Abstract
Cellular mechanisms of secondary damage progression following spinal cord injury remain unclear. We have studied the extent of tissue damage from 15 min to 10 weeks after injury using morphological and biochemical estimates of lesion volume and surviving grey and white matter. This has been achieved by semi-quantitative immunocytochemical methods for a range of cellular markers, quantitative counts of white matter axonal profiles in semi-thin sections and semi-quantitative Western blot analysis, together with behavioural tests (BBB scores, ledged beam, random rung horizontal ladder and DigiGait™ analysis). We have developed a new computer-controlled electronic impactor based on a linear motor that allows specification of the precise nature, extent and timing of the impact. Initial (15 min) lesion volumes showed very low variance (1.92±0.23 mm3, mean±SD, n = 5). Although substantial tissue clearance continued for weeks after injury, loss of grey matter was rapid and complete by 24 hours, whereas loss of white matter extended up to one week. No change was found between one and 10 weeks after injury for almost all morphological and biochemical estimates of lesion size or behavioural methods. These results suggest that previously reported apparent ongoing injury progression is likely to be due, to a large extent, to clearance of tissue damaged by the primary impact rather than continuing cell death. The low variance of the impactor and the comprehensive assessment methods described in this paper provide an improved basis on which the effects of potential treatment regimes for spinal cord injury can be assessed.
Highlights
Spinal cord trauma is often devastating for the patients as it can cause permanent loss of motor, sensory and autonomic nervous system functions below the level of the injury
From an examination of the literature it is apparent that pathological processes following spinal cord injury, which are involved in clearing damaged tissue resulting from the primary injury and progressive cyst formation, may not be clearly distinguished from further loss of grey and/or white matter due to apoptosis and continuing axonal degeneration in the subsequent days and weeks
In this paper we describe a contusion model with low variance, the progression in lesion size, neuron numbers and myelinated axon numbers, as well as various biochemical parameters and behavioural performance, in the hours, days and weeks following a spinal injury in young adult rats
Summary
Spinal cord trauma is often devastating for the patients as it can cause permanent loss of motor, sensory and autonomic nervous system functions below the level of the injury. From an examination of the literature it is apparent that pathological processes following spinal cord injury, which are involved in clearing damaged tissue resulting from the primary injury and progressive cyst formation, may not be clearly distinguished from further loss of grey and/or white matter due to apoptosis and continuing axonal degeneration in the subsequent days and weeks. Understanding which tissue is at risk of secondary destruction following spinal cord injury and the time course over which this damage occurs, is critical for the design and assessment of therapies aimed at limiting consequences of trauma. In this paper we describe a contusion model with low variance, the progression in lesion size, neuron numbers and myelinated axon numbers, as well as various biochemical parameters and behavioural performance, in the hours, days and weeks following a spinal injury in young adult rats. Consistent with these observations, no change was found between one and 10 weeks after injury for most of the morphological and biochemical estimates of lesion size or quantitative behavioural methods used
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