{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:04:55Z","timestamp":1792011895745,"version":"4.4.0"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T00:00:00Z","timestamp":1711756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background and Objectives: Although classical gross features are known in hypothermia victims, they lack specific diagnosis features. The aim of our study was to reveal specific brain and lung pathological features in a group of hypothermia-related fatalities. Materials and Methods: The study group comprised 107 cases from our files associated with hypothermia. Routine hematoxylin\u2013eosin (H&amp;E) staining and postmortem immunohistochemistry were performed. Results: The microscopic cerebral exam revealed diffuse perineuronal and perivascular edema, gliosis, mononuclear cell infiltration, acute brain injuries, focal neuronal ischemia, lacunar infarction, and variable hemorrhages. Variable alveolar edema, pulmonary emphysema, intra-alveolar and\/or pleural hemorrhage, and bronchopneumonia, as well as other pre-existing lesions, were identified in lung tissue samples. Glial cells displayed S100\u03b2 expression, while neurons showed moderate Hsp70 immunopositivity. Alveolar basal membranes exhibited diffuse ICAM-1 positive expression, while ICAM-1 and AQP-1 positivity was observed in the alveolar septum vascular endothelium. Statistical analysis revealed a significant correlation between S100\u03b2 and Hps70 immunoexpression and cerebral pathological features, between ICAM-1 immunoexpression and alveolar edema and pulmonary emphysema, and between AQP-1 immunoexpression and pulmonary emphysema. Conclusions: Our results add supplementary data to brain and lung pathological findings in hypothermia-related fatalities, with potential therapeutic value in hypothermia patients.<\/jats:p>","DOI":"10.3390\/diagnostics14070739","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:44:52Z","timestamp":1711892692000},"page":"739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Advanced Diagnostic Tools in Hypothermia-Related Fatalities\u2014A Pathological Perspective"],"prefix":"10.3390","volume":"14","author":[{"given":"Andreea Alexandra","family":"Hle\u0219cu","sequence":"first","affiliation":[{"name":"Legal Medicine Department, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Grigora\u0219","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences I, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Histopathology, Institute of Legal Medicine, 700455 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2191-6697","authenticated-orcid":false,"given":"Victor","family":"Ianole","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences I, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8228-104X","authenticated-orcid":false,"given":"Cornelia","family":"Amalinei","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences I, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Histopathology, Institute of Legal Medicine, 700455 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/PAF.0000000000000484","article-title":"Biomarkers of cerebral damage in fatal hypothermia: Preliminary results","volume":"40","author":"Morleo","year":"2019","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/20961790.2021.1886656","article-title":"Histopathological, histochemical and biochemical postmortem changes in induced fatal hypothermia in rats","volume":"7","author":"Ibrahim","year":"2021","journal-title":"Forensic Sci. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hlescu, A.A., Grigoras, A., Covatariu, G., Moscalu, M., and Amalinei, C. (2022). The Value of myocardium and kidney histopathological and immunohistochemical findings in accidental hypothermia-related fatalities. Medicina, 58.","DOI":"10.3390\/medicina58111507"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"824395","DOI":"10.3389\/fmed.2022.824395","article-title":"Physiological changes in subjects exposed to accidental hypothermia: An update","volume":"9","author":"Reierth","year":"2022","journal-title":"Front. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.15386\/cjm.2014.8872.871.iij1","article-title":"The pathophysiological mechanisms of the onset of death through accidental hypothermia and the presentation of \u201cThe little match girl\u201d case","volume":"87","author":"Jeican","year":"2014","journal-title":"Clujul Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.autneu.2016.02.009","article-title":"Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure","volume":"196","author":"Castellani","year":"2016","journal-title":"Auton. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.forsciint.2012.01.015","article-title":"Evaluation of human brain damage in fatalities due to extreme environmental temperature by quantification of basic fibroblast growth factor (bFGF), glial fibrillary acidic protein (GFAP), S100\u03b2 and single-stranded DNA (ssDNA) immunoreactivities","volume":"219","author":"Wang","year":"2012","journal-title":"Forensic Sci. Int."},{"key":"ref_8","first-page":"106","article-title":"Postmortem diagnosis of induced fatal hypothermia in adult albino rats","volume":"24","author":"Elshama","year":"2016","journal-title":"Rom. J. Leg. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3389\/fncel.2017.00386","article-title":"Transcriptome analysis of gene expression provides new insights into the effect of mild therapeutic hypothermia on primary human cortical astrocytes cultured under hypoxia","volume":"11","author":"Salman","year":"2017","journal-title":"Front. Cell Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1111\/jnc.12748","article-title":"S100\u03b2 as an early biomarker of excitotoxic damage in spinal cord organotypic cultures","volume":"130","author":"Mazzone","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.neurobiolaging.2018.05.029","article-title":"Longitudinal serum S100\u03b2 and brain aging in the Lothian Birth Cohort 1936","volume":"69","author":"Cox","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Oh, J.S., Park, J., Kim, K., Jeong, H.H., Oh, Y.M., Choi, S., and Choi, K.H. (2021). HSP70-mediated neuroprotection by combined treatment of valproic acid with hypothermia in a rat asphyxial cardiac arrest model. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0253328"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1007\/s00018-004-4464-6","article-title":"Hsp70 chaperones: Cellular functions and molecular mechanism","volume":"62","author":"Mayer","year":"2005","journal-title":"Cell Mol. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kim, J.Y., Barua, S., Huang, M.Y., Park, J., Yenari, M., and Lee, J.E. (2020). Heat shock protein 70 (HSP70) induction: Chaperonotherapy for neuroprotection after brain injury. Cells, 9.","DOI":"10.3390\/cells9092020"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s12192-017-0782-0","article-title":"Hypothermia decreased the expression of heat shock proteins in neonatal rat model of hypoxic ischemic encephalopathy","volume":"22","author":"Lee","year":"2017","journal-title":"Cell Stress. Chaperones"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Tian, K., Wang, Y., Zhang, R., Shang, J., Jiang, W., and Wang, A. (2016). The effects of aquaporin-1 in pulmonary edema induced by fat embolism syndrome. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071183"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.forsciint.2013.03.007","article-title":"Molecular pathology of pulmonary edema in forensic autopsy cases with special regard to fatal hyperthermia and hypothermia","volume":"228","author":"Wang","year":"2013","journal-title":"Forensic Sci. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.5858\/2006-130-1297-HAHMIO","article-title":"Hypothermia and hyperthermia medicolegal investigation of morbidity and mortality from exposure to environmental temperature extremes","volume":"130","author":"Hunsaker","year":"2006","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Paal, P., Pasquier, M., Darocha, T., Lechner, R., Kosinski, S., Wallner, B., Zafren, K., and Brugger, H. (2022). Accidental hypothermia: 2021 update. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19010501"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.wem.2018.02.004","article-title":"Reported resuscitation of a hypothermic avalanche victim with assisted ventilation in 1939","volume":"29","author":"Zafren","year":"2018","journal-title":"Wilderness Environ. Med."},{"key":"ref_21","first-page":"989487","article-title":"Brain temperature: Physiology and pathophysiology after brain injury","volume":"2012","author":"Mrozek","year":"2012","journal-title":"Anesthesiol. Res. Pract."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Patabendige, A., Singh, A., Jenkins, S., Sen, J., and Chen, R. (2021). Astrocyte activation in neurovascular damage and repair following ischaemic stroke. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084280"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11629","DOI":"10.1096\/fj.201900895R","article-title":"Molecular chaperones in the brain endothelial barrier: Neurotoxicity or neuroprotection?","volume":"33","author":"Thuringer","year":"2019","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.17691\/stm2020.12.5.11","article-title":"Emerging trends in the use of therapeutic hypothermia as a method for neuroprotection in brain damage (Review)","volume":"12","author":"Usmanov","year":"2021","journal-title":"Sovrem. Tekhnologii Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1590\/S0004-282X2010000400021","article-title":"Expression of HSP70 in cerebral ischemia and neuroprotetive action of hypothermia and ketoprofen","volume":"68","author":"Tirapelli","year":"2010","journal-title":"Arq. Neuropsiquiatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.3892\/ijmm.2017.3106","article-title":"Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia\/reperfusion injury","volume":"40","author":"Xiao","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1379\/1466-1268(2004)009<0058:IOMCIC>2.0.CO;2","article-title":"Induction of molecular chaperones in carbon tetrachloride-treated rat liver: Implications in protection against liver damage","volume":"9","author":"Lee","year":"2004","journal-title":"Cell Stress Chaperones"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s00221-003-1683-2","article-title":"Lack of neuroprotection by heat shock protein 70 overexpression in a mouse model of global cerebral ischemia","volume":"154","author":"Olsson","year":"2004","journal-title":"Exp. Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/qjmed\/95.12.775","article-title":"Pathophysiology of accidental hypothermia","volume":"95","author":"Mallet","year":"2002","journal-title":"Q. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/s41598-020-79025-3","article-title":"Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia","volume":"11","author":"Autilio","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e15286","DOI":"10.14814\/phy2.15286","article-title":"Effect of therapeutic hypothermia on physiologic, histologic and metabolomic markers of lung injury in experimental acute respiratory distress syndrome","volume":"10","author":"Angus","year":"2022","journal-title":"Physiol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0065-1281(99)80034-8","article-title":"Effects of preservation of rat lungs in a hypothermic medium on alveolar morphology","volume":"101","author":"Arbak","year":"1999","journal-title":"Acta Histochem."},{"key":"ref_33","first-page":"898","article-title":"Morphological changes in canine lungs perfused with modified Euro-Collins solution","volume":"22","author":"Meng","year":"2002","journal-title":"Di Yi Jun Yi Da Xue Xue Bao"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"32","DOI":"10.21037\/atm.2017.12.18","article-title":"New insights into the mechanisms of pulmonary edema in acute lung injury","volume":"6","author":"Herrero","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_35","first-page":"846716","article-title":"Mild hypothermia attenuates intercellular adhesion molecule-1 induction via activation of extracellular signal-regulated kinase-1\/2 in a focal cerebral ischemia model","volume":"2011","author":"Choi","year":"2011","journal-title":"Stroke Res. Treat."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s00134-008-1235-0","article-title":"NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network. Soluble intercellular adhesion molecule-1 and clinical outcomes in patients with acute lung injury","volume":"35","author":"Calfee","year":"2009","journal-title":"Intensive Care Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1399-6576.2005.00593.x","article-title":"Mild hypothermia reduces expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of neutrophils after acid-induced lung injury in the rat","volume":"49","author":"Kira","year":"2005","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1559325820970821","DOI":"10.1177\/1559325820970821","article-title":"Expression of aquaporin-1 and aquaporin-5 in a rat model of high-altitude pulmonary edema and the effect of hyperbaric oxygen exposure","volume":"18","author":"Tan","year":"2020","journal-title":"Dose Response"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s40001-016-0233-x","article-title":"The impact of mild induced hypothermia on the rate of transfusion and the mortality in severely injured patients: A retrospective multi-centre study","volume":"21","author":"Jensen","year":"2016","journal-title":"Eur. J. Med. Res."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/7\/739\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:21:19Z","timestamp":1760106079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/7\/739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,30]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["diagnostics14070739"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics14070739","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,30]]}}}