Alpha-2 agonist attenuates ischemic injury in spinal cord neurons.

Autor: Freeman KA; Department of Surgery, University of Colorado, Denver, Colorado. Electronic address: kirsten.freeman@ucdenver.edu., Puskas F; Department of Anesthesiology, University of Colorado, Denver, Colorado., Bell MT; Department of Surgery, University of Colorado, Denver, Colorado., Mares JM; Department of Surgery, University of Colorado, Denver, Colorado., Foley LS; Department of Surgery, University of Colorado, Denver, Colorado., Weyant MJ; Department of Surgery, University of Colorado, Denver, Colorado., Cleveland JC Jr; Department of Surgery, University of Colorado, Denver, Colorado., Fullerton DA; Department of Surgery, University of Colorado, Denver, Colorado., Meng X; Department of Surgery, University of Colorado, Denver, Colorado., Herson PS; Department of Anesthesiology, University of Colorado, Denver, Colorado., Reece TB; Department of Surgery, University of Colorado, Denver, Colorado.
Jazyk: angličtina
Zdroj: The Journal of surgical research [J Surg Res] 2015 May 01; Vol. 195 (1), pp. 21-8. Date of Electronic Publication: 2014 Dec 23.
DOI: 10.1016/j.jss.2014.12.033
Abstrakt: Background: Paraplegia secondary to spinal cord ischemia-reperfusion injury remains a devastating complication of thoracoabdominal aortic intervention. The complex interactions between injured neurons and activated leukocytes have limited the understanding of neuron-specific injury. We hypothesize that spinal cord neuron cell cultures subjected to oxygen-glucose deprivation (OGD) would simulate ischemia-reperfusion injury, which could be attenuated by specific alpha-2a agonism in an Akt-dependent fashion.
Materials and Methods: Spinal cords from perinatal mice were harvested, and neurons cultured in vitro for 7-10 d. Cells were pretreated with 1 μM dexmedetomidine (Dex) and subjected to OGD in an anoxic chamber. Viability was determined by MTT assay. Deoxyuridine-triphosphate nick-end labeling staining and lactate dehydrogenase (LDH) assay were used for apoptosis and necrosis identification, respectively. Western blot was used for protein analysis.
Results: Vehicle control cells were only 59% viable after 1 h of OGD. Pretreatment with Dex significantly preserves neuronal viability with 88% viable (P < 0.05). Dex significantly decreased apoptotic cells compared with that of vehicle control cells by 50% (P < 0.05). Necrosis was not significantly different between treatment groups. Mechanistically, Dex treatment significantly increased phosphorylated Akt (P < 0.05), but protective effects of Dex were eliminated by an alpha-2a antagonist or Akt inhibitor (P < 0.05).
Conclusions: Using a novel spinal cord neuron cell culture, OGD mimics neuronal metabolic derangement responsible for paraplegia after aortic surgery. Dex preserves neuronal viability and decreases apoptosis in an Akt-dependent fashion. Dex demonstrates clinical promise for reducing the risk of paraplegia after high-risk aortic surgery.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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