title: Protection against ischemic injury in primary cultured mouse astrocytes by bis(7)-tacrine, a novel acetylcholinesterase inhibitor [corrected].
abstract: The effects of bis(7)-tacrine, a novel acetylcholinesterase inhibitor, on ischemia-induced cell death and apoptosis were investigated in primary cerebral cortical astrocytes of mice. Following a 6 h in vitro ischemic incubation 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 underwent apoptosis. Treatment with bis(7)-tacrine (1-10 nM) during ischemic incubation effectively inhibited the ischemia-induced apoptosis, as demonstrated by morphological and biochemical tests. Our results demonstrated that bis(7)-tacrine could protect astrocytes against ischemia-induced cell injury, indicating that the drug might be beneficial for the treatment of vascular dementia, in addition to Alzheimer's disease.
authors.affiliation: Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: D C
authors.initials: DC
authors.lastname: Wu
authors.forename: X Q
authors.initials: XQ
authors.lastname: Xiao
authors.forename: A K
authors.initials: AK
authors.lastname: Ng
authors.forename: P M
authors.initials: PM
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: Chung
authors.forename: N T
authors.initials: NT
authors.lastname: Lee
authors.forename: P R
authors.initials: PR
authors.lastname: Carlier
authors.forename: Y P
authors.initials: YP
authors.lastname: Pang
authors.forename: A C
authors.initials: AC
authors.lastname: Yu
authors.forename: Y F
authors.initials: YF
authors.lastname: Han
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.forename: Y
authors.initials: Y
authors.lastname: Pang
authors.forename: Y
authors.initials: Y
authors.lastname: Han
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology*; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013619:Tacrine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D002800:Cholinesterase Inhibitors; D013619:Tacrine