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 attribut ed to irreversible impairment of inhibitory neurons. However, the condition s required for selective and irreversible impairment of inhibitory interneu rons in vitro are unknown. In this study, we found that a combination of lo w temperature and hypoxia produced hyperexcitability in the neocortex. Neoc ortical tissue blocks isolated from rats were exposed to low temperature (1 -3 degrees C) for 45 min and subsequently to room temperature (21-23 degree s C) for 60 min in the non-oxygenated medium. In experimental slices prepar ed from the processed blocks, hyperexcitability, similar to that elicited b y an antagonist of GABA(A) receptors, was observed. Exposure of the neocort ical tissue blocks to low temperature alone or room temperature alone did n ot elicit hyperexcitability. The excitability of pyramidal neurons, excitat ory synaptic transmission and inhibitory effects of an agonist of GABA(A) r eceptors were normal in experimental slices. However, excitation of pyramid al neurons was inhibited after local stimulation of inhibitory neurons in c ontrol slices, but not in experimental slices. Nitric oxide (NO) release fr om cortical interneurons was also markedly reduced in experimental slices. These results indicate that irreversible impairment of neocortical inhibito ry neurons was produced by low temperature combined with hypoxia produced i n vitro. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.