Mishima Kenichi, Ikeda Tomoaki, Yoshikawa Tetsuya, Aoo Naoya, Egashira Nobuaki, Xia Yi X, Ikenoue Tsuyomu, Iwasaki Katsunori, Fujiwara Michihiro
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma 8-19-1, Fukuoka 814-0180, Japan.
Behav Brain Res. 2004 May 5;151(1-2):209-17. doi: 10.1016/j.bbr.2003.08.018.
We previously reported that rats exposed to neonatal hypoxic-ischemic (HI) insult showed selective and long-lasting learning and memory impairments in the plus maze, 8-arm radial maze, choice reaction time (CRT) task, and water maze, and that they showed severe brain injury to areas such as parietal cortex, hippocampus, striatum and thalamus. In this study, we examined the effects of hypothermia and hyperthermia on learning and memory deficits following neonatal HI insult. Seven-day-old Wistar rats were subjected to left carotid artery ligation followed by 2 h of hypoxia (8% O2/92% N2) under three different temperature conditions: 27 degrees C (hypothermia), 33 degrees C (normothermia) and 37 degrees C (hyperthermia) in temperature-controlled chambers. Hypothermia significantly reduced attentional deficits in the CRT task and spatial learning deficits in the water maze, and protected against severe brain injury in comparison with the control temperature. On the other hand, hyperthermia aggravated the behavioral deficits and brain injury. These outcomes clearly show that temperature regulation during HI insult plays an important role in the induction of behavioral and histological changes following neonatal HI insult in rats.
我们之前报道过,暴露于新生儿缺氧缺血(HI)损伤的大鼠在加迷宫、八臂辐射迷宫、选择反应时(CRT)任务和水迷宫中表现出选择性且持久的学习和记忆障碍,并且它们的顶叶皮质、海马体、纹状体和丘脑等区域出现了严重的脑损伤。在本研究中,我们研究了低温和高温对新生儿HI损伤后学习和记忆缺陷的影响。将7日龄的Wistar大鼠在三种不同温度条件下进行左颈动脉结扎,随后缺氧2小时(8% O₂/92% N₂):在温度控制箱中分别为27℃(低温)、33℃(正常体温)和37℃(高温)。与对照温度相比,低温显著减少了CRT任务中的注意力缺陷和水迷宫中的空间学习缺陷,并预防了严重的脑损伤。另一方面,高温加剧了行为缺陷和脑损伤。这些结果清楚地表明,HI损伤期间的温度调节在大鼠新生儿HI损伤后行为和组织学变化的诱导中起着重要作用。