Age-dependent effects of testosterone in experimental stroke

Jian Cheng, Weidong Hu, Thomas J. Toung, Zhizheng Zhang, Susan M. Parker, Charles E. Roselli, Patricia D. Hurn

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Although male sex is a well-recognized risk factor for stroke, the role of androgens in cerebral ischemia remains unclear. Therefore, we evaluated effects of testosterone on infarct size in both young adult and middle-aged rats (Wistar, 3-month versus 14-month old) and mice (C57/BL6, 3-month versus 12-month old) subjected to middle cerebral artery occlusion. In young adult groups, castrates displayed less ischemic damage as compared with intact males and castrates with testosterone replacement (Cortex: 24% in castrates versus 42% in intact versus 40% with testosterone; Striatum: 45% versus 73% versus 70%) at 22 h reperfusion. Surprisingly, supplementing testosterone in middle-aged rats to the physiologic levels ordinarily seen in young males reduced infarction (Cortex: 2% with testosterone versus 31%; Striatum: 38% with testosterone versus 68%). Testosterone effects on infarct size were blocked by the androgen receptor (AR) antagonist flutamide and further confirmed in young versus middle-aged mice. Baseline cerebral aromatase mRNA levels and activity were not different between young and middle-aged rats. Aromatase activity increased in ischemic tissue, but only in young males. Lastly, stroke damage was not different in aging aromatase knockout mice versus wild-type controls. Our findings indicate that testosterone's effects in experimental stroke are age dependent, mediated via AR, but not cerebral aromatase.

Original languageEnglish (US)
Pages (from-to)486-494
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume29
Issue number3
DOIs
StatePublished - Jan 1 2009

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Keywords

  • Aging
  • Androgen receptor
  • Aromatase
  • Cerebral ischemia
  • Stroke
  • Testosterone

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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