Abstract：
:Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with severe liver disease. Although the mechanisms responsible for HE remain elusive, ammonia is generally considered to be involved in its pathogenesis, and astrocytes are thought to be the principal target of ammonia neurotoxicity. Altered bioenergetics and oxidative stress are also thought to play a major role in this disorder. In this paper, we present data invoking the mitochondrial permeability transition (MPT) as a factor in the pathogenesis of HE/hyperammonemia. The MPT is a Ca2+-dependent, cyclosporin A (CsA) sensitive process due to the opening of a pore in the inner mitochondrial membrane that leads to a collapse of ionic gradients and ultimately to mitochondrial dysfunction. Many of the factors that facilitate the induction of the MPT are also known to be implicated in the mechanism of HE, including free radicals, Ca2+, nitric oxide, alkaline pH, and glutamine. We have recently shown that treatment of cultured astrocytes with 5 mM NH4Cl resulted in a dissipation of the mitochondrial membrane potential (delta(psi)m), which was sensitive to CsA. Similarly treated cultured neurons failed to show a loss of the delta(psi)m. Further support for the ammonia induction of the MPT was obtained by observing an increase in mitochondrial permeability to 2-deoxyglucose-6-phosphate, and a decrease in calcein fluorescence in astrocytes after ammonia treatment, both of which were also blocked by CsA. CsA was likewise capable of exerting a protective effect against hyperammonemia in mice. Taken together, our data suggest that the MPT represents an important component of the pathogenesis of HE and other hyperammonemic states.
journal_name
Metab Brain Disjournal_title
Metabolic brain diseaseauthors
Rama Rao KV,Jayakumar AR,Norenberg DMdoi
10.1023/a:1023858902184subject
Has Abstractpub_date
2003-06-01 00:00:00pages
113-27issue
2eissn
0885-7490issn
1573-7365journal_volume
18pub_type
杂志文章,评审abstract：:Mutations in NADH dehydrogenase (ND) subunits of complex I lead to mitochondrial encephalomyopathies associated with various phenotypes. This report aims to present the patient's clinical symptomatology in the context of a very rare 13042G>A de novo mutation and with an emphasis on changing phenotypic expression and p...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-014-9645-x
更新日期：2015-08-01 00:00:00
abstract：:Mitochondrial glutathione (mGSH) is a critical factor in the cell defense against oxidative and nitrosative stress (ONS), and ONS is a key pathogenic event in hepatic encephalopathy (HE). Acute HE in the thioacetamide (TAA) model caused a 54 % decrease of mGSH content in the rat prefrontal cortex (pfc), but not in the...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-012-9342-6
更新日期：2013-03-01 00:00:00
abstract：:Cadmium is a toxic environmental and industrial pollutant. Cadmium toxicity has been reported to produce biochemical and behavioral dysfunction that may cause adverse effects on several organs including the central nervous system. The present study was designed to investigate the neurotoxic effects of Cadmium Chloride...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-014-9578-4
更新日期：2015-02-01 00:00:00
abstract：:We investigated the effects of age and nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on protein kinase C (PKC), adenylyl cyclase, calcium/calmodulin-independent cyclic-AMP phosphodiesterase (cyclic-AMP PDE) and voltage-dependent L-type calcium channels in Fischer rat brain using autoradio...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/BF02676356
更新日期：1997-03-01 00:00:00
abstract：:The radiological spectrum of neuromyelitis optica has become broader since the detection of aquaporin4 antibodies. We report a case of neuromyelitis optica patient with pseudotumoral encephalic lesion. A 66 year-old woman presented with sudden left lateral homonymous hemianopsia. A brain MRI showed an isolated and ext...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-017-0141-y
更新日期：2018-02-01 00:00:00
abstract：:In the brain hyperammonemia interferes with ion homeostasis, membrane potentials, neurotransmission, and neurotransmitter recycling and reduces metabolic rates for oxygen and glucose. Because, cerebral blood flow (CBF) is closely coupled to metabolism, CBF is most often reduced in diseases associated with hyperammonem...
journal_title：Metabolic brain disease
pub_type： 杂志文章,评审
doi：10.1023/a:1021941414605
更新日期：2002-12-01 00:00:00
abstract：:The mitogen-activated protein kinase (MAP kinase) pathway participates in a number of reactions of the cell when responding to various external stimuli. These stimuli include growth factor binding to its receptor as well as stressful situations such as hypoxia and oxidative stress. It has been postulated that one of t...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1023/a:1012541011123
更新日期：2001-12-01 00:00:00
abstract：:Applying different technologies to monitor disease activity and treatment efficacy are essential in a complex disease such as multiple sclerosis. Combining current assays with flow cytometry could create a powerful tool for such analyses. The cell surface expression level of CD74, the MHC class II invariant chain, is ...
journal_title：Metabolic brain disease
pub_type： 杂志文章,评审
doi：10.1007/s11011-014-9634-0
更新日期：2015-08-01 00:00:00
abstract：:Severe neurological symptoms, cerebral edema, and atrophy are common features of the inherited metabolic disorder propionic acidemia. However, the pathomechanisms involved in the neuropathology of this disease are not well established. In this study, we investigate the effects of propionic acid (PA), a metabolite accu...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-006-9002-9
更新日期：2006-03-01 00:00:00
abstract：:The availability of an animal model is crucial in studying the pathophysiological mechanisms of disease and to test possible therapies. Now, there are several models for the study of liver diseases, but there still remains a lack of a satisfactory animal model of chronic liver disease with hepatic encephalopathy (HE) ...
journal_title：Metabolic brain disease
pub_type： 杂志文章,评审
doi：10.1007/s11011-005-7925-1
更新日期：2005-12-01 00:00:00
abstract：:The synthesis, storage and release of acetylcholine (ACh) requires the expression of several specialized proteins, including choline acetyltransferase (ChAT) and the vesicular ACh transporter (VAChT). The VAChT gene is located within the first intron of the ChAT gene. This unique genomic organization permits coordinat...
journal_title：Metabolic brain disease
pub_type： 杂志文章,评审
doi：10.1007/BF02680013
更新日期：2000-03-01 00:00:00
abstract：:Due to the high ability of cadmium to cross the blood-brain barrier, cadmium (Cd) causes severe neurological damages. Hence, the purpose of this study was to investigate the possible protective effect of Mangifera indica leaf extract (MLE) against Cd-induced neurotoxicity. Rats were divided into eight groups. Group 1 ...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-018-0222-6
更新日期：2018-08-01 00:00:00
abstract：:Despite the existence of many preclinical studies, scientific evidence is lacking on the clinical use of alpha-lipoic acid (ALA) for central nervous system disorders. Therefore, we aimed at revising the literature concerning the use of ALA for the treatment of psychiatric and neurological conditions and to point out w...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-018-0344-x
更新日期：2019-02-01 00:00:00
abstract：:The selective vulnerability of pyramidal neurons in the CA1 hippocampal region in ischemic rat brain may be preceded by regional alterations of energy metabolism during early reperfusion. We measured ATP, phosphocreatine (PCr), and glucose in paramedian and lateral CA1 and in an area showing little postischemic cell l...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/BF00999235
更新日期：1988-09-01 00:00:00
abstract：:Effects of sertraline, haloperidol or olanzapine administration on ketamine-induced behaviours in mice were examined. The aim was to ascertain the degree of reversal of such behaviours by sertraline, and compare its effectiveness to haloperidol and olanzapine. Ten-week old mice (N = 120) were equally divided into main...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-017-0031-3
更新日期：2017-10-01 00:00:00
abstract：:Amyloid-beta (Aβ) interacts with the serine/threonine protein kinase AKT (also known as protein kinase B)/glycogen synthase kinase 3β (GSK3β) pathway and deactivates GSK3β signaling, which result in microtubule protein tau phosphorylation. Atorvastatin, a HMG-CoA reductase inhibitor, has been proven to improve learnin...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-016-9803-4
更新日期：2016-06-01 00:00:00
abstract：:Hyperammonemia is necessary for development of the cerebral complications to liver disease including hepatic encephalopathy and cerebral edema but the mechanisms are unclear. Ammonia is taken up by the brain in proportion to its arterial concentration. The flux into the brain is most likely by both diffusion of NH3 an...
journal_title：Metabolic brain disease
pub_type： 杂志文章,评审
doi：10.1007/s11011-014-9494-7
更新日期：2014-12-01 00:00:00
abstract：:Transient bilateral common carotid artery occlusion (tBCCAO), followed by reperfusion, is a model of transient global hypoperfusion. In the present study we aimed to investigate the probable effects of Vanillic acid (VA) on some physiological parameters including cerebral hyperemia, blood-brain barrier (BBB) disruptio...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-018-0187-5
更新日期：2018-06-01 00:00:00
abstract：:Aberrant brain functional connectivity has been considered as the important mechanism underlying minimal hepatic encephalopathy (MHE); however, little is known about the change in interhemispheric connection in MHE patients. Twenty patients with HBV-related cirrhosis and MHE and 15 healthy controls were included in th...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-014-9505-8
更新日期：2014-09-01 00:00:00
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journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/BF02674671
更新日期：1997-12-01 00:00:00
abstract：:The impaired insulin signaling has been recognized as a common pathogenetic mechanism between diabetes and Alzheimer's disease (AD). In the progression of AD, brain is characterized by defective insulin receptor substrate-1 (IRS-1) and increased oxidative stress. Thymol, a monoterpene phenol isolated from medicinal he...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-016-9921-z
更新日期：2017-04-01 00:00:00
abstract：:Cadmium (Cd) exposure leads to production of reactive oxygen species (ROS), which are associated with Cd-induced neurotoxicity and nephrotoxicity. Selenium nanoparticles (Se-NPs) have high bioavailability and antioxidant activities so it attracted wide spread attention. The present study examined the possible ameliora...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-017-0053-x
更新日期：2017-10-01 00:00:00
abstract：:To investigate the hypothesis that neurotoxic metals can exert their toxicity through the direct inhibition of monoamine oxidases (MAOs), the effects of several neurotoxic metal ions on type A (MAO-A) and type B (MAO-B) monoamine oxidase activities in rat forebrain nonsynaptic mitochondria and rat liver mitochondria w...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/BF01000159
更新日期：1992-09-01 00:00:00
abstract：:The free radical scavenging abilities of the structurally related steroids beta-sitosterol, beta-sitosterol glucoside (plant sterols and sterolins), cholesterol, and dehydroepiandrosterone sulphate (DHEAS) were compared with melatonin (an efficient free radical scavenger) in an in vitro system which measures lipid per...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1023/a:1011167023695
更新日期：2000-12-01 00:00:00
abstract：:Central pontine myelinolysis (CPM) is a demyelinating condition affecting not only the pontine base, but also involving other brain areas. It usually occurs on a background of chronic systemic illness, and is commonly observed in individuals with alcoholism, malnutrition and liver disease. Studies carried out 25-30 ye...
journal_title：Metabolic brain disease
pub_type： 历史文章,杂志文章
doi：10.1007/s11011-010-9175-0
更新日期：2010-03-01 00:00:00
abstract：:Multiple sclerosis (MS) is a demyelinating and degenerative disease of the central nervous system (CNS) with a strong inflammatory component that affects more than 2 million people worldwide (and at least 400,000 in the United States). In MS, macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (D...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-018-0331-2
更新日期：2019-02-01 00:00:00
abstract：:Brain glucose uptake is usually reduced in type 2 diabetes owing to downregulation of brain glucose transporters. The ability of Vernonia amygdalina to stimulate glucose uptake as well as ameliorate glucose-induced oxidative stress and proinflammation were investigated in rat brain. Hot infusion of V. amygdalina leave...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-018-0363-7
更新日期：2019-06-01 00:00:00
abstract：:Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Usually diagnosed within the first month of birth, it is essential that the patient strictly follow the dietary restriction of natural protein intake. Otherwise, PKU impacts the development of the brain severely and may result in microceph...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-019-00472-7
更新日期：2019-12-01 00:00:00
abstract：:The aim of the present work was to investigate the role of ondansetron on the high fat diet (HFD) induced obese mice for behavioral and biochemical alterations using chronic unpredictable mild stress (CUMS) model of depression. Animals were fed with high fat diet for 14 weeks and subjected to different stress procedur...
journal_title：Metabolic brain disease
pub_type： 杂志文章
doi：10.1007/s11011-014-9574-8
更新日期：2014-09-01 00:00:00
abstract：:The integrity of the blood-brain barrier (BBB) is an important aspect of normal central nervous system (CNS) function. Recently, it was shown that the BBB breakdown is one of the predisposing factors in the pathogenesis of thiamine-deficiency encephalopathy. The result is discussed along with some reviews on previous ...
journal_title：Metabolic brain disease
pub_type： 杂志文章,评审
doi：10.1007/BF02080931
更新日期：1996-03-01 00:00:00
