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

Author:

Hasan David M.1,Chalouhi Nohra2,Jabbour Pascal2,Dumont Aaron S.2,Kung David K.1,Magnotta Vincent A.3,Young William L.45,Hashimoto Tomoki5,Richard Winn H.6,Heistad Donald7

Affiliation:

1. Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA

2. Department of Neurosurgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, PA

3. Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA

4. Department of Neurological Surgery, University of California San Francisco, San Francisco, CA

5. Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA

6. Department of Neurosurgery, Hofstra University and Lenox Hill Hospital, New York City, NY

7. Departments of Internal Medicine and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA

Abstract

Background Inflammatory 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 Results Eleven 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. Conclusions This study provides preliminary radiographical and histological evidence that ASA may attenuate the inflammatory process in the walls of human cerebral aneurysms. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01710072.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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