Background and Purpose-Estrogen is a known neuroprotective and vasoprotecti
ve agent in experimental cerebral ischemia. Preischemic steroid treatment p
rotects animals of both sexes from focal cerebral ischemia. This study dete
rmined whether intravenous estrogen acts as a vasodilator when administered
on reperfusion and whether the resulting increase in cerebral blood flow (
CBF) provides tissue protection from middle cerebral artery occlusion.
Methods-Adult male Wistar rats were treated with reversible middle cerebral
artery occlusion (2 hours), then infused with intravenous estrogen (Premar
in; 1 mg/kg) or vehicle during the first minutes of reperfusion (n=15 per g
roup). Cortical laser-Doppler flowmetry was used to assess adequacy of occl
usion, Ischemic lesion volume was determined at 22 hours after occlusion by
2,3,5-triphenyltetrazolium chloride staining and image analysis. Cortical
and striatal CBF was measured by (14)[C]iodoantipyrine autoradiography at 1
0 (n=10) or 90 (n=11) minutes of reperfusion.
Results-As expected, supraphysiological plasma estrogen levels were achieve
d during reperfusion (estrogen, 198+/-45 pg/mL; vehicle, 6+/-5; P=0.001). P
hysiological variables were controlled and not different between groups. To
tal hemispheric infarction was reduced in estrogen-treated rats (estrogen,
49+/-4% of ipsilateral structure; vehicle, 33+/-5%; P=0.02), which was most
pronounced in striatum (estrogen, 40+/-6% of ipsilateral striatum; vehicle
, 60+/-3%; P=0.01). CBF recovery was strikingly increased by estrogen infus
ion at 10 minutes in frontal (estrogen, 102+/-12 mL/100 g per minute; vehic
le, 45+/-15; P=0.01) and parietal cortex (estrogen, 74+/-15 mL/100 g per mi
nute; vehicle, 22+/-13; P=0.028) and throughout striatum (estrogen, 87+/-13
mL/100 g per minute; vehicle, 25+/-20; P=0.02). Hemispheric volume with lo
w CBF recovery leg, <20 mL/100 g per minute) was smaller in estrogen-treate
d animals (estrogen, 73+/-18 mm(3); vehicle, 257+/-46; P=0.002). However, d
ifferences in CBF recovery could not be appreciated between groups by 90 mi
nutes of reperfusion.
Conclusions-Acute estrogen therapy during reperfusion improves tissue outco
me from experimental stroke. The steroid rapidly promotes CBF recovery and
reduces hemispheric no-reflow zones. This beneficial effect appears only du
ring early reperfusion and likely complements other known mechanisms by whi
ch estrogen salvages brain from focal necrosis.