Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine is one of the inhibitory neuromodulators in the brain. The present study was carried out to elucidate the effect of adenosine on the pentylenetetrazol (PTZ)-induced seizure threshold in mice. Further, the study also correlated the brain adenosine levels in PTZ-induced seizure threshold. PTZ (0.5%, w/v) was infused through lateral tail vein of mouse at a constant rate of 0.3 ml/min until various stages of convulsions were observed. Minimal dose of PTZ (mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extensor) of PTZ convulsions were noted as an index of seizure threshold. Intravenous infusion of PTZ resulted in a significant decrease in brain adenosine levels. Systemic administration of adenosine (100 and 200 mg/kg, i.p.), 30 min before PTZ infusion, produced a dose-dependent elevation of PTZ-seizure threshold and also enhanced brain adenosine levels as compared to vehicle treated group. The behavioral and neurochemical observations demonstrated a relationship between adenosine levels in the brain and the PTZ seizure threshold in mice.
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PMID:Effect of systemic administration of adenosine on brain adenosine levels in pentylenetetrazol-induced seizure threshold in mice. 1772 Mar 12

Adenosine is a modulator of brain function uniquely positioned to integrate excitatory and inhibitory neurotransmission. The past few years brought a wealth of new data fostering our understanding of how the adenosine system is involved in the pathogenesis of neurological diseases. Thus, dysregulation of the adenosine system is implicated in epileptogenesis and cell therapies have been developed to locally augment adenosine in an approach to prevent seizures. While activation of inhibitory adenosine A(1) receptors is beneficial in epilepsy, chronic pain and cerebral ischemia, inhibition of facilitatory A(2A) receptors has profound neuroprotective effects, which are currently exploited in clinical trials in Parkinson's disease. A new era of adenosine-based therapies has begun, with the prospect to cover a wide range of neurological diseases.
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PMID:Adenosine as a neuromodulator in neurological diseases. 1794 68

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

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

The present study was performed to examine the involvement of nitric oxide (NO) signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol seizure threshold in mice. Minimal dose of pentylenetetrazol (i.v., mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extension) of convulsions was recorded as an index of seizure threshold. Adenosine (100 or 200 mg/kg i.p.) produced a significant increase in the seizure threshold for convulsions induced by pentylenetetrazol i.v. infusion. The anti-convulsant effect of adenosine (100 mg/kg i.p.) was prevented by either L-arginine (50 mg/kg i.p.) [substrate for nitric oxide synthase (NOS)] or sodium nitroprusside (3 mg/kg i.p.) [a NO donor]. On the other hand, N(G)-nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg i.p.) [a non-selective NOS inhibitor] or 7-nitroindazole (7-NI) (25 mg/kg i.p.) [a specific neuronal nitric oxide synthase (nNOS) inhibitor] potentiated the anti-convulsant action of sub-effective dose of adenosine (50 mg/kg i.p.). Aminoguanidine (100 mg/kg i.p.) [a specific inducible NOS (iNOS) inhibitor] pre-treatment was not effective in inducing anti-convulsant effect with sub-effective dose of adenosine (50 mg/kg i.p.). Furthermore, the increase in seizure threshold elicited by adenosine (100 mg/kg i.p.) was also inhibited by concomitant administration with sildenafil (5 mg/kg i.p.) [phosphodiesterase 5 inhibitor]. In contrast, treatment of mice with methylene blue (1 mg/kg i.p.) [a direct inhibitor of both nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC)] failed to induce anti-convulsant action with adenosine (50 mg/kg i.p.) against pentylenetetrazol i.v. infusion. The results demonstrated that the anti-convulsant action of adenosine in the pentylenetetrazol i.v. seizure threshold paradigm may possibly involve an interaction with the L-arginine-NO-cGMP pathway which may be secondary to the activation of adenosine receptors.
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PMID:Nitric oxide signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol-induced seizure threshold in mice. 1845 33

Adenosine augmentation therapies (AAT) make rational use of the brain's own adenosine-based seizure control system and hold promise for the therapy of refractory epilepsy. In an effort to develop an AAT compatible with future clinical application, we developed a novel silk protein-based release system for adenosine. Adenosine releasing brain implants with target release doses of 0, 40, 200, and 1000ng adenosine per day were prepared by embedding adenosine containing microspheres into nanofilm-coated silk fibroin scaffolds. In vitro, the respective polymers released 0, 33.4, 170.5, and 819.0ng adenosine per day over 14 days. The therapeutic potential of the implants was validated in a dose-response study in the rat model of kindling epileptogenesis. Four days prior to the onset of kindling, adenosine releasing polymers were implanted into the infrahippocampal cleft and progressive acquisition of kindled seizures was monitored over a total of 48 stimulations. We document a dose-dependent retardation of seizure acquisition. In recipients of polymers releasing 819ng adenosine per day, kindling epileptogenesis was delayed by one week corresponding to 18 kindling stimulations. Histological analysis of brain samples confirmed the correct location of implants and electrodes. We conclude that silk-based delivery of around 1000ng adenosine per day is a safe and efficient strategy to suppress seizures.
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PMID:Silk polymer-based adenosine release: therapeutic potential for epilepsy. 1851 14

Adenosine is an endogenous inhibitor of excitatory synaptic transmission with potent anticonvulsant properties in the mammalian brain. Given adenosine's important role in modulating synaptic transmission, several mechanisms exist to regulate its extracellular availability. One of these is the intracellular enzyme adenosine kinase (ADK), which phosphorylates adenosine to AMP. We have investigated the role that ADK plays in regulating the presence and effects of extracellular adenosine in area CA1 of rat hippocampal slices. Inhibition of ADK activity with 5'-iodotubercidin (IODO; 5 muM) raised extracellular adenosine, as measured with adenosine biosensors, and potently inhibited field excitatory post-synaptic potentials (fEPSPs) in an adenosine A(1)R-dependent manner. In nominally Mg(2+)-free aCSF, which facilitated the induction of electrically-evoked epileptiform activity, adenosine biosensor recordings revealed that seizures were accompanied by the transient release of adenosine. Under these conditions, IODO also inhibited the fEPSP and greatly suppressed epileptiform activity evoked by brief, high-frequency stimulation. During spontaneous seizures evoked by the A(1)R antagonist CPT, adenosine release was unaffected by IODO. This suggests that ADK activity does not limit activity-dependent adenosine release. On the basis of strong ADK immunoreactivity in GFAP-positive cells, astrocytes are likely to play a key role in regulating basal adenosine levels. It is this action of ADK on the basal adenosine tone that is permissive to seizure activity, and, by extension, other forms of activity-dependent neuronal activity such as synaptic plasticity.
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PMID:Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus. 1895 98

Single seizure and epilepsy is one of the most commonly encountered neurologic disorders in elderly individuals, arising as a result of complex and often multiple acquired underlying pathologies. Adenosine, acting at A1 receptors, exhibits anticonvulsant effects in experimental epilepsy and inhibits progression to status epilepticus. Adenosine deaminase is the enzyme for the regulation of adenosine levels. Therefore any change in adenosine deaminase levels will reflect to adenosine levels. Adenosine deaminase levels were decreased in the groups that were given progesterone. Progesterone may have an antiseizure effect with the additional finding decreased levels of adenosine deaminase that would have resulted in increased adenosine levels that exerts anticonvulsant effect via GABA-A receptors. Further studies are needed to evaluate the role of progesterone effects on adenosine deaminase levels and its mechanism(s) in the pathogenesis.
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PMID:Effects of progesterone on total brain tissue adenosine deaminase activity in experimental epilepsy. 1912 74

Adenosine, a potent anticonvulsant, can be produced in the body by the hydrolysis of adenine nucleotides through the action of ecto- or soluble nucleotidases. Changes in nucleotide hydrolysis occur after pentylenetetrazol-induced epileptic events. We evaluated serum ATP, ADP and AMP hydrolysis rates and soluble nucleotide phosphodiesterase (PDEase) activity at 5, 10, 15, 30 and 60 min, and 12h following an epileptic event. Fifteen patients (seven female, eight male; mean age 15.5 years) were included in the study. The type of seizure was generalized in four patients and was localization related in the remaining 11. There were no differences in adenine nucleotide hydrolysis rates between patients and healthy subjects in the interictal stage. In comparison with controls, ATP, ADP and AMP hydrolysis rates were significantly increased at 5 min (53+/-1.4%, 79.2+/-2.8% and 37.0+/-2.6%, respectively) and up to 30 min following the epileptic event. In contrast to ADP and AMP, ATP hydrolysis remained significantly increased at 60 min (71.4+/-1.6%), returning to the basal level after 12h. Serum PDEase activity was also significantly higher in the patients than in healthy subjects, peaking at 15 min (61+/-2.9%) and remaining significantly increased up to 60 min (4.6+/-1.2%) following the epileptic episode. Globally, the variations in the postictal serum ADP hydrolysis rate almost overlapped those of AMP hydrolysis, whereas changes in the ATP hydrolysis rate overlapped those of PDEase activity. The clinical significance of this elevation in postictal soluble serum nucleotidase activity remains to be clarified. However, it is possible to hypothesize that the higher nucleotidase activity might play a role in the modulation of epileptic events.
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PMID:Postictal serum nucleotidases activities in patients with epilepsy. 1915 84

Adenosine has been shown to play a significant role as a modulator of neuronal activity in convulsive disorders, acting as an endogenous anticonvulsant agent. Any change in adenosine deaminase (ADA) levels will reflect to adenosine levels. In the present study, we have investigated the effect of glutathione on brain tissue ADA levels due to seizures induced by convulsive and subconvulsive dose of pentylenetetrazol (PTZ) in mice. ADA levels due to seizures induced by convulsive and subconvulsive pentylenetetrazol were measured using the Giusti method. ADA levels were higher in the experimental epilepsy groups than in the control and sham groups. ADA levels significantly decreased in the glutathione groups, which may have antiseizure effects. Decreased levels of ADA would be due to increased adenosine levels, protecting against oxidative stress.
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PMID:Antiepileptogenic effects of glutathione against increased brain ADA in PTZ-induced epilepsy. 1928 89


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