Journal Article

Motor axon excitability during Wallerian degeneration

Mihai Moldovan, Susana Alvarez and Christian Krarup

in Brain

Published on behalf of The Guarantors of Brain

Volume 132, issue 2, pages 511-523
Published in print February 2009 | ISSN: 0006-8950
Published online December 2008 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awn332
Motor axon excitability during Wallerian degeneration

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Axonal loss and degeneration are major factors in determining long-term outcome in patients with peripheral nerve disorders or injury. Following loss of axonal continuity, the isolated nerve stump distal to the lesion undergoes Wallerian degeneration in several phases. In the initial ‘latent’ phase, action potential propagation and structural integrity of the distal segment are maintained. The aim of this study was to investigate in vivo the changes in membrane function of motor axons during the ‘latent’ phase of Wallerian degeneration. Multiple indices of axonal excitability of the tibial nerve at ankle distal to axotomy were monitored by ‘threshold-tracking’. The plantar compound muscle action potentials (CMAPs) were recorded under anesthesia in three animal models: 8-week-old wild-type mice, 8-week-old slow Wallerian degeneration mutant mice and 3-year-old cats. We found that the progressive decrease in CMAP following crush injury was associated with slowing of conduction and marked abnormalities in excitability: increased peak threshold deviations during both depolarizing and hyperpolarizing threshold electrotonus, enhanced superexcitability during the recovery cycle and increased rheobase. In the context of decreased current-threshold slope and increased chronaxie, these deviations in excitability were consistent with a decrease in voltage-dependent Na+ and K+ conductances. Our data suggest that during the ‘latent phase’ of Wallerian degeneration there is a gradual disruption in ion-channel function leading to abnormalities in excitability that precede conduction failure and axonal disintegration. These findings may have clinical relevance and should be taken into consideration in interpretation of the specificity of abnormalities in excitability measures in disorders characterized by axonal degeneration.

Keywords: excitability; internode; ion channels; node of Ranvier; nerve activity; regeneration

Journal Article.  5868 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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