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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of chronic administration of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on N-methyl-D-aspartate (NMDA)-evoked seizures was studied in C57BL/6 mice (20/group). Animals were injected i.p. for 9 days with either 1.0 mg/kg CPA or 1.0 mg/kg CPX followed by 2 injection-free days (the washout period) and subsequent administration of a single dose of 60 mg/kg NMDA. As in our previous study, this dose of NMDA caused clonic/tonic seizures resulting in high (60%) mortality within 3 h after injection of the drug. Despite insignificant changes in seizure latency, chronic pretreatment with CPA increased the incidence of clonic/tonic episodes and end-point mortality. Conversely; chronic exposure to CPX completely eliminated clonic/tonic episodes, significantly increased average survival time, and reduced end-point mortality (P < 0.05). The results indicate that chronic treatment with adenosine A1 receptor antagonist may protect against NMDA-evoked seizures to the same degree as previously observed following a single, acute exposure to CPA. Since the density of adenosine receptor binding sites was unchanged after chronic treatment with either CPX or CPA, it is likely that the mechanism behind the observed protection may rest at the level of second messenger systems coupled to adenosine A1 receptors.
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PMID:Chronic adenosine A1 receptor agonist and antagonist: effect on receptor density and N-methyl-D-aspartate induced seizures in mice. 801 54

To elucidate the consequences of convulsions, we examined biochemically and electrophysiologically the brains of mice that had sustained two complete tonic-clonic convulsions after administration of pentylenetetrazol (PTZ 50 mg/kg intraperitoneally, i.p.), 48 and 24 h before decapitation. Control mice were injected with saline. Input/output curves of the extracellular synaptic responses in the CA1 area of hippocampal slices showed that PTZ-induced seizures do not establish the persistent change in hippocampal excitability itself that can be detected in vitro. However, use of the paired-pulse stimulation paradigm showed that gamma-aminobutyric acid A (GABAA)-mediated recurrent inhibition was significantly weaker (by 19-25%) in the CA1 area of slices from PTZ-treated mice (PTZ slices) as compared with slices from control mice (control slices). The density of GABAA receptors (high-affinity component) was also lower in hippocampus (by 19%) and cortex (by 14%) of PTZ-treated mice. A GABA-related disinhibitory mechanism underlying PTZ seizures may thus persist for 1 day after the seizure, predisposing the brain to subsequent seizures. On the other hand, the depressant effect of a single dose of adenosine 10 microM on the CA1 synaptic response was stronger (by 35% on population spikes) and longer lasting in PTZ slices as compared with controls. This could be attributed to significantly higher adenosine A1 receptor density in hippocampus (Bmax of [3H]CHA was higher by 34%) as well as cortex and cerebellum of these animals. The phenomenon may reflect an adenosine A1-mediated adaptive mechanism that offers protection from subsequent seizures.
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PMID:Pentylenetetrazol-induced seizures decrease gamma-aminobutyric acid-mediated recurrent inhibition and enhance adenosine-mediated depression. 811 33

1. Systemic injections of kainic acid, 10 mg kg-1, into adult rats resulted in lesions in the hippocampus, as assessed by peripheral benzodiazepine ligand binding. Co-administration of clonazepam at 1 mg kg-1 or 0.2 mg kg-1 prevented major seizures associated with kainate injections, but did not alter significantly the production of hippocampal damage. 2. The co-administration of the adenosine A1 agonist R-phenylisopropyladenosine (R-PIA, 25 micrograms kg-1, i.p.) abolished the lesions induced by kainic acid. 3. The presence of the selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (250 or 50 micrograms kg-1, i.p.) abolished the R-PIA neuroprotective action. 4. The A1/A2 antagonist, 8-(p-sulphophenyl)theophylline (20 mg kg-1, i.p.) which cannot cross the blood brain barrier, did not alter significantly the neuroprotective action of R-PIA, indicating that the neuroprotective action of the purine may be predominantly central. 5. The time course of the neuroprotection was also examined. R-PIA was effective when administered 2 h before or after kainate administration. 6. The results emphasise the potential utility of systemically active adenosine A1 receptor ligands in reducing CNS gliosis induced by the activation of excitatory amino acid receptors.
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PMID:Mediation of the neuroprotective action of R-phenylisopropyl-adenosine through a centrally located adenosine A1 receptor. 822 Sep 9

Adenosine has been shown to be a major regulator of neuronal activity in convulsive disorders, exerting its anticonvulsant effect through central A1 adenosine receptors. The aim of the present study was to investigate the effect of generalized tonic-clonic seizures induced by pentylentetrazol on regional changes in A1 adenosine receptor density and distribution in the mouse brain by in vitro quantitative autoradiography. As radioligand the specific agonist of A1 receptors [3H]cyclohexyladenosine was used. After two consecutive (once daily) pentylentetrazol-induced convulsions a widespread upregulation of A1 receptor density was detected with a marked enhancement in structures that mediate seizure activity like hippocampus, mamillary bodies, septum, substantia nigra, thalamic nuclei and cerebral cortices. On the contrary, in basal ganglia a significant downregulation of A1 receptors was observed. These results indicate that: (i) the observed increases or decreases in A1 receptor density are organized in selective anatomical structures related to seizure development rather than uniform in the brain; and (ii) since the upregulation of A1 receptors is sufficient to enhance the physiological depressive response of adenosine, the overall evoked increases seen here may lead to a stronger inhibitory tone and accordingly to a more efficient anticonvulsant effect of endogenous adenosine.
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PMID:Effect of pentylentetrazol-induced seizures on A1 adenosine receptor regional density in the mouse brain: a quantitative autoradiographic study. 825 29

The effect of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on N-methyl-D-aspartate (NMDA)-evoked seizures was studied in C57BL/6 mice (20/group). Animals were injected i.p. either with CPA (0.5, 1, 2 mg/kg) or CPX (1, 2 mg/kg) 15 min prior to administration of NMDA (30, 60, 125 mg/kg). Administration of NMDA alone resulted in a complete locomotor arrest at 30 mg/kg, while clonic/tonic seizures and progressively increasing mortality were seen at higher doses. Prior administration of CPA resulted either in a delay of seizure onset and unchanged mortality (0.5 mg/kg CPA, 60 mg/kg NMDA) or in elimination of tonic episodes and a significant reduction in postictal mortality (1, 2 mg/kg CPA; 60, 125 mg/kg NMDA). Pretreatment with CPX at either 1 or 2 mg/kg eliminated locomotor depression in animals injected with NMDA at 30 mg/kg. At 60 mg/kg NMDA, the effect of CPX administration resulted in mortality equivalent to that seen with 125 mg/kg NMDA administered alone. The results indicate that A1 receptor agonists may protect against NMDA-evoked seizures and that the adenosine A1 receptor may be directly involved in these actions.
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PMID:Effects of N6-cyclopentyl adenosine and 8-cyclopentyl-1,3-dipropylxanthine on N-methyl-D-aspartate induced seizures in mice. 828 13

A significant increase of A1 adenosine receptor binding (48% increase of mean) was detected in human neocortex obtained from patients suffering from temporal lobe epilepsy as compared to control neocortex from non-epileptic patients. Such increase was equally distributed in the six cortical layers and reached similar levels in each of the five specimens tested independently of age, sex and pharmacological treatment of the patient. Since adenosine exerts a depressant effect on neocortical neurons in slices obtained from epileptic patients, this upregulation of A1 receptor binding may constitute a protective mechanism against subsequent seizures, which is exerted by elevating the depressant response of the brain to endogenous adenosine.
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PMID:Upregulation of A1 adenosine receptors in human temporal lobe epilepsy: a quantitative autoradiographic study. 829 23

The effects of long-term caffeine treatment on N-methyl-D-aspartate (NMDA)-induced seizures in mice were studied. Caffeine was added (0.3 g/l) to drinking water for 14 days and the mice ingested 60-70 mg/kg/day. During the treatment, the plasma concentrations of methylxanthines (caffeine, theophylline and/or paraxanthine, theobromine) were measured. NMDA (150 mg/kg i.p.) was administered to control mice and to mice during and after the caffeine administration. A1 adenosine receptor density in the gyrus dentatus of hippocampus, measured by quantitative receptor autoradiography with [3H]cyclohexyl adenosine as the ligand, was not significantly altered after long-term caffeine treatment. NMDA-induced clonic seizures, wet dog shakes and mortality were significantly reduced at the end of long-term caffeine treatment but returned towards control at 1 and 2 days after withdrawal. At the end of caffeine treatment, tonic seizures were also absent. These results show that long-term treatment with caffeine in a dose that gives plasma levels of 6-10 microM decreases the effects of NMDA on e.g. seizure susceptibility, and that this effect cannot be ascribed to changes of A1 adenosine receptor density.
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PMID:Long-term caffeine treatment leads to a decreased susceptibility to NMDA-induced clonic seizures in mice without changes in adenosine A1 receptor number. 833 Feb 5

The substantia nigra pars reticulata (SNr) has been reported to be critically involved in the development and propagation of epileptic seizures, while extracellular adenosine appears to be important for making seizures stop. In the present study, an adenosine A1 receptor agonist [N6-cyclohexyladenosine (CHA); 2.0 nmol/side, or vehicle] was injected bilaterally into the SNr shortly before each of the first five of a series of daily kindling stimuli delivered to the rat amygdala. Injections did not affect the acquisition of kindled afterdischarges or the rate at which seizures developed over subsequent kindling sessions, but convulsions occurring 48-72 h after treatment were significantly shortened. Thus, purinergic mechanisms in the SNr do not appear to be specifically involved in the acquisition of kindled seizures but may contribute to a postictal inhibitory process that shortens the convulsive component.
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PMID:Effect of an adenosine A1 agonist injected into substantia nigra on kindling of epileptic seizures and convulsion duration. 843 Jan 15

The protective effects of the selective adenosine A1 receptor agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA), the selective adenosine A2A receptor agonist, 2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA), and the non-selective agonist, 5'-N-ethylcarboxamidoadenosine (NECA) were studied against lethal seizures induced by intraperitoneal (i.p.) injection of pentylenetetrazole (80 mg/kg). In acute studies there was a dose-dependent reduction of lethal seizures, as shown by the low dose's protecting 50% of animals (PD50): 0.11, 0.05 and 0.05 mg/kg i.p. for CCPA, 2HE-NECA and NECA, respectively. In the repeated administration studies the animals received either vehicle or drug i.p. twice daily for 12 days. The drug doses were twice the PD50 value: 0.3 mg/kg for CCPA or 0.1 mg/kg for both 2HE-NECA and NECA. 2HE-NECA and NECA maintained their protective activity against pentylenetetrazole-induced seizures (63% or 60% vs. 60% or 58% in acute studies, respectively). Conversely, repeated treatment with CCPA resulted in a marked decrease of its effects (67% vs. 30% in acute studies; P < 0.05). The data indicate that in addition to adenosine A1 the A2A receptors also appear to be involved in the protection from seizures. The anticonvulsant effects induced by repeated stimulation of adenosine A1 receptors are subject to tolerance, whereas effects depending on adenosine A2A receptor activation are maintained.
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PMID:Effects of repeated administration of selective adenosine A1 and A2A receptor agonists on pentylenetetrazole-induced convulsions in the rat. 875 Jun 98

The effects of acute and chronic treatment with ethanol on the function of A1 adenosine receptor in the rat cerebellar cortex were investigated. Acute administration of ethanol (0.5-5 g/kg) had no effect on the binding of the A1-receptor agonist [3H]2-chloro-N6-cyclopentyladenosine ([3H]CCPA) or that the antagonist [3H]8-cyclopentyl-1-3-dipropylxanthine ([3H]DPCPX) in rat cerebellar cortical membranes. Rats were rendered ethanol dependent by repeated forced oral administration of ethanol (12-18 g/kg per day) for 6 days. [3H]CCPA binding was increased by 23% in cerebellar cortical membranes prepared from rats killed 3 h after ethanol withdrawal compared with saline-treated animals. The increase in [3H]CCPA binding was still apparent 12-24 h after the last ethanol administration, but was no longer detectable 3-6 days after ethanol withdrawal. In contrast, the binding of [3H]DPCPX was not modified in the cerebellar cortex of rats killed at various times after ethanol withdrawal. The acute administration of CCPA [0.25-1 mg/kg, intraperitoneally (IP)] suppressed the tremors and audiogenic seizures apparent 24 h after ethanol withdrawal. Moreover, repeated coadministration of CCPA (0.5 mg/kg, IP, four times daily) and ethanol did not prevent the generation of audiogenic seizures during withdrawal but completely prevented mortality. Finally, CCPA antagonized with similar potencies and efficacies the isoniazid-induced convulsions observed in control and ethanol-withdrawn rats. These results indicate that long-term treatment with intoxicating doses of ethanol enhances [3H]CCPA binding but does not reduce the anticonvulsant efficacy of CCPA or the function of A1 adenosine receptors.
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PMID:Chronic ethanol intoxication enhances [3H]CCPA binding and does not reduce A1 adenosine receptor function in rat cerebellum. 880 28


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