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

[ Vol. 17 , Issue. 4 ]

Author(s):

Yan Lu*, Zhendong Xu*, Fuyi Shen, Rong Lin, Haibing Li, Xiang Lv* and Zhiqiang Liu*   Pages 471 - 479 ( 9 )

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.

Affiliation:

Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, Department of Anesthesiology and Critical Care Medicine, Shanghai Ninth Peopole’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204



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