Dexmedetomidine modulates neuroinflammation and improves outcome via alpha2-adrenergic receptor signaling after rat spinal cord injury.

Autor:	Gao J; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Department of Anaesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China., Sun Z; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Department of Anaesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China., Xiao Z; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Department of Anaesthesiology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China., Du Q; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Department of Anaesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China., Niu X; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Department of Anaesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China., Wang G; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Department of Anaesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China., Chang YW; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Brain and Spinal Injury Center, University of California, San Francisco, San Francisco, CA, USA., Sun Y; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Department of Anaesthesiology, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China., Sun W; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Department of Anaesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China., Lin A; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Brain and Spinal Injury Center, University of California, San Francisco, San Francisco, CA, USA., Bresnahan JC; Brain and Spinal Injury Center, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA., Maze M; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA., Beattie MS; Brain and Spinal Injury Center, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. Electronic address: Michael.Beattie@ucsf.edu., Pan JZ; Department of Anaesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA; Brain and Spinal Injury Center, University of California, San Francisco, San Francisco, CA, USA. Electronic address: Jonathan.Pan@ucsf.edu.
Jazyk:	angličtina
Zdroj:	British journal of anaesthesia [Br J Anaesth] 2019 Dec; Vol. 123 (6), pp. 827-838. Date of Electronic Publication: 2019 Oct 14.
DOI:	10.1016/j.bja.2019.08.026
Abstrakt:	Background: Spinal cord injury induces inflammatory responses that include the release of cytokines and the recruitment and activation of macrophages and microglia. Neuroinflammation at the lesion site contributes to secondary tissue injury and permanent locomotor dysfunction. Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is anti-inflammatory and neuroprotective in both preclinical and clinical trials. We investigated the effect of DEX on the microglial response, and histological and neurological outcomes in a rat model of cervical spinal cord injury. Methods: Anaesthetised rats underwent unilateral (right) C5 spinal cord contusion (75 kdyne) using an impactor device. The locomotor function, injury size, and inflammatory responses were assessed. The effect of DEX was also studied in a microglial cell culture model. Results: DEX significantly improved the ipsilateral upper-limb motor dysfunction (grooming and paw placement; P<0.0001 and P=0.0012), decreased the injury size (P<0.05), spared white matter (P<0.05), and reduced the number of activated macrophages (P<0.05) at the injury site 4 weeks post-SCI. In DEX-treated rats after injury, tissue RNA expression indicated a significant downregulation of pro-inflammatory markers (e.g. interleukin [IL]-1β, tumour necrosis factor-α, interleukin (IL)-6, and CD11b) and an upregulation of anti-inflammatory and pro-resolving M2 responses (e.g. IL-4, arginase-1, and CD206) (P<0.05). In lipopolysaccharide-stimulated cultured microglia, DEX produced a similar inflammation-modulatory effect as was seen in spinal cord injury. The benefits of DEX on these outcomes were mostly reversed by an α2-adrenergic receptor antagonist. Conclusions: DEX significantly improves neurological outcomes and decreases tissue damage after spinal cord injury, which is associated with modulation of neuroinflammation and is partially mediated via α2-adrenergic receptor signaling. (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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