17-beta estradiol can reduce secondary ischemic damage and mortality of subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is a unique disorder commonly occurring when an aneurysm ruptures, leading to bleeding and clot formation, with a higher incidence in females. To evaluate the influence of 17-beta estradiol (E2) in the outcome of subarachnoid hemorrhage, SAH was induced by endovascular puncture of the intracranial segment of internal carotid artery in 15 intac t females (INT), 19 ovariectomized females (OVX), and 13 ovariectomized fem ale rats with E2 replacement (OVX + E2). Cerebral blood flow was recorded b efore and after SAH. All animals were decapitated immediately after death o r 24 hours after SAH for clot area analysis. Brains were sliced and stained with 2.3.5-triphenyltetrazolium chloride (TTC) for secondary ischemic lesi on analysis. The cortical cerebral blood flow (CBF), which was measured by a laser-Doppler flowmeter, decreased to 29.6% +/- 17.7%, 22.8% +/- 8.3%, an d 43.5% +/- 22.9% on the ipsilateral side (P = 0.01), and decreased to 63.4 % +/- 14.1%, 57.4% +/- 11.0%, and 66.6% +/- 17.9% on the contralateral side (P = 0.26) in INT, OVX, and OVX + E2, respectively. The subcortical CBF, w hich were measured by the H-2 clearance method, were 7.77 +/- 12.03, 7.80 /- 8.65, and 20.58 +/- 8.96 mL 100 g(-1) min(-1) on the ipsilateral side (P < 0.01), and 21.53 +/- 2.94, 25.13 +/- 3.01, and 25.30 +/- 3.23 mL 100 g(- 1) min(-1) on the contralateral side in INT, OVX, and OVX + E2, respectivel y. The mortality was 53.3%, 68.4%, and 15.4% in INT, OVX, and OVX + E2, res pectively (P = 0.01), whereas no significant difference in clot area was no ted among the groups. The secondary ischemic lesion volume was 9.3% +/- 8.4 %, 24.3% +/- 16.3%, and 7.0% +/- 6.4% in INT, OVX, and OVX + E2, respective ly (P < 0.01). This study demonstrated that E2 can reduce the mortality and secondary ischemic damage in a SAH model without affecting the clot volume .