Citation

Rui Q, Ni H, Lin X, Zhu X, Li D, Liu H, Chen G. Exp. Neurol. 2019; ePub(ePub): ePub.

Affiliation

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

Copyright

(Copyright © 2019, Elsevier Publishing)

DOI

10.1016/j.expneurol.2019.113044

PMID

31454490

Abstract

The astrocyte-endothelial cell interaction is crucial for normal brain homeostasis and blood-brain barrier (BBB) disruption in pathological conditions. However, the mechanism by which astrocytes control BBB integrity, especially after traumatic brain injury (TBI), remains unclear. Here, we present evidence that astrocyte-derived fatty acid-binding protein 7 (FABP7), a differentiation- and migration-associated molecule, may function as a modulator of BBB permeability in a rat weight-drop model of TBI. Immunohistochemical analysis revealed that TBI induced increased expression of FABP7 in astrocytes, accompanied by caveolin-1 (Cav-1) upregulation in endothelial cells. Administration of recombinant FABP7 significantly ameliorated TBI-induced neurological deficits, brain edema, and BBB permeability, concomitant with upregulation of endothelial Cav-1 and tight junction protein expression, while FABP7 knockdown resulted in the opposite effects. Furthermore, pretreatment with daidzein, a specific inhibitor of Cav-1, reversed the inhibitory effects of recombinant FABP7 on matrix metalloproteinase (MMP)-2/9 expression and abolished its BBB protection after TBI. Altogether, these findings suggest that astrocyte-derived FABP7 upregulation may represent an endogenous protective response to BBB disruption partly mediated through a Cav-1/MMP signaling pathway following TBI.

Copyright © 2018. Published by Elsevier Inc.

Language: en

Keywords

Astrocyte; Blood-brain barrier; Caveolin-1; FABP7; Traumatic brain injury