{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:03:29Z","timestamp":1792652609330,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Clinical studies have demonstrated that dynamic changes in regional cerebral oxygen saturation (rSO2) after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) have a role in predicting neurological outcomes after the return of spontaneous circulation (ROSC). Our study evaluated whether the timing of rSO2 decline shortly after CPR reflects the severity of brain injury in a rat model of CA. Rats were subjected to different durations of asphyxia to produce variable severities of brain injury, due to CA. Time from ROSC to achieving the initial minimum rSO2 was defined as Tnadir. A Tnadir cut-off of 24 min had optimal sensitivity and specificity for predicting good neurological outcomes at 72 h after ROSC (AUC, 0.88; sensitivity, 89%; specificity, 86%; p &lt; 0.01). Immunohistochemistry at 72 h post-CA revealed that the number of Fluoro-Jade B positive degenerating neurons in the hippocampus CA1 sector were markedly higher in animals with Tnadir &gt; 24 min than that in animals with Tnadir \u2264 24 min. There was no difference in the gene expressions of cytokines and mitochondrial fission proteins in the brain at 2 h after ROSC between rats with Tnadir &gt; 24 min and with Tnadir \u2264 24 min. In conclusion, Tnadir can be a novel predictor of good neurological outcomes after CA\/CPR.<\/jats:p>","DOI":"10.3390\/jcm11010131","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T01:18:15Z","timestamp":1640654295000},"page":"131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Real-Time Brain Monitoring by Near-Infrared Spectroscopy Predicts Neurological Outcome after Cardiac Arrest and Resuscitation in Rats: A Proof of Concept Study of a Novel Prognostic Measure after Cardiac Arrest"],"prefix":"10.3390","volume":"11","author":[{"given":"Ryosuke","family":"Takegawa","sequence":"first","affiliation":[{"name":"Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA"},{"name":"Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA"},{"name":"Department of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2287-3318","authenticated-orcid":false,"given":"Kei","family":"Hayashida","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA"},{"name":"Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai","family":"Yin","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA"},{"name":"Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-7516","authenticated-orcid":false,"given":"Rishabh C.","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA"},{"name":"Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago J.","family":"Miyara","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA"},{"name":"Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houman","family":"Khalili","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7686-2817","authenticated-orcid":false,"given":"Muhammad","family":"Shoaib","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA"},{"name":"Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Endo","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA"},{"name":"Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emesto P.","family":"Molmenti","sequence":"additional","affiliation":[{"name":"Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY 11549, USA"},{"name":"Department of Surgery, North Shore University Hospital, Northwell Health, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance B.","family":"Becker","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA"},{"name":"Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY 11030, USA"},{"name":"Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart Disease and Stroke Statistics-2021 Update","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13054-020-2773-2","article-title":"The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: A systematic review and meta-analysis","volume":"24","author":"Yan","year":"2020","journal-title":"Crit. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.resuscitation.2017.03.036","article-title":"Nationwide and regional trends in survival from out-of-hospital cardiac arrest in Japan: A 10-year cohort study from 2005 to 2014","volume":"115","author":"Okubo","year":"2017","journal-title":"Resuscitation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e714","DOI":"10.1161\/CIR.0000000000000611","article-title":"2018 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations Summary","volume":"138","author":"Soar","year":"2018","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1948070","DOI":"10.1155\/2017\/1948070","article-title":"Dynamic Changes of Mitochondrial Fusion and Fission in Brain Injury after Cardiac Arrest in Rats","volume":"2017","author":"Li","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1161\/CIRCULATIONAHA.108.190652","article-title":"Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council","volume":"118","author":"Neumar","year":"2008","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1111\/acem.12980","article-title":"Near-infrared Spectroscopy Monitoring during Cardiac Arrest: A Systematic Review and Meta-analysis","volume":"23","author":"Cournoyer","year":"2016","journal-title":"Acad. Emerg. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.resuscitation.2018.01.028","article-title":"Regional cerebral oxygen saturation during cardiopulmonary resuscitation as a predictor of return of spontaneous circulation and favourable neurological outcome\u2014A review of the current literature","volume":"125","author":"Schnaubelt","year":"2018","journal-title":"Resuscitation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1586\/17434440.3.2.235","article-title":"Cerebral oxygenation monitoring: Near-infrared spectroscopy","volume":"3","author":"Tobias","year":"2006","journal-title":"Expert Rev. Med. Devices"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1046\/j.1365-2044.2002.02826.x","article-title":"A comparison of cerebral oxygenation as measured by the NIRO 300 and the INVOS 5100 Near-Infrared Spectrophotometers","volume":"57","author":"Thavasothy","year":"2002","journal-title":"Anaesthesia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.resuscitation.2012.01.039","article-title":"A feasibility study evaluating the role of cerebral oximetry in predicting return of spontaneous circulation in cardiac arrest","volume":"83","author":"Parnia","year":"2012","journal-title":"Resuscitation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40560-017-0216-1","article-title":"The relationship between cerebral regional oxygen saturation during extracorporeal cardiopulmonary resuscitation and the neurological outcome in a retrospective analysis of 16 cases","volume":"5","author":"Ehara","year":"2017","journal-title":"J. Intensive Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"587930","DOI":"10.3389\/fmed.2020.587930","article-title":"Near-Infrared Spectroscopy Assessments of Regional Cerebral Oxygen Saturation for the Prediction of Clinical Outcomes in Patients with Cardiac Arrest: A Review of Clinical Impact, Evolution, and Future Directions","volume":"7","author":"Takegawa","year":"2020","journal-title":"Front. Med."},{"key":"ref_14","first-page":"138","article-title":"Biphasic changes of rSO2 after cardio\u2013pulmonary resuscitation preceded the good neurological outcome: A case report","volume":"29","author":"Takegawa","year":"2018","journal-title":"J. Jpn. Assoc. Acute Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41598-020-79780-3","article-title":"The evaluation of pituitary damage associated with cardiac arrest: An experimental rodent model","volume":"11","author":"Okuma","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0300-9572(02)00196-X","article-title":"Neurological recovery by EEG bursting after resuscitation from cardiac arrest in rats","volume":"55","author":"Geocadin","year":"2002","journal-title":"Resuscitation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e007721","DOI":"10.1161\/JAHA.117.007721","article-title":"Dissociated Oxygen Consumption and Carbon Dioxide Production in the Post-Cardiac Arrest Rat: A Novel Metabolic Phenotype","volume":"7","author":"Shinozaki","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nishikimi, M., Yagi, T., Shoaib, M., Takegawa, R., Rasul, R., Hayashida, K., Okuma, Y., Yin, T., Choudhary, R.C., and Becker, L.B. (2021). Phospholipid Screening Postcardiac Arrest Detects Decreased Plasma Lysophosphatidylcholine: Supplementation as a New Therapeutic Approach. Crit. Care Med.","DOI":"10.1097\/CCM.0000000000005180"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Young, L.M., Choudhary, R., and Jia, X. (2016, January 16\u201320). Multimodel quantitative analysis of somatosensory evoked potentials after cardiac arrest with graded hypothermia. Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Annual International Conference, Orlando, FL, USA.","DOI":"10.1109\/EMBC.2016.7591079"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s12028-017-0401-z","article-title":"Comparison of Quantitative Characteristics of Early Post-resuscitation EEG Between Asphyxial and Ventricular Fibrillation Cardiac Arrest in Rats","volume":"28","author":"Chen","year":"2018","journal-title":"Neurocrit. Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2483","DOI":"10.1097\/MD.0000000000002483","article-title":"Effects of Hypothermic Cardiopulmonary Bypass on Internal Jugular Bulb Venous Oxygen Saturation, Cerebral Oxygen Saturation, and Bispectral Index in Pediatric Patients Undergoing Cardiac Surgery: A Prospective Study","volume":"95","author":"Hu","year":"2016","journal-title":"Medicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/cc126","article-title":"Venous oxygen measurements in the inferior vena cava in neonates with respiratory failure","volume":"2","author":"Bos","year":"1998","journal-title":"Crit. Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/00003246-199401000-00017","article-title":"Carbon dioxide rebreathing method of cardiac output measurement during acute respiratory failure in patients with chronic obstructive pulmonary disease","volume":"22","author":"Neviere","year":"1994","journal-title":"Crit. Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0300-9572(94)00827-3","article-title":"Epinephrine and sodium bicarbonate during CPR following asphyxial cardiac arrest in rats","volume":"29","author":"Neumar","year":"1995","journal-title":"Resuscitation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0006-8993(00)02513-0","article-title":"Fluoro-Jade B: A high affinity fluorescent marker for the localization of neuronal degeneration","volume":"874","author":"Schmued","year":"2000","journal-title":"Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1161\/CIRCULATIONAHA.117.032488","article-title":"Improvement in Outcomes After Cardiac Arrest and Resuscitation by Inhibition of S-Nitrosoglutathione Reductase","volume":"139","author":"Hayashida","year":"2019","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1148\/radiology.148.3.6878708","article-title":"A method of comparing the areas under receiver operating characteristic curves derived from the same cases","volume":"148","author":"Hanley","year":"1983","journal-title":"Radiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.resuscitation.2015.10.009","article-title":"Predictive value of interleukin-6 in post-cardiac arrest patients treated with targeted temperature management at 33 \u00b0C or 36 \u00b0C","volume":"98","author":"Kjaergaard","year":"2016","journal-title":"Resuscitation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.resuscitation.2016.01.006","article-title":"Inflammatory markers following resuscitation from out-of-hospital cardiac arrest-A prospective multicenter observational study","volume":"103","author":"Peberdy","year":"2016","journal-title":"Resuscitation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.resuscitation.2008.10.001","article-title":"The cutoff values of intrathecal interleukin 8 and 6 for predicting the neurological outcome in cardiac arrest victims","volume":"80","author":"Oda","year":"2009","journal-title":"Resuscitation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1097\/CCM.0000000000000937","article-title":"Systemic Inflammatory Response and Potential Prognostic Implications after Out-of-Hospital Cardiac Arrest: A Substudy of the Target Temperature Management Trial","volume":"43","author":"Kjaergaard","year":"2015","journal-title":"Crit. Care Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/0885066618817518","article-title":"The Role of Inflammatory Cytokines in Cardiac Arrest","volume":"35","author":"Jou","year":"2020","journal-title":"J. Intensive Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1097\/CCM.0000000000000817","article-title":"Inhibition of the mitochondrial fission protein dynamin-related protein 1 improves survival in a murine cardiac arrest model","volume":"43","author":"Sharp","year":"2015","journal-title":"Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cascella, M. (2020). Monitoring Cerebral Oximetry by Near-Infrared Spectroscopy (NIRS) in Anesthesia and Critical Care: Progress and Perspectives. General Anesthesia Research, Springer.","DOI":"10.1007\/978-1-4939-9891-3"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"i3","DOI":"10.1093\/bja\/aep299","article-title":"Near-infrared spectroscopy as an index of brain and tissue oxygenation","volume":"103","author":"Murkin","year":"2009","journal-title":"Br. J. Anaesth."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S140","DOI":"10.1161\/CIR.0000000000000894","article-title":"Pediatric Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations","volume":"142","author":"Maconochie","year":"2020","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1213\/ANE.0b013e318297d763","article-title":"Factors affecting the performance of 5 cerebral oximeters during hypoxia in healthy volunteers","volume":"117","author":"Bickler","year":"2013","journal-title":"Anesth. Analg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1038\/s41390-020-0752-6","article-title":"Comparison of INVOS 5100C and Nonin SenSmart X-100 oximeter performance in preterm infants with spontaneous apnea","volume":"87","author":"Andresen","year":"2020","journal-title":"Pediatric Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1097\/ALN.0b013e31824c00d7","article-title":"Impact of extracranial contamination on regional cerebral oxygen saturation: A comparison of three cerebral oximetry technologies","volume":"116","author":"Davie","year":"2012","journal-title":"Anesthesiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1093\/bja\/aeq330","article-title":"Influence of ambient light on cerebral oximeters","volume":"105","author":"Zaouter","year":"2010","journal-title":"Br. J. Anaesth."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.resuscitation.2014.08.036","article-title":"Admission interleukin-6 is associated with post resuscitation organ dysfunction and predicts long-term neurological outcome after out-of- hospital ventricular fibrillation","volume":"85","author":"Vaahersalo","year":"2014","journal-title":"Resuscitation"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/1\/131\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:54:14Z","timestamp":1760169254000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/1\/131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,27]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["jcm11010131"],"URL":"https:\/\/doi.org\/10.3390\/jcm11010131","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,27]]}}}