{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:18Z","timestamp":1792789638191,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UKRI through access to STFC\u2019s Central Laser Facility\u2019s Octopus Facility","award":["LSF 26130012"],"award-info":[{"award-number":["LSF 26130012"]}],"id":[{"id":"https:\/\/ror.org\/05efe5r97","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Extracellular vesicles (EVs) play important roles in cell communication, including via transfer of cargo proteins, and are promising biomarkers for pathobiological processes. Reliable biomarkers for mild neonatal hypoxia ischaemia (HI) are scarce. Wrongly determined HI severity often leads to adverse long-term neurological outcomes, with more detrimental effects in males. Therefore, identification of sex-specific markers for HI is of great interest. We recently reported the potential of EVs from eye lavage as novel non-invasive biomarkers of neonatal HI brain injury, differing in proteomic cargoes between mild and severe HI brain insults. In continuation, the current study therefore focused on assessing sex-specific differences in the same mouse model of mild HI with respect to Annexin A6 (ANXA6) EV protein cargo, at different time points (0 h, 24 h and 48 h) post HI insult. Using direct stochastic optical reconstruction microscopy (dSTORM) quantifying and co-localising ANXA6 to EV subtypes, our results indicate more marked changes in males compared with females, with a peak of positive ANXA6 detection in EVs at 24 h post HI in males. PanEV+TT+ EVs contained most ANXA6, followed by the PanEV+-labelled EVs. In the females, less ANXA6-positive staining was observed in EVs of all three time points in the HI groups compared with the males. In the sham and na\u00efve control animals, ANXA6 detection suggested developmental reduction of ANXA6 in both sexes. However, in the male HI groups that developmental reduction was eliminated and ANXA6 remained at an increased level at all three time points. In addition, EV subtype labelling showed some differences between time points within each sex group and between sexes. PanEV+ single labelled EVs were more abundant in the females compared with the males in the 0 h and 24 h post-HI groups and PanEV+TT+-labelled EVs were more abundant in females than males at the 0 h post-HI time point. Our pilot findings indicate that increased ANXA6 labelling in eye-lavage EVs is associated with the mild HI model with more marked changes in males, where ANXA6 positivity peaked at 24 h post HI. Outcomes of this study contribute to EV-based biomarker development for HI diagnostics, with potential clinical value, including sex-specific differences. Future studies should include validation in further biological replicates in larger cohort sizes and assessment in human neonatal clinical samples.<\/jats:p>","DOI":"10.3390\/ijms27198875","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:51:29Z","timestamp":1791215489000},"page":"8875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Annexin A6 in Eye-Lavage Extracellular Vesicles\u2014a Candidate Biomarker for Sex-Specific Differences in Mild Hypoxic\u2013Ischaemic Brain Damage\u2014Findings from an Explorative Neonatal Mouse Model Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7193-3102","authenticated-orcid":false,"given":"Sigrun","family":"Lange","sequence":"first","affiliation":[{"name":"Pathobiology and Extracellular Vesicles Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK"},{"name":"Department of Neonatology, EGA Institute for Women\u2019s Health, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3311-1036","authenticated-orcid":false,"given":"Sarah R.","family":"Needham","sequence":"additional","affiliation":[{"name":"Lasers for Science Facility, Central Laser Facility, UKRI: Science & Technology Facilities Council, Rutherford Appleton Laboratory, Oxfordshire OX11 0QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1822-278X","authenticated-orcid":false,"given":"Igor","family":"Kraev","sequence":"additional","affiliation":[{"name":"Electron Microscopy Suite, Faculty of Science, Technology, Engineering and Mathematics, Open University, Milton Keynes MK7 6AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Benjamin M.","family":"Davis","sequence":"additional","affiliation":[{"name":"Lasers for Science Facility, Central Laser Facility, UKRI: Science & Technology Facilities Council, Rutherford Appleton Laboratory, Oxfordshire OX11 0QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Mariya","family":"Hristova","sequence":"additional","affiliation":[{"name":"Department of Neonatology, EGA Institute for Women\u2019s Health, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"ref_1","first-page":"4901014","article-title":"Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury","volume":"2016","author":"Hristova","year":"2016","journal-title":"Neural Plast."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1080\/14767058.2017.1321628","article-title":"Ante- and intrapartum risk factors for neonatal hypoxic ischemic encephalopathy","volume":"31","author":"Lundgren","year":"2018","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"106427","DOI":"10.1016\/j.earlhumdev.2025.106427","article-title":"Therapeutic hypothermia in mild hypoxic ischemic encephalopathy: A clinical dilemma with uncertain long-term outcomes","volume":"212","author":"Acun","year":"2026","journal-title":"Early Hum. Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"992","DOI":"10.4103\/0301-4738.145990","article-title":"Neuro-ophthalmic manifestations of prematurity","volume":"62","author":"Chhablani","year":"2014","journal-title":"Indian J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/dmcn.15468","article-title":"Retinopathy of prematurity","volume":"65","author":"Dammann","year":"2023","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_6","first-page":"372","article-title":"Review of Retinopathy of Prematurity","volume":"76","author":"Olevson","year":"2023","journal-title":"S. D. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/s12974-024-03304-3","article-title":"Imaging the eye as a window to brain health: Frontier approaches and future directions","volume":"21","author":"Banna","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, R., Needham, S.R., Kraev, I., Hristova, M., and Lange, S. (2025). Extracellular vesicle signatures from eye lavage as novel non-invasive biomarkers for hypoxic ischaemic insult-findings from a neonatal mouse model. Front. Med. Technol., 7.","DOI":"10.3389\/fmedt.2025.1715676"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41392-024-01735-1","article-title":"Extracellular vesicles as tools and targets in therapy for diseases","volume":"9","author":"Kumar","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41582-025-01080-z","article-title":"Extracellular vesicles: Translational research and applications in neurology","volume":"21","author":"Manolopoulos","year":"2025","journal-title":"Nat. Rev. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Amorim, M., Martins, B., Caramelo, F., Gon\u00e7alves, C., Trindade, G., Sim\u00e3o, J., Barreto, P., Marques, I., Leal, E.C., and Carvalho, E. (2022). Putative Biomarkers in Tears for Diabetic Retinopathy Diagnosis. Front. Med., 9.","DOI":"10.3389\/fmed.2022.873483"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109242","DOI":"10.1016\/j.exer.2022.109242","article-title":"Revealing the presence of tear extracellular vesicles in Keratoconus","volume":"224","author":"Hefley","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s10384-023-01028-0","article-title":"Profiling miRNAs in tear extracellular vesicles: A pilot study with implications for diagnosis of ocular diseases","volume":"68","author":"Torimura","year":"2024","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.survophthal.2025.01.003","article-title":"Extracellular vesicles in dry eye disease and Sj\u00f6gren\u2019s syndrome: A systematic review on their diagnostic and therapeutic role","volume":"70","author":"Chopra","year":"2025","journal-title":"Surv. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1002\/1873-3468.70004","article-title":"The enigmatic world of tear extracellular vesicles (EVs)-exploring their role in ocular health and beyond","volume":"599","author":"Fatima","year":"2025","journal-title":"FEBS Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.jtos.2025.05.001","article-title":"Tear fluid derived extracellular vesicles for new biomarker discovery","volume":"37","author":"Phan","year":"2025","journal-title":"Ocul. Surf."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tetorou, K., Sisa, C., Iqbal, A., Dhillon, K., and Hristova, M. (2021). Current Therapies for Neonatal Hypoxic-Ischaemic and Infection-Sensitised Hypoxic-Ischaemic Brain Damage. Front. Synaptic Neurosci., 13.","DOI":"10.3389\/fnsyn.2021.709301"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.paed.2024.10.004","article-title":"Unveiling the hidden risks: Therapeutic creep in mild hypoxic ischemic encephalopathy","volume":"35","author":"Chakkarapani","year":"2025","journal-title":"Paediatr. Child Health"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Acun, C., Sisman, J., and El-Dib, M. (2026). Mild neonatal hypoxic-ischemic encephalopathy: Current evidence and ongoing controversies. J. Neonatal Perinat. Med., online ahead of print.","DOI":"10.1177\/19345798261475683"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"F380","DOI":"10.1136\/adc.2004.067520","article-title":"Neuropsychological and educational problems at school age associated with neonatal encephalopathy","volume":"90","author":"Marlow","year":"2005","journal-title":"Arch. Dis. Child Fetal Neonatal Ed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13578-025-01402-0","article-title":"Hypoxia-ischemia and sexual dimorphism: Modeling mitochondrial dysfunction using brain organoids","volume":"15","author":"Disdier","year":"2025","journal-title":"Cell Biosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00401-025-02888-1","article-title":"Annexin A6 membrane repair protein protects against amyloid-induced dystrophic neurites and tau phosphorylation in Alzheimer\u2019s disease model mice","volume":"149","author":"Sadleir","year":"2025","journal-title":"Acta Neuropathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ydbio.2017.03.011","article-title":"Annexin A6 controls neuronal membrane dynamics throughout chick cranial sensory gangliogenesis","volume":"425","author":"Shah","year":"2017","journal-title":"Dev. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sakwe, N.I., Korolkova, O.Y., Vuong, N.B., Edwards, A.D., Black, P.J., Ball, D.D., McIntosh, A.R., Thomas, P.L., Whalen Melvin, D.S., and Beasley, H.K. (2026). Annexin A6 Modulates the Secretion of Pro-Inflammatory Cytokines and Exosomes via Interaction with SNAP23 in Triple-Negative Breast Cancer Cells. Cells, 15.","DOI":"10.3390\/cells15111013"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhang, S., Zhang, R., Chen, Z., Shao, Z., Li, A., Li, F., and Huang, F. (2025). Neuroinflammation mediates the progression of neonate hypoxia-ischemia brain damage to Alzheimer\u2019s disease: A bioinformatics and experimental study. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1511668"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e14639","DOI":"10.1111\/cns.14639","article-title":"Annexin A6 mitigates neurological deficit in ischemia\/reperfusion injury by promoting synaptic plasticity","volume":"30","author":"Wang","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1037\/0894-4105.15.3.411","article-title":"Neonatal hypoxic risk in preterm birth infants: The influence of sex and severity of respiratory distress on cognitive recovery","volume":"15","author":"Lauterbach","year":"2001","journal-title":"Neuropsychology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/01.PCC.0000192341.67078.61","article-title":"Male sex and intraventricular hemorrhage","volume":"7","author":"Tioseco","year":"2006","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1017\/S0012162207000199.x","article-title":"Sex and the pathogenesis of cerebral palsy","volume":"49","author":"Johnston","year":"2007","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e158107","DOI":"10.1172\/jci.insight.158107","article-title":"A conserved annexin A6-mediated membrane repair mechanism in muscle, heart, and nerve","volume":"7","author":"Demonbreun","year":"2022","journal-title":"JCI Insight"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"O\u2019Neill, C.P., Gilligan, K.E., and Dwyer, R.M. (2019). Role of Extracellular Vesicles (EVs) in Cell Stress Response and Resistance to Cancer Therapy. Cancers, 11.","DOI":"10.3390\/cancers11020136"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ye, J., and Liu, X. (2022). Interactions between endoplasmic reticulum stress and extracellular vesicles in multiple diseases. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.955419"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1152\/physrev.00030.2001","article-title":"Annexins: From structure to function","volume":"82","author":"Gerke","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e2401931","DOI":"10.1002\/smtd.202401931","article-title":"Single Extracellular Vesicle Profiling to Define Brain Specific Traumatic Brain Injury Induced Neuro-Inflammation","volume":"9","author":"Zhang","year":"2025","journal-title":"Small Methods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S70","DOI":"10.1016\/S0301-2115(03)00175-1","article-title":"Perinatal brain damage--from pathophysiology to prevention","volume":"110","author":"Jensen","year":"2003","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1080\/19336918.2016.1268318","article-title":"Annexin A6-A multifunctional scaffold in cell motility","volume":"11","author":"Grewal","year":"2017","journal-title":"Cell Adh Migr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.neuroscience.2016.08.026","article-title":"Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia-ischemia","volume":"335","author":"Demarest","year":"2016","journal-title":"Neuroscience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e86556","DOI":"10.7554\/eLife.86556","article-title":"Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repair","volume":"12","author":"Williams","year":"2023","journal-title":"eLife"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1158\/0008-5472.CAN-19-3803","article-title":"Extracellular Vesicles from Cancer-Associated Fibroblasts Containing Annexin A6 Induces FAK-YAP Activation by Stabilizing \u03b21 Integrin, Enhancing Drug Resistance","volume":"80","author":"Uchihara","year":"2020","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/s41556-018-0256-3","article-title":"Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models","volume":"21","author":"Keklikoglou","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.neuroscience.2025.12.027","article-title":"Super-resolution localization microscopy visualizes ischemia-related cytoskeletal and vascular alterations at the nanoscale level in a mouse model of stroke","volume":"594","author":"Mrestani","year":"2026","journal-title":"Neuroscience"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Sisa, C., Kholia, S., Naylor, J., Herrera Sanchez, M., Bruno, S., Deregibus, M.C., Camussi, G., Inal, J.M., Lange, S., and Hristova, M. (2019). Mesenchymal Stromal Cell Derived Extracellular Vesicles Reduce Hypoxia-Ischaemia Induced Perinatal Brain Injury. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.00282"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e70090","DOI":"10.1111\/ejn.70090","article-title":"Whispers in the Brain: Extracellular Vesicles in Neuropathology and the Diagnostic Alchemy of Neurological Diseases","volume":"61","author":"Isik","year":"2025","journal-title":"Eur. J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1186\/s13054-025-05477-6","article-title":"Extracellular vesicles as a biomarkers in traumatic brain injury: A systematic review of animal and clinical studies","volume":"29","author":"Vicente","year":"2025","journal-title":"Crit. Care"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e70093","DOI":"10.1002\/btm2.70093","article-title":"Therapeutic potential and translational challenges of extracellular vesicles in neonatal medicine","volume":"11","author":"Atoom","year":"2025","journal-title":"Bioeng. Transl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neuroscience.2024.03.014","article-title":"Neonatal Hypoxia-Ischemia alters Brain-Derived Contactin-2-Positive Extracellular Vesicles in the Mouse Plasma","volume":"545","author":"Liu","year":"2024","journal-title":"Neuroscience"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1136\/archdischild-2020-321096","article-title":"Neuronal exosome proteins: Novel biomarkers for predicting neonatal response to therapeutic hypothermia","volume":"107","author":"Pineles","year":"2022","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"867531","DOI":"10.1155\/2012\/867531","article-title":"Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent models: Implications for sex-specific neuroprotection in clinical neonatal practice","volume":"2012","author":"Hill","year":"2012","journal-title":"Neurol. Res. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/glia.20896","article-title":"Activation and deactivation of periventricular white matter phagocytes during postnatal mouse development","volume":"58","author":"Hristova","year":"2010","journal-title":"Glia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/jnc.12744","article-title":"Peptidylarginine deiminases: Novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates","volume":"130","author":"Lange","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Rocha-Ferreira, E., Vincent, A., Bright, S., Peebles, D.M., and Hristova, M. (2018). The duration of hypothermia affects short-term neuroprotection in a mouse model of neonatal hypoxic ischaemic injury. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199890"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e202500483","DOI":"10.1002\/jbio.202500483","article-title":"Profiling Protein Citrullination in Extracellular Vesicles by Single-Molecule Detection Using Direct Stochastic Optical Reconstruction Microscopy","volume":"19","author":"Needham","year":"2026","journal-title":"J. Biophotonics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1096\/fj.14-269837","article-title":"Annexin A4 is a novel direct regulator of adenylyl cyclase type 5","volume":"29","author":"Heinick","year":"2015","journal-title":"FASEB J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8875\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:35:00Z","timestamp":1791372900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":54,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198875"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198875","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]}}}