Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice

Didrik S. Frydenlund, Anish Bhardwaj, Takashi Otsuka, Maria N. Mylonakou, Thomas Yasumura, Kimberly G.V. Davidson, Emil Zeynalov, Øivind Skare, Petter Laake, Finn Mogens Haug, John E. Rash, Peter Agre, Ole P. Ottersen, Mahmood Amiry-Moghaddam

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

The aquaporin-4 (AQP4) pool in the perivascular astrocyte membranes has been shown to be critically involved in the formation and dissolution of brain edema. Cerebral edema is a major cause of morbidity and mortality in stroke. It is therefore essential to know whether the perivascular pool of AQP4 is up- or down-regulated after an ischemic insult, because such changes would determine the time course of edema formation. Here we demonstrate by quantitative immunogold cytochemistry that the ischemic striatum and neocortex show distinct patterns of AQP4 expression in the reperfusion phase after 90 min of middle cerebral artery occlusion. The striatal core displays a loss of perivascular AQP4 at 24 hr of reperfusion with no sign of subsequent recovery. The most affected part of the cortex also exhibits loss of perivascular AQP4. This loss is of magnitude similar to that of the striatal core, but it shows a partial recovery toward 72 hr of reperfusion. By freeze fracture we show that the loss of perivascular AQP4 is associated with the disappearance of the square lattices of particles that normally are distinct features of the perivascular astrocyte membrane. The cortical border zone differs from the central part of the ischemic lesion by showing no loss of perivascular AQP4 at 24 hr of reperfusion but rather a slight increase. These data indicate that the size of the AQP4 pool that controls the exchange of fluid between brain and blood during edema formation and dissolution is subject to large and region-specific changes in the reperfusion phase.

Original languageEnglish (US)
Pages (from-to)13532-13536
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number36
DOIs
StatePublished - Sep 5 2006
Externally publishedYes

Keywords

  • Astrocytes
  • Brain edema
  • Ischemia
  • Stroke
  • Water channels

ASJC Scopus subject areas

  • General

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    Frydenlund, D. S., Bhardwaj, A., Otsuka, T., Mylonakou, M. N., Yasumura, T., Davidson, K. G. V., Zeynalov, E., Skare, Ø., Laake, P., Haug, F. M., Rash, J. E., Agre, P., Ottersen, O. P., & Amiry-Moghaddam, M. (2006). Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice. Proceedings of the National Academy of Sciences of the United States of America, 103(36), 13532-13536. https://doi.org/10.1073/pnas.0605796103