The research on therapeutical effect of 4-AP-3-MeOH on chronic spinal cord injury in rats / 中华骨科杂志

ABSTRACT

Objective To investigate the therapeutic effect of the new K+ channel blocker 4-aminopyridine-3-methanol (4-AP-3-MeOH) on chronic spinal cord injury in rats.Methods 18 adult male Sprague-Dawley rats were randomly divided equally into 3 groups as follows4-AP-3-MeOH treatment group (A),normal saline control group (B) and sham operation group (C).T10 segment of spinal cord compression injury was applied in group A and group B.4 weeks later,the rats in group A were daily treated by injecting 4-AP-3-MeOH 1 μmol (1000 μmol/L× 1 ml) into the veins of the tails for 4 weeks.While the same volume of saline was administrated into the group B for 4 weeks.Lamina of vertebra of T10 was cut without spinal cord injury in the sham-operation group.After modeling,the locomotor functional recovery was assessed by using Basso Beattie Bresnahan (BBB) scores and inclined plane (IP) tests,and all rats were periodical inspected by the somatosensory evoked potential(SEP) and motor evoked potential(MEP) post-operatively.Results BBB scores of group A started to increase gradually and were higher than those of group B from the 6th week,but the 2 groups at each time point in BBB scores were less than group C.Until 8 weeks after surgery,the inclined-plated angles of group A and B did not show significantly difference,but the both groups were significantly lower compared with group C.Electrophysiology study found that the amplitude of SEP and MEP in group A was higher than group B from the fourth to 8 weeks,but less than in group C.Histological examination showed that the spinal cord of rats in group C were morphologically intact with a clear demarcation between the grey and white matter.The gray matter structures of rats in group A and B were gone and a big cavity appears in the center of the spinal cord injury,with varying degrees of demyelination in the white around.In addition,statistically significant differences were found in the percentage of residual myelin at the injury epicenter between group A and group B.Conclusion With a persistent demyelination change and poor motor function in chronic spinal cord injury,daily administration of 4-AP-3-MeOH can improve the sensory and motor functions.