Lymphatic Drainage of the Brain and Clinical Implications of the Protein Elimination Failure Arteriopathies

作者：Yildirim Can Hakan; Kaya Miktat; Tasdemiroglu Erol; Akbasak Aytac^*

来源：Neurosurgery Quarterly, 2013, 23(4): 278-285.

DOI：10.1097/WNQ.0b013e318281818a

• central nervous system (CNS)
• cerebral amyloid angiopathy (CAA)
• interstitial fluid (ISF)
• lymphatic drainage
• Alzheimer disease (AD)

In most organs of the body, lymphatic drainage involves the drainage of solutes, antigens, antigen-presenting cells, and tissue debris along the defined lymphatic channels to the regional lymph nodes. The central nervous system is considered to be an immunologically privileged organ without conventional lymphatic system and lymphatic drainage. Although there are no conventional lymphatic pathways in the brain, physiological studies revealed a substantial and immunologically significant lymphatic drainage from the brain to the cervical lymph nodes in humans. Besides, cerebrospinal fluid drains through the cribriform plate and nasal mucosa to cervical lymph nodes in humans. Lymphatic drainage of the interstitial fluid and solutes from the brain parenchyma is carried out along the walls of capillaries and cerebral arteries. None of the antigen-presenting cells and lymphocytes drains to cervical lymph nodes by the perivascular route, and this may be a factor in immunologic privilege of the brain. Disturbance of perivascular drainage of fluids and solutes (abnormal/garbage proteins) from the brain parenchyma is called protein elimination failure arteriopathies. These protein deposits are associated with the pathophysiology of these diseases and include cerebral amyloid angiopathy, Alzheimer diseases, Cruzfeld-Jacobs diseases, Parkinson disease, chronic traumatic encephalomyopathy, frontotemporal dementia, sporadic amyotrophic lateral sclerosis, other TDP-43 proteinopathies, etc. According to our opinion, protein elimination failure arteriopathy is a disease characterized by the failure of elimination of toxic, degenerated, possibly used, garbage (abnormal) proteins, from the extracellular milieu. This new idea on how abnormally folded versions of these proteins may be toxic and could lead to disease yields insights into the disease pathogenesis and may also provide some new therapeutic insights. In this review, we survey the evidence for the flow of brain interstitial fluid through the preferential pathways through the brain, its relation to cerebrospinal fluid, and the results of the blockage of lymphatic drainage from the brain parenchyma.

• 出版日期2013-11