Biomedical subjects

G Zoltay

Publications and source records attributed to G Zoltay.

13 recordsLinked to original sources

PubMed1994

Presynaptic modulation by eicosanoids in cortical synaptosomes.

In continuing experiments to determine the ionic basis of inhibitory presynaptic modulation, rat cortical synaptosomes were employed and receptor-activated K+ efflux was determined with a K+ sensitive electrode. When synaptosomes were sub-optimally depolarized by veratridine, the addition of agents that activated purinergic, alpha 2-adrenergic, muscarinic and opioid receptors all promoted K+ efflux. With 2-chloroadenosine as a model inhibitory presynaptic modulator, the increased K+ efflux evoked by this agent was blocked by the cyclooxygenase inhibitor indomethacin suggesting that arachidonic acid or its metabolites was an intermediary in opening the channel. When arachidonic acid and PGE2 were tested, both promoted K+ efflux that was inhibited by dendrotoxin and mast cell degranulating peptide, two agents that are known to inhibit a delayed rectifier K+ current. Our results suggest that via eicosanoid second messengers, inhibitory presynaptic modulators open a sub-class of K channels that hyperpolarize nerve terminals, therefore less Ca2+ would enter per nerve impulse and thus the evoked release of neurotransmitters would be decreased.

Animals↗

PubMed1994

Presynaptic modulation by dopamine and GABA opens a potassium channel in rat cortical, striatal and hippocampal synaptosomes via eicosanoids.

Using a K(+)-sensitive electrode in synaptosomal preparations, the presynaptic modulating effect of dopamine and GABA in opening a K+ channel was investigated. In cortical, striatal and hippocampal synaptosomes dopamine D1 and D2 agonists and a GABAB agonist promoted the efflux of K+ in all three preparations. The effect was blocked by the cyclooxygenase inhibitor, indomethacin suggesting that eicosanoids act as second messengers in these systems. The inference in these studies is that dopamine and GABA hyperpolarize presynaptic terminals thereby reducing Ca2+ influx and thus inhibiting the evoked release of transmitters.

Animals↗

PubMed1993

Dendrotoxin blocks a class of potassium channels that are opened by inhibitory presynaptic modulators in rat cortical synaptosomes and slices.

1. Rat cortical synaptosomes were prelabeled with radioactive acetylcholine and the release induced by veratridine was determined in the absence and presence of the inhibitory presynaptic modulators, 2-chloroadenosine, carbamylcholine, clonidine, and morphine. All four agents inhibited the evoked release of acetylcholine and this inhibition was reversed by dendrotoxin. 2. Using perfused cortical slices and an extracellular K-sensitive electrode, all modulators again increased K efflux that was blocked by dendrotoxin. In contrast, glybenclamide and tetraethylammonium did not block the modulator-induced efflux.

2-Chloroadenosine↗

PubMed1993

Receptor-activated modulation in rat cortical slices as measured with a K-sensitive electrode.

The effects of a variety of presynaptic receptor-activating modulating agents on potassium efflux have been investigated using a potassium (K)-sensitive extracellular electrode in rat brain cortical slices that are electrically stimulated. Purinergic, alpha 2-adrenergic, opioid and muscarinic drugs all increased K outflow. When these agents were used in combination at maximal concentrations, only morphine promoted a further increase in K efflux, suggesting that it utilized a different K channel or acted on cellular elements different from those of the other modulators.

2-Chloroadenosine↗

PubMed1993

An immediate morphopathologic response of neurons to electroshock; a reliable model for producing "dark" neurons in experimental neuropathology.

Ninety rats were electroshocked by a single condenser discharge 1 min. prior to perfusion fixation and delayed autopsy. Voltage and capacity of the condenser as well as surface area and position of the electrodes were varied between 125 and 1250 V, 20 and 200 microF, 2 and 24 mm2, and frontal to posterior, respectively. Within these ranges the electroshock rendered a varying number of brain neurons together with their dendritic arborization stainable by a special silver method. In toluidine blue preparations both somata and nuclei of these neurons appeared markedly shrunken and hyperchromatic, indicating morphological damage ("dark" neuron). A 250-V shock damaged only granule neurons of the hippocampal dentate gyrus. After a 750-V shock it was the substantia nigra, the lateral septal nucleus, the anterior amygdaloid area, and the lateral preoptic area that consistently contained electrically damaged neurons, without other kinds of parenchymal damage.

Animals↗

PubMed1992

Light microscopic response of neuronal somata, dendrites and axons to post-mortem concussive head injury.

Forty anesthetized rats were cooled below 3 degrees C by 30-min transcardial perfusion of chilled physiological saline before a concussive head injury. The animals were then perfusion-fixed with a buffered formaldehyde-glutaraldehyde solution. Another forty rats were fixed by 30-min transcardial perfusion of the same fixative before a similar concussive head injury. In brain sections of both groups of animals a new silver method stained, in a Golgi-like fashion, a number of neurons and long axonal segments scattered among unstained ones. The similarity between these findings and those obtained following in vivo concussive head injuries described in accompanying papers suggests that the formation of traumatically induced argyrophilic neuronal damage is independent of metabolic processes, i.e., it may be a primary morphopathological process.

Animals↗

PubMed1992

Formation of "dark" (argyrophilic) neurons of various origin proceeds with a common mechanism of biophysical nature (a novel hypothesis).

Based on recent findings described in accompanying reports as well as on relevant observations in the literature we hypothesize that: (1) the fundamental elements in the mechanism of the formation of "dark" (argyrophilic) neurons are independent of the causative conditions including post-mortem or in vivo mechanical injuries and various in vivo pathometabolic processes such as blood recirculation following ischemia; (2) the causative conditions, each in its own mechanical or metabolic way, induce the same morphopathological damage at one point only within each affected neuron; (3) this damage spreads throughout the respective somato-dendritic or axonal domain and entails type III argyrophilia; (4) the intraneuronal spread of the morphopathological damage consumes mechanical energy stored by the neurofilaments in the form of a metastable inner structure, and (5) is propagated by a process working, in certain structural and energetical respects, on the domino principle; and (6) the primary neuronal damage caused in the above manner might be secondarily modified in different directions by different postcausation conditions.

Animals↗

PubMed1992

An immediate light microscopic response of neuronal somata, dendrites and axons to non-contusing concussive head injury in the rat.

Sixteen rats were killed by transcardial perfusion fixation 1 min after a non-contusing concussive head injury, and seven rats 1 day later. In each of the "1-min" animals Golgi-like neurons and long axonal segments scattered in various proportions among unstained neurons and axons were demonstrated by a new silver method both near to and far from the impact site in a parenchymal environment unaffected by contusion. The silver-stained neurons, dendrites and axons were considered to have been damaged by the trauma because they were consistently absent from control brains. In the "1-day" brains silver-stained dendrites and axons had a beaded appearance, indicating an advanced stage of morphopathological damage. From details of these findings the following conclusions were drawn: (1) trauma can directly induce some kind of morphopathological damage in neurons which manifests itself in shrinkage of the soma and tortuosity of appendages as well as in type III argyrophilia; (2) different vulnerability of various brain areas is likely due to the inhomogeneity of the trauma-induced pressure wave propagating through the brain; and (3) the somato-dendritic and axonal domains of the neuron are selectively vulnerable to different values of the parameters of the intracranial pressure wave.

Animals↗

PubMed1992

An immediate light microscopic response of neuronal somata, dendrites and axons to contusing concussive head injury in the rat.

Thirty-four rats were killed by transcardial perfusion fixation 1 min after a contusing concussive head injury, and 17 rats 1 day later. From the results obtained with a new silver method demonstrating traumatically damaged neuronal somata, dendrites and axons the following conclusions were drawn: (1) outside the contused territories all features of traumatically induced neuronal argyrophilia are similar to those found in non-contusing concussive head injury, as reported in an accompanying paper; (2) within contused territories the neuronal argyrophilia is abolished by some substance released either from damaged blood vessels or damage parenchymal cells, while the neuronal damage otherwise underlying the induction of argyrophilia is present; (3) different phenotypes of neurons are vulnerable to different values of the parameters of the intracranial pressure wave generated by the trauma; (4) some of the neurons may recover from the traumatically induced argyrophilic damage; (5) traumatically induced inundation of neurons with extracellular tracers, as reported by other authors, and somato-dendritic argyrophilia may be different manifestations of one and the same phenomenon; and (6) diffuse primary traumatic axonal injury in human neuropathology may be closely correlated to axonal argyrophilia.

Animals↗

PubMed1990

Golgi-like demonstration of "dark" neurons with an argyrophil III method for experimental neuropathology.

A silver method is proposed for the selective, well-contrasted and reproducible demonstration of "dark" neurons in frozen, vibratome and paraffin sections cut at a thickness of 5 to 200 microns from aldehyde-fixed brains. The Golgi-like staining of the dendrites enables assorting of "dark" neurons according to characteristic neuron classifications. The staining procedure includes an esterification with 1-propanol, a treatment with diluted acetic acid and development. The esterification strongly increases the argyrophilia of both "dark" neurons and mitochondria. Unwanted co-staining of mitochondria is suppressed by the acetic acid treatment, while a special developer is used to render the staining controllable. The applicability of the method to experimental neuropathology is demonstrated by Golgi-like staining of "dark" neurons in rat brains exposed, before transcardial perfusion-fixation and delayed autopsy, to various pathological conditions including ischemia, hypoglycemia, trauma, status epilepticus, deafferentation and poisoning with kainic acid, colchicine and sodium azide, respectively.

Animals↗

PubMed1990

Ionic basis of inhibitory presynaptic modulation in rat cortical synaptosomes.

We have investigated the possibility that, regardless of the involvement of a second messenger system, the ultimate effect of presynaptic, receptor-activated inhibitory modulation is the opening of a K channel. With the consequent hyperpolarization of the terminal, less Ca2+ would enter and this would result in the observed diminished release of a neurotransmitter. This possibility was explored utilizing rat cortical synaptosomes that were prelabeled with either 86Rb or [3H]acetylcholine, depolarizing with either K+ or veratridine, and measuring either efflux of 86Rb or release of [3H]acetylcholine in the presence or absence of inhibitory presynaptic modulators. The modulating agents used were 2-chloroadenosine, carbamylcholine, clonidine, and morphine. In all instances, these agents promoted an increased efflux of 86Rb, indicating hyperpolarization, and decreased release of acetylcholine. These results are compatible with our suggestion that an increase in K conductance may be responsible for presynaptic inhibition of the release of neurotransmitters.

2-Chloroadenosine↗

PubMed1990

The ionic basis of inhibitory presynaptic modulation and substance B.

We have investigated the possibility that, regardless of the involvement of a second messenger system, the ultimate effect of presynaptic, receptor-activated inhibitory modulation is the opening of a K channel. This possibility was explored utilizing rat cortical synaptosomes that were prelabeled with either 86Rb or [3H]acetylcholine, depolarizing with either K+ or veratridine, and measuring either efflux of 86Rb or release of [3H]acetylcholine in the presence or absence of inhibitory presynaptic modulators. The modulating agents used were 2-chloroadenosine, carbamylcholine, clonidine, and morphine. In all instances, these agents promoted an increased efflux of 86Rb, indicating hyperpolarization, and decreased release of acetylcholine. These results support our contention that an increase in K conductance may be responsible for presynaptic inhibition of the release of neurotransmitters. We have also found that substance B, a compound that reverses presynaptic modulation, appears to act by closing K channels.

Acetylcholine↗

PubMed1987

[Value of the carotid compression test for the diagnosis of cerebrovascular disorders].

The carotid compression tests have been performed in 1940 outpatients and 233 hospitalized patients with clinical signs and symptoms of cerebrovascular disturbances. The frequency of EEG slowing, positivity of the compression tests and carotis sinus hypersensitivity was in patients with local neurological signs: 36%, 22.5%, and 24.8%, while the corresponding numbers for patients without neurological signs were: 24.6%, 21.8%, 14.7%. On the basis of the carotis angiography the following groups of the patients could be formed: Thrombosis of the internal carotid artery (A), thrombosis of the anterior or medial cerebral artery (B), carotis stenosis (C), other vascular pathological signs of the arteries (D), normal angiography (E). They were compared with the control group of patients with vertebrobasilar insufficiency (F). The frequency of EEG slowing (A = 92%, B = 72%, C = 58.9%, D = 57%, E = 40%, F = 22.5%). The percentage of the positivity of carotid compression tests (A = 54%, B = 32%, C = 46%, D = 26%, E = 12%) and occurrence of carotis sinus hypersensitivity (A = 26.8%, B = 16%, C = 17.7%, D = 10.8%, E = 11.3%, F = 6.9%) were proportionate to the pathological morphological signs. The results of the compression tests may give indication for detailed clinical investigation, and are helpful in the estimation of the functional capacity of the carotid arteries in the cerebral circulation.

Brain Ischemia↗