Elsevier

Progress in Neurobiology

Volume 47, Issue 6, December 1995, Pages 477-511
Progress in Neurobiology

Glutamate, GABA and epilepsy

https://doi.org/10.1016/0301-0082(95)00030-5Get rights and content

Abstract

The nature and value of various animal models of epilepsy for the study and understanding of the human epilepsies are reviewed, with special reference to the ILAE classification of seizures. Kindling as a model of complex-partial seizures with secondary generalisation is treated in detail, dwelling principally on the evidence that the neurotransmitters glutamate and GABA are centrally involved in the kindling process. Kindling in the entorhinal cortex-hippocampus system and its relationship to LTP are analysed in detail. Changes in amino acid content in animal and human brain tissue following onset of the epileptic state are reviewed with special reference to glutamate and GABA. Studies of changes in the extent of basal and stimulus-evoked release of glutamate and GABA both in vivo (microdialysis) and in vitro (brain slices) are evaluated. This includes both kindling and other models of epilepsy, and microdialysis of human patients with epilepsy. Experiments which study the influence of pre-synaptic metabotropic glutamate receptors on glutamate release, and consequently on the extent of electrical kindling, are described. This pre-synaptic control of glutamate release can be studied using synaptosomes. The significance of the ability of focal intracerebrally injected glutamate and NMDA to cause (chemical) kindling and the strong sensitivity of this process to pre-treatment with NMDA receptor antagonists is analysed. Electrical and chemical kindling effects are additive, indicating the existence of mechanisms in common. They are both sensitive to NMDA antagonists and the common mechanism is probably NMDA receptor activation due to the presence of exogenous (chemical) or endogenous (electrically-released) extracellular glutamate. The participation of the NMDA receptor in the generation of the spontaneous hyperactivity which characterises the chronic epileptic state is reviewed. This includes the entry of Ca2+ to stimulate various post-synaptic phosphorylation processes, and possible modulation of NMDA receptor population size and sensitivity. The question of whether neurotransmitter glutamate is involved in initiation and/or spread of seizures is discussed.

References (185)

  • E.T. Coffey et al.

    Phosphorylation of synapsin I and MARCKS in nerve terminals is mediated by Ca2+ entry via an Aga-GI sensitive Ca2+ channel which is coupled to glutamate exocytosis

    FEBS Lett.

    (1994)
  • V. Coffin et al.

    Selective antagonism of the anticonvulsant effects of felbamate by glycine

    Eur. J. Pharmac.

    (1994)
  • G.A. Cohen et al.

    Opioid inhibition of GABA release from pre-synaptic terminals of rat hippocampal interneurones

    Neuron

    (1992)
  • M.J. Croucher et al.

    Kindling of full limbic seizures by repeated microinjections of excitatory amino acids into the rat amygdala

    Brain Res.

    (1989)
  • M.J. Croucher et al.

    NMDA receptor blockade inhibits glutamate-induced kindling of the rat amygdala

    Brain Res.

    (1990)
  • M.J. Croucher et al.

    Inhibition of the development of electrical kindling of the prepyriform cortex by daily focal injections of excitatory amino acid antagonists

    Eur. J. Pharmac.

    (1988)
  • G. Davies et al.

    Normal extracellular calcium levels block kindled seizures

    Expl Neurol.

    (1989)
  • P.R. Dodd et al.

    Release of amino acids from the maturing cobalt-induced epileptic focus

    Brain Res.

    (1976)
  • M. Dragunow

    Purinergic mechanisms in epilepsy

    Prog. Neurobiol.

    (1988)
  • M.J. During et al.

    Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain

    The Lancet

    (1993)
  • M.A. Falconer et al.

    Treatment of temporal-lobe epilepsy by temporal lobectomy: A survey of findings and results

    Lancet I

    (1955)
  • R.S. Fisher

    Animal models of the epilepsies

    Brain Res. Rev.

    (1989)
  • B.B. Fredholm et al.

    In vivo pertussis toxin treatment attenuates some but not all adenosine A1 effects in slices of the rat hippocampus

    Eur. J. Pharmac.

    (1989)
  • D.P. Frush et al.

    Evidence implicating dentate granule cells in development of entorhinal kindling

    Expl Neurol.

    (1986)
  • J.W. Geddes et al.

    Altered distribution of excitatory amino acid receptors in temporal lobe epilepsy

    Expl Neurol.

    (1990)
  • C. Geula et al.

    Long-term enhancement of K+ evoked release of l-glutamate in entorhinal kindled rats

    Brain Res.

    (1988)
  • J. Giacchino et al.

    Lateral entorhinal cortical kindling can be established without potentiation of the entorhinal-granule cell synapse

    Expl Neurol.

    (1984)
  • A.C. Hamberger et al.

    Stimulus-evoked increase in the biosynthesis of the putative neurotransmitter glutamate in the hippocampus

    Brain Res.

    (1978)
  • A.C. Hamberger et al.

    Glutamate as a CNS transmitter I: Evaluation of glucose and glutamine as precursors for the synthesis of preferentially released glutamate

    Brain Res.

    (1979)
  • A.C. Hamberger et al.

    Glutamate as a CNS transmitter II: Regulation of synthesis of the releasable pool

    Brain Res.

    (1979)
  • A.C. Hamberger et al.

    Amino acids in the neuronal microenvironment of focal human epileptic lesions

    Epilepsy Res.

    (1991)
  • P.K.P. Harvey et al.

    The inhibitory effects of sodium dipropyl acetate on the degradative enzymes of the GABA shunt

    FEBS Lett.

    (1975)
  • P.A. Jarvie et al.

    Entorhinal kindling permanently enhances Ca2+ dependent l-glutamate release in region inferior of rat hippocampus

    Brain Res.

    (1990)
  • R.S.G. Jones

    Entorhinal-hippocampal connections: A speculative view of their functions

    Trends Neurosci.

    (1993)
  • S.M. Jones et al.

    Effects of amygdaloid kindling on NMDA receptor function and regulation

    Expl Neurol.

    (1989)
  • M. Kemp et al.

    Antagonism of pre-synaptically mediated depressant responses and cyclic AMP-coupled metabotropic glutamate receptors

    Eur. J. Pharmac.

    (1994)
  • W. Loscher et al.

    Further evidence for abnormal GABAergic circuits in amygdala kindled rats

    Brain Res.

    (1987)
  • W. Loscher et al.

    Valproic acid increases GABA in CSF of epileptic children

    Lancet

    (1984)
  • E.W. Lothman et al.

    Alterations in neurotransmitter amino acids in hippocampal kindled seizures

    Epilepsy Res.

    (1987)
  • E.W. Lothman et al.

    Functional anatomy of hippocampal seizures

    Prog. Neurobiol.

    (1991)
  • E. Maru et al.

    Alteration in dendate neuronal activities associated with perforant path kindling

    Expl Neurol.

    (1987)
  • H. Matsumoto et al.

    Cortical cellular phenomena in experimental epilepsy: Interictal manifestations

    Expl Neurol.

    (1964)
  • P.J.E. Attwell et al.

    Blockade of both epileptogenesis and glutamate release by (1S,3S)-ACPD, a pre-synaptic glutamate receptor agonist

    Brain Res.

    (1995)
  • P.J.E. Attwell et al.

    Pre-synaptically active glutamate receptor agonists block glutamate release and epileptogenesis

    (1995)
  • E.M. Airaksinen et al.

    Effects of taurine treatment on epileptic patients

  • C. Ajmone-Marsan

    Acute effects of topical epileptogenic agents

  • T.L. Babb et al.

    Temporal lobe volumetric cell densities in temporal lobe epilepsy

    Epilepsia

    (1984)
  • T.L. Babb et al.

    Distribution of pyramidal cell density and hyperexcitability in the epileptic human hippocampal formation

    Epilepsia

    (1984)
  • T.L. Babb et al.

    Glutamate decarboxylase-immunoreactive neurones are preserved in human epileptic hippocampus

    J. Neurosci.

    (1989)
  • H. Benveniste et al.

    Cellular reactions to implantation of a microdialysis tube in the rat hippocampus

    Acta Neuropathol. (Berl.)

    (1987)
  • Cited by (399)

    • Aptamer based biosensor platforms for neurotransmitters analysis

      2023, TrAC - Trends in Analytical Chemistry
    View all citing articles on Scopus

    Telephone: 0171 594 5246/5230/5229; Fax: 0171 225 0960.

    View full text