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considered, and further randomized placebo-controlled and more promising drug candidate for treating CAs.
study is warranted. Indeed, in animal models, celecoxib, a selective COX-2
inhibitor, effectively suppressed CA progression. [34,45]
Nonsteroidal antiinflammatory drugs are broad COX However, a recent clinical trial for colon cancer reported
inhibitors that involute symptoms of acute inflammation an increase of cardiac failure and myocardial infarction
such as fever, swelling etc. A recent experimental study with selective COX-2 inhibitor use [77] presumably due
revealed the involvement of COX-2, the inducible form to the impairing balance between thromboxane A and
2
of COX, in the pathway of CA formation and progression prostacyclin, suggesting that COX-2 inhibitors may not
by triggering and maintaining inflammation in lesions, be therapeutic drugs for preventing CA rupture. As
suggesting the therapeutic effect of NSAIDs on CA previously discussed, currently published case-control
rupture and progression. Conversely, NSAIDs inhibit studies have shown the controversy over the effect of
the production of thromboxane A (a prostaglandin NSAIDs on CA rupture. Although NSAIDs can be drug
2
formed by the sequential actions of COX and candidates for preventing the rupture of preexisting
thromboxane synthase from arachidonic acid) and CAs, future randomized-control studies are warranted.
thereby exert an antiplatelet effect, creating the potential
for an increase in CA rupture and exacerbation of a CONCLUSION
subarachnoid hemorrhage after rupture. Consistent
with these conflicting findings on NSAID treatment, Cerebral aneurysms are of social importance, because
results from recently published case-control studies of the resultant subarachnoid hemorrhage after rupture.
were controversial in terms of the preventive effect of The current problem with treating CAs is the lack
NSAIDs (i.e. the anti-inflammatory and antiplatelet of medical treatment to prevent their enlargement
effects) on CA rupture. [74-76] In a nested case-control or rupture. Recent studies on human samples and
study that enrolled patients from the International experimental models have revealed the crucial
Study of Unruptured Intracranial Aneurysms (58 cases role that chronic inflammatory responses play in
and 213 controls), frequent aspirin usage, 3 times/week, the pathogenesis of CAs. Some drug candidates for
suppressed CA rupture with an adjusted odds ratio of treating CAs have been identified through experimental
0.27 (P = 0.03) according to multivariable risk factor and case-control studies in humans. Therefore, the
analyses. [74] Careful attention is necessary to interpret development of medical treatment for CAs is more
the data, because enrolled patients had relatively likely in the near future.
large aneurysms located at the posterior circulation,
which are not representative of unruptured CAs. [74] ACKNOWLEDGMENTS
Another study also demonstrated the suppressive
effect of aspirin on CA rupture. [75] This study enrolled I would like to express my gratitude to all the
717 consecutive patients with CAs (30 patients were researchers, collaborators, technical assistants and
excluded due to clopidogrel and/or warfarin use) and secretaries contributing to our studies cited in the
897 CAs. During the follow-up, 274 patients presented present manuscript. I also express my sincere gratitude
with aneurysmal subarachnoid hemorrhage. The to grants supporting our research works.
rate of CA rupture (subarachnoid hemorrhage) was
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90 Neuroimmunol Neuroinflammation | Volume 2 | Issue 2 | April 15, 2015