Acute administration of oestradiol or progesterone in a spinal cord ischaemia-reperfusion model in rats

Abstract

Objectives: Despite research into protective pharmacological adjuncts, paraplegia persists as a dreaded complication after thoracic and thoracoabdominal aortic interventions. Reports on gender-related neurological outcomes after ischaemic and traumatic brain injuries have led to increased interest in hormonal neuroprotective effects and have generated other studies seeking to prove the neuroprotective effects of the therapeutic administration of 17β-oestradiol and of progesterone. We hypothesised that acute administration of oestradiol or progesterone would prevent or attenuate spinal cord ischaemic injury induced by occlusion of the descending thoracic aorta.

Methods: Male rats were divided into groups receiving 280 µg/kg of 17β-oestradiol or 4 mg/kg of progesterone or vehicle 30 min before transitory endovascular occlusion of the proximal descending thoracic aorta for 12 min. Hindlimb motor function was assessed by a functional grading scale (that of Basso, Beattie and Bresnahan) for 14 days after reperfusion. On the 14th day, a segment of the thoracolumbar spinal cord was harvested and prepared for histological and immunohistochemical analyses.

Results: There was significant impairment of the motor function of the hindlimb in the 3 study groups, with partial improvement noticed over time, but no difference was detected between the groups. On Day 1 of assessment, the 17β-oestradiol group had a functional score of 9.8 (0.0-16.5); the progesterone group, a score of 0.0 (0-17.1) and the control group, a score of 6.5 (0-16.9); on the 14th day, the 17β-oestradiol group had a functional score of 18.0 (4.4-19.4); the progesterone group had a score of 7.5 (0-18.5) and the control group had a score of 17.0 (0-19.9). Analysis of the grey matter showed that the number of viable neurons per section was not different between the study groups on the 14th day. Immunostaining of the spinal cord grey matter was also similar among the 3 groups.

Conclusions: Acute administration of oestradiol or of progesterone 30 min before transitory occlusion of the proximal descending thoracic aorta of male rats could not prevent or attenuate spinal cord ischaemic injury based on an analysis of functional and histological outcomes.

Keywords: Animal model; Aortic operation; Complication; Ischaemia–reperfusion injury; Paraplegia; Related subjects; Spinal cord; Surgery.