Functional reorganization of the motor cortex in adult rats after cortical lesion and treatment with monoclonal antibody IN-1

Abstract

We previously reported anatomical plasticity in the adult motor cortex after a unilateral sensorimotor cortex (SMC) lesion and treatment with monoclonal antibody (mAb) IN-1, which permits neurite outgrowth from the intact, opposite cortex into deafferented subcortical targets. This study was designed to investigate whether treatment with the mAb IN-1 after SMC lesion in the adult leads to functional reorganization of the intact, opposite motor cortex. Adult rats underwent unilateral SMC aspiration lesion and treatment with either mAb IN-1 or control antibody, or no treatment. After a 6 week survival period, the intact, opposite forelimb motor cortex was explored using intracortical microstimulation to evoke forelimb movements. A dramatic increase in ipsilateral movements of the lesion-impaired forelimb was found in animals treated with mAb IN-1 compared with control animals. These results resembled our previous findings of cortical reorganization in the spared hemisphere after neonatal cortical lesion and without any additional treatment. These results show that, after adult cortical lesion, treatment with mAb IN-1 induces a functional reorganization of the intact, opposite motor cortex.

Figure 1.

Dorsal view of a rat brain 6 weeks after aspiration lesion surgery and mAb IN-1 treatment. The typical size and location of an aspiration lesion cavity is outlined in the left hemisphere (dotted line). The points on the right hemisphere indicate the area of intracortical microstimulation. The ruler indicates millimeter increments; b, bregma landmark.

Figure 2.

Individual ICMS forelimb maps were combined into representative forelimb maps in the four experimental groups. Points indicate the stereotaxic coordinates at which forelimb movements were evoked with stimulating current at threshold values. Movements in the ipsilateral, lesion-affected forelimb were always evoked in the presence of contralateral movements. Open circles represent contralateral movements alone, and filled circles represent ipsilateral plus contralateral movements. The plus signs represent reference coordinates: 0.0 mm rostral and 0.5 mm lateral to bregma. Shaded gray areas represent the boundaries of the forelimb maps. Scale bar, 1 mm. Ab, Antibody.

Figure 3.

Treatment with mAb IN-1 after SMC lesions (filled bar) significantly increased ipsilateral output from the nonlesioned motor cortex when compared with all other groups (graybars). Percentage values represent the average number of ipsilateral points/total forelimb points. Error bars indicate mean ± SEM. Asterisks indicate significance compared with all of the groups: ^***p < 0.001, one-way ANOVA, post hoc Bonferroni's multiple comparison. Ab, Antibody.

Figure 4.

Treatment with mAb IN-1 after SMC lesions did not affect the characteristics of proximal (filled bars) and distal (gray bars) movements in the ipsilateral forelimb. There was a significantly greater percentage of proximal compared with distal movements in the forelimb in all of the treatment groups. There was no statistical difference between the mAb IN-1 treatment and the control groups (p > 0.05). Error bars indicate mean ± SEM. Asterisks indicate significance compared with ipsilateral distal movements within each group: ^**p < 0.01, ^***p < 0.001, one-way ANOVA, post hoc Bonferroni's multiple comparison. Ab, Antibody.