Nature Neuroscience 9, 487 - 488 (2006)
Published online: 26 March 2006; Corrected online: 10 April 2006 | doi:10.1038/nn1676
Inhibition of multidrug resistance transporter-1 facilitates neuroprotective therapies after focal cerebral ischemiaAnnett Spudich1, Ertugrul Kilic1, Hongyi Xing1, Ülkan Kilic1, Katharina M Rentsch2, Heidi Wunderli-Allenspach3, Claudio L Bassetti1
& Dirk M Hermann11
Department of Neurology, University Hospital Zurich, Frauenklinikstr. 26, CH-8091 Zurich, Switzerland. 2
Department of Clinical Chemistry, University Hospital Zurich, Rämistr. 100, CH-8091 Zurich, Switzerland. 3
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Wolfgang-Pauli-Str. 10, CH-8093 Zurich, Switzerland.
Correspondence should be addressed to Dirk M Hermann dirk.hermann@usz.ch The blood-brain barrier possesses active transporters carrying brain-permeable xenobiotics back into the blood against concentration gradients. We demonstrate that multidrug resistance transporter (Mdr)-1 is upregulated on capillary endothelium after focal cerebral ischemia; moreover, Mdr-1 deactivation by pharmacological inhibition or genetic knockout preferably enhances the accumulation and efficacy of two neuroprotectants known as Mdr-1 substrates in the ischemic brain. We predict that Mdr-1 inhibition may greatly facilitate neuroprotective therapies.
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