Manifestation of renin angiotensin system modulation in traumatic brain injury.

Traumatic brain injury (TBI) alters brain function and is a crucial public health concern worldwide. TBI triggers the release of inflammatory mediators (cytokines) that aggravate cerebral damage, thereby affecting clinical prognosis. The renin angiotensin system (RAS) plays a critical role in TBI pathophysiology. RAS is widely expressed in many organs including the brain. Modulation of the RAS in the brain via angiotensin type 1 (AT) and type 2 (AT) receptor signaling affects many pathophysiological processes, including TBI. ATR is highly expressed in neurons and astrocytes. The upregulation of ATR mediates the effects of angiotensin II (ANG II) including release of proinflammatory cytokines, cell death, oxidative stress, and vasoconstriction. The ATR, mainly expressed in the fetal brain during development, is also related to cognitive function. Activation of this receptor pathway decreases neuroinflammation and oxidative stress and improves overall cell survival. Numerous studies have illustrated the therapeutic potential of inhibiting ATR and activating ATR for treatment of TBI with variable outcomes. In this review, we summarize studies that describe the role of brain RAS signaling, through ATR and ATR in TBI, and its modulation with pharmacological approaches.