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Figure 1: Schematic drawing of the mechanisms that regulate aneurysmal formation and progression. PGE : prostaglandin E ; COX-2: cyclooxygenase-2;
2
2
MCP-1: monocyte chemoattractant protein-1; NF-κB: nuclear factor-kappa B
tissue degeneration observed in CAs [31,35] [Figure 1]. The and macrophage infiltration via the NF-κB-induced
critical contribution of MCP-1 mediated macrophages MCP-1 expression) seems to be two major mechanisms
recruitment/infiltration in the pathogenesis is clearly that contribute to the amplification, expansion, and
shown by recent experimental reports in which the chronicity of inflammatory responses.
deficiency of MCP-1, administration of the dominant
negative form of MCP-1 (7-ND), or depletion of This recent experimental evidence on the role of
macrophages by clodronate liposome all significantly inflammation in CAs may be useful in developing of
suppressed CA formation and progression. [31,35] therapeutic drugs for CA treatment. Recent experimental
studies in human and rodent models have greatly
The remaining question to be solved is whether the advanced our understanding of the pathogenesis of
processes are regulating the initiation and progression CAs, making it more likely that the current treatment
of CAs are different. This important issue remains to be of CAs will be improved.
elucidated. As an initiation, as well as the progression of
CAs, can be suppressed by inhibiting the inflammatory POTENTIAL OF ANTIINFLAMMATORY DRUGS
processes in lesions, these two steps of the pathogenesis FOR TREATING CEREBRAL ANEURYSMS IN
presumably share the same underlying mechanisms ANIMAL MODELS
in terms of inflammation. However, because the
hemodynamic status surrounding CA lesions is As discussed, a long-lasting inflammatory response is
completely different (e.g. a high hemodynamic status detected in CA lesions, which plays a crucial role in the
at the prospective site of the initiation [46,47] but a low pathogenesis of CAs. Recent findings in rodent models
hemodynamic status in the dome of the enlarging have amassed evidence indicating the therapeutic effect
CAs [48,49] ), there must be some differences in the of antiinflammatory drugs on the further enlargement
processes that regulate the initiation and progression or rupture of CAs and have proposed the potential of
of CAs, and this is worthy of investigation. these drugs for treating CA. [31,33-36,50-58] Among these
drugs that have a suppressive effect on CAs in animal
In summary, based on the recent studies on CAs, models, statin, [50,51,55] nifedipine, [52] and emedastine
long-lasting inflammatory responses in arterial walls play difumarate [53] are already used in humans with clinical
a crucial role in CA formation and progression, and NF-κB indications. Therefore, these drugs are good candidates
mediates this inflammation as a major transcription factor for treating CAs in humans to prevent rupture or
that regulates inflammation. In addition, the presence of a enlargement. We summarize the effect of these drugs
vicious cycle/positive feedback loop (i.e. NF-κB activation on CAs in animal models.

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