Evaluation of the Effects of Ceftriaxone and N-acetylcysteine on Functional Recovery after Spinal Cord Injury in Rats

Abstract

Background: Spinal cord injury(SCI) is a leading cause of long-term neurological disability in worldwide. The pathophysiology of SCI involves a primary mechanical injury followed by a cascade of secondary biochemical and cellular events. Current pharmacological options for significant recovery from SCI are limited. Methylprednisolone(MP) has been clinically used to reduce histological damage as well as neurological dysfunction after SCI, but its neuroprotective efficacy is controversial. β-lactam antibiotic ceftriaxone(CEF) and N-acetyl cysteine(NAC) have been reported to induce neuroprotection in animal models of neurodegenerative disorders. This study aimed to evaluate the effect of CEF, NAC, and their combination on functional recovery and histological damage in experimental spinal cord injury. Methods: Male rats were randomly divided into 6 groups (n=7): Saline; MP; PRE-CEF; POST-CEF; NAC and CEF+NAC. Spinal cord injury was performed on rats under general anesthesia using NSRC(Neurosciences Research Center) impactor. Locomotor recovery after SCI was monitored using the locomotor rating scale of Basso, Beattie and Bresnahan (BBB). At the end of the study, animals were perfused with 10% formaldehyde and cross-sections of tissue samples were stained with hematoxylin–eosin for histopathological analysis. Results: In comparison with the saline group, locomotor recovery in other treatment groups was significant. Locomotor recovery in PRE-CEF and CEF+NAC groups was more effective than other groups. On the other hand, quantification scores of histological analysis showed that CEF or NAC treatment alone and CEF+NAC administration significantly reduced the severity of histopathological damage as compared with saline group. Conclusion: The results suggest that treatment with CEF and NAC either separately or in combination promote long-term functional locomotor recovery after SCI that it is associated with effective reduction of histopathological lesion