Abstract
It has been shown previously that after spinal cord injury, the loss of grey matter is relatively faster than loss of white matter suggesting interventions to save white matter tracts offer better therapeutic possibilities. Loss of white matter in and around the injury site is believed to be the main underlying cause for the subsequent loss of neurological functions. In this study we used a series of techniques, including estimations of the number of axons with pathology, immunohistochemistry and mapping of distribution of pathological axons, to better understand the temporal and spatial pathological events in white matter following contusion injury to the rat spinal cord. There was an initial rapid loss of axons with no detectable further loss beyond 1 week after injury. Immunoreactivity for CNPase indicated that changes to oligodendrocytes are rapid, extending to several millimetres away from injury site and preceding much of the axonal loss, giving early prediction of the final volume of white matter that survived. It seems that in juvenile rats the myelination of axons in white matter tracts continues for some time, which has an important bearing on interpretation of our, and previous, studies. The amount of myelin debris and axon pathology progressively decreased with time but could still be observed at 10 weeks after injury, especially at more distant rostral and caudal levels from the injury site. This study provides new methods to assess injuries to spinal cord and indicates that early interventions are needed for the successful sparing of white matter tracts following injury.
Highlights
Injuries to the spinal cord, which are most prevalent in young people, often result in permanent life-long impairments of motor, sensory and autonomic nervous system functions
At 1-week post injury there was much more cell and myelin debris in the centre of the injury and some macrophages were present in the medial parts of the dorsal column (DC); part of this area had been cleared of tissue and a central cyst cavity had started to form
The appearance of the white matter tracts at 4 weeks was similar to that illustrated for 10 weeks (Fig. 1); only a small part of the DC remained at the injury centre located at the outer rim of cord immediately underneath the pial surface
Summary
Injuries to the spinal cord, which are most prevalent in young people, often result in permanent life-long impairments of motor, sensory and autonomic nervous system functions. Our previous study has shown that the majority of grey matter loss in the spinal cord following a contusion injury occurs within hours of the injury and is mostly complete by 24 hours [1] This may be too short a time window for effective intervention to be practicable in many clinical circumstances. Loss of white matter appears to extend over several days post injury [1] This longer period provides an opportunity for treatments aimed at axon-sparing to be effective in retaining functional connections. A better basic knowledge of these pathological events is needed in order to develop and evaluate new treatment regimes These needs are evident given that decades of SCI research have given numerous pre-clinical studies reporting various strategies to improve the outcome of spinal injuries, which have not been translated into the clinical setting [2,3]
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