Ang II-mediated effects on BBB integrity in psychiatric and neurological disorders

Alterations of the blood-brain barrier (BBB) integrity and permeability is a critical factor implicated in several brain pathologies, including stress-related and neurodegenerative disorders. Growing evidence suggests that the renin-angiotensin system (RAS), a key regulator of vascular homeostasis, also plays a significant role in the pathogenesis and progression of these neurological conditions. Notably, angiotensin II (Ang II) and its downstream signaling pathways contribute to the modulation of BBB properties, directly impacting brain health. While the pharmacological targeting of the RAS has been extensively explored and shown to alleviate neurological and psychiatric symptoms, the molecular mechanisms underlying the complex crosstalk between Ang II and the BBB in these disorders remain insufficiently understood. In this review, we highlight the current literature supporting the contribution of Ang II and its type 1 and type 2 receptor-mediated signaling pathways to the structural and functional integrities of the BBB. We systematically gathered and analyzed relevant studies describing how Ang II disrupts BBB function across various pathological contexts, with an emphasis on stress-related disorders, neurodegenerative diseases and traumatic brain injury (TBI). This consolidated understanding helps refine future research questions and guide hypothesis-driven studies to better dissect the mechanisms underlying the relationship between Ang II signaling and BBB vulnerability.