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Title: The dichotomy of memantine treatment for ischemic stroke: dose-dependent protective and detrimental effects
Authors: Trotman, Melissa
Vermehren, Philipp
Gibson, Claire L.
Fern, Robert
First Published: 19-Nov-2014
Publisher: Nature Publishing Group for International Society for Cerebral Blood Flow and Metabolism
Citation: Journal of Cerebral Blood Flow and Metabolism, 2015, 35 (2), pp. 230-239
Abstract: Excitotoxicity is a major contributor to cell death during the acute phase of ischemic stroke but aggressive pharmacological targeting of excitotoxicity has failed clinically. Here we investigated whether pretreatment with low doses of memantine, within the range currently used and well tolerated for the treatment of Alzheimer's disease, produce a protective effect in stroke. A coculture preparation exposed to modeled ischemia showed cell death associated with rapid glutamate rises and cytotoxic Ca(2+) influx. Cell death was significantly enhanced in the presence of high memantine concentrations. However, low memantine concentrations significantly protected neurons and glia via excitotoxic cascade interruption. Mice were systemically administered a range of memantine doses (0.02, 0.2, 2, 10, and 20 mg/kg/day) starting 24 hours before 60 minutes reversible focal cerebral ischemia and continuing for a 48-hour recovery period. Low dose (0.2 mg/kg/day) memantine treatment significantly reduced lesion volume (by 30% to 50%) and improved behavioral outcomes in stroke lesions that had been separated into either small/striatal or large/striatocortical infarcts. However, higher doses of memantine (20 mg/kg/day) significantly increased injury. These results show that clinically established low doses of memantine should be considered for patients 'at risk' of stroke, while higher doses are contraindicated.
DOI Link: 10.1038/jcbfm.2014.188
ISSN: 0271-678X
eISSN: 1559-7016
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2015. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit
Appears in Collections:Published Articles, School of Psychology

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