Enhancing Brain Plasticity to Promote Stroke Recovery

Abstract

Stroke disturbs both the structural and functional integrity of the brain. The understanding of stroke pathophysiology has improved greatly in the past several decades. However, effective therapy is still limited, especially for patients who are in the subacute or chronic phase. Multiple novel therapies have been developed to improve clinical outcomes by improving brain plasticity. These approaches either focus on improving brain remodeling and restoration or on constructing a neural bypass to avoid brain injury. This review describes emerging therapies, including modern rehabilitation, brain stimulation, cell therapy, brain-computer interfaces, and peripheral nervous transfer, and highlights treatment-induced plasticity. Key evidence from basic studies on the underlying mechanisms is also briefly discussed. These insights should lead to a deeper understanding of the overall neural circuit changes, the clinical relevance of these changes in stroke, and stroke treatment progress, which will assist in the development of future approaches to enhance brain function after stroke.

Keywords: brain remodeling; brain restoration; neural bypass; plasticity; stroke.

Figure 1

Summary of treatment approaches discussed in this review. The abscissa indicates the readiness of clinical application, and the ordinate indicates the involvement of the healthy hemisphere.

Figure 2

Brain stimulation to promote stroke recovery. Activation of the injured hemisphere can improve prognosis, and the underlying mechanisms may include the promotion of angiogenesis, mitochondrial integrity and neurotransmission and the inhibition of glial activation, pro-inflammatory mediator secretion and oxidative stress. Healthy hemisphere stimulation could have various influences on stroke recovery. Increased interhemispheric compensation (induced by activated stimulation) or reduced interhemispheric suppression (induced by inhibitory stimulation) may mediate clinical recovery.

Figure 3

Cell transplantation to promote stroke recovery. Cell therapy was shown to induce the replacement of dead neurons in the infarcted area; more importantly, it ameliorated the microenvironment of the whole brain to promote functional modulation. Treatment not only enhances the neural activity of the injured hemisphere but also improves the structural connection of the whole brain.

Figure 4

Contralateral seventh cervical nerve transfer (CC7) to promote stroke recovery. A neural bypass was constructed via CC7 surgery to functionally connect the paralyzed hand and healthy hemisphere. Various trials are ongoing regarding CC7 surgery, including a large-sample multicenter trial, L5-S1 transfer to the lower limb, and pre- and post-surgery rehabilitation to facilitate plasticity.