Randy Bent Barker , Eda Karakaya , Didem Baran , Adviye Ergul , Kaan Yagmurlu , Mehmet Albayram , Onder Albayram
{"title":"The glymphatic and meningeal lymphatic systems may converge, connecting traumatic brain injury progression with chronic traumatic encephalopathy onset","authors":"Randy Bent Barker , Eda Karakaya , Didem Baran , Adviye Ergul , Kaan Yagmurlu , Mehmet Albayram , Onder Albayram","doi":"10.1016/j.mcn.2025.104031","DOIUrl":null,"url":null,"abstract":"<div><div>Chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease marked by perivascular deposition of hyperphosphorylated tau (P-tau), is strongly linked to repetitive concussive traumatic brain injuries (TBIs). Emerging evidence implicates disruptions in the clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) from the brain—specifically within the glymphatic and meningeal lymphatic systems—as a pivotal driver of disease onset and progression. TBI disrupts glymphatic ISF–CSF exchange, compromising the clearance of pathogenic proteins—including P-tau, TDP-43, and inflammatory mediators—while promoting perivascular accumulation and neuroinflammation. Simultaneously, meningeal lymphatic dysfunction impedes CSF drainage and sustains neuroimmune activation, further amplifying glymphatic failure. Developmental trajectories of these systems suggest age-dependent susceptibilities to injury, potentially shaping both acute outcomes and long-term neurodegenerative risk. Species-specific differences between rodents and humans in brain fluid clearance pathways add translational complexity, emphasizing the need for refined models. This review reconceptualizes CTE as a disorder driven by disrupted brain fluid clearance, highlighting the convergent roles of glymphatic and meningeal lymphatic dysfunction in linking TBI to chronic neurodegeneration and identifying therapeutic targets to restore clearance and resilience.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"134 ","pages":"Article 104031"},"PeriodicalIF":2.6000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1044743125000417","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease marked by perivascular deposition of hyperphosphorylated tau (P-tau), is strongly linked to repetitive concussive traumatic brain injuries (TBIs). Emerging evidence implicates disruptions in the clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) from the brain—specifically within the glymphatic and meningeal lymphatic systems—as a pivotal driver of disease onset and progression. TBI disrupts glymphatic ISF–CSF exchange, compromising the clearance of pathogenic proteins—including P-tau, TDP-43, and inflammatory mediators—while promoting perivascular accumulation and neuroinflammation. Simultaneously, meningeal lymphatic dysfunction impedes CSF drainage and sustains neuroimmune activation, further amplifying glymphatic failure. Developmental trajectories of these systems suggest age-dependent susceptibilities to injury, potentially shaping both acute outcomes and long-term neurodegenerative risk. Species-specific differences between rodents and humans in brain fluid clearance pathways add translational complexity, emphasizing the need for refined models. This review reconceptualizes CTE as a disorder driven by disrupted brain fluid clearance, highlighting the convergent roles of glymphatic and meningeal lymphatic dysfunction in linking TBI to chronic neurodegeneration and identifying therapeutic targets to restore clearance and resilience.
期刊介绍:
Molecular and Cellular Neuroscience publishes original research of high significance covering all aspects of neurosciences indicated by the broadest interpretation of the journal''s title. In particular, the journal focuses on synaptic maintenance, de- and re-organization, neuron-glia communication, and de-/regenerative neurobiology. In addition, studies using animal models of disease with translational prospects and experimental approaches with backward validation of disease signatures from human patients are welcome.