Selective cortical alteration after hypoxic-ischemic injury in the very immature rat brain
Selective cortical alteration after hypoxic-ischemic injury in the very immature rat brain
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DOI：
10.1203/01.pdr.0000072517.01207.87
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发表时间：
2003-08-01
影响因子：
3.6
通讯作者：
Williams, C
中科院分区：
文献类型：
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作者：
Sizonenko, SV;Sirimanne, E;Williams, C
在极低出生体重儿（VLBW）中发现了发育中的白色物质中断的独特脑损伤。虽然缺氧缺血（HI）是一个因果关系的途径，脑白色物质损伤的发病机制在VLBW婴儿还没有完全了解。相关的小鼠模型将有助于调查的过程中，导致这些脑病变，使治疗策略的评价。出生后第3天（P3）大鼠处于皮质少突胶质细胞成熟和轴突生长的阶段，类似于极早产儿。我们的目的是描述P3时局灶性缺氧缺血性损伤对随后大脑发育的影响。3组P3 Wistar大鼠进行了研究：组I进行右侧颈动脉结扎，然后6%缺氧30分钟（HI），组2只颈动脉结扎，组3没有干预。在P21时，HI组的右侧皮质面积与对照组相比减少（p < 0.01）。背侧海马、纹状体和丘脑的大小没有显著变化。与对照组相比，HI动物的皮质有髓鞘面积减少（p < 0.01）。有髓轴突延伸到皮层的相应损失，深层皮层神经元和轴突结构明显中断。胶质细胞酸性蛋白免疫组化显示顶叶皮质深层有反应性胶质增生（P < 0.01）。中度HI损伤在未成熟的大鼠脑损害皮质生长，并导致皮质有髓轴突的选择性改变与持续的胶质细胞增生。单侧HI在P3诱导的这些改变与VLBW婴儿中发现的弥漫性白色病变具有神经病理学相似性。
Distinctive cerebral lesions with disruptions to the developing white matter are found in very low birth weight (VLBW) infants. Although hypoxia-ischemia (HI) is a causal pathway, the pathogenesis of cerebral white matter injury in the VLBW infant is not fully understood. Pertinent murine models would facilitate the investigation of the processes leading to these cerebral lesions and enable the evaluation of therapeutic strategies. Postnatal d 3 (P3) rats are at a stage of cortical oligodendroglial maturation and axonal outgrowth similar to very preterm infants. Our aim was to characterize the effects of a focal hypoxic-ischemic injury at P3 on subsequent cerebral development. Three groups of P3 Wistar rats were investigated: group I underwent right carotid ligation followed by 6% hypoxia for 30 min (HI), group 2 had carotid ligation only, and group 3 had no intervention. At P21, in the HI group, the right cortical area was reduced compared with controls (p < 0.01). There were no significant alterations in the size of the dorsal hippocampus, striatum, and thalamus. The cortical myelinated area was reduced in the HI animals compared with controls (p < 0.01). There was a corresponding loss of myelinated axons extending up into the cortex, with deep cortical neuronal and axonal architecture markedly disrupted. Glial fibrillary acidic protein immunohistology showed a reactive gliosis in the deep parietal cortex (p < 0.01). Moderate HI injury in the immature rat brain compromised cortical growth and led to a selective alteration of cortical myelinated axons with persistent gliosis. These alterations induced at P3 by unilateral HI share neuropathological similarities with the diffuse white matter lesions found in VLBW infants.