The effect of hypoxic-ischemic brain injury in perinatal rats on the abundance and proteolysis of brevican and NG2
The effect of hypoxic-ischemic brain injury in perinatal rats on the abundance and proteolysis of brevican and NG2
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DOI：
10.1016/j.expneurol.2004.11.021
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发表时间：
2005-05-01
影响因子：
5.3
通讯作者：
Gottschall, PE
中科院分区：
文献类型：
--
作者：
Aya-ay, J;Mayer, J;Gottschall, PE
少突胶质细胞（OL）祖细胞对围产期缺氧/缺血（H-I）特别敏感，导致髓鞘形成减少和白色物质纤维束的发育减弱。Brevican是由OL及其祖细胞在活跃发育髓鞘形成之前和期间分泌的聚集性硫酸软骨素蛋白聚糖（CSPG），而神经胶质抗原2（NG 2）是由早期OL祖细胞产生的跨膜CSPG。虽然这两种蛋白聚糖都与OL的成熟有关，但尚不清楚它们是否因新生儿H-I脑损伤而改变。因此，我们研究了H-I后新生大鼠海马中短蛋白聚糖和NG 2丰度和蛋白水解的变化的时间过程。在单侧颈动脉结扎和暴露于缺氧的标准H-I模型中，H-I后4天，大多数大鼠幼仔的大脑皮质、海马和纹状体的同侧顶叶和颞叶区域的空洞性梗死明显。H-I后1天和14天（相对于对侧），同侧海马中总可提取短蛋白聚糖的丰度显著降低。在这些时候，总G1蛋白水解片段的短蛋白聚糖是较低的同侧海马和蛋白酶产生的短蛋白聚糖片段的水平显着减少在OL丰富的海马伞。H-I后第1天和第4天海马NG 2水平也较低，但在第14天与对侧无差异。由于短蛋白聚糖、短蛋白聚糖GI片段和NG 2损失发生在进行性细胞死亡和梗死出现的时间附近，因此可能是H-I快速诱导细胞应答，该细胞应答主动地从海马基质中消耗这些蛋白聚糖。虽然这种损失的机制尚不清楚，但它似乎是该过程中的早期事件，可能涉及凋亡性细胞死亡和/或组织损伤。(c)2004爱思唯尔公司All rights reserved.
Oligodendrocyte (OL) progenitor cells are particularly susceptible to perinatal hypoxia/ischemia (H-I) resulting in decreased myelination and attenuated development of white matter fiber tracts. Brevican is an aggregating chondroitin sulfate proteoglycan (CSPG) secreted by OLs and their progenitors prior to and during active developmental myelination whereas neuron-glia antigen 2 (NG2) is a transmembrane CSPG produced by early OL progenitors. Although both proteoglycans are associated with maturation of OLs, it is not known if they are altered by H-I brain injury in the neonate. We have therefore examined the time course of changes in brevican and NG2 abundance and proteolysis in the neonatal rat hippocampus after H-I. In a standard H-I model of unilateral carotid artery ligation and exposure to hypoxia, a cavitary infarct involving the ipsilateral parietal and temporal regions of cerebral cortex, hippocampus, and striatum of most rat pups was clearly evident 4 days after H-I. The abundance of total extractable brevican was markedly reduced in the ipsilateral hippocampus at 1 and 14 days after H-I (relative to the contralateral side). At these times, the total G1 proteolytic fragment of brevican was lower in the ipsilateral hippocampus and the level of a protease-generated brevican fragment was significantly diminished in the OL-rich hippocampal fimbria. Hippocampal NG2 levels were also lower at I and 4 days after H-I, but were not different from the contralateral side at 14 days. Since brevican, brevican GI fragment, and NG2 loss occur around the time of progressive cell death and the appearance of the infarct, it may be that H-I rapidly induces a cellular response that actively depletes these proteoglycans from the hippocampal matrix. While the mechanism of this loss is unclear, it would appear to be an early event in the process that could be involved in apoptotic cell death and/or tissue injury. (c) 2004 Elsevier Inc. All rights reserved.