Enhancing Neuroplasticity and Regeneration After Stroke
A critical period of increased neuronal plasticity might exist after stroke. Earlier initiation of rehabilitation therapy is required for a better functional outcome. In one important experiment, rats were exposed to enriched rehabilitation 5, 14 and 30 days after middle cerebral artery occlusion (MCAO). Rats given early start rehabilitation (5 or 14 days after MCAO) showed significant recovery whereas those given delayed treatment (30 days after MCAO) displayed little improvement. However, Humm et al. reported that forced overuse of the impaired forelimb during the first 7 days postlesion, caused expansion of neuronal injury and exacerbated neurological function in a rat brain injury model, indicating that excessive rehabilitation at an early stage of injury can interfere with the restoration of function. Taken together with clinical findings, these results implied the existence of a critical period during which the brain can be sensitive to rehabilitative experience.
What decides a critical rehabilitation period? One widely held hypothesis is that the balance between positive factors and negative factors for neuroplasticity can determine this period. Both glial-derived synaptogenic thrombospondin 1/2 and proteins promoting growth processes, such as GAP43, CAP23 and MARCKS, which are highly expressed in the subacute phase of a stroke, are regarded as positive factors for neuroplasticity. On the other hand, inhibitory factors for the outgrowth of axons or sprouting, including Nogo-A, MAG, semaphorin 3A, CSPG and neurocan, are regarded as negative factors for neuroplasticity.
Time Window for Neuronal Plasticity in the Postischemic Brain
A critical period of increased neuronal plasticity might exist after stroke. Earlier initiation of rehabilitation therapy is required for a better functional outcome. In one important experiment, rats were exposed to enriched rehabilitation 5, 14 and 30 days after middle cerebral artery occlusion (MCAO). Rats given early start rehabilitation (5 or 14 days after MCAO) showed significant recovery whereas those given delayed treatment (30 days after MCAO) displayed little improvement. However, Humm et al. reported that forced overuse of the impaired forelimb during the first 7 days postlesion, caused expansion of neuronal injury and exacerbated neurological function in a rat brain injury model, indicating that excessive rehabilitation at an early stage of injury can interfere with the restoration of function. Taken together with clinical findings, these results implied the existence of a critical period during which the brain can be sensitive to rehabilitative experience.
What decides a critical rehabilitation period? One widely held hypothesis is that the balance between positive factors and negative factors for neuroplasticity can determine this period. Both glial-derived synaptogenic thrombospondin 1/2 and proteins promoting growth processes, such as GAP43, CAP23 and MARCKS, which are highly expressed in the subacute phase of a stroke, are regarded as positive factors for neuroplasticity. On the other hand, inhibitory factors for the outgrowth of axons or sprouting, including Nogo-A, MAG, semaphorin 3A, CSPG and neurocan, are regarded as negative factors for neuroplasticity.