Progesterone exacerbates striatal stroke injury in progesterone-deficient female animals

Background and Purpose-We have previously shown that female animals experie nce substantial protection from brain injury after reversible middle cerebr al artery occlusion (MCAO) compared with their male or ovariectomized femal e counterparts. The reproductive steroid estrogen has been shown to provide neuroprotection from a variety of experimental insults, but the importance of progesterone as an anti-ischemic treatment has not been well explored. We evaluated histological outcomes after MCAO in ovariectomized female rats with or without acute or chronic progesterone replacement therapy. Methods-Age-matched adult female Wistar rats were ovariectomized and treate d with 0, 30, or 60 mg/kg progesterone IP 30 minutes before ischemia (n=12 to 14 per group) or with 30 mg/kg progesterone IP daily for 7 to 10 days be fore ischemia (n=16). Each animal subsequently underwent 2 hours of MCAO wi th the intraluminal filament technique, followed by 22 hours of reperfusion . Ipsilateral parietal cortex perfusion was monitored with laser Doppler fl owmetry throughout ischemia. Cortical, caudate-putamen, and hemispheric inf arction volumes were determined with 2,3,5-triphenyltetrazolium chloride st aining and digital image analysis. Results-Intraischemic plasma progesterone levels were 5+/-3, 102+/-20,* 181 +/-28,* and 133+/-25* ng/mL in the 0, 30, and 60 mg/kg acute progesterone g roup and the 30 mg/kg chronic progesterone group, respectively (*P<0.05 com pared with 0 mg/kg). Caudate-putamen infarction volume (percent contralater al structure) was significantly increased by chronic progesterone treatment : 45.6+/-5.1%* in the 30 mg/kg chronic progesterone group and 29.2+/-5.3%, 35.8+/-5.1%, and 42.0+/-5.0% in the 0, 30, and 60 mg/kg acute progesterone groups, respectively (*P<0.05 compared with 0 mg/kg). Cortical and total he mispheric infarction volumes (percent contralateral structure) were unchang ed by progesterone treatment. Conclusions-Exogenous progesterone therapy does not ameliorate histological injury after MCAO in previously ovariectomized, adult female rats. Further more, chronic progesterone administration can exacerbate infarction in subc ortical regions.