In vitro hypoxia of cortical and hippocampal CA1 neurons: glutamate, nitric oxide, and platelet activating factor participate in the mechanism of selective neural death in CA1 neurons.
We prepared neuron-rich cultures from cortical and hippocampal CA1 regions of postnatal day 1 (P1) rats. Using these cultures, we investigated the sensitivity of neurons to hypoxic insults. The effects of MK-801, cycloheximide, NG-nitro-L-arginine (L-NNA), and anti-platelet-activating factor (anti-PAF) IgG on neuronal injury under hypoxic conditions also were examined. The percentage of astroglial cells was higher in CA1 than cortical cultures despite use of the same culture procedure. Despite this finding, the percentage of lactate dehydrogenase (LDH) released into the medium was greater in CA1 than cortical cultures under the conditions of 24-h hypoxia and 24-h incubation (P < 0.05). We then added MK-801 (500 nM), cycloheximide (3 microM), L-NNA (100 microM) and anti-PAF IgG (50 micrograms/ml) prior to inducing the hypoxia and measured LDH in the medium after 24-h hypoxia and 48-h incubation. Under the hypoxic condition, MK-801, L-NNA, and anti-PAF IgG significantly protected the CA1 neurons from hypoxic injury compared with cortical neurons, while cycloheximide protected both cultures equally. These results suggest that CA1 neurons are more sensitive to hypoxia than cerebral cortical neurons, and glutamate, nitric oxide, and PAF may participate in the mechanism of selective neural death in neurons of the CA1 region due to hypoxia.
Ohmori
T
T
Department of Neurosurgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Hirashima
Y
Y
Kurimoto
M
M
Endo
S
S
Takaku
A
A
D000818:Animals; D016923:Cell Death / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010972:Platelet Activating Factor; D011500:Protein Synthesis Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018698:Glutamic Acid