Age-dependent effects of testosterone in experimental stroke

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

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 - 2009

Fingerprint

Testosterone
Stroke
Aromatase
Young Adult
Androgen Receptor Antagonists
Flutamide
Middle Cerebral Artery Infarction
Androgen Receptors
Brain Ischemia
Knockout Mice
Infarction
Androgens
Reperfusion
Wistar Rats
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

Age-dependent effects of testosterone in experimental stroke. / Cheng, Jian; Hu, Weidong; Toung, Thomas J.; Zhang, Zhizheng; Parker, Susan M.; Roselli, Charles; Hurn, Patricia D.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 29, No. 3, 2009, p. 486-494.

Research output: Contribution to journalArticle

Cheng, Jian ; Hu, Weidong ; Toung, Thomas J. ; Zhang, Zhizheng ; Parker, Susan M. ; Roselli, Charles ; Hurn, Patricia D. / Age-dependent effects of testosterone in experimental stroke. In: Journal of Cerebral Blood Flow and Metabolism. 2009 ; Vol. 29, No. 3. pp. 486-494.
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