The effect of nimodipine and dextran on axonal function and blood flow following experimental spinal cord injury.

There is evidence that posttraumatic ischemia is important in the pathogenesis of acute spinal cord injury (SCI). In the present study spinal cord blood flow (SCBF), measured by the hydrogen clearance technique, and motor and somatosensory evoked potentials (MEP and SSEP) were recorded to evaluate whether the administration of nimodipine and dextran 40, alone or in combination, could increase posttraumatic SCBF and improve axonal function in the cord after acute SCI. Thirty rats received a 53-gm clip compression injury on the cord at T-1 and were then randomly and blindly allocated to one of six treatment groups (five rats in each). Each group was given an intravenous infusion of one of the following over 1 hour, commencing 1 hour after SCI: placebo and saline; placebo and dextran 40; nimodipine 0.02 mg/kg and saline; nimodipine 0.02 mg/kg and dextran 40; nimodipine 0.05 mg/kg and saline; and nimodipine 0.05 mg/kg and dextran 40. The preinjury physiological parameters, including the SCBF at T-1 (mean +/- standard error of the mean: 56.84 +/- 4.51 ml/100 gm/min), were not significantly different (p greater than 0.05) among the treatment groups. Following SCI, there was a significant decrease in the SCBF at T-1 (24.55 +/- 2.99 ml/100 gm/min; p less than 0.0001) as well as significant changes in the MEP recorded from the spinal cord (MEP-C) (p less than 0.0001), the MEP recorded from the sciatic nerve (MEP-N) (p less than 0.0001), and the SSEP (p less than 0.002). Only the combination of nimodipine 0.02 mg/kg and dextran 40 increased the SCBF at T-1 (43.69 +/- 6.09 ml/100 gm/min; p less than 0.003) and improved the MEP-C (p less than 0.0001), MEP-N (p less than 0.04), and SSEP (p less than 0.002) following SCI. With this combination, the changes in SCBF were significantly related to improvement in axonal function in the motor tracts (p less than 0.0001) and somatosensory tracts (p less than 0.0001) of the cord. This study provides quantitative evidence that an increase in posttraumatic SCBF can significantly improve the function of injured spinal cord axons, and strongly implicates posttraumatic ischemia in the pathogenesis of acute SCI.