Minocycline treatment inhibits lipid peroxidation, preserves spinal cord ultrastructure, and improves functional outcome after traumatic spinal cord injury in the rat.

STUDY DESIGN: A prospective, randomized experimental research.

OBJECTIVE: To evaluate the short- and long-term neuroprotective effects of minocycline on the secondary injury process of an experimental traumatic spinal cord injury (SCI) model.

SUMMARY OF BACKGROUND DATA: Traumatic SCI is a devastating problem of health that results in high morbidity and mortality rates. The loss of function after SCI results from both the primary mechanical insult and the subsequent, multifaceted secondary response.

METHODS: A total of 80 adult male Spraque-Dawley rats (breeded by the Baskent University Animal Research Center) were randomly divided into 4 groups. A T10 contusion injury was produced by using modified Allen technique in all groups except the control group. No medication was administered to the rats in the trauma group. Minocycline was administered intraperitoneally and intravenously to the treatment groups. Short-term and/or long-term neuroprotective effects of minocycline on the lipid peroxidation (malondialdehyde, glutathione), apoptosis (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling), ultrastructure of spinal cord (tissue electron microscopy), and behavioral assessments (Basso-Beattie-Bresnahan) were evaluated.

RESULTS: As compared with the trauma group, tissue malondialdehyde and glutathione levels demonstrated that minocycline significantly diminishes lipid peroxidation. Electromicroscopic study showed that minocycline preserves the ultrastructure of spinal cord tissue in the early post-traumatic period. Minocycline treatment significantly reduced the number of terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling positive cells both 1 day and 28 days after SCI. Behavioral assessments showed significant improvement in the hind limb functions of minocycline receiving rats starting 7 days after the SCI. Any statistically significant difference was not found between intraperitoneal or intravenous routes for minocycline injection.

CONCLUSION: Minocycline is neuroprotective and contributes to functional improvement after traumatic SCI by eliminating the destructive process of secondary injury. Having both satisfying anti-inflammatory and antiapoptotic effects in experimental models, it promises to be of therapeutic use in human SCI.