Glutathione monoethyl ester improves functional recovery, enhances neuron survival, and stabilizes spinal cord blood flow after spinal cord injury in rats.
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.
Guízar-Sahagún
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Research Unit for Neurological Diseases, Instituto Mexicano del Seguro Social, Mexico City, Mexico. guizarg@prodigy.net.mx
Ibarra
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Espitia
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Martínez
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Madrazo
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Franco-Bourland
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D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008833:Microcirculation; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D012012:Red Nucleus / Q000187:drug effects / Q000473:pathology; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology*
D005904:Glial Fibrillary Acidic Protein; C042431:S-ethyl glutathione; D005978:Glutathione