{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T13:08:23Z","timestamp":1783688903565,"version":"3.55.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med. Technol."],"abstract":"<jats:p>Polynitroxylated PEGylated hemoglobin (PNPH, aka SanFlow) possesses superoxide dismutase\/catalase mimetic activities that may directly protect the brain from oxidative stress. Stabilization of PNPH with bound carbon monoxide prevents methemoglobin formation during storage and permits it to serve as an anti-inflammatory carbon monoxide donor. We determined whether small volume transfusion of hyperoncotic PNPH is neuroprotective in a porcine model of traumatic brain injury (TBI) with and without accompanying hemorrhagic shock (HS). TBI was produced by controlled cortical impact over the frontal lobe of anesthetized juvenile pigs. Hemorrhagic shock was induced starting 5\u2005min after TBI by 30\u2005ml\/kg blood withdrawal. At 120\u2005min after TBI, pigs were resuscitated with 60\u2005ml\/kg lactated Ringer's (LR) or 10 or 20\u2005ml\/kg PNPH. Mean arterial pressure recovered to approximately 100 mmHg in all groups. A significant amount of PNPH was retained in the plasma over the first day of recovery. At 4 days of recovery in the LR-resuscitated group, the volume of frontal lobe subcortical white matter ipsilateral to the injury was 26.2\u2009\u00b1\u20097.6% smaller than homotypic contralateral volume, whereas this white matter loss was only 8.6\u2009\u00b1\u200912.0% with 20-ml\/kg PNPH resuscitation. Amyloid precursor protein punctate accumulation, a marker of axonopathy, increased in ipsilateral subcortical white matter by 132\u2009\u00b1\u200971% after LR resuscitation, whereas the changes after 10\u2005ml\/kg (36\u2009\u00b1\u200941%) and 20\u2005ml\/kg (26\u2009\u00b1\u200915%) PNPH resuscitation were not significantly different from controls. The number of cortical neuron long dendrites enriched in microtubules (length &amp;gt;50 microns) decreased in neocortex by 41\u2009\u00b1\u200924% after LR resuscitation but was not significantly changed after PNPH resuscitation. The perilesion microglia density increased by 45\u2009\u00b1\u200924% after LR resuscitation but was unchanged after 20\u2005ml\/kg PNPH resuscitation (4\u2009\u00b1\u200918%). Furthermore, the number with an activated morphology was attenuated by 30\u2009\u00b1\u200910%. In TBI pigs without HS followed 2\u2005h later by infusion of 10\u2005ml\/kg LR or PNPH, PNPH remained neuroprotective. These results in a gyrencephalic brain show that resuscitation from TBI\u2009+\u2009HS with PNPH protects neocortical gray matter, including dendritic microstructure, and white matter axons and myelin. This neuroprotective effect persists with TBI alone, indicating brain-targeting benefits independent of blood pressure restoration.<\/jats:p>","DOI":"10.3389\/fmedt.2023.1074643","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T04:57:44Z","timestamp":1676955464000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Polynitroxylated PEGylated hemoglobin protects pig brain neocortical gray and white matter after traumatic brain injury and hemorrhagic shock"],"prefix":"10.3389","volume":"5","author":[{"given":"Jun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanrong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyi","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee J.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Simoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohdan J.","family":"Soltys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carleton J. C.","family":"Hsia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond C.","family":"Koehler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1021\/acschemneuro.2c00196","article-title":"The role of neuroinflammatory mediators in the pathogenesis of traumatic brain injury: a narrative review","volume":"13","author":"Doganyigit","year":"2022","journal-title":"ACS Chem Neurosci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1111\/fcp.12767","article-title":"Oxidative stress and mitochondrial dysfunction following traumatic brain injury: from mechanistic view to targeted therapeutic opportunities","volume":"36","author":"Hakiminia","year":"2022","journal-title":"Fundam Clin Pharmacol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"831825","DOI":"10.3389\/fnmol.2022.831825","article-title":"Hyperacute excitotoxic mechanisms and synaptic dysfunction involved in traumatic brain injury","volume":"15","author":"Hoffe","year":"2022","journal-title":"Front Mol Neurosci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"825086","DOI":"10.3389\/fnagi.2022.825086","article-title":"Microglia and neuroinflammation: crucial pathological mechanisms in traumatic brain injury-induced neurodegeneration","volume":"14","author":"Shao","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1007\/s12031-021-01841-7","article-title":"Traumatic brain injury: mechanistic insight on pathophysiology and potential therapeutic targets","volume":"71","author":"Thapa","year":"2021","journal-title":"J Mol Neurosci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s12028-008-9175-7","article-title":"Monitoring of cerebrovascular autoregulation: facts, myths, and missing links","volume":"10","author":"Czosnyka","year":"2009","journal-title":"NeurocritCare"},{"key":"B7","doi-asserted-by":"publisher","first-page":"695","DOI":"10.3171\/2008.10.17686","article-title":"Time course for autoregulation recovery following severe traumatic brain injury","volume":"111","author":"Sviri","year":"2009","journal-title":"J Neurosurg"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.3171\/jns.2002.97.5.1054","article-title":"Dynamic autoregulatory response after severe head injury","volume":"97","author":"Hlatky","year":"2002","journal-title":"J Neurosurg"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e1205","DOI":"10.1542\/peds.2009-0550","article-title":"Continuous monitoring of cerebrovascular pressure reactivity after traumatic brain injury in children","volume":"124","author":"Brady","year":"2009","journal-title":"Pediatrics"},{"key":"B10","volume-title":"Potential value of polynitoxylated PEGylated hemoglobin (SanFlow) in pre-hospital medicine in austere environments including military deployments, disasters and remote emergencies","author":"Day","year":"2022"},{"key":"B11","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1111\/j.1525-1594.2011.01307.x","article-title":"A hemoglobin-based multifunctional therapeutic: polynitroxylated pegylated hemoglobin","volume":"36","author":"Hsia","year":"2012","journal-title":"Artif Organs"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1038\/jcbfm.2013.104","article-title":"Polynitroxylated-pegylated hemoglobin attenuates fluid requirements and brain edema in combined traumatic brain injury plus hemorrhagic shock in mice","volume":"33","author":"Brockman","year":"2013","journal-title":"J Cereb Blood Flow Metab"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1089\/neu.2016.4656","article-title":"Polynitroxylated pegylated hemoglobin-A novel, small volume therapeutic for traumatic brain injury resuscitation: comparison to whole blood and dose response evaluation","volume":"34","author":"Brockman","year":"2017","journal-title":"J Neurotrauma"},{"key":"B14","doi-asserted-by":"publisher","first-page":"511","DOI":"10.3109\/10731199209119677","article-title":"PEG-bovine hemoglobin: safety in a canine dehydrated hypovolemic-hemorrhagic shock model","volume":"20","author":"Nho","year":"1992","journal-title":"BiomaterArtifCells Immobilization Biotechnol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"H1313","DOI":"10.1152\/ajpheart.1998.275.4.H1313","article-title":"Effect of cross-linked hemoglobin transfusion on endothelial-dependent dilation in cat pial arterioles","volume":"275","author":"Asano","year":"1998","journal-title":"Am J Physiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"H1191","DOI":"10.1152\/ajpheart.00251.2005","article-title":"Role of nitric oxide scavenging in vascular response to cell-free hemoglobin transfusion","volume":"289","author":"Sampei","year":"2005","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"H1027","DOI":"10.1152\/ajpheart.00500.2005","article-title":"Dependence of acetylcholine and ADP dilation of pial arterioles on heme oxygenase after transfusion of cell-free polymeric hemoglobin","volume":"290","author":"Rebel","year":"2006","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1097\/00004872-199816100-00009","article-title":"Effect of diaspirin cross-linked hemoglobin on endothelin-1 and blood pressure in acute ischemic stroke in man","volume":"16","author":"Saxena","year":"1998","journal-title":"J Hypertens"},{"key":"B19","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1161\/01.STR.30.5.993","article-title":"Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke","volume":"30","author":"Saxena","year":"1999","journal-title":"Stroke"},{"key":"B20","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.ejphar.2018.07.026","article-title":"Gasotransmitters and the immune system: mode of action and novel therapeutic targets","volume":"834","author":"Fagone","year":"2018","journal-title":"Eur J Pharmacol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1186\/s12974-018-1226-1","article-title":"Carbon monoxide-releasing molecule-3 protects against ischemic stroke by suppressing neuroinflammation and alleviating blood-brain barrier disruption","volume":"15","author":"Wang","year":"2018","journal-title":"J Neuroinflammation"},{"key":"B22","doi-asserted-by":"publisher","first-page":"26026","DOI":"10.1074\/jbc.271.42.26026","article-title":"Do nitroxide antioxidants act as scavengers of O2-. or as SOD mimics?","volume":"271","author":"Krishna","year":"1996","journal-title":"J Biol Chem"},{"key":"B23","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.freeradbiomed.2004.04.008","article-title":"Polynitroxyl hemoglobin: a pharmacokinetic study of covalently bound nitroxides to hemoglobin platforms","volume":"37","author":"Buehler","year":"2004","journal-title":"Free RadicBiolMed"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0891-5849(99)00037-4","article-title":"Polynitroxylated hemoglobin-based oxygen carrier: inhibition of free radical-induced microcirculatory dysfunction","volume":"27","author":"Saetzler","year":"1999","journal-title":"Free Radic Biol Med"},{"key":"B25","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1080\/10715769900300591","article-title":"Polynitroxyl alpha alpha-hemoglobin (PNH) inhibits peroxide and superoxide-mediated neutrophil adherence to human endothelial cells","volume":"31","author":"Okayama","year":"1999","journal-title":"Free Radic Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1097\/CCM.0b013e318206b1fa","article-title":"Polynitroxylated pegylated hemoglobin: a novel neuroprotective hemoglobin for acute volume-limited fluid resuscitation after combined traumatic brain injury and hemorrhagic hypotension in mice","volume":"39","author":"Shellington","year":"2011","journal-title":"Crit Care Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/nrd1307","article-title":"Oxygen therapeutics: can we tame haemoglobin?","volume":"3","author":"Alayash","year":"2004","journal-title":"NatRevDrug Discov"},{"key":"B28","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.bbrc.2010.07.030","article-title":"Unusual peroxidase activity of polynitroxylated pegylated hemoglobin: elimination of H(2)O(2) coupled with intramolecular oxidation of nitroxides","volume":"399","author":"Stoyanovsky","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"B29","doi-asserted-by":"publisher","first-page":"26018","DOI":"10.1074\/jbc.271.42.26018","article-title":"Stimulation by nitroxides of catalase-like activity of hemeproteins. Kinetics and mechanism","volume":"271","author":"Krishna","year":"1996","journal-title":"J Biol Chem"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.006505","article-title":"Transfusion of polynitroxylated pegylated hemoglobin stabilizes pial arterial dilation and decreases infarct volume after transient middle cerebral artery occlusion","volume":"6","author":"Cao","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"B31","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12868-020-00571-7","article-title":"Resuscitation with macromolecular superoxide dismutase\/catalase mimetic polynitroxylated PEGylated hemoglobin offers neuroprotection in Guinea pigs after traumatic brain injury combined with hemorrhage shock","volume":"21","author":"Seno","year":"2020","journal-title":"BMC Neurosci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"413","DOI":"10.4103\/1673-5374.245334","article-title":"The pig as a preclinical traumatic brain injury model: current models, functional outcome measures, and translational detection strategies","volume":"14","author":"Kinder","year":"2019","journal-title":"Neural Regen Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1089\/neu.2010.1635","article-title":"Cyclosporin A preserves mitochondrial function after traumatic brain injury in the immature rat and piglet","volume":"28","author":"Kilbaugh","year":"2011","journal-title":"J Neurotrauma"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2810","DOI":"10.1089\/neu.2019.6405","article-title":"Controlled cortical impact leads to cognitive and motor function deficits that correspond to cellular pathology in a piglet traumatic brain injury model","volume":"36","author":"Kinder","year":"2019","journal-title":"J Neurotrauma"},{"key":"B35","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1089\/neu.2018.5711","article-title":"Mesenchymal stem cell-derived exosomes provide neuroprotection and improve long-term neurologic outcomes in a swine model of traumatic brain injury and hemorrhagic shock","volume":"36","author":"Williams","year":"2019","journal-title":"J Neurotrauma"},{"key":"B36","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1186\/s13054-021-03844-7","article-title":"17alpha-Ethinyl estradiol-3-sulfate increases survival and hemodynamic functioning in a large animal model of combined traumatic brain injury and hemorrhagic shock: a randomized control trial","volume":"25","author":"Mayer","year":"2021","journal-title":"Crit Care"},{"key":"B37","doi-asserted-by":"publisher","first-page":"658461","DOI":"10.3389\/fneur.2021.658461","article-title":"Reproducibility and characterization of head kinematics during a large animal acceleration model of traumatic brain injury","volume":"12","author":"Mayer","year":"2021","journal-title":"Front Neurol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.surg.2013.05.008","article-title":"Synergistic effects of fresh frozen plasma and valproic acid treatment in a combined model of traumatic brain injury and hemorrhagic shock","volume":"154","author":"Imam","year":"2013","journal-title":"Surgery"},{"key":"B39","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13049-014-0046-2","article-title":"Resuscitation speed affects brain injury in a large animal model of traumatic brain injury and shock","volume":"22","author":"Sillesen","year":"2014","journal-title":"Scand J Trauma Resusc Emerg Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.surg.2013.04.008","article-title":"Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock","volume":"154","author":"Hwabejire","year":"2013","journal-title":"Surgery"},{"key":"B41","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1097\/TA.0000000000000345","article-title":"Effect of pharmacologic resuscitation on the brain gene expression profiles in a swine model of traumatic brain injury and hemorrhage","volume":"77","author":"Dekker","year":"2014","journal-title":"J Trauma Acute Care Surg"},{"key":"B42","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.jamcollsurg.2015.01.057","article-title":"Early resuscitation with fresh frozen plasma for traumatic brain injury combined with hemorrhagic shock improves neurologic recovery","volume":"220","author":"Halaweish","year":"2015","journal-title":"J Am Coll Surg"},{"key":"B43","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.expneurol.2019.02.016","article-title":"Sex differences in pediatric traumatic brain injury","volume":"317","author":"Arambula","year":"2019","journal-title":"Exp Neurol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1002\/glia.23171","article-title":"Sexual dimorphism in the inflammatory response to traumatic brain injury","volume":"65","author":"Villapol","year":"2017","journal-title":"Glia"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1007\/s00381-022-05544-1","article-title":"National characteristics, etiology, and inpatient outcomes of pediatric traumatic brain injury: a KID study","volume":"38","author":"Lu","year":"2022","journal-title":"Childs Nerv Syst"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1073\/pnas.87.4.1561","article-title":"Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport","volume":"87","author":"Koo","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e59","DOI":"10.1097\/CCM.0000000000002800","article-title":"Improvement of blood-brain barrier integrity in traumatic brain injury and hemorrhagic shock following treatment with valproic acid and fresh frozen plasma","volume":"46","author":"Nikolian","year":"2018","journal-title":"Crit Care Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1089\/neu.2017.5044","article-title":"Effects of veliparib on microglial activation and functional outcomes after traumatic brain injury in the rat and pig","volume":"35","author":"Irvine","year":"2018","journal-title":"J Neurotrauma"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1089\/neu.2018.6303","article-title":"Traumatic brain injury results in dynamic brain structure changes leading to acute and chronic motor function deficits in a pediatric piglet model","volume":"36","author":"Kinder","year":"2019","journal-title":"J Neurotrauma"},{"key":"B50","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1159\/000339311","article-title":"Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: a longitudinal MRI study","volume":"34","author":"Conrad","year":"2012","journal-title":"Dev Neurosci"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1152\/japplphysiol.01079.2012","article-title":"Transfusion of hemoglobin-based oxygen carriers in the carboxy state is beneficial during transient focal cerebral ischemia","volume":"113","author":"Zhang","year":"2012","journal-title":"J Appl Physiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17705567","article-title":"Pharmacologically increasing collateral perfusion during acute stroke using a carboxyhemoglobin gas transfer agent (sanguinate) in spontaneously hypertensive rats","author":"Cipolla","year":"2017","journal-title":"J Cereb Blood Flow Metab"},{"key":"B53","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.expneurol.2018.07.004","article-title":"Criteria to define mild, moderate, and severe traumatic brain injury in the mouse controlled cortical impact model","volume":"310","author":"Siebold","year":"2018","journal-title":"Exp Neurol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jneumeth.2018.10.027","article-title":"Variability and uncertainty in the rodent controlled cortical impact model of traumatic brain injury","volume":"312","author":"Sellappan","year":"2019","journal-title":"J Neurosci Methods"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1089\/neu.2011.1756","article-title":"Traumatic axonal injury in the optic nerve: evidence for axonal swelling, disconnection, dieback, and reorganization","volume":"28","author":"Wang","year":"2011","journal-title":"JNeurotrauma"},{"key":"B56","doi-asserted-by":"publisher","first-page":"417","DOI":"10.2217\/nmt-2016-0017","article-title":"Traumatic brain injury as a risk factor for Alzheimer's disease: current knowledge and future directions","volume":"6","author":"Dams-O'Connor","year":"2016","journal-title":"Neurodegener Dis Manag"},{"key":"B57","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nrn2808","article-title":"Traumatic brain injury and amyloid-beta pathology: a link to Alzheimer's disease?","volume":"11","author":"Johnson","year":"2010","journal-title":"Nat Rev Neurosci"},{"key":"B58","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/j.1750-3639.2011.00513.x","article-title":"Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans","volume":"22","author":"Johnson","year":"2012","journal-title":"Brain Pathol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"882363","DOI":"10.3389\/fbioe.2022.882363","article-title":"Understanding the role and impact of poly (ethylene glycol) (PEG) on nanoparticle formulation: implications for COVID-19 vaccines","volume":"10","author":"Padin-Gonzalez","year":"2022","journal-title":"Front Bioeng Biotechnol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1007\/s12028-022-01468-5","article-title":"Left ventricular function in the initial period after severe traumatic brain injury in swine","volume":"37","author":"Adedipe","year":"2022","journal-title":"Neurocrit Care"}],"container-title":["Frontiers in Medical Technology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmedt.2023.1074643\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T04:57:48Z","timestamp":1676955468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmedt.2023.1074643\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,21]]},"references-count":60,"alternative-id":["10.3389\/fmedt.2023.1074643"],"URL":"https:\/\/doi.org\/10.3389\/fmedt.2023.1074643","relation":{},"ISSN":["2673-3129"],"issn-type":[{"value":"2673-3129","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,21]]},"article-number":"1074643"}}