A prognostic study on the effect of post-traumatic stress disorder on cerebral ischaemia reperfusion-induced stroke

Previous studies have been established that persons who experienced a stroke are soon likely to develop several anxiety disorders. In which one of the major anxiety disorders is Post-traumatic Stress Disorder (PTSD). Yet, the likelihood of PTSD in conjunction with cerebral stroke has not been well described. Hence, we evaluated the impact of PTSD on cerebral stroke in rodents subjected to single prolonged stress (SPS) and bilateral common carotid artery occlusion (BCCAo), respectively. The relation between PTSD and cerebral stroke is evaluated by performing behavioural, biochemical, histopathological, and brain lesion area measurement studies. Interestingly, SPS + BCCAo induction increased behavioural abnormalities like cognitive impairment and anxiety-like behaviour compared to SPS and BCCAo groups alone. Motor impairment was also observed in SPS + BCCAo rats compared to SPS rats, whereas no change with BCCAo rats. Furthermore, increased brain tissue MDA, acetylcholinesterase, and decreased SOD, catalase, and GSH were observed in SPS + BCCAo subjected rats compared to SPS and BCCAo rats alone. Additionally, SPS + BCCAo induction considerably increased the plasma corticosterone levels and caused severe neurotransmitter alterations. The SPS + BCCAo exposure significantly increased the brain lesion area in comparison with BCCAo rats. Moreover, severe histopathological alterations were observed in the hippocampus (CA1) of SPS + BCCAo rats compared to SPS and BCCAo rats alone. In conclusion, our study results suggested that SPS-induced PTSD may aggravate the BCCAo induced cerebral ischaemia-reperfusion injury.

既往研究表明，脑卒中患者后续罹患多种焦虑障碍的风险显著升高。创伤后应激障碍（Post-traumatic Stress Disorder, PTSD）即为这类主要焦虑障碍之一，但目前关于脑卒中合并PTSD的发病情况仍未得到充分阐明。为此，本研究分别采用单次延长应激（single prolonged stress, SPS）与双侧颈总动脉闭塞（bilateral common carotid artery occlusion, BCCAo）两种造模方式处理啮齿类动物，以此评估PTSD对脑卒中的影响。本研究通过行为学检测、生化指标分析、组织病理学观察及脑梗死体积测定等实验方法，评估PTSD与脑卒中的关联。值得注意的是，相较于单独SPS组与单独BCCAo组，SPS+BCCAo联合造模组的行为异常更为突出，具体表现为认知功能障碍与焦虑样行为；相较于SPS组，该联合组大鼠还出现了运动功能损伤，而BCCAo组大鼠未观察到此类变化。此外，相较于单独SPS组与单独BCCAo组，SPS+BCCAo联合组大鼠的脑组织丙二醛（malondialdehyde, MDA）、乙酰胆碱酯酶（acetylcholinesterase, AChE）水平显著升高，而超氧化物歧化酶（superoxide dismutase, SOD）、过氧化氢酶（catalase, CAT）与谷胱甘肽（glutathione, GSH）水平显著降低。同时，SPS+BCCAo联合造模可显著升高血浆皮质酮水平，并引发严重的神经递质紊乱。相较于BCCAo组，SPS+BCCAo联合组的脑梗死面积显著增大。此外，相较于单独SPS组与单独BCCAo组，SPS+BCCAo联合组大鼠的海马CA1区出现了更为严重的组织病理学改变。综上，本研究结果表明，SPS诱导的PTSD可加重BCCAo所致的脑缺血再灌注损伤。