Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema

Eefsen, Martin; Jelnes, Peter; Schmidt, Lars E.; Vainer, Ben; Bisgaard, Hanne Cathrine; Larsen, Fin Stolze

doi:10.1007/s11011-010-9213-y

Cited by 37 publications

(37 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An increase of Aqp-4 expression has been found in ammoniainduced swelling of cultured astrocytes (Rama Rao et al, 2003). Furthermore, an increase in expression of Aqp-4 in the brain, in association with brain edema, has been demonstrated in both ALF mice (Eefsen et al, 2010) and cirrhotic rats (Wright et al, 2010). However, on the contrary, the presence of brain edema was not related with an increase in brain Aqp-4 in either galactosamine treated or chronic hyperammonemic (induced by hyperammonemic diet) rats (Wright et al, 2010).…”

Section: Water Channelsmentioning

confidence: 98%

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

Bosoi

Rose

2013

Neurochemistry International

View full text Add to dashboard Cite

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.

show abstract

Section: Water Channelsmentioning

confidence: 98%

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

Bosoi

Rose

2013

Neurochemistry International

View full text Add to dashboard Cite

show abstract

“…Recent studies of the water channel Aqp4 indicate that Aqp4 has a role in the pathogenesis of brain edema in ALF models, although the up-regulation seems to be posttranslational. 17,24 We found that hypermagnesemia did not affect the messenger RNA or protein expression of Aqp4. This observation is in concordance with a study that found that hypermagnesemia did not affect cortical Aqp4 protein expression in a model of brain edema involving hypertensive pregnant rats, 25 but rather is in contrast to a study that found that hypermagnesemia gave a restoration of cerebral Aqp4 immunoreactivity after traumatic brain injury.…”

Section: Discussionmentioning

confidence: 79%

“…13 Magnesium sulfate may act as a neuroprotector by reducing the extracellular release of the excitatory neurotransmitter glutamate, down-regulating the expression of the water channel Aquaporin-4 (Aqp4), blocking induction of mitochondrial permeability transition, and attenuating generation of free radicals-all pathogenic mechanisms also thought to be involved in the cerebral complications of ALF. [16][17][18] The use of hypermagnesemia as a neuroprotectant in ALF has not been studied. Therefore, we decided to evaluate the effect of hypermagnesemia, achieved by administration of MgSO 4 on ICP and CBF with three different dosing regimens.…”

mentioning

confidence: 99%

Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia

et al. 2011

Self Cite

View full text Add to dashboard Cite

Intravenous infusion of magnesium sulfate prevents seizures in patients with eclampsia and brain edema after traumatic brain injury. Neuroprotection is achieved by controlling cerebral blood flow (CBF), intracranial pressure, neuronal glutamate release, and aquaporin-4 (Aqp4) expression. These factors are also thought to be involved in the development of brain edema in acute liver failure. We wanted to study whether hypermagnesemia prevented development of intracranial hypertension and hyperperfusion in a rat model of portacaval anastomosis (PCA) and acute hyperammonemia. We also studied whether hypermagnesemia had an influence on brain content of glutamate, glutamine, and aquaporin-4 expression. The study consisted of three experiments: The first was a dose-finding study of four different dosing regimens of magnesium sulfate (MgSO 4 ) in healthy rats. The second involved four groups of PCA rats receiving ammonia infusion/vehicle and MgSO 4 /saline. The effect of MgSO 4 on mean arterial pressure (MAP), intracranial pressure (ICP), CBF, cerebral glutamate and glutamine, and aquaporin-4 expression was studied. Finally, the effect of MgSO 4 on MAP, ICP, and CBF was studied, using two supplementary dosing regimens. In the second experiment, we found that hypermagnesemia and hyperammonemia were associated with a significantly higher CBF (P < 0.05, twoway analysis of variance [ANOVA]). Hypermagnesemia did not lead to a reduction in ICP and did not affect the brain content of glutamate, glutamine, or Aqp-4 expression. In the third experiment, we achieved higher P-Mg but this did not lead to a significant reduction in ICP or CBF. Conclusion: Our results demonstrate that hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in rats with PCA and hyperammonemia. (HEPATOLOGY 2011;53:1986-1994 A cute liver failure (ALF) is a condition with a substantial mortality rate because of a high risk of multiple organ failure. Of special interest are the cerebral complications in ALF that in the most severe cases can progress to cerebral edema, intracranial hypertension, and ultimately cerebral incarceration. The genesis for these cerebral complications is among other factors related to persistent hyperammonemia, 1,2 systemic inflammation, 2,3 and electrolyte disturbances 4 and is associated with cerebral hyperperfusion and loss of autoregulation of the cerebral blood flow (CBF). 5The complex and multifactorial nature has made the understanding of the pathogenesis of brain edema difficult. Both the therapeutic and prophylactic strategies related to brain edema in ALF are few and limited in efficacy. During surges of high intracranial pressure (ICP), intervention with mannitol, hypertonic saline, hyperventilation, hypothermia, and indomethacin has demonstrated a temporary beneficial effect on intracranial hypertension. 6,7 Recently, ammonia-lowering therapy with the compound of L-ornithine and phenylacetate has shown promising data in animal studies, 8 but no human data have yet been publishe...

show abstract

“…Its expression in the blood-brain barrier in astrocytic end feet provides a means of water influx into the brain. During ischemia, it facilitates cytotoxic edema formation by facilitating water inflow to the brain [4,16,17,26,29,31,35]. Also, aqp-4 molecular inhibitors have been shown to decrease the amount of cytotoxic edema [17-20, 24, 32].…”

Section: Discussionmentioning

confidence: 99%

Aquaporin-4 expression is not elevated in mild hydrocephalus

et al. 2011

View full text Add to dashboard Cite

show abstract

Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema

Cited by 37 publications

References 30 publications

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

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

Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia

Aquaporin-4 expression is not elevated in mild hydrocephalus

Contact Info

Product

Resources

About