Administration of low dose-estrogen attenuates persistent inflammation promotes angiogenesis and improves locomotor function following chronic spinal cord injury in rats

摘要

Spinal cord injury (SCI) causes loss of neurological function and, depending upon the severity of injury, may lead to paralysis. Currently, no FDA approved pharmacotherapy is available for SCI. High-dose methylprednisolone is widely used, but this treatment is controversial. We have previously shown that low doses of estrogen treatment reduced inflammation, attenuated cell death, and protected axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of the current study was to investigate whether low doses of estrogen treatment post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40 g•cm force) was induced at T10 in young adult male rats. Rats were treated with 10 or 100 μg 17β-estradiol for 7 days following injury and compared with vehicle treated injury and laminectomy (sham) controls. Histology (H&E), immunohistofluorescence, Doppler laser technique and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, expression of angiogenic factors, axonal degeneration and locomotor function (BBB rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42 days post-injury. A reduction in glial reactivity, attenuation of axonal and myelin damage, protection of cells, increased expression of angiogenic factors and microvessel growth, and improved locomotor function were found following estrogen treatment compared to vehicle treated injured rats. These results suggest that treatment with a very low dose of estrogen has significant therapeutic implications for the improvement of locomotor function in chronic SCI.