Title
The proteasome inhibitor VELCADE reduces infarction in rat models of focal cerebral ischemia
UMMS Affiliation
Department of Neurology; Graduate School of Biomedical Sciences
Publication Date
2006-02-23
Document Type
Article
Subjects
Animals; Boronic Acids; Brain Infarction; Brain Ischemia; Disease Models, Animal; Infarction, Middle Cerebral Artery; Intracranial Embolism; Male; Neuroprotective Agents; Proteasome Endopeptidase Complex; Pyrazines; Rats; Rats, Inbred WKY; Rats, Sprague-Dawley
Disciplines
Neurology | Neuroscience and Neurobiology
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.
DOI of Published Version
10.1016/j.neulet.2006.01.015
Source
Neurosci Lett. 2006 May 8;398(3):300-5. Epub 2006 Feb 21. Link to article on publisher's site
Journal/Book/Conference Title
Neuroscience letters
Related Resources
PubMed ID
16490315
Repository Citation
Henninger N, Sicard KM, Bouley JP, Fisher M, Stagliano NE. (2006). The proteasome inhibitor VELCADE reduces infarction in rat models of focal cerebral ischemia. Neurology Publications. https://doi.org/10.1016/j.neulet.2006.01.015. Retrieved from https://escholarship.umassmed.edu/neuro_pp/169