ISCHEMIA-INDUCED LONG-TERM HYPEREXCITABILITY IN RAT NEOCORTEX

The long-term structural and functional consequences of transient fore brain ischaemia were studied with morphological, immunohistochemical a nd in vitro electrophysiological techniques in the primary somatosenso ry cortex of Wistar rats, After survival times of 10-17 months postisc haemia, neocortical slices obtained from ischaemic animals were charac terized by a pronounced neuronal hyperexcitability in comparison with untreated age-matched controls, Extra- and intracellular recordings in supragranular layers revealed all-or-none long-latency recurrent resp onses to orthodromic synaptic stimulation of the afferent pathway. The se responses were characterized by durations up to 1.7 s, by multiple components and by repetitive synaptic burst discharges, The reversible blockade of this late activity by DL-amino-phosphonovaleric acid (APV ) suggested that this activity was mediated by N-methyl-D-aspartate (N MDA) receptors, The peak conductance of inhibitory postsynaptic potent ials was significantly smaller in neurons recorded in neocortical slic es obtained from ischaemic animals than those from the controls, Howev er; the average number of parvalbumin (PV)-labelled neurons per mm(3), indicative of a subpopulation of GABAergic interneurons, and the aver age number and length of dendritic processes arising from PV-containin g cells was not significantly different between ischaemic and control cortex, The prominent dysfunction of the inhibitory system in ischaemi c animals occurred without obvious structural alterations in PV-labell ed cells, indicating that this subpopulation of GABAergic interneurons is not principally affected by ischaemia, Our data suggest a long-ter m down-regulation of inhibitory function and a concurrent NMDA recepto r-mediated hyperexcitability in ischaemic neocortex, These alterations may result from structural and/or functional properties of inhibitory non-PV-positive neurons or permanent functional modifications on the subcellular molecular level, i,e. alterations in the phosphorylation s tatus of GABA and/or NMDA receptors. The net result of these long-term changes is an imbalance between the excitatory and inhibitory systems in the ischaemic cortex with the subsequent expression and manifestat ion of intracortical hyperexcitability,