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Pharmacologically induced NVU with subsequent neurological and cognitive defects was described in mice, but not in rats so far.<\/jats:p>\n            <jats:p>We used 32 male Hannover Wistar rats. NVU was induced by intraperitoneal administration of a pharmacological \u201ccocktail\u201d consisting of N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MSPPOH, a specific inhibitor of epoxyeicosatrienoic acid-producing epoxidases, 5\u2009mg kg<jats:sup>\u22121<\/jats:sup>), L-NG-nitroarginine methyl ester (L-NAME, a nitric oxide synthase inhibitor, 10\u2009mg kg<jats:sup>\u22121<\/jats:sup>) and indomethacin (a\u00a0nonselective inhibitor of cyclooxygenases, 1\u2009mg kg<jats:sup>\u22121<\/jats:sup>) and injected twice daily for 8 consecutive days.<\/jats:p>\n            <jats:p>Cognitive performance was tested in the Morris water-maze and fear-conditioning assays. We also monitored blood pressure. In a terminal operation a laser Doppler probe was used to detect changes in blood-flow (CBF) in the barrel cortex while the contralateral whisker pad was stimulated. Brain and small intestine tissue samples were collected <jats:italic>post mortem<\/jats:italic> and examined for prostaglandin E<jats:sub>2<\/jats:sub> (PGE2) level.<\/jats:p>\n            <jats:p>Animals treated with the \u201ccocktail\u201d showed no impairment in their performance in any of the cognitive tasks. They had higher blood pressure and showed cca. 50% decrease in CBF. Intestinal bleeding and ulcers\u00a0were found in some animals with significantly decreased levels of PGE2 in the brain and small intestine.<\/jats:p>\n            <jats:p>Although we could evoke NVU by the applied mixture of pharmacons, it also induced adverse side effects such as hypertension and intestinal malformations while the treatment did not cause cognitive impairment. Thus, further refinements are still required for the development of an applicable model.<\/jats:p>","DOI":"10.1556\/2060.2022.00226","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T14:24:26Z","timestamp":1662215066000},"update-policy":"https:\/\/doi.org\/10.1556\/policypage.crossmark.crossref.1","source":"Crossref","is-referenced-by-count":1,"title":["Introduction of a pharmacological neurovascular uncoupling model in rats based on results of mice"],"prefix":"10.1556","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1768-0439","authenticated-orcid":true,"given":"Bence Tam\u00e1s","family":"Varga","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"G\u00e1sp\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliz Judit","family":"Ernyey","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Hutka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitta Tekla","family":"Tajti","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n S\u00e1ndor","family":"Z\u00e1dori","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5727-1974","authenticated-orcid":true,"given":"Istv\u00e1n","family":"Gyerty\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"425","reference":[{"issue":"4","key":"B1","series-title":"Alzheimers Res Ther","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/alzrt269","article-title":"Alzheimer's disease drug-development pipeline: Few candidates, frequent failures","volume":"6","author":"Cummings \n                     JL","year":"2014","unstructured":"Cummings \n                     JL\n                  , \n                     Morstorf \n                     T\n                  , \n                     Zhong \n                     K\n                  \n               . 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