Ischemia as an excitotoxic lesion: protection against hippocampal nerve cell loss by denervation.

N H Diemer; Flemming Fryd Johansen; H Benveniste; T Bruhn; M Berg; E Valente; M B Jørgensen

Ischemia as an excitotoxic lesion: protection against hippocampal nerve cell loss by denervation.

N H Diemer, Flemming Fryd Johansen, H Benveniste, T Bruhn, M Berg, E Valente, M B Jørgensen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

23 Citationer (Scopus)

Abstract

Udgivelsesdato: 1993-null

Originalsprog	Engelsk
Bogserie	Acta Neurochirurgica - Supplements only
Vol/bind	57
Sider (fra-til)	94-101
Antal sider	7
ISSN	0065-1419
Status	Udgivet - 1993
Udgivet eksternt	Ja

Bibliografisk note

Keywords: Amino Acids; Animals; Blood Glucose; Brain Damage, Chronic; Brain Ischemia; Cell Death; Hippocampus; Nerve Degeneration; Neural Pathways; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission

Citationsformater

@article{8f5a8bb05e0b11dd8d9f000ea68e967b,

title = "Ischemia as an excitotoxic lesion: protection against hippocampal nerve cell loss by denervation.",

abstract = "There are several indications for an involvement of neuroexcitatory mechanisms in ischemic neuron damage. Since we forwarded the hypothesis in 1982 that the transmitter glutamate is playing a key role, several lines of evidence have substantiated this: there is a pronounced transmitter release induced by ischemia and there is uptake of Ca++ via NMDA-operated calcium channels. Under certain circumstances postischemic neuron death can be impaired by administration of either NMDA-antagonists or calcium blockers. Further proof for the induction of harmful excitatory mechanisms by ischemia has been obtained by preischemic denervation of the vulnerable nerve cells. After transient cerebral ischemia in rats or gerbils, there are signs of irreversible damage (eosinophilia) of neurons in the dentate hilus (somatostatin-positive cells) after 2-3 hours and of hippocampal pyramidal neurons after 2-3 days (delayed neuron death). In the first case, removal of the (main) input to hilus cells by degranulation (colchicine selectively eliminates granule cells) protects these. In the case of pyramidal neurons removal of Schaffer collaterals/commisurals or input from the entorhinal cortex have a protective effect. Recently, we have measured glutamate and calcium in CA1 of denervated rats during 10 min of ischemia, and it turns out that there is almost no extracellular glutamate release or lowering of calcium in contrast to ischemic animals with intact innervation. Also in the postischemic period there are indications of a continuation of the damaging processes induced by ischemia. Besides the well known postischemic hypoperfusion, a prolonged release of glutamate has been reported, as well as burst firing in some models.(ABSTRACT TRUNCATED AT 250 WORDS)",

author = "Diemer, {N H} and Johansen, {Flemming Fryd} and H Benveniste and T Bruhn and M Berg and E Valente and J{\o}rgensen, {M B}",

note = "Keywords: Amino Acids; Animals; Blood Glucose; Brain Damage, Chronic; Brain Ischemia; Cell Death; Hippocampus; Nerve Degeneration; Neural Pathways; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission",

year = "1993",

language = "English",

volume = "57",

pages = "94--101",

journal = "Acta Neurochirurgica - Supplements only",

issn = "0065-1419",

publisher = "Springer Wien",

}

TY - JOUR

T1 - Ischemia as an excitotoxic lesion: protection against hippocampal nerve cell loss by denervation.

AU - Diemer, N H

AU - Johansen, Flemming Fryd

AU - Benveniste, H

AU - Bruhn, T

AU - Berg, M

AU - Valente, E

AU - Jørgensen, M B

N1 - Keywords: Amino Acids; Animals; Blood Glucose; Brain Damage, Chronic; Brain Ischemia; Cell Death; Hippocampus; Nerve Degeneration; Neural Pathways; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission

PY - 1993

Y1 - 1993

N2 - There are several indications for an involvement of neuroexcitatory mechanisms in ischemic neuron damage. Since we forwarded the hypothesis in 1982 that the transmitter glutamate is playing a key role, several lines of evidence have substantiated this: there is a pronounced transmitter release induced by ischemia and there is uptake of Ca++ via NMDA-operated calcium channels. Under certain circumstances postischemic neuron death can be impaired by administration of either NMDA-antagonists or calcium blockers. Further proof for the induction of harmful excitatory mechanisms by ischemia has been obtained by preischemic denervation of the vulnerable nerve cells. After transient cerebral ischemia in rats or gerbils, there are signs of irreversible damage (eosinophilia) of neurons in the dentate hilus (somatostatin-positive cells) after 2-3 hours and of hippocampal pyramidal neurons after 2-3 days (delayed neuron death). In the first case, removal of the (main) input to hilus cells by degranulation (colchicine selectively eliminates granule cells) protects these. In the case of pyramidal neurons removal of Schaffer collaterals/commisurals or input from the entorhinal cortex have a protective effect. Recently, we have measured glutamate and calcium in CA1 of denervated rats during 10 min of ischemia, and it turns out that there is almost no extracellular glutamate release or lowering of calcium in contrast to ischemic animals with intact innervation. Also in the postischemic period there are indications of a continuation of the damaging processes induced by ischemia. Besides the well known postischemic hypoperfusion, a prolonged release of glutamate has been reported, as well as burst firing in some models.(ABSTRACT TRUNCATED AT 250 WORDS)

AB - There are several indications for an involvement of neuroexcitatory mechanisms in ischemic neuron damage. Since we forwarded the hypothesis in 1982 that the transmitter glutamate is playing a key role, several lines of evidence have substantiated this: there is a pronounced transmitter release induced by ischemia and there is uptake of Ca++ via NMDA-operated calcium channels. Under certain circumstances postischemic neuron death can be impaired by administration of either NMDA-antagonists or calcium blockers. Further proof for the induction of harmful excitatory mechanisms by ischemia has been obtained by preischemic denervation of the vulnerable nerve cells. After transient cerebral ischemia in rats or gerbils, there are signs of irreversible damage (eosinophilia) of neurons in the dentate hilus (somatostatin-positive cells) after 2-3 hours and of hippocampal pyramidal neurons after 2-3 days (delayed neuron death). In the first case, removal of the (main) input to hilus cells by degranulation (colchicine selectively eliminates granule cells) protects these. In the case of pyramidal neurons removal of Schaffer collaterals/commisurals or input from the entorhinal cortex have a protective effect. Recently, we have measured glutamate and calcium in CA1 of denervated rats during 10 min of ischemia, and it turns out that there is almost no extracellular glutamate release or lowering of calcium in contrast to ischemic animals with intact innervation. Also in the postischemic period there are indications of a continuation of the damaging processes induced by ischemia. Besides the well known postischemic hypoperfusion, a prolonged release of glutamate has been reported, as well as burst firing in some models.(ABSTRACT TRUNCATED AT 250 WORDS)

M3 - Journal article

C2 - 8380675

SN - 0065-1419

VL - 57

SP - 94

EP - 101

JO - Acta Neurochirurgica - Supplements only

JF - Acta Neurochirurgica - Supplements only

ER -