Virchow-Robin space and aquaporin-4: new insights on an old friend

摘要

Recent studies have strongly indicated that the classic circulationmodel of cerebrospinal fluid (CSF) is no longervalid. The production of CSF is not only dependent onthe choroid plexus but also on water flux in the peri-capillary(Virchow Robin) space. Historically, CSF flow throughthe Virchow Robin space is known as interstitial flow, thephysiological significance of which is now fully understood.This article briefly reviews the modern concept ofCSF physiology and the Virchow-Robin space, in particularits functionalities critical for central nervous system neuralactivities. Water influx into the Virchow Robin spaceand, hence, interstitial flow is regulated by aquaporin-4(AQP-4) localized in the endfeet of astrocytes, connectingthe intracellular cytosolic fluid space of astrocytes and theVirchow Robin space. Interstitial flow has a functionalityequivalent to systemic lymphatics, on which clearance ofβ-amyloid is strongly dependent. Autoregulation of brainblood flow serves to maintain a constant inner capillaryfluid pressure, allowing fluid pressure of the Virchow Robinspace to regulate regional cerebral blood flow (rCBF)based on AQP-4 gating. Excess heat produced by neuralactivities is effectively removed from the area of activationby increased rCBF by closing AQP-4 channels. This neuralflow coupling (NFC) is likely mediated by heat generatedproton channels.