Calcium uptake evoked by electrical stimulation is enhanced postischemically and precedes delayed neuronal death in CA1 of rat hippocampus: involvement of N-methyl-D-aspartate receptors.
Extracellular calcium concentration changes in the CA1 of the hippocampus during burst activity were measured during postischemic reflow, and the involvement of N-methyl-D-aspartate (NMDA) receptors was evaluated. In adult Wistar rats global ischemia was induced by four-vessel occlusion for 20 min. After 6 h of postischemic reflow, the animals were halothane-anesthetized and reintubated. A double-barrelled calcium-sensitive microelectrode was advanced through stratum oriens, pyramidale, and radiatum in 50-micron steps. At each step the perforant pathway was stimulated (15 Hz, 30 s), and changes in extracellular calcium concentration were recorded. High-frequency stimulation elicited burst firing and transient decreases in extracellular calcium concentration, which are interpreted as neuronal calcium uptake. In control hippocampus, the extracellular calcium decreases were maximal in the stratum pyramidale. Six to eight hours after ischemia, a threefold enhancement of extracellular calcium decreases was found in the dendritic layers of the CA1. The NMDA-receptor antagonist ketamine (15-30 mg/kg intraperitoneally) reduced these electrically evoked calcium decreases. Seven days after ischemia, there was a 60-90% loss of pyramidal cells in the CA1. In conclusion, the cellular calcium uptake, possibly through NMDA receptors evoked by neuronal activity, is enhanced during early postischemia and precedes delayed neuronal death.
Andiné
P
P
Institute of Neurobiology, University of Göteborg, Sweden.
Jacobson
I
I
Hagberg
H
H
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D004558:Electric Stimulation; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D002118:Calcium