{"title":"Astrocyte TrkB promotes brain injury and edema formation in ischemic stroke","authors":"","doi":"10.1016/j.nbd.2024.106670","DOIUrl":null,"url":null,"abstract":"<div><div>Following ischemic stroke astrocytes undergo rapid molecular and functional changes that may accentuate tissue damage. In this study we identified the neurotrophin receptor TrkB in astrocytes as a key promoter of acute CNS injury in ischemic stroke. In fact, TrkB protein was strongly upregulated in astrocytes after human and experimental stroke, and transgenic mice lacking astrocyte TrkB displayed significantly smaller lesion volume, lower brain atrophy and better motor performance than control animals after transient middle cerebral artery occlusion. Neuropathological studies evidenced that edema directly correlated with astrogliosis and was limited in transgenic mice. Importantly, adaptive levels of the water channel AQP4 was astrocyte TrkB-dependent as AQP4 upregulation after stroke did not occur in mice lacking astrocyte TrkB. <em>In vitro</em> experiments with wild-type and/or TrkB-deficient astrocytes highlighted TrkB-dependent upregulation of AQP4 <em>via</em> activation of HIF1-alpha under hypoxia. Collectively, our observations indicate that TrkB signaling in astrocytes contributes to the development of edema and worsens cerebral ischemia.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124002705/pdfft?md5=a3579dc67ed60f3eb452a11c17c6cf2c&pid=1-s2.0-S0969996124002705-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Disease","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0969996124002705","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Following ischemic stroke astrocytes undergo rapid molecular and functional changes that may accentuate tissue damage. In this study we identified the neurotrophin receptor TrkB in astrocytes as a key promoter of acute CNS injury in ischemic stroke. In fact, TrkB protein was strongly upregulated in astrocytes after human and experimental stroke, and transgenic mice lacking astrocyte TrkB displayed significantly smaller lesion volume, lower brain atrophy and better motor performance than control animals after transient middle cerebral artery occlusion. Neuropathological studies evidenced that edema directly correlated with astrogliosis and was limited in transgenic mice. Importantly, adaptive levels of the water channel AQP4 was astrocyte TrkB-dependent as AQP4 upregulation after stroke did not occur in mice lacking astrocyte TrkB. In vitro experiments with wild-type and/or TrkB-deficient astrocytes highlighted TrkB-dependent upregulation of AQP4 via activation of HIF1-alpha under hypoxia. Collectively, our observations indicate that TrkB signaling in astrocytes contributes to the development of edema and worsens cerebral ischemia.
期刊介绍:
Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.