期刊
JOURNAL OF NEUROCHEMISTRY
卷 137, 期 4, 页码 604-617出版社
WILEY
DOI: 10.1111/jnc.13610
关键词
angiogenesis; axonal protection; chronic spinal cord injury; locomotor function; low dose estrogen; neuroprotection
资金
- NIH [R01-NS31622, R01-NS45967]
- Veterans Administration [1IOBX00126, 1IOBX002349]
- South Carolina State Spinal Cord Research Fund [SCIRF-2015P-01, SCIRF-2015P-04, SCIRF-2015-I-01]
- Department of Neurosurgery, MUSC
- MUSC-CTSA program
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 reduces inflammation, attenuates cell death, and protects axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of this study was to investigate whether low doses of estrogen in post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 mu g 17 beta-estradiol (estrogen) for 7days following SCI and compared with vehicle-treated injury and laminectomy (sham) controls. Histology (H&E staining), immunohistofluorescence, Doppler laser technique, and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, the expression of angiogenic factors, axonal degeneration, and locomotor function (Basso, Beattie, and Bresnahan rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42days 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 with vehicle-treated SCI 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.
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