The Effect of Physical, Biochemical, and Electrical Culture Conditions on Articular Chondrocytes Used for Cartilage Tissue Engineering: A Narrative Review.

The function of adrenal gland is regulated by a tightly controlled neuroendocrine system involving the hypothalamic-pituitary-adrenal (HPA) axis and the renin-angiotensin-aldosterone system (RAAS), nervous system inputs, and local molecular pathways that together coordinate hormone production to maintain homeostasis, respond to stress, and regulate metabolism, blood pressure, and immune response (Herman et al. ; Charmandari et al. ; Correa et al. ). The sympathoadrenal system is a fundamental component of the rapid stress response, integrating the sympathetic nervous system with adrenal medullary function to coordinate a “fight-or-flight” reaction. Preganglionic sympathetic neurons innervating the adrenal gland in the rat are primarily located in the intermediolateral horn of the spinal cord, extending roughly from Th1 to L1 segments (Kesse et al. ). However, traumatic spinal cord injury (SCI) can significantly disrupt the descending autonomic innervation of the adrenal gland, profoundly impacting hormonal output and consequently immune function. The degree and type of autonomic dysfunction depend on the spinal level and completeness of the spinal cord lesion (Hou and Rabchevsky ). Thus, the finely tuned hormonal and immune balance regulated by the sympathoadrenal system after spinal cord trauma is significantly weakened. Angiotensin II, a key peptide hormone of the RAAS, best known for its role in regulating blood pressure and fluid balance, also plays a fundamental role in the neuroendocrine stress response through modulating the HPA axis. There is evidence for a bidirectional relationship between angiotensin II and the HPA axis, especially under pathological conditions (Kakehi et al. ). Although both major angiotensin II receptors have been reported, predominantly AT receptors are present throughout the HPA axis, including the hypothalamus (notably the paraventricular nucleus), anterior pituitary, and adrenal cortex (Leong et al. ). Through activation of AT, angiotensin II stimulates corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) secretion (Saavedra ), enhances adrenal glucocorticoid synthesis (Carey ; Saavedra and Armando ), and amplifies sympathetic outflow mechanisms (Feng et al. ) that collectively can contribute to immunosuppression and neuroimmune dysregulation following SCI (Lucin et al. ). The AT receptor is highly expressed in the adrenal medulla (Saavedra and Armando ), where it can influence catecholamine secretion in response to angiotensin II (Harada et al. ). The presence of the AT receptor mRNA in other HPA axis tissues was detected, but their functional role in modulating the axis is less prominent. SCI can disrupt the balance of the RAAS, favoring a more proinflammatory profile and increasing the activity of the angiotensin II/AT receptor axis (Zhang et al. ). The spleen plays a critical role in the immune response and serves as a significant source of inflammatory cells that can influence spinal cord pathology and systemic immune function after SCI. Angiotensin II is a potent immunomodulator in the spleen, influencing lymphocyte activation, cytokine production, and monocyte mobilization through AT receptor signaling (Sánchez-Lemus et al. ). The AT receptors are predominantly expressed in the red pulp of the spleen, where a large reservoir of monocytes and macrophages resides. Activation of AT receptors on splenic monocytes by angiotensin II promotes their recruitment out of the spleen into circulation, contributing to inflammation in distant tissues (Wang et al. ). This finding underlies the spleen´s important role in angiotensin II-driven inflammation and immune regulation.