title: Estrogen reduces the severity of autonomic dysfunction in spinal cord-injured male mice.
abstract: Autonomic dysreflexia is an autonomic behavioural condition that manifests after spinal cord injury (SCI) and is characterized by acute, episodic hypertension following afferent stimulation below the level of the injury. Common triggers of autonomic dysreflexia include colorectal distension (CRD), and various somatic stimuli. The development of autonomic dysreflexia is dependent, in part, upon the degree of intraspinal inflammation and the resultant spinal neuroplastic changes that occur following SCI. 17beta-estradiol (E) has neuroprotective, anti-inflammatory and smooth muscle relaxant properties, and is therefore a candidate drug for the treatment and/or prevention of autonomic dysreflexia. Autonomic dysreflexia was assessed in adult male mice treated with E. We investigated whether E could be acting centrally by altering: (1) the size of the small diameter primary afferent arbor, (2) the degree of microglia/macrophage infiltration at the site of the injury, or (3) the amount of fibrous scarring present at the injury site. To determine whether E could be working through uncoupling protein-2 (UCP-2), a protein involved with inflammation and regulated by estrogen in some tissues, autonomic dysreflexia was assessed in E-treated adult male mice lacking UCP-2 (UCP-2 KO). 17beta-estradiol was equipotent at reducing autonomic dysreflexia in both UCP-2 KO and WT mice following CRD but not tail pinch. We have shown that E reduces autonomic dysreflexic responses to visceral but not somatic stimulation in male mice independent of the size of the primary afferent arbour, the degree of chronic inflammation, and the presence of UCP-2.
authors.affiliation: Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada. webba@ucalgary.ca
authors.forename: Aubrey A
authors.initials: AA
authors.lastname: Webb
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Chan
authors.forename: Arthur
authors.initials: A
authors.lastname: Brown
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Saleh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D020211:Autonomic Dysreflexia / Q000188:drug therapy* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000378:metabolism; D004958:Estradiol / Q000627:therapeutic use*; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012720:Severity of Illness Index; D012737:Sex Factors; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D004958:Estradiol; D015740:Calcitonin Gene-Related Peptide