Na+-K+-Cl- cotransporter in rat focal cerebral ischemia

In cultured neurons, the authors previously demonstrated that the Na+-K+-Cl - cotransporter is significantly stimulated by elevated extracellular potas sium and glutamate, which are important factors in cerebral ischemic damage . These findings led the authors to hypothesize that stimulation of the cot ransporter after ischemia might result in Na+, K+, and Cl- influx, and migh t contribute to neuron damage. In the current study, the authors investigat ed such a role of the Na+-K+-Cl- cotransporter in focal cerebral ischemia. Cerebral ischemia was induced by 2-hour occlusion of the left middle cerebr al artery (MCA) and 24-hour reperfusion in male spontaneously hypertensive rats (SHRs). Immunocytochemical staining and immunoblotting revealed an up- regulation of expression of the cotransporter protein in neurons in cortex at 24 hours of reperfusion. Artificial cerebral spinal fluid (aCSF) or 100 mu mol/L bumetanide (a cotransporter inhibitor) in aCSF were continuously m icrodialyzed through a microdialysis probe into left cortices throughout 2- hour MCA occlusion and 24-hour reperfusion. Compared with the aCSF-treated group, infarction volume was significantly reduced in the bumetanide-treate d group (25%, P < 0.05). In addition, brain water content in the bumetanide -treated brains was decreased by 70% (P < 0.05). These results strongly sug gest that the Na+-K+-Cl- cotransporter may play an important role in cerebr al ischemic neuronal damage.