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 underlying mechanisms remain unclear. The subpial rim frequently contains thinly myelinated 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 subpopulation of axons. In the present study, we examined the changes in axonal conduction properties after chronic clip compression injury of the rat thoracic spinal cord, using the sucrose gap technique and quantitatively examined changes in the morphological and ultrastructural features of injured axonal fibers in order to clarify these issues. Chronically injured dorsal columns had a markedly reduced compound action potential amplitude (8.3% of control) and exhibited significantly reduced excitability. Other dysfunctional conduction properties of injured axons included a slower population conduction velocity, a longer refractory period and a greater degree of high-frequency conduction block at 200 Hz. Light microscopic and ultrastructural analysis 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 increased median diameters, with evidence of abnormally large swollen axons. Plots of axonal diameter versus myelination ratio showed that post-injury, dorsal column axons of all diameters had thinner myelin sheaths. Noninjured dorsal column axons had a median myelination ratio (1.56) which was within the optimal range (1.43-1.67) for axonal conduction, whereas injured dorsal column axons had a median myelination ratio (1.33) below the optimal value. These data suggest that maladaptive alterations occur postinjury to myelin sheath thickness which reduce the efficiency of axonal signal transmission.In conclusion, chronically injured dorsal column axons show physiological evidence of dysfunction and morphological changes in axonal diameter and reduced myelination ratio. These maladaptive alterations to injured axons, including decrease in myelin thickness and the appearance of axonal swellings, contribute to the decreased excitability of chronically injured axons. These results further clarify the mechanisms underlying neurological dysfunction after chronic neurotrauma and have significant implications regarding approaches to augment neural repair and regeneration.