Ibudilast inhibits cerebral aneurysms by down-regulating inflammation-related molecules in the vascular wall of rats

Neurosurgery
Kenji YagiS Nagahiro

Abstract

Phosphodiesterase-4 (PDE-4) is a cyclic adenosine monophosphate-specific enzyme involved in various inflammatory diseases. We studied its role in and the effect of ibudilast, which predominantly blocks PDE-4, on rat cerebral aneurysms. Cerebral aneurysms were induced at the anterior cerebral artery-olfactory artery bifurcation of female rats subjected to hypertension, increased hemodynamic stress, and estrogen deficiency. The effect of ibudilast (30 or 60 mg/kg/d for 3 months) on their cerebral aneurysms was studied by morphological and immunohistochemical assessment and quantitative real-time polymerase chain reaction assay. In our in vitro study, we grew endothelial cells stimulated by angiotensin II under estrogen-free conditions and examined the effect of ibudilast on PDE-4 activation and the cyclic adenosine monophosphate level. Morphological evaluation using vascular corrosion casts showed ibudilast significantly suppressed cerebral aneurysms in a dose-dependent manner. In rats with induced cerebral aneurysms, the gene and protein expression of PDE-4 was high, and endothelial leukocyte adhesion molecules (P-selectin, intracellular adhesion molecule 1, and vascular adhesion molecule 1), matrix metalloproteinase-9, and tumo...Continue Reading

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Citations

Jan 22, 2011·Journal of Biomedicine & Biotechnology·Tomohiro Aoki, Masaki Nishimura
Jan 1, 2014·Future Neurology·Joseph S HudsonDavid M Hasan
Oct 31, 2015·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration
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