Fan Lir-Wan, Lin Shuying, Pang Yi, Lei Manping, Zhang Feng, Rhodes Philip G, Cai Zhengwei
Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Behav Brain Res. 2005 Nov 30;165(1):80-90. doi: 10.1016/j.bbr.2005.06.033. Epub 2005 Sep 2.
Bilateral carotid artery occlusion (BCAO) followed by exposure to a hypoxic condition (8% oxygen for 10 or 15 min) was performed in postnatal day 4 SD rats. Brain injury and myelination changes were examined on postnatal day 21 (P21) and tests for neurobehavioral toxicity were performed from P3 to P21. BCAO followed by 10 or 15 min hypoxic insult resulted in mild and severe, respectively, brain injury, reduction in mature oligodendrocytes and tyrosine hydroxylase positive neurons and impaired myelination as indicated by decreased myelin basic protein immunostaining in the P21 rat brain. Hypoxia-ischemia also affected physical development (body weight gain and eye opening) and neurobehavioral performance, such as righting reflex, wire hanging maneuver, cliff avoidance, locomotor activity, gait analysis, responses in the elevated plus-maze and passive avoidance. BCAO followed by 15 min of hypoxia caused more severely impaired neurobehavioral performance as compared with BCAO followed by 10 min of hypoxia in the rat. The overall results demonstrate that hypoxia-ischemia-induced brain injury not only persists, but also is linked with neurobehavioral deficits in juvenile rats. The present data also indicate that the degree of brain injury and the deficits of neurobehavioral performance in the rat are dependent on the hypoxic-ischemic condition, i.e., the exposure time to hypoxia.
在出生后第4天的SD大鼠中进行双侧颈动脉闭塞（BCAO），随后使其暴露于低氧环境（8%氧气，持续10或15分钟）。在出生后第21天（P21）检查脑损伤和髓鞘形成变化，并在出生后第3天至第21天进行神经行为毒性测试。BCAO后再进行10或15分钟的低氧损伤，分别导致轻度和重度脑损伤，成熟少突胶质细胞和酪氨酸羟化酶阳性神经元减少，并且如P21大鼠脑内髓鞘碱性蛋白免疫染色降低所示，髓鞘形成受损。缺氧缺血还影响身体发育（体重增加和睁眼）以及神经行为表现，如翻正反射、悬线试验、避崖试验、运动活动、步态分析、高架十字迷宫反应和被动回避。与BCAO后再进行10分钟低氧的大鼠相比，BCAO后再进行15分钟低氧导致大鼠神经行为表现受损更严重。总体结果表明，缺氧缺血诱导的脑损伤不仅持续存在，而且与幼鼠的神经行为缺陷有关。目前的数据还表明，大鼠脑损伤的程度和神经行为表现缺陷取决于缺氧缺血条件，即低氧暴露时间。
