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Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity

Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity


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VOLBRACHT, Christiane, Johan van BEEK, Changlian ZHU, Klas BLOMGREN, Marcel LEIST, 2006. Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity. In: European Journal of Neuroscience. 23(9), pp. 2611-2622. ISSN 0953-816X. eISSN 1460-9568

@article{Volbracht2006Neuro-8114, title={Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity}, year={2006}, doi={10.1111/j.1460-9568.2006.04787.x}, number={9}, volume={23}, issn={0953-816X}, journal={European Journal of Neuroscience}, pages={2611--2622}, author={Volbracht, Christiane and Beek, Johan van and Zhu, Changlian and Blomgren, Klas and Leist, Marcel} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/8114"> <dc:format>application/pdf</dc:format> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:40:43Z</dcterms:available> <dc:creator>Leist, Marcel</dc:creator> <dcterms:title>Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity</dcterms:title> <dc:contributor>Volbracht, Christiane</dc:contributor> <dc:contributor>Beek, Johan van</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:40:43Z</dc:date> <dc:contributor>Leist, Marcel</dc:contributor> <dcterms:abstract xml:lang="eng">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-methyl-d-asparate receptor (NMDA-R). Attempts to use potent competitive NMDA-R antagonists as neuroprotectants have shown serious side-effects in patients. As an alternative approach, we were interested in the anti-excitotoxic properties of memantine, a well-tolerated low affinity uncompetitive NMDA-R antagonist presently used as an anti-dementia agent. We explored in a series of models of increasing complexity, whether this voltagedependent channel blocker had neuroprotective properties at clinically relevant concentrations. As expected, memantine protected neurons in organotypic hippocampal slices or dissociated cultures from direct NMDA-induced 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-methyl-4- phenylpyridinium (MPP+) or a nitric oxide (NO) donor. Furthermore, memantine reduced lethality and brain damage in vivo in a model of neonatal hypoxia ischemia (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-nitropropionic acid (3-NP). Potent NMDA-R antagonists, such as (+)MK-801, 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-R by memantine is sufficient to block excitotoxicity, while still allowing some degree of signalling.</dcterms:abstract> <dc:creator>Blomgren, Klas</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/8114"/> <dc:creator>Zhu, Changlian</dc:creator> <dcterms:issued>2006</dcterms:issued> <dc:language>eng</dc:language> <dcterms:bibliographicCitation>First publ. in: European Journal of Neuroscience 23 (2006), 9, pp. 2611-2622</dcterms:bibliographicCitation> <dc:creator>Volbracht, Christiane</dc:creator> <dc:contributor>Blomgren, Klas</dc:contributor> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103416863-3868037-7"/> <dc:creator>Beek, Johan van</dc:creator> <dc:contributor>Zhu, Changlian</dc:contributor> <dc:rights>deposit-license</dc:rights> </rdf:Description> </rdf:RDF>

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