{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T17:58:18Z","timestamp":1781805498832,"version":"3.54.5"},"reference-count":54,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T00:00:00Z","timestamp":1690675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>During pregnancy, reactive oxygen species (ROS) serve as crucial signaling molecules for fetoplacental circulatory physiology. Oxidative stress is thought to sustain the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). A retrospective study was performed on the brains and placentas of fetuses and newborns between 36\u201342 weeks of gestation (Group_1: Fetal intrauterine deaths, Group_2: Intrapartum deaths, Group_3: Post-partum deaths, Control group sudden neonatal death); all groups were further divided into two subgroups (Subgroup_B [brain] and Subgroup_P [placenta]), and the study was conducted through the immunohistochemical investigations of markers of oxidative stress (NOX2, 8-OHdG, NT, iNOS), IL-6, and only on the brain samples, AQP4. The results for the brain samples suggest that NOX2, 8-OHdG, NT, iNOS, and IL-6 were statistically significantly expressed above the controls. iNOS was more expressed in the fetal intrauterine death (Group_1) and less expressed in post-partum death (Group_3), while in intrapartum death (Group_2), the immunoreactivity was very low. IL-6 showed the highest expression in the brain cortex of the fetal intrauterine death (Group_1), while intrapartum death (Group_2) and post-partum death (Group_3) showed weak immunoreactivity. Post-partum death (Group_3) placentas showed the highest immunoreactivity to NOX2, which was almost double that of the fetal intrauterine death (Group_1) and intrapartum death (Group_2) placentas. Placental tissues of fetal intrauterine death (Group_1) and intrapartum death (Group_2) showed higher expression of iNOS than post-partum death (Group_3), while the IL-6 expression was higher in the fetal intrauterine death (Group_1) than the post-partum death (Group_3). The AQP4 was discarded as a possible marker because the immunohistochemical reaction in the three groups of cases and the control group was negative. The goal of this study, from the point of view of forensic pathology, is to provide scientific evidence in cases of medical liability in the Obstetric field to support the clinical data of the timing of HIE.<\/jats:p>","DOI":"10.3390\/ijms241512221","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T01:28:46Z","timestamp":1690766926000},"page":"12221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Oxidative Stress Markers in Human Brain and Placenta May Reveal the Timing of Hypoxic-Ischemic Injury: Evidence from an Immunohistochemical Study"],"prefix":"10.3390","volume":"24","author":[{"given":"Benedetta","family":"Baldari","sequence":"first","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"De Simone","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Section of Legal Medicine, University of Foggia, Viale Europa 12, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-3249","authenticated-orcid":false,"given":"Luigi","family":"Cipolloni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Section of Legal Medicine, University of Foggia, Viale Europa 12, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Frisoni","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Azienda USL di Ferrara, Via Arturo Cassoli 30, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-5525","authenticated-orcid":false,"given":"Letizia","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Legal Medicine University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"D\u2019Errico","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1686-3236","authenticated-orcid":false,"given":"Vittorio","family":"Fineschi","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Turillazzi","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Medical, Molecular and Critical Area, Institute of Legal Medicine, University of Pisa, Via Roma, 55\/57, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantaleo","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Obstetrics and Gynecology, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2824-5435","authenticated-orcid":false,"given":"Amerigo","family":"Vitagliano","sequence":"additional","affiliation":[{"name":"1st Unit of Obstetrics and Gynecology, Department of Biomedical and Human Oncological Science (DIMO), University of Bari, Policlinico, Piazza Giulio Cesare, 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Scutiero","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Obstetrics and Gynecology, University of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-1669","authenticated-orcid":false,"given":"Margherita","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Legal Medicine University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxidative Med. 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