Biomedical subjects

O Mameli

Publications and source records attributed to O Mameli.

At least 19 recordsLinked to original sources

PubMed2006

Effect of aluminum consumption on the vestibulo-ocular reflex.

The effects of chronic exposure (90 days) to Aluminum chloride (AlCl(3)) were analyzed in 3, 10 and 24 month old male rats (n=270) by investigating the function of the VOR (vestibulo-ocular reflex) in correlation with Aluminum (Al) concentrations in blood and brain. The VOR was chosen and tested in basal conditions (pre-exposure measures) and during the continuous administration of three different concentrations of AlCl(3) (0.5, 1, 2 g/l in drinking solution): the control animals being exposed to NaCl (0.125, 0.25 and 5 g/l in drinking solution). Results showed that LOAEL (Lowest Observed Adverse Effect Level) was 43.1+/-11.4 mg Al/kg-day. At this concentration the Al induced significant VOR impairment in all exposed rats, regardless of animal age. Neuroanatomical analysis showed that VOR impairment was not dependent on astrocyte damage nor evidences of amyloid deposits in the exposed rats was found. Significant changes of Al concentrations were observed in nervous tissue, while its concentration in whole blood was unaffected. Furthermore, results show that it is possible to identify an individual neurotoxic threshold for each animal and therefore hypothesize the clinical use of the VOR test for the evaluation of individual risk toxicity to chronic Al exposure.

Aluminum↗

PubMed2006

Sudden death in epilepsy: an experimental animal model.

INTRODUCTION: The physiopathogenetic mechanisms possibly involved in sudden unexplained epileptic death (SUDEP), were investigated in the hemispherectomized rat. METHODS: For this purpose, paroxysmal activity, vagal nerve firing, systemic blood pressure (BP), pulmonary artery pressure, and ECG were simultaneously recorded in an experimental animal model of epilepsy. Recordings were performed in basal conditions and during paroxysmal activity induced by topical application of penicillin-G at hypothalamic and mesencephalic level. During the experiment were also performed hemogas analysis and at end, samples of lung tissue were processed for histology. RESULTS: Activation of hypothalamic (HEF) and mesencephalic (MEF) epileptic foci induced a significant increase of spontaneous vagal nerve firing that was strictly correlated to ECG impairments and hypotension. When paroxysmal activity extinguished, vagal nerve activity and cardiovascular parameters returned to basal conditions. However, in 25% of the animals, co-activation of HEF and MEF always triggered a vagal hypertone which was temporally correlated to cardiac arrhythmias, but also to hyperkalemia, acidosis, pulmonary hypertension and to animal death. Histological control in lungs of deceased animals showed an alveolar and perivessel oedema with an oedematous infiltration in the alveolar and bronchial spaces and mucous secretion. During ictal activity, comparison between survived and deceased animals showed significant differences in the incidence of ECG impairment of pulmonary artery pressures, pO2, and pCO2 pressures, and [K+], [HCO3-], and [pH], concentrations. DISCUSSION: A possible explanation of the above observations is discussed in relationship to SUDEP physiopathogenesis.

Animals↗

PubMed2001

Frequency-dependent LTP/LTD in guinea pig Deiters' nucleus.

Synaptic plasticity was studied in the lateral vestibular nuclei (LVN) of the guinea pig in vivo. High frequency stimulation (HFS) of increasing or decreasing frequencies was applied to the ipsilateral vestibular nerve. Vestibular field potentials (VFPs) and extracellular single unit activity evoked in the LVN by electrical stimulation of the ipsilateral vestibular nerve, were analyzed before and after the application of different protocols of HFS. Results show that the monosynaptic component of the VFPs undergo long-term potentiation (LTP) with stimulation of 100 Hz applied for 20 s lower frequencies, applied for shorter periods, induce only a transient post-tetanic potentiation. This potentiation, although long lasting, is not permanent since it is susceptible of a reversal or cancellation by opposite patterns of HFS that determine a depression or depotentiation of the previously acquired potentiation. The results demonstrate that the plasticity phenomena that take place at the level of the LVN neurons are not steady but undergo continuous adjustment of their sign and gain depending on the variable flow of vestibular information that reach the nuclei from the labyrinthine receptors.

Animals↗

PubMed2001

Neurotoxic effect of lead at low concentrations.

The effects of lead exposure at low concentrations were evaluated by studying the post-rotatory nystagmus (PRN) in two groups of rats exposed for 3 months to 50 parts per million (ppm) of sodium acetate and 50 ppm of lead acetate, respectively, in the drinking water. Only animals treated with lead acetate showed changes of the PRN parameters which were significantly related to the concentration of lead in the blood and in brain structures. The patterns of PRN responses were characterized and classified into four types: progressively inhibitory (40%), prematurely inhibitory (25%), late inhibitory (25%), and excitatory-inhibitory (10%). No alterations of the PRN parameters were observed in the animals treated with sodium acetate. The results show that exposure to lead, even at low concentrations, impairs both sensory and motor functions. The findings also point out that the vestibular system and brain stem structures which generate and control the PRN represent targets of the action of this heavy metal. Finally, the results indicate that the evaluation of the vestibulo-ocular-reflex can provide a test suited for the screening of the neurotoxic effects of lead even in the absence of clinical signs typical of lead intoxication.

Animals↗

PubMed2001

Autonomic nervous system activity and life threatening arrhythmias in experimental epilepsy.

In the present study the possible derangement of the autonomic system and its influence in life threatening arrhythmias were analysed during paroxysmal activity. In hemispherectomized rats a paroxysmal activation of the hypothalamic and mesencephalic cardioarrhythmogenic triggers was performed by topical application of penicillin-G. Blood gas parameters and electrical activity of the thalamus, hypothalamus, vagal nerve fibre, ECG and arterial blood pressure were simultaneously monitored in basal conditions and repeated after the appearance of paroxysmal activity. Temporal correlation analysis was carried out. Results showed that during activation of these triggers, the spontaneous vagal nerve fibre activity significantly increased and triggered the appearance of cardiac arrhythmias which could become life threatening and induce animal death when blood gas and electrolytic parameters were simultaneously impaired. These experiments suggest that fatal evolution of the heart impairment is related not only to an autonomic cardiac trigger, but also to a concomitant metabolic derangement, which most likely shares the same autonomic origin.

Animals↗

PubMed2000

Disposition of propofol between red blood cells, plasma, brain and cerebrospinal fluid in rabbits.

The disposition of propofol in the blood and brain of New Zealand rabbits was studied in three groups of six rabbits. One group received a single anaesthetic dose; a second group received a 1-h infusion; and a third group was studied after the rabbits were judged to have recovered from a 1-h infusion. There was a high concentration of propofol in the red blood cell fraction and in the brain, however, the red blood cell concentration largely exceeded the one found in the brain in all groups of animals. This is consistent with the high fat solubility of diisopropylphenol. The possible effects of propofol sequestered in red blood cells is discussed.

Acidosis↗

PubMed1999

Epileptic discharge of cortical, subcortical and spinal neurons in penicillin induced experimental epilepsy.

The sensitivity and electrophysiological patterns of paroxysmal activity induced in different brain structures by topical application of penicillin-G were evaluated in the rat. Recordings were carried out in five groups of animals, in telencephalon, diencephalon, mesencephalon, rombencephalon and spinal cords. The following analysis were carried out: frequency distribution histograms, latency and time course duration of paroxysmal activity, duration and amplitude of epileptic bursts. The results obtained showed that the nervous structures tested with penicillin-G had a different epileptogenic sensitivity and response pattern which significantly changed along the cerebral cortex-spinal cord axis. The highest epileptic sensitivity was observed in somatosensory cortex (SI) at 500-600 microns depth; in the other cortical layers, a significant lenghtening in latency was observed. Among the other structures, the spinal cord seemed to be the most sensitive target to the epileptogenic action of penicillin-G, whereas in the remaining structures, sensitivity significantly decreased in rostro-caudal direction. As far as the features of the paroxysmal activity are concerned, significant differences among tested structures were observed. In particular, within the SI cortex, the main differences were represented by the gradual increase in burst frequency and voltage from the surface to the IVth layer and by their subsequent decrease in deeper layers (V-VI). In the diencephalon, the paroxysmal activity was similar to that observed in more superficial and deeper cortical layers even though epileptic bursts showed a lower amplitude. Mesencephalon and rombencephalon displayed a paroxysmal activity with a distinctive feature, characterized by long lasting bursts of low amplitude, although bulbar outbursts showed a shorter duration than the mesencephalic ones. In the spinal cord, the epileptiform activity displayed a different paroxysmal pattern, characterized by the longest duration and the highest amplitude. The different sensitivities of the investigated brain structures to penicillin-G and the characteristics of the induced paroxysmal activity have been extensively discussed.

Animals↗

PubMed1997

Beta-endorphin and cortisol levels in plasma and CSF following acute experimental spinal traumas.

beta-endorphin and cortisol were measured in cerebrospinal fluid (CSF) and plasma by radioimmunological method (RIA) in two groups of rabbits with spinal cord traumatic injuries at cervical and lumbar levels, respectively with and without concomitant spinal shock and arterial hypotension, and in a group of sham operated animals as controls. The two groups with spinal lesions displayed a significant beta-endorphin increase in CSF, whereas the cortisol level remained unchanged both in the spinal traumatized rabbits and in controls. Both the opioid and the cortisol concentration rose significantly in plasma in all three groups and in particular resulted significantly higher in the cervical traumatized group where spinal trauma was associated with spinal shock and hypotension. However, no significant difference was found when beta-endorphin concentrations in plasma were compared between the sham operated animals and the spinal lumbar traumatized animals without concomitant spinal shock. The results seem to suggest that the beta-endorphin increase in CSF is related to the nervous tissue lesion, while its increase in plasma, like that of cortisol, is due to surgery or other stress factors inherent in the experiment. This independent behaviour of beta-endorphin in plasma and in CSF suggests its different origin in these two compartments.

Animals↗

PubMed1995

Effect of fetal hypoxia on seizure susceptibility in rats.

In the present study, susceptibility to Pentylentetrazol (PTZ)-induced seizures was tested in 45 four-wk old rats born to mothers exposed to moderate asphyxia in the last week of pregnancy by breathing N2 99.9% for 6 min in two separate sessions, (Group I--experimental rats) and in 44 rats of the same age, born after a normal pregnancy (Group II--controls). The results showed that the experimental rats, following episodes of asphyxia in intrauterine life, had a higher susceptibility to PTZ-induced seizures than the controls, manifested by earlier onset of convulsions and a higher incidence of fetal epileptic status. This occurred despite normal development and the absence of neurological deficits in the experimental rats in the first 4 wk of extrauterine life.

Animals↗

PubMed1995

Olfactory influence on tongue activity.

Recent findings have shown that olfactory stimulation by brief puffs of air odorized with amyl acetate induces several patterns of response in rabbit hypoglossal neurons. It has been argued that the functional role of the olfactory input may be the modulation of tongue muscular tone during the oral phase of digestion. In the present research, the peripheral effect of olfactory-hypoglossal modulation was analyzed. Both the spike traffic along the fibers of the hypoglossal nerve and the electromyographic activity of single tongue muscles (genioglossus, styloglossus, superior longitudinal and hyoglossus) were recorded before, during and after olfactory stimulation. Results showed that brief puffs of air odorized with amyl acetate induced a significant change in the efferent volleys along the hypoglossal nerve, as well as a substantial modulation of tongue muscle activity. Olfactory stimulation induced a significant increase in the spontaneous activity of both type I and type II genioglossal fibers; excitation followed by inhibition both in tonic and phasic styloglossal fibers; excitatory responses in tonic and phasic superior longitudinal fibers and short-lasting excitatory responses in the hyoglossal fibers. The diverse patterns of activation of the tested muscle and the significant differences between fibers, tonically or phasically controlled by the XIIth neurons, indicate that olfaction may be strongly involved in tongue reflex regulation. Different functional hypothesis are discussed about the role played by olfaction in the economy of tongue muscle activity.

Action Potentials↗

PubMed1994

Cerebellar and mesencephalic influence on bulbar penicillin-G epileptogenesis in rats.

The influence of the cerebellum and mesencephalon on epileptic bulbar discharge induced by topical application of penicillin-G on the floor of the IVth ventricle was analyzed in rats. Bulbar multiunit activity was recorded at different depths. The animals were divided into two main groups: totally cerebellectomized rats (Group I) and lobus anterior cerebellectomized rats (Group II). Each main group was further subdivided into two subgroups: animals with intact mesencephalon and animals with transected mesencephalon. In Group I: the total cerebellectomy, in intact mesencephalic rats (first subgroup) induced a sudden disappearance of bulbar epileptic discharge. The mid-collicular transection (second subgroup) produced the immediate disappearance of bulbar paroxysms and the total cerebellectomy, subsequently performed, further decreased the spontaneous firing rate. In Group II: (first subgroup) the lobus anterior ablation in rats with intact mesencephalon, significantly enhanced the paroxysmal discharge. In the second subgroup, where the midcollicular transection had provoked the disappearance of bulbar paroxysms, the lobus anterior ablation induced the immediate reappearance of the paroxysmal activity. The penicillin-G epileptogenic activity showed a different intensity at different depths in the bulb with a maximum intensity at the level of the vestibular nuclei. In conclusion, the present study shows that both the mesencephalon and the cerebellum have a facilitating influence on bulbar epileptic discharge induced by the topical application of the GABA antagonist. However, not all the cerebellum has a facilitating effect, because the anterior lobus was found to have an inhibitory influence on bulbar discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Visual and vestibular projections to tongue motoneurons.

The rabbit hypoglossal neurons, localized in the mediocaudal part of the XIIth nucleus, receive visual and vestibular inputs able to induce reflex responses functionally driven both to prepare the oral cavity for food reception and to ensure a correct postural arrangement of the tongue. The aim of the present research was to show a possible convergence of visual input on the hypoglossal neurons modulated by the vestibular system and, thus, demonstrate that visual input plays a part in the control of the tongue posture. It was found that 78% of tested neurons responded to both photic stimulation of the retinae, performed by a conventional strobe unit, and electrical stimulation of the labyrinth, with different patterns of response. Moreover, visual input significantly modified both the hypoglossal neuron response and the electromyographic genioglossal response to caloric stimulation of the labyrinth. Because a significant visual influence on the hypoglossal nucleus response and the genioglossal muscle response to labyrinthine stimulation was observed, it can be concluded that vision does integrate the spatial information of the labyrinth to modulate the postural tone of the tongue muscles.

Animals↗

PubMed1993

The brainstem cardioarrhythmogenic triggers and their possible role in sudden epileptic death.

The cardiovascular effects of simultaneous activation of hypothalamic and mesencephalic cardioarrhythmogenic triggers were studied in hemispherectomized rats. Paroxysmal activity of hypothalamic neurons (HEF), elicited by topical application of penicillin G on the thalamus, triggered short-lasting bradyarrhythmic episodes, up to a maximum of 6 s, and alterations in repolarization. In the hypothalamic neurons, an additional penicillin G epileptic focus at mesencephalic level (MEF) induced the enhancement of paroxysmal activity by a recruitment of new units and potentiation of their background activity. HEF+MEF triggered second-degree 2:1-8:1 atrioventricular (A-V) blocks, impairment of the A-V conduction, alterations in the recovery phase and bundle branch blocks. After HEF, the arterial blood pressure decreased by 4-6%. HEF+MEF induced a further reduction of 17% in systolic pressure only. It is possible that the enhancement of the HEF following MEF could depend on MEF spreading upward. The HEF, in turn, by spreading downward could influence the MEF and so activate, between HEF and MEF, a circuitry with reciprocal co-excitation that could explain the more serious cardiovascular alterations observed during HEF+MEF compared with those observed during HEF only or during MEF only. However, this cardiovascular impairment, which must be neurogenic in origin as it was observed in animals with normal acid-base and blood parameter values, did not induce heart death. Thus, additional concomitances must be considered, such as metabolic derangement which can occur during seizures, to explain sudden death in epileptic patients. Some aspects of metabolic complications in cardiac activity during epilepsy are also discussed.

Acid-Base Equilibrium↗

PubMed1993

Olfactory modulation of hypoglossal neuron activity.

Amyl acetate stimulation of the neuroepithelial cells of the olfactory mucosa induced significant responses in the olfactory bulb and modulated the spontaneous electrical activity of the hypoglossal neurons localized in the mediocaudal part of the XIIth nucleus. Olfactory stimulation induced several patterns of responses characterized by excitation, inhibition and combined effects frequently dependent upon the stimulation intensity. In addition, olfactory inputs converge with the visual inputs on the same part of the XIIth nucleus. The olfactory inputs inducing hypoglossal excitatory responses increased the hypoglossal excitation produced by visual stimuli and decreased its inhibition. Viceversa, the olfactory inputs inducing hypoglossal inhibitory responses decreased excitation and increased hypoglossal inhibition to photic stimulation of the retinae. The possible pathways involved in carrying the olfactory inputs towards the hypoglossal nucleus, and the olfactory or non-olfactory origin of the hypoglossal responses were considered. With regard to the role played by this input in the economy of the hypoglossal function, it was concluded that olfactory inputs, alone or together with visual inputs, may induce tongue reflex adjustments associated with the oral phase of digestion to prepare the oral cavity for food reception.

Animals↗

PubMed1992

Visual and somatosensory information to tongue motoneurons.

The experiments were designed to show whether visual inputs and somatosensory signals travelling along the common radial nerves converge onto the same hypoglossal neurons. The hypoglossal neurons (HN) type I (45.77%) and II (33.89%) responded to both visual and somatosensory stimuli. The HN type III (15.26%) responded only to the retinae and type IV (5.08%) only to the forelimb nerves stimulation. In the convergent neurons, types I and II, the influence of the somatosensory stimulation on the hypoglossal visual response was also analyzed. The conditioning stimulation of the radial nerve significantly increased (31%) the hypoglossal response to the less effective retina and significantly reduced (17%) the response to the more effective retina. The recordings of the electromyographic activity of the genioglossus (GM) and the superior longitudinal muscle (SLM), showed that the somatosensory afferents synergize the excitatory effect of the visual messages on the extrinsic tongue muscles (GM) and antagonize the inhibitory effect that visual messages induce on the intrinsic tongue muscles (SLM). The results suggest that visual messages induce tongue reflex responses functionally directed not only to prepare the oral cavity better for food reception, as previously demonstrated, but also to modulate the postural tone of the tongue together with somatosensory signals.

Animals↗

PubMed1992

Propofol anticonvulsant activity in experimental epileptic status.

We have examined the anticonvulsant properties of propofol in high doses in two experimental models of status epilepticus: generalized pentylenetetrazol (PTZ)-induced seizures and partial, cortically applied penicillin G-induced seizures. Propofol was administered either as a single bolus injection or as a bolus injection followed by an infusion for 1 h. When administered as a single bolus injection, propofol 12 mg kg-1 suppressed electrical and clinical seizures in PTZ generalized epileptic status, and an infusion of 50 mg kg-1 h-1 prevented the reappearance of electrical and clinical signs. In focal epileptic status, the single dose stopped paroxysmal activity and the associated clonic jerks for a few seconds. When the bolus dose was followed by an infusion, the firing bursts were replaced by isolated spikes, and contralateral jerks became sporadic and feeble. The greater efficacy of propofol against PTZ convulsions may be a reflection of the opposite action of the two drugs on neural membrane conductance: PTZ induces paroxysmal neural discharge by enhancing membrane conductance while propofol appears to decrease membrane conductance, thus suppressing paroxysmal discharge. There was no close relationship between blood concentration of the anaesthetic and its clinical effects, at least after a short-term infusion, as used in the present experiments. We suggest that propofol may be a potentially useful drug in status epilepticus in patients in whom benzodiazepines, barbiturates and phenytoin have failed.

Action Potentials↗

PubMed1991

Penicillin-induced paroxysmal activity in brainstem neurons.

The spontaneous electrical activity of single mesencephalic and bulbar neurons was recorded in hemispherectomized rats, following topical application of the GABA-antagonist penicillin-G on the mesencephalon or on the rhombencephalon, to investigate whether these structures could develop a specific penicillin paroxysmal activity independently of the upper structures. Twenty minutes following penicillin-G, the mesencephalic neurons developed paroxysmal activity characterized by a significant increase in the spontaneous electrical activity, the appearance of multiunit activity and, frequently, phasic activity with rhythmical outbursts. The paroxysmal activity at bulbar level appeared later than that observed in the mesencephalon and was characterized by a significant increase of the spontaneous firing rate of the neurons, single short bursts and sometimes rhythmical outbursts. The bulbar outbursts always discharged at lower frequency than those at the mesencephalic level. Following a midcollicular transection the paroxysmal bulbar activity abruptly disappeared. This phenomenon might be explained by a loss of facilitation from superior structures on the bulbar neurons which in roditors show a poor GABA-receptor distribution. In other words, penicillin alone, due to the scarcity of GABA receptors, might not be sufficient to induce paroxysmal activity in bulbar neurons but the simultaneous presence of both the superior facilitation and the drug might enhance neuronal excitability to a critical level. However, the diffusion of the drug upwards to the mesencephalon, with consequent activation of a system allowing the downward propagation of paroxysmal activity, cannot be excluded. In conclusion, while the mesencephalic neurons demonstrate a proper ability to develop penicillin paroxysmal discharge, the bulbar neurons must be sustained by intact connections with upper structures to be able to do so.

Animals↗

PubMed1990

Analysis of central cardioarrhythmogenic triggers in experimental epilepsy.

The cardioarrhythmogenic potential of epileptic foci induced at mesencephalic and rhombencephalic levels was analyzed in hemispherectomized rats. Topical application of penicillin-G onto the mesencephalic quadrigeminal lamina or onto the fourth ventricle induced paroxysmal activity at the mesencephalic or bulbar neurone level. At the mesencephalic levels, the paroxysmal activity was characterized by a significant increase in the spontaneous frequency of the neurones, with the appearance of multiunit activity and rhythmical outbursts. The simultaneous recording of myocardial electrical activity and blood pressure showed that the paroxysmal activity triggered short-latency sinus bradyarrhythmias with wandering of the sinus pacemaker, the appearance of biphasic or negative P waves, some premature ventricular contractions and non-significant reduction of systolic and diastolic pressures. When the paroxysmal activity stopped, the cardiac rhythm and blood pressure returned to basal values. At the bulbar level, the paroxysmal activity appeared with longer latency and usually the rhythmical outbursts were not observed. Following bulbar paroxysmal activity only short-lasting episodes of sinus bradyarrhythmias appeared. Midcollicular transection eliminated paroxysmal activity at the bulbar level, and blood pressure and cardiac rhythm resumed basal values. After transection, an additional application of convulsant drug (penicillin-G or pentylenetetrazole) onto the fourth ventricle did not induce the reappearance of paroxysmal activity and the consequent cardiovascular alterations. The results showed the existence of a cardioarrhythmogenic trigger localized at the mesencephalic level which spreads paroxysmal activity upwards. A hypothesis to explain the appearance of fetal haemodynamic modifications and life-threatening arrhythmias has been proposed.

Animals↗