Protection against ischemic injury in primary cultured mouse astrocytes by bis(7)-tacrine, a novel acetylcholinesterase inhibitor [corrected]

Neurosci Lett. 2000 Jul 14;288(2):95-8. doi: 10.1016/s0304-3940(00)01198-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Astrocytes / enzymology
  • Astrocytes / pathology*
  • Brain Ischemia / enzymology
  • Brain Ischemia / pathology*
  • Brain Ischemia / prevention & control*
  • Cells, Cultured
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / pathology*
  • Cholinesterase Inhibitors / therapeutic use*
  • Female
  • Male
  • Mice
  • Mice, Inbred ICR
  • Tacrine / analogs & derivatives*
  • Tacrine / therapeutic use*

Substances

  • 1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
  • Cholinesterase Inhibitors
  • Tacrine