Ammonia-induced astrocyte swelling in primary culture

Norenberg, Michael D.; Baker, L.; Norenberg, Luz Oliva B.; Blicharska, J.; Bruce-Gregorios, Jocelyn; Neary, Joseph T.

doi:10.1007/bf00965694

Cited by 182 publications

(111 citation statements)

References 23 publications

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“…Increased brain water content has been described in both normal (Takahashi et al, 1991) and in portacaval shunted (Blei et al, 1994) rats infused with ammonia as well as in rats with liver devascularization (Rose et al, 1999). Similar results have been described in vitro following the exposure of cultured astrocytes to ammonia (Norenberg et al, 1991). Furthermore, prevention of brain edema in rats with ALF has been shown with ammonia-lowering strategies (Cordoba et al, 1999;Rose et al, 1999Rose et al, , 2000.…”

Section: Calcium-independent Glutamate Releasesupporting

confidence: 62%

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Rose

2002

Metabolic Brain Disease

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Glutamatergic dysfunction has been suggested to play an important role in the pathogenesis of hepatic encephalopathy (HE) in acute liver failure (ALF). Increased extracellular brain glutamate concentrations have consistently been described in different experimental animal models of ALF and in patients with increased intracranial pressure due to ALF. High brain ammonia levels remain the leading candidate in the pathogenesis of HE in ALF and studies have demonstrated a correlation between ammonia and increased concentrations of extracellular brain glutamate both clinically and in experimental animal models of ALF. Inhibition of glutamate uptake or increased glutamate release from neurons and/or astrocytes could cause an increase in extracellular glutamate. This review analyses the effect of ammonia on glutamate release from (and uptake into) both neurons and astrocytes and how these pathophysiological mechanisms may be involved in the pathogenesis of HE in ALF.

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Section: Calcium-independent Glutamate Releasesupporting

confidence: 62%

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Rose

2002

Metabolic Brain Disease

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“…In addition, marked intracellular swelling of the perivascular astroglial foot processes was present in patients who died in ALF-induced coma (Kato et al, 1992). In vitro experiments have also reported astrocyte swelling, by assessing the intracellular space using [ 3 H]-3-O-methylglucose ( Norenberg et al, 1991), or by microscopic measurements of cellular volume ( Hirrlinger et al, 2008), following the addition of pathogenic factors associated with HE. In CLD, astrocytes present a characteristic morphology, known as Alzheimer type II astrocytosis: large, swollen cells with enlarged swollen nuclei and cytoplasm, margination of chromatin, mitochondrial and rough endoplasmic reticulum proliferation and accumulation of glycogen ( Norenberg, 1977).…”

Section: Astrocyte Swelling and Brain Edema In Liver Disease/failurementioning

confidence: 99%

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

Bosoi

Rose

2013

Neurochemistry International

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Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that typically develops as a result of acute liver failure or chronic liver disease. Brain edema is a common feature associated with HE. In acute liver failure, brain edema contributes to an increase in intracranial pressure, which can fatally lead to brain stem herniation. In chronic liver disease, intracranial hypertension is rarely observed, even though brain edema may be present. This discrepancy in the development of intracranial hypertension in acute liver failure versus chronic liver disease suggests that brain edema plays a different role in relation to the onset of HE. Furthermore, the pathophysiological mechanisms involved in the development of brain edema in acute liver failure and chronic liver disease are dissimilar. This review explores the types of brain edema, the cells, and pathogenic factors involved in its development, while emphasizing the differences in acute liver failure versus chronic liver disease. The implications of brain edema developing as a neuropathological consequence of HE, or as a cause of HE, are also discussed. HighlightsBrain edema is a common feature in ALF and CLD. HE is inconsistently associated with the presence of brain edema. Fibrous and protoplasmic astrocytes are differentially implicated in the pathogenesis of HE. The pathogenesis of HE is multifactorial causing an array of neurological symptoms.

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“…In ALF, brain ammonia may reach millimolar concentrations, 7 and exposure of various in vitro brain preparations to millimolar concentrations of ammonia results in significant cell swelling. 8,9 Hyperammonemia is a feature of Reye' s Syndrome 10 and congenital urea cycle enzymopathies, 11 conditions in which cerebral edema is also consistently observed.Previous studies showed that hypothermia extended the survival time and prevented the development of brain edema in rats with ALF. 12 Furthermore, mild hypothermia (33°C-35°C) has been shown to be neuroprotective in experimental models of traumatic 13 and ischemic brain injury.…”

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confidence: 99%

Mild hypothermia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure

et al. 2000

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Mild hypothermia is effective in the prevention of brain edema associated with cerebral ischemia and traumatic brain injury. Brain edema is also a serious complication of acute liver failure (ALF). To assess the effectiveness of hypothermia in ALF, groups of rats were subjected to hepatic devascularization (portacaval anastomosis, followed 48 hours later by hepatic artery ligation), and body temperatures were maintained at either 35ЊC (hypothermic) or 37ЊC (normothermic). A major cause of death in patients with acute liver failure (ALF) is brain herniation resulting from raised intracranial pressure caused by a progressive increase in brain water content. 1 It has been estimated that up to 40% of patients with ALF die while on the waiting list for liver transplantation, 2 in whom, in almost all cases, death results from brain herniation. Despite several decades of investigation, the pathophysiological mechanisms responsible for the central nervous system consequences of ALF have not been fully elucidated. However, ammonia remains a prime candidate. Hyperammonemia is a consistent finding in experimental animal models of ALF resulting from hepatectomy, 3 hepatic devascularization, 4,5 or toxic liver injury 6 , and, in these cases, brain edema is invariably observed. In ALF, brain ammonia may reach millimolar concentrations, 7 and exposure of various in vitro brain preparations to millimolar concentrations of ammonia results in significant cell swelling. 8,9 Hyperammonemia is a feature of Reye' s Syndrome 10 and congenital urea cycle enzymopathies, 11 conditions in which cerebral edema is also consistently observed.Previous studies showed that hypothermia extended the survival time and prevented the development of brain edema in rats with ALF. 12 Furthermore, mild hypothermia (33°C-35°C) has been shown to be neuroprotective in experimental models of traumatic 13 and ischemic brain injury. 14 In the case of the latter, it was suggested that the beneficial effects of hypothermia were the result of inhibition of the release of neurotransmitters, rather than of an effect on cerebral energy metabolism. 15 The goals of the present investigation, therefore, were to study the effect of hypothermia on the development of hepatic encephalopathy and brain edema in relation to blood and cerebrospinal fluid (CSF) ammonia levels, and to extracellular glutamate and glutamine concentrations in rats with ALF caused by hepatic devascularization. MATERIALS AND METHODSO-phthaldialaldehyde reagent solution, 2-mercaptoethanol, Trisacetate, Ringer' s solution constituents, and amino acid standards were purchased from Sigma Chemical Co. (St. Louis, MO). Sodium phosphate (monobasic), methanol (high-performance liquid chromatography [HPLC]-grade), and tetrahydrofuran (HPLC-grade) were obtained from Anachemia (Montreal, Quebec, Canada). Doubledistilled deionized water was used for preparation of standard amino acid solutions and buffers. The mobile phase used for HPLC was filtered through 0.45-mm-pore-size membrane filters (Millipore Corp., B...

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Ammonia-induced astrocyte swelling in primary culture

Cited by 182 publications

References 23 publications

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Brain edema in acute liver failure and chronic liver disease: Similarities and differences

Mild hypothermia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure

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