Hypobaric Hypoxia (HH) is known to cause oxidative stress in the brain that leads to spatial memory deficit and neurodegeneration. For decades therapeutic hypothermia is used to treat global and focal ischemia in preserving brain functions that proved to be beneficial in humans and rodents. Considering these previous reports, the present study was designed to establish the therapeutic potential of hypothermia preconditioning on HH induced spatial memory, biochemical and morphological changes in adult rats. Male Sprague Dawley rats were exposed to HH (7620 m, ~ 282 mmHg) for 1, 3 and 7 days with and without hypothermic preconditioning. Spatial learning memory was assessed by Morris water maze (MWM) test along with evaluation of hippocampal pyramidal neuron damage by histological study. Oxidative stress was measured by studying the levels of nitric oxide (NO), reactive oxygen species (ROS), lipid peroxidation (LPO), oxidized and reduced glutathione (GSSG and GSH). Results of MWM test indicated prolonged path length and latency to reach the platform in HH groups that regained to normal in cold pre-treated groups. A likely neurodegeneration was evident in HH groups that lessen in the cold pre-treated groups. Hypothermic preconditioning prevented spatial memory impairment and neurodegeneration in animals subjected to HH via decreasing the NO, ROS and LPO compared to control animals. The GSH level and GSH/GSSG ratio was found to be higher in preconditioned animals as compared to respective HH exposed animals, indicative of redox scavenging and restoration of hippocampal neuronal structure as well as spatial memory. Therefore, hypothermic preconditioning improves spatial memory deficit by reducing HH induced oxidative stress and hippocampal neurodegeneration, hence can be used as a multi-target prophylactic measure to combat HH induced neurodegeneration.

已知低压缺氧 (HH) 会在大脑中引起氧化应激，从而导致空间记忆缺陷和神经退行性变。几十年来，低温治疗被用于治疗全局性和局灶性缺血，以保护被证明对人类和啮齿动物有益的大脑功能。考虑到这些先前的报道，本研究旨在确定低温预处理对成年大鼠 HH 诱导的空间记忆、生化和形态学变化的治疗潜力。雄性 Sprague Dawley 大鼠在有和没有低温预处理的情况下暴露于 HH (7620 m, ~ 282 mmHg) 1、3 和 7 天。莫里斯水迷宫评估空间学习记忆(MWM) 测试以及通过组织学研究评估海马锥体神经元损伤。通过研究一氧化氮(NO)、活性氧(ROS)、脂质过氧化的水平来测量氧化应激(LPO)、氧化型和还原型谷胱甘肽 (GSSG 和 GSH)。MWM 测试结果表明，HH 组到达平台的路径长度和潜伏期延长，而在冷预处理组中恢复正常。在冷预处理组中减轻的 HH 组中可能的神经退行性变很明显。与对照动物相比，低温预处理通过减少 NO、ROS 和 LPO 来预防经受 HH 的动物的空间记忆障碍和神经变性。与相应的 HH 暴露动物相比，预处理动物的 GSH 水平和 GSH/GSSG 比值更高，表明氧化还原清除和海马神经元结构以及空间记忆的恢复。所以，