developing brain against H/I. However, limited evidence is available concerning its effect on white matter injury.MethodsIn this study, P6 neonatal Sprague‐Dawley rats were subjected to normoxic (21% O2) or HPC (7.8% O2) for 3 hours followed 24 hours later by H/I brain injury. Neurological deficits were assessed by gait, righting reflex, foot fault, and Morris water maze tests. Compound action potential of the corpus callosum was recorded 35 days after surgery, and the correlation between axon myelination and neurological function was determined.ResultsHypoxic preconditioning significantly attenuated H/I brain injury at 7 days and remarkably improved both sensorimotor and cognitive functional performances up to 35 days after H/I. HPC‐afforded improvement in long‐term neurological outcomes was attributable, at least in part, to restoration of the differentiation and maturation capacity in oligodendrocyte progenitor cells, amelioration of microglia/macrophage activation and neuroinflammation, and continuation of brain development after H/I.ConclusionsHypoxic preconditioning restores white matter repair, development, and functional integrity in developing brain after H/I brain injury.