The role of angiotensin II type 1 receptor pathway in cerebral ischemia‒reperfusion injury: Implications for the neuroprotective effect of ARBs

• Published in: Neuroprotection (Chichester, England. Online) Vol. 2; no. 2; pp. 100 - 119
• Main Authors: Huang, Shuhan, Zhang, Meng
• Format: Journal Article
• Language: English
• Published: 01.06.2024
• Subjects: acute ischemic stroke; angiotensin II type 1 receptor blocker; ischemia–reperfusion injury; neuroinflammation; oxidative stress
• ISSN: 2770-7296; 2770-730X
• DOI: 10.1002/nep3.45

Cerebral ischemia–reperfusion (I/R) injury is a crucial factor that impacts the prognosis of recanalization therapy for acute ischemic stroke (AIS). It has been found that the brain renin–angiotensin system, especially the angiotensin II type 1 receptor (AT1R) pathway, plays a significant role in cerebral I/R injury. This pathway is involved in processes such as oxidative stress, neuroinflammation, apoptosis, and it affects cerebrovascular autoregulation and the maintenance of blood–brain barrier. AT1R blocker (ARB), widely used as an antihypertensive agent, has demonstrated stroke prevention capabilities in numerous prospective studies, independent of its antihypertensive characteristics. Studies focusing on neurological diseases like Alzheimer's disease, Parkinson's disease, and cognitive impairment have confirmed that ARBs exhibit neuroprotective effects and aid in improving neurological functions. Preclinical studies have shown that ARBs can reduce infarct volume and brain edema, inhibit multiple signaling pathways associated with I/R injury, restore energy levels in damaged brain regions, and rescue the penumbra by promoting neovascularization in cerebral I/R models. These findings suggest that ARBs have potential to become a novel category of neuroprotecting agents for clinical treatment of AIS. Therefore, this review primarily provides a theoretical foundation and practical evidence for the future clinical utilization of ARBs as neuroprotective agents following reperfusion therapy for AIS. It outlines the role of cerebral I/R injury through the AT1R pathway and highlights the research progress made on ARBs in I/R models. The performance of AT1R activation on ischemia–reperfusion injury. Highlights The mechanism of ischemia–reperfusion injury in acute ischemic stroke is elaborated from the perspective of brain RAS. The preclinical studies of several ARBs in ischemia–reperfusion injury in recent years are introduced. It is clear that ARB regulates brain RAS to alleviate ischemia–reperfusion injury and reveals its guiding role for the future research on neuroprotection in acute ischemic stroke.