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 (AT1) and type 2 (AT2) receptor signaling affects many pathophysiological processes, including TBI. AT1R is highly expressed in neurons and astrocytes. The upregulation of AT1R mediates the effects of angiotensin II (ANG II) including release of proinflammatory cytokines, cell death, oxidative stress, and vasoconstriction. The AT2R, 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 AT1R and activating AT2R for treatment of TBI with variable outcomes. In this review, we summarize studies that describe the role of brain RAS signaling, through AT1R and AT2R in TBI, and its modulation with pharmacological approaches.
Keywords: ANG II receptor antagonists; Angiotensin II receptor type 1; Angiotensin II receptor type 2; Neuroprotection; Renin angiotensin system; Traumatic brain injury.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.