Proceedings of The Physiological Society
King's College London (2011) Proc Physiol Soc 22, PC29
Characterising functional, anatomical and electrophysiological changes from acute to chronic stages of spinal contusion injury
N. James1, K. Bartus1, D. Rowlands1, C. Swain1, J. Grist1, S. B. McMahon1, E. J. Bradbury1
1. King's College London, London, United Kingdom.
Traumatic spinal cord injury (SCI) generally results in severe motor, sensory, and autonomic deficits below the level of the injury. As contusion injuries are the most common form of SCI in humans, an animal model of spinal contusion injury provides a clinically relevant tool for studying pathological changes that occur following SCI and to assess the efficacy of potential therapeutic interventions. We have performed a detailed characterisation of some of the physiological changes that occur from acute to chronic stages post injury in this model, using a novel electrophysiological technique to assess axonal conduction through the lesion over time. Anaesthetised adult rats (using a mixture of ketamine (60 mg/kg) and medetomidine (0.25 mg/kg), administered i.p.) received a 150kD (Infinite Horizons) contusion injury. Saline (3-5 ml) and baytril (5 mg/kg) were given subcutaneously twice daily for 3 and 7 days, respectively, post-injury. Electrophysiological recordings were performed at a number of time points (1, 7, 14, 28 and 84 days) post-injury. Animals were deeply anaesthetised with urethane (1.25 g/kg, i.p.), and depth of anaesthesia was regularly assessed by monitoring pedal withdrawal reflexes and respiratory rate. Acutely (1 day) post-injury there was a complete absence of conduction across the contusion site. This increased slightly in the sub-acute stage (1 week), with the percentage of axons conducting across the injury gradually increasing as the injury progressed to chronic stages (4 - 12 weeks). The behavioural assessments (BBB locomotor scale and ladder walking) exhibited a similar pattern to the electrophysiological data at earlier time points, highlighting an initial severe functional deficit, with gradual improvement over the sub-acute stage. There were however, no further improvements in performance beyond 4 weeks using behavioural assessments. Anatomical characterisation was also performed at the different injury time points, to assess the degree of tissue loss, cell death and glial scarring. Furthermore, demyelination and remyelination was assessed following contusion injury at the electron microscopic level. Thus, we have provided a detailed characterisation of changes over time in a clinically relevant spinal injury model. Such thorough assessments, which combine electrophysiological and behavioural function with anatomical measures, could prove invaluable to furthering our understanding of mechanisms underlying the pathological events that occur following spinal cord injury, and for assessing potential therapies aimed at promoting repair.
Where applicable, experiments conform with Society ethical requirements