{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:56:21Z","timestamp":1785232581222,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,6,30]],"date-time":"2019-06-30T00:00:00Z","timestamp":1561852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS084921"],"award-info":[{"award-number":["NS084921"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurosurgical procedures result in surgically induced brain injury (SBI) that causes postoperative complications including brain edema and neuronal apoptosis in the surrounding brain tissue. SBI leads to the release of cytokines that indirectly cause the stimulation of kynurenine 3\u2010monooxygenase (KMO) and the release of neurotoxic quinolinic acid (QUIN). This study tested a KMO inhibitor, RO 61\u20108048, to prevent postoperative brain edema and consequent neuronal apoptosis in an in vivo model of SBI. A rodent model of SBI was utilized which involves partial resection of the right frontal lobe. A total of 127 Sprague\u2010Dawley male rats (weight 275\u2013325\u00a0g) were randomly divided into the following groups: Sham surgical group, SBI, SBI\u00a0+\u00a0DMSO, SBI\u00a0+\u00a0RO 61\u20108048 (10\u00a0mg\/kg), SBI\u00a0+\u00a0RO 61\u20108048 (40\u00a0mg\/kg), and SBI\u00a0+\u00a0RO 61\u20108048 (40\u00a0mg\/kg)\u00a0+\u00a0KAT II inhibitor PF\u201004859989 (5\u00a0mg\/kg). RO 61\u20108048 was administered by intraperitoneal injection after SBI. Postoperative assessment at different time points included brain water content (brain edema), neurological scoring, and western blot. SBI increased brain water content (ipsilateral frontal lobe), decreased neurological function, and increased apoptotic markers compared with sham animals. Treatment with RO 61\u20108048 (40\u00a0mg\/kg) reduced brain water content and improved long\u2010term neurological function after SBI. RO 61\u20108048 increased the expression of kynurenic acid while reducing QUIN and apoptotic markers in the surrounding brain tissue after SBI. These neuroprotective effects were reversed by PF\u201004859989. This study suggests KMO inhibition via RO 61\u20108048 as a potential postoperative therapy following neurosurgical procedures.<\/jats:p>","DOI":"10.1002\/jnr.24489","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T03:48:58Z","timestamp":1561952938000},"page":"155-167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Modification of kynurenine pathway via inhibition of kynurenine hydroxylase attenuates surgical brain injury complications in a male rat model"],"prefix":"10.1002","volume":"98","author":[{"given":"George","family":"Zakhary","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Loma Linda University Loma Linda California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prativa","family":"Sherchan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Loma Linda University Loma Linda California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Loma Linda University Loma Linda California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-9280","authenticated-orcid":false,"given":"Jiping","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Loma Linda University Loma Linda California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-4285","authenticated-orcid":false,"given":"John H.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Loma Linda University Loma Linda California"},{"name":"Department of Neurosurgery Loma Linda University Loma Linda California"},{"name":"Department of Anesthesiology Loma Linda University Loma Linda California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,30]]},"reference":[{"issue":"53","key":"e_1_2_10_2_1","first-page":"2920","article-title":"Morris water maze test for learning and memory deficits in Alzheimer's disease model mice","volume":"20","author":"Bromley\u2010Brits K.","year":"2011","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00012"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199907000-00007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006123-199806000-00051"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)90685-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-015-0586-8"},{"issue":"1","key":"e_1_2_10_8_1","first-page":"15","article-title":"Postoperative complications in neurosurgery","volume":"58","author":"Fasano V. 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