Abstract 18584: Alpha-2 Agonist Attenuates Ischemic Injury in Isolated Spinal Cord Neurons
Background: Paraplegia secondary to spinal cord ischemia-reperfusion injury remains a devastating complication of thoracoabdominal aortic surgery. The complex interactions between the injured neurons and activated leukocytes have made investigation of neuron specific injury elusive. We hypothesize that isolated spinal motor neuron cell cultures subjected to oxygen-glucose deprivation (OGD) would simulate ischemia-reperfusion (IR) injury seen in aortic surgery, which could be attenuated by specific alpha-2a agonism, using dexmedetomidine, in an Akt dependent fashion.
Methods and Results: Spinal cords from perinatal mice were harvested and neurons cultured in vitro for 7-10 days. Cells were pretreated with 1μM dexmedetomidine (Dex) and subjected to OGD in a humidified hypoxic chamber. Indexed to non-ischemic controls, pretreatment with Dex significantly preserves neuronal viability after one hour of OGD with 88% viability compared to untreated OGD with 59% viability (p<0.05) . TUNEL staining demonstrated pretreatment with Dex significantly decreased the apoptotic cells compared to untreated OGD cells by over 50% (p<0.05). OGD increased IL-6 production nearly three-fold compared to non-ischemic control (p<0.05) with Dex reducing this production by half (p<0.05). Mechanistically, Dex treatment significantly increased phosphorylated Akt (p<0.05), but the protective effects of Dex seen by MTT assay were eliminated using an alpha-2a antagonist or an Akt inhibitor (p<0.05), with viability nearly half of non-ischemic control.
Conclusion: Using a novel spinal cord neuron cell culture, oxygen-glucose deprivation mimics neuronal metabolic derangement responsible for paraplegia following aortic surgery. Dexmedetomidine preserves neuronal viability and decreases apoptosis in an Akt dependent fashion. Dexmedetomidine demonstrates clinical promise for reducing the risk of paraplegia following high risk aortic surgery.
- © 2013 by American Heart Association, Inc.