Neuroprotective potential of ceftriaxone in in vitro models of stroke

Show simple item record Lipski, Janusz en Wan, Kenny en Bai, Jizhong en 2012-02-26T22:54:56Z en 2012-03-15T01:11:23Z en 2007 en
dc.identifier.citation Neuroscience 146(2):617-629 11 May 2007 en
dc.identifier.issn 0306-4522 en
dc.identifier.uri en
dc.description.abstract Astrocytic glutamate transporters are considered an important target for neuroprotective therapies as the function of these transporters is abnormal in stroke and other neurological disorders associated with excitotoxicity. Recently, Rothstein et al., [Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ, Gupta P, Fisher PB (2005) Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433:73-77] reported that beta-lactam antibiotics (including ceftriaxone, which easily crosses the blood-brain barrier) increase glutamate transporter 1 (GLT-1) expression and reduce cell death resulting from oxygen-glucose deprivation (OGD) in dissociated embryonic cortical cultures. To determine whether a similar neuroprotective mechanism operates in more mature neurons, which show a different pattern of response to ischemia than primary cultures, we exposed acute hippocampal slices obtained from rats treated with ceftriaxone for 5 days (200 mg/kg; i.p.) to OGD. Whole-cell patch clamp recording of glutamate-induced N-methyl-d-aspartate (NMDA) currents from CA1 pyramidal neurons showed a larger potentiation of these currents after application of 15 microM dl-threo-beta-benzyloxyaspartic acid (TBOA; a potent blocker of glutamate transporters) in ceftriaxone-injected animals than in untreated animals, indicating increased glutamate transporter activity. Western blot analysis did not reveal GLT-1 upregulation in the hippocampus. ... Thus we confirm the neuroprotective effect of antibiotic exposure on OGD-induced injury, but suggest that this action is related to independent modulation of transporter activity rather than to the level of GLT-1 protein expression. In addition, our results indicate that the protective effects of beta-lactam antibiotics are highly dependent on the experimental model. en
dc.publisher International Brain Research Organization en
dc.relation.ispartofseries Neuroscience en
dc.relation.replaces en
dc.relation.replaces 2292/12033 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.title Neuroprotective potential of ceftriaxone in in vitro models of stroke en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.neuroscience.2007.02.003 en
pubs.issue 2 en
pubs.begin-page 617 en
pubs.volume 146 en
dc.rights.holder Copyright: International Brain Research Organization en
dc.identifier.pmid 17363173 en
pubs.end-page 629 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 195826 en Medical and Health Sciences en Medical Sciences en Physiology Division en
pubs.record-created-at-source-date 2010-09-01 en
pubs.dimensions-id 17363173 en

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