RGD Reference Report - Suppression of cerebral aneurysm formation in rats by a tumor necrosis factor-alpha inhibitor. - Rat Genome Database
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Suppression of cerebral aneurysm formation in rats by a tumor necrosis factor-alpha inhibitor.

Authors: Yokoi, T  Isono, T  Saitoh, M  Yoshimura, Y  Nozaki, K 
Citation: Yokoi T, etal., J Neurosurg. 2014 May;120(5):1193-200. doi: 10.3171/2014.1.JNS13818. Epub 2014 Mar 14.
RGD ID: 10450592
Pubmed: (View Article at PubMed) PMID:24628611
DOI: Full-text: DOI:10.3171/2014.1.JNS13818

OBJECT: Although cerebral aneurysmal subarachnoid hemorrhage is a devastating disease for humans, effective medical treatments have not yet been established. Recent reports have shown that regression of some inflammatory-related mediators has protective effects in experimental cerebral aneurysm models. This study corroborated the effectiveness of tumor necrosis factor-alpha (TNF-alpha) inhibitor for experimentally induced cerebral aneurysms in rats. METHODS: Five-week-old male rats were prepared for induction of cerebral aneurysms and divided into 3 groups, 2 groups administered different concentrations of a TNF-alpha inhibitor (etanercept), and 1 control group. One month after aneurysm induction, 7-T MRI was performed. The TNF-alpha inhibitor groups received subcutaneous injection of 25 mug or 2.5 mug of etanercept, and the control group received subcutaneous injection of normal saline every week. The TNF-alpha inhibitor administrations were started at 1 month after aneurysm induction to evaluate its suppressive effects on preexisting cerebral aneurysms. Arterial circles of Willis were obtained and evaluated 3 months after aneurysm induction. RESULTS: Rats administered a TNF-alpha inhibitor experienced significant increases in media thickness and reductions in aneurysmal size compared with the control group. Immunohistochemical staining showed that treatment with a TNF-alpha inhibitor suppressed matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) expression through the luminal surface of the endothelial cell layer, the media and the adventitia at the site of aneurysmal formation, and the anterior cerebral artery-olfactory artery bifurcation. Quantitative polymerase chain reaction also showed suppression of MMP-9 and iNOS by TNF-alpha inhibitor administration. CONCLUSIONS: Therapeutic administration of a TNF-alpha inhibitor significantly reduced the formation of aneurysms in rats. These data also suggest that TNF-alpha suppression reduced some inflammatory-related mediators that are in the downstream pathway of nuclear factor-kappaB.


Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
TNF  (tumor necrosis factor)

Additional Information