Post-ischemic administration of the acetylcholinesterase inhibitor ENA-713 prevents delayed neuronal death in the gerbil hippocampus

Neurochem Res. 1995 Jun;20(6):663-7. doi: 10.1007/BF01705533.

Abstract

We examined by morphological methodology the effect of (S)-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate (ENA-713), an acetylcholinesterase (AChE) inhibitor, on ischemia-induced neuronal death in the gerbil hippocampus due to a 5-min ligation of bilateral common carotid arteries after light ether anesthesia. Pyramidal cells had been decreased to 27% of sham-operated controls and the number of hypertrophic astrocytes expressing glial fibrillary acidic protein (GFAP) markedly increased in the hippocampal CA1 subfield 14 days after ischemia. However, post-ischemic administration of ENA-713 (three times 0.2 mg/kg, i.p.) significantly ameliorated this ischemia-induced decrease in the number of pyramidal cells by 47% of sham-operated controls, furthermore, it reduced the ischemia-induced accumulation of GFAP-positive astrocyte in the CA1 region. Together with previous results showing that ENA-713 protected against the ischemia-induced cholinergic abnormalities in the gerbil brain and improved cholinergic dysfunctions in the senescent rat brain, our present findings suggest that ENA-713 prove to be useful for treatment with senile dementia such as cerebrovascular dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Carbamates / pharmacology*
  • Cell Death / drug effects*
  • Cholinesterase Inhibitors / pharmacology*
  • Gerbillinae
  • Glial Fibrillary Acidic Protein / analysis
  • Glial Fibrillary Acidic Protein / biosynthesis
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • Hypertrophy
  • Ischemic Attack, Transient / pathology*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / pathology*
  • Phenylcarbamates*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / pathology
  • Rivastigmine

Substances

  • Carbamates
  • Cholinesterase Inhibitors
  • Glial Fibrillary Acidic Protein
  • Phenylcarbamates
  • Rivastigmine