Demyelinating lesions induced by intraspinal injection of gliotoxin have been studied for many years in order to gain insights into reasons for failure of remyelination and to improve understanding of the axonal conduction disorders in multiple sclerosis. Although the electrophysiological correlates of experimental demyelination and remyelination are well established, the behavioural effects have not been investigated. In this study we aimed to determine whether behavioural deficits could be detected during spinal cord demyelination, and furthermore, whether remyelination was associated with return of lost function. We used injections of the gliotoxin ethidium bromide into the dorsal funiculus of the cervical spinal cord of the rat to induce zones of demyelination and compared the effects on locomotion with those resulting from saline injections. The resulting locomotor deficits were quantified by analysis of foot placement during traverse of a horizontal 18 mm diameter wooden beam. Following ethidium bromide injection there was a decrease in security of foot placement, that recovered by approximately 5 weeks post-injection. In a second experiment, remyelination was prevented by exposure of the spinal cord to 40 Gy of X-irradiation. Behavioural deficits were induced as before, but the animals failed to recover throughout the duration of the experiment. Saline-injected animals in both experiments exhibited minimal deficits and quickly recovered. We conclude that demyelination produces detectable behavioural deficits which disappear following spontaneous remyelination.

This study was designed to determine whether an intervention proven effective in the laboratory to ameliorate the effects of experimental spinal cord injury could provide sufficient benefit to be of value to clinical cases. Intraspinal olfactory ensheathing cell transplantation improves locomotor outcome after spinal cord injury in ‘proof of principle’ experiments in rodents, suggesting the possibility of efficacy in human patients. However, laboratory animal spinal cord injury cannot accurately model the inherent heterogeneity of clinical patient cohorts, nor are all aspects of their spinal cord function readily amenable to objective evaluation. Here, we measured the effects of intraspinal transplantation of cells derived from olfactory mucosal cultures (containing a mean of ∼50% olfactory ensheathing cells) in a population of spinal cord–injured companion dogs that accurately model many of the potential obstacles involved in transition from laboratory to clinic. Dogs with severe chronic thoracolumbar spinal cord injuries (equivalent to ASIA grade ‘A’ human patients at ∼12 months after injury) were entered into a randomized double-blinded clinical trial in which they were allocated to receive either intraspinal autologous cells derived from olfactory mucosal cultures or injection of cell transport medium alone. Recipients of olfactory mucosal cell transplants gained significantly better fore–hind coordination than those dogs receiving cell transport medium alone. There were no significant differences in outcome between treatment groups in measures of long tract functionality. We conclude that intraspinal olfactory mucosal cell transplantation improves communication across the damaged region of the injured spinal cord, even in chronically injured individuals. However, we find no evidence for concomitant improvement in long tract function.

Evidence of intervertebral disk degeneration (IVDD) is extremely common in dogs, and its prevalence increases with age. It has many important consequences because degeneration of the intervertebral disks often is a prelude to disk herniation, which can injure the spinal cord, spinal nerves, or both. This review summarizes the advances in diagnosis and treatment of IVDD that have been made since the 1950s when the first detailed description of the degenerative changes was published. It also discusses new approaches to treatment of the associated spinal cord injury and new methods by which to classify injury severity that are currently under development.

Objective—To determine whether magnetic resonance imaging findings in dogs with paraplegia caused by thoracolumbar intervertebral disk extrusion were predictive of clinical outcome. Design—Retrospective case series. Animals—77 dogs. Procedure—Medical records and magnetic resonance images were reviewed; clinical outcome was classified as successful (regained ability to walk with no more than mild neurologic deficits) or unsuccessful (severe neurologic deficits persisted). The prognostic value of magnetic resonance imaging was compared with prognostic value of deep pain perception, duration of clinical signs, and rate of onset of clinical signs. Result—33 (43%) dogs had areas of hyperintensity of the spinal cord greater than or equal to the length of the L2 vertebral body on T2-weighted magnetic resonance images. All 44 dogs without areas of hyperintensity on T2-weighted images had a successful outcome, but only 18 of the 33 (55%) dogs with an area of hyperintensity did. Only 5 of 16 dogs with an area of hyperintensity that had also lost deep pain perception had a successful outcome. The odds ratio for an unsuccessful outcome for a dog with an area of hyperintensity (29.87) was higher than the odds ratio for a dog that had lost deep pain perception (5.24). Duration and rate of onset of clinical signs were not associated with clinical outcome. Conclusions and Clinical Relevance—Findings suggest that results of magnetic resonance imaging can be used to predict clinical outcome in dogs with paraplegia caused by intervertebral disk extrusion. (J Am Vet Med Assoc 2005;227:1454–1460)