Excitotoxity and the NMDA receptor

Rothman, Steven M.; Olney, John W.

doi:10.1016/0166-2236(87)90177-9

Cited by 1,136 publications

(469 citation statements)

References 32 publications

Supporting

Mentioning

457

Contrasting

Unclassified

Order By: Relevance

“…The results demonstrate ischemia-induced in creases in glutamate level of a similar magnitude described by us previously in the striatum (Globus et al, 1988a). There is sufficient evidence implicat ing the N-methyl-o-aspartate (NMDA) receptor in the deleterious effect of glutamate (Gill et aI., 1987;Rothman and Olney, 1987). NE has been shown to decrease synaptic inhibition and to potentiate NMDA-linked events in the hippocampus and spi nal cord (Madison and Nicoll, 1988;Stanton et aI., 1987;Wohlberg et al, 1987).…”

Section: Resultsmentioning

confidence: 99%

Direct Evidence for Acute and Massive Norepinephrine Release in the Hippocampus during Transient Ischemia

Globus

Busto

Dietrich

et al. 1989

J Cereb Blood Flow Metab

165

View full text Add to dashboard Cite

Summary: Recent studies suggest the norepinephrine (NE) may play a regulatory role in neuronal cell death in the hippocampus after transient ischemia. However, isch emia-induced changes in extracellular NE release have not been demonstrated. In the present study, we utilized the microdialysis technique to measure extracellular NE levels in the hippocampus before, during, and after 20 min of global ischemia induced by two-vessel occlusion com bined with systemic hypotension in the rat. Stable basal concentrations of extracellular NE were detected in three consecutive samples collected prior to ischemia (1.86 ± 1.21 pmol/ml of perfusate mean ± SEM). During isch-

show abstract

Section: Resultsmentioning

confidence: 99%

Direct Evidence for Acute and Massive Norepinephrine Release in the Hippocampus during Transient Ischemia

Globus

Busto

Dietrich

et al. 1989

J Cereb Blood Flow Metab

165

View full text Add to dashboard Cite

show abstract

“…The rationale of the study was based on the premise that damage of neu rons in the penumbra of a focal ischemic infarction may result from liberation, by ischemia, of L-GlU (Olney and Sharpe, 1969;Benveniste et al, 1984;Choi, 1990). L-Glu, acting through the NMDA sub type of L-Glu receptor (Rothman and Olney, 1987;Siesjo and Bengtsson, 1989), will, by increasing in tracellular Ca2 +, activate the constitutive form of (MCA occlusion only; n = 6), rilmenidine-treated (RIL; 0.75 mg/kg; n = 4), and N-w-nitro-L-arginine-treated (NNA; 2.4 mg/kg/h for 1 h; n = 6) animals. This figure illustrates the superimposed distribution of all animals in each group at representative levels (13.7, 11.7, 9.7, 5.7, 3.7, and 1.7 mm from interaural line).…”

Section: Discussionmentioning

confidence: 99%

“…The argument derives from several observa tions: (a) First, cerebral ischemia markedly in creases the release of L-Glu (Benveniste et aI., 1984;Hagberg et aI., 1985). (b) Second, the neuro toxicity of L-Glu results from stimulation of gluta mate receptors of the N-methyl-D-aspartate (NMDA) subclass since treatment with NMDA an tagonists in vitro reduces the cytotoxicity of L-Glu (Rothman and Olney, 1987) and in vivo reduces the magnitude of cerebral damage produced by isch emia (Duverger et aI., 1987;Park et ai., 1988). (c) Third, activation of the NMDA receptor opens Ca2+ channels, increases the concentration of the intracellular Ca2+ (Siesj6 and Bengtsson, 1989), and activates NOS, thereby generating more NO (Knowles et aI., 1989).…”

mentioning

confidence: 99%

Inhibition of Nitric Oxide Synthesis Increases Focal Ischemic Infarction in Rat

Yamamoto

Golanov

Berger

et al. 1992

J Cereb Blood Flow Metab

229

View full text Add to dashboard Cite

Summary:We investigated whether inhibition of nitric oxide (NO) biosynthesis with N-w-nitro-L-arginine (NNA), a competitive inhibitor of NO synthase (NOS), would modify the volume of the focal ischemic infarction produced by occlusion of the middle cerebral artery (MCA) in spontaneously hypertensive rats. NNA was in fused for 1 h (2.4 mg/kg/h) immediately following occlu sion of the MCA. NNA increased lesion volume 24 h later by 32% over controls (150.8 ± 16.6 to 199.2 ± 17.4 mm3; p < 0.001, n = 6). This effect was antagonized by co infusion of L-but not D-arginine. The antihypertensive rilmenidine (0.75 mg/kg) reduced the lesion by 27% (p < 0.05, n = 4). Changes in lesion size were confined to the penumbra. NNA increased arterial pressure (AP) (118 ± There is increasing evidence that the endogenous vasodilator nitric oxide (NO) is synthesized in the brain from the amino acid L-arginine (L-Arg) by the enzyme NO synthase (NOS). The principal form of NOS expressed in brain appears to correspond to the constitutive form of the enzyme (Bredt and Sny der, 1990; Hope et ai., 1991)

show abstract

“…The increase in CSF glutamate and aspartate may also cause cell swelling. Increased extracellular concentrations of glutamate and aspartate, both excitatory neurotransmitters which can bind the N-Methyl-D-Aspartate receptor (NMDA), may result in NMDA-mediated glutamate neurotoxicity including cell swelling (47,48). Since NMDA receptors have been demonstrated on neurons (49), astrocytes (50) and on brain capillaries (51), this phenomenon could contribute to the increase in ICP in AI-PCS rats.…”

Section: Ad 3 Increased Intracranial Pressure and Higher Brain Watermentioning

confidence: 99%

The effects of ammonia and portal-systemic shunting on brain metabolism, neurotransmission and intracranial hypertension in hyperammonaemia-induced encephalopathy

Vogels¹,

Steynen²,

Maas³

et al. 1997

Journal of Hepatology

View full text Add to dashboard Cite

The effects of ammonia and portal-systemic shunting on brain metabolims, neurotransmission and intracranial hypertension in hyperammonaemia-induced encephalopathy Vogels, B.A.P.M.; van Steynen, B.; Maas, M.A.W.; Jorning, G.G.A.; Chamuleau, R.A.F.M. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Background/Aims: The pathogenetic factors contributing to encephalopathy in portacaval shunted rats with hyperammonaemia were studied. Methods: Hyperammonaemia was induced by ammonium-acetate infusions in portacaval shunted rats (2.8 mmol-kg bw-'*h-l; AI-portacaval shunted rats) and in sham-portacaval shunted rats (6.5 mmol-kg bw-l-h-'; AI-NORM rats). Severity of encephalopathy was quantified by clinical grading and EEG spectral analysis. Changes in brain metabolites were assessed by amino acid analysis of brain cortex homogenates, whereas changes in amino acids with neurotransmitter activity were assessed in cerebrospinal fluid; brain water content was measured by subtracting dry from wet brain weights and intracranial pressure was measured by a pressure transducer connected to a cisterna magna cannula. Results:Although similar increased blood and brain ammonia concentrations were obtained in both experimental groups, only AI-portacaval shunted rats developed encephalopathy, associated with a significant increase in intracranial pressure. HEPATIC encephalopathy (HE) is generally regarded to be a reversible neuropsychiatric syndrome in patients with liver failure. It is often associated with portal-systemic shunting of blood, which may occur spontaneously or be surgically induced. Although the pathogenesis of HE is probably multi- Conclusions: These results indicate that hyperammonaemia alone does not induce encephalopathy, whereas portal-systemic shunting adds an essential contribution to the pathogenesis of encephalopathy. It is hypothesised that the larger increase in brain glutamine in AI-portacaval shunted rats than in AI-NORM rats is responsible for increased brain concentrations of aromatic amino acids, for cell swelling and for extracellular release of glutamate and aspartate. This might promote encephalopathy. If cell swelling is not restricted, intracranial hypertension will develop

show abstract

Excitotoxity and the NMDA receptor

Cited by 1,136 publications

References 32 publications

Direct Evidence for Acute and Massive Norepinephrine Release in the Hippocampus during Transient Ischemia

Direct Evidence for Acute and Massive Norepinephrine Release in the Hippocampus during Transient Ischemia

Inhibition of Nitric Oxide Synthesis Increases Focal Ischemic Infarction in Rat

The effects of ammonia and portal-systemic shunting on brain metabolism, neurotransmission and intracranial hypertension in hyperammonaemia-induced encephalopathy

Contact Info

Product

Resources

About