Spinal cord injury (SCI) causes loss of neurological function and, depending on serverity, may cause
paralysis. The only recommended
pharmacotherapy for the treatment of SCI is high-dose
methylprednisolone, and its use is controversial. We have previously shown that
estrogen treatment attenuated cell death, axonal and myelin damage,
calpain and
caspase activities, and
inflammation in acute SCI. The aim of this study was to examine whether posttreatment of SCI with
estrogen would improve locomotor function by protecting cells and axons and reducing
inflammation during the chronic phase following injury. Moderately severe injury (40 g . cm force) was induced in male Sprague-Dawley rats following
laminectomy at T10. Three groups of animals were used:
sham (
laminectomy only), vehicle (
dimethyl sulfoxide;
DMSO)-treated injury group, and
estrogen-treated injury group. Animals were treated with 4 mg/kg
estrogen at 15 min and 24 hr postnjury, followed by 2 mg/kg
estrogen daily for the next 5 days.
After treatment, animals were sacrificed at the end of 6 weeks following injury, and 1-cm segments of spinal cord (lesion, rostral to lesion, and caudal to lesion) were removed for biochemical analyses.
Estrogen treatment reduced COX-2 activity, blocked
nuclear factor-kappaB translocation, prevented glial reactivity, attenuated neuron death, inhibited activation and activity of
calpain and
caspase-3, decreased axonal damage, reduced myelin loss in the lesion and penumbra, and improved locomotor function compared with vehicle-treated animals. These findings suggest that
estrogen may be useful as a promising therapeutic agent for prevention of damage and improvement of locomotor function in chronic SCI. (c) 2010 Wiley-Liss, Inc.