Changes in axonal physiology and morphology after chronic compressive injury of the rat thoracic spinal cord

The spinal cord is rarely transected after spinal cord injury. Dysfunction of surviving axons, which traverse the site of spinal cord injury, appears to contribute to post-traumatic neurological deficits, although the underly ing mechanisms remain unclear. The subpial rim frequently contains thinly m yelinated axons which appear to conduct signals abnormally, although it is uncertain whether this truly reflects maladaptive alterations in conduction properties of injured axons during the chronic phase of spinal cord injury or whether this is merely the result of the selective survival of a subpop ulation of axons. In the present study, we examined the changes in axonal c onduction properties after chronic clip compression injury of the rat thora cic spinal cord. using the sucrose gap technique and quantitatively examine d changes in the morphological and ultrastructural features of injured axon al fibers in order to clarify these issues. Chronically injured dorsal colu mns had a markedly reduced compound action potential amplitude (8.3% of con trol) and exhibited significantly reduced excitability. Other dysfunctional conduction properties of injured axons included a slower population conduc tion velocity, a longer refractory period and a greater degree of high-freq uency conduction block at 200 Hz. Light microscopic and ultrastructural ana lysis showed numerous axons with abnormally thin myelin sheaths as well as unmyelinated axons in the injured spinal cord. The ventral column showed a reduced median axonal diameter and the lateral and dorsal columns showed in creased median diameters, with evidence of abnormally large swollen axons. Plots of axonal diameter versus myelination ratio showed that post-injury, dorsal column axone of all diameters had thinner myelin sheaths. Noninjured dorsal column axone had a median myelination ratio (1.56) which was within the optimal range ( 1.43-1.67) for axonal conduction, whereas injured dors al column axone had a median myelination ratio (1.33) below the optimal val ue. These data suggest that maladaptive alterations occur postinjury to mye lin sheath thickness which reduce the efficiency of axonal signal transmiss ion. In conclusion. chronically injured dorsal column axons show physiological e vidence of dysfunction and morphological changes in axonal diameter and red uced myelination ratio. These maladaptive alterations to injured axons. inc luding decrease in myelin thickness and the appearance of axonal swellings. contribute to the decreased excitablity of chronically injured axons. Thes e results further clarify the mechanisms underlying neurological dysfunctio n after chronic neurotrauma and have significant implications regarding app roaches to augment neural repair and regeneration. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.