Abstract:

There is plenty of evidence that proves the beneficial and reliable effects of rehabilitation therapy, making it the most common treatment for patients with chronic stroke. It is believed that rehabilitation improves functional recovery through neural network remodeling, which is observed as a motor map reorganization or functional connectivity change assessed by intracortical microstimulation or functional magnetic resonance imaging (MRI). This neural network remodeling results from morphological changes, such as dendritic arborization, axonal sprouting, and synapse formation in surviving neurons. Among the various neural networks, descending spinal pathways play a pivotal role in executing voluntary motor tasks since these pathways send motor commands generated from the motor cortex to the spinal cord, which directly controls muscle contraction. Thus, destruction of these pathways causes impairment of motor functions. Descending spinal pathways include direct pathways (e.g., corticospinal pathway) and indirect pathways (e.g., rubrospinal and reticulospinal pathways). While most studies have focused on the corticospinal pathway, both direct and indirect descending spinal pathways are known to be reorganized through axonal remodeling after stroke, to compensate the functional roles of the destroyed neural pathways. Axonal remodeling in these pathways can be promoted by therapeutic intervention including brain stimulation (e.g., direct current stimulation, optogenetic stimulation), blockade of growth inhibiting molecules (e.g., anti-NogoA immunotherapy, chondroitinase ABC), and rehabilitative therapy. Recently, we demonstrated that rehabilitation-induced axonal remodeling in the corticospinal pathway plays a significant role in functional recovery after stroke.