Summary
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> 0.01) after ischemia, whereas the 3H-Ro-15-1788 binding decreased significantly (p< 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> 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 > 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 usefull in the treatment of ischemic CA1 pyramidal cell death in the rat.
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References
Andiné P, Jacobson I, Sandberg M, Hagberg H (1988) Calcium regulation in the CA1 of rat hippocampus during postischemic phase. In: Krieglstein J (ed) Pharmacology of cerebral ischemia. CRC Press Inc, Boca Raton F1, pp 197–200
Benveniste H, J. Drejer, A. Schousboe and NH Diemer (1984) Elevation of the extracellular concentrations of glutamate and aspartate in the rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43:1369–1376
Campochiaro P, Schwarcz R, Coyle JT (1977) GABA receptor binding in rat striatum: localization and effects of denervation. Brain Res 136:501–511
Chamberlin NL, Dingledine R (1988) GABAergic inhibition and the induction of spontaneous epileptiform activity by low chloride and high potassium in the hippocampal slice. Brain Res 445:12–18
Chang HS, Sasaki T, Kassel NF (1989) Hippocampal unit activity after transient cerebral ischemia in rats. Stroke 20(8): 1051–1058
Francis A, Pulsinelli W (1983) Increased binding of 3H-GABA to striatal membranes following ischemia. J Neurochem 40:1497–1499
Franck JE, Kunkel DD, Baksin DG, Schwartzkroin PA (1988) Inhibition in kainate-lesioned hyperexcitable hippocampi: physiologic, autoradiographic and immunocytochemical observations. J Neurosci 8:1991–2002
Fuxe K, Köhler C, Agnati LF, Anderson K, Ogren SO, Eneroth P, Ferez de la Mora M, Karobath M, Krogsgaard-Larsen P (1981) GABA and benzodiazepine receptor studies on their localization in the hippocampus and their interaction with central dopamine neurons in the rat brain. In: Costa E, Dichiara G, Gessa GL (eds) GABA and benzodiazepine receptors, Raven Press, New York
Hagberg H, Lehmann A, Sandberg M, Nyström B, Jacobsen I, Hamberger A (1985) Ischemia-induced shift of inhibitory and excitatory amino acids from intra- and extracellular compartments. J Cereb Blood Flow Metabol 5:413–419
Hallmayer J, Hossmann K-A, Mies G (1985) Low doses of barbiturates for prevention of hippocampal lesions after brief ischemic episodes. Acta Neuropathol (Berl) 68:27–31
Jahnsen H, Lauersen AM (1983) Brain slices. In: Baker JL (ed) Current methods in cellular neurobiology, Vol. III. Electrophysiological techniques. John Wiley and Sons, New York, pp 189–224
Jensen MS, Yaari Y (1988) The relationship between interictal and ictal paroxysms in an in vitro model of focal hippocampal epilepsy. Ann Neurol 24:591–598
Johansen FF, Diemer NH (1990) Enhancement of GABA neurotransmission after cerebral ischemia in the rat reduces loss of hippocampal CA1 pyramidal cells. Acta Neurol Scand (in press)
Johansen FF, Jørgensen MB, Diemer NH (1983) Resistance of hippocampal CA-1 interneurons to 20 min of transient cerebral ischemia in the rat. Acta Neuropathol (Berl) 61:135–140
Johansen FF, Lin C-T, Schousboe A, Wu J-Y (1989a) Immunocytochemical investigation of L-glutamic acid decarboxylase in the rat hippocampal formation: the influence of transient cerebral ischemia. J Comp Neurol 281:40–53
Johansen FF, O'Hare MMT (1989b) Loss of somatal neuropeptide Y immunoreactivity in the rat hippocampus following transient cerebral ischemia. J Neurosurg Anesth 1:339–345
Johansen FF, Zimmer J, Diemer NH (1987) Early loss of somatostatin neurons in dentate hilus after cerebral ischemia in the rat precedes CA-1 pyramidal cell loss. Acta Neuropathol (Berl) 73:110–114
Kirino T, Tamura A, Sano K (1986) A reversible type of neuronal injury following ischemia in the gerbil hippocampus. Stroke 17:455–459
Kuriyama K, Kurihara E, Yoshihisa I, Yoneda Y (1980) Increase in striatal 3H-muscimol binding following intrastriatal injection of kainic acid: a denervation hypersensitivity phenomenon. J Neurochem 35:343–348
Lindroth P, Hamberger A, Sandberg M (1985) Liquid Chromatographic determination of amino acids after precolumn fluorescence derivatization. In: Bouton AA, Baker GB, Wood JD (eds) Neuromethods, Vol 3. Amino acids. Humana Press Inc, Clifton, pp 97–116
Lowry OH, Janet V, Passonneau JV, Hasselberger FX, Schulz DW (1964) Effect of ischemia on known substrates and cofactors of the glycolytic pathway in the brain. J Biol Chem 239:18–30
Möhler H, Burkard WP, Keller HH, Richards JG, Haefely W (1981) Benzodiazepine antagonist Ro 15–1788: binding characteristics and interaction with drug-induced changes in dopamine turnover and cerebral cGMP levels. J Neurochem 37:714–722
Onodera H, Sato G, Kogure K (1987) GABA and benzodiazepine receptors in the gerbil brain after transient ischemia: demonstration by quantitative receptor autoradiography. J Cereb Blood Flow Metabol 7:82–88
Pellegrino LJ, Pellegrino AS, Cushman AJ. (1979) A stereotaxic atlas of the rat brain. Plenum Press, New York
Pulsinelli WA, Brierley JB (1979) A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke 10:267–272
Sabato UC, Augilar JS, Medina JH, De Robertis E (1981) Changes in rat hippocampal benzodiazepine receptors and lack of changes in muscarinic receptors after fimbria-fornix lesions. Neurosci Lett 27:193–197
Saji M, Reis DJ (1987) Delayed transneuronal death of substantia nigra neurons prevented by γ-aminobutyric acid agonist. Science 235:66–69
Santori EM, Collins RC (1988) Effects of cronic cortical seizures on GABA and benzodiazepine receptors within seizure pathways. Brain Res 442:261–269
Shin C, Pedersen HP, McNamara JO (1985) γ-aminobutyric acid and benzodiazepine receptors in the kindling model of epilepsy: a quantitative radiohistochemical study. J Neurosci 5:2696–2701
Sternau LL, Lust WD, Ricci AJ, Ratcheson R (1989) Role for γ-aminobutyric acid in selective vulnerability in gerbils. Stroke 20:281–287
Suzuki R, Yamaguchi T, Li CL, Klatzo I (1983) The effect of 5-minnute ischemia in mongolian gerbils. II. Changes of spontaneous neuronal activity in cerebral cortex and CA-1 sector of hippocampus. Acta Neuropathol (Berl) 60:217–22
Young WS, Kuhar MJ (1979) Autoradiographic localisation of benzodiazepine receptors in the brains of humans and animals. Nature 280:393–395
Zanotto L, Heinemann U (1983) Aspartate and glutamate induced reductions in extracellular free calcium and sodium concentrations in area CA-1 of in vitro hippocampal slices of rats. Neurosci Lett 35:79–84
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Johansen, F.F., Christensen, T., Jensen, M.S. et al. Inhibition in postischemic rat hippocampus: GABA receptors, GABA release, and inhibitory postsynaptic potentials. Exp Brain Res 84, 529–537 (1991). https://doi.org/10.1007/BF00230965
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DOI: https://doi.org/10.1007/BF00230965