Voluntary Exercise and Molecular Targeting to Promote Motor Recovery After Brain Injury

Abstract

Brain injury often causes severe motor dysfunction, which interferes with patients' independence and social life. Although injured neural circuits need to be reconstructed for functional recovery, the adult central nervous system shows limited ability to restore neuronal connections. Various therapeutic approaches, including molecular targeting and rehabilitative exercise have been investigated to promote reorganization of spared neural circuits and recovery in animal models; however, these strategies were not shown to achieve complete recovery. Therefore, a novel therapeutic concept or combinational approaches need to be developed. For example, we previously investigated src homology 2-containing phosphatase-1 (SHP-1), an inhibitor of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, as a molecule that can promote reorganization. We observed that rehabilitative exercise decreased SHP-1 and increased BDNF/TrkB expression in the spared motor cortex after brain injury in mice. Furthermore, genetic reduction of SHP-1 and rehabilitative training operate synergistically to promote reorganization of motor circuits and functional recovery. In this review, we discuss advances in therapeutic approaches and the underlying mechanisms that enhance neuronal reorganization and recovery after brain injury.