Sustained levels of progesterone prior to the onset of cerebral ischemia are not beneficial to female mice

Female gender, which is abolished following ovariectomy and reproductive senescence, is associated with improved outcome following cerebral stroke. Estrogen replacement partially restores this benefit of the female gender but the effect of progesterone in hormone-deficient animals is currently unknown. We evaluated various outcomes following middle cerebral artery occlusion (MCAO) in ovariectomised female mice, with a physiologically relevant restoration of progesterone levels. Ovariectomised female mice had significantly elevated plasma (P = < 0.05) and brain progesterone levels (P = < 0.01) following implantation of a 21-day release pellet (50 mg) compared with mice that received placebo implants 7 days prior to undergoing 60 min MCAO. Assessment of well-being (body weight recovery) and neurological score at 24 h and 48 h post-MCAO indicated that MCAO significantly worsened outcome compared with sham-operated mice but progesterone had no effect. MCAO resulted in a substantial lesion formation and a significant increase (P < 0.05) in ipsilateral brain water content, both of which were not affected by progesterone treatment. Furthermore, there was no significant alteration in ipsilateral Aquaporin-4 (AQP4) expression following MCAO or progesterone treatment. The present study indicates that sustained physiologically relevant levels of progesterone prior to cerebral ischemia neither benefited nor worsened outcomes in previously ovariectomised female mice.

Research Highlights
► Cerebral ischemia in ovariectomised females causes lesion/edema formation and behavioural deficits.
► Female gender is believed to be neuroprotective following cerebral ischemia.
► Elevated progesterone levels at the time of ischemic injury did not offer any protection or risk.