Pathophysiology of Intracranial Aneurysms

With this knowledge, WHAT ARE THE NEXT STEPS TO PREVENT THESE ANEURYSMS FROM BURSTING? No next steps, useless research.

Pathophysiology of Intracranial Aneurysms

COX-2 Expression, Iron Deposition in Aneurysm Wall, and Correlation With Magnetic Resonance Imaging

Jan Rodemerk ,
Andreas Junker ,
Bixia Chen ,
Daniela Pierscianek ,
Philipp Dammann ,
Marvin Darkwah Oppong ,
Alexander Radbruch ,
Michael Forsting ,
Stefan Maderwald , … See all authors

Originally published10 Jul 2020https://doi.org/10.1161/STROKEAHA.120.030590Stroke. ;0

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.

Footnotes

For Sources of Funding and Disclosures, see page xxx.

Correspondence to: Jan Rodemerk, Department of Neurosurgery, University Hospital Essen, Hufelandstraße 55, 45122 Essen, Germany. Email jan.rodemerk@uk-essen.de