Weller Roy O, Djuanda Effie, Yow Hong-Yeen, Carare Roxana O
Clinical Neurosciences, Southampton General Hospital, University of Southampton School of Medicine, LD74, South Lab and Path Block, Southampton, SO16 6YD, UK.
Acta Neuropathol. 2009 Jan;117(1):1-14. doi: 10.1007/s00401-008-0457-0. Epub 2008 Nov 11.
There are no conventional lymphatics in the brain but physiological studies have revealed a substantial and immunologically significant lymphatic drainage from brain to cervical lymph nodes. Cerebrospinal fluid drains via the cribriform plate and nasal mucosa to cervical lymph nodes in rats and sheep and to a lesser extent in humans. More significant for a range of human neurological disorders is the lymphatic drainage of interstitial fluid (ISF) and solutes from brain parenchyma along capillary and artery walls. Tracers injected into grey matter, drain out of the brain along basement membranes in the walls of capillaries and cerebral arteries. Lymphatic drainage of antigens from the brain by this route may play a significant role in the immune response in virus infections, experimental autoimmune encephalomyelitis and multiple sclerosis. Neither antigen-presenting cells nor lymphocytes drain to lymph nodes by the perivascular route and this may be a factor in immunological privilege of the brain. Vessel pulsations appear to be the driving force for the lymphatic drainage along artery walls, and as vessels stiffen with age, amyloid peptides deposit in the drainage pathways as cerebral amyloid angiopathy (CAA). Blockage of lymphatic drainage of ISF and solutes from the brain by CAA may result in loss of homeostasis of the neuronal environment that may contribute to neuronal malfunction and dementia. Facilitating perivascular lymphatic drainage of amyloid-beta (Abeta) in the elderly may prevent the accumulation of Abeta in the brain, maintain homeostasis and provide a therapeutic strategy to help avert cognitive decline in Alzheimer's disease.
大脑中不存在传统的淋巴管，但生理学研究表明，从大脑到颈部淋巴结存在大量且具有免疫学意义的淋巴引流。在大鼠和绵羊中，脑脊液通过筛板和鼻黏膜引流至颈部淋巴结，在人类中这种引流作用相对较弱。对于一系列人类神经系统疾病而言，更重要的是脑实质中的间质液（ISF）和溶质沿毛细血管和动脉壁的淋巴引流。注入灰质的示踪剂沿着毛细血管壁和脑动脉壁的基底膜排出大脑。通过这种途径，大脑中抗原的淋巴引流可能在病毒感染、实验性自身免疫性脑脊髓炎和多发性硬化症的免疫反应中发挥重要作用。抗原呈递细胞和淋巴细胞均不会通过血管周围途径引流至淋巴结，这可能是大脑免疫特权的一个因素。血管搏动似乎是沿动脉壁淋巴引流的驱动力，随着年龄增长血管变硬，淀粉样肽作为脑淀粉样血管病（CAA）沉积在引流途径中。CAA导致脑内ISF和溶质的淋巴引流受阻，可能会导致神经元环境的稳态失衡，进而导致神经元功能障碍和痴呆。促进老年人血管周围β淀粉样蛋白（Aβ）的淋巴引流可能会防止Aβ在大脑中蓄积，维持稳态，并提供一种治疗策略，以帮助避免阿尔茨海默病患者的认知能力下降。
