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Biomedical subjects

A Fernández-Guardiola

Publications and source records attributed to A Fernández-Guardiola.

At least 19 recordsLinked to original sources

Vagus nerve prolonged stimulation in cats: effects on epileptogenesis (amygdala electrical kindling): behavioral and electrographic changes.

PURPOSE: To analyze the effect of prolonged (daily) electrical vagus nerve stimulation (VNS) on daily amygdaloid kindling (AK) in freely moving cats. METHODS: Fifteen adult male cats were implanted in both temporal lobe amygdalae, both lateral geniculate bodies, and prefrontal cortices. A bipolar hook (5-mm separation) stainless steel electrode also was implanted in the unsectioned left vagus nerve. AK only was performed on five of the cats as a control. The remaining 10 cats were recorded under the following experimental conditions: VNS (1.2-2.0 mA, 0.5-ms pulses, 30 Hz) for 1 min along with AK (1-s train, 1-ms pulses, 60 Hz, 300-600 microA), followed by VNS alone for 1 min, four times between 11:00 a.m. and 2 p.m. At different times, VNS was arrested, and AK was continued until stage VI kindling was reached. RESULTS: The behavioral changes evoked by VNS were as follows: left miosis, blinking, licking, abdominal contractions, swallowing, and eventually yawning, meowing, upward gaze, and short head movements. Compulsive eating also was present with a variable latency. Outstanding polygraphic changes consisted of augmentation of eye movements and visual evoked potentials while the animal was awake and quiet, with immobility and upward gaze. An increase of the pontogeniculooccipital (PGO) wave density in rapid eye movement (REM) sleep also was noticeable. AK was completed (to stage VI) in the control animals without a vagus nerve implantation in 23.4+/-3.7 trials. In animals with VNS, the AK was significantly delayed, remaining for a long time in the behavioral stages I-III and showing a reduction of afterdischarge duration and frequency. Stage VI was never reached despite 50 AK trials, except when the vagus nerve electrodes were accidentally broken or vagal stimulation was intentionally arrested. Under these circumstances, 24.4+/-8.16 AK trials alone were necessary to reach stage VI of kindling. CONCLUSIONS: Our results indicate that left, electrical VNS interferes with AK epileptogenesis. This anticonvulsant effect could be related to the increase of REM sleep.

Amygdala↗

The assessment of residual effects of a single dose of diazepam on visually-defined EEG patterns.

The aim of this single-blind study was to evaluate the residual effects of a 10-mg dose of diazepam on cortical activation 11 h after oral intake. The electroencephalographic segments (from O1-O2) delimited by a sequence of photic stimuli presented every 10 sec during a simple reaction-time task (36 min duration) were arbitrarily classified into nine cerebral patterns (EEGP). EEGP segment classifications were grouped into six peri-stimulus transitions expressed in percentages: alpha-blockade; alpha-persistence; beta-persistence; alpha-induction; activation and deactivation. A sample of 42 young healthy university students (21 females and 21 males) each underwent three counterbalanced experimental conditions (control, placebo and diazepam). Diazepam affected all the subjects, although the women showed a greater number of EEGP transitions which indicated deactivation, than did the men. The results show that this type of visual EEG analysis is a useful technique for detecting the residual effects of benzodiazepines.

Adult↗

Changes in TRH and its degrading enzyme pyroglutamyl peptidase II, during the development of amygdaloid kindling.

Pyroglutamyl peptidase II (PPII) is a neuronal ectoenzyme responsible for thyrotropin releasing hormone (TRH) degradation at the synaptic cleft. PPII, heterogeneously distributed in different brain regions and adenohypophysis, is regulated under various endocrine conditions where TRH is involved in thyrotropin or prolactin regulation but only at the adenohypophyseal level. TRH can downregulate PPII activity in cultured adenohypophyseal cells. TRH present in extrahypothalamic brain areas has been postulated to serve as a neuromodulator and levels of this peptide increase in amygdala, hippocampus and cortex after electrical stimulation (kindling or electroshock). To study whether brain PPII could be regulated in conditions that stimulate TRHergic neurons, TRH and PPII activity were determined during the development of amygdaloid kindling in the rat. TRH levels increased from stage II to V in amygdala and hippocampus in the ipsi- and contralateral side to stimulation. In n. accumbens a decrease, compared to sham was observed at stage II, but levels raised through stage V. In contrast, PPII activity was increased at stage II, in amygdala of both sides and in hipppocampus, frontal cortex, n. accumbens and hypothalamus of the contralateral side; levels decreased at stage V to sham values in most structures (except amygdala and hippocampus where the activity was 30% below controls). These results suggest that PPII activity in the central nervous system can be regulated in conditions known to affect TRHergic neurons.

Aminopeptidases↗

Penicillin-G induced interictal activity increases both opioid peptide tissue content and in vitro release in the rat brain.

Penicillin-G has been used as a common agent to produce epileptic foci and interictal activity. The development of the interictal spikes has been associated with enhanced inhibitory effects. There is evidence that the opioid peptides play an important role in the production of some transient postictal behaviors. In order to test whether enkephalins are involved during the interictal activity, we analyzed immunoreactive met- and leu-enkephalin content and their release in vitro, after the injection of 50 IU of penicillin-G into the left amygdala. Male Wistar rats were injected once daily for 5 days, and sacrificed by decapitation (15 min after the penicillin-G infusion) on the fifth day. The rats were divided into two groups: 1. In one group we analyzed the tissue content of enkephalins in hypothalamus, hippocampus, amygdala, striatum and cerebral cortext. 2. The second group was used for the assessment of the in vitro release of enkephalins from amygdala slices. In the amygdala, the drug treatment produced an increase in the tissue content of IR-ME. No changes occurred in the other structures. The content of IR-Leu-enkephalin increased in all structures analyzed except the cerebral cortex. In vitro release of both enkephalins increased in drug treated animals. These results suggest that the enkephalins could be involved in postictal mechanisms, as a result of repetitive interictal spiking.

Amino Acid Sequence↗

Repeated penicillin-induced amygdala epileptic focus in freely moving cats. EEG, polysomnographic (23-h recording), and brain mapping study.

The effect of repeated Na-penicillin (PCN) microinjections in the temporal lobe amygdala (AM) of free-moving cats was investigated in order to establish if kindling epileptogenesis is possible with this procedure. The cortical propagation of the PCN-induced post-discharge in AM and the sequence of behavioral changes induced by PCN were similar to those of AM electrical kindling. Nevertheless, the epileptogenic effect of PCN had a different evolution from that of electrical kindling, since some PCN habituation was observed after several doses. Repeated microinjections of PCN did not produce lasting alterations in sleep onset and organization. The only mild changes recorded in the 23 h following PCN microinjections were an increased latency of the first rapid eye movement (REM) sleep episode, a SWS II total time and percentage increase, and, with the highest PCN doses, a not very significant diminution of REM sleep total time. Another finding was the occurrence of REM sleep ponto-geniculo-occipital (PGO) waves, coinciding with a depression of the frequency and amplitude of interictal amygdaloid and cortical spikes. The results showed that a microinjection of PCN in the AM produced a reliable model of interictal spikes, paroxysms and generalized convulsive seizures. Nevertheless, long lasting kindling effect was not observed.

Amygdala↗

EEG frequency and time domain mapping study of the cortical projections of temporal lobe amygdala afterdischarge during kindling in the cat.

EEG frequency and time domain color maps were computed during amygdala kindling in cats. The pattern of the amygdala afterdischarge (AM/AD) propagation to the cortex was assessed as kindling evolved. Our results show that the AM/AD has 4 components that coincide with the activation of certain cortical areas during specific behavioral stages. The pattern of the cortical projection follows an asymmetrical temporo-fronto-occipital direction, the ipsilateral temporal lobe being the first activated zone, followed by the ipsilateral and contralateral prefrontal areas. The contralateral temporal activation is a late phenomenon. We conclude that the electrographic and behavioral manifestations of this model of complex partial epilepsy are asymmetrical during the whole process, including the convulsive stage.

Amygdala↗

Effects of 1 week administration of two benzodiazepines on the sleep and early daytime performance of normal subjects.

This study analyzed the effects of 1 week administration of alprazolam (AL; 0.25 mg), lorazepam (LO; 1 mg) and placebo (PL) on sleep as well as their residual effects on attention upon awakening. Under a crossed, double-blind design, six healthy male volunteer subjects between 19 and 30 years of age were studied. After two habituation sessions and a control session, each substance was given orally, twice a day for 7 days, with a 1-week washout period between administrations. At the end of each administration period, sleep studies were conducted from 2300 to 0700 hours. Evaluation of attention was carried out by means of a simple visuomotor reaction time (RT) task, and a time estimation (TE) task, that started at 0700 hours, lasting 1 h. Neither drug significantly affected any sleep variable. Both benzodiazepines tended to increase RT, but only LO did so significantly at the beginning of the attention test. No significant changes in predictive and failure responses during the RT task were produced by either drug. Also, no significant changes were observed in the TE. Even though only LO produced a significant increase of RT at the selected doses and with 1 week administration, it is suggested that both benzodiazepines could have residual effects on attention.

Adult↗

Naloxone facilitates sensory precipitation of focal and generalized seizures: evoked potentials and power spectral analysis in the cat.

To analyze the role of endogenous opioids on epileptogenesis the effect of repeated doses of naloxone alone (NA) (2, 4, and 8 mg/kg every 15 min) or along with intermittent photic stimulation (NPS) (1, 3, and 10 Hz) was tested on acute "Encephale isolé" cats. The electrical activity recordings of sensorimotor cortex (SMC), visual cortex, and right and left amygdalae revealed progressive changes as naloxone was administered: (A) slow spindle activity (4-6 Hz) in SMC, (B) 12 Hz rhythmic activity in both amygdalae, (C) generalized paroxysms, and (D) spontaneous tonic-clonic electrographic seizures. These changes occurred in both experimental groups (NA, NPS), and their onset was dose-related. Photic stimulation precipitated these phenomena. The amplitude of the visual evoked potential components (N1-P1, P1-N2, N2-P2) and power spectral analysis of spontaneous and evoked activity underwent progressive changes. Our results confirm a facilitatory effect of naloxone on epileptogenesis and suggest a possible role of endogenous opioids in this process and on sensory pathways' excitability.

Amygdala↗

Amygdala kindling in totally cerebellectomized cats.

This work describes the effect of total cerebellectomy on the development of kindled seizures produced by daily electrical stimulation of the temporal lobe amygdala. When the kindling was established, the cerebellectomized cats showed an increase in the afterdischarge and in the duration of generalized seizures. Henceforth, this duration increased persistently in the experimental cats, whereas it did not in the controls. Prior to the establishment of generalized seizures, no kindling behavioral stages or EEG differences were observed between experimental and control cats, despite the motor activity in the cerebellectomized cats being associated with persistent ataxia. In these animals there was also an increase in postictal EEG spikes after the establishment of generalized seizures. We conclude that total cerebellectomy induces anatomical and functional changes in the brain stem structures (mainly in the inferior olive and red nucleus) leading to a facilitation of tonic-clonic neocortical activity.

Amygdala↗

Effects of clonidine in narcolepsy.

The antihypertensive drug clonidine was given in an open trial to two treatment-resistant (psychostimulants and tricyclic antidepressants) narcoleptic patients. When given acutely, clonidine suppressed REM sleep. However, patients became tolerant after repeated doses but did not lose the drug's beneficial clinical effects. This suggests that REM suppression may not be necessary for improvement in narcolepsy. Assessments of both clinical and polysomnographic variables before and after the trial indicate that clonidine may have a place in the treatment of some patients with narcolepsy.

Adult↗

Phasic activity of the basolateral amygdala, cingulate gyrus, and hippocampus during REM sleep in the cat.

We analyzed the electrical activity of the basolateral amygdala (BLA), anterior and posterior regions of the cingulate gyrus (A-CG and P-CG), the dorsal hippocampus (DH), the anterior ventral thalamic nucleus (AVTN), and the sensory motor cortex during the rapid eye movements and ponto-geniculo-occipital (PGO) activity of REM sleep in cats in chronic preparation. Polygraphic recordings and computational perievent averages using the phasic contractions of the lateral rectus muscle (LR) of the eyeball as the triggering signal of the analysis were performed. We observed biphasic potentials (200-300 ms) of variable amplitude, related to the phasic phenomena of REM sleep, in the BLA, A-CG, P-CG, DH, and AVTN. The latencies of the potentials of these regions were always greater than those of the geniculate PGO activities. We propose that the recorded limbic potentials resulted from propagation of PGO activity and that this phenomenon may reflect the limbic structure of the hallucinatory, vegetative, and emotional components of REM sleep.

Amygdala↗

Polysomnographic effects of thyroid hormones primary myxedema.

Nine primary myxedematous patients were subjected to all-night polysomnographic recordings under the following conditions: (1) basal or myxedematous state; (2) acute replacement therapy (treatment with thyroid hormones at doses that increased weekly to the maximal replacement dose, Mrd); and (3) chronic replacement therapy (maintenance on the Mrd; euthyroid state). The most striking abnormality found in the sleep pattern during the myxedematous state was observed in both young adult (greater than 20 years old) and adult (greater than 50 years old) patients, consisting of either a complete absence or very low levels of slow wave sleep (SWS). Replacement therapy was accompanied by a restoration of the normal sleep pattern in 3 of the 4 patients that were followed. In contrast, younger patients (14-18 years old with a bone age of less than or equal to 10 years) had normal levels of SWS, with the exception of an adolescent with a bone age of less than 3 years. The latency for rapid eye movement (REM) sleep tended to increase during acute replacement therapy and became normal when euthyroidism was reached. These results lend support to the proposal that thyroid hormones exert central effects on the adult CNS.

Adolescent↗

Sleep alterations following total cerebellectomy in cats.

Polygraphic sleep studies were conducted in six cats just before cerebellectomy and 3 and 10 days after the operation. These studies were continued in the four surviving animals 30, 100, 200, 300, and 315 days days post-operatively. The findings confirmed the existence of two postoperative phases correlated with the degeneration of brainstem structures: an initial period (day 3) was characterized by a significant increase in wakefulness; a second, later period (days 10 and 30) was distinguished by numerous slow waves and sleep spindles in the electrocorticogram. There was a stable increase in the amplitude and density of rapid eye movements, perhaps reflecting the ataxia evident during the waking state after cerebellectomy. At day 3, there was a significant decrease in the duration of paradoxical sleep (PS) periods, followed by a significant increase at day 10 that continued to the end of the study. The number of PS states tended to decrease and the PS latency tended to increase in the long-term survivors. All other sleep parameters appeared to normalize by day 100. These findings suggest that the cerebellum plays a modulatory role with respect to the pontine structures responsible for the generation of phasic activity during PS.

Animals↗

Purkinje cell responses to a cerebral penicillin-induced epileptogenic focus in the cat.

A penicillin focus was induced in the postcruciate region of the cerebral cortex of the cat. Analyzing the Purkinje cell unit responses to consecutive interictal paroxysms, 60% of the cells studied (total number, 148) were found to respond with activation and 25%, with deactivation; the others were not uniform in their responses. These different response patterns were attributed to the high patchy topographic relation between the cerebral cortex and the cerebellar system as well as to the two basic patterns of neural activity, which are generated in the epileptic focus (activation), and its periphery (inhibition). The climbing fiber response to the interictal paroxysms was observed in only 41% of the Purkinje cells of the tuber vermis. This was interpreted as an interference of the epileptic interictal propagation at the inferior olivary complex level. An increase in the simple action potential discharge frequency was found during the ictal phase in intermedial regions of the cerebellar cortex in contrast with the more lateral regions, which showed a decrease; this pattern was inverted during the postictal depression phase. A tentative explanation is made relative to the different functions of the intermedial and lateral cerebellum. During ictal and postictal depression phases, no significant changes were found in the climbing fiber activity.

Action Potentials↗

Kindling in the spinal cord: differential effects on mono- and polysynaptic reflexes and its modifications by atropine and naloxone.

We have used the kindling paradigm at the spinal cord level. In spinal, unanaesthetized, paralysed (gallamine 20 mg/kg) cats, the cutaneous afferent (sural) or the muscle afferent (gastrocnemius, tibial and peroneal) nerves were electrically stimulated at 20 min intervals with a 3 sec train (100 Hz, 2 msec pulse duration, 200-400 microA). Kindling was assessed by averaging 16 mono- or polysynaptic ventral root reflex responses produced by constant intensity single shocks. Atropine sulphate (0.5 mg/kg) and naloxone (0.4 mg/kg) effects were measured in the kindled preparation. Kindling induced a progressive increment of the amplitude, ipsilateral propagation and after-discharge frequency. This was greater in polysynaptic responses. When testing monosynaptic responses during the kindling of cutaneous afferents, a cumulative inhibitory effect was observed. In both types of kindled response, atropine had a transient inhibitory effect. Naloxone noticeably augmented the kindled polysynaptic reflexes.

Animals↗

Brain content of leu5- and met5-enkephalin changes independently during the development of kindling in the rat.

Brain content of leucine-enkephalin and methionine-enkephalin changes independently during kindling of the amygdala. Both peptides were measured after 4, 8, 15 and 21 days of stimulation. Leu-enkephalin showed a progressive increase during the kindling: the results on the 4th day did not differ significantly from the controls, whereas those on the 8th day displayed an increase only in the stimulated left hemisphere and those on the 15th day showed an increase in both hemispheres. This increase was also seen after 21 days of stimulation. In contrast, Met-enkephalin was not modified during the early stages of kindling, but was found to be increased after the animals had presented five or more generalized seizures. These results show that Leu-enkephalin is related to the development of kindling, whereas Met-enkephalin levels change only as a consequence of the generalized seizures.

Amygdala↗