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R Spreafico

Publications and source records attributed to R Spreafico.

At least 73 records · Page 4Linked to original sources
PubMed1996

Cortical versus thalamic mechanisms underlying spike and wave discharges in GAERS.

Genetic absence epilepsy rats from Strasbourg (GAERS) have non-convulsive generalized seizures associated with spike-wave (SW) discharges, which are due to a hyperexcitable state of the thalamo-cortico circuits involving the reticular thalamic nucleus (nRt). Investigation of the primary genetically-determined defect responsible for GAERS epilepsy revealed the following abnormalities: (1) increased effectiveness of AMPA receptors dependent glutamate-mediated transmission; (2) impairment of GABA-mediated transmission in the neocortex; (3) increased amplitude of the voltage-dependent low-threshold Ca2(+)-current (I(T)) in the nRt. The maturational profile of these abnormalities supports the conclusion that the abnormality in the I(T) current in the nRt is the primary genetically-determined defect, which may secondarily induce the other changes found in the neocortex and thalamus of GAERS.

2-Amino-5-phosphonovalerate↗
PubMed1996

Neuronal migration disorders and epilepsy: a morphological analysis of three surgically treated patients.

Despite the increasing number of patients affected by neuronal migration disorders (NMDs) recently diagnosed in vivo by means of magnetic resonance imaging (MRI), few detailed data on the correlation between the neuroradiological and the anatomical features in the single NMD case are available. The present paper reports a combined cytoarchitectural and immunocytochemical analysis, by means of antisera recognizing specific neuronal and glial markers, of three MRI diagnosed NMD patients surgically treated for the relief of intractable seizures. The first case was a giant subcortical nodular heterotopia of morphologically normal neurons lacking any type of cortical lamination. The second case was a layered polymicrogyria with an abnormal amount of ectopic neurons in the underlying white matter. The third case was a focal cortical dysplasia characterized by a dramatic disruption of the normal cortical layering associated with marked cytological abnormalities. The present data demonstrate that the macroscopical and microscopical brain abnormalities can be markedly different in different NMD subtypes, and suggest that different anatomical substrates can underlie the intrinsic hyperexcitability of these brain malformations. The relevance of further prospective clinico-morphological studies for a better understanding of the mechanisms determining the development of these brain malformations is underlined.

Brain↗
PubMed1996

Supratentorial cavernous angiomas and epileptic seizures: preoperative course and postoperative outcome.

OBJECTIVE: Patients operated on for supratentorial cavernous angiomas were studied to define the incidence and the course of seizures in their clinical history. Electroclinical and neuroradiological data were correlated with the location of cavernomas. The impact of lesionectomy on the outcome of seizures was evaluated. METHODS: Preoperative clinical data on the history of the seizures, semeiology, incidence, severity, and response to antiepileptic drugs were analyzed. The location of the cavernomas, revealed by magnetic resonance imaging, was correlated with electroencephalographic and clinical data. Postoperative clinical and neuroradiological data were evaluated, with particular consideration to the outcome of the seizures, antiepileptic drug withdrawal, and the completeness of the lesion excision. RESULTS: A higher incidence of severe epilepsy was observed in the patients with mesiotemporal and cortical angiomas. In most of the patients (78.7%), a good concordance between the site of the lesion and the electroclinical data was found. The complete removal of the lesion led to a favorable outcome, with discontinuation of antiepileptic drugs achieved in one-quarter of the patients. CONCLUSION: A high percentage of patients with cortical cavernomas had epileptic seizures. They often presented with chronic intractable epilepsy (44.7% in our series). In cases of good concordance between the electroclinical data and the location of the angioma, complete lesionectomy led to the disappearance of seizures. Removal of the hemosiderin ring did not correlate with better outcome. Preoperative ictal scalp recordings to assess the topographic relationship between the cavernoma and the epileptic seizures could improve outcome, which suggests different surgical strategies (lesionectomy versus enlarged resection) in patients without a clear-cut concordance between the site of the lesion and the ictal semeiology.

Adult↗
PubMed1996

Schizencephaly: neuroradiologic and epileptologic findings.

PURPOSE: Nine patients affected by schizencephaly were analyzed, and the epileptologic findings prospectively studied, to define the relations between the anatomic brain malformations and clinical outcome. METHODS: The schizencephaly was diagnosed by means of magnetic resonance imaging (eight cases) or computed tomography (one case). The clinical histories of all the patients were analyzed, and a psychometric evaluation was made. The electroclinical features and course of epilepsy in the six patients with epilepsy were prospectively followed up for a period ranging from 3 to 14 years. RESULTS: The patients were divided into those who were unilaterally (six) and those bilaterally (three) affected. The former were characterized by mild neurologic deficits and late-onset epilepsy; their epileptologic features were consistent in terms of age of onset, seizure semiology, the absence of secondary generalization, and resistance to antiepileptic treatment. The patients with bilateral schizencephaly associated with other brain malformations were characterized by severe neurologic deficits but were only rarely affected by epilepsy, which was always completely controlled by antiepileptic treatment. CONCLUSIONS: Our data show that the extent of anatomic malformation is strictly related to the severity of motor and mental impairment but not to the presence or severity of epilepsy. The absence of prenatal risk factors for brain damage in our series, previously described familial cases of schizencephaly, and the recent report of mutations in homeobox gene EMX2 associated with cases of schizencephaly all indicate that genetic factors may play a key role in the pathogenesis of this brain malformation.

Adolescent↗
PubMed1996

Direct and semi-direct posterior composite restorations.

Since the introduction of composite resins in dentistry, the adhesive properties of the material to enamel and dentin surfaces have been improved considerably, resulting in more conservative cavity preparation and the preservation of natural tooth structure. Patient demand for aesthetic metal-free restorations in the posterior region has resulted in the utilization of tooth-colored composite restorations. The primary disadvantage of composite resins-material shrinkage-can be minimized, but not eliminated. Various techniques have been developed and proposed in order to overcome this important limitation. The learning objective of this article is to provide indications for the direct and semi-direct techniques and to illustrate effective clinical procedures for placement of posterior composite resin restorations. The article outlines the treatment concepts, principles of cavity preparation, direct and semi-direct restorative methods, and the technique-sensitive luting procedures. Several cases are used to illustrate the clinical aspects.

Bicuspid↗
PubMed1995

Branching pattern of corticothalamic projections from the somatosensory cortex during postnatal development in the rat.

In adult animals corticothalamic (CT) axons pass through the thalamic reticular nucleus (Rt) where they give off collateral branches innervating the Rt neurons. The postnatal development of CT projections from the somatosensory cortex, with particular reference to the branching pattern within Rt, ventrobasal (VB) and posterior (PO) nuclei, was investigated in the rat with anterograde tracing. Biotinylated dextran-amine (BDA) was iontophoretically injected into the somatosensory cortex of rats ranging from postnatal day (P) 0 to P30. At P1 most of the cortical axons traversed unbranched Rt and terminates in VB and PO, whereas at P3 they formed rudimentary branches in these nuclei. From P6 to P9 a progressive increase in the amount of dense clusters of terminal arborizations was evident in Rt, and by the second postnatal week more complex arborizations with a clear topographic arrangement were observed in Rt, VB and PO. Our findings indicate that CT fibers show a quantitative increase both in R1 and in somatosensory thalamic nuclei during the first postnatal week, although their terminal arborizations are however still incomplete. The pattern of collateralization of CT projections achieves an adult configuration at the end of the second postnatal week.

Animals↗
PubMed1995

In situ labeling of apoptotic cell death in the cerebral cortex and thalamus of rats during development.

Apoptosis is a form of naturally occurring cell death that plays a fundamental role during development and is characterized by internucleosomal DNA fragmentation. In this study we used specific in situ labeling of DNA breaks (Gavrieli et al. [1992] J. Cell. Biol. 119:493-501) to analyze the distribution of apoptotic cells in rat cerebral cortex and thalamus at different developmental stages from embryonic day 16 to adulthood. Control experiments and electron microscopy confirmed that the reaction product was confined to the nucleus of selected cells. Plotting and counting of labeled nuclei in counterstained paraffin sections showed that apoptosis occurred mainly during the first postnatal week and was absent in embryonic and adult samples. In the cortex, the number of apoptotic cells progressively increased from birth to the first postnatal week, with a peak between postnatal (P) day 5 and P8, and subsequently decreased. At the time of maximal expression of apoptosis, labeled nuclei were present mainly in layer VIb and underlying white matter and at the border between cortical plate and layer I. Only a few apoptotic cells were found scattered in the thalamus, without a particular concentration in selected areas, but with a peak at P5. Differences in the number of apoptotic cells between cortex and thalamus suggest that apoptotic cell death may have a different functional significance in the two brain areas.

Animals↗
PubMed1995

Ultrastructural immunolocalization of muscarinic acetylcholine receptor in the dorsal thalamus of rat.

The ultrastructural distribution of muscarinic acetylcholine receptor (mAChR) in the dorsal thalamus of the adult rat was studied by means of pre-embedding immunocytochemistry using the monoclonal antibody M35. mAChR immunoreactivity (ir) was present with variable intensity in the different thalamic nuclei, but with a similar subcellular localization. Labeling was restricted to neuronal cell bodies and dendrites, where it was both in the cytoplasm and along the cytoplasmic side of the plasma membrane, in areas post-synaptic to small terminals with round clear vesicles but also in non-synaptic areas. Glial cells were unlabeled. By combining the pre-embedding immunostaining for mAChR with post-embedding immunogold labeling for GABA it was shown that GABAergic terminals made synaptic contacts with cholinoceptive structures, but no mAChR ir was present at their post-synaptic sites.

Animals↗
PubMed1994

Parvalbumin immunoreactivity in the thalamus of guinea pig: light and electron microscopic correlation with gamma-aminobutyric acid immunoreactivity.

The relationship of the calcium binding protein parvalbumin (PV) with gamma-aminobutyric acidergic (GABAergic) neurons differs within different thalamic nuclei and animal species. In this study, the distribution of PV and GABA throughout the thalamus of the guinea pig was investigated at the light microscopic level by using immunoperoxidase methods. Intense PV labelling was found in all the GABAergic neurons of the reticular nucleus and in scattered GABAergic neurons in the anteroventral nucleus, whereas GABAergic interneurons in the ventrobasal and lateral geniculate nuclei were not PV labelled. At the electron microscopic level, preembedding immunoperoxidase for PV was combined with postembedding immunogold for GABA. In the ventrobasal nucleus, four types of profiles were recognized: 1) terminals with flattened vesicles and forming symmetric synapses, which were labelled with both PV and GABA and could therefore be identified as afferents from the reticular nucleus; 2) boutons morphologically similar to presynaptic dendrites of interneurons, labelled only with GABA; 3) large terminals with round vesicles and asymmetric synapses, labelled only with PV, which contacted GABAergic presynaptic dendrites in glomerular arrangements and resembled ascending excitatory afferents; and 4) terminals unlabelled by either antiserum. In the ventrobasal nucleus of the guinea pig a double immunocytochemical labelling permits therefore the differentiation of two populations of GABAergic vesicle-containing profiles, i.e., the terminals originating from reticular nucleus (that are double labelled) and the presynaptic dendrites originating from interneurons (that are GABA-labelled only). The possibility to differentiate GABAergic inputs from the reticular nucleus and from interneurons can shed light to the functional interpretation of synaptic circuits in thalamic sensory nuclei.

Animals↗
PubMed1994

Distribution of AMPA selective glutamate receptors in the thalamus of adult rats and during postnatal development. A light and ultrastructural immunocytochemical study.

The regional, cellular and subcellular distribution of AMPA receptors was demonstrated immunocytochemically within the thalamus of adult and young (from 1 to 20 days postnatal, P1-P20) rats. The antipeptide antibodies used recognize individual subunit proteins of the AMPA-preferring glutamate receptor, i.e., GluR1, GluR2-3 and GluR4. Our results demonstrate that these AMPA receptor subunits are generally not highly expressed in the thalamus, as compared to other brain areas and that they are enriched differentially within different thalamic nuclei. GluR1 is mostly found in intralaminar and midline nuclei throughout life, whereas GluR2-3 is moderately expressed in the thalamus, with no major developmental changes. GluR4 is the predominant subunit expressed in the reticular nucleus in adult rats, but not in young animals, where until P9 it is instead present in the ventrobasal complex. Samples of paraventricular and lateral geniculate nuclei stained with GluR1 and of reticular nucleus as well as ventrobasal complex stained with GluR4 were used for the ultrastructural study. In all the samples, labelling was in the somatic and dendritic cytoplasm, with dense patches of reaction product apposing post-synaptic densities of terminals with round clear vesicles and asymmetric specializations. Glial staining was observed only with the GluR1 antiserum and there was no evidence of labelled synaptic terminals. The differential distribution of GluR subunits in the thalamus suggests that certain subunits may participate more than others in mediating post-synaptic responses in distinct neuronal populations and also that other GluR types may be involved in the thalamic networks.

Aging↗
PubMed1994

A reticuloreticular commissural pathway in the rat thalamus.

To further characterize the communication between the thalami of the two hemispheres, a connection linking the rostral reticular nuclei of the two thalamic sides was investigated in the rat by retrograde and anterograde tracing. The rostral reticular nucleus can be divided into a medial region, with densely packed fusiform neurons, and a lateral region, with less densely packed, polymorphic neurons. After injections of Fluorogold (FG) in the medial region, retrogradely labeled, small fusiform neurons were found in the corresponding contralateral region. The retrograde labeling data were confirmed by the anterograde-tracing experiments. Thin, beaded axons, anterogradely labeled after injection of biocytin or biotinylated dextranamine in the medial region, innervate the corresponding region in the contralateral reticular nucleus. The present data suggest the existence of a commissural pathway specifically devoted to the crosstalk between the rostral reticular nuclei of the two thalamic sides. The commissural gamma aminobutyric acid (GABA)-ergic input on the GABAergic neurons of the rostral reticular nucleus could modulate the generation of sleep spindles. The reticuloreticular pathway may, moreover, synchronize the diffuse modulatory effect of the rostral reticular nucleus on nonprimary cortical areas through the bilateral projections of the nucleus to the ventromedial, intralaminar, and anterior thalamic nuclei.

Animals↗
PubMed1994

Enrichment of glutamate immunoreactivity in lemniscal terminals in the ventropostero lateral thalamic nucleus of the rat: an immunogold and WGA-HRP study.

BACKGROUND: The ventropostero lateral nucleus (VPL) is a thalamic somatosensory center receiving inputs from limbs and trunk; some of this input is via terminals of the dorsal column medial lemniscal pathway. These fibers convey non-noxious somesthesic information. METHODS: In this study the neurochemical content of lemniscal afferents in VPL of rats was investigated at the electron microscopic level by combining anterograde transport of horseradish peroxidase conjugated to wheat germ agglutinin, injected in the dorsal dorsal column nuclei, with postembedding immunogold labeling for glutamate (Glu). RESULTS: Anterograde labeling in VPL was detected only in myelinated axons and in large terminals containing round synaptic vesicles, interpreted as lemniscal afferents. Quantitative evaluation of gold particle density showed enrichment of Glu immunolabeling in the identified lemniscal terminals with respect to other neuronal profiles. Observation of serial sections immunoreacted for Glu demonstrated consistency of labeling, whereas in alternate sections immunoreacted for Glu and for the inhibitory amino acid GABA these two antigens were always present in distinct types of terminals. CONCLUSIONS: These findings are in agreement with several lines of evidence, obtained with different experimental approaches, supporting the hypothesis that Glu plays a major role in conveying sensory stimuli to the thalamus from second order neurons in the dorsal column nuclei.

Animals↗
PubMed1994

Primary antiphospholipid syndrome (PAPS) and isolated partial seizures in adolescence. A case report.

The case of a young male patient presenting isolated clustered partial seizures is reported. Despite the normality of the neurological features, as well as of ictal and interictal EEG, the MRI (performed three days after the symptoms) disclosed bilateral signal alterations in the parietal cortical region. These abnormalities disappeared at the MRI control examination performed one month later. The finding of positive anticardiolipine antibodies made possible the diagnosis of partial epileptic seizures symptomatic of a vascular disorder ascribed to a Primary antiphospholipid Syndrome (PAPS).

Adolescent↗
PubMed1994

Ultrastructural features of the isolated guinea-pig brain maintained in vitro by arterial perfusion.

The morphological features of cerebral tissue in the isolated guinea-pig brain maintained in vitro by arterial perfusion are described. Light and electron microscopic analysis of the thalamus, the somatosensory cortex and the limbic cortices (hippocampus, piriform and entorhinal cortices) was performed after different periods of incubation in vitro (1, 7 and 12 h), in parallel with an electrophysiological study. The morphological analysis showed that neuronal elements retained their normal appearance at both cellular and subcellular level in the examined brain regions up to an incubation period of 12 h. Immunoreactivity for GABA was also preserved for up to 12 h of in vitro perfusion. Vasogenic edema and perivascular extracellular swelling appeared after 7 h, together with signs of progressive astrocytic deterioration. These findings show that normal electrophysiological recordings correlate with good anatomical preservation of the isolated guinea-pig brain preparation after prolonged times of arterial in vitro perfusion.

Animals↗
PubMed1994

GABAergic interneurons in the somatosensory thalamus of the guinea-pig: a light and ultrastructural immunocytochemical investigation.

This work was performed to confirm previous data reporting the presence of GABAergic interneurons in the ventrobasal complex of guinea-pig, and to investigate the intrinsic organization of this nucleus compared to that of thalamic nuclei lacking interneurons. Immunocytochemical experiments were performed on the thalamus of adult guinea-pigs perfused with mixed aldehydes using an anti-GABA serum. At light microscopy, the immunoreaction on floating Vibratome sections showed that GABAergic neurons are present only in the reticular and lateral geniculate nuclei and in the ventrobasal complex. Quantitative evaluation of their number indicated that they are 20 and 15% of the total neuronal population in lateral geniculate nucleus and ventrobasal complex, respectively, while they are less than 1% in ventrolateral nucleus. At the ultrastructural level, the postembedding immunogold procedure showed the presence, in the ventrobasal complex, of GABA-labeled profiles involved in complex synaptic arrangements similar to those found in carnivores and primates. Conversely, GABA-labeled terminals in thalamic nuclei devoid of interneurons formed exclusively axo-dendritic or axo-somatic contacts, like in rats and mice. The present data suggest that GABAergic neurons in the ventrobasal complex of guinea-pigs give rise to functionally important rearrangements of its intrinsic synaptic organization and that they represent the morphological basis for an intrinsic modulatory mechanism that is absent in other thalamic nuclei lacking inhibitory interneurons. The phylogenetic implications of these findings are also discussed in comparison to other animal species.

Animals↗
PubMed1993

Branching projections from mesopontine nuclei to the nucleus reticularis and related thalamic nuclei: a double labelling study in the rat.

Branching projections from pedunculopontine and laterodorsal tegmental nuclei to different thalamic targets were studied by means of a double retrograde tracing technique. The results show a topographic distribution of mesopontine neurons projecting to different thalamic targets. In addition, the present data demonstrate that a small percentage (< or = 5%) of mesopontine neurons projecting to the intralaminar nuclei or to the rostral pole of the reticular nucleus innervate both these areas by means of branching axons. By contrast, a large number of mesopontine neurons projecting to the sensorimotor thalamic nuclei send axon collaterals to the caudal part of the reticular nucleus. The present findings support the hypothesis of an inhomogeneity of different sectors of the thalamic reticular nucleus. Thus, this nucleus can be differentiated into two functional areas, in accordance with their connections with functionally different cortical fields and thalamic districts. The possibility that these two areas of the thalamic reticular nucleus subserve different mechanisms during sleep phenomena is discussed.

Animals↗
PubMed1993

GABAA-receptor immunoreactivity in the rat dorsal thalamus: an ultrastructural investigation.

The ultrastructural localization of GABAA-receptor (GABAA-R) immunoreactivity (ir) in representative nuclei of the rat dorsal thalamus was investigated using the monoclonal antibody 62-3G1 to the beta 2 and beta 3 subunits of the GABAA-R [8]. The pattern of distribution and the subcellular localization of ir were similar in all the thalamic nuclei examined, with the exception of the reticular nucleus that was unlabeled. The reaction product was present along somatic and dendritic plasma membranes of thalamic neurons and on their intracellular membranes. No labelling was observed in glial cells. The ir was present in areas of plasma membranes related and non related to terminals containing flat vesicles, and also on invaginated plasma membranes suggesting a recycling process of the receptor complex. The distribution and mismatches between GABA neurotransmitter and its receptor localization are discussed.

Animals↗