School of Medical Biology, South Ural State University , Chelyabinsk , Russia.
Laboratory for Regulatory Mechanisms of Stress and Adaptation, Institute of General Pathology and Pathophysiology , Moscow , Russia.
J Appl Physiol (1985). 2018 Sep 1;125(3):931-937. doi: 10.1152/japplphysiol.01123.2017. Epub 2018 Jun 21.
Nonpharmacological treatments of stress-induced disorders are promising, since they enhance endogenous stress defense systems, are free of side effects, and have few contraindications. The present study tested the hypothesis that intermittent hypoxia conditioning (IHC) ameliorates behavioral, biochemical, and morphological signs of experimental posttraumatic stress disorder (PTSD) induced in rats with a model of predator stress (10-day exposure to cat urine scent, 15 min daily followed by 14 days of stress-free rest). After the last day of stress exposure, rats were conditioned in an altitude chamber for 14 days at a 1,000-m simulated altitude for 30 min on day 1 with altitude and duration progressively increasing to 4,000 m for 4 h on day 5. PTSD was associated with decreased time spent in open arms and increased time spent in closed arms of the elevated X-maze, increased anxiety index, and increased rate of freezing responses. Functional and structural signs of adrenal cortex degeneration were also observed, including decreased plasma concentration of corticosterone, decreased weight of adrenal glands, reduced thickness of the fasciculate zone, and hydropic degeneration of adrenal gland cells. The thickness of the adrenal fasciculate zone negatively correlated with the anxiety index. IHC alleviated both behavioral signs of PTSD and morphological evidence of adrenal cortex dystrophy. Also, IHC alone exerted an antistress effect, which was evident from the increased time spent in open arms of the elevated X-maze and a lower number of rats displaying freezing responses. Therefore, IHC of rats with experimental PTSD reduced behavioral signs of the condition and damage to the adrenal glands. NEW & NOTEWORTHY Intermittent hypoxia conditioning (IHC) has been shown to be cardio-, vaso-, and neuroprotective. For the first time, in a model of posttraumatic stress disorder (PTSD), this study showed that IHC alleviated both PTSD-induced behavioral disorders and functional and morphological damage to the adrenal glands. Also, IHC alone exerted an antistress effect. These results suggest that IHC may be a promising complementary treatment for PTSD-associated disorders.
非药物治疗应激相关障碍有很大的前景，因为它们可以增强内源性应激防御系统，没有副作用，并且禁忌症很少。本研究测试了一个假设，即间歇性低氧预处理（IHC）可以改善应激诱导的创伤后应激障碍（PTSD）大鼠的行为、生化和形态学的变化，该模型采用的是捕食者应激（10 天暴露于猫尿气味，每天 15 分钟，然后 14 天无应激休息）。在应激暴露的最后一天，大鼠在海拔模拟室中进行 14 天的预处理，第 1 天在 1000 米的高度进行 30 分钟，海拔和时间逐渐增加到第 5 天的 4000 米高度进行 4 小时。PTSD 与在高架 X 迷宫的开放臂中花费的时间减少和在封闭臂中花费的时间增加有关，焦虑指数增加，冻结反应的频率增加。还观察到肾上腺皮质退化的功能和结构迹象，包括皮质酮的血浆浓度降低、肾上腺重量降低、束状带变薄和肾上腺细胞水肿变性。肾上腺束状带的厚度与焦虑指数呈负相关。IHC 缓解了 PTSD 的行为表现和肾上腺皮质萎缩的形态证据。此外，IHC 本身就具有抗应激作用，这表现在高架 X 迷宫的开放臂中花费的时间增加和表现出冻结反应的大鼠数量减少。因此，实验性 PTSD 大鼠的 IHC 减轻了这种疾病的行为表现和对肾上腺的损害。 新的和值得注意的是，间歇性低氧预处理（IHC）已被证明具有心脏保护、血管保护和神经保护作用。这是首次在创伤后应激障碍（PTSD）模型中，本研究表明 IHC 不仅缓解了 PTSD 引起的行为障碍，还缓解了肾上腺的功能和形态损伤。此外，IHC 本身就具有抗应激作用。这些结果表明，IHC 可能是一种有前途的 PTSD 相关疾病的辅助治疗方法。
