• Héctor E López-Valdés, Andrew N Clarkson, Yan Ao, Andrew C Charles, Stanley Thomas Carmichael, Michael V Sofroniew, and Kevin C Brennan.
• From the Departments of Neurology (H.E.L.-V., A.N.C., A.C.C., S.T.C., K.C.B.) and Neurobiology (Y.A., M.V.S.), David Geffen School of Medicine at UCLA; Department of Anatomy and Psychology, University of Otago, Dunedin, New Zealand (A.N.C.); and Department of Neurology, University of Utah School of Medicine, Salt Lake City (K.C.B.).
• Stroke. 2014 Jul 1; 45 (7): 2093-100.

Background And PurposeStroke treatment is constrained by limited treatment windows and the clinical inefficacy of agents that showed preclinical promise. Yet animal and clinical data suggest considerable poststroke plasticity, which could allow treatment with recovery-modulating agents. Memantine is a well-tolerated N-methyl-D-aspartate glutamate receptor antagonist in common use for Alzheimer disease.MethodsMemantine, 30 mg/kg per day, or vehicle, was delivered chronically in drinking water beginning >2 hours after photothrombotic stroke.ResultsAlthough there was no difference in infarct size, behavior, or optical intrinsic signal maps in the first 7 days after stroke, mice treated chronically with memantine showed significant improvements in motor control, measured by cylinder test and grid-walking performance, compared with vehicle-treated animals. Optical intrinsic signal revealed an increased area of forepaw sensory maps at 28 days after stroke. There was decreased reactive astrogliosis and increased vascular density around the infarcted cortex. Peri-infarct Western blots revealed increased brain-derived neurotrophic factor and phosphorylated-tropomyosin-related kinase-B receptor expression.ConclusionsOur results suggest that memantine improves stroke outcomes in an apparently non-neuroprotective manner involving increased brain-derived neurotrophic factor signaling, reduced reactive astrogliosis, and improved vascularization, associated with improved recovery of sensory and motor cortical function. The clinical availability and tolerability of memantine make it an attractive candidate for clinical translation.© 2014 American Heart Association, Inc.

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