EXPERIMENTAL STUDY ON GLIAL RESPONSES TO NEONATAL HYPOXIC/ISCHEMIC ENCEPHALOPATYH

在研究项目的第一年，我们研究了新生大鼠对缺氧/缺血性脑病的细胞反应。结扎7日龄大鼠左颈总动脉，将幼鼠置于缺氧室。免疫细胞化学检测神经胶质反应。结果表明，发育中的小胶质细胞是新生儿期对缺氧/缺血损伤作出反应的首要胶质细胞。星形胶质细胞反应发生较晚。这些神经胶质反应可能在神经元变性和/或组织重塑中起重要作用。在研究项目的第二年，我们研究了血小板衍生生长因子（PDGF） b链和PDGF β受体在缺氧/缺血性损伤的未成熟大脑中的表达。免疫细胞化学和northern分析分别检测PDGF b链及其特异性受体蛋白和mRNA的表达。结果表明，新生儿缺氧/缺血损伤可诱导缺氧后神经元中PDGF b链和β受体的表达上调。然而，这种上调在大多数神经元中是试探性的。梗死周围神经元的亚致死性损伤诱导PDGF b链和β受体的持续和长期上调。PDGF b链分子可能通过自分泌和旁分泌机制在发育中的缺氧/缺血性脑损伤中发挥神经保护因子的作用。

In the first year of the research project, we have investigated the cellular responses to hypoxic/ischemic encephalopathy in the neonatal rats. Left common carotid artery of the 7-day-old rats was ligated, and the pups were placed in a hypoxic chamber. The glial responses were examined using the immunocytochemistry. The results indicate that developing microglia are the first and principle glial element that responds to hypoxic/ischemic injury during the neonatal period. The astrocyte respose occurs later. These glial responses may play important roles in the neuronal degeneration and/or tissue remodeling.In the second year of the research project, expressions of platelet-derived growth factor (PDGF) B-chain and PDGF beta-receptor have been investigated in the immature brains with hypoxic/ischemic injury. The expressions of PDGF B-chain and its specific receptor protein and mRNA were examined using an immunocytochemistry and a northern analysis, respcetively. The results indicate that neonatal hypoxic/ischemic insult induces the upregulation of PDGF B-chain and beta-receptor expressions in neurons immediately after hypoxia. This upregulation, however, was tentative in most neurons. Sublethal damage on neurons in peri-infarct areas induces the sustained and long-term upregulations of PDGF B-chain and beta-receptor. PDGF B-chain molecules may act as a neuroprotective factor in developing brain with hypoxic/ischemic injury through autocrine and paracrine mechanisms.