Protection against ischemic injury in primary cultured astrocytes of mousecerebral cortex by bis(7)-tacrine, a novel anti-Alzheimer's agent

The effects of bis(7)-tacrine, a novel acetylcholinesterase inhibitor, on i schemia-induced cell death and apoptosis were investigated in primary cereb ral cortical astrocytes of mice. Following a 6 h in vitro ischemic incubati on of the cultures, a marked decrease in the percentage of viable cells was observed by lactate dehydrogenase (LDH) release assay. Furthermore, using bisbenzimide staining, we determined that approximately 65% of the cells un derwent apoptosis. Treatment with bis(7)-tacrine (1-10 nM) during ischemic incubation effectively inhibited the ischemia-induced apoptosis, as demonst rated by morphological and biochemical tests. Our results demonstrated that bis(7)-tacrine could protect astrocytes against ischemia-induced cell inju ry, indicating that the drug might be beneficial for the treatment of vascu lar dementia, in addition to Alzheimer's disease. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.