Abstract
The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics.
Highlights
Blood-Brain BarrierThe blood-brain barrier (BBB) is the result of unique properties of brain capillary endothelium, namely the presence of tight junctions and active suppression of aquaporin-1 (AQP-1) expression, the water channel abundantly expressed in common capillaries and choroid plexus epithelium [1,2,3,4]
Water permeability through the BBB is highly restricted through suppression of expression of AQP-1 and the presence of tight junctions
Brain water dynamics is effectively isolated from the systemic circulation, and AQP-4, a water channel abundantly expressed at the endfeet of astrocytes, plays a critical role in the water dynamics inside the BBB
Summary
The blood-brain barrier (BBB) is the result of unique properties of brain capillary endothelium, namely the presence of tight junctions and active suppression of aquaporin-1 (AQP-1) expression, the water channel abundantly expressed in common capillaries and choroid plexus epithelium [1,2,3,4]. While some accessory proteins specific to brain endothelium, such as cingulin, AF-6 and 7H6, have been identified, other epithelial tight junction proteins have far not been detected. Ibnyctohnetaraustto,ncoampiilclanreiervsolaucsksycostnetmra.cAtilltehsoturugchtucorenstraanctdil,ethfuenrecftoiorne,ocfappeilrliacryytebslaonodd iftlsonweucarontnraont sbme idttierrecctolnytrcoolnhtraoslbleedenbpyrtohpeoaseudto[n11o]m, ciocnnseidrveoriunsgsiytsstceomm.mAolnth, owuigdhe scpornetardacftuilnecftuionncatliiotyn roeflapteerdictyoteasnagniodgietns enseisuraontdrasntsemmitcteelrl clioknetrboelhhaavsiobre[e1n2]p,riot pisodseifdfic[1u1l]t,tcooancscidepertitnhgatitpsecroicmymteosna,rewtihdee psprirmeaadryfustnrcutciotunraaliltycormelpaotendentot faonrgflioogwenreesgiuslaantidons.teImt isc,etlhl elirkeefobreeh, havigiohrly[1p2l]a,uitsiibsleditfoficcounltstiodearctcheaptt that pericytes are the primary structural component for flow regulation. Sci. 2017, 18, 1798 capillary flow dynamics are a passive phenomenon which are significantly affected by the architectural properties of the capillaries per se
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