Propofol Protects Against TNF-α-induced Blood-brain Barrier Disruption via the PIM-1/eNOS/NO Pathway

Author(s): Yan Lu*, Zhendong Xu*, Fuyi Shen, Rong Lin, Haibing Li, Xiang Lv*, Zhiqiang Liu*

Journal Name: Current Neurovascular Research

Volume 17 , Issue 4 , 2020


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Abstract:

Background: The Inflammatory cytokine, tumor necrosis factor-α (TNF-α), disrupts blood-brain barrier (BBB). Propofol reportedly exerts an anti-inflammatory effect in the central nervous system.

Objective: We hypothesized that propofol could provide a protective effect against TNF-α-induced disruption in human cerebral microvascular endothelial cells (hCMEC/D3 cells) and explored the underlying mechanisms.

Methods: The hCMEC/D3 cell monolayers were pretreated with propofol, followed by TNF-α treatment. The integrity of BBB was reflected by assessing the trans-endothelial electrical resistance (TEER) and determining the expression of proteins within tight junctions (TJs). The effect of propofol on TNF-α-modulated nitric oxide production was measured by a nitrate reductase assay kit. The expression of ZO-1, claudin-5, occludin, TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), proviral-integration site for Moloney murine leukaemia virus (PIM)-1kinase, the phosphorylation of endothelial nitric oxide synthase at ser633 (peNOS-ser633) were detected by western blot.

Results: In hCMEC/D3 cells, TNF-α treatment markedly disrupted the integrity of BBB. Further, we found TNF-α treatment could increase the expression of PIM-1, then activate the phosphorylation of eNOS and induce the release of nitric oxide (NO). More importantly, we found that TNF- α-impaired BBB integrity could be reversed by propofol.

Conclusion: These results suggest that the PIM-1/eNOS/NO pathway plays a vital role, in which Propofol protects against TNF-α-induced blood-brain barrier disruption.

Keywords: Propofol, blood-brain barrier, postoperative cognitive dysfunction, TNF-α, interleukin, endothelial cells.

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Article Details

VOLUME: 17
ISSUE: 4
Year: 2020
Published on: 14 December, 2020
Page: [471 - 479]
Pages: 9
DOI: 10.2174/1567202617999200819142021
Price: $65

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