Evidence that acetylsalicylic acid attenuates inflammation in the walls of human cerebral aneurysms: preliminary results
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.
Medical Subject Headings
Aged; Angiography, Digital Subtraction; Anti-Inflammatory Agents, Non-Steroidal (therapeutic use); Aspirin (therapeutic use); Cerebral Angiography (methods); Cerebral Arteries (drug effects, immunology, metabolism, pathology); Cyclooxygenase 1 (metabolism); Cyclooxygenase 2 (metabolism); Female; Humans; Immunohistochemistry; Inflammation (diagnosis, drug therapy, immunology, surgery); Inflammation Mediators (metabolism); Intracranial Aneurysm (diagnosis, drug therapy, immunology, surgery); Intramolecular Oxidoreductases (metabolism); Iowa; Macrophages (drug effects, immunology); Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Prostaglandin-E Synthases; Time Factors; Tomography, X-Ray Computed; Treatment Outcome
Journal of the American Heart Association
Digital Object Identifier (DOI)
Hasan, David M.; Chalouhi, Nohra; Jabbour, Pascal; Dumont, Aaron S.; Kung, David K.; Magnotta, Vincent A.; Young, William L.; Hashimoto, Tomoki; Richard Winn, H; and Heistad, Donald, "Evidence that acetylsalicylic acid attenuates inflammation in the walls of human cerebral aneurysms: preliminary results" (2013). Translational Neuroscience. 1672.