Deletion of aquaporin-4 improves capillary blood flow distribution in brain edema

Luca Bordoni, Anna E. Thoren, Eugenio Gutiérrez-Jiménez, Knut S. Åbjørsbråten, Daniel M. Bjørnstad, Wannan Tang, Mette Stern, Leif Østergaard, Erlend A. Nagelhus, Sebastian Frische, Ole P. Ottersen, Rune Enger*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Brain edema is a feared complication to disorders and insults affecting the brain. It can be fatal if the increase in intracranial pressure is sufficiently large to cause brain herniation. Moreover, accruing evidence suggests that even slight elevations of intracranial pressure have adverse effects, for instance on brain perfusion. The water channel aquaporin-4 (AQP4), densely expressed in perivascular astrocytic endfeet, plays a key role in brain edema formation. Using two-photon microscopy, we have studied AQP4-mediated swelling of astrocytes affects capillary blood flow and intracranial pressure (ICP) in unanesthetized mice using a mild brain edema model. We found improved regulation of capillary blood flow in mice devoid of AQP4, independently of the severity of ICP increase. Furthermore, we found brisk AQP4-dependent astrocytic Ca2+ signals in perivascular endfeet during edema that may play a role in the perturbed capillary blood flow dynamics. The study suggests that astrocytic endfoot swelling and pathological signaling disrupts microvascular flow regulation during brain edema formation.

Original languageEnglish
JournalGlia
Volume71
Issue11
Pages (from-to)2559-2572
Number of pages14
ISSN0894-1491
DOIs
Publication statusPublished - Nov 2023

Keywords

  • astrocyte endfoot
  • brain edema
  • Ca signals
  • capillary blood flow
  • intracranial pressure

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