Pathophysiology of Intracranial Aneurysms: COX-2 Expression, Iron Deposition in Aneurysm Wall, and Correlation With Magnetic Resonance Imaging. Issue 8 (August 2020)

• Record Type: Journal Article
• Authors: Rodemerk, Jan; Junker, Andreas; Chen, Bixia; Pierscianek, Daniela; Dammann, Philipp; Darkwah Oppong, Marvin; Radbruch, Alexander; Forsting, Michael; Maderwald, Stefan; Quick, Harald H.; Zhu, Yuan; Jabbarli, Ramazan; Sure, Ulrich; Wrede, Karsten H.
• Is Part Of: Stroke. Volume 51:Issue 8(2020)
• Publication Date: 2020-08
• Subjects: aneurysm -- cyclooxygenase 2 -- inflammation -- intracranial aneurysm -- magnetic resonance imaging; Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.120.030590
• Languages: English
• ISSNs: 0039-2499

Abstract

Abstract : Background and Purpose: The pathophysiology of development, growth, and rupture of intracranial aneurysms (IAs) is only partly understood. Cyclooxygenase 2 (COX-2) converts arachidonic acid to prostaglandin H2, which, in turn, is isomerized to prostaglandin E2 . In the human body, COX-2 plays an essential role in inflammatory pathways. This explorative study aimed to investigate COX-2 expression in the wall of IAs and its correlation to image features in clinical (1.0T, 1.5T, and 3.0T) magnetic resonance imaging (MRI) and ultra-high-field 7T MRI. Methods: The study group comprised 40 patients with partly thrombosed saccular IAs. The cohort included 17 ruptured- and 24 unruptured IAs, which had all been treated microsurgically. Formaldehyde-fixed paraffin-embedded samples were immunohistochemically stained with a monoclonal antibody against COX-2 (Dako, Santa Clara, CA; Clone: CX-294). We correlated Perls Prussian blue staining, MRI, and clinical data with immunohistochemistry, analyzed using the Trainable Weka Segmentation algorithm. Results: Aneurysm dome size ranged between 2 and 67 mm. The proportion of COX-2 positive cells ranged between 3.54% to 85.09%. An upregulated COX-2 expression correlated with increasing IA dome size ( P =0.047). Furthermore, there was a tendency of higher COX-2 expression in most ruptured IAs ( P =0.064). At all field strengths, MRI shows wall hypointensities due to iron deposition correlating with COX-2 expression ( P =0.022). Conclusions: Iron deposition and COX-2 expression in IAs walls correlate with signal hypointensity in MRI, which might, therefore, serve as a biomarker for IA instability. Furthermore, as COX-2 was also expressed in small unruptured IAs, it could be a potential target for specific medical treatment.