Protective role of early aquaporin 4 induction against postischemic edema formation.
Aquaporin 4 (AQP4) is a water channel involved in water movements across the cell membrane and is spatially organized on the cell surface in orthogonal array particles (OAPs). Its role in edema formation or resolution after stroke onset has been studied mainly at late time points. We have shown recently that its expression is rapidly induced after ischemia coinciding in time with an early swelling of the ischemic hemisphere. There are two isoforms of AQP4: AQP4-M1 and AQP4-M23. The ratio of these isoforms influences the size of the OAPs but the functional impact is not known. The role of the early induction of AQP4 is not yet known. Thrombin preconditioning in mice provides a useful model to study endogenous protective mechanisms. Using this model, we provide evidence for the first time that the early induction of AQP4 may contribute to limit the formation of edema and that the AQP4-M1 isoform is predominantly induced in the ischemic tissue at this time point. Although it prevents edema formation, the early induction of the AQP4 expression does not prevent the blood-brain barrier disruption, suggesting an effect limited to the prevention of edema formation possibly by removing of water from the tissue.
Hirt
Lorenz
L
Neurology Department, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Ternon
Béatrice
B
Price
Melanie
M
Mastour
Nabil
N
Brunet
Jean-François
JF
Badaut
Jérôme
J
D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001812:Blood-Brain Barrier; D002545:Brain Ischemia / Q000378:metabolism*; D004195:Disease Models, Animal; D004487:Edema / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020521:Stroke / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D051401:Aquaporin 4; D020033:Protein Isoforms; D013917:Thrombin