{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:57:16Z","timestamp":1792814236248,"version":"4.5.0"},"reference-count":60,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2006,5,16]],"date-time":"2006-05-16T00:00:00Z","timestamp":1147737600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The pathogenesis of stroke, trauma and chronic degenerative diseases, such as Alzheimer's disease (AD), has been linked to excitotoxic processes due to inappropriate stimulation of the\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methyl\u2010\n                    <jats:sc>d<\/jats:sc>\n                    \u2010asparate receptor (NMDA\u2010R). Attempts to use potent competitive NMDA\u2010R antagonists as neuroprotectants have shown serious side\u2010effects in patients. As an alternative approach, we were interested in the anti\u2010excitotoxic properties of memantine, a well\u2010tolerated low affinity uncompetitive NMDA\u2010R antagonist presently used as an anti\u2010dementia agent. We explored in a series of models of increasing complexity, whether this voltage\u2010dependent channel blocker had neuroprotective properties at clinically relevant concentrations. As expected, memantine protected neurons in organotypic hippocampal slices or dissociated cultures from direct NMDA\u2010induced excitotoxicity. However, low concentrations of memantine were also effective in neuronal (cortical neurons and cerebellar granule cells) stress models dependent on endogenous glutamate stimulation and mitochondrial stress, i.e. exposure to hypoxia, the mitochondrial toxin 1\u2010methyl\u20104\u2010phenylpyridinium (MPP\n                    <jats:sup>+<\/jats:sup>\n                    ) or a nitric oxide (NO) donor. Furthermore, memantine reduced lethality and brain damage\n                    <jats:italic>in vivo<\/jats:italic>\n                    in a model of neonatal hypoxia\u2010ischemia (HI). Finally, we investigated functional rescue (neuronal capacity to migrate along radial glia) by memantine in cerebellar microexplant cultures exposed to the indirect excitotoxin 3\u2010nitropropionic acid (3\u2010NP). Potent NMDA\u2010R antagonists, such as (+)MK\u2010801, are known to block neuronal migration in microexplant cultures. Interestingly, memantine significantly restored the number of neurons able to migrate out of the stressed microexplants. These findings suggest that inhibition of the NMDA\u2010R by memantine is sufficient to block excitotoxicity, while still allowing some degree of signalling.\n                  <\/jats:p>","DOI":"10.1111\/j.1460-9568.2006.04787.x","type":"journal-article","created":{"date-parts":[[2006,5,16]],"date-time":"2006-05-16T09:02:18Z","timestamp":1147770138000},"page":"2611-2622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":146,"title":["Neuroprotective properties of memantine in different\n                    <i>in vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    models of excitotoxicity"],"prefix":"10.1111","volume":"23","author":[{"given":"Christiane","family":"Volbracht","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Van 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