Inhibition in postischemic rat hippocampus: GABA receptors, GABA release, and inhibitory postsynaptic potentials.
We have investigated the GABAergic system in rat hippocampus at 1 hour and up to 21 days following 20 min of global cerebral ischemia. Distribution of 3H-GABA (in excess of unlabeled baclofen) and 3H-Ro-15-1788 (benzodiazepine antagonist) binding sites in hippocampus was studied utilizing quantitative autoradiography. The 3H-GABA binding was unchanged (p greater than 0.01) after ischemia, whereas the 3H-Ro-15-1788 binding decreased significantly (p less than 0.01) in all hippocampal subfields 1-21 days after ischemia. Using microdialysis in CA1, we found that K(+)-stimulated GABA release at 1 hour and 1 day after ischemia was unchanged (p greater than 0.01) in comparison to preischemic controls. Electrophysiological recordings were made from CA1 of hippocampal slices prepared from rats sacrificed 1 hour, 1 day and 2 days after ischemia. Field potentials evoked by stimulation of the Schaffer collaterals showed no differences (p greater than 0.01) from those taken from controls. Postischemic intracellular recordings from the CA1 pyramidal cells showed that fast and slow inhibitory postsynaptic potentials were readily evoked on orthodromic stimulation. Together with our previous morphological results, demonstrating survival of hippocampal interneurons following ischemia, we conclude that hippocampal GABAergic interneurons preserve their inhibitory potential in the period preceding delayed CA1 pyramidal cell death. This conclusion taken together with the observation that postischemic 3H-Ro-15-1788 binding in hippocampus declined, suggest that benzodiazepines (by increasing the receptor affinity), GABA analogs, and GABA uptake inhibitors may be useful in the treatment of ischemic CA1 pyramidal cell death in the rat.
Johansen
F F
FF
PharmaBiotec Research Center, University of Copenhagen, Denmark.
Christensen
T
T
Jensen
M S
MS
Valente
E
E
Jensen
C V
CV
Nathan
T
T
Lambert
J D
JD
Diemer
N H
NH
D000818:Animals; D001345:Autoradiography; D002545:Brain Ischemia / Q000503:physiopathology*; D003956:Dialysis; D004594:Electrophysiology; D005442:Flumazenil / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D011712:Pyramidal Tracts / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid