The dichotomy of memantine treatment for ischemic stroke: dose-dependent protective and detrimental effects.

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, 1

SUBMITTER: Trotman M 

PROVIDER: S-EPMC4426739 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature