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

Previous studies indicated that several cytokines influenced the seizure propensity in convulsive disorders and were the cause of encephalopathies in childhood. We studied the role of one inflammatory cytokine, interleukin-6 (IL-6), in hyperthermia-induced seizures in developing rats. Twenty-four male Lewis rats (23-28 days old) were divided into three groups (n=8/IL-6 (500 ng), IL-6 (50 ng), and saline control groups). We applied human recombinant IL-6 intra-nasally to developing rats 1h before seizures induced by moist heated air (50 degrees C). The seizure latency was defined as the time from hyperthermia onset until the appearance of continuous seizure discharges on electroencephalography (EEG), and the seizure duration as the duration of continuous spike and wave discharges on EEG. Five of the eight rats in the IL-6 (500 ng) group, two in the IL-6 (50 ng) group, and one in the control group exhibited no seizure discharges during the 360 s heating period. In these cases, the seizure latency time was regarded as 360 s and the seizure duration time as 0 s. The median seizure latency for the IL-6 (500 ng) group, 360 s (range: 256-360), was significantly longer than that for the control one, 249 (121-360) (P<0.05). The seizure duration for the IL-6 (500 ng) group, 0 s (0-20), was significantly shorter than that for the control one, 33 (0-76) (P<0.025). Also, the adenosine receptor antagonist, aminophylline, prevented these effects of IL-6 on hyperthermia-induced seizures. These results indicate that IL-6 plays an anti-convulsive role through the adenosine system in hyperthermia-induced seizures, which might be relevant as to human febrile seizures.
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PMID:Interleukin-6 attenuates hyperthermia-induced seizures in developing rats. 1755 44

In this study, the effect of A1 and A2A adenosine receptor activity of the piriform cortex (PC) on amygdala-kindled seizures was investigated in rats. Animals were kindled by daily electrical stimulation of the amygdala. In fully kindled rats, N6-cyclohexyladenosine (CHA, a selective A1 agonist), 8-cyclopentyl-1,3-dimethylxanthine (CPT, a selective A1 antagonist), CGS21,680 hydrochloride (CGS, a selective A2A agonist), and ZM241,385 (ZM, a selective A2A antagonist) were microinjected bilaterally into the PC. Rats were stimulated 5 min post-drug microinjection and seizure parameters were measured. Results showed that intra-PC CHA (10 and 100 micromol/L) decreased the duration of both afterdischarge and stage 5 seizure and significantly increased the latency to stage 4 seizure. Intra-PC CPT increased afterdischarge and stage 5 seizure duration at the dose of 20 micromol/L. The anticonvulsant effect of CHA (100 micromol/L) was eliminated by CPT (10 micromol/L) pretreatment. On the other hand, neither intra-PC CGS nor ZM had a significant effect on kindled seizures. These results suggest that activity of A1, but not A2A, receptors of the PC have anticonvulsant effects on kindled seizures elicited from electrical stimulation of the amygdala.
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PMID:Anticonvulsant effect of A1 but not A2A adenosine receptors of piriform cortex in amygdala-kindled rats. 1782 22

Adenosine is one of the inhibitory neuromodulators in the brain and is considered to be responsible for seizure arrest and postictal refractoriness. Adenosine, adenosine receptor agonists, and adenosine uptake blockers are known to reduce the severity and duration of amygdala-kindled seizures. The present study was carried out to elucidate the anticonvulsant and neuromodulatory effect of systemic adenosine on the pentylenetetrazol (PTZ)-induced chemical kindling in mice. Kindling was induced by chronic administration of a subconvulsive dose of PTZ (40 mg/kg, i.p.) on every other day for a total period of 9 days. Adenosine was administered daily, 30 min before PTZ or vehicle. The kindling score was recorded immediately following PTZ administration according to a prevalidated scoring scale. Various behavioral and biochemical estimations were performed on day 10 (i.e. 24 h after the last dose of PTZ). Chronic PTZ treatment progressively increased the seizure score with the maximum score reached on day 9. Behavioral analysis found hyperlocomotor activity, anxiogenic response, hyperalgesia and amnesia in kindled mice. Biochemical analysis revealed that chronic treatment with PTZ significantly increased lipid peroxidation (malondialdehyde levels), nitrite (NO(2-) levels), adenosine deaminase (ADA) and total RNA levels and decreased catalase, reduced glutathione (GSH) levels in brain homogenates, and a depletion of adrenal ascorbic acid. Daily treatment with adenosine (25 and 50 mg/kg, i.p.) for 9 days led to a significant decrease in PTZ-induced kindling score and also reversed various behavioral and biochemical alterations produced by PTZ. The results of the present study suggested that systemic adenosine administration reversed the behavioral and biochemical alterations induced by chronic PTZ.
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PMID:Systemic administration of adenosine ameliorates pentylenetetrazol-induced chemical kindling and secondary behavioural and biochemical changes in mice. 1803 59

Multiple lines of investigations have explored the role of cyclooxygenases (COX) in epilepsy and related neuropsychiatric disorders. Cyclooxygenase particularly, COX-2 expression was found to increase in brain during seizure paradigms. The present study was carried out to investigate the effect of rofecoxib, a selective COX-2 inhibitor against pentylenetetrazol (PTZ i.v.) seizure threshold in mice. The study was further extended to elucidate the possible involvement of adenosinergic mechanism in mediating its anticonvulsant action. Minimal dose of PTZ (i.v., mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extension) of PTZ convulsions were noted as an index of seizure threshold. Acute administration of rofecoxib (4mg/kg, i.p.) before PTZ infusion produced an elevation of seizure threshold for all the phases of convulsions. A lower dose of rofecoxib (2mg/kg, i.p.) showed an increase in PTZ seizure threshold for the onset of myoclonic jerks and tonic extension phases but not for generalized clonus. A still lower dose of rofecoxib (1mg/kg, i.p.) failed to increase the threshold in any of the convulsive phases induced by PTZ i.v. infusion. Pretreatment with sub-effective dose of rofecoxib (1mg/kg, i.p.) enhanced the action of sub-protective doses of either adenosine (25mg/kg, i.p.) or 2-chloroadenosine (1 or 2mg/kg, i.p.) in increasing the seizure threshold. On the contrary, treatment with caffeine (100 or 200mg/kg, i.p.) or theophylline (50 or 100mg/kg, i.p.), both non-selective A(1)/A(2) adenosine receptor antagonists reversed the anticonvulsant effect of rofecoxib (4mg/kg, i.p.). Further, dipyridamole (5mg/kg, i.p.), an adenosine uptake inhibitor displayed an anticonvulsant effect with rofecoxib (1mg/kg, i.p.). The study for the first time demonstrated the possible involvement of adenosinergic system in the anticonvulsant effects of rofecoxib against PTZ i.v. seizure threshold paradigm in mice.
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PMID:Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor increases pentylenetetrazol seizure threshold in mice: possible involvement of adenosinergic mechanism. 1805 63

Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individuals with surgically implanted stimulation electrodes, the cellular pathways involved in mediating the effects of DBS remain unknown. Here we show that DBS is associated with a marked increase in the release of ATP, resulting in accumulation of its catabolic product, adenosine. Adenosine A1 receptor activation depresses excitatory transmission in the thalamus and reduces both tremor- and DBS-induced side effects. Intrathalamic infusion of A1 receptor agonists directly reduces tremor, whereas adenosine A1 receptor-null mice show involuntary movements and seizure at stimulation intensities below the therapeutic level. Furthermore, our data indicate that endogenous adenosine mechanisms are active in tremor, thus supporting the clinical notion that caffeine, a nonselective adenosine receptor antagonist, can trigger or exacerbate essential tremor. Our findings suggest that nonsynaptic mechanisms involving the activation of A1 receptors suppress tremor activity and limit stimulation-induced side effects, thereby providing a new pharmacological target to replace or improve the efficacy of DBS.
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PMID:Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor. 1818 Jul 13

Current therapies for epilepsy are largely symptomatic and do not affect the underlying mechanisms of disease progression, i.e. epileptogenesis. Given the large percentage of pharmacoresistant chronic epilepsies, novel approaches are needed to understand and modify the underlying pathogenetic mechanisms. Although different types of brain injury (e.g. status epilepticus, traumatic brain injury, stroke) can trigger epileptogenesis, astrogliosis appears to be a homotypic response and hallmark of epilepsy. Indeed, recent findings indicate that epilepsy might be a disease of astrocyte dysfunction. This review focuses on the inhibitory neuromodulator and endogenous anticonvulsant adenosine, which is largely regulated by astrocytes and its key metabolic enzyme adenosine kinase (ADK). Recent findings support the "ADK hypothesis of epileptogenesis": (i) Mouse models of epileptogenesis suggest a sequence of events leading from initial downregulation of ADK and elevation of ambient adenosine as an acute protective response, to changes in astrocytic adenosine receptor expression, to astrocyte proliferation and hypertrophy (i.e. astrogliosis), to consequential overexpression of ADK, reduced adenosine and - finally - to spontaneous focal seizure activity restricted to regions of astrogliotic overexpression of ADK. (ii) Transgenic mice overexpressing ADK display increased sensitivity to brain injury and seizures. (iii) Inhibition of ADK prevents seizures in a mouse model of pharmacoresistant epilepsy. (iv) Intrahippocampal implants of stem cells engineered to lack ADK prevent epileptogenesis. Thus, ADK emerges both as a diagnostic marker to predict, as well as a prime therapeutic target to prevent, epileptogenesis.
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PMID:The adenosine kinase hypothesis of epileptogenesis. 1824 58

In the present study, the effects of adenosine agonists on the development of sensitization to withdrawal signs precipitated after sporadic treatment with diazepam, in mice, were investigated. To obtain the sensitization, the animals were divided into groups: continuously and sporadically treated with diazepam (15.0 mg/kg, s.c.). The adenosine receptor agonists (CPA, CGS 21,680 and NECA) were administered in sporadically diazepam treated mice during two diazepam-free periods. Concomitant administration of pentetrazole (55.0 mg/kg, s.c.) with flumazenil (5.0 mg/kg, i.p.) after the last injection of diazepam or vehicle, induced the withdrawal signs, such as clonic seizures, tonic convulsion and death episodes. The major finding of our experiments is attenuation of withdrawal signs in sensitized mice, inducing by all adenosine agonists. Only higher dose of CPA produced significantly decreased the number of withdrawal incidents, while both used doses of CGS 21,680 and NECA produced more clear effects. These results support the hypothesis that adenosinergic system is involved in the mechanisms of sensitization to the benzodiazepine withdrawal signs, and adenosine A(2A) receptors play more important role in that process.
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PMID:Adenosine receptor agonists attenuate the development of diazepam withdrawal-induced sensitization in mice. 1846 97

Electrographic seizures are a feature of organophosphate anticholinesterase intoxication. Clinical studies of pesticide poisonings suggest that seizures are more common in children than in adults. Since flaccid paralysis, a characteristic sign of organophosphate poisoning, can mask convulsions, the most reliable indicator of seizures is the electroencephalogram, but this has not been widely used in clinical studies. Seizures can rapidly progress to status epilepticus, contributing to mortality and, in survivors, to neuronal damage and neurological impairment. Anticonvulsant drugs can significantly reduce the lethal and toxic effects of these compounds. A benzodiazepine, usually diazepam, is the treatment currently indicated for control of seizures. Animal studies have indicated that the early phase of seizure activity (0-5 min after seizure onset) is purely cholinergic, predominantly involving muscarinic mechanisms. Seizure activity subsequently progresses through mixed cholinergic and noncholinergic modulation (5-40 min) into a final noncholinergic phase. Neuropathology caused by seizures is most likely associated with glutamatergic excitotoxicity. Future prospects for improved treatments include new benzodiazepines, glutamate receptor antagonists, antimuscarinics with additional antiglutamatergic activity and adenosine receptor antagonists.
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PMID:Seizure activity post organophosphate exposure. 1927 3

Pentylenetetrazole (PTZ) is a convulsant used to model epileptic seizures in rats. In the PTZ-model, altered heat shock protein 27 (HSP-27) expression highlights seizure-affected astrocytes, which play an important role in glutamate and GABA metabolism. This raises the question whether impaired neurotransmitter metabolism leads to an imbalance in neurotransmitter receptor expression. Consequently, we investigated the effects of seizures on the densities of seven different neurotransmitter receptors in rats which were repeatedly treated with PTZ (40 mg/kg) over a period of 14 days. Quantitative in vitro receptor autoradiography was used to measure the regional binding site densities of the glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptors, the adenosine receptor type 1 (A(1)), which is part of the system controlling glutamate release, and the gamma-aminobutyric acid (GABA) receptors GABA(A) and GABA(B) as well as the GABA(A)-associated benzodiazepine (BZ) binding sites in each rat. Our results demonstrate altered receptor densities in brain regions of PTZ-treated animals, including the HSP-27 expressing foci (i.e. amygdala, piriform and entorhinal cortex, dentate gyrus). A general decrease of kainate receptor densities was observed together with an increase of NMDA binding sites in the hippocampus, the somatosensory, piriform and the entorhinal cortices. Furthermore, A(1) binding sites were decreased in the amygdala and hippocampal CA1 region (CA1), while BZ binding sites were increased in the dentate gyrus and CA1. Our data demonstrate the impact of PTZ induced seizures on the densities of kainate, NMDA, A(1) and BZ binding sites in epileptic brain. These changes are not restricted to regions showing glial impairment. Thus, an altered balance between different excitatory (NMDA) and modulatory receptors (A(1), BZ binding sites, kainate) shows a much wider regional distribution than that of glial HSP-27 expression, indicating that receptor changes are not following the glial stress responses, but may precede the HSP-27 expression.
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PMID:Pentylenetetrazole-induced seizures affect binding site densities for GABA, glutamate and adenosine receptors in the rat brain. 1934 22

Sudden unexpected death in epilepsy (SUDEP) is a significant cause of mortality in people with epilepsy. Two postulated causes for SUDEP, cardiac and respiratory depression, can both be explained by overstimulation of adenosine receptors. We hypothesized that SUDEP is a consequence of a surge in adenosine as a result of prolonged seizures combined with deficient adenosine clearance; consequently, blockade of adenosine receptors should prevent SUDEP. Here we induced impaired adenosine clearance in adult mice by pharmacologic inhibition of the adenosine-removing enzymes, adenosine kinase and deaminase. Combination of impaired adenosine clearance with kainic acid-induced seizures triggered sudden death in all animals. Most importantly, the adenosine receptor antagonist caffeine, when given after seizure onset, increased survival from 23.75 +/- 1.35 min to 54.86 +/- 6.59 min (p < 0.01). Our data indicate that SUDEP is due to overactivation of adenosine receptors and that caffeine treatment after seizure onset might be beneficial.
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PMID:A novel mouse model for sudden unexpected death in epilepsy (SUDEP): role of impaired adenosine clearance. 1967 57


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