Neurochemical pathology最新文献

Free fatty acids (FFA), diacylglycerols (DG), and water content were measured in the right and left cerebral hemispheres of rats with brain edema cryogenically induced to the right cerebral hemisphere. The effect of dexamethasone pretreatment was also studied. Twenty-four hours after lesion, maximal edema was attained concomitant with an accumulation of FFA (8.5-fold) and DG (2.9-fold). Polyunsaturated fatty acids (PUFA), primarily docosahexaenoic acid, increased greatly in both lipid pools. In the contralateral hemisphere, only DG levels increased, especially those containing stearate and arachidonate, which increased by almost 50%. By 48 h, FFA had decreased 60%, whereas DG had attained sham levels. These changes occurred prior to edema resolution. Dexamethasone decreased the degree of edema and the accumulation of PUFA-containing DG by 30% in both hemispheres. There was a complete inhibition of FFA and arachidonic acid accumulation in the lesioned side. These results suggest that dexamethasone: (1) inhibits phospholipases A2 that, in turn, decrease membrane phospholipid breakdown; and (2) has a limited effect on the enzymatic systems involved in PUFA-DG accumulation. Hence, in experimentally induced vasogenic brain edema, PUFA-containing DG, rather than FFA, may be related closely to the spreading of edema fluid.

Long-chain polyisoprenoid alcohols (dolichols) were measured in different brain regions dissected postmortem from 26 histopathologically confirmed cases of Alzheimer's disease and 24 age-matched nonAlzheimer control patients. They were significantly elevated in all parts of the cerebrum, but not in the cerebellum, of Alzheimer patients. The highest values were found in the temporal cortex and hippocampus. Out of the individual dolichol molecular species, the one with the most isoprene units (C105) was significantly increased in the temporal cortex, hippocampus, and basal forebrain of Alzheimer patients, compared with the controls. Dolichols were normal in the urinary sediment of 10 Alzheimer patients and nine patients with Down's syndrome, in comparison to age-matched controls for both groups. This is in contrast to neuronal ceroid-lipofuscinosis patients in whom dolichols are elevated in cerebral cortex, as well as in the cells of the urinary sediment, indicating generalized ceroid-lipofuscin storage.

Exposure of Mongolian gerbils to trichloroethylene (TCE) (320 ppm) in an inhalation chamber continuously for 3 mo resulted in an altered fatty acid pattern of phospholipid in discrete areas of the brain. Lipids were extracted from four brain regions: the cerebral cortex, the hippocampus, the cerebellar vermis posterior, and the brain stem. No changes induced by TCE were found in lipid class distribution among the different regions examined. Whole brain weights and weights of the dissected pieces were also unchanged. In ethanolamine phosphoglycerides from the cerebral cortex and the hippocampus, a decrease was found among long-chain fatty acids derived from linolenic acid with a corresponding increase of the linoleic acid family. The cerebellar vermis and the brain stem were less affected. Since areas rich in gray matter were affected more than those with a high proportion of white matter, it seems reasonable to assume that the fatty acid alterations of ethanolamine phosphoglycerides occur mainly in the gray matter. Furthermore, we suggest that the alterations can be a compensatory mechanism for the membrane fluidizing properties of TCE.

Isolated nerve endings (synaptosomes) that show high rates of metabolic activity have been prepared up to 24 h postmortem from the brains of patients who have died suddenly. In contrast, similar preparations from brains of patients dying after a prolonged terminal illness showed little or no respiration. These data suggest that the agonal state of the patient is of major importance when investigating specific defects in neurotransmitter function in cerebral disorders and effects of neuroactive drugs on human tissue.

Amino acid and protein metabolism has been studied in the dorsal root ganglia of rabbits with experimental allergic neuritis (EAN). The concentrations of a number of nonessential amino acids (glutamine, serine, aspartate, and glutamate) were reduced in the spinal ganglia of EAN animals without any comparable change in the blood plasma. The short-term influx of glycine and GABA was decreased in EAN animals, whereas that of histidine and valine was not altered. The prolonged accumulation of all the four amino acids was unchanged. These results suggest alterations in the cell metabolism of the dorsal root ganglia, rather than unspecific changes in cellular permeability. Furthermore, incorporation of tritiated valine, histidine, and glycine into proteins of EAN-ganglia in vitro was significantly increased. Autoradiography of the protein-bound [3H]-valine indicated alterations in the protein synthesis of the ganglion neurons: A decreased grain density was found in ganglion neurons of EAN animals. The increased grain densities in the affected ganglia were observed in macrophages, and possible in activated Schwann cells, over the demyelinated spots. The results suggest intraneuronal changes in the dorsal root ganglia of amino acid and protein metabolism, possibly in response to peripheral axonal injury and/or to nonspecific cytotoxic effect of active lymphocytes and macrophages.

Globoid cell leukodystrophy (Krabbe disease) in man is a rare genetic disorder caused by deficiency of galactosylceramidase activity. Clinical and pathological manifestations are almost exclusively confined to the nervous system, particularly to the white matter and the peripheral nerve. The disease also occurs in four other mammalian species: dog, cat, sheep and mouse. Except for the feline disease, for which enzymatic information is lacking, these animal models are genetically equivalent to the human disease. The clinical and pathological features are fundamentally similar in all species, as might be expected from the same underlying genetic defect. Nevertheless, significant species differences are observed in the clinical course, severity of pathological alterations, and analytical biochemistry. These genetically "authentic" animal models provide an invaluable tool for studies of the rare human genetic disorder. Results of studies already done and the future potentials are discussed.

The effect of streptozotocin (STZ)-induced diabetes on lipid uptake was studied in the rat retina. The intravitreal incorporation of [2-3H]glycerol was followed in retinal lipids from the first day of diabetes (acute state) up to 20 wk (chronic state). Total lipid incorporation decreased 50% 2 d after injection of STZ; the labeling remained lower than the control values throughout the 20 wk period studied. In the chronic state of diabetes, the time-course of the incorporation of [2-3H]glycerol during the first 2 h after its injection displayed a pattern of incorporation similar to that of the controls. The possibility that the decreased utilization of [2-3H]glycerol in the lipid pathway results from a competition between the injected [3H]glycerol and the glycolytic pathway during diabetes in rat retina in vivo is discussed.

The highly reproducible histochemical localization of glial fibrillary acidic protein (GFAP)+ qualifies it as an important marker of astrocytes in both research and clinical applications. The primary objective of this study was to produce monoclonal antibodies having the advantage of invariant specificity, affinity, and titer to GFAP-specific epitopes of wide species distribution. We report here the characterization of four monoclonal antibodies that recognize the same or spatially close epitopes specific to GFAP. The epitope(s) detected has been phylogenetically conserved; human, bovine, ovine, canine, porcine, rabbit, guinea pig, rat, murine, and chicken brain homogenates all specifically absorb monoclonal antibody activity. Of importance to the routine application of these new anti-GFAP monoclonal antibodies is the demonstration here of the stability of the antigen-antibody interaction in normal, reactive, and neoplastic astrocytes of both rat and human origin following various methods of fixation.

Cerebellar perikarya isolated from neonatal rats were exposed to 0-20 microM methyl mercury to simultaneously compare the effect on RNA and protein synthesis. Although 50% inhibition was found at approximately 8 microM for both [3H]uridine and [3H]phenylalanine incorporation, lower concentrations of methyl mercury produced 10-15% greater inhibition of RNA than protein synthesis. In vivo methyl mercury experiments also indicated a greater sensitivity of RNA synthesis in isolated cerebellar perikarya. The observed inhibition of RNA synthesis was not caused by a defect in cellular [3H]uridine uptake or by increased degradation of RNA. Both of these activities were altered by less than 10% at concentrations of methyl mercury that produced greater than 60% inhibition of RNA synthesis. Experiments showing that the specific activity of cerebellar cell RNA synthesis peaks and remains high between 4 and 10 d of age, whereas the specific activity of protein synthesis declines rapidly emphasize the potential importance of transcriptional perturbation in neonatal rats.

The current report describes a new technique for producing chronic experimental allergic encephalomyelitis (EAE)+ accompanied by demyelination in adult strain 13 guinea pigs. The disease is induced by a combination of passive transfer of lymph node cells sensitized to myelin basic protein (BP) and active challenge of the recipients with homologous spinal cord in Freund's complete adjuvants. The clinical-pathologic spectrum ranges from a progressively fatal form of chronic EAE leading to death in 4-7 wk, through a remitting-relapsing form, to a chronic-stable form lasting many months. In all of these forms large subpial plaques of demyelination occur in the spinal cord with active phagocytosis of myelin debris, especially at the edges. The axons are swollen, but remain intact throughout. The histologic appearances of the lesions suggest that lysis of myelin occurs before phagocytosis, one of the hypotheses proposed for the pathogenesis of lesions occurring in humans with multiple sclerosis.