Role of selective estrogen receptor modulator on the formation and rupture of intracranial aneurysms

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19972
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: The University of Tokushima
• Principal Investigator: TADA Yoshiteru 徳島大学, 大学院医歯薬学研究部(医学系), 講師 (30547964)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 脳・神経 / 脳神経疾患 / 選択的エストロゲン受容体作動薬 / 脳動脈瘤破裂 / くも膜下出血

Outline of Final Research Achievements

Estrogen and estrogen receptor agonist prevented the formation and rupture of intracranial aneurysms in animal models. However, estrogen replacement therapy is associated with side effects such as endometrial- and breast cancer. We tested our hypothesis that bazedoxifene, a clinically used selective estrogen receptor modulator with fewer estrogenic side effects, prevented aneurysmal rupture in our aneurysm model rats. Intracranial aneurysms were induced by hemodynamic stress, hypertension, and estrogen deficiency in female rats. Bazedoxifene prevented aneurysmal rupture without affecting the blood pressure. The protective effects against the aneurysmal rupture of bazedoxifene was associated with the increased expression of estrogen receptors and the decreased in the ratio of the matrix metalloproteinase-9 to the tissue inhibitor of metalloproteinase-2 expression.

Free Research Field

脳血管障害