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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

Liu, Jiao, MS; Zhang, Shuangshuang, MS; Fan, Xiaona, MS; Yuan, Fen, BS; Dai, Jun, BS; Hu, Ji, BS

doi: 10.1097/BRS.0000000000002772
BASIC SCIENCE
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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

Department of Anesthesiology, Liyuan Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Address correspondence and reprint requests to Ji Hu, BS, Department of Anesthesiology, Liyuan Hospital of Tongji Medical College, Huazhong University of Science and Technology, No.39 Lake Avenue, Wuchang District, Wuhan 430077, China; E-mail: hbwhly01@163.com

Received 12 April, 2018

Revised 3 June, 2018

Accepted 6 June, 2018

The manuscript submitted does not contain information about medical device(s)/drug(s).

The Fundamental Research Funds for the Central Universities [grant numbers 2016YXZD024, 2017KFYXJJ085 and 2017KFYXJJ086] funds were received in support of this work.

No relevant financial activities outside the submitted work.

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