Effects of methylprednisolone and MK-801 on functional recovery after experimental chronic spinal cord injury

Study design: An experimental study was conducted to evaluate the effects of methylprednisolone and MK-801 after the compressive injury of spinal cord in rats. Objectives: To investigate the effect of methylprednisolone and non-competitive NMDA antagonist MK-801 in long-term functional outcome after spinal cord injury (SCI). Methods: A randomized group A of Sprague-Dawley rats were treated with MK-801 (1.0 mg/kg, n= 10; Group A) after a compression injury. A group of methylprednisolone (MP)-treated (30 mg/kg, n=10; Group B) and non-treated animals (n=9; Group C) were included for comparison. The functional motor outcome such as inclined plane (IP), toe spreading reflex (TSR), and modified Tarlov scale (TS) were measured in each animal at regular time points up to 8 weeks post-treatment. Histologically the injury site was scored in four groups and immunohistochemically Wallerian Degeneration (WD), astrocytosis and expression of β-amyloid protein was identified. Results: In examining the IP data, no significant difference was recognized between the group means (P-value>0.5). For the TSR, there were no differences in the group responses. For the TS, the differences were not statistically significant. Only group B showed significance in cavitation scores compared to group A (P>0.0094), WD was significantly different than group C (P>0.03), astrocytosis was significantly higher than group A (P>0.001) and modest presence of β-amyloid protein. Conclusion: Our data indicate that one time bolus administration of MK-801 lacks any significant effect on axonal function in chronically injured rats. Daily bolus administration of MP at 30 mg/kg also did not ensure a better functional outcome. Immunohistochemically we have been able to show significant differences in WD, astrocytosis and small insignificant changes in β-amyloid protein.