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In the early phase, the cytotoxic edema and eventual acute lysis take place; with reperfusion, additional damage should be assigned to excitotoxicity and oxidative stress. Finally, a later phase involves all the inflammatory activity and long-term neural tissue repairing and remodeling. In this model mechanism, loss of mitochondrial function is supposed to be the hallmark of secondary injury progression, and autophagy which is lysosome-mediated play a role in enhancing brain injury. Early-induced molecules driven by hypoxia, as chaperonins HSPs and ORP150, besides common markers for inflammatory responses, have predictive value in timing the onset of neonatal HII; on the other hand, clinical biomarkers for HII diagnosis, as CK-BB, LDH, S-100beta, and NSE, could be useful to predict outcomes.<\/jats:p>","DOI":"10.1155\/2017\/6024959","type":"journal-article","created":{"date-parts":[[2017,8,13]],"date-time":"2017-08-13T17:02:11Z","timestamp":1502643731000},"page":"1-11","source":"Crossref","is-referenced-by-count":29,"title":["A Controversial Medicolegal Issue: Timing the Onset of Perinatal Hypoxic-Ischemic Brain Injury"],"prefix":"10.1155","volume":"2017","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1686-3236","authenticated-orcid":true,"given":"Vittorio","family":"Fineschi","sequence":"first","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00185 Rome, Italy"},{"name":"IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9571-2013","authenticated-orcid":true,"given":"Rocco Valerio","family":"Viola","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-7122","authenticated-orcid":true,"given":"Raffaele","family":"La Russa","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00185 Rome, Italy"},{"name":"IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-3719","authenticated-orcid":true,"given":"Alessandro","family":"Santurro","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Frati","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00185 Rome, Italy"},{"name":"IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2016.04.003"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2016.1176137"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.03.043"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2016.1265930"},{"issue":"1","key":"5","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1159\/000110211","volume":"4","year":"1985","journal-title":"Neuroepidemiology"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.2350\/15-06-1658-OA.1"},{"key":"7","year":"2014"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2010.05.010"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000389"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.206"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-7687.2006.00499.x"},{"issue":"2","key":"12","first-page":"79","volume":"37","year":"2016","journal-title":"Neuro Endocrinology Letters"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2003.047985"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2016.04.010"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.06.094"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23647"},{"issue":"1","key":"18","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1365-2990.1991.tb00691.x","volume":"17","year":"1991","journal-title":"Neuropathology and Applied Neurobiology"},{"issue":"11","key":"19","first-page":"1325","volume":"145","year":"1991","journal-title":"The American Journal of Diseases of Children"},{"issue":"4","key":"20","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1365-2990.1997.tb01300.x","volume":"23","year":"1997","journal-title":"Neuropathology and Applied Neurobiology"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2004.12.026"},{"issue":"3","key":"22","doi-asserted-by":"crossref","first-page":"F176","DOI":"10.1136\/fn.87.3.F176","volume":"87","year":"2002","journal-title":"Archives of Disease in Childhood - 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