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Topic: The Role of Inflammation in Cerebral Aneurysm

Inflammation and intracranial aneurysms:

mechanisms of initiation, growth, and rupture

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

ABSTRA CT
Outcomes following aneurysmal subarachnoid hemorrhage remain poor in many patients, despite advances in microsurgical and
endovascular management. Consequently, considerable effort has been placed in determining the mechanisms of aneurysm formation,
growth, and rupture. Various environmental and genetic factors are implicated as key components in the aneurysm pathogenesis.
Currently, sufficient evidence exists to incriminate the inflammatory response as the common pathway leading to aneurysm generation
and rupture. Central to this model is the interaction between the vessel wall and inflammatory cells. Dysfunction of the endothelium
and vascular smooth muscle cells (VSMCs) promotes a chronic pathological inflammatory response that progressively weakens the
vessel wall. We review the literature pertaining to the cellular and chemical mechanisms of inflammation that contribute to aneurysm
development. Hemodynamic stress and alterations in blood flow are discussed regarding their role in promoting chronic inflammation.
Endothelial cell and VSMC dysfunction are examined concerning vascular remodeling. The contribution of inflammatory cytokines,
especially tumor necrosis factor-α is illustrated. Inflammatory cell infiltration, particularly macrophage-mediated deterioration of
vascular integrity, is reviewed. We discuss the inflammation as a means to determine aneurysms at greatest risk of rupture. Finally,
future therapeutic implications of pharmacologic modulation of the inflammation are discussed.

Key words: Aneurysm, endothelium, inflammation, subarachnoid hemorrhage, vascular smooth muscle cells

INTRODUCTION to avoid the catastrophic sequelae associated with
SAH. Despite the prevalence of these lesions, the
Intracranial aneurysms and subarachnoid hemorrhage often-devastating nature of the disease, and the risks
(SAH) represent significant disease entities, with associated with treatment, relatively little is known
ruptured aneurysms accounting for severe disability about the aneurysm pathogenesis and natural history.
and death in approximately 27,000 Americans each As a result, there has been a significant effort to define
year. Among the general population, approximately the mechanisms underlying aneurysm formation and
[1]
[2]
4-5% of individuals harbor an unruptured aneurysm. growth. Although the evolution of aneurysms from
However, with the evolution of sophisticated imaging initiation to rupture is undoubtedly multifactorial in
modalities, such as magnetic resonance imaging (MRI), nature, the inflammatory response appears to play a
magnetic resonance angiography, and computed critical role in the pathogenesis of these lesions.
tomographic angiography, unruptured incidental
aneurysms are continually discovered with increasing Further understanding of the relationship between
frequency. Microsurgical and endovascular obliteration the inflammatory response and aneurysm evolution
remains the mainstays of treatment, yet both are may have important clinical implications in the
associated with a significant risk of morbidity and future. Identification of patients prone to pathologic
mortality. [3,4] In addition, a significant number of inflammatory states could allow detection of a
unruptured aneurysms are treated preemptively population more likely to suffer aneurysm rupture.
Additionally, the genetic and cellular processes
Access this article online mediating inflammation represent attractive targets
Quick Response Code: for possible pharmacologic intervention. We review the
Website: current literature pertaining to the role of inflammation
www.nnjournal.net
in the generation of aneurysm formation and rupture.
DOI: The various vascular inflammatory stimuli are
10.4103/2347-8659.153975 discussed, with special attention paid to hemodynamic
stress and alterations in blood flow. Endothelial cell

Corresponding Author: Dr. Ricky Medel, Department of Neurosurgery, Tulane University School of Medicine, 131 S Robertson
St #8047, New Orleans, LA 70112, USA. E‑mail: rmedel@tulane.edu

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