Inhibition of Transient Receptor Potential Vanilloid 1 Attenuates Blood-Brain Barrier Disruption after Traumatic Brain Injury in Mice.

Abstract:

:Transient receptor potential vanilloid 1 (TRPV1) is expressed widely in the central nervous system and is activated by various stimuli. Inhibiting TRPV1 has neuroprotective effects in cerebral ischemia. The role of inhibiting TRPV1 to maintain blood-brain barrier (BBB) integrity after traumatic brain injury (TBI) remains unclear, however. Therefore, we investigated the effects of capsazepine-mediated TRPV1 inhibition on the BBB in a mouse model of TBI. Adult male C57BL/6 mice underwent controlled cortical impact injury and received capsazepine (1 μmol/kg body weight, twice daily, intraperitoneally) until sacrifice. Further, mouse brain microvascular endothelial (bEnd.3) cells were cultured and underwent biaxial stretch injury to investigate the mechanisms underlying the protective effects of capsazepine. The TRPV1 expression was upregulated in the pericontusional area after TBI, peaking at 24 h post-TBI. Capsazepine-treated mice demonstrated decreased brain edema (p = 0.010), Evans Blue extravasation (p = 0.001), tissue hemoglobin levels (p = 0.002), and loss of tight junction proteins (p = 0.016 ZO-1 expression; p = 0.013 occludin expression) after TBI compared with the vehicle-treated group. Capsazepine significantly alleviated early-stage apoptosis by attenuating activation of JNK, P38, and caspase-3, resulting in a protective effect on the level of ZO-1 in bEnd.3 cells after stretch injury. We conclude that the expression of TRPV1 is upregulated after TBI, and inhibition of TRPV1 attenuated disruption of the BBB in a mouse model of TBI, at least partly, through its antiapoptotic effects on brain endothelial cells. Blocking TRPV1 may be a promising pharmacotherapeutic intervention to protect against BBB disruption after TBI.

journal_name

J Neurotrauma

journal_title

Journal of neurotrauma

authors

Yang DX,Jing Y,Liu YL,Xu ZM,Yuan F,Wang ML,Geng Z,Tian HL

doi

10.1089/neu.2018.5942

subject

Has Abstract

pub_date

2019-04-15 00:00:00

pages

1279-1290

issue

8

eissn

0897-7151

issn

1557-9042

journal_volume

36

pub_type

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