Project 1: Abstract We have shown that DNRAb, antibodies that cross-react with DNA and N-methyl D-aspartate receptor, cause cognitive impairment when they penetrate the hippocampus. The neural injury proceeds in two stages. First, there is excitotoxic neuronal death; second, there is microglial activation and dendritic loss in surviving neurons. Microglial suppression by angiotensin converting enzyme (ACE) inhibition restores neuronal integrity and cognitive function. We propose now to study the mechanism of microglial activation and dendritic loss and the mechanism of action of ACE inhibition. These studies have the potential to suggest additional therapeutic targets for ameliorating cognitive impairment in neuropsychiatric lupus.