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F E Pontieri

Publications and source records attributed to F E Pontieri.

42 records · Page 3Linked to original sources

Treatment with cyclosporine A promotes axonal regeneration in rats submitted to transverse section of the spinal cord.

The abortive axonal regeneration in the central nervous system (CNS) of mammals has been attributed to a series of inhibitory factors. Previous reports suggest the development of autoimmune reactions following CNS lesion in mammals. In this study we investigated whether immunosuppressive treatment with cyclosporine A is able to facilitate axonal regeneration in rats submitted to complete transverse section of the spinal cord at the level of T7-T8. Treated animals received daily subcutaneous injections of cyclosporine A (2.5 mg/kg), while control rats were given a similar treatment with saline. Immunosuppression was begun immediately after spinal cord transection. Strong evidence of morphological axonal regeneration was observed 15 days after surgery in all cyclosporine A treated animals. Furthermore, treatment with cyclosporine A markedly reduced the seric immune reaction elicited by the lesion. The results of this study, although preliminary, provide further evidence for the development of autoimmune processes following lesion in the CNS, and suggest that blocking of the immune reaction facilitates axonal regeneration in the rat.

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Metabolic mapping of the synergism between MK-801 and SKF 38393 in rats with unilateral lesions of the dopaminergic nigrostriatal pathway.

In rats with a unilateral lesion of the dopaminergic nigrostriatal pathway with 6-hydroxydopamine, blockade of N-methyl-D-aspartate receptors by MK-801 strongly potentiated the turning behavior induced by D-1 receptor stimulation. To determine the functional consequences of such positive interaction we measured the local rates of cerebral glucose utilization (lCMRglc) in lesioned rats treated with MK-801 (0.1 mg/kg) and the D-1 agonist SKF 38393 (1.5 mg/kg), either alone or in combination. Treatment with each drug separately did not induce any substantial change in lCMRglc besides an increase in the metabolic activity of the dorsomedial caudate and entopeduncular nucleus (EP) of the lesioned side of MK-801 treated rats, as compared to the same side of lesioned rats treated with vehicle. Combined administration of MK-801 + SKF 38393 increased lCMRglc in the EP (+77%) and in the substantia nigra pars reticulata (SNr) (+30%) of the lesioned side as compared with the intact side, while it decreased lCMRglc in the lateral habenula (-26%). These changes were also significant when compared to the lesioned side of vehicle treated rats. The results suggest that while the caudate putamen might be the primary site of MK-801 and SKF 38393 positive interaction, the EP and SNr are the striatal efferent areas where this positive interaction is expressed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Alterations in opiate receptor binding in MPTP-induced hemiparkinsonian monkeys.

Quantitative autoradiography was used to study [3H]naloxone binding in the striatum of normal monkeys and monkeys made hemiparkinsonian by the unilateral infusion of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The density of [3H]naloxone binding sites was significantly higher in the caudate and putamen on the MPTP-treated side of hemiparkinsonian monkeys, as compared with binding on the untreated side and in the striatum of normal monkeys. A more extensive patchy distribution of binding sites was evident throughout the striatum on the MPTP-treated side than seen in the striatum of the untreated side or in normal striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Bilateral carotid occlusion in normotensive rats: olds facts and new observations.

This work describes that prolonged mild cerebral ischemia may lead to either general or regional derangement of brain morphofunctional integrity. Normotensive adult Wistar rats were used. Under anesthesia with volatile agents or thiopental, the common carotid arteries were ligated permanently. In one group of animals local cerebral blood flow (1CBF) was measured two hours after carotid occlusion using the [14C]iodoantipyrine method. The other carotid-occluded animals were used for clinical rating and histological evaluation, which was performed two days to 4 weeks after surgical operation. The [14C]iodoantipyrine method showed widespread reduction in the cerebral circulation of carotid-occluded animals. Several hours after carotid occlusion, 40% of the animals showed dramatic neurological signs and died on the day of operation. In 35% of surviving animals, brain infarctions were observed in one and exceptionally two areas of the sensorimotor cortex, thalamus, hippocampus or cerebellum. The evolutionary sequence of the histopathological changes seems to date the induction of the infarcts to the early period of carotid occlusion. In conclusion, reduction of cerebral blood flow causes, in a high percentage of animals, various degrees of acute brain damage after an apparent symptom-free interval.

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Metabolic mapping of the effects of intravenous methamphetamine administration in freely moving rats.

The 2-[14C]deoxyglucose method was used to examine the effects of acute intravenous administration of methamphetamine (0.5-2.5 mg/kg) on rates of local cerebral glucose utilization in freely-moving rats. These effects were correlated with the effects of methamphetamine on locomotor activity assessed simultaneously in the same animals. Methamphetamine administration resulted in widespread dose-dependent increases in glucose utilization within structures of the extrapyramidal motor system. Rates of glucose utilization were positively correlated with locomotor activity in the globus pallidus, substantia nigra reticulata, entopeduncular nucleus, subthalamic nucleus, and the lateral cerebellar cortex. In contrast, within the limbic system alterations in metabolic activity were smaller and more selective. Glucose utilization was increased in the nucleus accumbens at all doses tested, but alterations in glucose utilization in the ventral tegmental area, amygdala, and anterior cingulate were observed only at the highest doses of methamphetamine tested. Significant increases in rates of glucose metabolism were also found in the substantia nigra compacta and in the median and dorsal raphe nuclei. Dopamine and serotonin are depleted in these regions, as well as in the ventral tegmental area where glucose utilization was also increased, following chronic treatment with high doses of methamphetamine. These changes in glucose utilization may be indicative of disturbances in the biochemical processes involved in the neurotoxic effects of methamphetamine.

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Mapping of functional changes associated with administration of substances of abuse in the rat.

The [14C]2-deoxyglucose method allows us to investigate whether a drug affects cerebral functional activity in selected brain regions or along discrete neural pathways. Employment of the method in laboratory animals has shown that substances of abuse produce a wide variety of cerebral functional changes which depend upon a number of different variables including the kind of substance, the dose, the modality of administration, and the context. In spite of such a variability, different substances of abuse, when injected in a rat at doses, or with modalities effective in inducing self-administration, have in common the property of selectively modifying glucose utilization of the nucleus accumbens, in particular in the shell portion. It is likely that the change reflects a functional change of a neural circuitry which mediates motivational properties associated with addiction.

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