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Biomedical subjects

T Kukorelli

Publications and source records attributed to T Kukorelli.

At least 19 recordsLinked to original sources

Nerve conduction velocity and spinal reflexes may change in rats after fumonisin B1 exposure.

Mycotoxin fumonisin B1 (FB1) a natural inhibitor of ceramide synthase contaminating mainly the corn-based food and feed may cause dysfunctions in the nervous system. In the present study peripheral neural dysfunctions were biomonitored after dietary FB1 exposure in rats. Daily oral doses of 6.2 mg/kg body weight/day FB1 were applied in rats for 2 weeks. Before and after FB1 treatment nerve conduction velocities of tibial and sciatic nerves and spinal reflexes were analyzed in vivo. Electrophysiological recordings of biphasic plantar EMG (M and H components) and evaluation of sensory and motor nerve conduction velocities were carried out. Nerve conduction velocities revealed decreasing tendencies after FB1 exposure. The flexor reflex and the H-components of the extensor reflex were significantly reduced. The proposed in vivo biomonitoring can reveal functional impairment of the peripheral nervous system caused by mycotoxin exposure. Reduction of conduction velocity and altered reflexes after FB1 exposure are suspected to be associated with modified signal transmission due to toxic systemic effects and possible changes in sphingolipid metabolism.

Animals↗

Differential EEG effects of the anxiolytic drugs, deramciclane (EGIS-3886), ritanserin and chlordiazepoxide in rats.

The influence of serotonergic and benzodiazepine type anxiolytic drugs on the cortical activation and sleep-wakefulness cycle were compared by evaluating the effects of ritanserin and deramciclane (EGIS-3886), two 5-HT2 receptor antagonists, and chlordiazepoxide on the electroencephalogram (EEG) in freely moving rats. Following drug administration (1, 3, and 10 mg/kg, PO for all drugs), EEG was continuously sampled for 6 h and power spectra were calculated for every 5 s to assess changes in slow wave activity and sleep phases. In a separate test, anticonvulsant effects of the drugs were examined in mice. Both deramciclane and ritanserin slightly increased total time spent in deep sleep (DS) and lengthened sleep episodes. In contrast, chlordiazepoxide had a strong inhibitory action on DS, sleep time being shifted to more superficial light sleep (LS). The incidence and length of the high voltage spindle (HVS) episodes characteristic for the motionless, awake rat were increased at the highest dose of both deramciclane and ritanserin, while it was decreased by chlordiazepoxide. In mice, chlordiazepoxide had a marked anticonvulsant effect, while deramciclane was moderately effective and ritanserin ineffective. In conclusion, the 5-HT2 receptor antagonist anxiolytic drugs seem to be superior compared to the benzodiazepine type anxiolytic drug, chlordiazepoxide, as ritanserin and deramciclane improved sleep quality by increasing sleep episode length and time spent in DS, while chlordiazepoxide enhanced sleep fragmentation and decreased DS.

Analysis of Variance↗

Bimoclomol improves early electrophysiological signs of retinopathy in diabetic rats.

A silent process involving both neural and vascular structures in diabetic retina persists for several years before clinically detectable retinopathy. Recordings of the electroretinogram (ERG) and visual evoked potential (VEP) provide early warning of abnormalities in the visual pathway of diabetic patients and animal models. Treatment of streptozotocin-diabetic rats for 1 or 2 months with the heat-shock protein coinducer bimoclomol, a drug ameliorating experimental neuropathy, prevented and corrected the abnormal increase in latency and reduction of amplitude of ERG and VEP waves both in acute and chronic experiments. Improvements may be explained by cytoprotective effect of bimoclomol on retinal glia and/or neurons against diabetes-related ischemic cell damages. These findings suggest that bimoclomol may have future therapeutic use in diabetic retinopathy.

Anesthesia↗

Bimoclomol (BRLP-42) ameliorates peripheral neuropathy in streptozotocin-induced diabetic rats.

A reduction in nerve conduction velocity and an increase in resistance to ischemic conduction failure are early signs of neural dysfunction in both diabetic patients and animal models of diabetes. The effect of Bimoclomol (BRLP-42), a drug under clinical development for the treatment of diabetic complications, on experimental peripheral neuropathy was examined in rats made diabetic by injection of streptozotocin. Daily oral doses of Bimoclomol (10 or 20 mg/kg) or control dose of gamma-linolenic acid (260 mg/kg), an agent with known neuropathy-improving effects, were administered for 3 months. Treatments began 1 day after diabetes induction to assess the prophylactic efficacy of Bimoclomol. Neuropathy was evaluated electrophysiologically by measuring motor and sensory nerve conduction velocities and resistance to ischemic conduction failure of sciatic nerve in vivo. Bimoclomol significantly reduced nerve conduction slowing and retarded the typical elevated ischaemic resistance due to streptozotocin-induced neuropathy, suggesting that the drug might be a useful treatment for diabetic peripheral neuropathies.

Animals↗

Effects of viscerosensory stimulation on hypothalamically elicited predatory behavior in cats.

Hypnogenic (HS) or arousing (AS) stimulations of the small intestine (INT), splanchnic (SPL), and vagal (VAG) nerves were used to modify the predatory behavior (PB) elicited by stimulating the lateral hypothalamus (LHS). HS induced EEG synchronization and sleep. AS aroused the cat from slow-wave sleep. LHS induced the cat to attack an anesthetized rat and bite its neck after an exploratory activity. The following parameters of PB were determined: biting latency (BL), the interval between the beginning of LHS and the touching the rat by the cat's muzzle; exploratory time (ET), which begins with an environmental search and culminates in orienting toward the rat; attack time (AT), in which the cat stalks and bites the rat. HS, delivered for 5, 10, 15 min to INT, SPL, and VAG prior to LHS, increased BL and ET and did not affect AT. AS, delivered for 10 s to INT or VAG prior to LHS, decreased BL by reducing ET. SPL AS shortened BL by decreasing both ET and AT. The viscerosensory effects on PB were decreased by increasing the intensity of LHS; a ferocious attack with BL less than 10 s was not influenced by either HS or AS. These results indicate that the viscerosensory influence can modify PB by inhibiting or facilitating the priming events of the attack.

Afferent Pathways↗

Long-term sleep deprivation by hypothalamic stimulation in cats.

Several techniques were developed to prevent sleep in animals in order to examine the biological role fulfilled by sleep; however, most were either stressful or difficult to accomplish routinely, especially in such a large animal as the cat. Electrical stimulation of activating structures in the brain presents a very attractive alternative to peripheral stimulation used by the usual sleep deprivation methods although it has been rarely tried. The paper describes a microcomputer-based system used to achieve sleep deprivation in cats by stimulating the hypothalamic predatory area with short trains. During control days and deprivation the electrocorticogram (EEG), electromyogram (EMG) and electrooculogram (EOG) were continuously digitalized by the computer in 5 s epochs and the integrated power of the 4 usual frequency bands of the EEG (alpha, beta, delta, theta) as well as the variance of EMG and EOG signals were calculated. Criteria for stimulus delivery were based on the integrated power of the delta band and on the variance of EMG but the flexibility of the computer ensures that any other parameter can be used to achieve total or selective sleep deprivation.

Animals↗

Neuronal firing in the pallidal region: firing patterns during sleep-wakefulness cycle in cats.

Neuronal activity was investigated by extracellular microelectrodes in the pallidal region of freely moving cats during wakefulness (W), slow-wave sleep (SWS) and paradoxical sleep (PS). The firing of 150 units from 35 points was examined. On the basis of the modifications of firing rates and patterns during the sleep-wakefulness cycle, 5 groups of neurons were distinguished. Two of these groups were characterized by strong increase of firing rate in W and PS and in one of them this increase preceded the cortical activation at the SWS-PS transition by an average of 26 sec. The role played by the basal forebrain area in the regulation of the sleep-wakefulness cycle is discussed.

Action Potentials↗

Effect of glutaurine on sleep-wakefulness cycle and aggressive behaviour in the cat.

The effects of glutaurine (gamma-L-glutamyl taurine, Litoralon, Chinoin, Budapest) on the aggressive behaviour and sleep-wakefulness cycle were studied in freely moving cats. Glutaurine, even in doses as low as 0.1 microgram/kg, was found significantly to shorten the latency of the rat-killing reaction elicited by hypothalamic stimulation. On the other hand, the same doses failed to modify the sleep-wakefulness cycle to any significant degree throughout the study period of 4 hours. On the grounds of these and previous data, the possible brain site of the glutaurine action is discussed.

Aggression↗

Effects of hypnogenic vagal stimulation on thalamic neuronal activity in cats.

Neuronal responses from the ventro-postero-medial (VPM) and reticular (NR) nuclei of cat thalamus to vagal stimulation was recorded during wakefulness (W), slow-wave-sleep (SWS), and paradoxical sleep (PS) using chronically implanted microelectrodes. Cellular firing was facilitated in NR and depressed in VPM when weak, hyponogenic stimuli were delivered to the vagal nerve during W and SWS. Higher intensity vagal stimulation increased firing frequency and duration of discharge in both nuclei. Vagally induced discharges of several VPM neurons were depressed by NR stimulation. We speculate that intrathalamic mechanisms play a role in the genesis of induced synchronization and sleep.

Animals↗

Firing properties of cat basal forebrain neurones during sleep-wakefulness cycle.

Neuronal activity was studied in the basal forebrain area (BFA) of freely moving cats during wakefulness (W), slow wave sleep (SWS) and paradoxical sleep (PS). Two classically synchronizing and hypnogenic regions, the preoptic area (POA) and the olfactory tubercle (OT) were explored by microelectrodes. Compared to W, the discharge rate in most of the POA cells was not modified or was slightly reduced by SWS, but it was increased by PS. Half of the OT cells increased slightly their firing frequency during falling asleep. A great proportion of OT neurones showed facilitation of activity during PS also, which in half of the cells started already in the last seconds of SWS. The results are discussed from the point of view of the synchronizing and hypnogenic influence attributed to POA and OT.

Animals↗

Effect of stimulation of vagal and radial nerves on neuronal activity in the basal forebrain area of anaesthetized cats.

The effects of vagal and radial stimulation on neuronal activity in the basal forebrain area (BFA) of chloralose-anaesthetized cats were studied. Sixty-five neurones were examined from 29 points of BFA. The observed neurones were divided into four groups according to spike amplitudes and spontaneous firing rates. Most of the cells responded with a short latency (10-15 ms) excitation-inhibition sequence, but the pattern and parameters of the responses changed with the cell groups and stimulus types. The results indicate that the BFA neurones receive both excitatory and inhibitory inputs from the visceral and cutaneous receptors.

Anesthesia↗

Tonic and phasic modifications of viscerosensory evoked potentials during sleep in cats.

Modification of the viscerosensory evoked potentials (EPs) were studied during the sleep-wakefulness cycle of the rat. Electrical stimuli of various intensity were delivered either to the mucosal surface of a fistula of the small intestine or to the left splanchnic nerve during wakefulness (W), drowsiness (D), slow-wave-sleep (SWS), and paradoxical sleep (PS). The average EPs were recorded from the somatosensory (SI and SII) and associative (AS) areas of the cortex, the ventrobasal complex of the thalamus (VPL), the posterior hypothalamus (HPT) and the dorsal hippocampus (HPC). The amplitude of each component of the EPs in all explored structures were the largest in SWS and the smallest in W. A phasic increase in amplitude was observed in the EPs recorded immediately before the appearance of the spindles of SWS and during the REM episodes of PS. The peak latencies of the late components were the longest in SWS. These changes of the amplitudes and latencies were greater in the responses to weak stimulation than in EPs to strong ones. The possible synaptic events of the sleep-dependent control of viscerosensory activity are discussed.

Afferent Pathways↗

Conditioned modification of viscerosensory evoked potentials during sleep and wakefulness in cats.

The effects of classic conditioning on the viscerosensory evoked potentials (EPs) were studied in twenty cats during wakefulness (W), slow-wave-sleep (SWS) and paradoxical sleep (PS). Four types of the experiment were performed on four groups of animals. Weak, non-painful stimulation of the small intestine or of the left splanchnic nerve was used as conditional stimulus (CS) in all experiments. A painful or non-painful shock on the left radial nerve served as unconditional stimulus (US) which followed the CS with a delay of 500 ms. In the first and second series of experiments, the CS was paired with non-painful or painful CS during W. In the third and fourth types of experiment, weak US was used and conditioning was done during SWS or PS. The evoked responses were recorded from the primary (SI) and secondary (SII) somatosensory and associative (AS) cortex, the thalamus (VPL), hypothalamus (HPT) and dorsal hippocampus (HPC). In each experiment, the stimulus pairings resulted in a complex electrographic conditional response (CR) which included an amplitude increase of the late components of EP's (early CR) and the development of a wave of 500 ms latency (delayed CR). In the second experiment, however, a behavioural CR (limb flexion) also appeared. All these CRs proved to be extinguishable. The recall of CR established during W was successful in SWS. The traces of CS-US pairings during SWS could, however, be elicited only in SWS. Both establishment and recall of CR were unsuccessful during PS. The possible mechanism of the effects originating from an interaction of conditioning and sleep on the viscerosensory inputs of the brain are discussed.

Animals↗

Sleep induced by intestinal stimulation in cats.

The influence of afferent impulses of intestinal origin on the sleep stages was studied in fed and starved cats. Low-frequency electrical stimulation of the mucosal surface in a small intestinal fistula reduced the latency of sleep onset. The number of slow wave sleep episodes decreased, but their mean duration increased during stimulation. Conversely, the number of paradoxical sleep episodes increased, but their mean duration was not significantly modified by the intestinal stimulation. The role of viscerosensory events in the control of sleep is discussed in relationship to these results.

Afferent Pathways↗

Electroencephalographic synchronization induced by stimulation of small intestine and splanchnic nerve in cats.

1. In freely moving cats, the cortical desynchronization elicited by painless rhythmic distension, or by low voltage electric stimulation, of the small intestine in drowsiness and slow wave sleep is extinguished following a few repetitions. After extinction of the arousal reaction, similar intestinal stimulation was systematically followed by the appearance of synchronized activity, or an increase of spontaneous synchronization, in the explored cortical areas (parieto-occipital). 2. Intestinal or splanchnic stimulation at an intensity below threshold for cortical desynchronization immediately induced synchronized activity without any need of previous repetitions of stimulation. 3. Stimuli which were followed by synchronization excited only the large (Abeta) splanchnic afferents. The authors conclude that intestinal receptors may be one of the sources of synchronizing influence which can contribute to the regulation of the sleep-wakefulness cycle and that the large splanchnic afferents may play a role in the induction of synchronization.

Afferent Pathways↗