Summary
Rats were exposed for 24 min to bilateral clamping of the common carotid arteries (BCCA) in pentobarbital anaesthesia. The GABA content was measured 24 hours, 48 hours, 4 days, 14 days and 3 months after BCCA. In other groups of rats seizures were elicited by i.p. injection of (+)-bicuculline (3 mg/kg) 24 hours, 48 hours, 4 days, 14 days and 3 months after BCCA. Analysis of the GABA content revealed significant increase compared with controls in the hippocampus, frontal cortex and substantia nigra from 24 hours up to 3 months. Bicuculline treatment induced tonic/clonic seizures and status epilepticus in sham operated animals; these effects were drastically diminished at various time points after BCCA. The present results suggest that BCCA produces a longlasting increase in GABA content and as a consequence protection from bicuculline-induced seizures.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amano ST, Obata T, Hazama F, Kashiro N, Shimada M (1990) Hypoxia prevents seizures and neuronal damages of the hippocampus induced by kainic acid in rats. Brain Res 523: 121–126
Blennow G, Brierley JB, Meldrum BS, Siesjö BK (1978) Epileptic brain damage. The role of systemic factors that modify cerebral energy metabolism. Brain 101: 687–700
Block F, Sieklucka M, Osborne NN, Heim C, Sontag KH (1990) Electrophysiological metabolic and biochemical approaches to the effects of bilateral clamping of carotid arteries in normotensive rats. In: Krieglstein J, Oberpichler H (eds) Pharmacology of cerebral ischemia 1990. Wissenschaftliche Verlagsgesellschaft, Stuttgart, pp 47–52
Bortolotto ZA, Heim C, Sieklucka M, Block F, Sontag KH, Cavalheiro EA (1991) Effects of bilateral clamping of carotid arteries on hippocampal kindling in rats. Physiol Behav 49: 667–671
Crain BJ, Westerham WD, Harrison, Nadler J (1984) Selective neuronal death after transient forebrain ischemia in the Mongolian gerbil: a silver impregnation study. Neuroscience 27: 387–402 (1988)
Eklöf B, Siesjö BK (1972a) The effect of bilateral carotid artery ligation upon the blood flow and the energy state of the rat brain. Acta Physiol Scand 86: 155–165
Eklöf B, Siesjö BK (1972b) The effect of bilateral carotid artery ligation upon acid-base parameters and substrate levels in the rat brain. Acta Physiol Scand 86: 528–538
Erecinska M, Nelson D, Wilson DF, Silver IA (1984) Neurotransmitter amino acids in the CNS. I. Regional changes in amino acid levels in rat brain during ischemia and reperfusion. Brain Res 304: 9–22
Fariello RG, Hornykiewicz O (1979) Substantia nigra and pentylenetetrazol threshold in rats: correlation with striatal dopamine metabolism. Exp Neurol 65: 202–208
Gale K, Iadarola MJ (1980) Seizure protection and increased nerve-terminal GABA: delayed effects of GABA transaminase inhibition. Science 208: 288–291
Hagberg H, Lehmann A, Sandberg M, Nyström B, Jacobson I, Hamberger A (1985) Ischemia-induced shift of inhibitory and excitatory amino acids from intra- to extra-cellular compartments. J Cereb Blood Flow Metab 5: 413–419
Heim C, Sieklucka-Dziuba M, Bortolotto ZA, Löscher W, Cavalheiro EA, Sontag KH (1988) Is the protection against pilocarpine induced seizures after transient oligemic hypoxia caused by increased GABA-levels in different vulnerable structures? Psychopharmacology [Suppl 96]: 272 (Abstr 16th CINP Congress, Munich)
Heim C, Sieklucka M, Block F, Schmidt-Kastner R, Jaspers R, Sontag KH (1990) Transient occlusion of carotid arteries leads to disturbed spatial learning and memory in the rat. In: Krieglstein J, Oberpichler H (eds) Pharmacology of cerebral ischemia 1990. Wissenschaftliche Verlagsgesellschaft, Stuttgart, pp 53–61
Heim C, Bortolotto ZA, Cavalheiro EA, Sontag KH (1991) Transient occlusion of rat carotid arteries decreases susceptibility to pilocarpine seizure. Brain Res 544: 253–259
Iadarola MJ, Gale K (1982) Substantia nigra: site of anticonvulsant activity mediated by γ-aminobutyric acid. Science 218: 1237–1240
Jaspers RMA, Block F, Heim C, Sontag KH (1990) Spatial learning is affected by transient occlusion of common carotid arteries (2VO): comparison of behavioural and histopathological changes after “2VO” and four-vessel-occlusion in rats. Neurosci Lett 117: 149–153
Kleinrok Z, Turski L (1980) Kainic acid induced wet-dog shakes in rats. The relation to central neurotransmitters. Naunyn-Schmiedebergs Arch Pharmacol 314: 37–46
Korf J, Klein HC, Venema K, Postema F (1988) Increases in striatal and hippocampal impedance and extracellular levels of amino acids by cardiac arrest in freely moving rats. J Neurochem 50: 1087–1096
Lowe JP, Robinson E, Eyerman GS (1958) The fluorimetric measurements of glutamic decarboxylase and its distribution in brain. J Neurochem 3: 8–18
Meldrum BS (1975) Epilepsy and γ-aminobutyric acid-mediated inhibition. Int Rev Neurobiol 17: 1–36
Olney JW, De Gubareff T, Labruyere J (1983) Seizure-related brain damage induced by cholinergic agents. Nature (London) 301: 520–522
Pulsinelli WA, Brierley JB, Plum F (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11: 491–498
Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32: 281–294
Schmidt-Kastner R, Hossmann KH (1988) Distribution of ischemic cell change in the dorsal hippocampus of rat. Acta Neuropathol 78: 411–421
Schmidt-Kastner R, Freund TF (1991) Selective vulnerability of the hippocampus in brain ischemia. Neuroscience 40: 599–636
Sieklucka M, Bortolotto Z, Heim C, Block F, Sontag KH (1991 a) Decreased susceptibility to seizures induced by bicuculline after transient bilateral clamping of the carotid arteries in rats. J Neural Transm [GenSect] 83: 127–137
Sieklucka M, Heim C, Sontag KH, Osborne NN (1991 b) Transient occlusion of rat carotid arteries increases formation of inositol phosphate. Evidence for a specific effect on α-receptors. Neurochem Int 18: 175–184
Smith ML, Auer RN, Siesjö BK (1984) The density and distribution of ischemic brain injury in the rat following 2–20 min of forebrain ischemia. Acta Neuropathol (Berl) 64: 319–332
Sutton J, Simmonds M (1974) Effects of acute and chronic pentobarbitone on the γ-aminobutyric acid system in rat brain. Biochem Pharmacol 23: 1801–1808
Turski WA, Czuzwar SJ, Kleinrok Z, Turski L (1983) Cholinomimetics produce seizures and brain damage in rats. Experientia 39: 1408–1411
Wood JD, Watson WJ, Ducker AJ (1968) The effect of hypoxia on brain γ-aminobutyric acid levels. J Neurochem 15: 603–608
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sieklucka, M., Heim, C., Block, F. et al. Transient reduction of cerebral blood flow leads to longlasting increase in GABA content in vulnerable structures and decreased susceptibility to bicuculline induced seizures. J. Neural Transmission 88, 87–94 (1992). https://doi.org/10.1007/BF01244814
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01244814