Evidence That Acetylsalicylic Acid Attenuates Inflammation in the Walls of Human Cerebral Aneurysms: Preliminary Results

Abstract

BackgroundInflammatory cells and molecules may play a critical role in formation and rupture of cerebral aneurysms. Recently, an epidemiologic study reported that acetylsalicylic acid (ASA) decreases the risk of aneurysm rupture. The goal of this study was to determine the effects of ASA on inflammatory cells and molecules in the walls of human cerebral aneurysms, using radiographic and histological techniques.Methods and ResultsEleven prospectively enrolled patients harboring unruptured intracranial aneurysms were randomized into an ASA‐treated (81 mg daily) group (n=6) and an untreated (control) group (n=5). Aneurysms were imaged at baseline using ferumoxytol‐enhanced MRI to estimate uptake by macrophages. After 3 months, patients were reimaged before undergoing microsurgical clipping. Aneurysm tissues were collected for immunostaining with monoclonal antibodies for cyclooxygenase‐1 (COX‐1), cyclooxygenase‐2 (COX‐2), microsomal prostaglandin E2 synthase‐1 (mPGES‐1), and macrophages. A decrease in signal intensity on ferumoxytol‐enhanced MRI was observed after 3 months of ASA treatment. Expression of COX‐2 (but not COX‐1), mPGES‐1, and macrophages was lower in the ASA group than in the control group.ConclusionsThis study provides preliminary radiographical and histological evidence that ASA may attenuate the inflammatory process in the walls of human cerebral aneurysms.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01710072.

Review of Cerebral Aneurysm Formation, Growth, and Rupture

“…35 Although this study provided novel data that ASA may attenuate the inflammatory process in the walls of human CAs, larger studies with long follow-up periods are needed to address whether ASA also prevents aneurysmal SAH. Bringing confirmation to the work of Hasan et al 34 is a recently published study from Europe that showed that chronic low dose aspirin therapy has a protective effect against SAH and does not increase the risk of intracerebral hemorrhage.…”

“…It also is useful as an intravascular contrast agent and an inflammatory marker when imaging is delayed because it is cleared by macrophages (usually within 24-72 hours). Hasan et al 9,35,84 have investigated the possibility of using ferumoxytol-enhanced MRI for noninvasive assessment of the inflammatory status of CAs through the detection of the activity of macrophages. In their initial work, they found that the optimal technique for imaging macrophages in human CA walls is infusion of 5 mg/kg of ferumoxytol and imaging at 72 hours after injection.…”

A comprehensive literatures update of clinical researches of superparamagnetic resonance iron oxide nanoparticles for magnetic resonance imaging

“…They found that patients treated with aspirin prior to imaging had decreased ferumoxytol uptake in the aneurysm wall compared to patients treated after imaging. This suggested that aspirin caused a decrease in inflammation, an observation which was corroborated on histopathological specimens (110,111). Therefore ferumoxytol-enhanced MRI may provide a noninvasive prognostic assessment of aneurysm stability, risk-stratify lesions in need of early intervention, and may be useful for following the response to medical therapy.…”

Inflammation in human cerebral aneurysms: pathogenesis, diagnostic imaging, genetics, and therapeutics

“…[58] An exploration of acetylsalicylic acid's effect on inflammatory mediators through ferumoxytol enhanced MRI and immunostaining found aspirin-treated patients to have both decreased macrophage infiltration and COX-2 and mPGES-1 expression. [52] These pro-inflammatory enzymes were found to be overexpressed in ruptured IA tissue. Taken together, these findings suggest that low doses of aspirin (81 mg daily for 3 months) may effectively attenuate inflammation in IA, preventing acute SAH.…”

“…[48] Given the role of macrophages in IA pathogenesis, several studies conducted by Hasan et al [49][50][51][52] investigated the possibility of in vivo aneurysm wall macrophage quantification through infusion of a carbohydrate coated superparamagnetic iron oxide nanoparticle, ferumoxytol (AMAG Pharmaceuticals, Lexington, Massachusetts, USA). Ferumoxytol is cleared by macrophages in either the arterial lumen or subendothelium of IAs, thus allowing for delayed visualization of macrophage activity as a surrogate biomarker for inflammatory status of a particular lesion.…”