6533b7cffe1ef96bd1258ec2

RESEARCH PRODUCT

Endothelial Cell Swelling and Brain Perfusion

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Background: Whereas the contribution of glial swelling to no-reflow conditions in the ischemic penumbra or during reperfusion after global ischemia is widely discussed, little is known about cell volume control of endothelial cells under reperfusion conditions. Methods: The effect of extracellular acidosis-a key mediator of secondary brain damage-on cell volume was studied in the GM7373 endothelial cell line. Experiments were performed at pH = 6.0 in the presence or absence of bicarbonate, and during exposure to inhibitors of specific transport systems such as ethyl isopropyl amiloride or 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. Results: Endothelial swelling to 111.1 ± 3.4% was found at pH e = 6.0 in bicarbonate-buffered media. In hydroxyethyl piperin ethanesulfonic acid-buffered media, swelling was only 107.9 ± 0.3%. 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid reduced swelling to 102.8 ± 0.6% in bicarbonate media, whereas swelling was completely prevented in the presence of ethyl isopropyl amiloride in hydroxyethyl piperin ethanesulfonic acid-buffered media. Conclusions: Endothelial swelling can be expected to occur in severely ischemic tissue sections and may then advance noreflow. Therapeutic strategies should be established to prevent acidosis-induced endothelial swelling, e.g., by specific antagonists of the transport systems involved, or to reduce swelling by osmotic treatment such as hypertonic-hyperoncotic solutions.