Chu Ting-Ting, Sun Chen, Zheng Yong-Hui, Gao Wen-Ying, Zhao Lin-Lin, Zhang Jing-Yu
Department of Neurology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of General Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
CNS Neurosci Ther. 2025 Feb;31(2):e70153. doi: 10.1111/cns.70153.
This study aimed to investigate the impact of ischemic stroke (IS) on sleep homeostasis and circadian rhythms in rats, as well as the underlying mechanisms.
The middle cerebral artery occlusion model was employed to induce IS in rats. Sixty young and sixty aged rats were randomly divided into six groups for experiments. Neurological function was assessed using the Garcia score, and infarct size was evaluated through 2,3,5-triphenyltetrazolium chloride staining. Sleep-wake cycles were monitored by implanting electrodes into the neck muscles to record electroencephalograms and electromyograms. Parameters such as sleep latency, waking time, non-rapid eye movement (NREM) sleeping, rapid eye movement sleeping, NREM delta power, and waking theta power were measured. Serum cortisol and melatonin levels were measured using enzyme-linked immunosorbent assay. Gene and protein expression of circadian regulators period 1 (Per1) and cryptochrome 1 (Cry1) in the pineal gland were assessed using real-time quantitative reverse transcription polymerase chain reaction and western blot.
Compared to the sham groups, IS-induced rats showed a decrease in Garcia scores and an increase in cerebral infarction area. Besides, relative to young rats, aged rats exhibited more severe cerebral infraction damage, lower melatonin levels, higher cortisol levels, disrupted sleep-wake cycles, and altered gene and protein expression levels of Per1 and Cry1 in the pineal gland.
IS can lead to neurological impairments and brain damage, with aged rats showing more severe effects. IS also disturbs melatonin and cortisol levels, affects sleep homeostasis, and results in disordered Per1 and Cry1 gene and protein expression levels. These findings underscore the role of circadian disruption and stress response in the pathology of IS, especially in aging populations.
本研究旨在探讨缺血性中风（IS）对大鼠睡眠稳态和昼夜节律的影响及其潜在机制。
采用大脑中动脉闭塞模型诱导大鼠发生IS。将60只年轻大鼠和60只老年大鼠随机分为6组进行实验。使用Garcia评分评估神经功能，通过2,3,5-三苯基四氮唑氯化物染色评估梗死面积。通过将电极植入颈部肌肉以记录脑电图和肌电图来监测睡眠-觉醒周期。测量睡眠潜伏期、清醒时间、非快速眼动（NREM）睡眠、快速眼动睡眠、NREMδ功率和清醒θ功率等参数。使用酶联免疫吸附测定法测量血清皮质醇和褪黑素水平。使用实时定量逆转录聚合酶链反应和蛋白质印迹法评估松果体中昼夜节律调节因子周期蛋白1（Per1）和隐花色素1（Cry1）的基因和蛋白表达。
与假手术组相比，IS诱导的大鼠Garcia评分降低，脑梗死面积增加。此外，与年轻大鼠相比，老年大鼠表现出更严重的脑梗死损伤、更低的褪黑素水平、更高的皮质醇水平、睡眠-觉醒周期紊乱以及松果体中Per1和Cry1的基因和蛋白表达水平改变。
IS可导致神经功能障碍和脑损伤，老年大鼠的影响更为严重。IS还会扰乱褪黑素和皮质醇水平，影响睡眠稳态，并导致Per1和Cry1基因及蛋白表达水平紊乱。这些发现强调了昼夜节律紊乱和应激反应在IS病理过程中的作用，尤其是在老年人群中。
