Cortical stimulation leads to shortened myelin sheaths and increased axonal branching in spared axons after cervical spinal cord injury

• Published in: Glia Vol. 71; no. 8; pp. 1947 - 1959
• Main Authors: Kondiles, B. R., Murphy, R. L., Widman, A. J., Perlmutter, S. I., Horner, P. J.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-08-2023; Wiley Subscription Services, Inc
• Subjects: Animals; Axonal plasticity; Axons; Axons - pathology; Central nervous system; Cervical Cord - pathology; Contusions; Contusions - metabolism; Contusions - pathology; Cortex (motor); Demyelination; Dendritic branching; Electrical stimuli; Immunohistochemistry; Injuries; Lesions; Myelin; Myelin Sheath - metabolism; Myelination; neural activity; Neural plasticity; Neuromodulation; Nodes of Ranvier; Plastic properties; Plasticity; Pyramidal tracts; Rats; Sheaths; Spinal Cord - metabolism; Spinal cord injuries; Spinal Cord Injuries - metabolism; spinal cord injury; Stimulation; Substantia alba; white matter plasticity; myelin; neuromodulation; spinal cord injury; white matter plasticity; neural activity
• ISSN: 0894-1491; 1098-1136; 1098-1136
• DOI: 10.1002/glia.24376

Neural activity and learning lead to myelin sheath plasticity in the intact central nervous system (CNS), but this plasticity has not been well‐studied after CNS injury. In the context of spinal cord injury (SCI), demyelination occurs at the lesion site and natural remyelination of surviving axons can take months. To determine if neural activity modulates myelin and axon plasticity in the injured, adult CNS, we electrically stimulated the contralesional motor cortex at 10 Hz to drive neural activity in the corticospinal tract of rats with sub‐chronic spinal contusion injuries. We quantified myelin and axonal characteristics by tracing corticospinal axons rostral to and at the lesion epicenter and identifying nodes of Ranvier by immunohistochemistry. Three weeks of daily stimulation induced very short myelin sheaths, axon branching, and thinner axons outside of the lesion zone, where remodeling has not previously been reported. Surprisingly, remodeling was particularly robust rostral to the injury which suggests that electrical stimulation can promote white matter plasticity even in areas not directly demyelinated by the contusion. Stimulation did not alter myelin or axons at the lesion site, which suggests that neuronal activity does not contribute to myelin remodeling near the injury in the sub‐chronic period. These data are the first to demonstrate wide‐scale remodeling of nodal and myelin structures of a mature, long‐tract motor pathway in response to electrical stimulation. This finding suggests that neuromodulation promotes white matter plasticity in intact regions of pathways after injury and raises intriguing questions regarding the interplay between axonal and myelin plasticity.
Main Points
Electrical stimulation of motor cortex induces white matter plasticity far from the lesion after adult spinal cord injury.
Corticospinal tract internodes are shorter, axons are thinner, & more axons branch.
Myelin at the lesion is unaffected.