{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:32:38Z","timestamp":1791361958187,"version":"4.3.1"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tenol\u00f3gico","award":["303828\/2025-0"],"award-info":[{"award-number":["303828\/2025-0"]}]},{"award":["303828\/2025-0"],"award-info":[{"award-number":["303828\/2025-0"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perinatal asphyxia is a major contributor to neonatal morbidity and mortality, particularly among preterm infants, whose brains are highly vulnerable to hypoxic\u2013ischemic injury. The germinal matrix (GM), owing to its vascular fragility and high metabolic demand, is especially susceptible in this context. This study analyzed 118 germinal matrix samples from neonates, stratified into three groups according to gestational age\u2014Extremely Preterm (EP), Late Preterm (LP), and Term (T)\u2014to investigate the immunopositivity of hypoxia-inducible factor 1-alpha (HIF-1\u03b1) and brain-derived neurotrophic factor (BDNF), correlating these findings with gestational age, the presence of asphyxia, neuronal injury, and survival time. BDNF expression showed a positive association with postnatal survival in neonates without neuronal injury (\u03c1 = 0.309; p = 0.012). Linear regression analysis further demonstrated that BDNF immunopositivity was a significant predictor of survival time, with each 11.82% increase in positive staining corresponding to an additional predicted hour of survival (p &lt; 0.001). HIF-1\u03b1 expression was positively associated with survival in asphyxiated extremely preterm neonates (\u03c1 = 0.492; p = 0.024) and demonstrated a strong correlation that approached, but did not reach, conventional statistical significance in late preterm neonates with neuronal injury (\u03c1 = 0.949; p = 0.051). Collectively, these findings suggest a complementary role for BDNF and HIF-1\u03b1 in neonatal neuroprotective responses, with BDNF showing potential as a prognostic biomarker in neonates without neuronal injury and HIF-1\u03b1 reflecting adaptive responses to hypoxic\u2013ischemic stress in a gestational age-dependent manner. However, additional studies are required to validate these associations and further clarify their prognostic and therapeutic relevance in neonatal hypoxic\u2013ischemic conditions.<\/jats:p>","DOI":"10.3390\/ijms27115125","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:18:16Z","timestamp":1780679896000},"page":"5125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Involvement of HIF-1\u03b1 and BDNF in Neonatal Hypoxic\u2013Ischemic Insult to the Cerebral Germinal Matrix"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5360-3281","authenticated-orcid":false,"given":"Felipe Paes Gomes","family":"da Silva","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francys De Luca Fernandes","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas Pereira","family":"Gerber","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seigo","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"},{"name":"Postgraduate Program of Health Sciences, School of Medicine and Life Sciences, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6136-2660","authenticated-orcid":false,"given":"Eduardo Morais","family":"de Castro","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"},{"name":"Department of Medical Pathology, Universidade Federal do Paran\u00e1 (UFPR), Curitiba 80060-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Yumie Watanabe","family":"Liberalesso","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Frederico","family":"Oldenburg Neto","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3574-4638","authenticated-orcid":false,"given":"Gustavo David","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1123-5154","authenticated-orcid":false,"given":"Fernanda Gimenez","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula Camargo","family":"Martins","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"de Noronha","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"},{"name":"Postgraduate Program of Health Sciences, School of Medicine and Life Sciences, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"},{"name":"Department of Medical Pathology, Universidade Federal do Paran\u00e1 (UFPR), Curitiba 80060-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Busatta Vaz","family":"de Paula","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"},{"name":"Postgraduate Program of Health Sciences, School of Medicine and Life Sciences, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR), Curitiba 80215-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4395","DOI":"10.1590\/1413-812320182412.25082019","article-title":"Economic Crises, Child Mortality and the Protective Role of Public Health Expenditure","volume":"24","author":"Tejada","year":"2019","journal-title":"Cienc. 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