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Topic: The Role of Inflammation in Cerebral Aneurysm

Inflammation of the cerebral arteries: lifting

the veil on the pathobiology of intracranial

aneurysms

Dale Ding
Department of Neurosurgery, University of Virginia, Charlottesville, VA 22908, USA.

Cerebral aneurysms (CAs) are the most common cause continue to improve interventional outcomes for CAs,
of spontaneous subarachnoid hemorrhage (SAH). treatment of unruptured CAs continues to expose
[1]
Despite significant improvements in microsurgical and patients to potential morbidity and mortality. [9,10]
endovascular aneurysm therapies and in neurocritical Therefore, a medical therapy that effectively reduces the
care since the turn of the century, the outcomes after hemorrhage risk of an unruptured CA with a reasonable
CA rupture remain dismal. The mortality associated safety profile may improve the long-term outcomes for
with aneurysmal SAH is approximately 50%, and of patients harboring these lesions. Unfortunately, such a
the survivors, approximately one-third have long-term therapy does not currently exist, although the efficacies
neurocognitive deficits and one-half require permanent of novel and existing pharmacologic agents have been
assistance. [2,3] Since post-SAH management outcomes investigated. [11]
have seemingly plateaued in the past decade, the ideal
window for improving overall outcomes in CA patients A crucial component to the development of an
is prior to rupture. [4] effective drug to stabilize or induce regression of CAs
is acquiring an understanding of their pathogenesis.
However, interventions for unruptured CAs are not Two common pathogenic features shared by CAs and
without risk, so their risk to benefit profiles must be extracranial aneurysms are (1) chronic inflammation,
compared to the natural history of unruptured CAs. [5,6] with an accompanying increase in the expression of
Naggara et al. performed a systematic review of pro-inflammatory cytokines and matrix metalloproteinases,
[7]
endovascular treatment outcomes for unruptured CAs initiates and exacerbates CA development, and (2)
and found a 5% rate of unfavorable outcomes. Similarly, progressive loss of smooth muscle cells (SMCs) in an
Kotowski et al. performed a systematic review artery’s tunica media, which are critical for providing
[8]
of surgical outcomes for unruptured CAs and contractility and mechanical stability of the vessel wall.
reported a 7% rate of unfavorable outcomes. Even One of the difficulties in evaluating CA pathophysiology
as advances in neurointerventional techniques and is the lack of animal models that accurately recapitulate
endovascular technologies, including newer generation the human disease. A mouse CA model is advantageous
flow-diverting stents (i.e. Surpass, flow redirection over models in other animals, due to the plethora of
endoluminal device), intermediate coverage different genetic knockouts that are available in mice.
stents (i.e. LVIS), aneurysm neck and bifurcation An increasingly popular mouse CA model was initially
reconstruction devices (i.e. PulseRider, Barrel, Eclips), devised by Nuki et al., in which CAs are generated by
[12]
and intrasaccular flow disruptors (i.e. WEB, Luna), a combination of induced systemic hypertension and
intracranial elastase injection into the basal cisterns. A
Access this article online
number of recent studies have used this mouse model to
Quick Response Code: investigate the role of various endogenous factors in CA
Website: [13-16]
www.nnjournal.net pathogenesis.

DOI: Inflammation has been shown to be a central contributor
10.4103/2347-8659.153968 to the pathogenesis of CAs. Hasan et al. [17] showed
that ferumoxytol-enhanced magnetic resonance

Corresponding Author: Dr. Dale Ding, Department of Neurosurgery, University of Virginia, P.O. Box 800212, Charlottesville,
VA 22908, USA. E‑mail: dmd7q@virginia.edu

Neuroimmunol Neuroinflammation | Volume 2 | Issue 2 | April 15, 2015 49