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Topic: The Role of Inflammation in Cerebral Aneurysm

Inflammation mediates the pathogenesis of

cerebral aneurysm and becomes therapeutic target

Tomohiro Aoki
Center for Innovation in Immunoregulation Technology and Therapeutics, Graduate School of Medicine, Kyoto University,
Kyoto 606‑8501, Japan.

ABSTRA CT

The treatment of cerebral aneurysms (CAs) is of social importance, because poor outcomes result in subarachnoid hemorrhages
after rupture. However, there is currently no medical treatment available to prevent the progression and rupture of CAs, which results
in a large number of patients without receiving treatment. Recent studies using human samples have revealed the presence of
inflammatory responses in lesions and also the possible correlation of inflammation with CA progression or rupture. Furthermore,
experimental studies using animal models of CAs have supported the notion from human studies and have clarified the crucial
contribution of inflammation to the pathogenesis. In this process, a vicious cycle/positive feedback loop includes the nuclear
factor-kappa B (NF-κB) activation, which plays a role in amplifying inflammatory responses to the point of chronicity. In addition, the
infiltration of macrophages via NF-κB-mediated monocyte chemotactic protein 1 induction expands inflammation in whole arterial
walls and contributes to the degeneration of media by producing various cytokines and tissue-destructive proteases. These series
of studies have provided an important insight - antiinflammatory drugs can be therapeutically significant in the treatment of CAs.
Indeed, in animal models, some drugs with an antiinflammatory effect effectively suppressed CA formation and progression, which
supports this hypothesis. In addition, in human cases, some case-control studies have reported the preventive effect of statins
and nonsteroidal antiinflammatory drugs on CA rupture. Therefore, the development of novel medical treatment for preventing the
progression and rupture of CAs is needed in the near future. In this literature review, articles were selected by performing a PubMed
search using the key words “cerebral aneurysm” and “inflammation”.
Key words: Cerebral aneurysm, inflammation, macrophage, nuclear factor‑kappa B

INTRODUCTION those with a higher probability of rupture (e.g. CAs with
a large size or irregular shape) are selected for surgical
Cerebral aneurysms (CAs) have a great impact on treatment. [1-3,5] Importantly, the remaining portion of
society because of their high incidence and subsequent CAs, more than half, receive no treatment, except
[3]
subarachnoid hemorrhages after rupture. [1,2] In recent for the treatment of risk factors related with rupture,
times, a large cohort study in Japan reported that the and are only followed-up with monitoring rupture
annual rate of CA rupture was 0.95%, and the risk and enlargement. Considering that there is a high
was increased according to the size of CA. Since incidence of CAs in the general population and poor
[3]
subarachnoid hemorrhages have a high mortality outcomes resulting from subarachnoid hemorrhages
rate of up to 50%, the prevention of CA rupture and despite intensive treatment, the development of a new
enlargement are of considerable significance to society. drug therapy for unruptured CAs is indispensable.
[4]
Many CAs are detected through brain examinations Therefore, the mechanisms underlying the formation
before the rupture, so there is a chance for preventative and progression of CAs need to be clarified.
treatment. Among these incidentally detected CAs, only
INFLAMMATION AND CEREBRAL ANEURYSM
Access this article online FORMATION, PROGRESSION AND RUPTURE
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studies have examined the underlying mechanism of

DOI: CA formation, progression and rupture by investigating
10.4103/2347-8659.154381 human CA specimens. These series of studies
have identified the presence of the inflammatory

Corresponding Author: Dr. Tomohiro Aoki, Center for Innovation in Immunoregulation Technology and Therapeutics,
Graduate School of Medicine, Kyoto University, Kyoto 606‑8501, Japan. E‑mail: tomoaoki@kuhp.kyoto‑u.ac.jp

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