Page 97 - Read Online

Statin, a hydroxyl-3-methylglutaryl coenzyme chymase. [66-70] In human CAs, the presence of mast cells
A reductase inhibitor, is widely used as a has been identified, [11] and the increasing number of
cholesterol-lowering drug. In addition, it has an infiltrated mast cells in ruptured CAs indicates this
antiinflammatory and an anti-NF-κB effect, which cell’s role in the pathogenesis of CAs. [11] The significant
are well known as “pleiotropic effects of statins”, contribution of mast cells to CAs was shown by a recent
although the precise mechanisms underlying its study [53] in which there was an increase in mast cells
antiinflammatory effect remain to be elucidated. [59-61] during CA formation and progression. Further, the
Different kinds of statins orally administered to rat all pharmacological inhibition of the degranulation in
effectively suppress inflammatory responses in CA mast cells by emedastine difumarate or tranilast, which
lesions, which is evident by the activation of NF-κB are widely used antiallergy drugs in humans, effectively
and the expression of pro-inflammatory factors. [50,51] suppresses CA formation and progression by inhibiting
Furthermore, simvastatin orally given to rats exerts the inflammatory responses of lesions. These findings
[53]
a protective effect on the endothelial cells in CA suggest the potential of the degranulation inhibitor of
lesions. [51] Thereby, statins significantly suppress CA mast cells as drugs for treating CAs in humans.
formation and enlargement of preexisting CAs in the
rat model through their pleiotropic antiinflammatory POTENTIAL OF ANTIINFLAMMATORY DRUGS
effect. [50,51,55] Statins are prescribed to many patients FOR TREATING CEREBRAL ANEURYSMS IN
with hypercholesterolemia, and since its safety is well HUMANS
established, statins may be promising drugs for treating
patients with CAs and hypercholesterolemia [Figure 1]. In human cases, the beneficial effect of statins and
nonsteroidal antiinflammatory drugs (NSAIDs) on CA
Nifedipine is a Ca channel blocker and a widely rupture has been demonstrated, especially through
2+
used antihypertensive drug. In addition to its prospective intervention trials.
antihypertensive effect, recently published in vitro
experiments demonstrated its suppressive effect on A recent hospital-based case-control study implicated
the activation/induction of pro-inflammatory factors the potential of statins for preventing CA rupture in
such as NF-κB and MCP-1 in cultured cells. [62-64] humans. [71] They enrolled 117 cases (patients with
Consistently, nifedipine subcutaneously injected into subarachnoid hemorrhage due to CA rupture) and
rat with CAs inhibits the activation of NF-κB and 304 controls (patients with unruptured CAs) from 15
suppresses the infiltration of macrophages via the institutions in Japan, and the use of statins in each group
NF-κB-mediated MCP-1 induction. The CA formation was statistically compared. The patients’ background
[52]
and the enlargement of preexisting CAs are inhibited characteristics including age were similar. [71] As
due to the reduction of the inflammatory response. [52] expected from previous reports, the size of the CAs
Since hypertension is a major risk factor for rupture and the patients’ current smoking status were properly
of preexisting CAs, nifedipine may be a promising selected as factors that correlated with rupture; [3,5,72,73]
drug candidate for preventing CA rupture through therefore, this study’s results seemed reliable. Stains
its synergistic preventive effects on hypertension were used in 9.4% of cases (11/117 cases) and 26.0%
and inflammation [Figure 1]. Similarly, imidapril, a of the controls (79/304 controls), and the ratio of
widely used angiotensin-converting enzyme inhibitor, statins used between the groups was statistically
exerts the potent suppressive effect on CAs induced different (P < 0.001). [71] Furthermore, after stratifying
in rat models through its anti-MMP-9 effect, which is the data by the serum cholesterol level, administration
[54]
independent of its antihypertensive effect. Therefore, of a statin was still inversely correlated with the risk
imidapril may also be a good drug candidate for treating of CA rupture in patients with serum cholesterol
CAs. levels > 130 mg/dL. [71] According to logistic regression
analysis, the use of any statins, independent of the type
The mast cell is a major cell type that regulates allergic of statins, was inversely correlated with CA rupture with
inflammation through the release of histamines an adjusted odds ratio of 0.30. [71] Therefore, statins can
from its granules. [65] Since it is a tissue-dwelling cell be promising drugs for preventing CA rupture in humans
and contains a variety of cytokines and proteinases with hypercholesterolemia. However, statins have a
in its granules, it can rapidly respond to outward potent cholesterol-lowing effect and can sometimes
inflammatory stimuli and trigger inflammation. [65] decrease the serum cholesterol level below the normal
Indeed, in inflammation-related diseases, such as limit even in patients without hypercholesterolemia.
vascular disease, atherosclerosis and aortic aneurysm, Although hypercholesterolemia was not a risk factor
mast cells contribute to their pathogenesis by for CAs, and about 74% patients were without
triggering and regulating inflammation through the hypercholesterolemia in this study, the safety of statins
release of cytokines and proteinases such as IL-6 and on patients without hypercholesterolemia should be

Neuroimmunol Neuroinflammation | Volume 2 | Issue 2 | April 15, 2015 89