Glutamate: A Role in Both Cerebral Ischaemia and Dementia of the Alzheimer Type
Glutamate has two major roles in the CNS under normal circumstances. As well as being involved in intermediary metabolism, this amino acid is the major excitatory neurotransmitter in the cerebral cortex, mediating both corticocortical and corticofugal transmission. In addition to these physiological roles for glutamate in the normal brain, its neurotoxic actions have been known for many years. Glutamate neurotoxicity has been implicated in the pathophysiology of a variety of neurodegenerative conditions, including cerebral ischaemia, dementia of the Alzheimer type (DAT), Huntington’s chorea and epilepsy. The evidence supporting glutamate-induced neuronal death in the last three conditions is at present somewhat circumstantial. However, there is convincing experimental evidence for glutamate neurotoxicity in cerebral ischaemia. Extracellular concentrations of glutamate are markedly elevated in cerebral ischaemia [2,5,14, 16], and specific glutamate antagonists have neuroprotective effects [34,35,38].
KeywordsNMDA Receptor Cerebral Ischaemia Middle Cerebral Artery Occlusion Focal Cerebral Ischaemia Cereb Blood Flow
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- 1.Aebischer B, Frey P, Haerter H-P, Herding PL, Mueller W (1989) 115 Synthesis and NMDA antagonist properties of the enantiomers of 4-(3-phosphonopropyl)piperazine-2-carboxylic acid (CPP) and of the unsaturated analogue (E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CPP-ene). Helv Chim Acta 72:1043–1051CrossRefGoogle Scholar
- 5.Butcher SP, Bullock R, Graham DI, McCulloch J (1990) Release of neuroexcitatory amino acids from rat brain following middle cerebral artery occlusion. Br J Pharmacol 99:277PGoogle Scholar
- 9.Choi DW (1990) Methods for antagonizing glutamate neurotoxicity. Cerebro Brain Metab Rev 2:105–147Google Scholar
- 11.Fonnum F, Soreide A, Kvale I, Walker J, Walaas I (1981) Glutamate in corticofugal fibres, In: Di Chiara G, Gessa GL (eds) Glutamate as a neurotransmitter. Advances in biochemical psychopharmacology, vol 27. Raven, New York, pp 29–41Google Scholar
- 15.Gotoh F, Fukuuchi Y, Amaon T, Tanaka K, Kawamura J, Yamawaki T, Obara K, Ito N, Muramatsu K, Takahashi K (1989) Effects of tissue plasminogen activator on microcirculation and size of infarction following MCA occlusion in cat. J Cereb Blood Flow Metab 9:9Google Scholar
- 20.Kemp JA, Foster AC, Wong EHF (1987) Non-competitive antagonists of excitatory amino acid receptors. TINS 10:294–298Google Scholar
- 26.MacKenzie ET, Gotti B, Nowicki J-P and Young AR (1984) Adrenergic blockers as cerebral antiischaemic agents, In: MacKenzie ET, Seylaz J, Bès A (eds) Neurotransmitters and the cerebral circulation, vol 2. Raven, New York, pp 219–243Google Scholar
- 30.Meldrum B (1990) Protection against ischaemic neuronal damage by drugs acting on excitatory neurotransmission. Cerebro Brain Metab Rev 2:27–57Google Scholar
- 37.Shank RP, Campbell G (1983) Glutamate, In: Lajtha A (ed) Handbook of neurochemistry, vol 3. Plenum, New York, pp 381–404Google Scholar
- 39.Sugiyama H, Ito H, Hirono C (1987) A new type of glutamate receptor linked to inositol phospholipid metabolism. Nature 15:597–617Google Scholar
- 40.Watkins JC, Olverman HJ (1987) Agonists and antagonists for excitatory amino acid receptors. TINS 10:265–272Google Scholar