Cannabidiol Alleviates Neurological Deficits After Traumatic Brain Injury by Improving Intracranial Lymphatic Drainage

作者：Shiying Dong, Hongwei Zhao, Meng Nie, Zhuang Sha, Jiancheng Feng, Mingqi Liu, Chuanxiang Lv, Yupeng Chen, Weiwei Jiang, Jiangyuan Yuan, Qian Yu, Honggang Wan, Chuang Gao, Rongcai Jiang · 发表于：Journal of Neurotrauma · 年份：2024 · DOI：10.1089/neu.2023.0539 · 被引用次数：23 · 研究领域：Cerebrospinal fluid and hydrocephalus、Neuroscience of respiration and sleep、Cannabis and Cannabinoid Research

Traumatic brain injury (TBI) persists as a substantial clinical dilemma, largely because of the absence of effective treatments. This challenge is exacerbated by the hindered clearance of intracranial metabolic byproducts and the continual accrual of deleterious proteins. The glymphatic system (GS) and meningeal lymphatic vessels (MLVs), key elements of the intracranial lymphatic network, play critical roles in the clearance of harmful substances. Cannabidiol (CBD) has shown promise in reducing metabolite overload and bolstering cognitive performance in various neurodegenerative diseases. The precise mechanisms attributing to its beneficial effects in TBI scenarios, however, are yet to be distinctly understood. Utilizing a fluid percussion injury paradigm, our research adopted a multifaceted approach, encompassing behavioral testing, immunofluorescence and immunohistochemical analyses, laser speckle imaging, western blot techniques, and bilateral cervical efferent lymphatic ligation. This methodology aimed to discern the influence of CBD on both neurological outcomes and intracranial lymphatic clearance in a murine TBI model. We observed that CBD administration notably ameliorated motor, memory, and cognitive functions, concurrently with a significant reduction in the concentration of phosphorylated tau protein and amyloid-β. In addition, CBD expedited the turnover and elimination of intracranial tracers, increased cerebral blood flow, and enhanced the efficacy of fluorescent...