Spontaneous Electrical Discharges Research Articles

Repetitive transcranial photobiomodulation but not long-term omega-3 intake reduces epileptiform discharges in rats with stroke-induced epilepsy.

Epilepsy is a yet under-recognized consequence after a stroke and nearly 30% of cases are pharmacoresistant. There is an unmet need for therapeutic interventions during epileptogenesis for better long-term disease outcomes. Transcranial photobiomodulation (PBM) and omega-3 (Ω-3) dietary supplementation are two approaches that have been shown promising neuroprotective effects after brain injuries. Here, we studied the PBM treatment or Ω-3 diet during epileptogenesis in long-term recurrent spontaneous abnormal electrical discharges after stroke. Wistar rats received repetitive 780 nm-laser in the scalp or oral diet with Ω-3 for 2-months after photothrombotic stroke. EEG recordings were performed 60 days after treatment end. PBM but not Ω-3 reduced both electrographic seizure duration and spikes number in the ipsilateral and contralateral cortices and ventral posteromedial thalamic nucleus. Conclusively, PBM reduced epileptiform discharges in stroke-induced epilepsy. Our results suggest the PBM as a therapeutic approach for stroke-induced epileptogenesis to minimize long-term disease outcomes.

Coupled Oscillators Model of Hyperexcitable Neuroglial Networks.

Glial populations within neuronal networks of the brain have recently gained much interest in the context of hyperexcitability and epilepsy. In this paper, we present an oscillator-based neuroglial model capable of generating Spontaneous Electrical Discharges (SEDs) in hyperexcitable conditions. The network is composed of 16 coupled Cognitive Rhythm Generators (CRGs), which are oscillator-based mathematical constructs previously described by our research team. CRGs are well-suited for modeling assemblies of excitable cells, and in this network, each represents one of the following populations: excitatory pyramidal cells, inhibitory interneurons, astrocytes, and microglia. We investigated various pathways leading to hyperexcitability, and our results suggest an important role for astrocytes and microglia in the generation of SEDs of various durations. Analysis of the resultant SEDs revealed two underlying duration distributions with differing properties. Particularly, short and long SEDs are associated with deterministic and random underlying processes, respectively. The mesoscale of this model makes it well-suited for (a) the elucidation of glia-related hypotheses in hyperexcitable conditions, (b) use as a testing platform for neuromodulation purposes, and (c) a hardware implementation for closed-loop neuromodulation.

The effects of dairy products on seizure tendency in mice

Epilepsy is a common neurological disorder which occurs as a result of a spontaneous electrical discharge in the brain. According to recent studies there might be a relationship between specific diet and seizure occurrence. Casein is an important protein of milk which often causes hypersensitivity. It seems the release of inflammatory cytokines during the process of immune system response alter the blood-brain-barrier (BBB) integrity and lead to neuronal inflammation which could constitute on epileptogenic focus. On the other hand, several studies represent full-fat milk or higher fat dairy products as an effective anti-inflammatory factor which elevate seizure threshold. The aim of present study was investigation of acute and chronic effects of dairy products including dough (a yogurt-based beverage), cheese, low and high fat yogurt and milk on pentylenetetrazole (PTZ)-induced seizures or electroshock in mice. The results of study indicated that lower fat dairy products reduced seizure threshold in intravenous PTZ-induced seizure as well as reduction in myoclonic and clonic jerk latencies in intraperitoneal PTZ-induced seizure. High fat products or cheese reduced seizure activity in both PTZ-induced models. Meanwhile both acute and chronic administration of dairy products had no effect on an electroshock-induced seizure. Therefore, diet-related seizures may depend upon the method which seizures are provoked.

Effects of Mechanical Load and Ionizing Radiation on Glass

This paper develops an approach to investigation of a solid as an integral system whose fundamental properties are determined by the energetics of its structure. Addressing the subject from a unified viewpoint, we consider the formation, accumulation, and transformations of defects in silicate and aluminophosphate glasses, which emit electromagnetic waves in a wide frequency range as a result of cracking. It has been shown that electron irradiation causes spontaneous electrical discharges, whose magnitude depends on the electron energy and irradiation time. The discharges occur at surface defects. Brush discharges develop in a layer where charged particles are distributed. In a thin layer of a charged dielectric, we observe a breakdown effect. The electrical discharge concentrates at surface defects, which can be produced in advance. A discharge can be initiated by approaching a grounded metallic tip to a charged surface even some time after irradiation. A discharge, mechanical loading, cooling, or heating of glass is accompanied by not only a light burst but also electromagnetic emission (EME), which correlates well with a polymorphic transformation process, thermoluminescence, etc. Thus, the release of accumulated energy from unirradiated and irradiated inorganic glasses on heating and cooling is accompanied by pulsed EME, whose intensity depends on the energy stored in the material.

Low-to-High Cross-Frequency Coupling in the Electrical Rhythms as Biomarker for Hyperexcitable Neuroglial Networks of the Brain.

One of the features used in the study of hyperexcitablility is high-frequency oscillations (HFOs, >80Hz). HFOs have been reported in the electrical rhythms of the brain's neuroglial networks under physiological and pathological conditions. Cross-frequency coupling (CFC) of HFOs with low-frequency rhythms was used to identify pathologic HFOs in the epileptogenic zones of epileptic patients and as a biomarker for the severity of seizure-like events in genetically modified rodent models. We describe a model to replicate reported CFC features extracted from recorded local field potentials (LFPs) representing network properties. This study deals with a four-unit neuroglial cellular network model where each unit incorporates pyramidal cells, interneurons, and astrocytes. Three different pathways of hyperexcitability generation-Na - ATPase pump, glial potassium clearance, and potassium afterhyperpolarization channel-were used to generate LFPs. Changes in excitability, average spontaneous electrical discharge (SED) duration, and CFC were then measured and analyzed. Each parameter caused an increase in network excitability and the consequent lengthening of the SED duration. Short SEDs showed CFC between HFOs and theta oscillations (4-8 Hz), but in longer SEDs the low frequency changed to the delta range (1-4 Hz). Longer duration SEDs exhibit CFC features similar to those reported by our team. First, Identifying the exponential relationship between network excitability and SED durations; second, highlighting the importance of glia in hyperexcitability (as they relate to extracellular potassium); and third, elucidation of the biophysical basis for CFC coupling features.

The Annual Epilepsy Review

Epilepsy is a group of disorders in which fits or seizures occur as a result of spontaneous abnormal electrical discharge in any part of the brain. This may be primary and often due to a genetic tendency (idiopathic epilepsy) or secondary to a structural abnormality of the cerebral cortex, for example as a result of tumour or trauma (symptomatic epilepsy). Seizures take many forms but usually show the same pattern on each occasion for a given individual. An average GP practice will have approximately 20 patients with epilepsy. The Quality and Outcomes Framework requires that a register of patients with epilepsy is kept and patients with epilepsy are reviewed annually. This article aims to provide an overview of epilepsy and its ongoing management and guidance on the areas that should be covered in the annual review.

Ciliary neurotrophic factor (CNTF) affects the excitable and contractile properties of innervated skeletal muscles.

The well-established trophic role of CNTF upon neurons led to performing clinical trials in patients of neurodegenerative diseases. However, trials were suspended due to side effects such as severe weight loss, hyperalgesia, coughing, muscle cramps and pain. So far it is not known how CNTF triggers the problems related to skeletal muscle cramps and pain. CNTF has also been described as a myotrophic factor for denervated skeletal muscles, but the possibility that it affects innervated muscles has also been considered. Since a myotrophic factor could be a valuable tool for treatment of several muscle diseases, we studied the effects of low doses of CNTF delivered systemically by an osmotic pump, over the electrical and mechanical properties of innervated and denervated fast and slow muscles. CNTF induced spontaneous electrical discharges and slowed twitches in innervated muscles, but did not prevent the changes induced by denervation. We postulate that the spontaneous discharges induced by CNTF in innervated muscles may be the cause of the cramps, coughing, and muscle ache reported by patients. At low doses, CNTF does not exert its myotrophic role over denervated muscles but clearly affects the excitable and contractile properties of innervated muscles.

Efficient syntheses of regioisomers of tiagabine

Abstract

Long-term regulation of serotonergic activity in the rat brain via activation of protein kinase A.

Serotonergic neurons located at the base of the mammalian brain innervate practically every region of the brain and the spinal cord. These neurons exhibit spontaneous electrical discharges in a rhythmical way. Their firing frequency is modulated by serotonin autoreceptors which also regulate intracellular cAMP levels. We have investigated how elevated levels of cAMP alter the development and the functional properties of serotonergic neurons in culture. To study the influence of cAMP on the expression of genes underlying serotonergic activity, a quantitative RT-PCR approach using internal standards was developed. Cultures of embryonic rat brain serotonergic neurons were continuously treated with cAMP analogues. Increased cAMP levels had three effects. First, the neuronal morphology was changed towards that typical for mature serotonergic neurons. Second, the expression of tryptophan hydroxylase, the rate-limiting enzyme in serotonin production, was increased in dibutyryl-cAMP treated cultures. Third, the expression of the inhibitory autoreceptor (5-HT1A) was down-regulated. These results suggest the existence of a mechanism by which the neurons react to synaptic input regulating intracellular cAMP levels. Increased cAMP concentrations affect the development and cause a prolonged activation of serotonergic transmission. Since 5-HT1A receptors inhibit cAMP formation, their down-regulation argues against a negative feedback control in this system, consistent with observations in vivo.

Neuromyotonia in hereditary motor neuropathy.

Two siblings with a distal motor neuropathy experienced cramping and difficulty in relaxing their muscles after voluntary contraction. Electromyographic recordings at rest revealed repetitive high voltage spontaneous electrical discharges that were accentuated after voluntary contraction and during ischaemia. Regional neuromuscular blockage with curare indicated hyperexcitability of peripheral nerve fibres and nerve block suggested that the ectopic activity originated in proximal segments of the nerve. Symptoms were improved with diphenylhydantoin, carbamazepine and tocainide.

Day-night differences in the sensitivity of adrenoceptors in the Syrian hamster pineal gland: an in vivo iontophoretic study

Investigations on the regulation of pineal melatonin synthesis in the Syrian hamster revealed distinct differences compared to this well-understood mechanism in rat. E.g., a circadian profile of pineal norepinephrine (NE) is absent, there is no β-adrenoceptor sensitivity during daytime and adrenergic receptor supersensitivity is not easily achieved. To elucidate the action of NE on pineal receptor sites, the effects of iontophoretic application of adrenergic compounds on spontaneous electrical discharge rates of pinealocytes were investigated during day- and nighttime. Following application of either NE, isoproterenol or clonidine, cells were activated, inhibited or not affected. Whereas about one-third of the units responded to iontophoretic application of sympathomimetics at daytime, the number of affected cells was doubled during the night. These results demonstrate the involvement of adrenoceptors in the regulation of circadian rhythms in electrophysiological properties of Syrian hamster pinealocytes. Since relatively few cells responded during daytime and inhibitory adrenergic mechanisms dominated at night, the classification of receptors by means of iontophoresis may provide a basis to explain the difficulty to influence pineal melatonin synthesis by sympathomimetics in the Syrian hamster.

In Vitro Studies on the Mode of Action of Pinacidil

(+/-) Pinacidil inhibited noradrenaline-induced contractions in rat aorta and portal vein. The spontaneous tone of guinea-pig bronchial and taenia caeci muscles was relaxed and the spontaneous mechanical activity of rat portal vein was abolished. (+/-) Pinacidil abolished contractions produced by low concentrations of KCl in rat aorta and portal vein, but had relatively little effect on responses to high KCl concentrations. The mechano-inhibitory effects of (+/-) pinacidil were antagonised by tetraethylammonium or procaine. In studies with the purified enantiomers of pinacidil, (-) pinacidil was approximately 20 times more potent that (+) pinacidil. Measurements of electrical activity showed that low concentrations of (+/-) pinacidil selectively inhibited spontaneous electrical discharges in rat portal vein. The duration of multispike electrical complexes was shortened, but spike frequency within a complex and the rate of spike rise and fall were unaffected. At higher concentrations, a dose-dependent hyperpolarisation was observed in both rat aorta and portal vein and the membrane potential approached EK. Using both 86Rb and 42K, (+/-) pinacidil produced a concentration-dependent increase in isotope exchange which correlated with those concentrations at which electrical and mechanical inhibitory effects were observed. Using radioimmunoassay, no pinacidil-induced changes in cyclic AMP or cyclic GMP concentrations were detected in rat aorta. These electrical, ion flux and biochemical measurements suggest that the in vitro mechano-inhibitory effects of pinacidil are associated with the opening of 86Rb-permeable K+ channels in smooth muscle. These effects were observed at concentrations of pinacidil similar to those found in vivo in the plasma of experimental animals and man. It is thus concluded that the hypotensive and antihypertensive effects of pinacidil are the consequence of the cessation of ongoing electrical activity and hyperpolarisation which follows the opening of K+ channels in vascular smooth muscle.

Investigations differentiating the mechanism of specific bradycardic agents from that of calcium channel blockers.

The effects of two "specific bradycardic agents", falipamil (AQ-A 39) and the alinidine-congener STH 2148 (2-[N-(cyclopropylmethyl)-N-(2,6-dibromophenyl)amino]-2-imidazolin e), on the spontaneous electrical discharge rate of intact guinea-pig sinus node preparations were investigated in comparison to that of the "calcium channel blocker" verapamil. Addition of falipamil (10 micrograms/ml) to a maximally rate lowering concentration of STH 2148 (30 micrograms/ml) exerted no further bradycardic effect. In contrast, verapamil (0.1 microgram/ml) added to either STH 2148 (30 micrograms/ml) or a maximally effective concentration of falipamil (30 micrograms/ml) resulted in a further, significant reduction of sinus rate. The results are compatible with the idea of a common mechanism of the two specific bradycardic agents, different from that of calcium channel blockers.

Involvement of the cholinergic mechanism in DDT and dieldrin action in the insect central nervous system

The effects of DDT and dieldrin on cholinergic neurotransmission were studied using the sixth abdominal ganglion of the cockroach. Spontaneous electrical discharges in the ganglion recorded with an extracellular electrode were augmented by 0.1 mM DDT and 1 μM dieldrin. This stimulating action was partly blocked by 0.5 mM d-tubocurarine and 0.1 mM hemicholinium-3 and disappeared in a high Mg 2+-low Ca 2+ medium. DDT and dieldrin increased both ACh release and ACh content in the ganglion. These results suggested that DDT and dieldrin stimulate both ACh release and synthesis.

Evidence that endogenous thyrotropin-releasing hormone (TRH) may control vagal efferents to thyroid gland: neural inhibition by central administration of TRH antiserum.

The intracerebroventricular (i.c.v.) injection of rabbit antiserum to thyrotropin-releasing hormone (TRH) to the urethane anesthetized rat inhibited the spontaneous electrical discharge of the superior laryngeal nerve (n.sl). On the other hand, the i.c.v. injection of rabbit antiserum to somatostatin (SRIF) failed to influence the nerve activity whereas SRIF itself is capable of inhibiting the n.sl activity. These findings suggest that TRH in the brain takes a role continuously in regulating the neural activity while SRIF is involved in the neuronal circuits as an agent for the down regulation of the autonomic nervous system.

Selective modification by opiates of neuronal activity of the medial basal hypothalamus

Multiunit activity was recorded from medial basal hypothalamic (MBH) neurons in freely behaving rats previously implanted with permanent Nichrome electrodes (62 μm in diameter). The effects of cumulative doses of morphine (0.5, 1.0, 5.0, 10.0, and 30.0 mg/kg, i.p.) and one dose of naloxone (1.0 mg/kg, i.p.) on spontaneous electrical discharges were studied. Dose-related responses were observed, i.e., each incremental dose of morphine elicited additional alterations of multiunits (25, 38, 59, 72, and 78% after 0.5, 1.0, 5.0, 10.0, and 30.0 mg/kg morphine, respectively). This procedure was utilized to identify and classify the MBH neurons with relation to the response patterns induced by morphine and its antagonist, naloxone. Four patterns (increase, decrease, biphasic changes in firing rates, or no effect) of response to morphine and three to naloxone (reversal, no effect, sensitivity to naloxone but not to morphine) were identified, i.e., a total of seven different patterns which may provide insights into neurophysiological actions relating to different functional properties of medial basal hypothalamic neurons. It was noticed that only the decreases of firing produced by morphine were blocked by naloxone. These observations also provide fundamental information of importance in studies of the physiological properties such as tolerance and dependence underlying chronic effects of opiates.

Mechanical, electrical, and biochemical effects of hypoxia and substrate removal on spontaneously active vascular smooth muscle.

Effects of hypoxia and glucose-free solution on the isolated rat portal vein were studied. Decrease of extracellular PO2 below 50 mm Hg caused graded inhibition of spontaneous mechanical activity; below 7 mm Hg, inhibition was complete in most preparations. Contracture force of depolarized portal vein was less sensitive to decreases in PO2. Responses to noradrenaline at all concentrations were markedly depressed at extreme hypoxia. Sucrose-gap experiments showed that hypoxia reduced the spontaneous electrical spike discharge. Mean tissue contents of PCr, ATP and glycogen (expressed as glucose) were 3.02, 2.47 and 5.07 micromol/g cell wt. in spontaneously active control muscles and 1.07, 1.65 and 1.83 after 20 min anoxia. Physiological variations in PO2 may influence myogenic activity of vascular smooth muscle largely through an action at the membrane level and this mechanism may participate in local blood flow control. Caculations indicated that the graded response to hypoxia in the present in vitro experiments was not due to diffusion limitation. Spontaneous mechanical activity was relatively well maintained even after prolonged exposure to glucose-free solution, whereas the responses to K+ and noradrenaline were markedly suppressed. Electrophysiological recordings during spontaneous activity indicated desynchronization and impaired conduction. PCr and ATP were maintained at control levels and glycogen reduced by 50 per cent after 2 h in glucose-free medium. Indications of the use of amino acids (glutamate) as substrate under these conditions were obtained.

Spontaneous versus driven activity in intracerebellar nuclei: A tissue culture study

Intracerebellar nuclei in cerebellar explants derived from newborn mice were recognized as focal points of converging Purkinje cell axons. Morphological studies demonstrated characteristic architectonic features and abundant typical large and small intracerebellar nucleus neurons. Spontaneous electrical activity was recorded extracellularly from cortical regions of cerebellar cultures, but no endogenous activity was evident in recording from intracerebellar nuclei. These neurons were pharmacologically isolated from the inhibitory influence of Purkinje cells by application of bicuculline and lidocaine-HCl, without the resultant emergence of endogenous activity. Intracerebellar nucleus neurons in deafferented cerebellar cultures proved incapable of generating spontaneous electrical discharge, suggesting that background excitatory activity in intracerebellar nuclei in situ may be driven by collaterals of cerebellar afferent fibers.

Effect of calcium chelation by L-phenylalanine on (Na + + K +)-stimulated ATPase of chick brain microsomes

Previous work from this laboratory has revealed that chicks showed a reversible narcosis when injected with 1.62 nmole of L-phenylalanine [ 1 ] . After 4 hr, the brain phenylalanine level was as high as 3.8 pmole/g tissue [2]. It has been shown that some amino acids are chelators of divalent cations [3-61. Since membrane-bound Ca2+ is essential for the maintenance of cellular and axonal membrane excitability and low Ca2+ leads to depolarization, spontaneous electrical discharges and eventually suppression of membrane excitability [7151, it was of interest to test the hypothesis that high concentrations of L-phenylalanine (up to 5 mM) might compete for Ca2+ and displace it from the membrane surface. This displacement, in vim, would lead to reduction (and ultimate blockage) of the action potential. This communication reports studies of the effect of L-phenylalanine on membrane-bound (Na+ + K+)ATPase as compared with the effects of strong chelators such as EDTA and EGTA on the same system.

EFFECTS OF X-RAYS ON ELECTRICAL ACTIVITY IN THE COCKROACH BLABERUS GIGANTEUS.

SIGNIFICANT changes in electroretinograms (ERG) and in spontaneous electrical activity recorded from the compound eyes of cockroaches have been found here during investigations of the effects of radiation on insects. These electrical discharges, although similar to the activity recorded from the optic nerve of Limulus1, do not exhibit as marked a change in frequency with light stimulation. In this communication, we present the results of preliminary studies of the effects of X-rays on both the ERG and the spontaneous electrical discharges in the eye of the cockroach B. giganteus.