LAUSR

0123456789();: In 1978, Wylie Vale and colleagues isolated corticotropin-releasing hormone (CRH) from sheep hypothalami and published a study of the modulation of stress-induced adrenocorticotropic hormone (ACTH) release by CRH. The study suggested that endogenous CRH has a physiological role in regulating ACTH secretion. In subsequent studies, the Vale team confirmed the peptide sequence of CRH, produced a CRH-specific antibody, identified central CRH receptors (and cloned the subtypes CRHR1 and CRHR2) and identified new family members of the urocortin family (1, 2 and 3). Since these publications, numerous fruitful findings from scientists around the world have supported the hypothesis that CRH from the hypothalamus, via the CRH receptors, controls every cell in the body in terms of maintenance and adaptive responses for homeostasis. In 2003, Peter Agre (Nobel Laureate in Chemistry) discovered the water channel (aquaporin, AQP) and answered the question of how water crosses cell membranes. In 2014, Chen et al. showed that hypoxia (8% O2 for 8 h) induces cerebral oedema and neuronal apoptosis, and also increases the expression of CRH, CRHR1 and AQP4 in the rat cortex. CRH, acting through CRHR1, triggers cAMP–PKA signalling and intracellular Ca2+ release; in addi tion, PKCε contributes to the phos phorylation and expression of AQP4 to enhance water influx into astrocytes. In 2020, Kitchen et al. found that the cell-surface abundance of AQP4 increases in response to hypoxia-induced (5% O2 for 6 h) cell swelling in a calmodulin-dependent manner. Calmodulin binds to the AQP4 C-terminus, causing a specific conformational change and driving AQP4 cell-surface localization. In a rat model of spinal cord injury, inhibition of calmodulin with trifluoperazine inhibits AQP4 localization in astrocytes to the blood–spinal cord barrier, eliminates oedema in the central nervous system and accelerates functional recovery.