Axonal remodeling of the corticospinal tract during neurological recovery after stroke

Abstract

Stroke remains the leading cause of long-term disability. Hemiparesis is one of the most common post-stroke motor deficits and is largely attributed to loss or disruption of the motor signals from the affected motor cortex. As the only direct descending motor pathway, the corticospinal tract (CST) is the primary pathway to innervate spinal motor neurons, and thus, forms the neuroanatomical basis to control the peripheral muscles for voluntary movements. Here, we review evidence from both experimental animals and stroke patients, regarding CST axonal damage, functional contribution of CST axonal integrity and remodeling to neurological recovery, and therapeutic approaches aimed to enhance CST axonal remodeling after stroke. The new insights gleaned from preclinical and clinical studies may encourage the development of more rational therapeutics with a strategy targeted to promote axonal rewiring for corticospinal innervation, which will significantly impact the current clinical needs of subacute and chronic stroke treatment.

Keywords: axonal degeneration; axonal integrity; axonal remodeling; corticospinal tract; motor performance; neurological recovery; stroke; therapeutic strategy.

Figure 1

A diagram showing corticospinal tract (CST) axonal degeneration and remodeling after stroke. In rodents, the main part of the CST is located in the dorsal funicular of the spinal cord. After a stroke, CST axons originating from ipsilesional hemisphere partially degenerate (indicated by dotted line), while in the denervated side of the spinal gray matter, cortical innervation may be recovered by axonal sprouting and outgrowth from both ipsilesional and contralesional hemispheres (indicated by blue lines). To facilitate axonal rewiring and thereby enhance neurological recovery, strategies for development of therapeutic approaches and agents could include: a) promoting neuronal capacity for axonal outgrowth, either in the ipsilesional and/or the contralesional cortex; b) reducing inhibitory factors of regeneration in the neural tracts; and c) enhancing axonal connectivity specifically in the denervated side of the spinal gray matter.