The extended renin-angiotensin system: a promising target for traumatic brain injury therapeutics

摘要

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Global assessments estimate that over 27 million cases of TBI occur annually, resulting in over 8 million years lived with disability (GBD?2016?Dementia Collaborators, 2019). Over 30 clinical trials have failed to show efficacy in TBI, and patients are currently left without any promising therapeutic options (Villapol et al., 2015). The pathophysiology of TBI is commonly divided into primary and secondary injuries. Primary injury refers to the parenchymal damage that occurs as an immediate consequence of acute kinetic energy transfer to the brain (i.e., membrane rupture, hemorrhage, axotomy, etc.). Secondary injury encompasses the deleterious molecular and cellular responses that occur in response to the primary injury in the minutes, hours or days following. The search for therapeutics that mitigate the effects of the secondary injury and/or assist endogenous repair processes remains a large focus of TBI research (Umschweif et al., 2014; Villapol et al., 2015; Janatpour et al., 2019).