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Topic: The Role of Inflammation in Cerebral Aneurysm

Role of the complement cascade in cerebral

aneurysm formation, growth, and rupture

1,3
1,2
1
3,4
Blake E. S. Taylor 1,2,3 , Geoff Appelboom , Robert Zilinyi , Ariana Goodman , David Chapel ,
Melissa LoPresti , Edward Sander Connolly Jr. 1,2,3,6
1,5
1 Department of Neurosurgery, Cerebrovascular Lab, Columbia University Medical Center, New York, NY 100027, USA.
2 Department of Neurosurgery, Columbia University, New York, NY 100027, USA.
3 College of Physicians and Surgeons, Columbia University, New York, NY 100027, USA.
4 Department of Pathology and Cell Biology, Columbia University, New York, NY 100027, USA.
5 New York University School of Medicine, New York, NY 100027, USA.
6 Neuro‑intensive Care Unit, Columbia University Medical Center, New York, NY 100027, USA.
ABSTRA CT
Rupture of intracranial aneurysms is the most common cause of nontraumatic subarachnoid hemorrhage, but the intricate
neuroinflammatory processes which contribute to aneurysm pathophysiology are not well-understood. Mounting evidence has
implicated the complement cascade in the progression of aneurysms from their formation to rupture. In this article, we identify and
review studies that have sought to determine the role of the complement system in the aneurysm pathogenesis. The studies were
generally conducted by immunhistological analyses on aneurysm tissue collected intraoperatively, and multiple components of the
complement cascade and its modulators were identified in specific regions of the aneurysm wall. The results of the studies suggest
that the complement cascade is locally upregulated and disinhibited in the perianeurysmal environment, and that it contributes
to chronic as well as acute immunological damage to the aneurysm wall. In the future, understanding the mechanisms at work in
complement-mediated damage is necessary to leading the development of novel therapies.

Key words: Aneurysm, complement, neuroinflammation, rupture, subarachnoid hemorrhage

INTRODUCTION of novel diagnostic and therapeutic strategies, and
histopathological findings may contribute to conventional
Saccular or “berry” aneurysms, which are characterized clinical and radiological factors. [9,10] Recently, there has
by an outpouching from one side of an affected artery, been growing evidence that the complement cascade,
have a prevalence of 3.2% in the general population [1,2] and a major effector arm of the innate immune system,
[11]
account for 90% of intracranial aneurysms. [3,4] Ruptured plays a role in the pathophysiology of intracranial
saccular aneurysms are responsible for 85% of cases aneurysms, and more broadly, in cerebrovascular
of nontraumatic subarachnoid hemorrhage (SAH), conditions. In this article, we review the complement
[5]
which carries a high case-fatality rate of 27-44% and system as it relates to the pathogenesis of intracranial
[6]
often leaves survivors with significant functional and saccular aneurysms. A thorough review of the literature
cognitive deficits. [2,7] Clinically, aneurysms have mainly was conducted on PubMed, MEDLINE, EMBASE, and
been characterized by their location and morphological Cochrane library databases using the search terms:
features (size, shape, etc.), but less attention has been paid “complement”, “aneurysm”, “SAH”, “hemorrhagic
[8]
to the underlying immune processes, which contribute to stroke”, “neuroinflammation”, and “saccular” in varying
their formation, growth, or rupture. Understanding these combinations. Only original research articles that, at least
mechanisms is important to facilitate the development in part, investigated the role of the complement cascade
in intracranial aneurysms were selected.
Access this article online
Quick Response Code: HISTOPATHOLOGICAL MECHANISMS OF
Website: SACCULAR ANEURYSM FORMATION,
www.nnjournal.net
GROWTH, AND RUPTURE
DOI:
10.4103/2347-8659.154888 The progression of saccular aneurysms from formation
to rupture involves a complex interplay of hemodynamic

Corresponding Author: Dr. Geoff Appelboom, Cerebrovascular Lab, Columbia University Medical Center, 630 West 168th Street
Suite 5‑454, New York, NY 100027, USA. E‑mail: gappelbo@gmail.com

Neuroimmunol Neuroinflammation | Volume 2 | Issue 2 | April 15, 2015 93