Background: Subarachnoid hemorrhage due to the rupture of intracranial aneurysms is catastrophic. To prevent this event, its pathogenesis must be understood. We created a rat model of intracranial aneurysm rupture by subjecting rats to ovariectomy (OVX), hemodynamic change, and hypertension. In the vulnerable aneurysm wall prone to rupture, matrix metallopoteinase-9 (MMP-9) and interleukin-1β (IL-1β)were highly expressed. However, the relationship between estrogen deficiency and the activation of inflammasome remains obscure. As estrogen acts estrogen receptor-dependently and independently, we compared the relationship between estrogen receptors and inflammasome in our model rats with estrogen-deficient (OVX+) and model rats subjected to hemodynamic changes and hypertension but not estrogen deficiency (OVX-).
Methods: Ten-week-old female Sprague-Dawley rats were subjected to hemodynamic change and hypertension to induce aneurysms. They were then randomly divided into two groups and ovariectomized or not ovariectomized. Sham-operated rats were the control.
Result: During 12-week observation, aneurysms ruptured in 47% of the OVX+ and 16% of the OVX- rats (p<0.05). Immunohistochemically, in OVX+ rats the expression of estrogen receptor (ER)α,but not of ERβ,was decreased while the expression of the inflammasome components NLRP3, caspase1, IL-1β of MMP-9, and of the mRNA level of NLRP3, IL-1β and MMP-9 was increased. These findings suggest that intracranial aneurysm rupture is related, via inflammasome activation, to a decrease in ERα due to estrogen deficiency.
Conclusion: Additional studies are needed to elucidate the relationship between intracranial aneurysm rupture and the activation of inflammasome under estrogen deficiency.

Estrogen deficiency activates inflammasome in a rat model of intracranial aneurysms