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Biomedical subjects

M A Caria

Publications and source records attributed to M A Caria.

At least 19 recordsLinked to original sources

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↗

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↗

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.

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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.

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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.

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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↗

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.

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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.

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Functional organization of the projection from area 2 to area 4gamma in the cat.

It has been shown that tetanic stimulation of area 2 of the somatosensory cortex produces long-term potentiation in neurons in area 4gamma, and this has been suggested as the basis of learning new motor skills. The purpose of this study was to further elucidate the characteristics of this projection by the use of evoked potentials in area 4gamma elicited by intracortical microstimulation of area 2. The experiments were carried out in cats and the following results were obtained. 1) In six animals, stimulation of a given site in area 2 elicited evoked potentials in a restricted region of area 4gamma, the size of which ranged from 1 to 1.5 mm2. These responses were labeled "localized responses." The evoked potentials were recorded from the superficial layers of the cortex, and were positive monophasic in shape. 2) In 16 animals, stimulation of a given site in area 2 elicited a focal response that was surrounded by smaller positive and monophasic potentials of <50% amplitude that spread broadly over area 4gamma. These responses were labeled "graded responses." 3) The sites that produced focal evoked potentials in area 4gamma extended along the direction of the radial fibers in area 2. These sites were defined as most effective segments (MESs). 4) The receptive fields of neurons along the MES in area 2 were similar to those of neurons recorded at the foci of the evoked potentials in area 4gamma. The results demonstrate that some of the projections from area 2 to area 4gamma are highly specific and that the somatosensory and motor areas that are connected by these specific projections receive functionally related peripheral input. These results are discussed in relation to possible mechanisms underlying motor learning.

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Does long-term potentiation occur in guinea-pig Deiters' nucleus?

Long-term potentiation (LTP) was studied in the lateral vestibular nucleus (LVN-Deiters' nucleus) in guinea-pigs in vivo. Field potentials and extracellular single unit discharges were recorded in the LVN following electrical stimulation of the ipsilateral VIIIth nerve. High-frequency stimulation (HFS) of the VIIIth nerve fibres produced LTP of the monosynaptic component of the vestibular field potential. The LTP of the field potentials was paralleled by an increase of the evoked spike activity. Intranuclear administration of the NMDA antagonist MK-801 prevented LTP of the monosynaptic component of the vestibular field potentials and significantly suppressed the spontaneous firing of lateral vestibular neurones in a dose-dependent fashion. These results demonstrate that synapses between primary afferent fibres and second order LVN neurones undergo long lasting changes following HFS of the ipsilateral vestibular nerve.

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Trigeminal motoneuron responses to vestibular stimulation in the guinea pig.

Experiments performed in the guinea pig were aimed at evaluating the effect of electric or caloric stimulations of the vestibular afferents on the electrical activity of the jaw-closing and jaw-opening trigeminal motoneurons. Results showed that masseter and digastric motoneurons mainly responded to vestibular ampullar activation with excitatory responses, with latencies being shorter for contralateral than ipsilateral ampullar stimulation. Differences in latencies between the jaw-closing and jaw-opening trigeminal motoneurons were observed: the masseter motoneurons constantly responded about 2 msec earlier than the digastric motoneurons. These results suggest that the vestibular-trigeminal relationship is quite complex and uses multiple systems to connect the vestibular apparatus with the trigeminal motor nuclei. From the functional point of view, the vestibular-trigeminal relationship may play a role in the dynamic control of the jaw muscle tone during head movements.

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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↗

Long-term potentiation within the cat motor cortex.

Synaptic plasticity in the motor cortex of anesthetized cats was examined using intracellular recording and labeling techniques. Intracortical microstimulation (ICMS) was delivered in the superficial layers and recordings were made from cells in layer V. When the neuron responded to ICMS with an excitatory postsynaptic potential (EPSP), tetanic ICMS (100-200 Hz, 10-20 s) was delivered to the same site. Five of 19 cells which were examined and labeled with biocytin showed long-term potentiation (LTP) of the EPSP, and 12 cells showed post-tetanic potentiation (PTP) following the tetanic stimulation. All the examined cells were pyramidal neurons. These results demonstrate that plasticity exists within the intracortical connection of the motor cortex that may be involved in motor learning.

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Information processing within the motor cortex. I. Responses of morphologically identified motor cortical cells to stimulation of the somatosensory cortex.

Inputs from the somatosensory cortex to the motor cortex have been proposed to function in learning of motor skills. In an attempt to analyze how these somatosensory inputs were processed in the motor cortex, neurons in the superficial layer of the cat motor cortex were classified into three groups on the basis of synaptic responses elicited by intracortical microstimulation (ICMS) of area 2. ICMS was delivered through seven electrodes implanted in area 2. When ICMS through one of the seven sites produced a response that was greater than 50% of the response produced by stimulating the seven sites at a time, the site was called a "dominant" site. Type I cells were those that had a dominant stimulation site and showed a constant response latency when examined by a double shock test. Type II cells were those that had a dominant site but displayed a variable latency. Type III cells had no dominant site and showed a variable latency. Latency of type I responses was 1.2-2.6 milliseconds, which was much shorter than that of type II and type III responses. Seventy-nine neurons in layers II/III of the motor cortex, which responded to ICMS in area 2, were stained by intracellular injection of biocytin. From the presence of an apical dendrite and rich spines on the dendrites, 23 type I, 21 type II, and 15 type III cells were classified as pyramidal cells. Type II pyramidal cells were located more superficially than type I and type III pyramidal cells. On the basis of the absence or sparseness of dendritic spines, three type I and four type II cells in layers II/III were classified as nonpyramidal cells. These cells consisted of five small multipolar cells in layer II and a large multipolar cell and a small bitufted cell in layer III. The remaining 11 cells were not classified because of insufficient staining. Since type I and type II cells are considered to represent monosynaptic and polysynaptic responses to stimulation of area 2, respectively, information flow from type I cells to more superficially located type II cells is presumed in layers II/III of the motor cortex. Type III responses suggest the presence of a convergent flow of impulses inside of and/or between areas 2 and 4.

Animals↗

Information processing within the motor cortex. II. Intracortical connections between neurons receiving somatosensory cortical input and motor output neurons of the cortex.

Connections between motor cortical neurons receiving somatosensory inputs from area 2 and large pyramidal cells in layer V were examined in the cat via intracellular injection of biocytin and immunohistochemistry of nonphosphorylated neurofilament proteins (npNFP). Biocytin was injected into pyramidal cells in layers II/III of the motor cortex that responded monosynaptically and polysynaptically to microstimulation of the somatosensory cortex and subsequently stained black by the avidin-biotinylated peroxidase complex method with diaminobenzidine (DAB) and nickel. By using a monoclonal antibody SMI-32 and a modified peroxidase-antiperoxidase method with Tris-aminophenyl-methane (TAPM) and p-cresol as a chromogen, pyramidal cells in layers III and V of the motor cortex were stained red for npNFP. In particular, all the large pyramidal cells in layer V, Betz cells, displayed intense npNFP immunoreactivity not only in the perikarya but also in the dendrites. Double staining with DAB/nickel and TAPM/p-cresol showed that biocytin-filled axon varicosities of the pyramidal cells, which were thought to receive monosynaptic inputs from area 2, made contacts with npNFP-positive dendrites in layers I-III around the biocytin-injected cell and in layers V-VI beneath the cell. The present results suggest that the corticocortical input from area 2 to pyramidal cells in layers II/III of the motor cortex is transferred to layer V pyramidal cells, including Betz cells, as well as to neighboring layer II/III pyramidal cells. Since tetanic stimulation of the somatosensory cortex reportedly produces long-term potentiation in layer II/III cells of the motor cortex, it seems reasonable to assume that a given area of the somatosensory cortex can produce a long-lasting change in the activity of a given group of output cells in the motor cortex.

Animals↗

Muscle spindle and periodontal trigeminal afferents modulate the hypoglossal motoneuronal activity.

Hypoglossal responses to electrical or natural activation of the afferent fibers of the masseteric nerve and to periodontal mechanoreceptors were recorded in rats. Electrical stimulation of the masseteric nerve, at an intensity adequate to excite prevalently the primary spindle afferents, induced various sequences of excitation-inhibition and inhibition-excitation in 55% of the tested hypoglossal motoneurons. Responses were characterized by excitation, inhibition or excitation-inhibition sequences occurring at short and long latencies. Different pattern of responses were evoked in both the protrusive and the retractive motoneurons of the homolateral hypoglossal nucleus. Moreover, jaw lowering and pressure on the incisor tooth induced antagonistic and synergistic effects on the electrical activity of the same hypoglossal motoneurons. The results show for the first time that afferent signals from both muscle spindles and periodontal receptors modulate the activity of the hypoglossal motoneurons aimed at controlling the tongue position in the mouth during mastication.

Action Potentials↗

Vestibular projections to hypothalamic supraoptic and paraventricular nuclei.

The effects of electrical stimulation of the eighth nerve and caloric stimulation of the labyrinth were tested on the spontaneous or evoked electrical activity of single neurons located in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. It was found that these neurons responded to both kinds of stimulation. In particular, the neurons of the SON showed a predominant response pattern characterized by a sequence of excitation-inhibition, whereas the neurons of the PVN showed different patterns of response with various combinations of inhibition and excitation sequences. The latencies of these neuronal responses to the electrically induced eight nerve volleys were compatible only with a polysynaptic connection. The possible pathways involved in this vestibulo-hypothalamic relation as well as their functional role are discussed.

Animals↗

Responses of hypoglossal motoneurons to mechanical stimulation of the teeth in rats.

Reflex discharges were evoked in the XIIth nerve single fibers and in the genioglossal muscle following mechanical stimulation of the homolateral incisor tooth in rats. The tooth mechanoreceptors affected the firing rate of 70% of the tested motoneurons mainly localized in the ventral region of the hypoglossal nucleus. Different types of response in relation to stimulus direction were recorded. Type A responded with excitation to labio-lingual and with inhibition to linguo-labial stimulus direction. Opposite effects were observed in type B motoneurons. However, these neurons did not respond to mechanical stimuli applied in medio-distal or disto-medial directions. Type C showed excitatory or inhibitory responses to mechanical stimulation in all directions. Type D only responded to one direction of stimulation. The stimulus was often able to excite motoneurons previously silent (type E). Some motoneurons showed complex responses to one stimulus direction. The results demonstrate that stimulation of the periodontal mechanoreceptors can evoke hypoglossal responses probably aimed at controlling tongue position in the mouth during mastication.

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