{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T04:38:33Z","timestamp":1773203913056,"version":"3.50.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1142862"],"award-info":[{"award-number":["APP1142862"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Cognitive impairment is a common and disruptive outcome for stroke survivors, which is recognized to be notoriously difficult to treat. Previously, we have shown that low oxygen post-conditioning (LOPC) improves motor function and limits secondary neuronal loss in the thalamus after experimental stroke. There is also emerging evidence that LOPC may improve cognitive function post-stroke. In the current study we aimed to explore how exposure to LOPC may improve cognition post-stroke. Experimental stroke was induced using photothrombotic occlusion in adult, male C57BL\/6 mice. At 72 h post-stroke animals were randomly assigned to either normal atmospheric air or to one of two low oxygen (11% O<jats:sub>2<\/jats:sub>) exposure groups (either 8 or 24 h\/day for 14 days). Cognition was assessed during the treatment phase using a touchscreen based paired-associate learning assessment. At the end of treatment (17 days post-stroke) mice were euthanized and tissue was collected for subsequent histology and biochemical analysis. LOPC (both 8 and 24 h) enhanced learning and memory in the 2nd week post-stroke when compared with stroke animals exposed to atmospheric air. Additionally we observed LOPC was associated with lower levels of neuronal loss, the restoration of several vascular deficits, as well as a reduction in the severity of the amyloid-beta (A\u03b2) burden. These findings provide further insight into the pro-cognitive benefits of LOPC.<\/jats:p>","DOI":"10.3389\/fneur.2021.585189","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T06:09:44Z","timestamp":1616566184000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Exploring How Low Oxygen Post Conditioning Improves Stroke-Induced Cognitive Impairment: A Consideration of Amyloid-Beta Loading and Other Mechanisms"],"prefix":"10.3389","volume":"12","author":[{"given":"Zidan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca J.","family":"Hood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin Kooi","family":"Ong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Pietrogrande","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Sanchez Bezanilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirby E.","family":"Warren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Ilicic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murielle G.","family":"Kluge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford","family":"TeBay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole P.","family":"Ottersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah J.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick R.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1001\/jama.2015.6968","article-title":"Trajectory of cognitive decline after incident stroke","volume":"314","author":"Levine","year":"2015","journal-title":"JAMA."},{"key":"B2","doi-asserted-by":"publisher","first-page":"80","DOI":"10.3978\/j.issn.2305-5839.2014.08.05","article-title":"Post-stroke cognitive impairment: epidemiology, mechanisms and management","volume":"2","author":"Sun","year":"2014","journal-title":"Ann Transl Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1161\/STROKEAHA.110.598839","article-title":"Self-reported long-term needs after stroke","volume":"42","author":"McKevitt","year":"2011","journal-title":"Stroke."},{"key":"B4","doi-asserted-by":"publisher","first-page":"CD002842","DOI":"10.1002\/14651858.CD002842.pub2","article-title":"Cognitive rehabilitation for attention deficits following stroke","volume":"2013","author":"Loetscher","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"CD008391","DOI":"10.1002\/14651858.CD008391.pub2","article-title":"Cognitive rehabilitation for executive dysfunction in adults with stroke or other adult non-progressive acquired brain damage","volume":"2013","author":"Chung","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1161\/STROKEAHA.117.020557","article-title":"Growth hormone improves cognitive function after experimental stroke","volume":"49","author":"Ong","year":"2018","journal-title":"Stroke."},{"key":"B7","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.bbr.2009.05.023","article-title":"Delayed and chronic treatment with growth hormone after endothelin-induced stroke in the adult rat","volume":"204","author":"Pathipati","year":"2009","journal-title":"Behav Brain Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"606","DOI":"10.3390\/ijms21020606","article-title":"Growth hormone promotes motor function after experimental stroke and enhances recovery-promoting mechanisms within the peri-infarct area","volume":"21","author":"Sanchez-Bezanilla","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4563","DOI":"10.3390\/ijms21124563","article-title":"Growth hormone treatment promotes remote hippocampal plasticity after experimental cortical stroke","volume":"21","author":"Sanchez-Bezanilla","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1177\/1535370217712691","article-title":"Hypoxic conditioning and the central nervous system: a new therapeutic opportunity for brain and spinal cord injuries?","volume":"242","author":"Baillieul","year":"2017","journal-title":"Exp Biol Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1533317519896725","DOI":"10.1177\/1533317519896725","article-title":"Intermittent hypoxia training for treating mild cognitive impairment: a pilot study","volume":"35","author":"Wang","year":"2020","journal-title":"Am J Alzheimers Dis Other Demen."},{"key":"B12","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/nature20173","article-title":"Hypoxia induces heart regeneration in adult mice","volume":"541","author":"Nakada","year":"2017","journal-title":"Nature."},{"key":"B13","doi-asserted-by":"publisher","first-page":"409625","DOI":"10.1155\/2015\/409625","article-title":"Efficacy of acute intermittent hypoxia on physical function and health status in humans with spinal cord injury: a brief review","volume":"2015","author":"Astorino","year":"2015","journal-title":"Neural Plast."},{"key":"B14","doi-asserted-by":"publisher","first-page":"4841","DOI":"10.1038\/s41598-019-39493-8","article-title":"Low oxygen post conditioning prevents thalamic secondary neuronal loss caused by excitotoxicity after cortical stroke","volume":"9","author":"Pietrogrande","year":"2019","journal-title":"Sci Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1007\/s12975-018-0656-5","article-title":"Low oxygen post conditioning as an efficient non-pharmacological strategy to promote motor function after stroke","volume":"10","author":"Pietrogrande","year":"2018","journal-title":"Transl Stroke Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.expneurol.2018.05.018","article-title":"Hypoxic postconditioning enhances functional recovery following endothelin-1 induced middle cerebral artery occlusion in conscious rats","volume":"306","author":"Nguyen","year":"2018","journal-title":"Exp Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3349","DOI":"10.1161\/STROKEAHA.109.557314","article-title":"Delayed hypoxic postconditioning protects against cerebral ischemia in the mouse","volume":"40","author":"Leconte","year":"2009","journal-title":"Stroke."},{"key":"B18","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/jcbfm.2013.15","article-title":"Post ischemia intermittent hypoxia induces hippocampal neurogenesis and synaptic alterations and alleviates long-term memory impairment","volume":"33","author":"Tsai","year":"2013","journal-title":"J Cereb Blood Flow Metab."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e24001","DOI":"10.1371\/journal.pone.0024001","article-title":"Intermittent hypoxia after transient focal ischemia induces hippocampal neurogenesis and c-Fos expression and reverses spatial memory deficits in rats","volume":"6","author":"Tsai","year":"2011","journal-title":"PLoS One."},{"key":"B20","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.expneurol.2019.05.001","article-title":"Visual discrimination impairment after experimental stroke is associated with disturbances in the polarization of the astrocytic aquaporin-4 and increased accumulation of neurotoxic proteins","volume":"318","author":"Sanchez-Bezanilla","year":"2019","journal-title":"Exp Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/325733a0","article-title":"The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor","volume":"325","author":"Kang","year":"1987","journal-title":"Nature."},{"key":"B22","doi-asserted-by":"publisher","first-page":"12787","DOI":"10.1523\/JNEUROSCI.3657-09.2009","article-title":"The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential","volume":"29","author":"Vassar","year":"2009","journal-title":"J Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1002\/neu.1064","article-title":"Neuronal localization of the TNFalpha converting enzyme (TACE) in brain tissue and its correlation to amyloid plaques","volume":"49","author":"Skovronsky","year":"2001","journal-title":"J Neurobiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/nm890","article-title":"RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain","volume":"9","author":"Deane","year":"2003","journal-title":"Nat Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1046\/j.1471-4159.2002.00855.x","article-title":"Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?","volume":"81","author":"Carson","year":"2002","journal-title":"J Neurochem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"24540","DOI":"10.1074\/jbc.M007579200","article-title":"Degradation of the Alzheimer's amyloid beta peptide by endothelin-converting enzyme","volume":"276","author":"Eckman","year":"2001","journal-title":"J Biol Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1172\/JCI10498","article-title":"Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier","volume":"106","author":"Shibata","year":"2000","journal-title":"J Clin Invest."},{"key":"B28","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1172\/JCI81108","article-title":"Endothelial LRP1 transports amyloid-beta(1-42) across the blood-brain barrier","volume":"126","author":"Storck","year":"2016","journal-title":"J Clin Invest."},{"key":"B29","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3389\/fnagi.2014.00093","article-title":"The low-density lipoprotein receptor-related protein 1 and amyloid-beta clearance in Alzheimer's disease","volume":"6","author":"Kanekiyo","year":"2014","journal-title":"Front Aging Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/jcbfm.2010.220","article-title":"Animal research: reporting in vivo experiments\u2013the ARRIVE guidelines","volume":"31","author":"Kilkenny","year":"2011","journal-title":"J Cereb Blood Flow Metab."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1177\/0271678X16654920","article-title":"Chronic stress exposure following photothrombotic stroke is associated with increased levels of amyloid beta accumulation and altered oligomerisation at sites of thalamic secondary neurodegeneration in mice","volume":"37","author":"Ong","year":"2017","journal-title":"J Cereb Blood Flow Metab."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3709","DOI":"10.1177\/0271678X17696100","article-title":"Chronic stress induced disruption of the peri-infarct neurovascular unit following experimentally induced photothrombotic stroke","volume":"37","author":"Zhao","year":"2017","journal-title":"J Cereb Blood Flow Metab."},{"key":"B33","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jneumeth.2007.02.020","article-title":"Pepsin pretreatment allows collagen IV immunostaining of blood vessels in adult mouse brain","volume":"163","author":"Franciosi","year":"2007","journal-title":"J Neurosci Methods."},{"key":"B34","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.jneumeth.2004.04.029","article-title":"Infarct volume quantification in mouse focal cerebral ischemia: a comparison of triphenyltetrazolium chloride and cresyl violet staining techniques","volume":"139","author":"Tureyen","year":"2004","journal-title":"J Neurosci Methods."},{"key":"B35","doi-asserted-by":"publisher","first-page":"10607","DOI":"10.1038\/srep10607","article-title":"Strategies to improve quantitative assessment of immunohistochemical and immunofluorescent labelling","volume":"5","author":"Johnson","year":"2015","journal-title":"Sci Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.neuroscience.2015.09.061","article-title":"A combined cumulative threshold spectra and digital reconstruction analysis reveal structural alterations of microglia within the prefrontal cortex following low-dose LPS administration","volume":"310","author":"Kongsui","year":"2015","journal-title":"Neuroscience."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1161\/01.STR.0000169933.88903.cf","article-title":"Transformation of diffuse beta-amyloid precursor protein and beta-amyloid deposits to plaques in the thalamus after transient occlusion of the middle cerebral artery in rats","volume":"36","author":"van Groen","year":"2005","journal-title":"Stroke."},{"key":"B38","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/sj.jcbfm.9600529","article-title":"Coaccumulation of calcium and beta-amyloid in the thalamus after transient middle cerebral artery occlusion in rats","volume":"28","author":"Makinen","year":"2008","journal-title":"J Cereb Blood Flow Metab."},{"key":"B39","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/0165-0270(84)90007-4","article-title":"Developments of a water-maze procedure for studying spatial learning in the rat","volume":"11","author":"Morris","year":"1984","journal-title":"J Neurosci Methods."},{"key":"B40","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.bbr.2017.07.039","article-title":"Behavioral outcome measures to improve experimental stroke research","volume":"352","author":"Balkaya","year":"2018","journal-title":"Behav Brain Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s12031-016-0837-1","article-title":"Translational assays for assessment of cognition in rodent models of Alzheimer's disease and dementia","volume":"60","author":"Shepherd","year":"2016","journal-title":"J Mol Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1038\/nprot.2013.122","article-title":"The touchscreen operant platform for testing learning and memory in rats and mice","volume":"8","author":"Horner","year":"2013","journal-title":"Nat Protoc."},{"key":"B43","doi-asserted-by":"publisher","first-page":"19545","DOI":"10.1038\/s41598-020-76560-x","article-title":"Similar cognitive deficits in mice and humans in the chronic phase post-stroke identified using the touchscreen-based paired-associate learning task","volume":"10","author":"Chow","year":"2020","journal-title":"Sci Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/ijs.12275","article-title":"Cognitive performance after stroke\u2013the Framingham Heart Study","volume":"9","author":"Weinstein","year":"2014","journal-title":"Int J Stroke."},{"key":"B45","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/nature04533","article-title":"A specific amyloid-beta protein assembly in the brain impairs memory","volume":"440","author":"Lesne","year":"2006","journal-title":"Nature."},{"key":"B46","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1097\/00005768-199902000-00010","article-title":"Intermittent hypobaric hypoxia stimulates erythropoiesis and improves aerobic capacity","volume":"31","author":"Rodriguez","year":"1999","journal-title":"Med Sci Sports Exerc."},{"key":"B47","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1580\/1080-6032(2000)0110172:IVCHEO2.3.CO;2","article-title":"Intermittent vs continuous hypoxia: effects on ventilation and erythropoiesis in humans","volume":"11","author":"Garcia","year":"2000","journal-title":"Wilderness Environ Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2238","DOI":"10.1152\/jappl.1992.72.6.2238","article-title":"Brain adaptation to chronic hypobaric hypoxia in rats","volume":"72","author":"LaManna","year":"1992","journal-title":"J Appl Physiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1523\/JNEUROSCI.17-01-00171.1997","article-title":"Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain","volume":"17","author":"Nielsen","year":"1997","journal-title":"J Neurosci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/2045-824X-5-4","article-title":"The importance of microglia in the development of the vasculature in the central nervous system","volume":"5","author":"Arnold","year":"2013","journal-title":"Vasc Cell."},{"key":"B51","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s00401-014-1372-1","article-title":"Perivascular microglia promote blood vessel disintegration in the ischemic penumbra","volume":"129","author":"Jolivel","year":"2015","journal-title":"Acta Neuropathol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.bbi.2013.02.005","article-title":"Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro","volume":"32","author":"Chhor","year":"2013","journal-title":"Brain Behav Immun."},{"key":"B53","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3390\/brainsci10080503","article-title":"The increased densities, but different distributions, of both C3 and S100A10 immunopositive astrocyte-like cells in Alzheimer's disease brains suggest possible roles for both A1 and A2 astrocytes in the disease pathogenesis","volume":"10","author":"King","year":"2020","journal-title":"Brain Sci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"3697","DOI":"10.1093\/brain\/awr300","article-title":"Cerebrovascular lesions induce transient beta-amyloid deposition","volume":"134","author":"Garcia-Alloza","year":"2011","journal-title":"Brain."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3934\/medsci.2017.1.1","article-title":"Is stroke a neurodegenerative condition? A critical review of secondary neurodegeneration and amyloid-beta accumulation after stroke","volume":"4","author":"Ong","year":"2017","journal-title":"AIMS Med Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1093\/brain\/awt062","article-title":"Brain amyloid-beta oligomers in ageing and Alzheimer's disease","volume":"136","author":"Lesne","year":"2013","journal-title":"Brain."},{"key":"B57","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nrm2101","article-title":"Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide","volume":"8","author":"Haass","year":"2007","journal-title":"Nat Rev Mol Cell Biol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"26239","DOI":"10.1073\/pnas.1902301116","article-title":"Oligomeric abeta in the monkey brain impacts synaptic integrity and induces accelerated cortical aging","volume":"116","author":"Beckman","year":"2019","journal-title":"Proc Natl Acad Sci USA."},{"key":"B59","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1006\/exnr.2001.7732","article-title":"Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer's disease: identification of a cellular activation mechanism","volume":"171","author":"Lue","year":"2001","journal-title":"Exp Neurol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s11481-012-9427-3","article-title":"Amyloid-beta-induced astrocytic phagocytosis is mediated by CD36, CD47 and RAGE","volume":"8","author":"Jones","year":"2013","journal-title":"J Neuroimmune Pharmacol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3389\/fnagi.2016.00160","article-title":"Mechanisms of abeta clearance and degradation by glial cells","volume":"8","author":"Ries","year":"2016","journal-title":"Front Aging Neurosci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"483453","DOI":"10.1101\/483453","article-title":"Low oxygen post conditioning improves stroke-induced cognitive impairment","volume":"2018","author":"Zhao","year":"2018","journal-title":"bioRxiv"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.585189\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T06:09:47Z","timestamp":1616566187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.585189\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,24]]},"references-count":62,"alternative-id":["10.3389\/fneur.2021.585189"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.585189","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,24]]},"article-number":"585189"}}