Constraint induced movement therapy promotes contralesional-oriented structural and bihemispheric functional neuroplasticity after stroke

The mechanism behind constraint-induced movement therapy (CIMT) in promoting motor recovery after stroke remains unclear. We explored the bilateral structural and functional reorganization of the brain induced by CIMT after left middle cerebral artery occlusion (MCAO) in rats. CIMT started on the 8th day (D8) after MCAO surgery and lasted for 3 weeks. Skilled walking was assessed by Foot-Fault tests. The efferent neuron network innervating the paralyzed forelimb was labeled by pseudorabies virus (PRV) to explore neuron recruitment. Synapsin I was used as an indicator of the number of synapses. Additionally, C-fos expression 1 h after walking was detected to explore the activation of the brain. As a result, CIMT significantly improved skilled walking and elicited more neuron recruitment into the innervating network of a paralyzed forelimb in the contralesional rather than the ipsilesional motor cortex and red nucleus. CIMT also increased the synapse number in the contralesional cortex but there was no corresponding effect in the intact ipsilesional cortex. Furthermore, MCAO decreased ipsilesional motor cortex activation, but CIMT partially compensated for this by increasing the number of activated neurons (c-fos(+)) in both the left and right motor cortex. In conclusion, the contralesional motor cortex and red nucleus might play more important roles than corresponding ipsilesional regions in structural reorganization during CIMT-induced motor recovery after stroke. However, CIMT promotes bilateral motor cortex activity without a side preference.