PAK1 contributes to cerebral ischemia/reperfusion injury by regulating the blood-brain barrier integrity

Ming Huang; Jinshun Zhang; Mengwei Li; Haowei Cao; Qiuju Zhu; Dejun Yang

doi:10.1016/j.isci.2023.107333

PAK1 contributes to cerebral ischemia/reperfusion injury by regulating the blood-brain barrier integrity

iScience. 2023 Jul 11;26(8):107333. doi: 10.1016/j.isci.2023.107333. eCollection 2023 Aug 18.

Authors

Ming Huang¹, Jinshun Zhang¹, Mengwei Li¹, Haowei Cao¹, Qiuju Zhu¹, Dejun Yang¹

Affiliation

¹ Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou 221004, China.

Abstract

Globally, stroke is one of the leading causes of death and significant contributors to disability. Gaining a thorough comprehension of the underlying pathogenic processes is essential for stroke treatment and prevention. In this study, we investigated the role of p21-activated kinase 1 (PAK1) in stroke by using oxygen-glucose deprivation (OGD) and transient middle cerebral artery occlusion and reperfusion (tMCAO/R) models. We reported that focal ischemia and reperfusion affect the PAK1 expression and activity levels. We further demonstrated that PAK1 is responsible for the endothelial hyperpermeability that occurs in the early stages of ischemia and reperfusion. Additionally, inhibition of PAK1 was discovered to alleviate blood-brain barrier disruption and protect against brain injury induced by tMCAO/R. Mechanistically, we provide the evidence that PAK1 regulates the formation of stress fibers and expression of surface junctional proteins. Together, our findings reveal a pathogenic function of PAK1 in stroke.

Keywords: Health sciences; Molecular biology; Neuroscience.