Protection of Hippocampal Neurons from “Ischemic” Insult in Vitro by Acidic Amino Acid Antagonists
Processes involved in ischemia-induced neuronal cytotoxicity were studied using hippocampal dissociated cell cultures and tissue slices. Acidic amino acid antagonists and phencyclidine (PCP) agonists were evaluated for their ability to protect neurons from the cellular responses to oxygen deprivation. The addition of both competitive and noncompetitive N-methyl-D-aspartate (NMDA) antagonists to the culture medium during the hypoxic or NMDA-mediated insult afforded the neurons protection from cell death. The rank order of potency corresponded to the relative binding affinities of these compounds for NMDA and PCP receptors. Extracellular AC and DC recordings were used to monitor the course of acute processes, induced by ischemia-like conditions, in area CA1 of the rat hippocampal slice. At D-glucose concentrations below 5mM, the replacement of O2 with N2 led to the abolition of the field excitatory postsynaptic potential (EPSP) succeeded by a reappearance of the EPSP, anoxic depolarization and a long-term failure of the EPSP. D-2-amino-7-phosphonoheptanoate (D-AP7) and 15mM Mg2+, but not MK-801 or 5mM Mg2+, delayed or blocked anoxic depolarization. The results indicate that acidic amino acid antagonists can influence the acute processes induced by hypoxia plus lowered glucose, but that normal calcium-dependent synaptic release is not critically involved.
KeywordsHippocampal Neuron Hippocampal Slice Acidic Amino Acid Population Spike Stratum Pyramidale
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