Therapeutic Strategy Enhancing Neuronal Plasticity
Many research teams have tried to enhance neuronal plasticity to realize better functional recovery. Keeping the time window of neuroplasiticity open for a longer period by suppressing negative factors or by upregulating positive factors for neuroplasticity is now regarded as a possible therapeutic strategy. Rats that received an injection of anti-Nogo-A antibody via the intracerebroventricular or lumbar intrathecal space from 1 week after MCAO showed a significantly greater recovery of sensorimotor function than rats that received a control antibody. Anti-Nogo-A immunotherapy exhibited significant recovery from hemispatial neglect, which was produced by targeted cortical lesions, in the rodent model. Nogo-A immunotherapy has resulted in robust sprouting of new projections from contralateral brain regions into subcortical structures, which are thought to contribute to functional recovery. In addition, both MAG and semaphorin 3A are thought to be important therapeutic targets contributing to the lack of regenerative capacity of the CNS after injury. By contrast, amphetamine, which is a potent psychomotor stimulant that induces neuronal release of norepinephrine/dopamine/serotonin, has been regarded as a candidate for upregulation of neuroplasiticity. Amphetamine therapy increases the expression of GAP43 and synaptophysine. Moreover, amphetamine therapy enhances neocortical neuronal sprouting, synaptogenesis and behavioral recovery in the adult rat. However, clinical trials in humans failed to show evident effectiveness of amphetamine therapy after a stroke. BDNF has a role in homeostatic plasticity and enhances the intrinsic ability of surviving neurons to extend new connections. This BDNF effect, enhancing the intrinsic potential of retinal ganglion cells to extend new axons, was upregulated by degrading CSPG with chondroitinase ABC. Combination therapy, in which negative factors for neuroplasiticity are suppressed and positive factors are enhanced, might be a promising new therapeutic method that can extend the time window, leading to better functional recovery. In addition, electromagnetic stimulation may be promising as a possible plasticity-enhancing therapy. Lindenberg et al. reported that bihemispheric transcranial direct-current stimulation improved motor functions even in chronic stroke patients.