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“In this study we tested the hypothesis that dantrolene, an established inhibitor of the skeletal

muscle isoform of the ryanodine receptor, may interfere with activity of NMDA receptors in neurons. We assessed the effects of dantrolene on [H-3]MK-801 and [H-3]glycine binding to isolated rat cortical membranes. Dantrolene inhibited [H-3]MK-801 binding in the presence of 100 mu M NMDA with an IC50 of 58.4 mu M. The IC50 Value increased to 99.6, 343.0 and 364.6 mu M in the presence of 10, 30 and 50 mu M glycine, respectively, suggesting that dantrolene competes with glycine for binding site at the NMDA receptor complex. A binding assay using Foretinib in vivo [3H]glycine confirmed this supposition: dantrolene inhibited strychnine-insensitive glycine binding in a dose-dependent way. Thus, our results selleck chemicals show that dantrolene at concentrations of 50-100 mu M and higher blocks the glycine binding site of the NMDA receptor complex and in this way inhibits activation of the NMDA ion channel. These data reveal a new mechanism of dantrolene action in neuronal tissue. Our results also suggest that the neuroprotective effect of dantrolene may be at least partly explained by

its activity as a non-competitive antagonist of NMDA receptors. (c) 2007 Elsevier Ireland Ltd. All rights reserved.”
“Rous sarcoma virus (RSV) can be used for the simple generation of high-titer replication-competent retroviral (RCR) vectors. Retroviruses undergo frequent genomic recombination, however, and vectors with reduced replication kinetics are rapidly overgrown by mutant forms. Vector design is hence critical to vector efficacy. Bcl-w In this study, two different designs of RSV-based RCR vectors were evaluated. Vectors in which transgene expression was facilitated by the v-src splice acceptor were revealed to have greatly reduced replication kinetics and genomic stability in comparison to vectors

in which transgene expression was mediated by an internal ribosome entry site in the 3′ untranslated region.”
“The mouse model of transcranial permanent occlusion of the middle cerebral artery (tpMCAO) is widely used in stroke research. Here we quantified infarct size using a conventional histological method at several post-ischaemic times, going beyond the commonly analysed period of up to 2 days, following artery occlusion. Two different mouse strains, which are widely used for pharmacological studies of neuroprotection and for genetic engineering, were used. A drill whole was made into the skull of anaesthetised mice and ischaemia was induced by electrocoagulation of the middle cerebral artery. In both mouse strains tested (C57Black/6 and NMRI), the measured infarct volumes decreased significantly during the first days after tpMCAO.