Post-ischemic administration of the acetylcholinesterase inhibitor ENA-713 prevents delayed neuronal death in the gerbil hippocampus.
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.
Tanaka
K
K
Department of Neuroscience, Okayama University Medical School, Japan.
Mizukawa
K
K
Ogawa
N
N
Mori
A
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002219:Carbamates / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D006984:Hypertrophy; D002546:Ischemic Attack, Transient / Q000473:pathology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D048448:Phenylcarbamates; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D000068836:Rivastigmine
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D005904:Glial Fibrillary Acidic Protein; D048448:Phenylcarbamates; D000068836:Rivastigmine