Objectives: Delayed paraplegia developed postoperatively after thoracoabdominal aneurysm surgery is primarily associated with spinal cord ischemia/reperfusion injury. Our previous study suggested that spinal cord stimulation postconditioning protected the spinal cord from ischemia/reperfusion injury through microglia inhibition. In this study, we further investigated whether α7 nicotinic acetylcholine receptors were involved in the neuroprotective mechanism of spinal cord stimulation.
Methods: Rabbits were randomly assigned to sham, control, 2 Hz, α-bungarotoxin, and 2 Hz-α-bungarotoxin groups (n = 24/group). Transient spinal cord ischemia was performed on all rabbits except rabbits in the sham group. Rabbits in the control group received no further intervention, rabbits in the 2 Hz group were given 2 Hz spinal cord stimulation, rabbits in the α-bungarotoxin group received prescribed intrathecal α-bungarotoxin (α-bungarotoxin, a specific α7 nicotinic acetylcholine receptor antagonist) injections, and rabbits in the 2 Hz-α-bungarotoxin group received both α-bungarotoxin injections and 2 Hz spinal cord stimulation. Hind-limb neurologic function was assessed, and spinal cord histologic examination, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and microglia staining were performed at 8 hours, 1 day, 3 days, and 7 days of reperfusion.
Results: Rabbits in the 2 Hz group had significantly better neurologic functions, more α-motor neurons, and lower terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive neuron rates and microglia area/anterior horn area ratios (microglia area ratios) than the control group. The neurologic functions of the α-bungarotoxin group were significantly worse than those of the control group, whereas other results were not significantly different from the control group. The results of the 2 Hz-α-bungarotoxin group were insignificant to the control group except for the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive neuron rates, which were significantly lower than in the control group.
Conclusions: The neuroprotective effects of spinal cord stimulation postconditioning against spinal cord ischemia/reperfusion injury were partially mediated by activating α7 nicotinic acetylcholine receptors.
Keywords: spinal cord ischemia/reperfusion injury; spinal cord stimulation postconditioning; α-bungarotoxin; α7 nicotinic acetylcholine receptor.
Copyright © 2019. Published by Elsevier Inc.