Alzheimer's Drug May Enhance Stroke Recovery

Megan Brooks

August 05, 2014

Memantine, used widely for Alzheimer's disease (AD), may aid recovery from stroke in a non-neuroprotective manner, new research suggests.

In a mouse model of ischemic stroke, long-term treatment with memantine in doses similar to those used in humans improved stroke outcome.

"The translational significance of our findings is 2-fold," say Héctor E. López-Valdés, PhD, Department of Neurology, David Geffen School of Medicine at University of California Los Angeles, and colleagues.

"First, it suggests a treatment for stroke recovery that is clinically feasible. Second, it suggests that stroke recovery can be improved without the stringent time-dependency of neuroprotective strategies," they explain.

The study was published online June 17 in Stroke.

Memantine is a well-tolerated N-methyl-D-aspartate antagonist used to treat AD. Prior studies have shown that memantine is neuroprotective, reducing infarct size when given acutely within the first 2 hours of stroke. However, memantine has mechanisms that may be relevant beyond the acute setting, the researchers note.

To investigate, they treated mice with memantine, 30 mg/kg per day, or vehicle, in drinking water beginning more than 2 hours after photothrombotic stroke, a model of ischemic stroke.

Memantine was given in doses designed to mimic usual serum concentrations in people and delivered to avoid neuroprotection and isolate recovery effects, they explain.

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.

Memantine-treated mice also showed increased sensory recovery in the forepaw at 28 days after stroke, as well as decreased reactive astrocytosis, increased vascular density, and increased expression of brain-derived neurotrophic factor, which promotes neuronal survival.

The researchers are "fairly confident" that neuroprotection did not play a significant role in recovery because infarct size did not differ between memantine- and vehicle-treated mice.

"The clinical availability and tolerability of memantine make it an attractive candidate for clinical translation," they conclude.

They note that memantine has recently been used to successfully treat aphasia, further demonstrating its "promise in poststroke populations."

Stroke. 2014;45:2093-2100. Abstract

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