title: Testosterone exacerbates neuronal damage following cardiac arrest and cardiopulmonary resuscitation in mouse.
abstract: Male animals exhibit greater neuronal damage following focal cerebral ischemic injury in many experimental injury models, however the mechanism of this is unknown. This study used cardiac arrest and cardiopulmonary resuscitation (CA/CPR) in male mice exposed to physiological vs. pharmacological doses of testosterone and tested the hypothesis that testosterone increases damage following global cerebral ischemia. Analysis of histological damage 72h after resuscitation revealed a complex dose-response curve for testosterone, such that low and high doses of testosterone exacerbated ischemic neuronal damage, while intermediate doses had no effect on neuronal survival. In agreement with these histological observations of neuronal damage, both low and high doses of testosterone increased sensorimotor deficit following CA/CPR compared to vehicle treated animals. Finally, the androgen receptor antagonist flutamide inhibited the increase in neuronal damage and sensorimotor impairment observed in testosterone treated mice. Our data showed that low and supra-physiological levels of testosterone increase neuronal damage following global cerebral ischemia and that blockade of androgen receptors limits this injury. Therefore, this study indicated that testosterone may have a role in determining sex-linked differences in cerebrovascular disease as well as having important health implications in clinical conditions of elevated testosterone.
authors: Department of Anesthesiology and Peri-Operative Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.
authors: Takaaki
authors: T
authors: Nakano
authors: Patricia D
authors: PD
authors: Hurn
authors: Paco S
authors: PS
authors: Herson
authors: Richard J
authors: RJ
authors: Traystman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D016887:Cardiopulmonary Resuscitation; D004305:Dose-Response Relationship, Drug; D006323:Heart Arrest / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D013739:Testosterone