PMID- 29975331
OWN - NLM
STAT- MEDLINE
DCOM- 20190520
LR  - 20210115
IS  - 1528-1159 (Electronic)
IS  - 0362-2436 (Linking)
VI  - 44
IP  - 2
DP  - 2019 Jan 15
TI  - 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 kappaB Signaling 
      Pathway.
PG  - E74-E81
LID - 10.1097/BRS.0000000000002772 [doi]
AB  - 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 kappaB (HMGB1-TLR4-NF-kappaB) 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 kappaB (TLR4-NF-kappaB) 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-kappaB, and tumor necrosis factor alpha (TNF-alpha) 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-kappaB, and 
      TNF-alpha 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-kappaB, TNF-alpha, 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-kappaB signaling pathway 
      to protect spinal cord from ischemia/reperfusion injury. LEVEL OF EVIDENCE: 2.
FAU - Liu, Jiao
AU  - Liu J
AD  - Department of Anesthesiology, Liyuan Hospital of Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Zhang, Shuangshuang
AU  - Zhang S
FAU - Fan, Xiaona
AU  - Fan X
FAU - Yuan, Fen
AU  - Yuan F
FAU - Dai, Jun
AU  - Dai J
FAU - Hu, Ji
AU  - Hu J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Spine (Phila Pa 1976)
JT  - Spine
JID - 7610646
RN  - 0 (Adrenergic alpha-2 Receptor Agonists)
RN  - 0 (HMGB1 Protein)
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 67VB76HONO (Dexmedetomidine)
SB  - IM
MH  - Adrenergic alpha-2 Receptor Agonists/*pharmacology/therapeutic use
MH  - Animals
MH  - Dexmedetomidine/*pharmacology/therapeutic use
MH  - Down-Regulation/drug effects
MH  - HMGB1 Protein/genetics/metabolism
MH  - Inflammation/etiology/metabolism
MH  - Male
MH  - NF-kappa B/genetics/metabolism
MH  - Rabbits
MH  - Reperfusion Injury/etiology/*metabolism/*physiopathology/prevention & control
MH  - Signal Transduction/*drug effects
MH  - Spinal Cord Ischemia/complications
MH  - Toll-Like Receptor 4/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
EDAT- 2018/07/06 06:00
MHDA- 2019/05/21 06:00
CRDT- 2018/07/06 06:00
PHST- 2018/07/06 06:00 [pubmed]
PHST- 2019/05/21 06:00 [medline]
PHST- 2018/07/06 06:00 [entrez]
AID - 00007632-201901150-00004 [pii]
AID - 10.1097/BRS.0000000000002772 [doi]
PST - ppublish
SO  - Spine (Phila Pa 1976). 2019 Jan 15;44(2):E74-E81. doi: 
      10.1097/BRS.0000000000002772.