Effects Of Dexmedtomidine On Inflammation And Blood-spinal Cord Barrier After Spinal Cord Ischemia Reperfusion Injury In Rabbits

[Objective] To investigate the effects and underlying mechanisms of Dexmedtomidine on inflammation and blood-spinal cord barrier after spinal cord ischemia-reperfusion injury in rabbits.[Methods] Forty-eight male Japanese white rabbits were randomly divided into 3 groups(n = 16): sham-operation group(group sham),ischemia-reperfusion group(group I/R)and Dexmedetomidine preconditioning group(group Dex+I/R).The abdominal aorta at the level of the left renal artery in group I/R and group Dex+I/R was clamped for 30 minutes to induce spinal cord ischemia wherase in the group sham only exposing without clamping.Dexmedetomidine was intravenously infused at 60 minutes before ischemia to the moment of reperfusion in group Dex.The group sham and group I/R received the same amount of 0.9% sodium chloride at the same time.The hind-limb motor function was assessed at 12 h intervals for 48 h after reperfusion using the modified Tarlov scale score.The hiatopathological outcome was observed by hematoxylin and eosin staining.The expression of HMGB1,TLR4,NF-kB,tumor necrosis factor a(TNF-a),MMP-8,MMP-9 and claudin-5 was evaluated by RT-PCR and western blotting.The permeability of BSCB was examined via Evans blue(EB)extravasation.[Results] Compared with sham group,spinal cord I/R induced the decline of the score of hind-limb motor function,up-regulation of the expression of HMGB1,TLR4,NF-kB,TNF-a,MMP-8 and MMP-9,down-regulation of claudin-5 and increased the permeability of BSCB(P < 0.05).However,preconditioning with Dex improved the motor function and hiatopathological outcome,attenuated the up-regulation of the expression of HMGB1,TLR4,NF-kB,TNF-a,MMP-8 and MMP-9 as well as the down-regulation of claudin-5,stabilized the permeability of BSCB(P < 0.05).[Conclusion] Dexmedetomidine preconditioning may inhibit the inflammatory response and stabilize the integrity of BSCB at least partially by inhibiting the HMGB1-TLR4-NF-kB signaling pathway as well as the down-regulation of claudin-5 to protect spinal cord from ischemia-reperfusion injury.