{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:28:48Z","timestamp":1790742528703,"version":"4.1.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071681 81871193"],"award-info":[{"award-number":["82071681 81871193"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Neonatal hypoxic-ischemic brain damage (HIBD) often results in various neurological deficits. Among them, a common, yet often neglected, symptom is circadian rhythm disorders. Previous studies revealed that the occurrence of cysts in the pineal gland, an organ known to regulate circadian rhythm, is associated with circadian problems in children with HIBD. However, the underlying mechanisms of pineal dependent dysfunctions post HIBD remain largely elusive. Here, by performing 10x single cell RNA sequencing, we firstly molecularly identified distinct pineal cell types and explored their transcriptome changes at single cell level at 24 and 72\u00a0h post neonatal HIBD. Bioinformatic analysis of cell prioritization showed that both subtypes of pinealocytes, the predominant component of the pineal gland, were mostly affected. We then went further to investigate how distinct pineal cell types responded to neonatal HIBD. Within pinealocytes, we revealed a molecularly defined \u03b2 to \u03b1 subtype conversion induced by neonatal HIBD. Within astrocytes, we discovered that all three subtypes responded to neonatal HIBD, with differential expression of reactive astrocytes markers. Two subtypes of microglia cells were both activated by HIBD, marked by up-regulation of<jats:italic>Ccl3<\/jats:italic>. Notably, microglia cells showed substantial reduction at 72\u00a0h post HIBD. Further investigation revealed that pyroptosis preferentially occurred in pineal microglia through NLRP3-Caspase-1-GSDMD signaling pathway. Taken together, our results delineated temporal changes of molecular and cellular events occurring in the pineal gland following neonatal HIBD. By revealing pyroptosis in the pineal gland, our study also provided potential therapeutic targets for preventing extravasation of pineal pathology and thus improving circadian rhythm dysfunction in neonates with HIBD.<\/jats:p>","DOI":"10.3389\/fcell.2022.794012","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T10:07:39Z","timestamp":1646734059000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Profiling Temporal Changes of the Pineal Transcriptomes at Single Cell Level Upon Neonatal HIBD"],"prefix":"10.3389","volume":"10","author":[{"given":"Xin","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyan","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren S","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Xiao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Xi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1053\/j.nainr.2011.07.004","article-title":"Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments","volume":"11","author":"Allen","year":"2011","journal-title":"Newborn Infant Nurs. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nrn.2016.159","article-title":"Functional Diversity of Astrocytes in Neural Circuit Regulation","volume":"18","author":"Ben Haim","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nrmicro2070","article-title":"Pyroptosis: Host Cell Death and Inflammation","volume":"7","author":"Bergsbaken","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3389\/fped.2014.00144","article-title":"Neuroinflammation and Neuroimmune Dysregulation after Acute Hypoxic-Ischemic Injury of Developing Brain","volume":"2","author":"Bhalala","year":"2014","journal-title":"Front. Pediatr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.mce.2011.07.009","article-title":"Circadian Regulation of Pineal Gland Rhythmicity","volume":"349","author":"Borjigin","year":"2012","journal-title":"Mol. Cell Endocrinol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1146\/annurev-pathol-012414-040431","article-title":"The Inflammasomes and Autoinflammatory Syndromes","volume":"10","author":"Broderick","year":"2015","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"B7","first-page":"185","article-title":"Postnatal Development of Cell Types in the Rat Pineal Gland","volume":"137","author":"Calvo","year":"1983","journal-title":"J. Anat."},{"key":"B8","first-page":"405","article-title":"Ultrastructure of the Pineal Gland in the Adult Rat","volume":"138","author":"Calvo","year":"1984","journal-title":"J. Anat."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.14670\/HH-15.1005","article-title":"Cell Proliferation in the Developing Rat Pineal Gland. A Bromodeoxyuridine Immunohistochemical Study","volume":"15","author":"Calvo","year":"2000","journal-title":"Histol. Histopathol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"137","DOI":"10.14670\/HH-19.137","article-title":"Time of Origin of the Rat Pineal Gland Cells. A Bromodeoxyuridine Immunohistochemical Study","volume":"19","author":"Calvo","year":"2004","journal-title":"Histol. Histopathol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1186\/s12974-020-01879-1","article-title":"NLRP3 Inflammasome-Mediated Microglial Pyroptosis Is Critically Involved in the Development of Post-Cardiac Arrest Brain Injury","volume":"17","author":"Chang","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41590-018-0303-z","article-title":"SERPINB1-Mediated Checkpoint of Inflammatory Caspase Activation","volume":"20","author":"Choi","year":"2019","journal-title":"Nat. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"ENEURO.0288-18.2019","DOI":"10.1523\/ENEURO.0288-18.2019","article-title":"Brain Region-Specific Gene Signatures Revealed by Distinct Astrocyte Subpopulations Unveil Links to Glioma and Neurodegenerative Diseases","volume":"6","author":"Cuevas-Diaz Duran","year":"2019","journal-title":"eNeuro"},{"key":"B14","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.ajpath.2013.09.007","article-title":"New Insights into Mechanisms Controlling the NLRP3 Inflammasome and its Role in Lung Disease","volume":"184","author":"De Nardo","year":"2014","journal-title":"Am. J. Pathol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"F220","DOI":"10.1136\/adc.2008.148205","article-title":"Long-Term Outcome after Neonatal Hypoxic-Ischaemic Encephalopathy","volume":"95","author":"De Vries","year":"2010","journal-title":"Arch. Dis. Child. - Fetal Neonatal Edition"},{"key":"B16","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.neulet.2015.12.061","article-title":"Distinctive Sleep Problems in Children with Perinatal Moderate or Mild Hypoxic-Ischemia","volume":"614","author":"Ding","year":"2016","journal-title":"Neurosci. Lett."},{"key":"B17","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","article-title":"Reactive Astrocyte Nomenclature, Definitions, and Future Directions","volume":"24","author":"Escartin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1002\/glia.23687","article-title":"Questions and (Some) Answers on Reactive Astrocytes","volume":"67","author":"Escartin","year":"2019","journal-title":"Glia"},{"key":"B19","doi-asserted-by":"publisher","first-page":"338","DOI":"10.2174\/1871527311312030007","article-title":"Age-Dependent Microglial Activation in Immature Brains after Hypoxia- Ischemia","volume":"12","author":"Ferrazzano","year":"2013","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1056\/nejmra041996","article-title":"Neonatal Brain Injury","volume":"351","author":"Ferriero","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s12974-014-0230-3","article-title":"Anti-Inflammatory Effects of BHBA in Both In Vivo and In Vitro Parkinson's Disease Models Are Mediated by GPR109A-Dependent Mechanisms","volume":"12","author":"Fu","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e12742","DOI":"10.1111\/jpi.12742","article-title":"A Hypothetical Role for Autophagy during the Day\/Night Rhythm-Regulated Melatonin Synthesis in the Rat Pineal Gland","volume":"71","author":"Ge","year":"2021","journal-title":"J. Pineal Res."},{"key":"B23","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.4049\/jimmunol.133.4.1710","article-title":"Cell Cycle Analysis of a Cell Proliferation-Associated Human Nuclear Antigen Defined by the Monoclonal Antibody Ki-67","volume":"133","author":"Gerdes","year":"1984","journal-title":"J. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1038\/nm.3893","article-title":"Inflammasomes: Mechanism of Action, Role in Disease, and Therapeutics","volume":"21","author":"Guo","year":"2015","journal-title":"Nat. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/nrneurol.2015.13","article-title":"The Role of Inflammation in Perinatal Brain Injury","volume":"11","author":"Hagberg","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.immuni.2018.11.004","article-title":"Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes","volume":"50","author":"Hammond","year":"2019","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated Analysis of Multimodal Single-Cell Data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e12616","DOI":"10.1111\/jpi.12616","article-title":"The Lhx4 Homeobox Transcript in the Rat Pineal Gland: Adrenergic Regulation and Impact on Transcripts Encoding Melatonin-Synthesizing Enzymes","volume":"68","author":"Hertz","year":"2020","journal-title":"J. Pineal Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1111\/j.1471-4159.2009.06457.x","article-title":"Modulation ofAanatgene Transcription in the Rat Pineal Gland","volume":"112","author":"Ho","year":"2010","journal-title":"J. Neurochem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"9841","DOI":"10.1523\/jneurosci.1993-06.2006","article-title":"Matrix Metalloproteinase-2 Facilitates Wound Healing Events that Promote Functional Recovery after Spinal Cord Injury","volume":"26","author":"Hsu","year":"2006","journal-title":"J. Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e0167063","DOI":"10.1371\/journal.pone.0167063","article-title":"Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator","volume":"11","author":"Iba\u00f1ez Rodriguez","year":"2016","journal-title":"PLoS One"},{"key":"B32","doi-asserted-by":"publisher","first-page":"4233","DOI":"10.1074\/jbc.r600036200","article-title":"Arylalkylamine N-Acetyltransferase: \u201cThe Timezyme\u201d","volume":"282","author":"Klein","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1101\/gad.340919.120","article-title":"mTOR Inhibition Acts as an Unexpected Checkpoint in P53-Mediated Tumor Suppression","volume":"35","author":"Kon","year":"2021","journal-title":"Genes Dev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s12974-019-1423-6","article-title":"The Role of Microglial Inflammasome Activation in Pyroptotic Cell Death Following Penetrating Traumatic Brain Injury","volume":"16","author":"Lee","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"B35","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/s41586-020-2795-6","article-title":"Microglia-Organized Scar-Free Spinal Cord Repair in Neonatal Mice","volume":"587","author":"Li","year":"2020","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/aps.2013.89","article-title":"Inflammatory Responses in Hypoxic Ischemic Encephalopathy","volume":"34","author":"Liu","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"B37","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1016\/j.bbrc.2019.11.003","article-title":"The Role of Microglia Mediated Pyroptosis in Neonatal Hypoxic-Ischemic Brain Damage","volume":"521","author":"Lv","year":"2020","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e0205883","DOI":"10.1371\/journal.pone.0205883","article-title":"Single-Cell RNA Sequencing of the Mammalian Pineal Gland Identifies Two Pinealocyte Subtypes and Cell Type-Specific Daily Patterns of Gene Expression","volume":"13","author":"Mays","year":"2018","journal-title":"PLoS One"},{"key":"B39","doi-asserted-by":"publisher","first-page":"a026716","DOI":"10.1101\/cshperspect.a026716","article-title":"Caspase Functions in Cell Death and Disease","volume":"7","author":"McIlwain","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"E6065","DOI":"10.1073\/pnas.1722041115","article-title":"Caspase-1 Inhibition Prevents Glial Inflammasome Activation and Pyroptosis in Models of Multiple Sclerosis","volume":"115","author":"McKenzie","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B41","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s00441-002-0580-5","article-title":"The Anatomy and Innervation of the Mammalian Pineal Gland","volume":"309","author":"M\u00f8ller","year":"2002","journal-title":"Cell Tissue Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1542\/peds.2004-0863","article-title":"Sleep-Wake Cycling on Amplitude-Integrated Electroencephalography in Term Newborns with Hypoxic-Ischemic Encephalopathy","volume":"115","author":"Osredkar","year":"2005","journal-title":"Pediatrics"},{"key":"B43","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/bf01257021","article-title":"On the Presence of Different Populations of Pinealocytes in the Mammalian Pineal Gland","volume":"40","author":"Pevet","year":"1977","journal-title":"J. Neural Transm."},{"key":"B44","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1210\/en.2008-0882","article-title":"Developmental and Diurnal Dynamics of Pax4 Expression in the Mammalian Pineal Gland: Nocturnal Down-Regulation Is Mediated by Adrenergic-Cyclic Adenosine 3\u2032,5\u2032-Monophosphate Signaling","volume":"150","author":"Rath","year":"2009","journal-title":"Endocrinology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.1210\/en.2015-1888","article-title":"Melatonin Synthesis: Acetylserotonin O-Methyltransferase (ASMT) Is Strongly Expressed in a Subpopulation of Pinealocytes in the Male Rat Pineal Gland","volume":"157","author":"Rath","year":"2016","journal-title":"Endocrinology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The Influence of Immaturity on Hypoxic-Ischemic Brain Damage in the Rat","volume":"9","author":"Rice","year":"1981","journal-title":"Ann. Neurol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"3033","DOI":"10.1210\/endo.137.7.8770929","article-title":"Melatonin Synthesis: Analysis of the More Than 150-fold Nocturnal Increase in Serotonin N-Acetyltransferase Messenger Ribonucleic Acid in the Rat Pineal Gland","volume":"137","author":"Roseboom","year":"1996","journal-title":"Endocrinology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1038\/nm.4397","article-title":"Microglia Emerge as central Players in Brain Disease","volume":"23","author":"Salter","year":"2017","journal-title":"Nat. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1001\/archneur.1976.00500100030012","article-title":"Neonatal Encephalopathy Following Fetal Distress. A Clinical and Electroencephalographic Study","volume":"33","author":"Sarnat","year":"1976","journal-title":"Arch. Neurol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/0006-8993(93)91042-q","article-title":"Single-Cell [Ca2+]i Analysis and Biochemical Characterization of Pinealocytes Immobilized with Novel Attachment Peptide Preparation","volume":"614","author":"Schaad","year":"1993","journal-title":"Brain Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/s1389-9457(02)00071-0","article-title":"Neonatal EEG-Sleep Disruption Mimicking Hypoxic-Ischemic Encephalopathy after Intrapartum Asphyxia","volume":"3","author":"Scher","year":"2002","journal-title":"Sleep Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.earlhumdev.2004.06.003","article-title":"Hypoxic-Ischemic Brain Injury in the Term Infant-Current Concepts","volume":"80","author":"Shalak","year":"2004","journal-title":"Early Hum. Develop."},{"key":"B53","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41587-020-0605-1","article-title":"Cell Type Prioritization in Single-Cell Data","volume":"39","author":"Skinnider","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"3836","DOI":"10.1038\/s41596-021-00561-x","article-title":"Prioritization of Cell Types Responsive to Biological Perturbations in Single-Cell Data with Augur","volume":"16","author":"Squair","year":"2021","journal-title":"Nat. Protoc."},{"key":"B55","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/BF00210513","article-title":"Morphologic Development of Neonatal Rat Pinealocytes in Monolayer Culture","volume":"220","author":"Steinberg","year":"1981","journal-title":"Cel. Tissue Res."},{"key":"B56","first-page":"130","article-title":"Immunohistochemical Studies on Supporting Cells in the Adrenal Medulla and Pineal Gland of Adult Rat, Especially on S-100 Protein, Glial Fibrillary Acidic Protein and Vimentin","volume":"70","author":"Suzuki","year":"1995","journal-title":"Kaibogaku Zasshi"},{"key":"B57","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.jpeds.2011.01.006","article-title":"Delayed Onset of Sleep-Wake Cycling with Favorable Outcome in Hypothermic-Treated Neonates with Encephalopathy","volume":"159","author":"Takenouchi","year":"2011","journal-title":"J. Pediatr."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.4103\/1673-5374.300453","article-title":"TP53-Induced Glycolysis and Apoptosis Regulator Alleviates Hypoxia\/ischemia-Induced Microglial Pyroptosis and Ischemic Brain Damage","volume":"16","author":"Tan","year":"2021","journal-title":"Neural Regen. Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1111\/j.1651-2227.1990.tb11324.x","article-title":"Normal Pattern of the Cerebral Function Monitor Trace in Term and Preterm Neonates","volume":"79","author":"Thornberg","year":"1990","journal-title":"Acta Paediatr."},{"key":"B60","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/j.1469-8749.1984.tb04426.x","article-title":"Cerebral Function Monitor in the Neonate. I: Normal Patterns","volume":"26","author":"Verma","year":"1984","journal-title":"Dev. Med. Child. Neurol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1182\/blood.v97.4.1144","article-title":"Specialized Roles of the Chemokine Receptors CCR1 and CCR5 in the Recruitment of Monocytes and T(H)1-Like\/CD45RO(+) T Cells","volume":"97","author":"Weber","year":"2001","journal-title":"Blood"},{"key":"B62","doi-asserted-by":"publisher","first-page":"eabe0726","DOI":"10.1126\/sciadv.abe0726","article-title":"Strontium Ions Protect Hearts against Myocardial Ischemia\/reperfusion Injury","volume":"7","author":"Xing","year":"2021","journal-title":"Sci. Adv."},{"key":"B63","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.brainres.2017.05.001","article-title":"Up-Regulation of miR-325-3p Suppresses Pineal Aralkylamine N-Acetyltransferase (Aanat) after Neonatal Hypoxia-Ischemia Brain Injury in Rats","volume":"1668","author":"Yang","year":"2017","journal-title":"Brain Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1097\/00005072-198509000-00004","article-title":"Immunocytochemistry of Pineal Astrocytes: Species Differences and Functional Implications","volume":"44","author":"Zang","year":"1985","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/sj.cdd.4401545","article-title":"The Influence of Age on Apoptotic and Other Mechanisms of Cell Death after Cerebral Hypoxia-Ischemia","volume":"12","author":"Zhu","year":"2005","journal-title":"Cell Death Differ."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.794012\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T15:56:35Z","timestamp":1674921395000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.794012\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":65,"alternative-id":["10.3389\/fcell.2022.794012"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2022.794012","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,8]]},"article-number":"794012"}}