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Topic: The Role of Inflammation in Cerebral Aneurysm

The role of leukocytes in the formation and

rupture of intracranial aneurysms

Michael J. Strong, Peter S. Amenta, Aaron S. Dumont, Ricky Medel
Department of Neurosurgery, Tulane University School of Medicine, New Orleans, LA 70112, USA.

ABSTRA CT
Ruptured intracranial aneurysms (IAs) affect a small proportion of the population; however, the morbidity and mortality is
disproportionally high. Although little is known about IA formation, progression, and rupture, mounting evidence suggests that
inflammation may play an important role in IA pathogenesis. There is emerging evidence to suggest that leukocytes play a key role
in generating and maintaining a pathologic inflammatory response that leads to aneurysm formation and rupture. We present the
current literature pertaining to the role of leukocytes in aneurysm formation, progression, and rupture. The contributions of individual
cell types are detailed, with special attention paid to the cytokine and molecular profiles. The role of magnetic resonance imaging as
a means by which to evaluate aneurysm-associated inflammation is reviewed. Finally, we discuss leukocytes as potential targets
of pharmacologic intervention.

Key words: Aneurysm, inflammation, inflammatory cells, leukocytes, lymphocytes, macrophages, mast cells, neutrophils

INTRODUCTION Chronic hypertension, binge drinking, and cigarette
smoking have all been linked to aneurysm development
Stroke is the fourth leading cause of death in the and rupture. [5-7] Inflammation represents a potential
United States and is a prominent cause of long-term common endpoint through which these diverse
disability. The prevalence of stroke among adults environmental stimuli enact pathologic changes in
[1]
age 20 or older is estimated at 6.8 million, with the intracranial vasculature, thus leading to aneurysm
795,000 individuals experiencing a new or recurrent formation.
stroke annually. Subarachnoid hemorrhage (SAH),
[1]
secondary to ruptured intracranial aneurysms (IAs) Animal aneurysm models, as well as analysis of
comprises 1-7% of all strokes. On an average 3.6-6% human aneurysms, suggest that inflammation is
[2]
of the adult population harbor IAs; however, the rate a key mediator in the formation, progression, and
of rupture is estimated to be between 0.05% and rupture. [5,8-19] Multiple studies have demonstrated the
0.5%. The small number of IAs that do rupture inflammatory response to be associated with persistent
[3]
have a poor prognosis with a mortality rate of roughly pathologic vascular remodeling in response to an insult
50%. Of those that survive the initial hemorrhage, to the vessel wall. Abnormal blood flow, chronically
[3]
approximately 30% remain severely disabled, resulting elevated blood pressure, and shear stress have all been
in a poor quality of life. [4] linked to the induction of the inflammatory response
as well as IA pathogenesis. [6,12,20-29] Central to the
The mechanisms of aneurysm genesis, maturation, and process of inflammation-driven vascular remodeling
eventual rupture remain incompletely defined, yet new is endothelial and vascular smooth muscle cell (VSMC)
studies highlight multiple genetic and environmental dysfunction resulting in vessel weakening. [30] The
factors that may contribute to the pathogenesis. inflammatory response associated with vascular
remodeling is composed of multiple complex cellular
Access this article online and biochemical processes. VSMCs, endothelial cells,
Quick Response Code: and inflammatory cells participate in intercellular
Website: signaling, resulting in the recruitment of immune cells,
www.nnjournal.net
such as leukocytes, to the vessel walls.
DOI:
10.4103/2347-8659.153972 We review the current literature pertaining to the role
of leukocytes in aneurysm formation, progression,

Corresponding Author: Dr. Michael J. Strong, Department of Neurosurgery, Tulane University School of Medicine,
New Orleans, LA 70112, USA. E‑mail: mstrong@tulane.edu

Neuroimmunol Neuroinflammation | Volume 2 | Issue 2 | April 15, 2015 107