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Giuseppe Ferraro

Publications and source records attributed to Giuseppe Ferraro.

10 recordsLinked to original sources

Effects of nitric oxide-active drugs on the discharge of subthalamic neurons: microiontophoretic evidence in the rat.

The presence of nitric oxide (NO) synthase and of soluble guanylyl cyclase, the main NO-activated metabolic pathway, has been demonstrated in many cells of the subthalamic nucleus. In this study, the effects induced on the firing of 96 subthalamic neurons by microiontophoretically administering drugs modifying NO neurotransmission were explored in anaesthetized rats. Recorded neurons were classified into regularly and irregularly discharging on the basis of their firing pattern. Nomega-nitro-L-arginine methyl ester (L-NAME; a NO synthase inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1; a NO donor), S-nitroso-glutathione (SNOG; another NO donor) and 8-Br-cGMP (a cell-permeable analogue of cGMP, the main second-messenger of NO neurotransmission) were iontophoretically applied while performing single-unit extracellular recordings. The activity of most neurons was influenced in a statistically significant way: in particular, both current-related inhibitory L-NAME-induced effects (20/39 tested cells) and excitatory effects of SIN-1 (25/41 tested neurons), SNOG (19/32 tested cells) and 8-Br-cGMP (13/19 tested neurons) were demonstrated. Neither statistically significant differences between the responses of regularly and irregularly discharging cells, nor specific topographical clustering of responding neurons, were demonstrated. Neurons administered drugs oppositely modulating the NO neurotransmission often displayed responses to only one treatment. We hypothesize that NO neurotransmission could exert a modulatory influence upon subthalamic neurons, with a prevalent excitatory effect. However, in the light of the presence of some responses of opposite sign to the same drug displayed by different subthalamic neurons, more complex effects of NO neurotransmission could be suggested, probably due to interactions with other classical neurotransmitter systems.

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The discharge of subthalamic neurons is modulated by inhibiting the nitric oxide synthase in the rat.

The effects induced on the discharge of subthalamic spontaneously active neurons by inhibiting the enzyme nitric oxide synthase was studied in two groups of urethane-anesthetized rats. In the first group of animals (n = 10), the activity of subthalamic single units was recorded before and after the systemic administration of 7-nitro-indazole (7-NI, 50 mg/kg i.p.), a selective inhibitor of neuronal nitric oxide synthase. In the second group of rats (n = 15), Nomega-nitro-L-arginine methyl ester (L-NAME), another inhibitor of nitric oxide synthase, was iontophoretically administered while performing single unit extracellular recordings. The activity of most tested spontaneously discharging neurons (8/10) was influenced by 7-NI administration, which always caused a statistically significant decrease in the firing rate of the responsive cells. In contrast, the iontophoretic administration of L-NAME, although influencing many cells (24/32), did not have univocal effects: in fact, 18 cells were inhibited while 6 neurons were excited in a statistically significant manner. We hypothesize that nitric oxide neurotransmission could exert a tonic modulatory influence upon spontaneously discharging subthalamic neurons, with a prevalent excitatory effect.

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Abdominoplasty: thromboembolic risks for both sexes.

During surgical procedures, coagulation complications may occur. Discriminating factors are multiple and may vary because of the anatomical regions involved and because of preexisting diseases. The aim of this study was to analyze changes in such hematological parameters of patients undergoing conventional abdominoplasty with standard surgical procedures under general anaesthesia. For the study, 40 patients (20 men and 20 women) 30 to 60 years with normal coagulation assessments, no previous or current history of hemorrhagic or thrombotic disease, and no primary family history of such problems were selected. All the patients underwent conventional abdominoplasty surgical procedures. Analysis of the results suggests that immediately after surgery, in the absence of any preexisting hypo- or hypercoagulability state, there was no circumstantial modification in coagulation factors considered predictive for thromboembolic risk. However, an interesting difference between male and female patients was noted. In the male group, there was an insignificant uniform downward trend of all values immediately after surgery. In conclusion, women are less hypercoagulative than men in the postoperative period, suggesting that women have limited protection from the development of thromboembolic complications immediately after surgical procedures.

Abdomen↗

High mobility group A1 expression correlates with the histological grade of human glial tumors.

Glioblastoma is one of the most aggressive tumors in mankind with 50% of patients dying within the 1st year of diagnosis, and being refractory to conventional therapies. The aim of our work has been to analyse the expression of the HMGA1 proteins in human astrocytomas and glioblastomas in order to verify whether the detection of these proteins might be of some help in the diagnosis of these neoplasias. Here we report the analysis of 27 cases, including 12 astrocytomas and 15 glioblastomas, for HMGA1 expression. All the neoplastic samples showed positive staining even though the number of positive cells and the staining intensity was higher in glioblastomas compared to astrocytomas. Conversely, HMGA1 proteins were not detected in normal brain. Accordingly, expression of the hmga1 gene, analysed by RT-PCR, was higher in glioblastomas than in astrocytomas.

Adult↗

Nitric oxide-induced inhibition on striatal cells and excitation on globus pallidus neurons: a microiontophoretic study in the rat.

Single units were recorded in the striatum and in the globus pallidus (GP) of urethane-anesthetized rats under microiontophoretic administration of either Nomega-nitro-L-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), or 3-morpholino-sydnonimin-hydrocloride (SIN-1, nitric oxide, NO donor). A steady baseline firing of sporadically discharging striatal neurons (basal firing rate <0.1 spikes/s) was evoked by a pulsed microiontophoretic ejection of glutamate. On striatal neurons, microiontophoretic application of SIN-1 induced a current-dependent inhibition (11/13), whereas L-NAME administration produced a clear excitation (9/9). On GP cells, the administration of SIN-1 had excitatory effects (10/15), whereas the administration of L-NAME reduced the neuronal activity (6/6). We hypothesize that NO could exert an intrinsic regulatory action on the activity of both striatal and GP cells.

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Nitric oxide modulates striatal neuronal activity via soluble guanylyl cyclase: an in vivo microiontophoretic study in rats.

It is now well established that nitric oxide (NO) acts as a neuromodulator in the central nervous system. To assess the role of NO in modulating striatal activity, single-unit recording was combined with iontophoresis to study presumed spiny projection neurons in urethane-anesthetized male rats. Striatal neurons recorded were essentially quiescent and were therefore activated to fire by the iontophoretic administration of glutamate, pulsed in cycles of 30 sec on and 40 sec off. In this study, iontophoresis of 3-morpholinosydnonimine hydrochloride (SIN 1), a nitric oxide donor, produced reproducible, current-dependent inhibition of glutamate-induced excitation in 12 of 15 striatal neurons, reaching its maximal inhibitory effect (76.2 +/- 5.6% below baseline) during the application of a 100 nA current. Conversely, microiontophoretic application of N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, produced clear and reproducible excitation of glutamate evoked firing in 7 of 10 cells (51.4 +/- 2.3%, at 100 nA). To evaluate the involvement of cyclic guanosine monophosphate (cGMP) in the electrophysiological effects produced by the NO donor, the effects of methylene blue, an inhibitor of guanylyl cyclase, on the responses of nine neurons to SIN 1 were tested. In six of nine neurons the effect of SIN 1 was significantly reduced during continuous iontophoretic administration (50 nA) of methylene blue. Taken together, these data show that NO modulates the striatal network and that inhibitory control of the output neurons is involved in this effect. These results also suggest that the effects of nitric oxide on striatal neurons are partially mediated via cGMP.

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CCK-nitric oxide interaction in rat cortex, striatum and pallidum.

We have chosen to study the effects of both nitric oxide (NO) and cholecystokinin neuromodulatory systems in some motor structures that are frequently involved in excitotoxic phenomena. In particular, 7-nitroindazole, a selective inhibitor of neuronal NO synthase, was administered in control and sulfated cholecystokinin octapeptide-treated rats. Cortical surface, striatal and pallidal depth bioelectric activities were examined through Fast Fourier Transform analysis. Cortical and pallidal recordings revealed an increase of rapid standard rhythms after the inhibition of neuronal NO synthase; in contrast, striatal depth recordings showed a marked increase of slow standard rhythms. All these effects were completely abolished by chronic pre-treatment with sulfated cholecystokinin octapeptide. The results suggest a functional co-operation between cholecystokinin and NO systems in the modulation of the bioelectric activity of all the motor structures examined, and the possibility of preventing excitotoxic damages induced by an anomalous balance between excitatory and inhibitory neurotransmitters in these areas.

Animals↗

Inhibition of nitric oxide synthase influences the activity of striatal neurons in the rat.

The activity of single units in the striatum of urethane-anesthetized rats was recorded before and after the systemic administration of 7-nitro-indazole (7-NI; 50 mg/kg intraperitoneally), a selective inhibitor of neuronal nitric oxide (NO) synthase. Two neuronal types were clearly distinguishable electrophysiologically, on the basis of either discharge frequency pattern or features of the individual spike waveform (spike duration, negative phase/total duration ratio, and negative phase/total amplitude ratio). Only sporadically discharging neurons (basal firing rate, <0.1 spikes/s) were influenced by 7-NI, which caused a statistically significant increase in their firing rate. In contrast, the activity of continuously discharging neurons (basal firing rate, 4-6 spikes/s) was not affected. We hypothesize that NO neurotransmission could exert a tonic inhibitory influence upon sporadically discharging striatal neurons, which are presumably striatal output neurons.

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CCK-8S systemic administration blocks the 7-nitroindazole-induced effects on the EEG of striatum and globus pallidus: a FFT analysis in the rat.

BACKGROUND: Nitric oxide (NO) and cholecystokinin (CCK) are involved in the modulation of several neurotransmitter systems in the basal ganglia, and a functional interaction between their modulatory effects could be hypothesised. MATERIALS AND METHODS: We studied the effects exerted by the administration of 7-nitroindazole (7-NI) (50 mg kg(-1) i.p.), a selective inhibitor of neuronal NO synthase, on the depth EEG activity of the striatum and of the globus pallidus in both not pre-treated and sulphated CCK octapeptide (CCK-SS)-treated (100 nM kg(-1) i.p.) rats. Striatal and pallidal depth EEG power spectra were examined by means of a Fast Fourier Transform analysis. RESULTS: Striatal depth recordings showed a marked increase of % power of slow standard rhythms after 7-NI systemic treatment. In contrast, pallidal recordings revealed an increase of % power of rapid standard rhythms after i.p. injection of 7-NI. The same modifications were not evidenced in CCK-8S pre-treated rats after 7-NI administration. CONCLUSION: The results show an influence exerted by peripheral CCK on the nitrergic modulation of the bioelectric activities of the striatum and of the globus pallidus. This effect could be of particular interest in the light of NO and CCK involvement in the neuroprotective mechanisms.

Animals↗

Nitric oxide and brain hyperexcitability.

Nitric oxide (NO) is a gaseous messenger involved in atypical forms of intercellular communications, able to exert a strong functional modulation of several neurotransmitter systems. In particular, NO heavily influences the excitatory neurotransmitter glutamate, mainly through NMDA receptors, and the inhibitory neurotransmitter GABA, mainly through GABA A receptors. Due to the involvement of glutamate and GABA in a delicate balance conditioning the functional status of the neural cells, this interaction suggests a role for NO in regulating neuronal excitability and its transition towards hyperexcitability phenomena. This article reviews the main knowledge about the relationships existing between the activity of the NO system and the experimental aspects of epilepsy, focusing on the somewhat antithetic findings about the proconvulsant or the anticonvulsant roles exerted by nitric oxide.

Animals↗