PATHOLOGY OF CEREBROSPINAL-FLUID AND INTERSTITIAL FLUID OF THE CNS - SIGNIFICANCE FOR ALZHEIMER-DISEASE, PRION DISORDERS AND MULTIPLE-SCLEROSIS

Extracellular fluid in the central nervous system (CNS) is composed of cerebrospinal fluid (CSF), derived from the choroid plexus, and of in terstitial fluid (ISF) in gray and white matter. Investigation of CSF plays a significant role in diagnosis and management of neurological d isease and pathologies involving the CSF have important effects on the CNS itself. Hydrocephalus has many causes; clinical effects are due t o a mixture of obstruction to CSF flow and damage to periventricular w hite matter with CSF edema, axonal loss and gliosis. Meningitis and su barachnoid hemorrhage are mainly confined to the subarachnoid space em phasising how this compartment is separated from the CNS by the pia ma ter and glia limitans; brain damage results from thrombosis of leptome ningeal vessels and infarction of CNS tissue. ISF from white matter ap pears to drain mainly to CSE but ISF from gray matter drains along per iarterial pathways in CNS and meninges, to lymph nodes in experimental animals, and probably in humans. beta-amyloid in Alzheimer disease an d prion proteins accumulate in the extracellular spaces of gray matter and in periarterial ISF drainage pathways as cerebral amyloid angiopa thy, emphasising the role of periarterial drainage for the elimination of high molecular weight substances from the brain, possibly to regio nal lymph nodes. Lymphatic drainage of ISF drainage plays a major role in B- and T-lymphocyte mediated immune reactions in the CNS in animal s. By analogy with experimental autoimmune encephalomyelitis, lymphati c drainage of brain antigens in ISF from the human CNS may play a key role in the pathogenesis of Multiple Sclerosis.