The brain glutamate system in liver failure

Vaquero, Javier; Butterworth, Roger F.

doi:10.1111/j.1471-4159.2006.03918.x

Cited by 56 publications

(50 citation statements)

References 92 publications

(155 reference statements)

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“…⁄ p <0.05, (ANOVA repeated measures). explain the well-described increase in brain extracellular glutamate observed in multiple models of acute and chronic liver failure [29]. The study was not specifically designed to assess the relationship between the activation of NMDA receptors and extracellular glutamate.…”

Section: Discussionmentioning

confidence: 99%

Ornithine phenylacetate prevents disturbances of motor-evoked potentials induced by intestinal blood in rats with portacaval anastomosis

Oria

Romero-Giménez

Arranz

et al. 2012

Journal of Hepatology

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Section: Discussionmentioning

confidence: 99%

Ornithine phenylacetate prevents disturbances of motor-evoked potentials induced by intestinal blood in rats with portacaval anastomosis

Oria

Romero-Giménez

Arranz

et al. 2012

Journal of Hepatology

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“…Therefore, this evidence suggests that cytokines mediated inflammatory response plays a role in the pathogenesis and progression of disease in Krabbe patients and twi mouse. It is clear that the combined effects of psychosine and cytokines on hepatocytes and peroxisomal function compromise the homeostasis of liver and possibly of other organs, as indicate by the many reports that suggest that liver function plays an important role in brain homeostasis and vice versa [56][57][58].…”

Section: Discussionmentioning

confidence: 99%

Psychosine-induced alterations in peroxisomes of twitcher mouse liver

Contreras

Haq

Uto

et al. 2008

Archives of Biochemistry and Biophysics

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Krabbe's disease is a neuroinflammatory disorder in which galactosylsphingosine (psychosine) accumulates in nervous tissue. To gain insight into whether the psychosine-induced effects in nervous tissue extend to peripheral organs, we investigated the expression of cytokines and their effects on peroxisomal structure/function in twitcher mouse liver (animal model of Krabbe disease). Immunofluorescence analysis demonstrated TNF-α and IL-6 expression, which was confirmed by mRNAs quantitation. Despite the presence of TNF-α, lipidomic analysis did not indicate a significant decrease in sphingomyelin or an increase in ceramide fractions. Ultrastructural analysis of catalasedependent staining of liver sections showed reduced reactivity without significant changes in peroxisomal contents. This observation was confirmed by assaying catalase activity and quantitation of its mRNA, both of which were found significantly decreased in twitcher mouse liver. Western blot analysis demonstrated a generalized reduction of peroxisomal matrix and membrane proteins. These observations indicate that twitcher mouse pathobiology extends to the liver, where the induction of TNF-α and IL-6 compromise peroxisomal structure and function.

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“…Such swelling can lead to edema, increased intracranial pressure, brain herniation and death (Ganz et al, 1989;Vaquero and Butterworth, 2006). The absence of any significant MSO-induced increase in survival time during HEA for rainbow trout and goldfish suggests that glutamine accumulation was not likely toxic to these fish during the 48h experiment.…”

Section: P Wilkie and Othersmentioning

confidence: 99%

The relationship between NMDA receptor function and the high ammonia tolerance of anoxia-tolerant goldfish

Wilkie

Pamenter

Duquette

et al. 2011

Journal of Experimental Biology

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SUMMARY Acute ammonia toxicity in vertebrates is thought to be characterized by a cascade of deleterious events resembling those associated with anoxic/ischemic injury in the central nervous system. A key event is the over-stimulation of neuronal N-methyl-D-aspartate (NMDA) receptors, which leads to excitotoxic cell death. The similarity between the responses to acute ammonia toxicity and anoxia suggests that anoxia-tolerant animals such as the goldfish (Carassius auratus Linnaeus) may also be ammonia tolerant. To test this hypothesis, the responses of goldfish were compared with those of the anoxia-sensitive rainbow trout (Oncorhynchus mykiss Walbaum) during exposure to high external ammonia (HEA). Acute toxicity tests revealed that goldfish are ammonia tolerant, with 96 h median lethal concentration (LC50) values of 199 μmol l–1 and 4132 μmol l–1 for NH3 and total ammonia ([TAmm]=[NH3]+[NH4+]), respectively. These values were ∼5–6 times greater than corresponding NH3 and TAmm LC50 values measured in rainbow trout. Further, the goldfish readily coped with chronic exposure to NH4Cl (3–5 mmol l–1) for 5 days, despite 6-fold increases in plasma [T] to ∼1300 μmol l–1 and 3-fold increases in brain [TAmm] to 6700 μmol l–1. Muscle [TAmm] increased by almost 8-fold from ∼900 μmol kg–1 wet mass (WM) to greater than 7000 μmol kg–1 WM by 48 h, and stabilized. Although urea excretion rates (JUrea) increased by 2–3-fold during HEA, the increases were insufficient to offset the inhibition of ammonia excretion that occurred, and increases in urea were not observed in the brain or muscle. There was a marked increase in brain glutamine concentration at HEA, from ∼3000 μmol kg–1 WM to 15,000 μmol kg–1 WM after 48 h, which is consistent with the hypothesis that glutamine production is associated with ammonia detoxification. Injection of the NMDA receptor antagonists MK801 (0.5–8 mg kg–1) or ethanol (1–8 mg kg–1) increased trout survival time by 1.5–2.0-fold during exposure to 2 mmol l–1 ammonia, suggesting that excitotoxic cell death contributes to ammonia toxicity in this species. In contrast, similar doses of MK801 or ethanol had no effect on ammonia-challenged (8–9.5 mmol l–1TAmm) goldfish survival times, suggesting that greater resistance to excitotoxic cell death contributes to the high ammonia-tolerance of the goldfish. Whole-cell recordings measured in isolated brain slices of goldfish telencephalon during in vitro exposure to 5 mmol l–1 or 10 mmol l–1TAmm reversibly potentiated NMDA receptor currents. This observation suggested that goldfish neurons may not be completely resistant to ammonia-induced excitotoxicity. Subsequent western blot and densitometric analyses revealed that NMDA receptor NR1 subunit abundance was 40–60% lower in goldfish exposed to 3–5 mmol l–1TAmm for 5 days, which was followed by a restoration of NR1 subunit abundance after 3 days recovery in ammonia-free water. We conclude that the goldfish brain may be protected from excitotoxicity by downregulating the abundance of functional NMDA receptors during periods when it experiences increased internal ammonia.

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The brain glutamate system in liver failure

Cited by 56 publications

References 92 publications

Ornithine phenylacetate prevents disturbances of motor-evoked potentials induced by intestinal blood in rats with portacaval anastomosis

Ornithine phenylacetate prevents disturbances of motor-evoked potentials induced by intestinal blood in rats with portacaval anastomosis

Psychosine-induced alterations in peroxisomes of twitcher mouse liver

The relationship between NMDA receptor function and the high ammonia tolerance of anoxia-tolerant goldfish

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