Dexmedetomidine Preconditioning Ameliorates Inflammation and Blood–Spinal Cord Barrier Damage After Spinal Cord Ischemia-Reperfusion Injury by Down-Regulation High Mobility Group Box 1-Toll-Like Receptor 4-Nuclear Factor κB Signaling Pathway. Issue 2 (15th January 2019)

• Record Type: Journal Article
• Authors: Liu, Jiao; Zhang, Shuangshuang; Fan, Xiaona; Yuan, Fen; Dai, Jun; Hu, Ji
• Is Part Of: Spine. Volume 44:Issue 2(2019)
• Publication Date: 2019-01-15
• Subjects: blood–spinal cord barrier -- dexmedetomidine -- high mobility group box 1 -- inflammatory response -- ischemia-reperfusion injury -- nuclear factor κB -- spinal cord -- Toll-like receptor 4; Spine -- Abnormalities -- Periodicals; Spine -- Diseases -- Periodicals; Spine -- Surgery -- Periodicals; 616.73005
• DOI: 10.1097/BRS.0000000000002772
• Languages: English
• ISSNs: 0362-2436

Abstract

Abstract : Study Design: To evaluate the effect of Dexmedetomidine (Dex) on the inflammatory response and the integrity of blood–spinal cord barrier (BSCB) after spinal cord ischemia-reperfusion injury (SCIRI). Objective: To investigate the role of Dex in spinal cord I/R, particularly in the high mobility group box 1-toll-like receptor 4-nuclear factor κB (HMGB1-TLR4-NF-κB) pathway and the integrity of BSCB. Summary of Background Data: High mobility group box 1 (HMGB1) has been identified as a key mediator for the inflammatory response after spinal cord injury. Toll-like receptor 4-nuclear factor κB (TLR4-NF-κB) signaling pathway is the downstream of HMGB1. Dex preconditioning could protect the spinal cord from I/R injury by inhibiting HMGB1 and stabilizing the integrity of BSCB. But its underlying mechanism is not fully understood. Methods: Forty-eight male Japanese white rabbits were randomly assigned to three groups (16 rabbits/group): sham, I/R, and Dex + I/R. The hind-limb motor function was assessed at 12 hours intervals for 48 hours after reperfusion using the modified Tarlov scale score. The expression of HMGB1, TLR4, NF-κB, and tumor necrosis factor α (TNF-α) was evaluated by real-time polymerase chain reaction (RT-PCR) and Western blot. The permeability of BSCB was examined via Evans blue (EB) extravasation. Results: Compared with sham group, spinal cord I/R increased the expression of HMGB1, TLR4, NF-κB, and TNF-α as well as the permeability of BSCB ( P < 0.05). Spinal cord I/R induced the decline of the score of hind-limb motor function ( P < 0.01). Preconditioning with Dex attenuated the up-regulation of the express of HMGB1, TLR4, NF-κB, TNF-α, and stabilized the permeability of BSCB ( P < 0.05). Dex preconditioning also improved the hiatopathological outcome and the motor function ( P < 0.01). Conclusion: Dex preconditioning may inhibit the inflammatory response and stabilize the integrity of BSCB at least partially by inhibiting the HMGB1-TLR4-NF-κB signaling pathway to protect spinal cord from ischemia/reperfusion injury. Level of Evidence: 2 Abstract : It is reported Dexmedetomidine (Dex) preconditioning could protect the spinal cord from I/R injury but without fully understood mechanism. This study aims to investigate the role of Dex in spinal cord I/R, particularly in the high mobility group box 1-toll-like receptor 4-nuclear factor B pathway and the integrity of blood-spinal cord barrier.