The effects of cyclosporin-A on axonal conduction deficits following traumatic brain injury in adult rats.

Abstract

Immunophilin ligands, including cyclosporin-A (CsA), have been shown to be neuroprotective in experimental models of traumatic brain injury (TBI) and to attenuate the severity of traumatic axonal injury. Prior studies have documented CsA treatment to reduce essential components of posttraumatic axonal pathology, including impaired axoplasmic transport, spectrin proteolysis, and axonal swelling. However, the effects of CsA administration on axonal function, following TBI, have not been evaluated. The present study assessed the effects of CsA treatment on compound action potentials (CAPs) evoked in corpus callosum of adult rats following midline fluid percussion injury. Rats received a 20 mg/kg bolus of CsA, or cremaphor vehicle, at either 15 min or 1 h postinjury, and at 24 h postinjury CAP recording was conducted in coronal brain slices. To elucidate how injury and CsA treatments affect specific populations of axons, CAP waveforms generated largely by myelinated axons (N1) were analyzed separately from the CAP signal, which predominantly reflects activity in unmyelinated axons (N2). CsA administration at 15 min postinjury resulted in significant protection of CAP area, and this effect was more pronounced in N1, than in the N2, CAP component. This treatment also significantly protected against TBI-induced reductions in high-frequency responding of the N1 CAP signal. In contrast, CsA treatment at 1 h did not significantly protect CAPs but was associated with atypical waveforms in N1 CAPs, including decreased CAP duration and reduced refractoriness. The present findings also support growing evidence that myelinated and unmyelinated axons respond differentially to injury and neuroprotective compounds.

• Authors: Beverly S Colley, Linda L Phillips, Thomas M Reeves
• Journal: Experimental neurology (Exp Neurol) Vol. 224 Issue 1 Pg. 241-51 (Jul 2010) ISSN: 1090-2430 [Electronic] United States
• PMID: 20362574 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Neuroprotective Agents
• Cyclosporine

Topics

• Action Potentials (drug effects, physiology)
• Analysis of Variance
• Animals
• Axons (drug effects)
• Brain Injuries (drug therapy, physiopathology)
• Corpus Callosum (drug effects, injuries, physiopathology)
• Cyclosporine (pharmacology)
• Cytoprotection (drug effects)
• Electrophysiology
• Male
• Nerve Fibers, Myelinated (drug effects)
• Neural Conduction (drug effects, physiology)
• Neurons (drug effects)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects)