The Impact of Neutrophil Depletion and Granulocyte-Colony Stimulating Factor Inhibition on Aneurysm Healing

Abstract

Intracranial aneurysms (IAs) are weakened brain blood vessels at risk of rupture, often leading to subarachnoid hemorrhage, a condition with approximately 44% mortality (Bugazia et al., 2024). Endovascular coil embolization, which induces clot formation within the aneurysm sac, is a common intervention. However, it often faces complications. Inflammation is critical in this healing process, with neutrophils playing a key role by releasing enzymes to clear damaged tissue. However, excessive neutrophil activity can weaken the aneurysm wall and hinder complete healing (Rosales, 2018).

This study investigates the effects of neutrophil depletion and granulocyte-colony stimulating factor (G-CSF) inhibition on aneurysm healing using the murine aneurysm model. Elastase-induced aneurysm was created and then an endovascular coil was placed in the carotid artery of mice to mimic the effects of endovascular coiling. Mice received an anti-PNM antibody to deplete neutrophils or an anti-G-CSF antibody to inhibit neutrophil activation. Anti-PMN was administered 7 days before coiling and every other day until day 21; anti-G-CSF was given 2 days before coiling, on the day of, and every other day thereafter.

To assess the effects of these interventions, we measured tissue ingrowth into the aneurysm and conducted cytokine arrays for 144 different cytokines. Results showed a trend toward improved tissue ingrowth in the anti-PMN group (p = 0.06) and significant improvement in the anti-G-CSF group (p = 0.04). The cytokine array results revealed significant elevations in G-CSF, RANTES, and IL-17F, with G-CSF showing the most substantial increase due to its crucial role in recruiting neutrophils and modulating inflammation. These findings suggest potential cell-targeted treatments for intracranial aneurysms.