Improvement of ischemic damage in gerbil hippocampal neurons by procaine

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 μmol) 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 μmol/l) on the Ca²⁺ accumulation were examined. Additionally, the effect of procaine (100 μmol/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 μmol/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 μmol/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.