17-β 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-β estradiol (E2) in the outcome of subarachnoid hemorrhage, SAH was induced by endovascular puncture of the intracranial segment of internal carotid artery in 15 intact females (INT), 19 ovariectomized females (OVX), and 13 ovariectomized female rats with E2 replacement (OVX + E2). Cerebral blood flow was recorded before and after SAH. All animals were decapitated immediately after death or 24 hours after SAH for clot area analysis. Brains were sliced and stained with 2,3,5-triphenyltetrazolium chloride (TTC) for secondary ischemic lesion 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%, and 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, which were measured by the H₂ 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, respectively. The mortality was 53.3%, 68.4%, and 15.4% in INT, OVX, and OVX + E2, respectively (P = 0.01), whereas no significant difference in clot area was noted 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, respectively (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.