Secondary damage after spinal cord (SC) injury remains without a clinically effective
drug treatment. To explore the
neuroprotective effects of cell-permeable
reduced glutathione monoethyl
ester (GSHE), rats subjected to SC
contusion using the New York University impactor were randomly assigned to receive intraperitoneally GSHE (total dose of 12 mg/kg),
methylprednisolone sodium succinate (total dose of 120 mg/kg), or
saline solution as vehicle. Motor function, assessed using the Basso-Beattie-Bresnahan scale for 8 weeks, was significantly better in GSHE (11.2+/-0.6, mean+/-S.E.M., n=8, at 8 weeks) than
methylprednisolone (9.3+/-0.6) and vehicle (9.4+/-0.7) groups. The number of neurons in the red nuclei labeled with FluoroRuby placed caudally to the injury site was significantly higher in GSHE (158+/-9.3 mean+/-S.E.M., n=4) compared with
methylprednisolone (53+/-14.7) and vehicle (46+/-16.4) groups. Differences in the amount of spared SC tissue at the epicenter and neighboring areas were not significant among experimental groups. In a second series of experiments, using similar treatment groups (n=6), regional changes in microvascular SC blood flow were evaluated for 100 min by
laser-Doppler flowmetry after
clip compression injury. SC blood flow fell in vehicle-treated rats 20% below baseline and increased significantly with
methylprednisolone approximately 12% above baseline; changes were not greater than 5% in rats given GSHE. In conclusion, GSHE given to rats early after moderate SC
contusion/compression improves functional outcome and red nuclei neuron survival significantly better than
methylprednisolone and vehicle, and stabilizes SC blood flow. These results support further investigation of
reduced glutathione supplementation after acute SC injury for future clinical application.