Comprehensive gene expression analysis of cerebral cortices from mature rats after neonatal hypoxic-ischemic brain injury

Neonatal hypoxic-ischemic (HI) encephalopathy can lead to severe brain damage and is a common cause of neurological handicaps in adulthood. To elucidate the molecular events occurring in cerebral cortices of mature rats (8 weeks old) after neonatal HI brain insult, we performed comprehensive gene expression and gene network analyses using a DNA microarray system (Agilent 4x44K). A rat model of neonatal HI encephalopathy (Rice model) was obtained by unilateral ligation of the common carotid artery of 7-day-old rats with hypoxia (exposure to 8% oxygen). Due to the HI insult-related breakdown of the ipsilateral hemisphere in the brain, RNAs were prepared from the contralateral cerebral cortices of 8-week-old rats and analyzed by DNA microarray. Biofunctional analysis of differentially regulated genes revealed that many upregulated genes were related to cell death signaling, such as the arachidonic acid cascade. In contrast, many downregulated genes were related to gene expression, reflecting progressive damage by the HI insult, even within the contralateral cerebral hemisphere.新生儿缺氧缺血性脑病（neonatal hypoxic-ischemic encephalopathy，简称HI）可引发严重脑损伤，亦是成年期神经系统残疾的常见诱因。为阐明新生儿HI脑损伤后，8周龄成年大鼠大脑皮层内发生的分子事件，本研究采用DNA微阵列系统（Agilent 4x44K）开展了全基因组表达与基因网络综合分析。本研究通过对7日龄大鼠实施单侧颈总动脉结扎，并暴露于8%氧气的缺氧环境，构建了新生儿HI脑病大鼠模型（莱斯模型，Rice model）。鉴于HI脑损伤会导致同侧大脑半球出现组织破坏，本研究从8周龄大鼠的对侧大脑皮层中提取RNA，通过DNA微阵列完成分析。对差异表达基因的生物功能分析显示，大量上调基因与细胞死亡信号通路相关，例如花生四烯酸级联反应；与之相反，多数下调基因则与基因表达调控过程相关，这一结果反映出即便在对侧大脑半球中，HI脑损伤仍会引发进行性脑损伤。