51795
The Modulation of Inflammation by Gonadal Steroids in the Cerebral Vasculature
Mariam Seddiqi
Mentor: Sue Duckles & Diana Krause
Recently, there has been a focus on stroke incidence and gender differences. Pre-menopausal women
have a lower risk of stroke than men. However, these gender differences disappear after clinical
menopause. Activation of inflammatory pathways contributes to the pathophysiology of stroke. We
hypothesize that the gonadal hormones, estrogen and testosterone, modulate the development of
inflammation in the cerebral vasculature. Specifically, estrogen will decrease, while testosterone will
increase, the expression of two markers of vascular inflammation: cyclooxygenase-2 (COX-2) and
inducible nitric oxide synthase (iNOS). First, we determined the time course of expression of these
inflammatory markers in male rat brain vessels after intraperitoneal injection of lipopolysaccharide
(LPS), a bacterial endotoxin. Western blot analysis demonstrated the peak induction of both COX-2
and iNOS occurred at 6 hr post-LPS injection in male rat cerebral vessels. To investigate the effects
of estrogen or testosterone on vascular inflammation, four groups of male rats were used, intact,
orchiectomized (ORX), estrogen treated (ORX+E), and testosterone treated (ORX+T). COX-2 and
iNOS expression were induced by LPS in cerebral arteries from intact and ORX rats. However, the
induction of both inflammatory markers was noticeably suppressed in ORX+E. In contrast, there
was a significant amplification in LPS-induced COX-2 and iNOS levels in ORX+T. Thus, it is likely
that the effects of gonadal hormones on cerebral vascular inflammation may contribute to the wellknown gender differences in stroke incidence.