Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA 22908, USA; Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA.
Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA 22908, USA; Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA.
Neuron. 2018 Oct 24;100(2):375-388. doi: 10.1016/j.neuron.2018.09.022.
The nature of fluid dynamics within the brain parenchyma is a focus of intensive research. Of particular relevance is its participation in diseases associated with protein accumulation and aggregation in the brain, such as Alzheimer's disease (AD). The meningeal lymphatic vessels have recently been recognized as an important player in the complex circulation and exchange of soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). In aging mammals, for example, impaired functioning of the meningeal lymphatic vessels can lead to accelerated accumulation of toxic amyloid beta protein in the brain parenchyma, thus aggravating AD-related pathology. Given that meningeal lymphatic vessels are functionally linked to paravascular influx/efflux of the CSF/ISF, and in light of recent findings that certain cytokines, classically perceived as immune molecules, exert neuromodulatory effects, it is reasonable to suggest that the activity of meningeal lymphatics could alter the accessibility of CSF-borne immune neuromodulators to the brain parenchyma, thereby altering their effects on the brain. Accordingly, in this Perspective we propose that the meningeal lymphatic system can be viewed as a novel player in neurophysiology.
脑实质内的流体动力学性质是密集研究的焦点。特别相关的是，它参与了与脑内蛋白质积累和聚集相关的疾病，如阿尔茨海默病（AD）。脑膜淋巴管最近被认为是脑脊液（CSF）和间质液（ISF）之间复杂循环和可溶性物质交换的重要参与者。例如，在衰老的哺乳动物中，脑膜淋巴管功能障碍会导致脑实质中有毒淀粉样β蛋白的加速积累，从而加重 AD 相关的病理学。鉴于脑膜淋巴管与 CSF/ISF 的血管周围流入/流出功能相关，并且鉴于最近发现某些细胞因子，经典上被认为是免疫分子，发挥神经调节作用，因此可以合理地假设脑膜淋巴管的活动可以改变 CSF 携带的免疫神经调节剂到达脑实质的可及性，从而改变它们对大脑的影响。因此，在本观点中，我们提出脑膜淋巴管系统可以被视为神经生理学的一个新的参与者。
