Progress in diagnosis of and therapy for idiopathic normal-pressure hydrocephalus--Lymphatic drainage of CSF and ISF from the brain: recent concept and hypothesis

Abstract

Cerebrospinal fluid (CSF) drains via the cribriform plate and nasal mucosa to cervical lymph nodes. 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. Interstitial fluid (ISF) and solutes from brain parenchyma drain along capillary and perivascular space of artery, and path through the skull base, then reach to the cervical lymph nodes. CSF and ISF appear to drain by separate routes from the brain, especially in humans. However, there are interrelationships between the two fluid compartments that become more significant when drainage of CSF or ISF is impaired by disease processes. Vessel pulsations appear to be the driving force for the perivascular lymphatic drainage along artery walls, and as vessels stiffen with age, amyloid peptides (Aβ) 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. Such failure of perivascular drainage may associated with the pathoetiology of Alzheimer's disease, cerebral small artery disease and idiopathic normal pressure hydrocephalus (iNPH).