The Importance of Glutamate Receptors in Brain Ischemia
The chapter reviews some aspects of the hypothesis that excitatory amino acids under pathological conditions stimulate neuronal glutamate receptors and cause the cells to die. A number of neurological conditions have been related to this excitotoxic hypothesis, but we limit the description to conditions in which acute and substantial changes are at hand, such as brain ischemia. Here excitatory amino acids are released from brain cells and major changes of the interstitial ion composition are observed. In the following a description of the chain of events in the central nervous system leading to cell necrosis will be given. We shall concentrate on the events in global ischemia because these are the conditions that have been most extensively described. First, some details of the glutamate transmitter system are given.
KeywordsGlutamate Receptor Brain Ischemia AMPA Receptor Excitatory Amino Acid NMDA Antagonist
Unable to display preview. Download preview PDF.
- Andine, P., Jacobson, I., and Hagberg, H. (1992) Enhanced calcium uptake by CA1 pyramidal cell dendrites in the postischemic phase despite subnormal evoked field potentials: Excitatory amino acid receptor dependency and relationship to neuronal damage. J. Cereb. Blood Flow Metab. 12: 773–783.PubMedCrossRefGoogle Scholar
- Buchan, A., and Pulsinelli, W.A. (1990)Hypothermia but not the N-methyl-D-asparte antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischemia. J. Neurosci. 10 (1): 311–316.Google Scholar
- Pulsinelli, W., Dimagl, U, Jacewicz, M., and Buchan, A. (1992) Antagonists of excitatory amino acid neurotransmitters: A comparison of their effects on global versus focal ischemia. In: Drug Research Related to Neuroactive Amino Acids (Schousboe, A., Diemer, N., Kofok, H., eds.), Munksgaard, Copenhagen, pp. 225–238.Google Scholar
- Sheardown, M.J., Hansen, A.J., Eskesen, K., Suzdak, P., Diemer, N.H., and Honore, T. (1990a)Blockade of AMPA receptors in the CA1 region of the hippocampus prevents ischemia induced cell death. In: Pharmacology of Cerebral Ischemia (Krieglstein, J., Oberpichler, H., eds), Stuttgart, Wissenschaftliche Verlagsgesellschaft mbH, pp. 245–253.Google Scholar
- Smith, S.E., and Meldrum, B.S. (1993) Cerebroprotective effect of anon-methyl-D-aspartate antagonist, NBQX, after focal ischemia in the rat. Functional Neurol., in press.Google Scholar
- Trombley, P.Q., and Westbrook, G.L. (1992) L-AP4 inhibits calcium currents and synaptic transmission via a G-protein-coupled glutamate receptor. J. Neurosci. 12 (6): 2043–2050.Google Scholar
- Wieloch, T., Lindvall, O., Blomqvist, P. and Gage, F.H. (1984) Evidence for amelioration of ischemic neuronal damage in the hippocampal formation by lesions of the perforant path. Neurol. Res. 7: 24–26.Google Scholar