The basis of the glymphatic circulation proposal: evidence from fluorescence imaging studies Recent studies on perivascular routes for entry into and exit from the cortex Possible alternative routes for CSF outflow from the ventriclesĬaveats on PC-MRI results for net flow through the aqueduct Measurement of CSF flow by phase contrast magnetic resonance imaging (PC-MRI)Ĭommunicating hydrocephalus and the possibility of reverse net flow Studies of CSF flow and the implications of the flow patterns for sites and rates of production and absorption of CSF and ISF Studies of movement of substances and routes of outflow from the brain parenchyma.Įvaluation of the proposal that periarterial spaces provide an efflux route for markersĮxtracellular spaces of the arterial smooth muscle layer as routes of efflux Ongoing approaches to the investigation of brain fluid dynamics Secretion by the choroid plexuses and the blood-brain barrier Uses of tracers or marker substances and lessons from the peripheryĪpplication of basic principles to blood vessels in the brainĭiffusion and convection within the parenchyma Instances and relative importance of diffusion and bulk flow This review provides a critical evaluation of the data.Īnatomical basis of barriers and routes of fluid transferīasic principles of fluid movements in the brain and lessons from studies on peripheral tissues Modern techniques have revealed complex fluid movements within the brain. Whether this represents net fluid flow and whether there is subsequent flow through the interstitium and net flow out of the cortex via perivenous routes, described as glymphatic circulation, remains to be established. Fluorescent tracer analysis has shown that fluid flow can occur from CSF into parenchyma along periarterial spaces. Such reversed flow requires there to be alternative sites for both generation and removal of CSF. ![]() ![]() ![]() Flow rates measured using phase contrast magnetic resonance imaging reveal CSF movements to be more rapid and variable than previously supposed, even implying that under some circumstances net flow through the cerebral aqueduct may be reversed with net flow into the third and lateral ventricles. CSF is thought to be derived primarily from secretion by the choroid plexuses. Any flow due to hydrostatic pressures driving water across the barrier soon ceases unless accompanied by solute transport because water movements modify solute concentrations. Fluid secretion at the blood-brain barrier is provided by specific transporters that generate solute fluxes so creating osmotic gradients that force water to follow. ISF flow, estimated from rates of removal of markers from the brain, has been thought to reflect rates of fluid secretion across the blood-brain barrier, although this has been questioned because measurements were made under barbiturate anaesthesia possibly affecting secretion and flow and because CSF influx to the parenchyma via perivascular routes may deliver fluid independently of blood-brain barrier secretion. Structures associated with this regular fluid turnover include the choroid plexuses, brain capillaries comprising the blood-brain barrier, arachnoid villi and perineural spaces penetrating the cribriform plate. Regulation of the composition and volume of these fluids is important for effective functioning of brain cells and is achieved by barriers that prevent free exchange between CNS and blood and by mechanisms that secrete fluid of controlled composition into the brain and distribute and reabsorb it. Interstitial fluid (ISF) surrounds the parenchymal cells of the brain and spinal cord while cerebrospinal fluid (CSF) fills the larger spaces within and around the CNS.
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