Fluid and ion transfer across the blood–brain and blood–cerebrospinal fluid barriers; a comparative account of mechanisms and roles

Abstract

The two major interfaces separating brain and blood have different primary roles. The choroid plexuses secrete cerebrospinal fluid into the ventricles, accounting for most net fluid entry to the brain. Aquaporin, AQP1, allows water transfer across the apical surface of the choroid epithelium; another protein, perhaps GLUT1, is important on the basolateral surface. Fluid secretion is driven by apical Na+-pumps. K+ secretion occurs via net paracellular influx through relatively leaky tight junctions partially offset by transcellular efflux. The blood–brain barrier lining brain microvasculature, allows passage of O2, CO2, and glucose as required for brain cell metabolism. Because of high resistance tight junctions between microvascular endothelial cells transport of most polar solutes is greatly restricted. Because solute permeability is low, hydrostatic pressure differences cannot account for net fluid movement; however, water permeability is sufficient for fluid secretion with water following net solute transport. The endothelial cells have ion transporters that, if appropriately arranged, could support fluid secretion. Evidence favours a rate smaller than, but not much smaller than, that of the choroid plexuses. At the blood–brain barrier Na+ tracer influx into the brain substantially exceeds any possible net flux. The tracer flux may occur primarily by a paracellular route. The blood–brain barrier is the most important interface for maintaining interstitial fluid (ISF) K+ concentration within tight limits. This is most likely because Na+-pumps vary the rate at which K+ is transported out of ISF in response to small changes in K+ concentration. There is also evidence for functional regulation of K+ transporters with chronic changes in plasma concentration. The blood–brain barrier is also important in regulating HCO3 − and pH in ISF: the principles of this regulation are reviewed. Whether the rate of blood–brain barrier HCO3 − transport is slow or fast is discussed critically: a slow transport rate comparable to those of other ions is favoured. In metabolic acidosis and alkalosis variations in HCO3 − concentration and pH are much smaller in ISF than in plasma whereas in respiratory acidosis variations in pHISF and pHplasma are similar. The key similarities and differences of the two interfaces are summarized.

The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future

“…Whereas in peripheral organs ISF is formed as a product of hydrostatic filtration of blood plasma through a fenestrated capillary bed, owing to the presence of tight junctions between adjacent endothelial cells of the BBB (9, 64), the same is not true in the CNS, where ISF is instead actively secreted by the cerebrovascular endothelium (11). The endothelial layer of brain blood vessels is thought to behave analogously to the epithelium of the choroid plexus, and has been noted to have an increased mitochondrial content relative to peripheral endothelial cells to energetically support this secretory function (65).…”

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

“…The evidence for origin of ISF as a secretion across the brain capillary endothelium is well established; in vivo studies show good regulation of brain ions in the face of large changes in plasma concentration, and the necessary ion channels and transporters are expressed at the BBB [1,151]. Careful studies in primary cultured brain endothelial cells have provided a complex map of ion transporters and channels on apical and basal membranes, and the ways in which they could generate the required fluid flow [78]. As the flow rate per unit area is low compared with choroid plexus secretion of CSF, it is not possible to demonstrate fluid production from segments of isolated brain capillary, but the net result is to supply local regions of the neuropil with fresh fluid of optimal composition for neural function.…”

Acid–base physiology, neurobiology and behaviour in relation to CO2-induced ocean acidification

“…Can this process result in changes in [Cl − ] and in the CSF consistent with the GABA A R model? This question can only be answered by performing experiments to elucidate fish CSF and BIF composition and regulatory mechanisms, which should consider the following points: (1) the high P CO2 and low pH in the CSF imply that OA-relevant P CO2 elevations will induce smaller A-B disturbances in CSF compared with blood plasma; (2) in mammals, HCO 3 − secretion into the CSF and BIF takes place by both Cl − -and Na + -dependent mechanisms (Damkier et al, 2013;Hladky and Barrand, 2016) …”