17beta-estradiol is protective in spinal cord injury in post- and pre-menopausal rats.
The neuroprotective effects of 17 beta -estradiol have been shown in models of central nervous system injury, including ischemia, brain injury, and more recently, spinal cord injury (SCI). Recent epidemiological trends suggest that SCIs in elderly women are increasing; however, the effects of menopause on estrogen-mediated neuroprotection are poorly understood. The objective of this study was to evaluate the effects of 17beta-estradiol and reproductive aging on motor function, neuronal death, and white matter sparing after SCI of post- and pre-menopausal rats. Two-month-old or 1- year-old female rats were ovariectomized and implanted with a silastic capsule containing 180 microg/mL of 17beta-estradiol or vehicle. Complete crush SCI at T8-9 was performed 1 week later. Additional animals of each age group were left ovary-intact but were spinal cord injured. The Basso, Beattie, Bresnahan (BBB) locomotor test was performed. Spinal cords were collected on post-SCI days 1, 7, and 21, and processed for histological markers. Administration of 17beta-estradiol to ovariectomized rats improved recovery of hind-limb locomotion, increased white matter sparing, and decreased apoptosis in both the post- and pre-menopausal rats. Also, ovary-intact 1-year-old rats did worse than ovary-intact 2-month-old rats, suggesting that endogenous estrogen confers neuroprotection in young rats, which is lost in older animals. Taken together, these data suggest that estrogen is neuroprotective in SCI and that the loss of endogenous estrogen-mediated neuroprotective seen in older rats can be attenuated with exogenous administration of 17beta-estradiol.
Chaovipoch
Pimonporn
P
Department of Neurological Surgery, University of California, Davis, California 95616, USA. clfloyd@ucdavis.edu
Jelks
Karen A Bozak
KA
Gerhold
Lynnette M
LM
West
Eric J
EJ
Chongthammakun
Sukumal
S
Floyd
Candace L
CL
D000818:Animals; D048588:Benzoxazines; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D004958:Estradiol / Q000627:therapeutic use*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006614:Hindlimb / Q000502:physiology; D020287:In Situ Nick-End Labeling; D007211:Indoles; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents; D009930:Organic Chemicals; D010052:Ovariectomy; D010078:Oxazines; D051381:Rats; D012741:Sexual Maturation / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D014554:Urination / Q000187:drug effects
D048588:Benzoxazines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007211:Indoles; D018696:Neuroprotective Agents; D009930:Organic Chemicals; D010078:Oxazines; C435731:fluoro jade; C018588:Luxol Fast Blue MBS; C028911:cresyl violet; D004958:Estradiol