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Stroke. 2014 Jul;45(7):2093-2100. doi: 10.1161/STROKEAHA.113.004476. Epub 2014 Jun 17.

Memantine enhances recovery from stroke.

Author information

1
Neurology, David Geffen School of Medicine at UCLA.
2
Anatomy and Psychology, University of Otago.
3
Neurobiology, David Geffen School of Medicine at UCLA.
4
Neurology, University of Utah School of Medicine.
#
Contributed equally

Erratum in

  • Stroke. 2014 Nov;45(11):e238.

Abstract

BACKGROUND AND PURPOSE:

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.

KEYWORDS:

brain-derived neurotrophic factor; memantine

PMID:
24938836
PMCID:
PMC4142682
DOI:
10.1161/STROKEAHA.113.004476
[Indexed for MEDLINE]
Free PMC Article

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