Protective effect of L-carnitine in ammonia-precipitated encephalopathy in the portacaval shunted rat.

L-carnitine administration prevents the neurological symptoms of acute ammonia toxicity. To further evaluate its efficacy in the prevention of hepatic encephalopathy in hyperammonemic conditions, L-carnitine (16 mmol/kg, intraperitoneally [i.p.

Increased density of catalytic sites and expression of brain monoamine oxidase A in humans with hepatic encephalopathy.

Altered biogenic amine metabolism and function are believed to underlie certain of the neuropsychiatric symptoms, e.g., depression, mania, and anxiety, encountered in clinical hepatic encephalopathy (HE).

Portacaval shunting and hyperammonemia stimulate the uptake of L-[3H] arginine but not of L-[3H]nitroarginine into rat brain synaptosomes.

Elevated activities of nitric oxide synthase (NOS) have been reported previously in the brains of portacaval-shunted (PCS) rats, a model of chronic hepatic encephalopathy (HE). As L-arginine availability for nitric oxide synthesis depends on a specific uptake mechanism in neurons, we studied the kinetics of L-[3H]-arginine uptake into synaptosomes prepared from the brains of PCS rats. Results demonstrate that L-arginine uptake is significantly increased in cerebellum (60%; p < 0.

Vesicular dysfunction during experimental thiamine deficiency is indicated by alterations in dopamine metabolism.

Experimental and clinical studies indicate that catecholamines play an important role in the neurobehavioural symptomatology of thiamine deficiency. Given the cerebral region-selective vulnerability and the behavioural impairment commonly encountered in thiamine deficiency, we undertook to investigate regional catecholamine metabolism in the brains of pyrithiamine-induced thiamine-deficient rats. Dopamine metabolism was unaffected in the striatum.

Ammonium acetate challenge in experimental chronic hepatic encephalopathy induces a transient increase of brain 5-HT release in vivo.

Ammonia has been shown to cause release of neurotransmitters such as serotonin (5-hydroxytryptamine; 5-HT) from synaptosomal preparations in vitro. In the present study, frontal neocortical extracellular levels of 5-HT and its major metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), were determined in vivo by the use of microdialysis in portacaval shunted (PCS) rats, an experimental model of chronic hepatic encephalopathy (HE), prior to and after an acute coma-inducing administration of ammonium acetate (NH4Ac; 5.2 mmol/kg, i.

Increased blood manganese in cirrhotic patients: relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms.

Increasing evidence suggests that manganese deposition is responsible for the T1-weighted magnetic resonance imaging (MRI) signal hyperintensity consistently observed in pallidum of cirrhotic patients. However, the relationship between blood manganese and the etiology or severity of liver disease, as well as the neurological symptomatology in these patients, has not been well established. In the present study, blood manganese concentrations were measured by atomic absorption spectrometry together with MRI and neurological evaluation in 57 cirrhotic patients with various etiologies and severity of liver disease.

Serum neuron-specific enolase, carnosinase, and their ratio in acute stroke. An enzymatic test for predicting outcome?

Background And Purpose: Few admission variables adequately predict neuronal damage and prognosis in individual patients after stroke. Therefore, there is a need for a reliable non-invasive surrogate measure of clinical outcome.

Methods: We have developed a surrogate measure of stroke outcome using the ratio of serum neuron-specific enolase (NSE) to human serum carnosinase (HSC) in 124 patients with acute ischemic or hemorrhagic stroke and 61 matched control subjects.

Brain extracellular quinolinic acid in chronic experimental hepatic encephalopathy as assessed by in vivo microdialysis: acute effects of L-tryptophan.

Increased brain quinolinic acid (QUIN) levels have been suggested to play a role in hepatic encephalopathy (HE). Previous brain tissue studies have been unable to confirm this hypothesis. Because QUIn is a potent NMDA-receptor agonist, it also is relevant to determine brain extracellular QUIN levels in HE.

Portacaval anastomosis results in altered neuron--astrocytic metabolic trafficking of amino acids: evidence from 13C-NMR studies.

13C-NMR spectroscopy was used to evaluate the dynamic consequences of portacaval anastomosis on neuronal and astrocytic metabolism and metabolic trafficking between neurons and astrocytes. Glutamate is predominantly labeled from [1-13C]glucose, whereas [2-13C]acetate is more efficient in labeling glutamine, in accordance with its primary metabolism in astrocytes. Alanine and succinate labeling was only observed with [1-13C]glucose as precursor.

Neuroactive amino acids and glutamate (NMDA) receptors in frontal cortex of rats with experimental acute liver failure.

It has been proposed that alterations of excitatory and inhibitory amino acids play a role in the pathogenesis of hepatic encephalopathy in acute liver failure. To evaluate this possibility, in vivo cerebral microdialysis was used to sample extracellular concentrations of amino acids in the frontal cortex of unanesthetized rats at various times during the progression of encephalopathy resulting from acute liver failure. Liver failure was induced by portacaval anastomosis followed 24 hours later by hepatic artery ligation.

Portacaval anastomosis induces region-selective alterations of the endogenous opioid system in the rat brain.

Portacaval anastomosis (PCA) in the rat results in a broad spectrum of neurological and neurobehavioral changes, including alterations of circadian rhythms, impaired locomotor activity, and reflexes, as well as decreased threshold to noxious stimuli. In addition, following portacaval shunting, rats drink significantly more ethanol in a free-choice drinking paradigm. Available evidence suggests that many of these behavioral changes may be modulated by the endogenous opioid system of the brain.

Arginine-related guanidino compounds and nitric oxide synthase in the brain of ornithine transcarbamylase deficient spf mutant mouse: effect of metabolic arginine deficiency.

The sparse-fur (spf) mouse, with an X-linked hepatic ornithine transcarbamylase (OTC, E.C.2.

L-[3H]nitroarginine and L-[3H]arginine uptake into rat cerebellar synaptosomes: kinetics and pharmacology.

Characteristics of the transport of the nitric oxide synthase substrate L-arginine and its inhibitor, NG-nitro-L-arginine (L-NOARG), into rat cerebellar synaptosomes were studied. Uptake of both L-arginine and L-NOARG was linear with increasing amount of protein (up to 40 micrograms) and time of incubation (up to 5 min) at 37 degrees C. Uptake of both compounds reached a steady state by 20 min.

Alterations in serotonin parameters in brain of thiamine-deficient rats are evident prior to the appearance of neurological symptoms.

Biochemical alterations of serotoninergic parameters have been demonstrated in experimental thiamine deficiency. In addition, hypophagia and hypothermia, two physiological processes associated with changes in the serotonin [5-hydroxytryptamine (5-HT)] system, are manifest early during the progression of thiamine deficiency. The binding of selected 5-HT radioligands was therefore investigated in discrete brain regions of pyrithiamine-induced thiamine-deficient rats.

Central muscarinic cholinergic M1 and M2 receptor changes in congenital ornithine transcarbamylase deficiency.

Congenital ornithine transcarbamylase (OTC) deficiency results in neuropathologic damage to the cerebral cortex, basal ganglia, and thalamus. However, the precise nature of the cell loss, as well as the pathophysiologic mechanisms responsible for it, have not been fully elucidated. In the present study, densities of the M1 and M2 subclasses of muscarinic cholinergic binding sites were assessed using quantitative receptor autoradiography in the brains of sparse-fur (spf) mice with congenital OTC deficiency and in age-matched CD-1 controls.

Neuroactive amino acids in hepatic encephalopathy.

There is abundant evidence to suggest that alterations of excitatory and inhibitory amino acids play a significant role in the pathogenesis of hepatic encephalopathy (HE) in both acute and chronic liver diseases. Brain glutamate concentrations are reduced in patients who died in hepatic coma as well as in experimental HE, astrocytic reuptake of glutamate is compromised in liver failure and postsynaptic glutamate receptors (both NMDA and non-NMDA subclasses) are concomitantly reduced in density. Recent studies in experimental acute liver failure suggest reduced capacity of the astrocytic glutamate transporter in this condition.

Quantitative autoradiography using selective radioligands for central and peripheral-type benzodiazepine receptors in experimental Wernicke's encephalopathy: implications for positron emission tomography imaging.

Wernicke's encephalopathy (WE) is difficult to diagnose during life, with up to 80% of cases being missed by routine neurological evaluation in both alcoholics and AIDS patients. Therefore, there is a need for noninvasive diagnostic procedures. Using the pyrithiamine-treated rat, an animal model of WE, we have studied, using radioligands for central (neuronal) and "peripheral-type" (glial) benzodiazepine receptors, the regional distribution of changes in the densities of these receptors in relation to the degree of reactive gliosis accompanying neuronal loss.

Nitric oxide synthase activities are selectively decreased in vulnerable brain regions in thiamine deficiency.

Pyrithiamine-induced thiamine deficiency in the rat exhibits many neuropathological and biochemical similarities to Wernicke's Encephalopathy in human. Activities of constitutive nitric oxide synthase (NOS) were measured in vulnerable (thalamus and cerebellum) and non-vulnerable (hippocampus and striatum) brain regions of pyrithiamine-induced thiamine-deficient rats. NOS activities were significantly decreased in the thalamus (by 26%, P < 0.

Na+,K(+)-ATPase activity is selectively increased in thalamus in thiamine deficiency prior to the appearance of neurological symptoms.

The relationship between progression of neurological status and the activities of both Na+,K(+)- and Mg(2+)-dependent-ATPase (adenosine 5'-triphosphate phosphohydrolase) was investigated in brain regions of pyrithiamine-induced thiamine deficient rats. Thalamic Na+,K(+)-ATPase activity was selectively increased by 200% (P < 0.01) prior to the appearance of symptoms of thiamine deficiency and normalized in symptomatic rats.

Regional distribution of binding sites for the nitric oxide synthase inhibitor L-[3H]nitroarginine in rat brain.

The regional distribution of NG-nitro-L-[(3)H]arginine (L-[(3)H]NOARG) binding to different regions of rat brain was studied by quantitative autoradiography. These studies revealed highest density of binding sites in cerebellum, anterior olfactory nucleus, islands of Calleja and substantia nigra with appreciable binding site densities in inferior colliculus, superior colliculus, olfactory tubercle and dorsal tegmental nucleus. The regional distribution of L-[(3)H]NOARG binding, is in good agreement with the distribution of nitric oxide synthase studied previously by NADPH-diaphorase staining and immunohistochemistry using antibodies against neuronal nitric oxide synthase.

Alterations of thiamine phosphorylation and of thiamine-dependent enzymes in Alzheimer's disease.

There is a growing body of evidence to suggest that thiamine neurochemistry is disrupted in Alzheimer's Disease (AD). Studies in autopsied brain tissue from neuropathologically proven AD patients reveal significantly reduced activities of the thiamine phosphate dephosphorylating enzymes thiamine diphosphatase (TDPase) and thiamine monophosphatase (TMPase) as well as the thiamine diphosphate-dependent enzymes, pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase (alpha KGDH) and transketolase. Reductions in enzyme activities are present both in affected areas of AD brain as well as in relatively well conserved tissue.