Agmatine-reduced collagen scar area accompanied with surface righting reflex recovery after complete transection spinal cord injury

Abstract

STUDY DESIGN: Intended to investigate whether agmatine treatment reduces collagen scar area in mice subjected to spinal cord injury (SCI).

OBJECTIVE: The purpose of the present study is to demonstrate the protective effect of agmatine on complete transection SCI mice. SUMMARY OF BACK GROUND DATA: The deposition of collagen that occurs at the lesion site, during the SCI, was well known. Agmatine has been reported to exert neuroprotective effect in various stress models including central nervous system injuries. In the present investigation, we hypothesized that agmatine treatment could rescue the mice subjected to SCI.

METHODS: Complete SCI was made at the T9 level. Agmatine was dissolved in normal saline (100 mg/kg, Sigma, St. Louis, MO) and given intraperitoneally 5 minutes after complete transection daily for 4 weeks (agmatine-treated mice, n = 30). Controls received normal saline in the same manner (experimental control, n = 30). Surface righting reflex test, expression of bone morphogenetic protein-7 (BMP-7), TGFβ-2 (transforming growth factor β-2), and collagen scar area were measured and the results were compared with Mann-Whitney U test using SAS.

RESULTS: Agmatine treatment improved the surface righting reflex of mice at 4 weeks after SCI (P = 0.030). The collagen scar, physical barrier to axon regeneration, was noticeably diminished by agmatine treatment at 4 weeks after SCI (P = 0.001). The expression of BMP-7, which is considered both neuroprotective and neuroregenerative, was increased in agmatine treatment group compared with experimental control group in the early stages after SCI (P = 0.015 at 1 day after SCI; P = 0.010 at 3 days; P = 0.035 at 1 week; P = 0.826 at 2 weeks). The expression of TGFβ-2 correlated with the deposition of the collagen matrix at the lesion site was decreased with agmatine treatment at 1 and 2 weeks after SCI (P = 0.001 at 1 week; P = 0.002 at 2 weeks). Survival rate was found to be higher in agmatine treatment group than in the experimental control group for 4 weeks after SCI (P = 0.076).

CONCLUSION: These results suggest that agmatine treatment could support neuroregeneration by reducing the collagen scar area through decreasing the expression of TGFβ-2 and increasing the expression of BMP-7 after SCI. Especially, the improved surface righting reflex of agmatine-treated group proposes that agmatine treatment have the potency to facilitate functional recovery after SCI. However, the drug (agmatine) warrants further investigation in higher mammals.