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: J Chen, N Adachi, K Liu, T Nagaro, T Arai
• Journal: Brain research (Brain Res) Vol. 792 Issue 1 Pg. 16-23 (May 04 1998) ISSN: 0006-8993 [Print] Netherlands
• PMID: 9593805 (Publication Type: Journal Article)
• Copyright: Copyright 1998 Elsevier Science B.V.

Chemical References

• Anesthetics, Local
• Procaine
• Sodium
• Calcium

Topics

• Anesthetics, Local (administration & dosage, therapeutic use)
• Animals
• Brain Ischemia (drug therapy, metabolism, pathology)
• Calcium (metabolism)
• Electrophysiology
• Gerbillinae
• Hippocampus (metabolism, pathology)
• Injections, Intraventricular
• Male
• Microscopy, Fluorescence
• Procaine (administration & dosage, therapeutic use)
• Sodium (metabolism)