Biomedical subjects

D Mattia

Publications and source records attributed to D Mattia.

28 records · Page 2Linked to original sources

PubMed1996

Synchronization of rat hippocampal neurons in the absence of excitatory amino acid-mediated transmission.

Extracellular and intracellular recordings and measurements of extracellular K+ concentration ([K+]o) were performed in the adult rat hippocampus in an in vitro slice preparation. Excitatory amino acid receptor antagonists, as well as the K(+)-channel blockers 4-aminopyridine (4AP, 50 microM) and/or tetraethylammonium (TEA, 5 mM), were added to the bath. Synchronous, negative-going field potentials were recorded in the CA3 stratum radiatum during application of 4AP and excitatory amino acid receptor antagonists. Each of these events was associated with an intracellular long-lasting depolarization and a concomitant rise in [K+]o that attained peak values of 4.3 +/- 0.1 mM (mean +/- S.E.M., n = 6 slices) and lasted 29 +/- 3 s. These field potentials were still recorded in CA3 stratum radiatum after addition of TEA. Under these conditions, prolonged field potentials (40.2 +/- 4.5 s, n = 18) characterized by a prominent positive component; discharge of population spikes also occurred. [K+]o increases associated with these prolonged field-potential discharges had a considerable variability in magnitude (peak value = 3.8-14.1 mM, 6.1 +/- 0.7 mM, n = 5) and duration (14-210 s; 48 +/- 13 s, n = 5). In 8% of the cases spreading depression-like episodes were observed. [K+]o increases during spreading depression-like episodes attained peak values of 11-27 mM (22.8 +/- 0.2 mM, n = 2) and had a duration of 160-396 s (244 +/- 29 s, n = 2). All types of synchronous activity were abolished by the GABAA-receptor antagonist bicuculline methiodide (10 microM) (n = 11). A similar effect was obtained by applying Ca(2+)-free/high-Mg2+ medium (n = 5). Simultaneous field-potential recordings in CA3, CA1, dentate area and subiculum demonstrated that negative-going potentials and prolonged field-potential discharges occurred in all areas in a synchronous fashion. Spreading depression-like episodes were more frequently recorded in the CA1 than in the CA3 area and were not seen in the subiculum or dentate area. These experiments indicate that a glutamatergic-independent, synchronous GABA-mediated potential which is elicited by 4AP in the adult rat hippocampus continues to occur in the presence of TEA. In addition, concomitant application of these K(+)-channel blockers induces a novel type of prolonged field-potential discharge as well as spreading depression-like episodes. Since all synchronous potentials (including spreading depression-like episodes) were abolished by bicuculline methiodide, we conclude that their occurrence is presumably dependent upon the post-synaptic activation of GABAA receptors located on neuronal and glial elements. As excitatory synaptic transmission was nominally blocked under our experimental conditions, we also propose that rises in [K+]o and consequent redistribution processes are per se sufficient to make all types of synchronous activity propagate.

4-Aminopyridine↗

PubMed1996

Effect of lamotrigine on EEG paroxysmal abnormalities and background activity: a computerized analysis.

1. Little information is available about the action of lamotrigine (LTG) on EEG paroxysmal abnormalities and background activity. On the contrary, several clinical trials have shown the therapeutic efficacy of the drug in preventing partial and generalized seizures. 2. We performed computerized EEG monitoring in 21 patients suffering from focal and generalized epilepsy before and 4 months after addition of LTG. The anticonvulsant modified the EEG ictal events by reducing their frequency and duration. A statistically significant decrease of the interictal spikes was observed. The decrease involved mainly the spreading component of the interictal events leading to a better spatial definition of the epileptic focus. 3. In the presence of LTG, generalized tonic-clonic attacks were completely controlled, whereas partial seizures were decreased. 4. The EEG background activity was not modified by the addition of the drug. 5. Our findings suggest a specific role for LTG in the generation and propagation processes of epileptiform activity without interfering with the EEG background activity.

Adolescent↗

PubMed1995

Seizure-like discharges recorded in human dysplastic neocortex maintained in vitro.

Application of the convulsant drug 4-aminopyridine (50 to 100 microM) induced spontaneous seizure-like discharges (duration = 76.3 +/- 46.8 sec, mean +/- SD; interval of occurrence = 225.2 +/- 87.9 sec) in slices of neocortex obtained from patients with a diagnosis of focal neuronal migration disorders during neurosurgical procedures for relief of drug-resistant seizures. Similar epileptiform discharges could also be elicited in these slices by single-shock stimuli delivered in the underlying white matter or within the gray matter. By contrast, neocortical slices obtained from patients suffering from temporal lobe epilepsy (which is characterized by Ammon's horn sclerosis but relatively normal neocortex) did not generate any epileptiform activity during 4-aminopyridine application. Thus, our study is the first to provide experimental evidence for the intrinsic epileptogenicity that characterizes neuronal migration disorders.

4-Aminopyridine↗

PubMed1994

Potassium channel activators counteract anoxic hyperexcitability but not 4-aminopyridine-induced epileptiform activity in the rat hippocampal slice.

The K+ channel activators diazoxide and cromakalim were investigated for effects on 4-aminopyridine (4AP)-induced epileptiform activity in adult rat hippocampal slices maintained in vitro. Under normal conditions of oxygenation, 4AP (50 microM) induced two types of field potentials in extracellular recordings from the CA3 stratum radiatum (apical dendritic region): epileptiform interictal discharge-like events occurring at a frequency of 0.75 +/- 0.36 Hz and long-lasting negative-going potentials mediated by GABA receptor activation that occurred at 0.03 +/- 0.01 Hz (n = 36 slices). Neither diazoxide (0.65-1.3 mM, n = 21 slices) nor cromakalim (50-200 microM, n = 6 slices) altered these two types of discharge. Brief periods of anoxia (4-6 min) reduced the frequency of the 4AP-induced interictal-like events (from 0.75 +/- 0.36 Hz to 0.19 +/- 0.15 Hz, n = 20 slices). In 45% of the experiments, the depressant effect of anoxia was preceded by a period of hyperexcitability consisting of a transient (36.1 +/- 12.9 sec) increase in the frequency of interictal-like events riding on a negative-going DC shift (n = 9 slices). Both responses to anoxia were reversible upon reoxygenation. In contrast, the rate of occurrence of the GABA-mediated potentials was unaffected by the anoxic episodes. Perfusion with cromakalim (n = 4 slices) or diazoxide (n = 5 slices) abolished the initial period of hyperexcitability produced by O2 deprivation but did not alter the subsequent depression of activity. Our experiments indicate that the K+ channel activators can prevent the initial hyperexcitability produced by anoxia, but do not influence 4AP-induced epileptiform activity in normoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

PubMed1994

Quantitative EEG modifications during the Cold Water Pressor Test: hemispheric and hand differences.

In a study designed to investigate the neurophysiological correlates of the Cold Water Pressor Test, a standardized experimental model of tonic pain, spectral EEGs were examined during the test in 15 young right-handed adults. Each subject performed a "cold water" and a "warm water" session. The subject immersed in cold water (0 degree C) either the right or the left hand alone, in a randomized way. EEG activity was recorded for an initial 3 min baseline and for the first and second minute epochs after immersion. A further EEG recording was obtained after a 30-min rest. Pain intensity was measured with a visual analogue scale. The EEG recordings showed several patterns of cortical activation during the test. Alpha 2 desynchronization was more evident on the contralateral parietal electrodes of the stimulated hand and lasted longer over all the right hemisphere. Delta activity increased bilaterally, predominantly in the frontal leads. Stimulation of the left hand resulted in a higher delta increase during the second minute after immersion.

Adult↗

PubMed1994

Pharmacology and electrophysiology of a synchronous GABA-mediated potential in the human neocortex.

Spontaneous synchronous field potentials of negative polarity (duration = 200-700 ms, inter-event interval = 9.1 +/- 2.9 s; n = 27 slices) were recorded, during application of 4-aminopyridine (50 microM), from the superficial/middle layers of slices of human neocortex obtained in the course of neurosurgery for the relief of intractable seizures. The negative-going field potential corresponded to an intracellular long-lasting (duration = 200-1600 ms) depolarization that could be preceded by preceded by an excitatory postsynaptic potential-hyperpolarizing inhibitory postsynaptic potential sequence and followed by a long-lasting hyperpolarization. This synchronous activity continued to occur following blockade of excitatory synaptic transmission by excitatory amino acid receptor antagonists, but was greatly reduced and eventually disappeared during application of the GABAA receptor antagonist bicuculline methiodide. Simultaneous extracellular recordings from three sites in the slice located along an axis parallel to the pia showed that successive synchronous field potentials could originate from any of the three areas. They invaded the other two sites in c. 35.5% of the cases, while propagation to another site only or no propagation at all was observed, respectively, in 44.4% and 20% of instances. The velocity of lateral propagation of the synchronous field potential was 7.9 +/- 2.5 mm/s (range = 4.5-11.8 mm/s, n = 6). The modalities of origin and propagation remained the same after blockade of excitatory amino acid receptors. Under these conditions, however, there was a higher incidence of non-propagation and the velocity was significantly lower than in control (5.6 +/- 1.9 mm/s; range = 2.8-7.7 mm/s, n = 6). These data indicate that, in the human neocortex, 4-aminopyridine can reveal a synchronous field potential that correlates with an intracellular long-lasting depolarization and is mainly due to the activation of postsynaptic GABAA receptors. The action of excitatory amino acid receptors is not necessary for the generation and propagation of these GABA-mediated potentials. We propose that this potential represents a novel mechanism for synchronization and spread of neuronal activity, including seizure-like discharges in the human neocortex.

2-Amino-5-phosphonovalerate↗

PubMed1993

Epileptiform activity induced by 4-aminopyridine in guinea-pig and rat neocortices.

Extracellular field recordings were performed in guinea-pig and rat neocortical slice preparations maintained in vitro. Bath application of the convulsant drug 4-aminopyridine (4-AP, 100 microM) induced spontaneous epileptiform potentials in 80% of the guinea-pig neocortical slices and only in 6% of the neocortical slices from rat. In both species spontaneous epileptiform activity consisted of a 4-16 s long ictal-like discharge that recurred with a frequency range of 0.01-0.02 Hz. In rat neocortical slices stimulus-induced responses resembled the spontaneous occurring epileptiform events. Ictal-like discharges in guinea-pig neocortical slices were blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist 3-((+/-)-2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (5 microM), while those in the rat disappeared during perfusion with the non-NMDA excitatory amino acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (1-3 microM). These results indicate that the neocortex of guinea-pig has a higher propensity to generate 4-AP-induced spontaneous epileptiform activity than that of rat. Furthermore the epileptiform activity in these two species requires a different involvement of excitatory amino acid receptors.

4-Aminopyridine↗

PubMed1993

Membrane properties of rat subicular neurons in vitro.

1. Conventional intracellular recordings were performed in rat hippocampal slices to investigate the electrophysiological properties of subicular neurons. These cells had a resting membrane potential (RMP) of -66 +/- 7.2 mV (mean +/- SD; n = 50), input resistance of 23.6 +/- 8.2 M omega (n = 51), time constant of 7.1 +/- 1.9 ms (n = 51), action potential amplitude of 85.8 +/- 13.8 mV (n = 50), and duration of 2.9 +/- 1.2 ms (n = 48). Analysis of the current-voltage relationship revealed membrane inward rectification in both depolarizing and hyperpolarizing direction. The latter type was readily abolished by Cs+ (3 mM; n = 6 cells). 2. Injection of depolarizing current pulses of threshold intensity induced in all subicular neurons (n = 51) recorded at RMP a burst of two to three fast action potentials (frequency = 212.7 +/- 90 Hz, n = 13 cells). This burst rode on a slow depolarizing envelope and was followed by an afterhyperpolarization and later by regular spiking mode once the pulse was prolonged. Similar bursts were also generated upon termination of a hyperpolarizing current pulse. 3. The slow depolarization underlying the burst resembled a low-threshold response, which in thalamic cells is caused by a Ca2+ conductance and is contributed by the Cs(+)-sensitive inward rectifier. However, bursts in subicular cells persisted in medium containing the Ca(2+)-channel blockers Co2+ (2 mM) and Cd2+ (1 mM) (n = 5 cells) but disappeared during application of TTX (1 microM; n = 3 cells). Hence they were mediated by Na+. Blockade of the hyperpolarizing inward rectification by Cs+ did not prevent the rebound response (n = 3 cells). 4. Our findings demonstrate that intrinsic bursts, presumably related to a "low-threshold" Na+ conductance are present in rat subicular neurons. Similar intrinsic characteristics have been suggested to underlie the rhythmic activity described in other neuronal networks, although in most cases the low-threshold electrogenesis was caused by Ca2+. We propose that the bursting mechanism might play a role in modulating incoming signals from the classical hippocampal circuit within the limbic system.

Animals↗

PubMedDate not supplied

Neurophysiologic and neuropsychologic profiles of lamotrigine in epilepsy.

The anticonvulsant potential of lamotrigine (LTG) has been extensively assessed in open and double-blind clinical trials including patients with different types of epilepsy. In this review, the neurophysiologic and neuropsychologic profile of LTG is discussed. The electroencephalographic (EEG) findings reveal that the drug induces a decrease both in frequency and in probability of propagation of the EEG epileptiform abnormalities (interictal and ictal), whereas the background activity appears unmodified. In contrast with the traditional antiepileptic drugs (AEDs), LTG does not affect evoked responses (brainstem auditory evoked potentials and somatosensory and visual evoked potentials), indicating only a minor toxic effect on the nervous system. The neuropsychologic assessment shows that LTG does not alter the cognitive functions. In conclusion, the neurophysiologic and neuropsychologic data confirm the efficacy and safety of LTG and support its clinical use as monotherapy in epilepsy.

Anticonvulsants↗

PubMedDate not supplied

Lamotrigine add-on therapy in focal epilepsy: electroencephalographic and neuropsychological evaluation.

The effect of lamotrigine (LTG) as add-on therapy on electroencephalogram (EEG) background activity was studied in 11 patients with refractory partial seizures with or without secondary generalization. The computerized EEG study was performed at rest with eyes closed (EC), during blocking reaction (BR), fixation (FIX), and mental arithmetic (MA) tasks. EEG spectral values were analyzed statistically using three-way ANOVA. The neuropsychological evaluation included a battery of six tests. Epileptic patients before LTG therapy, compared with control subjects, displayed at rest condition EEG changes consisting of higher delta and theta relative power coupled with lower alpha and beta power. During performance of attentive (BR) and cognitive (FIX) tasks, a decrease in alpha reactivity associated with a decrease of beta 1 and beta 2 power was found. The addition of LTG to previous therapy induced changes, although subtle, consisting of an increase in both alpha reactivity and beta power to attentive task. Neuropsychological evaluation did not evidence any impairment of cognitive functions. During LTG therapy, a decrease in seizure frequency occurred in 9 of the 11 patients whereas no changes were observed in the remaining 2. On the basis of these neurophysiologic and neuropsychological findings, LTG as add-on therapy does not seem to produce adverse side effects on mental activity; moreover, EEG data indicate a slight improvement in attentional processes.

Adolescent↗