{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:42:31Z","timestamp":1781880151970,"version":"3.54.5"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":107,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["K08 NS121599-01"],"award-info":[{"award-number":["K08 NS121599-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R35 NS116852"],"award-info":[{"award-number":["R35 NS116852"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mild hypoxic-ischaemic encephalopathy is common in neonates, and there are no evidence-based therapies. By school age, 30\u201340% of those patients experience adverse neurodevelopmental outcomes. The nature and progression of mild injury is poorly understood. We studied the evolution of mild perinatal brain injury using longitudinal two-photon imaging of transgenic fluorescent calcium-sensitive and insensitive proteins to provide a novel readout of neuronal viability and activity at cellular resolution in vitro and in vivo. In vitro, perinatal organotypic hippocampal cultures underwent 15\u201320\u2005min of oxygen-glucose deprivation. In vivo, mild hypoxia-ischaemia was completed at post-natal day 10 with carotid ligation and 15\u2005min of hypoxia (FiO2, 0.08). Consistent with a mild injury, minimal immediate neuronal death was seen in vitro or in vivo, and there was no volumetric evidence of injury by ex vivo MRI 2.5 weeks after injury (n = 3 pups\/group). However, in both the hippocampus and neocortex, these mild injuries resulted in delayed and progressive neuronal loss by the second week after injury compared to controls; measured by fluorophore quenching (n = 6 slices\/group in vitro, P &amp;lt; 0.001; n = 8 pups\/group in vivo, P &amp;lt; 0.01). Mild hypoxia-ischaemia transiently suppressed cortical network calcium activity in vivo for over 2\u2005h after injury (versus sham, n = 13 pups\/group; P &amp;lt; 0.01). No post-injury seizures were seen. By 24\u2005h, network activity fully recovered, and there was no disruption in the development of normal cortical activity for 11 days (n = 8 pups\/group). The participation in network activity of individual neurons destined to die in vivo was indistinguishable from those that survived up to 4 days post-injury (n = 8 pups\/group). Despite a lack of significant immediate neuronal death and only transient disruptions of network activity, mild perinatal brain injury resulted in a delayed and progressive increase of neuronal death in the hippocampus and neocortex. Neurons that died late were functioning normally for days after injury, suggesting a new pathophysiology of neuronal death after mild injury. Critically, the neurons destined to die late demonstrated multiple biomarkers of viability long after mild injury, suggesting their later death may be modified with neuroprotective interventions.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf153","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T12:02:22Z","timestamp":1744977742000},"source":"Crossref","is-referenced-by-count":1,"title":["Ongoing loss of viable neurons for weeks after mild hypoxia-ischaemia"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-4402","authenticated-orcid":false,"given":"Melanie A","family":"McNally","sequence":"first","affiliation":[{"name":"Department of Neurology, Harvard Medical School and Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3312-183X","authenticated-orcid":false,"given":"Lauren A","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School and Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Granak","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School and Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hike","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School and Massachusetts General Hospital , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School and Massachusetts General Hospital , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9890-5489","authenticated-orcid":false,"given":"Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School and Massachusetts General Hospital , Boston, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A","family":"Donahue","sequence":"additional","affiliation":[{"name":"Department of Medicine, Biostatics, Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6293-806X","authenticated-orcid":false,"given":"Lori B","family":"Chibnik","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School and Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]},{"name":"Department of Epidemiology, Harvard TH Chan School of Public Health , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John V","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Chavez-Valdez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Johns Hopkins School of Medicine , Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances J","family":"Northington","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Johns Hopkins School of Medicine , Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J","family":"Staley","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School and 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