CLINICAL NEUROSCIENCE AND NEUROPATHOLOGYNeuroprotection achieved with a novel proteasome inhibitor which blocks NF-κB activationBuchan, A M.1,3; Li, H1; Blackburn, B2Author Information 1Alberta Stroke Program, Department of Clinical Neurosciences, University of Calgary, 1403-29 Street N.W., Room 1162, Calgary, Alberta T2N 2T9, Canada 2CV Therapeutics Inc., 3172 Porter Drive, Palo Alto, CA, USA 3Corresponding Author: A. M. Buchan Received 10 November 1999; accepted 26 November 1999 NeuroReport: February 7, 2000 - Volume 11 - Issue 2 - p 427-430 Buy Abstract Activated NF-κB contributes to cerebral infarction by triggering a neuro-inflammatory response. Rats subjected to 90 min middle cerebral artery occlusion developed a cortical infarct of 20 ± 4% of hemispheric volume (n = 8). Treatment with the proteasome inhibitor CVT-634 resulted in a significantly smaller infarct of 13 ± 2% (n = 7, p <0.01) and 12 ± 2% (n = 8, p <0.001) of hemispheric volume at 1 day and 7 days, respectively. Since regional cerebral blood flows for the core and penumbral regions were not affected, we concluded that all animals received the same ischemic insult. The reduction in infarction persisted for 7 days. This is the first indication that a proteasome inhibitor can reduce infarct volume in a focal model of cerebral ischemia. © 2000 Lippincott Williams & Wilkins, Inc.