TBI remains a leading cause of mortality and long-term disability worldwide, characterized by complex secondary cascades of injury due to inflammation, oxidative stress, blood-brain barrier (BBB) disruption, excitotoxicity, and neuronal apoptosis. While clinical practice and research have focused primarily on supportive care and intracranial pressure management, there is a growing interest in pharmacological agents that can prevent secondary injury mechanisms. Among these, ARBs, traditionally used for cardiovascular conditions, have emerged as potential neuroprotective agents in TBI.

Preclinical models of TBI have demonstrated that blood-brain barrier-crossing ARBs reduce cerebral edema, improve BBB integrity, reduce dysfunctional cerebrovascular remodeling, and attenuate neuroinflammatory markers by controlling angiotensin II and AT1 & 2 receptors. AT1 receptors and PPAR-γ have an inverse effect: by inhibiting AT1 receptors, there’s an upregulation of PPAR-γ. PPAR-γ reduces proinflammatory cytokines via gene level inhibition (NFkB and AP-1), mitigating the effects of excessive inflammation, oxidative stress, and apoptosis in various tissues, including the brain. 

ARBs represent a promising class of neuroprotective agents in the management of TBI due to their multifaceted roles in modulating neuroinflammation, oxidative stress, and vascular dysfunction. Future research should prioritize prospective clinical trials, biomarker-guided treatment strategies, and investigation into the synergistic effects of ARBs with other neuroprotective agents.