School of Medicine, Ministry of Education, College of Life Science, Nankai University, Tianjin, PR China.
J Neurotrauma. 2009 Oct;26(10):1695-706. doi: 10.1089/neu.2008.0519.
This study investigates the influence of heat stress preconditioning on cognitive outcome for rats with diffuse axonal injury (DAI), and attempts to examine the underlying mechanisms. Wistar rats were divided into four groups: rats subjected to heat stress preconditioning 24 h before induction of DAI (n = 10; HSDAI group), a DAI alone group (n = 10), a heat stress alone group (n = 10), and a sham-injury group (n = 10). From day 14 post-injury, the rats' learning abilities and memory were tested using the Morris water maze (MWM) task, followed by long-term potentiation (LTP) recording of the hippocampus. In addition, hematoxylin and eosin staining (H&E) and immunohistochemical staining (IHC) were conducted to determine the presence of brain lesions and expression of heat shock protein 70 (HSP70) at 24 h, and on days 14 and 20 post-injury. The rats in the DAI group displayed impaired MWM performance and attenuated LTP compared to the sham group (p < 0.05); the rats in the HSDAI and HS groups showed significant improvement in both MWM and LTP compared with the DAI group (p < 0.05), and no significant differences with the sham group (p > 0.05). Following injury, retraction balls, shrunken neurons, and HSP70 expression were visible in the brains of rats from the DAI and HSDAI groups; recovery was expedited in the rats belonging to the HSDAI group, as these pathological changes were alleviated, coincident with higher expression of HSP70. The rats' abilities for learning and memory were impaired following DAI; this may be due to the disconnection of brain regions, damage to neurons in the hippocampus, and a decrease in synaptic plasticity. Heat stress preconditioning is able to significantly attenuate this cognitive impairment, possibly mediated by the neuroprotective effect of HSP70.
本研究旨在探讨热应激预处理对弥漫性轴索损伤（DAI）大鼠认知结果的影响，并试图探讨其潜在机制。Wistar 大鼠分为四组：热应激预处理 24 小时后诱导 DAI 的大鼠（n = 10；HSDAI 组）、单纯 DAI 组（n = 10）、单纯热应激组（n = 10）和假损伤组（n = 10）。伤后第 14 天，采用 Morris 水迷宫（MWM）任务测试大鼠的学习能力和记忆能力，然后记录海马长时程增强（LTP）。此外，在伤后 24 小时、第 14 天和第 20 天，进行苏木精和伊红染色（H&E）和免疫组织化学染色（IHC），以确定脑损伤和热休克蛋白 70（HSP70）的表达。与假损伤组相比，DAI 组大鼠的 MWM 表现受损，LTP 减弱（p < 0.05）；HSDAI 和 HS 组大鼠的 MWM 和 LTP 均明显改善，与 DAI 组相比差异有统计学意义（p < 0.05），与假损伤组相比差异无统计学意义（p > 0.05）。损伤后，DAI 和 HSDAI 组大鼠的大脑中可见回缩球、缩小的神经元和 HSP70 的表达；HSDAI 组大鼠的恢复加快，这些病理变化减轻，HSP70 的表达增加。DAI 后大鼠的学习和记忆能力受损；这可能是由于脑区连接中断、海马神经元损伤和突触可塑性降低所致。热应激预处理能够显著减轻这种认知障碍，可能是通过 HSP70 的神经保护作用介导的。
