Pathological changes of isolated spinal cord axons in response to mechanical stretch

White matter strips extracted from adult guinea-pig spinal cords were maintained in vitro and studied physiologically using a double sucrose gap technique and anatomically using a horseradish peroxidase assay. The amplitude of compound action potentials was monitored continuously before, during, and after elongation. Three types of conduction blocks resulting from stretch injury were identified: an immediate, spontaneously reversible component. which may result from a transient increase in membrane permeability and consequent disturbance of ionic distributions a second component that was irreversible within 30 60 min of recording, perhaps resulting from profound axolemmal disruption; and a third component, which may be due to perturbation of the myelin sheath, that was reversible with application of 100 muM of the potassium channel blocker, 4-aminopyridine. The intensity of the conduction deficits correlated with the extent of initial stretch over a Call range of severity. Stimulus-response data indicate that mechanical damage to axons in stretch was evenly distributed across the caliber spectrum, Morphological examinations revealed that a small portion of axons exhibited membrane damage at 2 min following stretch and appeared to be largely sealed at 30 min after injury. Further, in the entire length of the cord strip subjected to stretch. axons closer to the surface were found to be more likely to suffer membrane damage, which distinguished stretch injury from compression injury. In summary. we have developed an in vitro model of axonal stretch that provides the ability to monitor changes in the properties of central myelinated axons following stretch injury in the absence of pathological variables related to vascular damage. This initial investigation found no evidence of secondary deterioration of axons in the first 30 min after stretch in vitro, although there was evidence of both transient and lasting physiological and anatomical damage to axons and their myelin sheaths. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.