SYMPATHETIC INTEGRITY DETERMINES ANGIOTENSIN II RECEPTOR–MEDIATED NEUROENDOCRINE–IMMUNE RESPONSES AFTER SPINAL CORD INJURY

Spinal cord injury (SCI) disrupts descending sympathetic control of neuroendocrine and immune organs, leading to systemic complications. Because sympathetic pathways innervating the adrenal gland and spleen originate from defined thoracic segments, injuries at different levels distinctly compromise sympathoadrenal regulation and stress-axis feedback. This study aimed to determine how partial versus near-complete sympathoadrenal denervation after SCI shapes angiotensin II receptor signaling and associated neuroendocrine–immune responses. Using a rat compression model of severe SCI, time-dependent changes following low-thoracic injury (Th9) were analyzed over a 28-day survival period, while acute effects of high-thoracic injury (Th1) were assessed at 3 days post-injury. Angiotensin II receptor expression (AT1 and AT2) was quantitatively evaluated in components of the hypothalamic-pituitary-adrenal (HPA) axis and spleen, together with circulating angiotensin II and endocrine profiling including corticotropin-releasing hormone, adrenocorticotropic hormone, corticosterone, aldosterone, norepinephrine, and epinephrine. Th9 SCI induced sustained, tissue-specific remodeling of angiotensin II receptor expression within the HPA axis and spleen, largely independent of circulating angiotensin II and accompanied by dynamic alterations in adrenal steroidogenesis and catecholamine secretion. In contrast, Th1 SCI caused a marked suppression of angiotensin II receptor signaling, characterized by downregulation of angiotensin II receptors across HPA components and the spleen, and associated with reduced corticotropin-releasing hormone, aldosterone, and norepinephrine, preserved adrenocorticotropic hormone, and elevated corticosterone and epinephrine. These findings demonstrate that sympathetic innervation integrity is a critical determinant of angiotensin II receptor–mediated neuroendocrine-immune regulation after SCI, providing insight into level-dependent endocrine and immune dysfunction following spinal trauma.
Supported by VEGA No.2/0123/23 and APVV-22-0248