Age-dependent effects of testosterone in experimental stroke.

Area of Science:

• Neuroscience
• Endocrinology
• Cardiovascular Research

Background:

• Male sex is a known stroke risk factor, but the specific role of androgens, like testosterone, in cerebral ischemia is not fully understood.
• Understanding how testosterone influences stroke outcomes is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the age-dependent effects of testosterone on infarct size following middle cerebral artery occlusion in rats and mice.
• To determine the involvement of the androgen receptor (AR) and cerebral aromatase in testosterone's neuroprotective or detrimental effects.

Main Methods:

• Experimental stroke was induced via middle cerebral artery occlusion in young and middle-aged male rats and mice.
• Testosterone levels were manipulated through castration and supplementation.
• The androgen receptor antagonist flutamide and aromatase knockout models were used to elucidate mechanisms.
• Infarct size was quantified at 22 hours of reperfusion.

Main Results:

• In young rats, castration reduced infarct size, while testosterone replacement increased it.
• In middle-aged rats, testosterone supplementation significantly reduced infarct size compared to controls.
• Testosterone's effects were blocked by the AR antagonist flutamide, indicating AR mediation.
• Cerebral aromatase activity increased in ischemic tissue in young males but not middle-aged males; aromatase knockout mice showed no difference in stroke damage.

Conclusions:

• Testosterone's impact on experimental stroke is age-dependent, exacerbating damage in younger animals and offering protection in middle-aged ones.
• The androgen receptor (AR) is the primary mediator of testosterone's effects on stroke outcomes.
• Cerebral aromatase does not appear to play a significant role in mediating these age-dependent effects of testosterone in stroke.