[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-452013-105":59,"doc-detail-452013-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","promoting-astrocyte-neuron-triiodothyronine-shuttling-attenuates-brain-damage-in-neonatal-hypoxic-ischemic-encephalopathy","Promoting astrocyte-neuron triiodothyronine shuttling attenuates brain damage in neonatal hypoxic-ischemic encephalopathy","","Neonatal hypoxic-ischemic encephalopathy (HIE) causes severe, lifelong disability and lacks effective disease-modifying therapies. This study investigates astrocyte-neuron crosstalk signaling as a therapeutic entry point. Using the Rice–Vannucci hypoxic–ischemic model in postnatal day 7 rat pups, injury was validated structurally and hemodynamically. Whole-brain single-cell RNA sequencing, astrocyte proteomics after oxygen–glucose deprivation, and multiplex immunofluorescence mapped astrocyte diversity and pathways.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/promoting-astrocyte-neuron-triiodothyronine-shuttling-attenuates-brain-damage-in-neonatal-hypoxic-ischemic-encephalopathy/452013/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/promoting-astrocyte-neuron-triiodothyronine-shuttling-attenuates-brain-damage-in-neonatal-hypoxic-ischemic-encephalopathy/452013.png","ImageObject",300,407,{"name":92,"@type":93},"Ben ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the central research focus regarding neonatal HIE?","Question",{"text":112,"@type":113},"The study examines whether astrocyte-neuron triiodothyronine (T3) shuttling can attenuate brain damage in neonatal hypoxic-ischemic encephalopathy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was hypoxic-ischemic injury modeled and verified?",{"text":117,"@type":113},"Hypoxic–ischemic brain damage was induced in postnatal day 7 rat pups using the Rice–Vannucci model, then verified structurally and hemodynamically with histopathology and laser speckle contrast imaging.",{"name":119,"@type":110,"acceptedAnswer":120},"Which cell population and therapeutic mechanism were identified?",{"text":121,"@type":113},"A Dio2+Slc1a2+ astrocyte subpopulation showed metabolic and neuroprotective features, depleted after injury, and boosting Dio2 or delivering exogenous T3 enhanced neural repair and behavior via astrocyte–neuron crosstalk.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},452013,1790792234,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},2336478951081,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Yu etal. Journal of Neuroinflammation (2026) 23:5 Journal of Neuroinflammation  \n[https://doi.org/10.1186/s12974-025-03641-x](https://doi.org/10.1186/s12974-025-03641-x)  \nRESEARCH Open Access  \nPromoting astrocyte-neuron triiodothyronine  shuttling attenuates brain damage in neonatal hypoxic-ischemic encephalopathy  \nGuoSheng Yu 1,2,3†, Yun Yang4†, Wei Zhou 1,2,3, XinYi Wang 1,2,3, YaNi Feng 1,2,3, XingYun Wang5* and ZhenLang Lin 1,2,3*  \nAbstract  \nBackground Neonatal Hypoxic-Ischemic Encephalopathy (HIE) is a critical lifelong disabling neonatal disease withinsufficient effective therapies. Signaling molecules derived from Astrocyte-Neuron Crosstalk have the potential to improve the prognosis, but relevant HIE research is limited.  \nMethods We established hypoxic–ischemic brain damage (HIBD) in postnatal day 7 rat pups using the Rice– Vannucci model, and verified the injury both structurally and hemodynamically by histopathology and laser speckle contrast imaging. Whole-brain single-cell RNA sequencing was performed at P10, and proteomic profiling was conducted on astrocytes subjected to oxygen–glucose deprivation. We charted astrocyte diversity in situ using multiplex immunofluorescence. Thyroid hormones and signaling pathways were quantified by ELISA and Western blotting. Therapeutic efficacy was assessed by histopathology and the Morris water maze.  \nResults A brain-wide single-cell transcriptomic atlas revealed a strong transcriptional coupling between astrocytes and neurons. Among astrocytes, we identified and functionally characterized a Dio2⁺Slc1a2⁺ subpopulation  \nwith metabolic and neuroprotective features, which was markedly depleted after HIBD. Pseudotime trajectories showed dynamic astrocyte state transitions over time, contextual izing the loss and reparative potential of the Dio2⁺ subpopulation. In vivo and in vitro, boosting astrocytic Dio2 or delivering exogenous Triiodothyronine(T3) enhanced neural repair and improved behavior across both early and long-term stages.  \nConclusions We defined a previously unrecognized neuroprotective astrocyte subpopulation and revealed temporal heterogeneity in astrocytic inflammatory responses in HIE. We also identified aT3-mediated astrocyte–neuron crosstalk mechanism that mitigated HIBD, highlighting a tractable therapeutic avenue.  \nKeywords HIE, Astrocyte, Astrocyte-neuron crosstalk, T3, ScRNA-seq  \n†GuoSheng Yu andYun Yang contributed equally to this article.  \n*Correspondence:  \nXingYun Wang [wxy@shsmu.edu.cn](wxy@shsmu.edu.cn)[ ](wxy@shsmu.edu.cn)ZhenLang Lin [linzhenlang0801@163.com](linzhenlang0801@163.com)  \n1Department of Neonatology, the Second Affiliated Hospital andYuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China  \n2Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang Province, China  \n3Key Laboratory of Perinatal Medicine of Wenzhou, The Second Affiliated Hospital andYuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China  \n4Department of Child Health Care, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China  \n5Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China  \n© The Author(s) 2025, modified publication 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercialNoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated","cbCaiciUkYegJOPG","https://ap.wps.com/l/cbCaiciUkYegJOPG","pdf",4191963,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n## Clinical context of neonatal HIE\n## Role of astrocyte–neuron crosstalk","[{\"question\":\"What is the central research focus regarding neonatal HIE?\",\"answer\":\"The study examines whether astrocyte-neuron triiodothyronine (T3) shuttling can attenuate brain damage in neonatal hypoxic-ischemic encephalopathy.\"},{\"question\":\"How was hypoxic-ischemic injury modeled and verified?\",\"answer\":\"Hypoxic–ischemic brain damage was induced in postnatal day 7 rat pups using the Rice–Vannucci model, then verified structurally and hemodynamically with histopathology and laser speckle contrast imaging.\"},{\"question\":\"Which cell population and therapeutic mechanism were identified?\",\"answer\":\"A Dio2+Slc1a2+ astrocyte subpopulation showed metabolic and neuroprotective features, depleted after injury, and boosting Dio2 or delivering exogenous T3 enhanced neural repair and behavior via astrocyte–neuron crosstalk.\"}]","Promoting astrocyte-neuron triiodothyronine shuttling attenuates brain damage in neonatal hypoxic-ischemic encephalopathy | PDF",1790736317,48]