The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange.

数十年来，人们一直认为脊椎动物的大脑在没有经典的淋巴引流管的情况下仍能正常运作。相反，新发现表明功能性淋巴引流确实存在于大脑中。脑淋巴引流系统由基于基底膜的血管周围通路，脑全淋巴通路和脑脊髓液（CSF）引流途径组成，包括窦相关的脑膜淋巴管和嗅觉/宫颈淋巴途径。脑淋巴系统的生理功能是从脑实质到附近淋巴结的组织液（ISF）的引流途径。脑淋巴引流有助于维持ISF的水和离子平衡，废物清除以及大分子溶质的重吸收。第二种生理功能包括与免疫系统的交流，调节免疫监视和大脑的反应。这些生理功能受衰老，遗传表型，睡眠-觉醒周期和身体姿势的影响。脑淋巴系统的损伤和功能障碍在与年龄相关的脑功能变化以及神经血管，神经退行性疾病和神经炎性疾病以及脑损伤和肿瘤的发病机理中起着至关重要的作用。在这篇综述中，我们总结了脑淋巴系统的关键组成元素（区域，细胞和水转运蛋白）及其调节剂，将其作为治疗神经系统疾病及其并发症的潜在治疗靶标。最后，