Neuroprotection achieved with a novel proteasome inhibitor which blocks NF-κB activation

Activated NF-kappa B 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. NeuroReport 11:427-430 (C) 2000 Lippincott Williams & Wilkins.