{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:35:05Z","timestamp":1771468505405,"version":"3.50.1"},"reference-count":96,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100021077","name":"Vice Chancellor for Research and Technology, Kerman University of Medical Sciences","doi-asserted-by":"publisher","award":["IR.KMU.AH.REC.1399001106"],"award-info":[{"award-number":["IR.KMU.AH.REC.1399001106"]}],"id":[{"id":"10.13039\/501100021077","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>In this study, we aimed to investigate the inflammatory factors, oxidative stress, and histopathological consequences of the brain\u2010gut axis in male and female rats prenatally exposed to VPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant Wistar rats were randomly divided into two groups. The animals received saline, and valproic acid (VPA) (600\u2009mg\/kg, i.p.) on embryonic day 12.5 (E12.5). All offspring were weaned on postnatal day 21, and the experiments were done in male and female rats on day 60. The brain and intestine tissues were extracted to assess histopathology, inflammation, and oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An increase of interleukin\u20101\u03b2 (IL\u20101\u03b2) and interleukin\u20106 (IL\u20106) and a decrease of interleukin\u201010 (IL\u201010) were observed in the two sexes and two tissues of the autistic rats. In the VPA\u2010exposed animals, malondialdehyde (MDA) and protein carbonyl (PC) increased in the brain of both sexes and the intestines of only the males. The total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased in both tissues of male and female autistic groups. Histopathological evaluation showed that the %apoptosis of the cortex in the autistic male and female groups was more than in controls whereas this parameter in the CA1 and CA3 was significant only in the male rats. In the intestine, histopathologic changes were seen only in the male autistic animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The inflammatory and antioxidant factors were in line in the brain\u2010gut axis in male and female rats prenatally exposed to VPA. Histopathological consequences were more significant in the VPA\u2010exposed male animals.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2310","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T15:37:42Z","timestamp":1712072262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sex\u2010dependent alterations of inflammatory factors, oxidative stress, and histopathology of the brain\u2010gut axis in a VPA\u2010induced autistic\u2010like model of rats"],"prefix":"10.1002","volume":"116","author":[{"given":"Zahra","family":"Salari","sequence":"first","affiliation":[{"name":"Gastroenterology and Hepatology Research Center Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amirhossein","family":"Moslemizadeh","sequence":"additional","affiliation":[{"name":"Department of Immunology Tehran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara Sheibani","family":"Tezerji","sequence":"additional","affiliation":[{"name":"Department of Behavioural and Molecular Neurobiology, Regensburg Center for Neuroscience University of Regensburg Regensburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazanin","family":"Sabet","sequence":"additional","affiliation":[{"name":"Physiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali Saeidpour","family":"Parizi","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Research Center Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Khaksari","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vahid","family":"Sheibani","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman Iran"},{"name":"Department of Physiology and Pharmacology, Afzalipour School of Medicine Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elham","family":"Jafari","sequence":"additional","affiliation":[{"name":"Pathology and Stem Cells Research Center, Department of Pathology, Afzalipour School of Medicine Kerman University of Medical Science Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Shafieipour","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Research Center Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamideh","family":"Bashiri","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman Iran"},{"name":"Department of Physiology and Pharmacology, Afzalipour School of Medicine Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4236\/ojmip.2015.51002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2012.12.027"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-019-05412-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyy043"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2009.03.011"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3442"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114044"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2008.07.006"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.09.039"},{"issue":"5","key":"e_1_2_9_11_1","first-page":"563","article-title":"Sumatriptan ameliorates renal injury induced by cisplatin in mice","volume":"22","author":"Bazmandegan G.","year":"2019","journal-title":"Iranian Journal of Basic Medical Sciences"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/0028-3886.115074"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.11.078"},{"key":"e_1_2_9_14_1","first-page":"2314","volume-title":"Molecular neurobiology","author":"Bj\u00f8rklund G.","year":"2020"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)01356-4"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3992"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-304270"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2011.02.038"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000509109"},{"issue":"2","key":"e_1_2_9_20_1","first-page":"131","article-title":"Effect of ethanolic extract of Eugenia jambolana seeds on gastric ulceration and secretion in rats","volume":"51","author":"Chaturvedi A.","year":"2007","journal-title":"Indian Journal of Physiology and Pharmacology"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathophys.2006.05.007"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2004.04.038"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1970.01340280030009"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2270"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2012-0900N"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/1362361315577517"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2018"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715760100300611"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4065118"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(99)00060-X"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2013.06.024"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2020.110185"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3844\/ajbbsp.2008.114.120"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22053"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11689-009-9023-x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology11010079"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/41.12.1819"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.17485\/ijst\/2016\/v9i4\/80499"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.12025SC"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.10.027"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003140"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(99)70052-1"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-002-0071-6"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00071"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(01)00421-0"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145711001714"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2013.04.043"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2022.109023"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.5487\/TR.2013.29.3.173"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2010.12.018"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104918"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1338"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.5607\/en.2015.24.4.285"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2011.12.003"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3071"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201400075"},{"issue":"6","key":"e_1_2_9_57_1","first-page":"22","article-title":"Oxidative stress in autism","volume":"10","author":"McGinnis W. R.","year":"2004","journal-title":"Alternative Therapies in Health and Medicine"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-010-8840-9"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/jdn.10046"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2019.02.003"},{"issue":"1","key":"e_1_2_9_61_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.55782\/ane-2023-003","article-title":"Effects of varied\u2010intensity endurance exercise training on oxidative and antioxidant factors in the liver of rats with valproic acid\u2010induced autism","volume":"83","author":"Mirzavandi F.","year":"2023","journal-title":"Acta Neurobiologiae Experimentalis (Wars)"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.11.007"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-00460-0"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120744"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-1848.2004.00076.x"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22581"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.04.017"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2006.08.020"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2006.03.014"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.46101-0"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/297153"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.04.045"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.04.004.2008"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhm117"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-022-02938-w"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300767"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/smi.1176"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2021.107050"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2023.03.003"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2851"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/dev.20337"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(03)00119-0"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092115"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111322"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.12.024"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2003.60702.x"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2022.113739"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0b013e31821bd06a"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k1609"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13007"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1080\/02701960.2016.1247073"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep15787"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1995.1362"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1054\/plef.2002.0439"},{"key":"e_1_2_9_95_1","article-title":"Estimated prevalence of autism and other developmental disabilities following questionnaire changes in the 2014 National Health Interview Survey","author":"Zablotsky B.","year":"2015","journal-title":"National Health Statistics Reports"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111516"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-004-0456-7"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.2310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T14:12:08Z","timestamp":1731679928000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.2310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":96,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/bdr2.2310"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.2310","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"value":"2472-1727","type":"print"},{"value":"2472-1727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2023-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2310"}}