title: Memantine enhances recovery from stroke.
abstract: OBJECTIVE
  Stroke 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.
  
  
  METHODS
  Memantine, 30 mg/kg per day, or vehicle, was delivered chronically in drinking water beginning >2 hours after photothrombotic stroke.
  
  
  RESULTS
  Although 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Neurology, David Geffen School of Medicine at UCLA.
authors.forename: Héctor E
authors.initials: HE
authors.lastname: López-Valdés
authors.affiliation: Neurology, David Geffen School of Medicine at UCLA.|Anatomy and Psychology, University of Otago.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Clarkson
authors.affiliation: Neurobiology, David Geffen School of Medicine at UCLA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ao
authors.affiliation: Neurology, David Geffen School of Medicine at UCLA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Charles
authors.affiliation: Neurology, David Geffen School of Medicine at UCLA.
authors.forename: S Thomas
authors.initials: ST
authors.lastname: Carmichael
authors.affiliation: Neurobiology, David Geffen School of Medicine at UCLA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sofroniew
authors.affiliation: Neurology, David Geffen School of Medicine at UCLA.|Neurology, University of Utah School of Medicine.
authors.forename: K C
authors.initials: KC
authors.lastname: Brennan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008559:Memantine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D020127:Recovery of Function / Q000187:drug effects*; D016037:Single-Blind Method; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008559:Memantine
keywords: brain-derived neurotrophic factor; memantine