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Estrogen as a neuroprotective agent in rat spinal cord injury
Author(s) -
Banik N. L.,
Sribnick E. A.,
Wingrave J. M.,
Matzelle D. D.,
Wilford G. G.,
Ray S. K.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.41_3.x
Subject(s) - estrogen , neuroprotection , spinal cord injury , calpain , endocrinology , penumbra , medicine , lesion , ovariectomized rat , pharmacology , chemistry , spinal cord , pathology , ischemia , biochemistry , psychiatry , enzyme
Spinal cord injury (SCI) is a neurological problem affecting approximately 11 000 Americans each year. Several treatment agents have been proposed; however, only methylprednisolone has limited efficacy. Estrogen is a multiactive neuroprotectant with antioxidant and anti‐inflammatory properties and attenuates calcium (Ca 2+ ) influx following neuronal injury. To examine the neuroprotective effects of estrogen in SCI, we induced SCI (40 g/cm injury) in rats. Treatment groups were sham (laminectomy only), SCI plus vehicle, and SCI plus estrogen. Injured rats were treated with either 4 mg/kg 17 β‐estradiol (estrogen group) or dimethylsulfoxide (vehicle group) at 15 min and 24 h following injury. All rats were killed at 48 h to analyze SCI segments for calpain content and Bax/Bcl‐2 ratio by Western blotting. Tissue was also examined using calcium green‐2 to measure intracellular [Ca 2+ ], JC‐1 to measure mitochondrial membrane potential, and double immunofluorescence for macrophages and calpain. Calpain content in the lesion penumbra, adjacent to the injury, was higher in vehicle than sham and this increase was attenuated in estrogen treated rats. In the lesion penumbra, the Bax/Bcl‐2 ratio was increased in vehicle rats as compared to sham. This increase was attenuated in estrogen treated rats. Estrogen treated rats had less Ca 2+ influx, less inflammatory cell infiltration, and increased maintenance of mitochondrial membrane potential compared to vehicle treated rats. Our preliminary data suggest that estrogen may be effective in decreasing Ca 2+ influx, inflammatory cell infiltration, and Bax/Bcl‐2 ratio following SCI. Acknowledgements: Supported in part by grants from NIH‐NINDS and South Carolina Electric and Gas.