The long-term effects of pre-treatment with activated protein C in a rat model of compression-induced spinal cord injury

Abstract

Objectives: Recently, we demonstrated that activated protein C (APC) can lessen the severity of spinal cord injury (SCI) in rats during the acute and subacute phases. The purpose of the present study is to determine the long-term effects of pre-treatment with APC following SCI in rats. Methods: The motor function of rats was assessed using the inclined-plane test during 8 weeks after SCI, and the grid runway test 7 weeks after the trauma. Somatosensory evoked potentials (SEPs), brainstem-derived motor evoked potentials (B-MEPs) and corticomotor evoked potentials (CMEPs) were used to quantify axonal function 8 weeks after SCI. Morphometric analysis of the spinal cord lesion was carried out to determine lesion size. Twelve male Sprague-Dawley rats were randomly allocated to either APC (25 IU/kg) or saline group and then subjected to 20 g compression injury of the spinal cord for 20 min at T12. The sham group (n=6) received laminectomy alone. Results: APC significantly reduced the motor disturbances and electrophysiological impairments induced by SCI. APC-treated animals also showed a trend towards a reduction in lesion size. However, this change, was not significant. Conclusion: Pre-treatment with APC attenuates the harmful effect of SCI not only during the acute and subacute phases but also in the chronic stage.