School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264005, PR China.
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264005, PR China.
Biomed Pharmacother. 2022 Jul;151:113146. doi: 10.1016/j.biopha.2022.113146. Epub 2022 May 26.
Approximately, one in three ischemic stroke survivors suffered from depression, namely, post-stroke depression (PSD). PSD affects functional rehabilitation and may lead to poor quality of life of patients. There are numerous explanations about the etiologies of PSD. Here, we speculated that PSD are likely to be the result of specific changes in brain pathology. We hypothesized that the stroke-induced hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis plays an important role in PSD. Stroke initiates a complex sequence of events in neuroendocrine system including HPA axis. The HPA axis is involved in the pathophysiology of depression, especially, the overactivity of the HPA axis occurs in major depressive disorder. This review summarizes the possible etiologies of PSD, focusing on the stroke-induced activation of HPA axis, mainly including the stress followed by severe brain damage and the proinflammatory cytokines release. The role of hyperactive of HPA axis in PSD was discussed in detail, which includes the role of high level corticotropin-releasing hormone in PSD, the effects of glucocorticoids on the alterations in specific brain structures, the expression of enzymes, excitotoxicity, the change in intestinal permeability, and the activation of microglia. The relationship between neuroendocrine regulation and inflammation was also described. Finally, the therapy of PSD by regulating HPA axis, neuroendocrine, and immunity was discussed briefly. Nevertheless, the change of HPA axis and the occurring of PSD maybe interact and promote on each other, and future investigations should explore this hypothesis in more depth.
大约三分之一的缺血性脑卒中幸存者患有抑郁症，即脑卒中后抑郁（PSD）。PSD 影响功能康复，并可能导致患者生活质量下降。PSD 的病因有很多解释。在这里，我们推测 PSD 可能是大脑病理学特定变化的结果。我们假设脑卒中引起的下丘脑-垂体-肾上腺（HPA）轴活性增强在 PSD 中起重要作用。脑卒中引发了包括 HPA 轴在内的神经内分泌系统的一系列复杂事件。HPA 轴参与了抑郁症的病理生理学，特别是在重度抑郁症中，HPA 轴过度活跃。本综述总结了 PSD 的可能病因，重点介绍了脑卒中引起的 HPA 轴激活，主要包括应激后严重脑损伤和促炎细胞因子释放。详细讨论了 HPA 轴活性增强在 PSD 中的作用，包括 CRH 水平升高在 PSD 中的作用、糖皮质激素对特定脑结构改变的影响、酶的表达、兴奋性毒性、肠道通透性的变化和小胶质细胞的激活。还描述了神经内分泌调节与炎症之间的关系。最后，简要讨论了通过调节 HPA 轴、神经内分泌和免疫来治疗 PSD。然而，HPA 轴的变化和 PSD 的发生可能相互作用并相互促进，未来的研究应该更深入地探讨这一假设。
