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

Abstract

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.

Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma

“…After experimental TSCI, a profound reduction in spinal cord blood flow occurs, which progressively worsens (21) and may last for 24 h (22). In a recent study assessing the effects of EPO on the clinical course after subarachnoid hemorrhage in a rabbit model, rhEPO treatment dramatically attenuated the intense intracerebral arterial spasm Extensive white matter preservation can be observed in the rhEPO-treated group.…”

Effects of MK801 on evoked potentials, spinal cord blood flow and cord edema in acute spinal cord injury in rats

“…27,28 Changes in evoked potential amplitude correlate with severity of the SCI and posttraumatic ischemia, and the latter is reversible by pharmacological intervention. Increase in SCBF at the site of SCI correlates with improvement in the function of acutely injured spinal axons, 25,29 and glutamate signaling may play a role in modulation of blood¯ow and blood brain barrier permeability. 30 Therefore, we hypothesize that treatment with an NMDA antagonist after acute SCI would a ect axonal function by blocking NMDA receptors and reducing neurotoxicity at the injury site, and that there would be an increase in blood¯ow and a decrease in edema in the injured spinal cord.…”

Quantitative assessment of spinal cord perfusion by using contrast-enhanced ultrasound in a porcine model with acute spinal cord contusion

“…A majority of studies reported significant posttraumatic hypoperfusion in adjacent segments of spinal cord. [17][18][19] Likewise, a number of clinical and experimental studies had shown less cerebral blood flow in and around contused brain parenchyma. 20,21 However, this study showed that on CDFI and CEUS there was a correspondingly significant hypervascularity and hyperperfusion in the adjacent region, which at least lasted 120 min.…”