Central neuroendocrine dysregulation in ischaemic stroke sequelae: pathophysiological mechanisms—a narrative review

Han Gong, Dan Liu, Xiang-Zheng Wang, Jia‐Sheng Rao, Xiao-Xia Du

Ischemic stroke (IS) prognosis is frequently compromised by secondary systemic and neuropsychiatric complications extending beyond the initial brain injury. The hypothalamic–pituitary–adrenal (HPA) axis, the primary neuroendocrine regulator, plays a pivotal yet underappreciated role in the pathogenesis of these sequelae. This review analyzes the adverse impact of HPA axis dysregulation on post-stroke outcomes across disease phases. In the acute phase, maladaptive glucocorticoid surges and circadian disruption drive metabolic disturbances, blood–brain barrier (BBB) breakdown leading to hemorrhagic transformation, and stroke-induced immunodepression that predisposes patients to pneumonia. In the chronic phase, persistent HPA hyperactivity, driven by impaired negative feedback and glucocorticoid receptors (GRs) resistance, induces structural remodeling in emotional and cognitive circuits. This serves as a shared pathophysiological mechanism underpinning post-stroke depression, anxiety, and cognitive impairment. Consequently, elucidating these neuroendocrine-immune interactions provides a novel pathophysiological framework for understanding post-stroke multidimensional complications.