glycogen and Brain-Diseases

The cerebrohepatorenal syndrome of Zellweger (CHRS) is remarkable not only for a distinctive combination of congenital anomalies, but also for an unusual variety of profound metabolic disturbances. After a discussion of the clinical diagnosis of CHRS, abnormalities in the metabolism of peroxisomes, mitochondria, iron, pipecolic acid, glycogen, bile acids, and organic acids are discussed and related to the clinical and other biochemical findings in the syndrome. Attention is also drawn to syndromes with biochemical or clinical abnormalities similar to those of CHRS. Although the biochemical findings indicate major abnormalities in oxidative metabolism, the primary defect remains obscure.

Topics: Abnormalities, Multiple; Amino Acids, Dicarboxylic; Bile Acids and Salts; Brain Diseases; Glutarates; Glycogen; Humans; Iron; Kidney Diseases; Liver Diseases; Microbodies; Mitochondria; Pipecolic Acids; Syndrome

Topics: Absorption; Adult; Animals; Blood Proteins; Brain Diseases; Cell Differentiation; Cerebral Hemorrhage; Cerebral Ventricles; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Cholesterol; Choroid Neoplasms; Choroid Plexus; Cilia; Cysts; Ependyma; Epithelium; Female; Glycogen; Glycoproteins; Glycosaminoglycans; Granuloma; Humans; Infant; Infant, Newborn; Lipid Metabolism; Macrophages; Male; Microscopy, Electron; Mucins; Phagocytosis; Rats

In isolated white matter, ischemic tolerance changes dramatically in the period immediately before the onset of myelination. In the absence of an extrinsic energy source, postnatal day 0 to 2 (P0 to P2) white matter axons are here shown to maintain excitability for over twice as long as axons >P2, a differential that was dependent on glycogen metabolism. Prolonged withdrawal of extrinsic energy supply tended to spare axons in zones around astrocytes, which are shown to be the sole repository for glycogen particles in developing white matter. Analysis of mitochondrial volume fraction revealed that neither axons nor astrocytes had a low metabolic rate in neonatal white matter, while oligodendroglia at older ages had an elevated metabolism. The astrocyte population is established early in neural development, and exhibits reduced cell density as maturation progresses and white matter expands. The findings show that this event establishes the necessary conditions for ischemia sensitivity in white matter and indicates that astrocyte proximity may be significant for the survival of neuronal elements in conditions associated with compromised energy supply.

Topics: Animals; Astrocytes; Axons; Brain; Brain Diseases; Brain Ischemia; Energy Metabolism; Female; Glycogen; Male; Myelin Sheath; Rats; White Matter

The action of an Agaricus blazei aqueous extract pretreatment on paracetamol injury in rats was examined not only in terms of the classical indicators (e.g., levels of hepatic enzymes in the plasma) but also in terms of functional and metabolic parameters (e.g., gluconeogenesis). Considering solely the classical indicators for tissue damage, the results can be regarded as an indication that the A. blazei extract is able to provide a reasonable degree of protection against the paracetamol injury in both the hepatic and brain tissues. The A. blazei pretreatment largely prevented the increased levels of hepatic enzymes in the plasma (ASP, ALT, LDH, and ALP) and practically normalized the TBARS levels in both liver and brain tissues. With respect to the functional and metabolic parameters of the liver, however, the extract provided little or no protection. This includes morphological signs of inflammation and the especially important functional parameter gluconeogenesis, which was impaired by paracetamol. Considering these results and the long list of extracts and substances that are said to have hepatoprotective effects, it would be useful to incorporate evaluations of functional parameters into the experimental protocols of studies aiming to attribute or refute effective hepatoprotective actions to natural products.

Topics: Acetaminophen; Administration, Oral; Agaricus; Alanine; Animals; Antioxidants; Biomarkers; Brain; Brain Diseases; Chemical and Drug Induced Liver Injury; Complex Mixtures; Enzyme Assays; Glucose; Glycogen; Lactic Acid; Lipid Metabolism; Liver; Male; Oxidative Stress; Rats; Rats, Wistar; Time Factors

We report here a glycogen storage myopathy type V associated with multifocal encephalopathy. The patient, a 43-year-old male with increased serum CK, a heavy drinker and smoker, had been affected by generalized epilepsy since age 24, after a cranial injury. He had had a right hemiparesis 2 years before coming to our observation and a transient left hemiparesis the following year. CT and MRI of the brain showed multiple hemispheric lesions consistent with an ischemic process, as suggested by single photon emission tomography of the brain. Muscle biopsy showed a vacuolar myopathy, and myophosphorylase activity was 13% of the normal mean. Phosphorus magnetic resonance spectroscopy (31P-MRS) performed on resting calf muscles showed increased PCr to ATP and decreased PCr to P(i) ratios. During both aerobic and ischemic exercise 31P-MRS failed to show any cytosolic acidification and phosphomonoesters (PME) accumulation, two MRS findings in agreement with McArdle's syndrome diagnosis. Mitochondrial respiration was also affected as shown by a low PCr to P(i) ratio at rest and by a low rate of PCr re-synthesis during recovery from aerobic exercise. This latter finding in McArdle's disease can be explained by decreased mitochondrial substrate availability, which in turn can contribute to the phenotypic manifestations of the disease.

Topics: Adult; Aerobiosis; Brain Diseases; DNA; Electrocardiography; Energy Metabolism; Exercise; Glycogen; Humans; Hydrogen-Ion Concentration; Lactates; Lactic Acid; Magnetic Resonance Imaging; Male; Mitochondria, Muscle; Muscles; Phosphorylases; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Ultrasonography

A 3-month-old infant with congenital hypotonia suffering from an unusual form of glycogenosis is reported. The most striking neuropathologic findings were vacuolation of neuropile and glycogen accumulation, especially in the cerebral cortex and cerebellar molecular layer. Ultrastructurally, glycogen accumulation was present mainly in neurites and astrocytic processes, and mostly appeared as rosettes (alpha glycogen particles). Biochemical analysis of glycogen in various regions of the central nervous system showed an increase of up to 100-fold. The cerebral cortex, deep nuclei, and cerebellar cortex had the highest glycogen elevations, while the cerebral white matter glycogen level was normal. Among other tissues, the heart showed a several-fold increase in glycogen content. Muscle, liver, and kidney glycogen levels were not elevated. Findings in this case and in three other reported patients with cerebral glycogenosis of alpha particle type are discussed.

Topics: Brain; Brain Chemistry; Brain Diseases; Glycogen; Glycogen Storage Disease; Humans; Infant, Newborn; Male

Recent advances in technology have made it possible to determine cerebral blood flow and metabolism in newborn infants. The mean cerebral blood flow rate falls from 60 to 30 ml/min/100 g during the first 3 hours of life and returns to the initial value after the first week. It increases by about 30% during rapid sleep and feeding. Cerebral blood flow is independent of gestational age and represents 20-25% of cardiac output as against 16% in adults. It is influenced by blood gases and its autoregulation is impaired by asphyxia. Infants with a cerebral blood flow rate below 20 ml/min/100 g are at high risk of leucomalacia. The high metabolic activity of the neonatal brain is reflected in its considerable consumption of oxygen (54% vs 30% in adults) and ketonic bodies which participate for 10% in cerebral energy metabolism. More than 80% of the endogenous glucose is utilized by the brain of neonates despite a transport capacity lower than in adults. In neonatal pathology, it is now possible to investigate cerebral metabolism using positron emission tomography or phosphorous magnetic resonance spectroscopy which provide for better diagnostic and prognostic evaluation of cerebral functions.

Topics: Animals; Animals, Newborn; Biological Transport; Brain; Brain Diseases; Cerebrovascular Circulation; Glycogen; Humans; Infant, Newborn; Oxidation-Reduction; Pentose Phosphate Pathway; Time Factors

We found marked accumulation of glycogen in the brain in one case of the cerebro-hepato-renal syndrome (CHRS). Glycogen in the form of beta-particles was deposited freely within the nucleus, perikaryon and cell processes of neurons and glial cells. The changes involved the gray matter diffusely but were more prominent in the cerebral cortex. The patient died at the age of 4 months after a clinical course characterized by severe hypotonia, seizures, and apneic episodes. Other neuropathologic findings were developmental malformations of the central nervous systen (CNS) (pachygyria, polymicrogyria, and hypoplasia of the inferior olives), white matter abnormalities (deficiency in myelination and diffuse accumulation of sudanophilic droplets within glial cells), clusters of peculiar "globoid" histiocytes with pleomorphic lipid inclusions, and microglial nodules in gray and white matter. This unusual combination of findings is regarded as characteristic of the CHRS.

Topics: Brain; Brain Diseases; Cerebral Cortex; Glycogen; Histocytochemistry; Humans; Infant; Kidney Diseases; Liver Diseases; Male; Neuroglia; Neurons; Syndrome

Topics: 1,4-alpha-Glucan Branching Enzyme; Adenine Nucleotides; Adrenal Cortex Hormones; Animals; Blood Glucose; Body Temperature Regulation; Brain; Brain Diseases; Brain Injuries; Catecholamines; Central Nervous System; Chemical Phenomena; Chemistry, Physical; Glycogen; Glycogen Synthase; Histocytochemistry; Histological Techniques; Humans; Hypoxia, Brain; Insulin; Ischemia; Nerve Degeneration; Phenobarbital; Phosphorylases; Radiation Effects; Radiation, Ionizing; Rats; Retina

The hepatic lesion in Reye's syndrome (acute encephalopathy with fatty degeneration of viscera) was studied by light microscopy of sequential biopsy specimens obtained in 49 children. The hepatic lesion is a morphologically characteristic, rapidly evolving, and reversible toxic hepatitis. In specimens obtained with 48 hr of onset of neurological deterioration, the severity of the diffuse microvesicular steatosis is best appreciated in frozen sections stained for lipid content. Variation in severity of hepatocyte glycogen depletion in early biopsies correlates with other histological measures of severity, and with the occurrence of hypoglycemia, severity of the encephalopathy at the time of admission, and mortality rate. Histochemical studies suggest that the hepatic lesion is attributable to mitochondrial injury and other evidence that supports this hypothesis is briefly reviewed. The etiology of the syndrome and its relationship to the viral disease which usually precedes it are unknown.

Topics: Brain Diseases; Chemical and Drug Induced Liver Injury; Fatty Liver; Glycogen; Humans; Lipid Metabolism; Liver; Mitochondria, Liver; Reye Syndrome

Topics: Aflatoxins; Animals; Blood Glucose; Brain Diseases; Drug Synergism; Enterovirus Infections; Fatty Acids, Unsaturated; Fatty Liver; Glycogen; Hexachlorocyclohexane; Hypoglycemia; Liver; Mengovirus; Mice; Microscopy, Electron; Mitochondria, Liver; Polychlorinated Biphenyls; Rats; Reye Syndrome; Syndrome; Toxins, Biological; Triglycerides; Valerates

Topics: Animals; Blood Glucose; Brain Diseases; Fatty Liver; Glucagon; Gluconeogenesis; Glucose; Glycogen; Growth Hormone; Haplorhini; Humans; Hypoglycemia; Insulin; Liver; Mice; Pyruvates; Rats; Reye Syndrome

Topics: Animals; Brain; Brain Diseases; Chlorpromazine; Glycogen; Histocytochemistry; Kidney; Liver; Microscopy, Electron; Rabbits; Thiazines; Time Factors

Topics: Brain Diseases; Cell Nucleus; Chromatin; Glycogen; Humans; Liver Cirrhosis; Male; Middle Aged; Neuroglia; Portacaval Shunt, Surgical; Proteins

Topics: Amino Acids; Brain Chemistry; Brain Diseases; Cerebellum; Cerebral Cortex; Cerebrosides; Cholesterol; Electroencephalography; Glycogen; Growth Disorders; Hair; Humans; Infant; Male; Nerve Degeneration; Pedigree; Phenobarbital; Phenytoin; Phospholipids; Plasmalogens; Seizures; Ubiquinone; Vitamin E

Topics: Animals; Brain Diseases; Cerebral Cortex; Cobalt; Dendrites; Glycogen; Histocytochemistry; Microscopy, Electron; Necrosis; Nerve Degeneration; Neuroglia; Rats

Topics: Animals; Brain; Brain Diseases; Glucosyltransferases; Glycogen; Rats

Topics: Brain Diseases; Glycogen; Humans; In Vitro Techniques; Liver Diseases; Staining and Labeling

Topics: Adolescent; Brain Diseases; Carbohydrate Metabolism; Child; Epilepsy; Epilepsy, Absence; Glycogen; Hexosamines; Humans; Metabolic Diseases; Myoclonic Epilepsies, Progressive; Neurochemistry; Pathology

Topics: Brain; Brain Diseases; Carbohydrate Metabolism; Glycogen; Humans; Lactates; Lactic Acid

Topics: Brain; Brain Diseases; Glycogen; Glycogen Storage Disease; Lipid Metabolism; Lipidoses; Liver

Topics: Blood; Brain; Brain Diseases; Dwarfism; Glycogen; Pituitary Diseases; Sexual Infantilism

Topics: Blood; Brain; Brain Diseases; Dwarfism; Glycogen; Pituitary Diseases; Sexual Infantilism