Effects of methylprednisolone and MK-801 on functional recovery after experimental chronic spinal cord injury.
METHODS
An experimental study was conducted to evaluate the effects of methylprednisolone and MK-801 after the compressive injury of spinal cord in rats.


OBJECTIVE
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 beta-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 beta-amyloid protein.


CONCLUSIONS
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 beta-amyloid protein.
Haghighi
S S
SS
Section of Neurosurgery, University of Nebraska Medical Center, Omaha, Nebraska 68198-2035, USA.
Agrawal
S K
SK
Surdell
D
D
Plambeck
R
R
Agrawal
S
S
Johnson
G C
GC
Walker
A
A
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001369:Axons / Q000187:drug effects / Q000473:pathology; D002908:Chronic Disease; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005911:Gliosis / Q000209:etiology / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008775:Methylprednisolone