VEGF regulates the blood‑brain barrier through MMP‑9 in a rat model of traumatic brain injury

Exp Ther Med. 2022 Oct 24;24(6):728. doi: 10.3892/etm.2022.11664. eCollection 2022 Dec.

Abstract

Blood-brain barrier (BBB) damage is closely related to morbidity and mortality in patients with traumatic brain injury (TBI). Inhibition of VEGF effectively protects BBB integrity in clinical ischemic stroke. Protecting BBB integrity, reducing brain edema and alleviating post-TBI secondary brain injury are key to a favorable patient prognosis. MMP-9 affects BBB integrity by destroying the tight junction of vascular endothelial cells and inhibiting the transport and enzymatic systems. The present study aimed to examine the possible interplay between VEGF and MMP-9 in TBI. A TBI model was established in 87 male Sprague-Dawley rats. Reverse transcription-quantitative PCR, western blotting, wet-dry brain edema assessment, TUNEL and Fluoro-Jade C staining were performed to analyze the brain tissue samples of the rats. The results showed that compared with in the Sham group rats, the mRNA and protein expression levels of VEGF and MMP-9 were increased at 24 h post-TBI. After bevacizumab treatment, BBB permeability and nerve cell apoptosis were markedly reduced. In conclusion, the present study revealed a potential role for TBI-associated VEGF and MMP-9 upregulation in BBB disruption and nerve damage post-TBI.

Keywords: MMP-9; VEGF; apoptosis; blood-brain barrier; traumatic brain injury.

Grants and funding

Funding: The present study was funded by the Zhangjiagang Health Youth Science and Technology Project (grant no. ZJGQNKJ202011), the Zhangjiagang Science and Technology Support Project (grant nos. ZKS2020, ZKS2029) and the Suzhou Science and Technology Development Project (grant nos. SKJY2021001 and SKJY2021003).