Differential effects of 17beta-estradiol upon stroke damage in stroke prone and normotensive rats

We previously reported that during pro-estrus (high endogenous estrogen levels), brain damage after middle cerebral artery occlusion (MCAO) was reduced in stroke-prone spontaneously hypertensive rats (SHRSP) but not in normotensive Wistar Kyoto rat (WKY). In the present study, we examined the effect of exogenous estrogen on brain damage after MCAO in SHRSP and WKY. A 17beta-estradiol (0.025mg or 0.25mg, 21 day release) or matching placebo pellet was implanted into ovariectomized WKY and SHRSP (3 to 4 months old) who then underwent distal diathermy-induced MCAO 2 weeks later. Plasma 17beta-estradiol levels for placebo and 17beta-estradiol groups were as follows: WKY 0.025 mg 16.4 plusminus 8.5 (pg/mL, mean plusminus SD) and 25.85 plusminus 12.6; WKY 0.25 mg 18.2 plusminus 9.0 and 69.8 plusminus 27.4; SHRSP 0.25 mg 20.7 plusminus 8.8 and 81.0 plusminus 16.9. In SHRSP, infarct volumes at 24 hours after MCAO were similar in placebo and 17beta-estradiol groups: SHRSP 0.025 mg 126.7 plusminus 15.3 mm3 (n = 6) and 114.0 plusminus 14.1 mm3 (n = 8) (not significant); SHRSP 0.25 mg 113.5 plusminus 22.3 mm3 (n = 8) and 129.7 plusminus 26.2 mm3 (n = 7) (not significant), respectively. In WKY, 17beta-estradiol significantly increased infarct volume by 65% with 0.025mg dose [36.1 plusminus 20.7 mm3 (n = 8) and 59.7 plusminus 19.3 mm3 (n = 8) (P = 0.033, unpaired t-test)] and by 96% with 0.25 mg dose [55.9 plusminus 36.4 mm3 (n = 8) and 109.7 plusminus 6.7 mm3 (n = 4) (P = 0.017)]. Thus, 17beta-estradiol increased stroke damage in normotensive rats with no significant effect in stroke-prone rats. Despite being contrary to our hypothesis, our findings add substance to the recently reported negative effects of 17beta-estradiol in clinical studies