{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:31:56Z","timestamp":1760243516779,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The rupture of an intracranial aneurysm (IA) leads to life-threatening subarachnoid hemorrhage. Aside from well-established risk factors, recently published genome-wide association studies of IA revealed the strong association of a common variant near the endothelin receptor type A (EDNRA) gene with IA risk. However, the role of EDNRA in the pathogenesis of IA remains unclear. The aim of this study was to investigate the influence of a genetic modification within the EDNRA gene on IA pathogenesis in a novel in vivo model. Adult wild-type Sprague\u2013Dawley rats (WT rats) and genetically modified rats (EDNRA rats) were used for the induction of IA using arterial hypertension (HT). Animals were stratified into four groups: WT rats without (WT_CTL) and with induction of HT (WT + HT), as well as EDNRA rats without (EDNRA_CTL) and with induction of HT (EDNRA + HT). Blood pressure (BP) was observed for 12 weeks. After the observation period, cerebral arteries were analyzed for morphological (i.e., aneurysmal) changes as well as histological and functional changes by immunofluorescence and functional investigation. In the groups of rats with induction of HT, BP was higher in EDNRA + HT compared with that in WT + HT. No IAs were observed in WT_CTL and EDNRA_CTL but were found in WT + HT and EDNRA + HT. There was no histological difference in the immunofluorescence of EDNRA between all groups. Contractility and potency of endothelin-1 differed between the groups in functional investigation. In summary, we created a new model that is suitable for further studies for better understanding of the role of EDNRA in IA pathogenesis.<\/jats:p>","DOI":"10.3390\/brainsci12091239","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T20:50:45Z","timestamp":1663188645000},"page":"1239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Experimental Induction of Intracranial Aneurysms in Rats: A New Model Utilizing a Genetic Modification within the EDNRA Gene"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2607-2024","authenticated-orcid":false,"given":"Tim","family":"Lampmann","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5905-4121","authenticated-orcid":false,"given":"Valeri","family":"Borger","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9771-7806","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Konczalla","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Hospital Frankfurt, 60528 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzana","family":"Gispert","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Medical Faculty, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Auburger","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Medical Faculty, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hartmut","family":"Vatter","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8319-0847","authenticated-orcid":false,"given":"Erdem","family":"G\u00fcresir","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0140-6736(16)30668-7","article-title":"Spontaneous subarachnoid haemorrhage","volume":"389","author":"Macdonald","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1161\/01.STR.28.3.660","article-title":"Case-Fatality Rates and Functional Outcome after Subarachnoid Hemorrhage: A systematic review","volume":"28","author":"Hop","year":"1997","journal-title":"Stroke"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S1474-4422(09)70126-7","article-title":"Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: A meta-analysis","volume":"8","author":"Nieuwkamp","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S1474-4422(11)70109-0","article-title":"Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: A systematic review and meta-analysis","volume":"10","author":"Vlak","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1212\/WNL.0b013e318295d751","article-title":"Genetic risk factors for intracranial aneurysms: A meta-analysis in more than 116,000 individuals","volume":"80","author":"Alg","year":"2013","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1161\/STROKEAHA.115.012162","article-title":"Patient- and Aneurysm-Specific Risk Factors for Intracranial Aneurysm Growth: A Systematic Review and Meta-Analysis","volume":"47","author":"Backes","year":"2016","journal-title":"Stroke"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1161\/STROKEAHA.113.001107","article-title":"Natural History of Small Unruptured Anterior Circulation Aneurysms: A prospective cohort study","volume":"44","author":"Vatter","year":"2013","journal-title":"Stroke"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1056\/NEJM199701023360106","article-title":"Intracranial Aneurysms","volume":"336","author":"Schievink","year":"1997","journal-title":"N. 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