Ratlarda Oluşturulan Medulla Spinalis Travma Modelinde Uzak İskemik Önkoşullamanın Nöroprotektif Etkinliğinin Araştırılması

Abstract

Objective: To investigate the neuroprotective effect of remote ischemic pre-conditioning (RIPC) and the role of kynurenic acid (KYNA), a product of tryptophan metabolism, in the mechanism of RIPC by comparing blood S100B levels and histopathological results in a rat model of spinal cord injury. Design: Experimental animal study. Setting: Faculty of Medicine, Hacettepe University, Ankara, Turkey. Interventions: Thirty-one male Sprague-Dawley rats were divided into 3 groups. In Group I (Sham, n=9), all procedures until laminectomy were performed. In Group II (I/R, n=11), laminectomy was performed and after 1 min of complete spinal cord ischemia, reperfusion was allowed for 1 h (I/R injury). In Group III (RIPC+I/R, n=8), 3 cycles of 10-minute RIPC was applied to the right hind leg, followed by laminectomy and I/R. All rats were sacrificed two hours after the procedure and blood and medulla spinalis tissue samples were collected. Outcome measures: The comparison of S100B and KYNA levels and histological scores in the Sham, I/R, and RIPC + I/R groups. Additionally, we aimed to assess whether KYNA concentration was associated with S100B (marker of neuronal injury) levels or histological scores of medulla spinalis injury. Results: KYNA and S100B levels were significantly different between the sham and I/R groups (p = 0.016 and p = 0.022, respectively). Although post-hoc pairwise comparisons for the I/R and RIPC+I/R groups were not significant in either comparison, rats treated with RIPC had relatively lower concentrations of KYNA and S100B compared to the I/R group. Histological analyses revealed significantly higher white and gray matter damage scores in both the I/R and RIPC+I/R groups than in the sham group (p = 0.001 and p < 0.001, respectively). Although median scores were relatively worse in the RIPC+I/R group than in the I/R group, these groups were statistically similar. There were no significant correlations between KYNA concentration, S100B concentration, and histological scores. Conclusion: This study showed that S100B and KYNA levels and histological scores for neuronal damage were significantly increased in a rat model of spinal I/R injury. S100B and KYNA levels were lower in the RIPC+I/R group than in the I/R group, albeit statistical significance was not reached. Histological analyses revealed worse tissue outcomes in the RIPC+I/R group than in the I/R group. Keywords: Medulla spinalis, remote ischemic preconditioning, reperfusion injury, S100B, KYNA