title: Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats.
abstract: 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 (40 g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 μg 17β-estradiol (estrogen) for 7 days 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 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 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. Experimental studies with low dose estrogen therapy in chronic spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes that could ameliorate the degenerative pathways in chronic SCI as shown in (a). Furthermore, the alterations in local spinal blood flow could be significantly alleviated with low dose estrogen therapy. This therapy led to the preservation of the structural integrity of the spinal cord (b), which in turn led to the improved functional recovery as shown (c).
authors.affiliation: Department of Neurology and Neurosurgery, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Supriti
authors.initials: S
authors.lastname: Samantaray
authors.affiliation: Department of Neurology and Neurosurgery, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Arabinda
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of Neurology and Neurosurgery, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Matzelle
authors.affiliation: Department of Anesthesia, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Shan P
authors.initials: SP
authors.lastname: Yu
authors.affiliation: Department of Anesthesia, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Neurology and Neurosurgery, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Abhay
authors.initials: A
authors.lastname: Varma
authors.affiliation: Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA.
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Ray
authors.affiliation: Department of Neurology and Neurosurgery, Medical University of South Carolina, Charleston, South Carolina, USA.|Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina, USA.
authors.forename: Naren L
authors.initials: NL
authors.lastname: Banik
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage*; D000818:Animals; D002908:Chronic Disease; D004958:Estradiol / Q000008:administration & dosage*; D004967:Estrogens / Q000008:administration & dosage; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D043925:Angiogenesis Inducing Agents; D004967:Estrogens; D004958:Estradiol
keywords: angiogenesis; axonal protection; chronic spinal cord injury; locomotor function; low dose estrogen; neuroprotection