• Ricardo A Peña Silva, Ian J Mitchell, David K Kung, Lecia L Pewe, Manuel F Granja, John T Harty, Frank M Faraci, Donald D Heistad, and David M Hasan.
• *Universidad de los Andes, Bogotá, Colombia; ‡Departments of Internal Medicine, §Neurosurgery, ¶Microbiology, and ‖Pharmacology, University of Iowa, Iowa City, Iowa.
• Neurosurgery. 2015 Oct 1; 77 (4): 613-20.

BackgroundInflammation plays an important role in formation and rupture of intracranial aneurysms. Expression of microsomal prostaglandin E2 (PGE2) synthase type 1 (mPGES-1) is increased in the wall of intracranial aneurysms in humans. PGE2, a by-product of mPGES-1, is associated with inflammation and cerebrovascular dysfunction.ObjectiveTo test the hypothesis that deletion of mPGES-1 decreases the formation and rupture of intracranial aneurysms in a murine model.MethodsIntracranial aneurysms were induced in wild-type and mPGES-1 knockout (mPGES-1 KO) mice by using a combination of deoxycorticosterone acetate-salt-induced hypertension and intracranial injection of elastase in the basal cistern. Prevalence of aneurysms, subarachnoid hemorrhage, and mortality were assessed. We also tested the effects of administration of aspirin (6 mg/kg/d) by gavage and PGE2 (1 mg/kg/d) by subcutaneous infusion.ResultsSystolic blood pressure and prevalence of aneurysm were similar in wild-type and mPGES-1 KO mice. However, mortality and the prevalence of subarachnoid hemorrhage were markedly increased in mPGES-1 KO mice (P < .05). Bone marrow reconstitution studies suggest that mPGES-1 derived from leukocytes does not appear to increase rupture of intracranial aneurysms. Aspirin, but not PGE2, attenuated the increased mortality in mPGES-1 KO mice (P < .05).ConclusionVascular mPGES-1 plays a protective role in blood vessels and attenuates rupture of cerebral aneurysms. In contrast to effects on abdominal aneurysms, mPGES-1 deficiency is associated with an increase in rupture of cerebral aneurysms and mortality, which are attenuated by low-dose aspirin.

24 keywords...

hide…