Conduction Failure following Spinal Cord Injury: Functional and Anatomical Changes from Acute to Chronic Stages

Abstract

In the majority of spinal cord injuries (SCIs), some axonal projections remain intact. We examined the functional status of these surviving axons since they represent a prime therapeutic target. Using a novel electrophysiological preparation, adapted from techniques used to study primary demyelination, we quantified conduction failure across a SCI and studied conduction changes over time in adult rats with a moderate severity spinal contusion (150 kdyn; Infinite Horizon impactor). By recording antidromically activated single units from teased dorsal root filaments, we demonstrate complete conduction block in ascending dorsal column axons acutely (1-7 d) after injury, followed by a period of restored conduction over the subacute phase (2-4 weeks), with no further improvements in conduction at chronic stages (3-6 months). By cooling the lesion site, additional conducting fibers could be recruited, thus revealing a population of axons that are viable but unable to conduct under normal physiological conditions. Importantly, this phenomenon is still apparent at the most chronic (6 month) time point. The time course of conduction changes corresponded with changes in behavioral function, and ultrastructural analysis of dorsal column axons revealed extensive demyelination during the period of conduction block, followed by progressive remyelination. A proportion of dorsal column axons remained chronically demyelinated, suggesting that these are the axons recruited with the cooling paradigm. Thus, using a clinically relevant SCI model, we have identified a population of axons present at chronic injury stages that are intact but fail to conduct and are therefore a prime target for therapeutic strategies to restore function.

Iron oxide nanoparticles and magnetic field exposure promote functional recovery by attenuating free radical-induced damage in rats with spinal cord transection

“…Although a gradual increase was observed in all groups over the post-injury weeks (SCI, F [2,18] Figure 3C). …”

“…[1][2][3][4][5][6][7][8][9][10][11][12] Cyst formation and robust infiltration of fibroblasts result in formation of fibrous scar tissue that creates a physical barrier, 13,14 preventing any severed axons or collateral branches of uninjured axons from growing past the area of the lesion. Therefore, reduction in the formation of fibrous scar tissue or secondary damage is positively correlated with functional recovery.…”

Motoneuron Death after Human Spinal Cord Injury

“…The forces associated with contusion and laceration injuries may stretch axons excessively, resulting in both central and peripheral demyelination that is followed by some remyelination. 2,53,54 Longitudinal examination of central and peripheral axon conduction latencies revealed improvements over time in hand muscles, which may indicate remyelination of central and/or peripheral axons after human SCI. 55 Thinner than usual myelin and shorter internodal distances with remyelination will diminish impulse propagation, which is consistent with the general slowing of single thenar motor axon conduction velocities measured 1.5-19 years after human SCI.…”

Keratan Sulfate Proteoglycans in Plasticity and Recovery after Spinal Cord Injury: Figure 1.

“…chABC treatment can exert neuroprotective and trophic effects; the extent to which K-II acts similarly remains unknown. Additionally, recent work by James et al (2011) identifies disruption of conduction in spared axons following contusive SCI as an alternative means by which functional recovery might be impeded, even into the chronic stages of injury. CS and KS inhibition of functional recovery might occur, in part, through the same process (Fig.…”