{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T16:54:15Z","timestamp":1784998455960,"version":"3.55.0"},"reference-count":37,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec>\n<jats:title>Object<\/jats:title>\n<jats:p>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\u2013\u03b1 (TNF-\u03b1) inhibitor for experimentally induced cerebral aneurysms in rats.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>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-\u03b1 inhibitor (etanercept), and 1 control group. One month after aneurysm induction, 7-T MRI was performed. The TNF-\u03b1 inhibitor groups received subcutaneous injection of 25 \u03bcg or 2.5 \u03bcg of etanercept, and the control group received subcutaneous injection of normal saline every week. The TNF-\u03b1 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.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Rats administered a TNF-\u03b1 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-\u03b1 inhibitor suppressed matrix metalloproteinase (MMP)\u20139 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\u2013olfactory artery bifurcation. Quantitative polymerase chain reaction also showed suppression of MMP-9 and iNOS by TNF-\u03b1 inhibitor administration.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Therapeutic administration of a TNF-\u03b1 inhibitor significantly reduced the formation of aneurysms in rats. These data also suggest that TNF-\u03b1 suppression reduced some inflammatory-related mediators that are in the downstream pathway of nuclear factor-\u03baB.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2014.1.jns13818","type":"journal-article","created":{"date-parts":[[2014,3,14]],"date-time":"2014-03-14T14:01:03Z","timestamp":1394805663000},"page":"1193-1200","source":"Crossref","is-referenced-by-count":28,"title":["Suppression of cerebral aneurysm formation in rats by a tumor necrosis factor\u2013\u03b1 inhibitor"],"prefix":"10.3171","volume":"120","author":[{"given":"Toshihiro","family":"Yokoi","sequence":"first","affiliation":[{"name":"Department of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Isono","sequence":"additional","affiliation":[{"name":"General Research Laboratory, Shiga University of Medical Science, Shiga, 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