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Biomedical subjects

G Nisticó

Publications and source records attributed to G Nisticó.

At least 19 recordsLinked to original sources
PubMed1997

Spontaneous induction of nitric oxide- and prostaglandin E2-release by hypoxic astroglial cells is modulated by interleukin 1 beta.

The effect of 0, 30, 60, 120, 240, 360 min hypoxia on the release of NO and PGE2 was investigated in human cultured astroglial cells. Exposure of astroglial cells to hypoxic injury produced a dose-dependent increase of the nitrite (the breakdown product of NO) level in the cell supernatant. In addition, a significant activation of the inducible isoform of NO synthase was seen, demonstrating that the enhancement on NO release produced by hypoxic injury was related to an increased biosynthesis of NO-generating enzyme(s). This effect was strongly antagonised by pretreating cells with dexamethasone (20 microM). The increase in NO release by hypoxic astroglial cells was accompanied by sustained release of PGE2, which was antagonised by the cyclooxygenase inhibitor indomethacin (10 microM), and partially attenuated by L-NAME (100 microM), a nitric oxide synthase inhibitor, showing that the release of PGE2 was driven by NO. Finally, inducible NOS activity elicited by hypoxic injury, was antagonised by incubating astroglial cells with antibodies directed against type 2 receptor for IL1 beta. In conclusion, hypoxia stimulates cytokine network in astroglial cells leading to enhanced release of NO and prostanoids and this may represent a key mechanism in cerebral blood flow disturbances.

Animals↗
PubMed1995

Melatonin reduces kainate-induced lipid peroxidation in homogenates of different brain regions.

Melatonin protection against in vitro kainic acid-induced oxidative damage in homogenates from different rat brain regions is shown. Brain-disrupted cell homogenates from cerebral cortex, cerebellum, hippocampus, hypothalamus, and corpus striatum were incubated with kainate (11.7 mM) with or without different concentrations of melatonin (0.1-4 mM). The concentration of malonaldehyde and 4-hydroxyalkenals was measured as an index of lipid peroxidation. Wistar and Sprague-Dawley rats were used. When administered with kainate, melatonin markedly reduced lipid peroxidation in every brain region of both rat strains. The reduction in lipid peroxidation by melatonin was concentration-dependent and varied from 10% to 100%. The protection conferred by melatonin is likely due, at least in part, to its newly discovered, free radical scavenging ability.

Animals↗
PubMed1994

A comparison of the muscarinic response and morphological properties of identified cells in the guinea-pig olfactory cortex in vitro.

The electrophysiological and morphological characteristics of neurons in the guinea-pig olfactory cortex brain slice were investigated using a combined intracellular recording and neurobiotin-dye filling technique, in an attempt to show whether a clear relation existed between cell morphology and excitatory muscarinic response profile. Out of 46 sampled neurons, 25 (termed type 1), responded to bath-application of the muscarinic agonist oxotremorine-M (10 microM, 2-3 min) with a strong and persistent excitation coupled with the appearance of a slow depolarizing afterpotential (10-20 mV amplitude) following a large depolarizing stimulus. These neurons were identified as deep pyramidal cells located in cortical layer III, with characteristic pyramidal/ovoid shaped cell bodies, prominent apical dendrites with branches extending to the surface, and extensive basal dendritic trees. The cells showed a regular spiking pattern in response to injected depolarizing current, with no evidence of bursting behaviour. Nine cells (termed type 2), were strongly excited by oxotremorine-M, but only generated a weak depolarizing afterpotential (< 5 mV) following stimulation. These neurons (located in layer III or at layer II-III border) had a variable, non-pyramidal morphology with either a fusiform/tripolar, stellate/multipolar or bipolar/bi-tufted appearance, respectively. Apart from a more prominent post-spike afterhyperpolarization observed in some type 2 cells, their resting membrane properties and firing patterns were indistinguishable from those of type 1 responding cells. Twelve cells (termed type 3) showed little or no excitatory response to oxotremorine-M, and never generated a post-stimulus slow afterdepolarization. These cells (within compact layer II) had the morphological features of superficial pyramidal cells, typified by their short apical trunks and well-developed apical dendritic trees. They could be distinguished electrophysiologically by their ability to show spike fractionation during injection of large depolarizing current pulses. The morphology and laminar position of neurobiotin-filled cells was also compared with those of cells stained by the Golgi-Cox method. Some factors that may have contributed to the observed differences in muscarinic response profile are discussed. It is proposed that the selective muscarinic induction of the slow depolarizing afterpotential phenomenon in deep pyramidal cells may be important in olfactory cortical learning and memory processes.

Animals↗
PubMed1994

Neurodegeneration produced by intrahippocampal injection of paraquat is reduced by systemic administration of the 21-aminosteroid U74389F in rats.

The behavioural, electrocortical (ECoG) and neurodegenerative effects of intrahippocampal injection of paraquat, a well-known free radical producing agent, were studied in rats. Injection of paraquat (100 nmol) into one dorsal hippocampus produced limbic motor and ECoG seizures. These effects were accompanied at 24 h by severe damage to CA1, CA3 and CA4 hippocampal pyramidal neurones and dentate gyrus granule cells. In comparison to the cell number counted in control, untreated, side of the hippocampus, significant (P < 0.05) neuronal loss was observed in the CA1 and CA3 pyramidal cell layers of the treated hippocampus. A lower dose of the herbicide (10 nmol) did not produce consistent motor and ECoG effects and in no instance was significant neuronal loss observed. A pretreatment with U74389F [21-4-(2,6-di-l-pyrrodinyl-4-pyridinyl)-1-piperazinyl-pregna-1,4,9 (11)triene-3,20-dione monomethansulfonate] (30 mg/kg i.p., 15 min before paraquat) completely protected rats from motor and ECoG epileptogenic effects induced by intrahippocampal paraquat (100 nmol). This dose of U74389F also reduced the hippocampal damage typically produced by paraquat and no significant neuronal loss was reported in the CA1 and CA3 pyramidal cell layers. A lower dose of U74389F (10 mg/kg i.p.) did not afford any protection against the epileptogenic effects produced by paraquat (100 nmol); in these animals hippocampal damage was still evident though neuronal loss did not reach statistical significance. In conclusion, the present data show that systemic administration of U74389F possesses neuroprotective effects against seizures and neurodegeneration typically elicited by intrahippocampal injection of paraquat.

Animals↗
PubMed1992

Cloricromene synergizes with antiplatelet drugs and nitric oxide-like factor derived from rat peritoneal polymorphonuclear cells.

We report that cloricromene (5-30 microM) inhibited thrombin-induced platelet aggregation and synergized with other antiplatelet compounds. The antiaggregatory effect of subthreshold concentrations of the prostaglandin (PG)I2 analogue, iloprost (0.2 nM), or of sodium nitroprusside (1 micron), acting through a nitric oxide (NO)-like mechanism, was significantly potentiated by co-incubation with cloricromene (5 microM). In addition, cloricromene enhanced the antiplatelet activity of the NO-like factor released by peritoneal rat polymorphonuclear cells. Thus, the present results show that cloricromene possesses direct antiplatelet properties and synergizes with other endogenous as well as exogenous antiplatelet compounds.

Animals↗
PubMed1992

Production of seizures and brain damage in rats by alpha-dendrotoxin, a selective K+ channel blocker.

alpha-Dendrotoxin (Dtx), a snake polypeptide, increases neuronal excitability by blocking certain fast-activating, voltage-dependent K+ channels. Thus, the behavioural, electrocortical (ECoG) and neuropathological effects of Dtx, injected into rat brain areas, were studied. A unilateral injection of 35 pmol of Dtx into the CA1 hippocampal area or the dendate gyrus (DG; upper blade) immediately produced motor and ECoG seizures, followed at 24 h by multi-focal brain damage and significant neuronal loss. Whilst brain damage was seen bilaterally, significant neuronal loss occurred only in regions (CA1, CA3, CA4 and DG) ipsilateral to the site of injection. A lower dose (3.5 pmol) of toxin elicited motor and ECoG seizures but failed to produce brain damage. Seizures were observed 50 min after injecting Dtx (35 pmol) into the amygdala, though significant neuronal loss was not evident. 4-Aminopyridine (100 nmol), given into the CA1 area elicited a similar motor and ECoG pattern to that of Dtx except no brain damage could be seen at 24 h. Systemic pretreatment with antagonists of N-methyl-D-aspartate receptors (MK-801 or CGP 37849) did not protect against the effects typically evoked by injecting Dtx into the CA1 area.

2-Amino-5-phosphonovalerate↗
PubMed1992

Evidence that pharmacological manipulations of central L-arginine-NO pathway influence blood pressure and heart rate in rats.

In the present study we have investigated whether pharmacological manipulations of central L-arginine-nitric oxide (L-Arg-NO) pathway could affect blood pressure (BP) and heart rate (HR) in normotensive rats either untreated or pretreated with E. coli lipopolysaccharide (LPS). The intracerebroventricular injection (i.c.v.) of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, caused a fall of BP and HR in LPS-treated but not in control rats. Furthermore, the pressor responses to i.c.v. injection of N-methyl-D-aspartate (NMDA) were enhanced by L-Arg or LPS treatment and, in both cases, this potentiation was blocked by L-NAME. The present results show that in some experimental conditions, such as activation of NMDA receptors or LPS pretreatment, the central microinfusion of drugs affecting the L-Arg-NO pathway may interfere with BP and HR.

Amino Acid Oxidoreductases↗
PubMed1991

Hippocampal damage produced by tetanus toxin in rats can be prevented by lesioning CA1 pyramidal cell excitatory afferents.

The neuropathological effects induced by tetanus toxin (TT) bilaterally microinjected into the hippocampus were studied in rats bearing a surgical unilateral lesion of the Schaffer collaterals. TT (1000 mouse minimum lethal doses, MLDs; n = 5 rats) produced neurodegeneration in the CA1 pyramidal cell layer in the unlesioned side of the hippocampus ten days after injection. By contrast, the injection of TT into the lesioned hippocampus produced no degeneration. In rats bilaterally treated with BSA (n = 3 rats) no neuropathological effects were observed in either hippocampi. In conclusion, our results have demonstrated that the lesion of the Schaffer collaterals may protect against the neuropathological effects induced by TT in rats.

Afferent Pathways↗
PubMed1991

High vulnerability of dentate granule cells to the neuropathological effects induced by intrahippocampal injection of tetanus toxin.

The behavioural and neuropathological effects of tetanus toxin, injected into the dentate gyrus, were studied in rats. The monolateral injection of a single dose (1000 mouse minimum lethal doses, MLDs; n = 14 rats) of tetanus toxin produced time-dependent behavioural stimulation. Wet-dog shakes and facial stereotypy were observed 3-4 days after the injection, culminating 4-5 days after treatment, in "limbic motor seizures". Ten days after injection, histological examination revealed death of dentate granule cells in the tetanus toxin-treated side but not in the contralateral, control side (treated with neutralized toxin). This effect was observed in all rats (n = 5) receiving tetanus toxin in the dentate gyrus and no damage was reported in other sectors (e.g. CA1 and CA3 pyramidal cell layers) of the hippocampus. Quantification of the neuronal damage yielded an approximately 70% reduction (P less than 0.01) in the number of granule cells in the toxin-injected dentate gyrus, compared with the control side. This was greater than that previously reported (30% reduction) in the CA1 pyramidal cell layer of rats receiving the same dose of toxin, into the regio superior of the hippocampus. In conclusion, the present experiments have shown that the focal injection of tetanus toxin into the dentate gyrus produced behavioural excitation and selective death of dentate granule cells.

Animals↗
PubMed1991

Effects of pertussis toxin, dibutyryl-cyclic-AMP, bromo-cyclic-AMP and forskolin on the behavioural and electrocortical power spectrum changes induced by microinfusion of interleukin-2 into the locus coeruleus.

Human recombinant interleukin-2 and rat recombinant IL-2 microinjected into the locus coeruleus of rats, induced typical dose-dependent behavioural sedation and/or sleep and electrocortical synchronization. During sleep induced by this lymphokine a dose-dependent increase in total voltage power (0.25-16 Hz) as well as in the 0.25-3, 3-6 and 6-9 Hz frequency bands was observed. The behavioural and electrocortical effects of interleukin-2 were blocked in animals pretreated with anti-IL-2 monoclonal antibodies and with naloxone, whereas they were still evident in rats pretreated with yohimbine. In addition, the behavioural and electrocortical slow-wave sleep effects observed after the administration of interleukin-2 into the locus coeruleus were reduced significantly or antagonized completely by a previous pretreatment with pertussis toxin, forskolin, dibutyryl-cyclic-AMP and 8-bromo-cyclic-AMP. These results are consistent with the hypothesis that the behavioural and electrocortical changes of this lymphokine are mediated at locus coeruleus level via a guanine regulatory Gi protein coupling IL-2 specific receptors to the adenylate cyclase system.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Tetanus toxin produces neuronal loss and a reduction in GABAA but not GABAB binding sites in rat hippocampus.

The neuropathological effects of tetanus toxin, microinjected in the rat CA1 hippocampal area, were studied by using a microscopical and autoradiographical approach. Tetanus toxin produced a dose- and time-dependent neuronal loss in the CA1 area accompanied by a reduction in the binding of gamma-[3H]aminobutyric acid ([3H]GABA) to GABAA but not GABAB sites in the pyramidal cell layer.

Animals↗
PubMed1990

Behavioural and neuropathological effects produced by tetanus toxin injected into the hippocampus of rats.

The behavioural effects of tetanus toxin, injected into the rostral hippocampus, have been studied in rats. A single dose (1000 mouse minimum lethal doses; n = 10) of the toxin produced tail rigidity, hunched back and sound- and touch-evoked stimuli, 48 hr after the injection in all rats treated and these culminated in generalized convulsions 5-7 days later. Seizures were also observed 4 days after the injection of 2000 MLDs (n = 10), whereas a dose of 500 MLDs (n = 10) was ineffective. Similarly, dose- and time-dependent lethal effects were observed. In comparison to the contralateral (untreated) hippocampus, tetanus toxin (1000 MLDs; n = 3) produced a statistically significantly reduction in the number of cells in the CA1 pyramidal cell layer of the injected side, 7 and 10 days after the injection. No changes were observed in other sectors (CA2 and CA3 areas) of the hippocampus. In conclusion, the present experiments have shown that the focal injection of tetanus toxin into the hippocampus produced dose- and time-dependent behavioural stimulation and lethal effects in rats.

Animals↗
PubMed1989

Epileptogenic activity of some beta-lactam derivatives: structure-activity relationship.

The epileptogenic activity of several derivatives of beta-lactam was compared following their intracerebroventricular administration in rats. At a dose of 0.033 mumol/kg cefazolin was the most powerful epileptogenic compound among the drugs tested; dramatic seizure signs (nodding, clonic convulsions and sometimes escape responses) were observed repeatedly. It was approximately three times more potent than benzylpenicillin and other similar compounds, such as ceftriaxone, cefoperazone and cefamandole. No epileptogenic signs were observed with equimolar doses of cefotaxime, cefonicid and ceftizoxime. All these derivatives differ from the substitution at position 3 and at position 7 of 7-aminocephalosporanic acid. The more convulsant compounds (i.e. cefazolin and ceftezole) are both derivatives of tetrazol and show a marked similarity with pentylentetrazol. In addition, aztreonam, a compound having only the beta-lactam ring substituted with a heterocyclic ring at the 4 position, possessed convulsant properties like those of cefoperazone and cefamandole. This suggests that the beta-lactam ring is able to produce epileptogenic activity and it seems likely that substitutions at the 7-aminocephalosporanic or 6-aminopenicillanic acid may increase or reduce the epileptogenic properties of beta-lactam derivatives.

Animals↗
PubMed1988

Anticonvulsant effects of some calcium entry blockers in DBA/2 mice.

1. The behavioural and anticonvulsant effects of several drugs acting by various mechanisms on calcium-channels or affecting intracellular Ca2+ concentrations were studied after both systemic and intracerebroventricular administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. 2. The anticonvulsant effects were evaluated on seizures evoked by means of auditory stimulation (109 dB) in animals placed singly under a perspex dome. 3. Flunarizine and dihydropyridine derivatives, belonging to class I of calcium entry blockers, administered intraperitoneally, were the most potent compounds. 4. Diltiazem, a benzothiazepine derivative belonging to class III, and HA 1004, a calcium antagonist, acting by inhibiting Ca2+ mobilization from intracellular stores, injected intraperitoneally, were 3-7.6 fold and 5.8-10.7 fold less potent than flunarizine respectively. 5. Verapamil and methoxyverapamil, two phenylalkylamine derivatives, given intraperitoneally, were completely ineffective in preventing sound-induced seizures in DBA/2 mice. In addition, high doses of verapamil and its methoxyderivative occasionally produced spontaneous tonic-clonic seizures. 6. After intracerebroventricular administration of the hydrosoluble calcium entry blockers, belonging to different classes, the anticonvulsant effects were similar to those observed after systemic administration. 7. The systemic administration of Bay K 8644, a dihydropyridine analogue, having the ability to stimulate calcium entry into cells produced a dose-dependent increase in clonic and tonic convulsions and other neurological side effects. 8. The present results strongly support the idea that some Ca2+ antagonists may be useful in human epilepsy.

Animals↗
PubMed1979

Evidence for a receptor supersensitivity following impairment of central serotoninergic activity in the rabbit.

In order to investigate whether a chronic impairment of neuronal serotoninergic transmission in the CNS could result in a receptor supersensitivity, rabbits were pretreated either with 5,6-dihydroxytryptamine (5,6-DHT) or p-chlorophenylalanine (PCPA) and then tested for their hyperthermic response to serotoninergic agonists. A previous (10 days before) intracerebroventricular injection of 5,6-DHT (75 microgram into each cerebral ventricle) significantly potentiated the increase in body temperature induced either by quipazine (1 mg/kg i.v.) or by 5-hydroxytryptophan (5-HTP 2 mg/kg i.v.) in combination with a MAO inhibitor (phenylethylhydrazine 10 mg/kg i.v. 16 h before). Pretreatment with PCPA (100 mg/kg s.c. four times on alternate days, the last dose 48 h before the experiment) also enhanced the hyperthermic effect of quipazine, whereas it inhibited the hyperthermic response to 5-HTP plus MAO inhibitor. These results suggest the existence of a receptor supersensitivity following prolonged blockade of serotoninergic neuronal transmission in the CNS.

5,6-Dihydroxytryptamine↗