Functional Redundancy of Ventral Spinal Locomotor Pathways

Abstract

Identification of long tracts responsible for the initiation of spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. Pathways derived from the mesencephalic locomotor region and pontomedullary medial reticular formation responsible for fictive locomotion in decerebrate preparations project to the thoracolumbar levels of the spinal cord via reticulospinal axons in the ventrolateral funiculus (VLF). However, white matter regions critical for spontaneous over-ground locomotion remain unclear because cats, monkeys, and humans display varying degrees of locomotor recovery after ventral SCIs. We studied the contributions of myelinated tracts in the VLF and ventral columns (VC) to spontaneous over-ground locomotion in the adult rat using demyelinating lesions. Animals received ethidium bromide plus photon irradiation producing discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, VC, VLF-VC, or complete ventral white matter (CV). Behavior [open-field Basso, Beattie, and Bresnahan (BBB) scores and grid walking] and transcranial magnetic motorevoked potentials (tcMMEP) were studied at 1, 2, and 4 weeks after lesion. VLF lesions resulted in complete loss or severe attenuation of tcMMEPs, with mean BBB scores of 18.0, and no grid walking deficits. VC lesions produced behavior similar to VLF-lesioned animals but did not significantly affect tcMMEPs. VC-VLF and CV lesions resulted in complete loss of tcMMEP signals with mean BBB scores of 12.7 and 6.5, respectively. Our data support a diffuse arrangement of axons within the ventral white matter that may comprise a system of multiple descending pathways subserving spontaneous over-ground locomotion in the intact animal.

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

“…This suggestion is supported by the report that a progressive oligodendrocyte and Schwann cell remyelination began in the adult rat spinal cord white matter during the first week following maximal demyelination at day 1 after contusive thoracic SCI (Totoiu and Keirstead, 2005). Additional support of this suggestion is the finding (Cao et al, 2005) that transcranial magnetic motor evoked potentials (Linden et al, 1999;Loy et al, 2002) that were abolished following contusive thoracic SCI recovered 1 week after transplantation of multineurotrophin-expressing glial-restricted precursor cells into the adult rat spinal cord ventrolateral funiculus (Cao et al, 2005). Their latencies significantly improved with time post-transplantation.…”

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

“…Moreover, plantar stepping that returned to a mouse hind-limb ipsilateral to a thoracic spinal cord hemisection was abolished by delayed, contralateral hemisection [18]. These results indicate that the spinal cord is able to adapt after incomplete injury by mechanisms involving functional redundancy [19], locomotor networks preserved after a second complete lesion [17], spared long-tract axon collateral sprouting [20], sprouting of spinal interneurons even capable of bridging a staggered hemisection [18], and/or adaptations of motoneurons [21] in the thoracolumbar spinal cord caudal to the SCI.…”

Diffusion Tensor Imaging at 3 Hours after Traumatic Spinal Cord Injury Predicts Long-Term Locomotor Recovery

“…In these experiments, all of the VLWM, including the ventral, lateral, and ventrolateral funiculi, was included in the region of interest based on previous reports in rats describing a diffuse arrangement of axons responsible for the initiation of locomotion within these regions (Loy et al, 2002a(Loy et al, , 2002b. Dorsal contusion injuries produce disproportionate axonal damage in VLWM compared to DC at severe displacements, a finding predicted by the viscoelastic properties of spinal cord (Blight and Decrescito, 1986;Loy et al, 2007).…”