The proteasome inhibitor VELCADE reduces infarction in rat models of focal cerebral ischemia
dc.contributor.author | Henninger, Nils | |
dc.contributor.author | Sicard, Kenneth M. | |
dc.contributor.author | Bouley, James P. | |
dc.contributor.author | Fisher, Marc | |
dc.contributor.author | Stagliano, Nancy E. | |
dc.date | 2022-08-11T08:09:27.000 | |
dc.date.accessioned | 2022-08-23T16:31:22Z | |
dc.date.available | 2022-08-23T16:31:22Z | |
dc.date.issued | 2006-02-23 | |
dc.date.submitted | 2008-04-28 | |
dc.identifier.citation | Neurosci Lett. 2006 May 8;398(3):300-5. Epub 2006 Feb 21. <a href="http://dx.doi.org/10.1016/j.neulet.2006.01.015">Link to article on publisher's site</a> | |
dc.identifier.issn | 0304-3940 (Print) | |
dc.identifier.doi | 10.1016/j.neulet.2006.01.015 | |
dc.identifier.pmid | 16490315 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/37626 | |
dc.description.abstract | The potential neuroprotective effects of VELCADE were investigated in two different models of focal cerebral ischemia. For time-window assessment, male Wistar-Kyoto rats were treated with 0.2 mg/kg VELCADE at 1, 2, or 3 h after the induction of permanent middle cerebral artery occlusion (MCAO) using the suture occlusion method (experiment 1). To evaluate effects in a different model, male Sprague-Dawley rats received 0.2 mg/kg VELCADE after embolic MCAO (experiment 2). Infarct volume was calculated based on TTC-staining 24 h postischemia and whole blood proteasome activity was fluorometrically determined in both experiments at baseline, 1 and 24 h post-MCAO. In experiment 1, a dose of 0.2 mg/kg inhibited proteasome activity by 77% and infarct volume was reduced to 175.7+/-59.9 mm3 and 205.9+/-83.9 mm3 (1 and 2 h group, respectively; p<0.05) compared to 306.5+/-48.5 mm3 (control). Treatment at 3 h was not neuroprotective (293.0+/-40.1 mm3). After embolic MCAO, infarct volume was 167.5+/-90.7 mm3 (treatment group) and 398.9+/-141.3 mm3 (control; p=0.002). In conclusion, VELCADE treatment inhibited whole blood proteasome activity and achieved significant neuroprotection in two rat models of focal cerebral ischemia at various time points poststroke. | |
dc.language.iso | en_US | |
dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16490315&dopt=Abstract ">Link to article in PubMed</a> | |
dc.relation.url | http://dx.doi.org/10.1016/j.neulet.2006.01.015 | |
dc.subject | Animals | |
dc.subject | Boronic Acids | |
dc.subject | Brain Infarction | |
dc.subject | Brain Ischemia | |
dc.subject | Disease Models, Animal | |
dc.subject | Infarction, Middle Cerebral Artery | |
dc.subject | Intracranial Embolism | |
dc.subject | Male | |
dc.subject | Neuroprotective Agents | |
dc.subject | Proteasome Endopeptidase Complex | |
dc.subject | Pyrazines | |
dc.subject | Rats | |
dc.subject | Rats, Inbred WKY | |
dc.subject | Rats, Sprague-Dawley | |
dc.subject | Neurology | |
dc.subject | Neuroscience and Neurobiology | |
dc.title | The proteasome inhibitor VELCADE reduces infarction in rat models of focal cerebral ischemia | |
dc.type | Journal Article | |
dc.source.journaltitle | Neuroscience letters | |
dc.source.volume | 398 | |
dc.source.issue | 3 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/neuro_pp/169 | |
dc.identifier.contextkey | 499351 | |
html.description.abstract | <p>The potential neuroprotective effects of VELCADE were investigated in two different models of focal cerebral ischemia. For time-window assessment, male Wistar-Kyoto rats were treated with 0.2 mg/kg VELCADE at 1, 2, or 3 h after the induction of permanent middle cerebral artery occlusion (MCAO) using the suture occlusion method (experiment 1). To evaluate effects in a different model, male Sprague-Dawley rats received 0.2 mg/kg VELCADE after embolic MCAO (experiment 2). Infarct volume was calculated based on TTC-staining 24 h postischemia and whole blood proteasome activity was fluorometrically determined in both experiments at baseline, 1 and 24 h post-MCAO. In experiment 1, a dose of 0.2 mg/kg inhibited proteasome activity by 77% and infarct volume was reduced to 175.7+/-59.9 mm3 and 205.9+/-83.9 mm3 (1 and 2 h group, respectively; p<0.05) compared to 306.5+/-48.5 mm3 (control). Treatment at 3 h was not neuroprotective (293.0+/-40.1 mm3). After embolic MCAO, infarct volume was 167.5+/-90.7 mm3 (treatment group) and 398.9+/-141.3 mm3 (control; p=0.002). In conclusion, VELCADE treatment inhibited whole blood proteasome activity and achieved significant neuroprotection in two rat models of focal cerebral ischemia at various time points poststroke.</p> | |
dc.identifier.submissionpath | neuro_pp/169 | |
dc.contributor.department | Graduate School of Biomedical Sciences | |
dc.contributor.department | Department of Neurology | |
dc.source.pages | 300-5 |