Irreversible impairment of inhibitory neurons and nitric oxide release in the neocortex produced by low temperature and hypoxia in vitro.
Brain ischemia causes irreversible hyperexcitability, which may be attributed to irreversible impairment of inhibitory neurons. However, the conditions required for selective and irreversible impairment of inhibitory interneurons in vitro are unknown. In this study, we found that a combination of low temperature and hypoxia produced hyperexcitability in the neocortex. Neocortical tissue blocks isolated from rats were exposed to low temperature (1-3 degrees C) for 45 min and subsequently to room temperature (21-23 degrees C) for 60 min in the non-oxygenated medium. In experimental slices prepared from the processed blocks, hyperexcitability, similar to that elicited by an antagonist of GABA(A) receptors, was observed. Exposure of the neocortical tissue blocks to low temperature alone or room temperature alone did not elicit hyperexcitability. The excitability of pyramidal neurons, excitatory synaptic transmission and inhibitory effects of an agonist of GABA(A) receptors were normal in experimental slices. However, excitation of pyramidal neurons was inhibited after local stimulation of inhibitory neurons in control slices, but not in experimental slices. Nitric oxide (NO) release from cortical interneurons was also markedly reduced in experimental slices. These results indicate that irreversible impairment of neocortical inhibitory neurons was produced by low temperature combined with hypoxia produced in vitro.
Department of Neurophysiology, Brain Research Institute, Niigata University, Japan.
T
T
Fujisaki
H
H
Wakatsuki
M
M
Kudoh
K
K
Shibuki
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology*; D003080:Cold Temperature; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D019579:Neocortex / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D009118:Muscimol; D009569:Nitric Oxide; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline