TY - JOUR
T1 - Differential effects of 17ß-oestradiol on stroke damage in stroke prone (SHRSP) and normotensive rats
AU - Carswell, H.V.O.
AU - Bingham, D.
AU - Wallace, K.
AU - Nilsen, M.
AU - Graham, D.I.
AU - Dominiczak, A.F.
AU - Macrae, I.M.
PY - 2004
Y1 - 2004
N2 - 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 17-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 17-estradiol levels for placebo and 17-estradiol groups were as follows: WKY 0.025 mg 16.4 8.5 (pg/mL, mean SD) and 25.85 12.6; WKY 0.25 mg 18.2 9.0 and 69.8 27.4; SHRSP 0.25 mg 20.7 8.8 and 81.0 16.9. In SHRSP, infarct volumes at 24 hours after MCAO were similar in placebo and 17-estradiol groups: SHRSP 0.025 mg 126.7 15.3 mm3 (n = 6) and 114.0 14.1 mm3 (n = 8) (not significant); SHRSP 0.25 mg 113.5 22.3 mm3 (n = 8) and 129.7 26.2 mm3 (n = 7) (not significant), respectively. In WKY, 17-estradiol significantly increased infarct volume by 65% with 0.025mg dose [36.1 20.7 mm3 (n = 8) and 59.7 19.3 mm3 (n = 8) (P = 0.033, unpaired t-test)] and by 96% with 0.25 mg dose [55.9 36.4 mm3 (n = 8) and 109.7 6.7 mm3 (n = 4) (P = 0.017)]. Thus, 17-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 17-estradiol in clinical studies.
AB - 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 17-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 17-estradiol levels for placebo and 17-estradiol groups were as follows: WKY 0.025 mg 16.4 8.5 (pg/mL, mean SD) and 25.85 12.6; WKY 0.25 mg 18.2 9.0 and 69.8 27.4; SHRSP 0.25 mg 20.7 8.8 and 81.0 16.9. In SHRSP, infarct volumes at 24 hours after MCAO were similar in placebo and 17-estradiol groups: SHRSP 0.025 mg 126.7 15.3 mm3 (n = 6) and 114.0 14.1 mm3 (n = 8) (not significant); SHRSP 0.25 mg 113.5 22.3 mm3 (n = 8) and 129.7 26.2 mm3 (n = 7) (not significant), respectively. In WKY, 17-estradiol significantly increased infarct volume by 65% with 0.025mg dose [36.1 20.7 mm3 (n = 8) and 59.7 19.3 mm3 (n = 8) (P = 0.033, unpaired t-test)] and by 96% with 0.25 mg dose [55.9 36.4 mm3 (n = 8) and 109.7 6.7 mm3 (n = 4) (P = 0.017)]. Thus, 17-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 17-estradiol in clinical studies.
KW - estrogen
KW - SHRSP
KW - middle cerebral artery occlusion
KW - brain damage
U2 - 10.1097/01.WCB.0000112322.75217.FD
DO - 10.1097/01.WCB.0000112322.75217.FD
M3 - Article
VL - 24
SP - 298
EP - 304
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 3
ER -