Inhibition of multidrug resistance transporter-1 facilitates neuroprotective therapies after focal cerebral ischaemia

Purpose and methods: The blood-brain barrier possesses transporters on its luminal surface, which carry back xenobiotics into the vasculature against concentration gradients. To define the role of one of them, multidrug resistance transporter (Mdr)-1, which is physiologically expressed in the brain and made responsible for pharmacoresistance in epilepsy, we subjected mice to middle cerebral artery occlusions. Results: In histochemical studies we show that Mdr-1 is upregulated on endothelial cells after ischemia. Following Mdr-1 deactivation by its pharmacological inhibitor, tariquidar, tissue concentrations of t…