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- Title
Conduction Failure following Spinal Cord Injury: Functional and Anatomical Changes from Acute to Chronic Stages.
- Authors
James, Nicholas D.; Bartus, Katalin; Grist, John; Bennett, David L. H.; McMahon, Stephen B.; Bradbury, Elizabeth J.
- Abstract
In the majority of spinal cord injuries (SCIs), some axonal projections remain intact.Weexamined 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.
- Subjects
SPINAL cord injuries; TARGETED drug delivery; ELECTROPHYSIOLOGY; CHRONIC diseases; ACUTE diseases; DEMYELINATION
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 50, p18543
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4306-11.2011