Spinal cord protection via alpha-2 agonist-mediated increase in glial cell-line–derived neurotrophic factor

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Abstract

Objectives:

Delayed paraplegia secondary to ischemia–reperfusion injury is a devastating complication of thoracoabdominal aortic surgery. Alpha-2 agonists have been shown to attenuate ischemia–reperfusion injury, but the mechanism for protection has yet to be elucidated. A growing body of evidence suggests that astrocytes play a critical role in neuroprotection by release of neurotrophins. We hypothesize that alpha-2 agonism with dexmedetomidine increases glial cell-line–derived neurotrophic factor in spinal cord astrocytes to provide spinal cord protection.

Methods:

Spinal cords were isolated en bloc from C57BL/6 mice, and primary spinal cord astrocytes and neurons were selected for and grown separately in culture. Astrocytes were treated with dexmedetomidine, and glial cell-line–derived neurotrophic factor was tested for by enzyme-linked immunosorbent assay. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess neuronal viability.

Results:

Spinal cord primary astrocytes treated with dexmedetomidine at 1 μmol/L and 10 μmol/L had significantly increased glial cell-line–derived neurotrophic factor production compared with control (P < .05). Neurons subjected to oxygen glucose deprivation had significant preservation (P < .05) of viability with use of dexmedetomidine-treated astrocyte media. Glial cell-line–derived neurotrophic factor neutralizing antibody eliminated the protective effects of the dexmedetomidine-treated astrocyte media (P < .05).

Conclusions:

Astrocytes have been shown to preserve neuronal viability via release of neurotrophic factors. Dexmedetomidine increases glial cell–derived neurotrophic factor from spinal cord astrocytes via the alpha-2 receptor. Treatment with alpha-2 agonist dexmedetomidine may be a clinical tool for use in spinal cord protection in aortic surgery.

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