{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:54:30Z","timestamp":1773035670708,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TR 726\/2\u20101"],"award-info":[{"award-number":["TR 726\/2\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Activin A, a multifunctional growth and differentiation factor and neuroglobin (Ngb), an oxygen\u2010dependent heme protein, have been proposed as novel oxygen\u2010dependent neuroprotectants. Both these endogenous cytoprotective factors are partially controlled by hypoxia\u2010inducible transcription factors (HIFs) and are strongly upregulated in various forms of acute brain injury, including traumatic, hypoxic and ischaemic lesions. Considering their potential role as biomarkers of neonatal brain injury, we investigated the regulatory effects of seizure\u2010induced excitotoxicity and acute hypoxia on the activin A and Ngb systems in the developing mouse brain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed the effects of acute pilocarpine\u2010induced seizures in the brains of neonatal C57BL\/6 WT mice (P10) on the age \u2013and region\u2010specific mRNA (real\u2010rime\u2010PCR) and protein expression (IHC) of Ngb and activin A (and activin A's receptors\u2014activin A receptor Type IB, ActRIB; activin A receptor type IIA, ActRIIA; and activin A receptor Type IIB, ActRIIB) after 0\u201372\u2009h of regeneration. Using the established mouse model of acute neonatal hypoxic brain injury, the same analyses were performed on the brains of another group of mouse pups (P7) subjected to acute hypoxia (FiO\n                      <jats:sub>2<\/jats:sub>\n                      8% for 6\u2009h) and the prolyl hydroxylase inhibitor (PHI) FG\u20104497, which stabilizes cerebral HIF accumulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:bold>Results<\/jats:bold>\n                      (Mean\u2009\u00b1\u2009SEM)\n                    <\/jats:title>\n                    <jats:p>\n                      Seizures induced significant changes in the regulation of both Ngb and activin A. Cerebral Ngb mRNA expression increased over time in response to acute seizure activity (Ngb mRNA ratio: 6\u2009h: 4.75\u2009\u00b1\u20090.79, 72\u2009h: 10.53\u2009\u00b1\u20091.71; vs. controls 6\u2009h: 6.23\u2009\u00b1\u20091.15, 72\u2009h: 8.12\u2009\u00b1\u20090.56,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), exceeding the expected age\u2010related increase. Activin A mRNA expression significantly decreased within 6\u2009h of regeneration in response to seizures compared to controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), while mRNA levels of specific receptors were unaffected. In response to acute hypoxia and FG\u20104497, a marked upregulation of cerebral Ngb mRNA concentrations was observed compared to controls (Ngb mRNA ratio: 1.99\u2009\u00b1\u20090.73 vs. 0.82\u2009\u00b1\u20090.09,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Contrary to the findings in the seizure\u2010exposed brains, a significant upregulation of activin A, ActRIB and ActRIIB was detected in response to hypoxia and high\u2010dose FG\u20104497 compared to controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present results demonstrate the differential regulation of Ngb and activin A in relation to time and type of injury and indicate their potential roles as biomarkers of excitotoxic and hypoxic injury in the developing brain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jdn.70048","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T06:24:06Z","timestamp":1756103046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Seizure Activity and Hypoxia Differentially Regulate Endogenous Neurotrophic Activin A and Neuroglobin Expression in the Immature Mouse Brain"],"prefix":"10.1002","volume":"85","author":[{"given":"Clara","family":"Becker","sequence":"first","affiliation":[{"name":"Division of Paediatric Neurology, Department of Paediatrics and Adolescent Medicine Friedrich\u2013Alexander University of Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Paediatric Neurology, Department of Paediatrics and Adolescent Medicine Friedrich\u2013Alexander University of Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6031-8537","authenticated-orcid":false,"given":"Regina","family":"Trollmann","sequence":"additional","affiliation":[{"name":"Division of Paediatric Neurology, Department of Paediatrics and Adolescent Medicine Friedrich\u2013Alexander University of Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"Centre for Rare Disorders Erlangen, University Hospital Erlangen Friedrich\u2013Alexander University of Erlangen\u2010N\u00fcrnberg  Erlangen 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