Aquaporin-4 functionality and virchow-robin space water dynamics: Physiological model for neurovascular coupling and glymphatic flow

Tsutomu Nakada, Ingrid Kwee, Hironaka Igarashi, Yuji Suzuki

Research output: Contribution to journalReview article

15 Scopus citations


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.

Original languageEnglish (US)
Article number1798
JournalInternational Journal of Molecular Sciences
Issue number8
StatePublished - Aug 18 2017



  • Glia limitans externa
  • Hagen-Poiseuille equation
  • Interstitial flow
  • RCBF
  • Starling resister

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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