Evaluation of spinal cord protective threshold of serum memantine, an NMDA receptor antagonist, in a rabbit model of paraplegia.

Abstract

To evaluate the threshold of serum memantine for prevention of spinal cord injury (SCI) in a rabbit paraplegic model. Forty-two New Zealand white rabbits were divided into 7 groups. Preoperatively, oral memantine was given starting from 60mg OD for 7days in the initial group, then reducing the dose and/or duration to 60mg OD for 5days, 30mg OD for 5days, 30mg OD for 3days, 15mg OD for 3days, 30mg single dose, and 60mg single dose, in subsequent 6 groups. A paraplegic model was created by clamping both infrarenal aorta and inferior vena cava (IVC) for 45min. Motor evoked potentials (MEPs), modified Tarlov score (0-5), serum memantine concentration, and histopathology of the spinal cord were evaluated. Half of all rabbits (21/42) showed spinal protection. Receiver operating characteristic (ROC) curve analysis showed serum level of 4.5ng/ml as a cutoff value for spinal protection (sensitivity 86%, specificity 62%, area under the curve (AUC) 0.785, P = .002). Sixteen rabbits had serum level ≥ 4.5ng/ml (group A), with 26 rabbits having < 4.5ng/ml (group B). Further comparison was done between groups A and B. The mean modified Tarlov score at 6, 24, 48, and 72h was 4.5 ± 0.9 and 2.4 ± 1.6, in groups A and B, respectively (P < .001). The modified Tarlov score showed positive correlation with serum memantine level (Spearman's rho = 0.618, P = .01). Results of MEP and histopathology were significantly better for group A. We showed that memantine is protective against SCI at serum levels ≥ 4.5ng/ml in a rabbit model; thus, it can be a potential adjunct for spinal protection during thoracic/thoracoabdominal aortic surgeries.