Differential effects of 17ß-oestradiol on stroke damage in stroke prone (SHRSP) and normotensive rats

H.V.O. Carswell, D. Bingham, K. Wallace, M. Nilsen, D.I. Graham, A.F. Dominiczak, I.M. Macrae

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Abstract

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.
Original languageEnglish
Pages (from-to)298-304
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume24
Issue number3
DOIs
Publication statusPublished - 2004

Fingerprint

Inbred WKY Rats
Estradiol
Stroke
Middle Cerebral Artery Infarction
Placebos
Estrogens
Diathermy
Estrus
Brain
Inbred SHR Rats

Keywords

  • estrogen
  • SHRSP
  • middle cerebral artery occlusion
  • brain damage

Cite this

Carswell, H.V.O. ; Bingham, D. ; Wallace, K. ; Nilsen, M. ; Graham, D.I. ; Dominiczak, A.F. ; Macrae, I.M. / Differential effects of 17ß-oestradiol on stroke damage in stroke prone (SHRSP) and normotensive rats. In: Journal of Cerebral Blood Flow and Metabolism. 2004 ; Vol. 24, No. 3. pp. 298-304.
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abstract = "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.",
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Differential effects of 17ß-oestradiol on stroke damage in stroke prone (SHRSP) and normotensive rats. / Carswell, H.V.O.; Bingham, D.; Wallace, K.; Nilsen, M.; Graham, D.I.; Dominiczak, A.F.; Macrae, I.M.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 24, No. 3, 2004, p. 298-304.

Research output: Contribution to journalArticle

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 -