[VELCADE reduces infarction in rat models of focal cerebral ischemia]
>>Neurosci Lett. 2006 Feb 18; [Epub ahead of print]
The proteasome inhibitor VELCADE((R)) reduces infarction in rat models of focal cerebral ischemia.
Henninger N, Sicard KM, Bouley J, Fisher M, Stagliano NE.
Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
The potential neuroprotective effects of VELCADE((R)) were investigated in two different models of focal cerebral ischemia. For time-window assessment, male Wistar-Kyoto rats were treated with 0.2mg/kg VELCADE((R)) at 1, 2, or 3h 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 0.2mg/kg VELCADE((R)) after embolic MCAO (experiment 2). Infarct volume was calculated based on TTC-staining 24h postischemia and whole blood proteasome activity was fluorometrically determined in both experiments at baseline, 1 and 24h post-MCAO. In experiment 1, a dose of 0.2mg/kg inhibited proteasome activity by 77% and infarct volume was reduced to 175.7+/-59.9mm(3) and 205.9+/-83.9mm(3) (1 and 2h group, respectively; p<0.05) compared to 306.5+/-48.5mm(3) (control). Treatment at 3h was not neuroprotective (293.0+/-40.1mm(3)). After embolic MCAO, infarct volume was 167.5+/-90.7mm(3) (treatment group) and 398.9+/-141.3mm(3) (control; p=0.002). In conclusion, VELCADE((R)) treatment inhibited whole blood proteasome activity and achieved significant neuroprotection in two rat models of focal cerebral ischemia at various time points poststroke.<<
Doubt we'll see this approach with Velcade in humans, given the side effects, but maybe next generation proteasome inhibitors?
Cheers, Tuck |
