Blood-brain barrier impairment by low pH buffer perfusion via the internal carotid artery in rat.

Abstract

Krebs-Ringer bicarbonate buffer (KRB) adjusted by lactic acid to low pH levels (6.6, 6.2, 6.0, 5.8, 5.5) was perfused via the internal carotid artery as a bolus into rat brain hemispheres. In one group of animals, the fluid phase tracer horseradish peroxidase (HRP) was perfused immediately following the low pH treatment. In the other group of animals, the brain hemispheres were fixed and the endothelial cells were stained with colloidal iron (CI) at pH 1.8. Widespread extravasation of HRP was detected indicating blood-brain barrier (BBB) opening to this tracer in hemispheres perfused with KRB at pH 6.2, 6.0, 5.8, or 5.5. HRP was seen in pools of endothelial tight junctions. Endothelial cell injury reflected by swelling and influx of HRP into the cytoplasm was occasionally encountered. CI evenly decorated the negatively charged surface of endothelial cells in the control brains, in contrast to markedly diminished iron binding capacity of endothelial cells in low pH-treated hemispheres. Our results suggest that the ionic milieu influences the negatively charged cell surface sialoglycoproteins and glycolipids, which are integral parts of the BBB system.