title: Acid fibroblast growth factor preserves blood-brain barrier integrity by activating the PI3K-Akt-Rac1 pathway and inhibiting RhoA following traumatic brain injury.
abstract: The blood-brain barrier (BBB) plays important roles in the recovery of traumatic brain injury (TBI) which is a major factor contributing to cerebral edema. Acid fibroblast growth factor (aFGF) contributes to maintain vascular integrity and restores nerve function. However, whether aFGF protects BBB following TBI remains unknown. The purpose of this study was to determine whether exogenous aFGF preserves BBB integrity by activating the PI3K-Akt-Rac1 pathway and inhibiting RhoA after TBI. BBB permeability was assessed using evans blue dye and fluorescein isothiocyanate dextran fluorescence. Neurofunctional tests, such as the garcia test, were conducted in a blinded fashion, and protein expression was evaluated via western blotting and immunofluorescence staining. Our results showed that aFGF improved neurofunctional deficits, preserved BBB integrity, and up-regulated tight junction proteins and adherens junction proteins 24 h after experimental TBI. However, the PI3K/Akt inhibitor LY294002 reversed the protective effects of aFGF on neurofunctional deficits and junction protein expression and significantly suppressed p-Akt and GTP-Rac1 activity. Furthermore, aFGF administration significantly decreased GTP-RhoA expression in the treated group compared with the vehicle group, while PI3K/Akt inhibition increased GTP-RhoA expression. Similar results were observedin vitro, as aFGF exerted protective effects on endothelial cell integrity by up-regulating junction proteins and PI3K-Akt-Rac1 pathway and down-regulating RhoA expression under oxygen-glucose deprivation/reoxygenation (OGD) conditions. These data suggest that exogenous aFGF reduces RhoA activity in part by activating the PI3K-Akt-Rac1 signaling pathway, thus improving neurofunctional deficits and preserving BBB integrity after TBI.
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University Ningbo 315300, Zhejiang, China.
authors.forename: Fenzan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University Ningbo 315300, Zhejiang, China.
authors.forename: Zaifeng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University Ningbo 315300, Zhejiang, China.
authors.forename: Chonghui
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University Ningbo 315300, Zhejiang, China.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University Ningbo 315300, Zhejiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University Ningbo 315300, Zhejiang, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zuo
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Emergency, The Second Affiliated Hospital, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
authors.forename: Daqing
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Nursing, Cangnan People's Hospital Wenzhou 325800, Zhejiang, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University Ningbo 315300, Zhejiang, China.
authors.forename: Xinlong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University Ningbo 315300, Zhejiang, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wei
keywords: RhoA; Traumatic brain injury; acid fibroblast growth factor; blood-brain barrier; junction protein