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Neuritogenesis and regeneration in the nervous system: an overview of the problem and on the promoting action of gangliosides.
No full textBlood-brain barrier preservation in the in vitro isolated guinea pig brain preparation
No full textThe morphofunctional preservation of the blood-brain barrier (BBB) was evaluated in the isolated guinea pig brain maintained in vitro by arterial perfusion. Electron microscopy evaluation after 5 hr in vitro demonstrated that cerebral capillaries and BBB specializations in this preparation retain features compatible with structural integrity. BBB-impermeable and -permeable atropine derivatives arterially perfused to antagonize carbachol-induced fast oscillatory activity confirmed the functional preservation of the BBB in vitro. To study BBB function further, changes in extracellular K+ concentration during arterial perfusion of a high-K+ solution were measured with K+-sensitive electrodes positioned in the cortex and, as control, at the brain venous outlet, where the solution perfused through the brain arterial system was collected. After 5 hr in vitro, the [K+]o values measured during high-K+ perfusion in the piriform and entorhinal cortices were 5.02 ± 0.17 mM (mean ± SE) and 5.2 ± 0.21 mM, respectively (n = 6). Coperfusion of the high-K+ solution with the Na+/K+ pump blocker ouabain (10 M; n = 4) induced consistently spreading depression preceded by a rise in [K+]o. Finally, sporadic, isolated spots of extravasation of the fluorescent marker fluorescein isothiocyanate (FITC)-dextran preferentially circumscribed to deep cortical layers was observed in brains perfused with FITC-dextran after 5 hr in vitro. The study demonstrates that the in vitro isolated guinea pig brain is viable for studying cerebrovascular interactions and BBB permeability of compounds active in the central nervous system
Gangliosides' dual mode of action: A Working hypothesis
No full textUsing in vitro preparations, we have tested the hypothesis that gangliosides, and more specifically GM1, may prevent progressive neural damage following a trauma by means of complex intracellular mechanisms that might be triggered originally by ganglioside interaction with neuronal membranes. We have recently shown that 2-hr ganglioside incubation in vitro stimulates the membrane Na/K pump in neuromuscular preparations. However, 5-6 hr incubation or in vivo treatment for 3 days with a daily injection of gangliosides at a dose of 1 or 10 mg/kg prevents the depolarization that normally occurs after several hours of exposure to K+-free solutions. In such undepolarized muscles, the electrogenic Na+/K+ pump does not seem to be activated. Hippocampal slices subjected to hypoxia undergo depolarization, which is reversed after oxygen readmission. The recovery phase is characterized by a huge hyperpolarization, probably reflecting electrogenic pump activity. In control preparations the depolarization occurs after 3.15 ± 0.4 min and has a value of 48.7 ± 5.7 Mv; GM1 treatment for at least 4-5 hr increases the latency to 7.3 ± 2.3 min, and the depolarization is reduced to 31.8 ± 4.5 mV. This protective effect is accompanied by a reduced hyperpolarization in treated preparations. The ionic studies performed on neuromuscular preparations indicate that the protective effect may be not solely dependent on K+ leakage; however, the experiments are not conclusive and must be repeated with more direct methods. The results obtained indicate a dual mode of action for gangliosides. The early one seems characterized by membrane-enzyme activation, perhaps in relationship to their incorporation in the membrane, which could be compatible with previously described effects, such as enhancement of neuronal sprouting and neuritogenesis. The late one, occurring 4-5 hr after ganglioside addition in vitro, might reflect intracellular events and be compatible with the protective action exhibited by gangliosides against neural damage
INVIVO TREATMENT WITH GM1 PREVENTS THE RAPID DECAY OF ATPASE ACTIVITIES AND MITOCHONDRIAL DAMAGE IN HIPPOCAMPAL SLICES
No full textSlices from rat CA3 hippocampal area show a 30% decrement in ATPase activity after 35 min of 'in vitro' incubation. Such a drop is accompanied by an alteration of mitochondrial ultrastructure. However, if rats are treated daily with GM1 ganglioside (10 mg/kg during 3 days) both phenomena are fully prevented. These results would suggest a protective effect of gangliosides onto membrane structures under stress conditions
GM1 ganglioside enhances regrowth of noradrenaline nerve terminals in rat cerebral cortex lesioned by the neurotoxin 6-hydroxydopamine
No full textThe effect of exogenous GM1 ganglioside on selectively noradrenaline-denervated rat cerebral cortex was investigated by measuring the spatial distribution of endogenous noradrenaline levels and by fluorescence histochemical analysis. A local noradrenaline denervation was produced by intracortical infusion of the selective catecholamine neurotoxin 6-hydroxydopamine for 3 or 7 days. The neurotoxin infusion caused an almost complete noradrenaline denervation in a restricted area around the infusion point as reflected by an almost complete long-term disappearance of noradrenaline nerve terminals and reduction of noradrenaline levels. There was with time a slow recovery of the levels, most likely related to a spontaneous noradrenaline nerve terminal regeneration. Post-treatment for 1 week with GM1 had very small effects on the 6-hydroxydopamine-induced reduction of the noradrenaline levels, while pretreatment with GM1 for 3 days before the neurotoxin infusion and continuing the GM1 administration for another 7-14 days significantly enhanced noradrenaline recovery, as observed both bio- and histochemically. GM1 had no effect on the 6-hydroxydopamine-induced noradrenaline depletion acutely, indicating that GM1 does not interfere with the direct neurotoxic actions of 6-hydroxydopamine. The present results thus indicate that exogenous GM1 enhances regrowth of noradrenaline nerve terminals which may be due to a regrowth stimulatory effect (regeneration/collateral sprouting) and/or related to protective actions of GM1 against retrograde degeneration of noradrenaline axons following the neurotoxin-induced lesion
Effect of GM1 ganglioside on neonatally neurotoxin induced degeneration of serotonin neurons in the rat brain
No full textThe effect of exogenous GM1 ganglioside on the 5,7-dihydroxytryptamine (5,7-HT; a selective serotonin neurotoxin) induced alteration of the postnatal development of central 5-hydroxytryptamine (5-HT; serotonin) neurons has been investigated using neurochemical and immunocytochemical techniques. Neonatal 5,7-HT (50 mg/kg s.c.) treatment is known to lead to a marked and a permanent degeneration of distant 5-HT nerve terminal projections (e.g. in cerebral cortex, hippocampus and spinal cord), while projections close to the 5-HT perikarya in the mesencephalon and pons-medulla increase their nerve density. These regional alterations are reflected by decreases and increases, respectively, of endogenous 5-HT, [3H]5-HT uptake in vitro and number of 5-HT nerve terminals demonstrated by immunocytochemistry. Treatment of newborn rats with GM1 (4 × 30 mg/kg s.c.; 24 h interval) had no significant effect on the postnatal development of 5-HT neurons. GM1 administration had furthermore no effect on the 5,7-HT induced alteration of the regional 5-HT levels and [3H]5-HT uptake in the cerebral cortex acutely, indicating that GM1 did not significantly interfere with the primary neurodegenerative actions of 5,7-HT. At the age of 1 month a clear counteracting effect of GM1 was observed, in particular of the 5,7-HT induced 5-HT denervations. The 5-HT levels in the frontal and occipital cortex were reduced to 25 and 20% of control after 5,7-HT alone, while these values were 70 and 40%, respectively, after 5,7-HT and GM1 treatment. A similar antagonizing effect of GM1 was found in the frontal cortex when measuring [3H]5-HT uptake. GM1 treatment also caused a minor reduction of the 5,7-HT induced increase of the 5-HT levels in striatum and mesencephalon. Quantitation of 5-HT nerve terminal density in sections processed for 5-HT immunocytochemistry using an automatic image analysis system showed markedly more nerve terminals in the frontal and occipital cortex after 5,7-HT + GM1 compared to 5,7-HT treatment alone. Minor counteracting effects of GM1 were noted in the hippocampus and spinal cord (thoracic-lumbar) as evaluated by chemical 5-HT assay, although substantial counteracting effects were observed locally in these areas by quantitative immunocytochemistry. The present data are compatible with the view that GM1 ganglioside administration has a preventing action on degeneration processes secondary to the direct 5,7-HT neurotoxicity and/or a growth stimulatory effect on central 5-HT neurons damaged by a selective chemical neurotoxin in the neonatal stage
GM1 GANGLIOSIDE PROMOTES RECOVERY OF CENTRAL AND PERIPHERAL NORADRENALINE NEURONS AFTER A SELECTIVE NEUROTOXIN INDUCED LESION
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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