A Direct Comparison of Three Clinically Relevant Treatments in a Rat Model of Cervical Spinal Cord Injury

Abstract

Recent preclinical studies have identified three treatments that are especially promising for reducing acute lesion expansion following traumatic spinal cord injury (SCI): riluzole, systemic hypothermia, and glibenclamide. Each has demonstrated efficacy in multiple studies with independent replication, but there is no way to compare them in terms of efficacy or safety, since different models were used, different laboratories were involved, and different outcomes were evaluated. Here, using a model of lower cervical hemicord contusion, we compared safety and efficacy for the three treatments, administered beginning 4 h after trauma. Treatment-associated mortality was 30% (3/10), 30% (3/10), 12.5% (1/8), and 0% (0/7) in the control, riluzole, hypothermia, and glibenclamide groups, respectively. For survivors, all three treatments showed overall favorable efficacy, compared with controls. On open-field locomotor scores (modified Basso, Beattie, and Bresnahan scores), hypothermia- and glibenclamide-treated animals were largely indistinguishable throughout the study, whereas riluzole-treated rats underperformed for the first two weeks; during the last four weeks, scores for the three treatments were similar, and significantly different from controls. On beam balance, hypothermia and glibenclamide treatments showed significant advantages over riluzole. After trauma, rats in the glibenclamide group rapidly regained a normal pattern of weight gain that differed markedly and significantly from that in all other groups. Lesion volumes at six weeks were: 4.8±0.7, 3.5±0.4, 3.1±0.3 and 2.5±0.3 mm ³ in the control, riluzole, hypothermia, and glibenclamide groups, respectively; measurements of spared spinal cord tissue confirmed these results. Overall, in terms of safety and efficacy, systemic hypothermia and glibenclamide were superior to riluzole.