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Chunk #19 — Perivascular Drainage

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New therapeutic approaches for Alzheimer's disease and cerebral amyloid angiopathy.
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Fluorescent tracers, injected to the striatum, spread diffusely through the extracellular spaces of the brain parenchyma and enter the walls of blood vessels almost immediately. Confocal microscopy showed tracers colocalize with laminin in the basement membranes of capillary walls. Injected tracers were cleared from the basement membranes in the walls of capillaries and arteries, while some tracers were taken up by smooth muscle cells and perivascular macrophages (Zhang et al., 1992; Carare et al., 2008). Studies using radiolabeled tracers showed that drainage of interstitial fluid (ISF) and solutes continues along tunica media and the tunica adventitia of leptomeningeal and major cerebral arteries, through the base of the skull to the deep cervical lymph nodes (Szentistványi et al., 1984; Weller et al., 2010). Tissue soluble Aβ was detected by enzyme immunoassay in meningeal arteries and intracranial arteries but not in extracranial vessels (Shinkai et al., 1995). The clearance system leading to cervical lymph nodes was confirmed by subsequent injection into the inferior colliculus (Ball et al., 2010). Theoretical models have indicated that arterial pulsations could be the motive force behind ISF