The glymphatic and meningeal lymphatic systems may converge, connecting traumatic brain injury progression with chronic traumatic encephalopathy onset

IF 2.6 3区 医学 Q3 NEUROSCIENCES
Randy Bent Barker , Eda Karakaya , Didem Baran , Adviye Ergul , Kaan Yagmurlu , Mehmet Albayram , Onder Albayram
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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.
淋巴系统和脑膜淋巴系统可能会聚,将创伤性脑损伤的进展与慢性创伤性脑病的发病联系起来
慢性创伤性脑病(CTE)是一种进行性神经退行性疾病,其特征是血管周围过度磷酸化的tau蛋白(P-tau)沉积,与重复性震荡创伤性脑损伤(tbi)密切相关。新出现的证据表明,脑内间质液(ISF)和脑脊液(CSF)的清除中断,特别是在淋巴和脑膜淋巴系统内,是疾病发生和进展的关键驱动因素。TBI破坏淋巴ISF-CSF交换,损害致病性蛋白(包括P-tau、TDP-43和炎症介质)的清除,同时促进血管周围积聚和神经炎症。同时,脑膜淋巴功能障碍阻碍脑脊液引流并维持神经免疫激活,进一步放大淋巴功能衰竭。这些系统的发育轨迹表明对损伤的年龄依赖性易感性,可能影响急性结果和长期神经退行性风险。啮齿类动物和人类在脑液清除途径上的物种特异性差异增加了翻译的复杂性,强调了改进模型的必要性。这篇综述将CTE重新定义为一种由脑液清除中断驱动的疾病,强调了淋巴和脑膜淋巴功能障碍在将TBI与慢性神经退行性变联系起来方面的共同作用,并确定了恢复清除和恢复能力的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.60
自引率
0.00%
发文量
65
审稿时长
37 days
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.
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