title: Improvement of ischemic damage in gerbil hippocampal neurons by procaine.
abstract: Acute cerebral ischemia induces membrane depolarization in the neuron, thereby incurring the simultaneous influx of various ions such as Na+ and Ca2+. Since procaine possesses the ability to inhibit the release of Ca2+ from intracellular Ca2+ stores to the cytosol as well as the ability to block Na+ channels, the effects of procaine on ischemia were investigated in the present study in gerbils both in vivo and in vitro. The histologic outcome was evaluated 7 days after 3 min of transient forebrain ischemia by assessing delayed neuronal death in hippocampal CA1 pyramidal cells in animals administered procaine (0.2, 0.4, or 2 micromol) intracerebroventricularly 10 min before ischemia and in animals given saline. The changes in the direct-current potential shift in the hippocampal CA1 area were measured using an identical animal model. A hypoxia-induced intracellular Ca2+ increase was evaluated by in vitro microfluorometry in gerbil hippocampal slices, and the effects of procaine (10, 50, and 100 micromol/l) on the Ca2+ accumulation were examined. Additionally, the effect of procaine (100 micromol/l) in a Ca2+-free condition was investigated. The histologic outcome was improved and the onset of the ischemia-induced membrane depolarization was prolonged by the preischemic administration of procaine. The increase in the intracellular concentration of Ca2+ induced by the in vitro hypoxia was suppressed by the perfusion of procaine-containing mediums (50 and 100 micromol/l), regarding both the initiation and the extent of the increase. A hypoxia-induced intracellular Ca2+ elevation in the Ca2+-free condition was observed, and the perfusion with procaine (100 micromol/l) inhibited this elevation. Procaine helps protect neurons from ischemia by suppressing the direct-current potential shift and by inhibiting the release of Ca2+ from the intracellular Ca2+ stores, as well as by inhibiting the influx of Ca2+ from the extracellular space.
authors.affiliation: Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: N
authors.initials: N
authors.lastname: Adachi
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Nagaro
authors.forename: T
authors.initials: T
authors.lastname: Arai
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007276:Injections, Intraventricular; D008297:Male; D008856:Microscopy, Fluorescence; D011343:Procaine / Q000008:administration & dosage / Q000627:therapeutic use*; D012964:Sodium / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D011343:Procaine; D012964:Sodium; D002118:Calcium