Neurochemical pathology最新文献

We have employed axonal transport and degeneration techniques to study the development of major rubral connections in the North American opossum. Opposums were chosen for study because they are born 12 d after conception and have a protracted postnatal development. Our results suggest that: The red nucleus innervates the spinal cord early in development, well before the somatic motor-sensory cortex (Cabana and Martin, 1984); the red nucleus projects to the spinal cord before it receives substantial projections from the cerebellum or cerebral cortex; and projections from the cerebellum reach the red nucleus significantly earlier than those from the cerebral cortex.

Developing and regenerating frog optic axons grow within optic pathways and form connections only with optic targets. However, unlike normal development, many regenerating optic axons in the adult frog are misrouted within optic pathways, including axons that grow into the opposite retina. Many of the axons misrouted during regeneration appear to be collaterals of axons that grow in normal directions. Ganglion cell loss of up to 60% occurs after optic nerve damage, beginning prior to reinnervation of optic targets. Massive axonal collateralization also takes place near the point of nerve damage, causing the normal order found within the nerve to be lost. Collaterals are eliminated as selective reinnervation is completed, and the smaller complement of optic cell axons remaining after regeneration form an expanded projection within optic targets. Evidence is reviewed that suggests that factors involved in axonal guidance and target recognition during development remain intact in the adult frog brain. Additional conditions resulting from nerve injury causes axonal guidance to be less successful during regeneration.

When spinal pathways are damaged in newborn animals and their behavior is examined in adulthood, motor function is superior to that seen in animals in which the same lesion was made in adulthood. This is the infant lesion effect. After neonatal sensorimotor cortex ablation, spinal hemisection, or spinal transection, sparing of contact placing is observed; in adults, all three lesions abolish contact placing permanently. The anatomical correlates of the infant lesion effect are different in each case. After neonatal unilateral cortical ablation, an exuberant crossed corticorubral pathway from the other cortex fails to retract (as it does normally), giving the remaining cortex a path for mediating contact placing. After neonatal spinal hemisection, late-developing corticospinal axons take an aberrant course around the lesion and mediate contact placing. After neonatal transection, the spinal inhibitory GABA-ergic system fails to develop to a normal extent. This may result in abnormal enhancement of spinal reflex pathways, especially since some dorsal roots increase their input after that lesion. Thus, a number of factors may influence the outcome of damage to the developing nervous system.

Gangliosides are present in nervous tissues of echinoderms and chordates, but the amounts and patterns differ widely. There are changes in the ganglioside contents of nervous tissues during development in most animals studied. To a large extent, regional differences and changes with development and degeneration in ganglioside composition reflect changing and different proportions of cellular types and subcellular organelles within the tissue. GM1 and GM4 are enriched in myelin; GD1a may be a marker for dendritic arborization. During regeneration of fish optic nerve and rat sciatic nerve there is an increased amount of ganglioside proximal to the regenerating axon tips, which may largely be a result of accumulation. This could provide a relatively large reservoir of ganglioside to become incorporated into the sprouting axolemma. Gangliosides added exogenously to growth medium can induce neuritogenesis of several types of neurons. The mechanisms of this action are unknown but may be related to nerve growth factor, microskeletal organization, membrane fluidity, and other factors. Gangliosides injected into young animals affect brain development, but further studies are required to determine these effects more specifically. Ganglioside administration increases the number of sprouts in regenerating peripheral nerves, but does not seem to accelerate axonal elongation. Parenterally administered gangliosides alter the recovery of brain tissue from a variety of types of lesions, and clinical trials are in progress to determine if they are of benefit in human neurological disorders. The biochemical mechanisms of these in vivo ganglioside effects are poorly understood, but may involve modulation of several enzyme systems as well as other properties of neural membranes, such as fluidity. It is possible that gangliosides may play similar roles and operate through some of the same mechanisms in developing and regenerating nervous tissues.

The effect of two dihydropyridine calcium (Ca) channel blocking drugs on cerebral glucose metabolism (LCGU), blood flow (LCBF), and blood flow-metabolism coupling were studied in thermally injured rat brain using quantitative radioautographic techniques. No reversal of the previously noted LCGU depression caused by the freezing lesion (Pappius, 1981) was detected following treatment with either PY-108-068 (PY) or nimodipine (NIM). These results therefore provided no support for the role of Ca in the mechanism of functional disturbances induced by cold injury (Pappius and Wolfe, 1983b), though they do not rule out its involvement. Treatment with PY, but not NIM, reestablished the normal LCBF-LCGU relationship in cortical areas, which has been shown to be disturbed by the freezing lesion and in subcortical and brainstem structures, in which the alteration caused by the injury was not as pronounced. The results suggest that the mechanism that apparently uncouples LCBF from LCGU in injured brain is altered in the presence of PY. However, since NIM did not have the same effect on LCBF, it is not clear whether the effects of PY relate to blockade of Ca channels or some other effect of PY.

This paper describes the changes caused by in vivo hyperoxygenation of rats in the brain synaptosomal actomyosin-like protein preparation. We demonstrate that this preparation is composed of protein and phospholipid components attached to each other. Upon hyperoxygenation, a peroxidation of phospholipids in the lipid component proceeds. Simultaneously, with the increase of malondialdehyde, conjugated double bonds, and fluorescence intensity levels, a decrease of protein -SH groups levels, and Mg2+-dependent ATPase activity is observed. The above changes reduce the ability of the protein to superprecipitate, which reflects a contractile reaction in vivo.

Graded hypoglycemia was induced with insulin in anesthetized and artificially ventilated rats. The brains were frozen in situ, and the regional glucose concentration was determined in different areas of the brain with the bioluminescent technique. In all nine brain structures analyzed, brain tissue glucose content assessed with the bioluminescent technique correlated closely with the plasma glucose levels; the tissue/plasma glucose concentration ratios approximating 0.3. There were, however, relatively marked regional differences. For example, whereas glucose concentrations in the neocortex, caudoputamen, hippocampus, and cerebellum were very low in rats having a plasma glucose concentration of less than 4 mumol/mL, higher glucose concentrations were present in these animals in the thalamus, hypothalamus, and brainstem. The lowest glucose content was found in the caudoputamen, which was depleted of glucose in animals with plasma levels below 3 mumol/mL. It is concluded that regional inhomogeneities in the glucose levels observed during hypoglycemia may, at least in part, explain differences in the vulnerability of different brain structures following reversible hypoglycemia.

The effects of phenytoin (PHT) treatment on brain weights and the zinc (Zn) and copper (Cu) concentrations in liver, kidney, and five parts of the brain have been studied in rats. After 32 wk of treatment (daily doses 72-88 mg/kg body weight), significantly reduced brain weights were found in rats sacrificed during treatment, but not in those sacrificed after 14 d of abstinence. The weight reduction mainly seemed to affect cortex, but cerebellum was also influenced. The PHT treatment during 18 wk did not significantly reduce the brain weights. At the end of treatment, significantly increased serum Cu concentrations were found, as well as decreased Zn levels in the liver and low Cu levels in the kidney. No large alterations were found in the trace element concentrations of different brain regions. The PHT treatment for 32 wk induced physical dependence, recorded as convulsions. It is suggested that PHT through a chelate binding with Zn and Cu interferes with the metabolism of the trace elements and the drug may cause a Zn deficiency. The observed decrease of the brain weights may have some parallel to the mental side effects of the drug observed during chronic epilepsy therapy.

Protein composition in different segments along nerves from rats intoxicated with 2,5-hexanedione (HD) was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by immunoblotting, using monoclonal antibodies specific for each of the three neurofilament polypeptide components (H, M, and L). Comparison with nerve protein extracts from normal (control) rats revealed a disappearance of the largest neurofilament polypeptide (H), accompanied by accumulation of higher-molecular-weight products that were immunoreactive with H-specific antibodies. Both the extent of this crosslinking and its localization in particular portions of peripheral nerves showed a correlation with HD dosage and with the known progression of ultrastructural features during HD-induced neuropathy. Similar changes were not detected for the M and L neurofilament components.

Lead (Pb) intoxication in developing mammals, including humans, produces serious brain damage. In addition, it is known that nutritional status influences the susceptibility to Pb toxicity. We developed an in utero undernutrition model based on restriction of blood supply to fetuses on d 17 of pregnancy (IUGR rats). The aim of this study was to investigate in vitro the possible effect of Pb on Na+, K+ATPase activity in the brain of developing IUGR and control rats from 6 to 60 d after birth. In addition, we measured the stimulation of Na+, K+ATPase by the monoamines noradrenaline and serotonin. Our results show that: The neurotoxic effect of Pb is an age-related phenomenon. Both IUGR and control rats were more sensitive to Pb in the first week of life. In adults, Pb had a weak inhibitory potency; the delayed matured brain in IUGR animals seemed less sensitive to Pb when compared to age-paired control rats; in the IUGR group, at 15 and 22 d, low doses of Pb had a stimulatory effect on Na+, K+ATPase instead of an inhibitory effect; noradrenaline and serotonin stimulated Na+, K+ATPase activity to an equivalent extent, but this was greater in IUGR than control rats; and at low Pb concentrations, the studied monoamines reversed Pb-induced inhibition.