Pyridoxine administration improves behavioral and anatomical outcome after unilateral contusion injury in the rat

Abstract

The purpose of this project was to evaluate the preclinical efficacy of pyridoxine, or vitamin B(6). Rats received a 3.0 mm unilateral controlled cortical impact (CCI) injury of the sensorimotor cortex or sham surgery. Treatment with vitamin B(6) (600 or 300 mg/kg IP) or vehicle was administered at 30 min and 24 h post-CCI. Somatosensory dysfunction was evaluated with the vibrissae-forelimb placing and bilateral tactile adhesive removal tests. Sensorimotor dysfunction was evaluated with the locomotor placing and the forelimb asymmetry tests. On the forelimb asymmetry test both treatment groups displayed no asymmetry bias on any of the testing days post-CCI and were statistically no different than the shams. Both vitamin B(6) groups displayed a significant improvement in behavioral performance on the locomotor placing test compared to the vehicle-treated group. Administration of 600 mg/kg also significantly reduced tactile adhesive removal latencies on days 2, 4, 6, and 12 post-CCI. Both treatment groups were improved in their rate of recovery post-CCI on the vibrissae-forelimb placing test, but only the recovery seen in the 600-mg/kg group was significantly improved compared to vehicle. Finally, the 600-mg/kg dose resulted in significant cortical sparing compared to the vehicle-treated group. In general, the effects of vitamin B(6) on recovery of function were dose-dependent, with the 600-mg/kg dose consistently showing greater recovery than the 300-mg/kg dose. More experimental analyses are warranted to evaluate the potential preclinical efficacy and mechanistic action of vitamin B(6).

FIG. 1.

Effects of administration of vitamin B₆ (600 or 300 mg/kg) or vehicle on the vibrissae–forelimb placing test. Plotted are the mean (±standard error of the mean) percentages of unsuccessful placing attempts. Significantly fewer unsuccessful placing attempts were observed over time for both treatment groups in a dose-dependent fashion, but only improvement in the 600-mg group was significant compared to vehicle. All groups appeared to reach a steady state of performance on this task by approximately day 14 post-injury.

FIG. 2.

Effects of administration of vitamin B₆ (600 and 300 mg/kg) or vehicle on the bilateral tactile adhesive removal test. Plotted are the mean (±standard error of the mean) latencies to remove the adhesive from the contralateral forelimb. Significant improvements in latencies to remove the adhesive were observed in the 600-mg group (∧p < 0.05), but not the 300-mg group (*p < 0.05).

FIG. 3.

Effects of administration of vitamin B₆ (600 and 300 mg/kg) or vehicle on the forelimb asymmetry test. Plotted is the percentage (±standard error of the mean) of contralateral forelimb use. Vitamin B₆ eliminated the initial behavioral deficit in both treatment groups (*p < 0.05). On all days, both treatment groups were not significantly different from shams.

FIG. 4.

Effects of administration of vitamin B₆ (600 or 300 mg/kg) or vehicle on the locomotor placing test. Plotted are the mean (±standard error of the mean) numbers of foot-faults with the contralateral forelimb. Significant improvements in behavioral performance were observed in both the 600- and 300-mg/kg vitamin B₆–treated animals compared to vehicle-treated animals.

FIG. 5.

Effects of administration of vitamin B₆ (600 or 300 mg/kg) or vehicle on the reduction of lesion volume. Plotted are the mean (±standard error of the mean) percent reductions in lesion volumes. Treatment with vitamin B₆ significantly reduced the cortical volume loss in a dose-dependent manner, with only the 600-mg group being significantly different from vehicle-treated animals (*p < 0.05).

FIG. 6.

Shown are coronal brain sections (40 μM, cresyl violet) at three levels through the injury cavity (1.70, 1.00, and 0.00 mm relative to the bregma). A large cortical cavity can be seen in the representative vehicle-treated brain compared to the vitamin B6–treated brains (scale bar = 2.0 mm).