Rewiring of the corticospinal tract in the adult rat after unilateral stroke and anti-Nogo-A therapy

摘要: Adult Long Evans rats received a photothrombotic stroke that destroyed >90% of the sensorimotor cortex unilaterally; they were subsequently treated intrathecally for 2 weeks with function blocking antibody against neurite growth inhibitory central nervous system protein Nogo-A. Fine motor control skilled forelimb grasping improved to 65% intact baseline performance in anti-Nogo-A rats, whereas animals recovered only 20% scores. Bilateral retrograde tract tracing two different tracers from and denervated side cervical spinal cord, at time points post-lesion, indicated corticospinal had extensively sprouted across midline into hemicord. The original axonal arbours fibres recrossed withdrawn, leading complete side-switch projection subpopulation contralesional axons. Anterograde showed 2-3-fold increase crossing additionally massive sprouting pre-existing ipsilateral ventral throughout entire enlargement antibody-treated compared group. laminar distribution pattern ipsilaterally projecting was similar cord. These plastic changes paralleled by somatotopic reorganization where formation an area observed. Intracortical microstimulation revealed low threshold currents evoked movements electromyography responses frequent cortical sites anti-Nogo-A, but not animals. Subsequent transection spared chronically animals, led reappearance initial lesion deficit observed after lesion. results demonstrate switch anatomically functionally adult neurons, induced destruction one neutralization CNS