Modulation of aquaporin-4 water transport in a model of TBI.
Our Laboratory has pursued the hypothesis that traumatic brain edema is predominantly cellular and recent supportive evidence has been obtained indicating a non-extracellular route for sodium and water entering brain. The aim of this study was to investigate if astrocytic endfeet are involved in this passage, using a potent activator of Protein Kinase C (phorbol ester) to modify and closing the Aquaporin 4 (AQP4), a water channel specific for astrocytic endfoot. Anaesthetized Sprague-Dawley rats were subjected to an intracerebroventricular bolus of phorbol ester (50 pmol/4 microl) or vehicle, in the right hemisphere and after 30 minutes they were exposed to the well-established conical contusion model (3 mm depth at 6 m/sec) on the same side. After trauma, they were subjected to 5 hours of drug continuous infusion, then sacrificed. Water content measurements for both right (injured) and left (uninjured) hemispheres were calculated using the wet weight/dry weight technique. Results of these experiments showed a significant decrease in water content in injured phorbol treated animals, underlying that AQP4 regulation plays an important role in brain edema following stroke, and supporting the concept of cellular formation for edema via astrocytic foot processes.
Amorini
A M
AM
Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0508, USA.
Dunbar
J G
JG
Marmarou
A
A
D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins / Q000378:metabolism*; D001692:Biological Transport; D001834:Body Water / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D004789:Enzyme Activation; D007276:Injections, Intraventricular; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology
C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate