Regulation of microglial expression of integrins by poly(ADP-ribose) polymerase-1

Excitotoxic brain lesions initially result in the primary destruction of br ain parenchyma, after which microglial cells migrate towards the sites of i njury. At these sites, the cells produce large quantities of oxygen radical s and cause secondary damage that accounts for most of the loss of brain fu nction, Here we show that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, regulated by th e nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) through the formati on of a nuclear PARP-NF-kappaB-protein complex. Downregulation of PARP or C D11a by transfection with antisense DNA abrogated microglial migration almo st completely and prevented neurons from secondary damage.