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

Adenosine is a potent inhibitory neuromodulator and has been proposed as an endogenous anticonvulsant. Depth electrodes modified to include a microdialysis probe were implanted for 10 to 16 days in the hippocampi of 4 patients with intractable complex partial epilepsy to test the hypothesis that during seizures extracellular adenosine reaches levels that may depress epileptiform activity. Samples were collected bilaterally at 3-minute intervals before, during, and after a single, spontaneous-onset seizure in each patient. All seizures commenced in one hippocampus and propagated to the contralateral hippocampus. Extracellular adenosine levels increased by 6- to 31-fold with the increase significantly greater in the epileptogenic hippocampus. During seizures, levels of adenosine in the dialysate reached concentrations as high as 2.5 microM, reflecting extracellular concentrations of approximately 65 microM. Adenosine at concentrations of 40 to 50 microM depresses epileptiform activity in vitro, so the levels we report may suppress seizure activity in vivo. Moreover, adenosine levels remain elevated above basal values for the entire 18-minute postictal period. These data support the role of adenosine in mediating seizure arrest and postictal refractoriness and suggest that treatments which facilitate adenosine may be effective in preventing seizures.
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PMID:Adenosine: a potential mediator of seizure arrest and postictal refractoriness. 144 42

Adenosine participates in the coupling of cerebral blood flow to oxygen consumption in the brain during such stimuli as hypoxia, ischemia, and seizures. It has been suggested that it also participates in the regulation of cerebral blood flow during somatosensory stimulation, a condition during which cerebral blood flow and oxygen consumption appear to be uncoupled. Interstitial adenosine was estimated by the microdialysis technique and cerebral blood flow was measured by hydrogen clearance in the hindlimb sensory-motor cortex during sciatic nerve stimulation. Cerebral blood flow increased from 102 to 188 ml min-1 100 g-1 (p less than 0.001) in the cortex contralateral to the stimulated leg without an associated increase in interstitial adenosine (baseline 0.624 microM, stimulation 0.583 microM). Infusion of the adenosine antagonist 8-sulfophenyltheophylline failed to block an increase in cerebral blood flow during central sciatic nerve stimulation, but decreased basal cerebral blood flow (69 ml min-1 100 g-1). These results suggest that adenosine does not mediate changes in cerebral blood flow during somatosensory stimulation, but may participate in the regulation of cerebral blood flow in the basal state.
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PMID:Sciatic nerve stimulation does not increase endogenous adenosine production in sensory-motor cortex. 959 50

In the central nervous system, adenosine has been shown to be a major regulator of neuronal activity in convulsive disorders, mainly via the A1 receptor subtype. In a previous work, we have shown that seizures lead to an age-dependent upregulation of cerebral adenosine A1 sites measured in isolated rat cerebral membranes. However, information concerning regional changes in the receptor density was so far lacking. In the present study, the effects of bicuculline-induced seizures were investigated by quantitative autoradiography of central adenosine A1 receptors in developing rats and in adults. Animals were sacrificed 30 min after an intraperitoneal injection of either saline or a convulsive dose of bicuculline. Adenosine A1 receptors in brain sections were labeled by [3H]N6-cyclohexyladenosine (CHA), a potent receptor agonist. Generalized seizures induced a widespread increase in CHA-specific binding, with a marked enhancement in structures that mediate seizure activity, such as substantia nigra, amygdala, septum and hippocampus. Moreover, the addition of guanylyl-5'-imidodiphosphate, a GTP analogue, to the incubation medium reduced CHA binding by the same order of magnitude whether rats were given saline or bicuculline, suggesting that additional adenosine A1 receptors are also functionally linked to G proteins. The age-related postictal increase in adenosine receptors might contribute to facilitate adenosine anticonvulsant effect, especially in newborns.
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PMID:Autoradiographic changes in brain adenosine A1 receptors and their coupling to G proteins following seizures in the developing rat. 191 42

It has been suggested that endogenous chemical substances such as adenosine, released during a seizure attack, may act as anticonvulsants in vivo. To further investigate this putative role, we have tested adenosine and stable adenosine analogues for anticonvulsant activity in vitro against ictal-like epileptiform activity induced by the removal of magnesium ions from medium superfusing wedges and slices of rat neocortex. Purinoceptor agonists attenuated such burst activity with a potency profile of L-phenylisopropyl-adenosine greater than 2-chloroadenosine greater than adenosine, suggesting that their anticonvulsant actions were mediated via the A1 adenosine receptor sub-type. Adenosine exerted no apparent effect on responses to agonists acting at glutamate receptor sub-types, implying no direct postsynaptic activity at glutamatergic synapses. Adenosine receptor antagonists, the methylxanthines (3-isobutyl-1-methylxanthine greater than theophylline) markedly enhanced established epileptiform activity and reversed the anticonvulsant action of adenosine. The selectivity of this reversal was demonstrated by the lack of effect of methylxanthines on pentobarbitone-induced inhibitions of epileptiform bursts. When added to a normal medium containing 1 mM magnesium, the methylxanthines were unable to induce long-lasting ictal-like epileptiform activity.
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PMID:A1 adenosine receptor-mediated block of epileptiform activity induced in zero magnesium in rat neocortex in vitro. 246 56

The goal of this study was to examine vascular responses of the dura mater. Microspheres were used to measure blood flow to the dura and brain in anesthetized dogs. Under control conditions, blood flow to the dura was 38 +/- 3 (SE) ml.min-1.100 g-1. Values for blood flow to the dura obtained with simultaneous injection of 15- and 50-microns microspheres were similar, which suggests that shunting of 15-microns spheres was minimal. Left atrial infusion of substance P (100 ng.kg-1.min-1) and serotonin (40 micrograms.kg-1.min-1), two agonists that have been reported to increase vascular permeability in the dura, increased blood flow to the dura two- to threefold. Adenosine (iv) produced vasodilatation in the dura. Adenosine and serotonin did not affect cerebral blood flow, but substance P increased blood flow to the brain by approximately 40%. Seizures, which produce pronounced dilatation of cerebral vessels despite activation of sympathetic nerves, produced vasoconstriction in the dura. Thus 1) the dura is perfused at a relatively high level of blood flow under normal conditions and is very responsive to vasoactive stimuli, and 2) substance P and serotonin, which have been implicated in the pathogenesis of vascular headache, produce pronounced vasodilator responses in the dura mater.
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PMID:Vascular responses of dura mater. 247 56

Adenosine is now recognized as an important endogenous modulator of neuronal excitability in the mammalian central nervous system. Adenosine is produced and released in the brain, where it exerts potent depressant effects on neuronal firing and synaptic transmission. Multiple adenosine receptor subtypes have been characterized using biochemical, electrophysiological, and radioligand binding techniques. Adenosine analogues have potent anticonvulsant actions in vitro and antagonize seizures in animals induced by a variety of mechanisms, including kindling. The future development of selective adenosine receptor agonists may provide new and more effective treatment for epilepsy.
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PMID:Adenosine receptors in brain: neuromodulation and role in epilepsy. 185 90

Adenosine has been proposed as a metabolic factor involved in the regulation of cerebral blood flow. The evidence in support of this hypothesis, presented in this review, includes information on the adenosine receptors associated with cerebral blood vessels, the synthesis and metabolism of adenosine, and the release of adenosine from the brain. Adenosine dilates cerebral blood vessels, acting at an A2 receptor. The critical evidence implicating an involvement of adenosine in cerebrovascular regulation is derived from experiments with adenosine antagonists and potentiators. The antagonists include methylxanthine adenosine receptor antagonists and the enzyme adenosine deaminase. Potentiators include transport inhibitors, enzyme inhibitors, and adenosine precursors. Adenosine has been implicated in vascular regulation during hypoxia/ischemia, hypercapnia, seizures, severe hypotension, and hypoglycemia. Adenosine possesses a number of properties that can be used to minimize neuronal degeneration during cerebral insults, such as ischemia, including vasodilatation, reduction of excitatory transmitter release, reduction of membrane calcium permeability, inhibition of platelets, and neutrophil aggregation. Several recent studies have demonstrated that manipulation of central adenosine tone can alter the extent of cerebral ischemic damage, indicating a potential new therapeutic approach for the treatment of stroke.
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PMID:Adenosine in the control of the cerebral circulation. 270 69

Dilazep (i.p.), a coronary vasodilator and an uptake inhibitor of adenosine, dose dependently potentiated acute ethanol-induced motor incoordination in mice. In view of peripheral cardiovascular depressive effects of dilazep, the effect of i.c.v. dilazep (25, 50 and 75 micrograms), and its metabolites, 1,4-bis(3-hydroxypropyl)perhydro-1,4-diazepine (BHPD) (15, 31 and 62 micrograms) and 1-[3-(3,4,5-trimethoxybenzoyloxy)propyl]perhydro-1,4-diazepine (TBPD) (62 and 125 micrograms) on ethanol-induced motor incoordination was studied. Dose-related potentiation of ethanol-induced motor incoordination was noted with dilazep and its metabolites. Whereas dilazep (i.p.) produced no apparent central nervous system (CNS) effects, by i.c.v. route, it caused CNS excitation including tonic-clonic seizures. Adenosine uptake inhibition, Ca2+ entry blockade or direct activation of adenosine receptors was ruled out as the possible mechanism of seizures because dipyridamole, verapamil or N6-(2-phenylisopropyl)-adenosine (R-PIA) administered i.c.v., while potentiating ethanol (i.p.)-induced motor incoordination did not produce seizures. The CNS excitation was minimal with BHPD and none with TBPD. Theophylline pretreatment partially blocked potentiation of ethanol-induced motor incoordination by dilazep and BHPD and not by TBPD. The data suggest dilazep-induced potentiation of ethanol-induced motor incoordination is partially due to central adenosine receptor mechanism and partly due to other yet unknown mechanism(s) and further supported our earlier reports about adenosine involvement in the CNS effects of ethanol. The data also suggest that dilazep (i.c.v.)-induced seizures are due to mechanism(s) other than adenosine uptake inhibition, Ca2+ entry blockade or direct adenosine receptor activation.
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PMID:Central nervous system effects and behavioral interactions with ethanol of centrally administered dilazep and its metabolites in mice. 275 78

Following the intraperitoneal administration of the adenosine analogues, 2-chloro-adenosine (1-4 mg/kg) or 5'-N-ethylcarboxamidoadenosine (NECA; 0.01-0.5 mg/kg) to audiogenic DBA/2 mice, there is a potent protection against sound-induced seizures and a simultaneous large (2-5 degrees) reduction in body temperature. The anticonvulsant potency of the adenosine analogues is almost completely abolished by pretreatment with methylxanthines or warming the mice to prevent the adenosine-induced temperature decrease. Adenosine (0.01-1 mM), 2-chloro-adenosine (0.1-1 mM) and NECA (0.1 mM) also significantly inhibit potassium-evoked release of 3H-D-aspartate from rat hippocampal slices. This inhibition is not affected by theophylline (1 mM).
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PMID:Adenosine analogues. The temperature-dependence of the anticonvulsant effect and inhibition of 3H-D-aspartate release. 374 84

We have examined effects of vasodilator stimuli on segmental resistance in the cerebral circulation. Our hypothesis was that resistance of large arteries, as well as small vessels, contributes to cerebral vascular responses to vasodilator stimuli. We measured cerebral blood flow with microspheres in anesthetized rabbits and measured pressure in pial arteries approximately 100 microns diameter using a servo-null method. These values were used to calculate resistance of large arteries (greater than 100 microns diameter) and small vessels (less than 100 microns diameter). Under control conditions, resistance of large arteries accounted for one-third to one-half of total cerebral vascular resistance. Intracarotid infusion of acetylcholine (1 microgram/min) reduced large arterial resistance by 69% and small vessel resistance by 58%. Adenosine also produced marked reductions in resistance of both large and small cerebral vessels. In contrast, seizures reduced large arterial resistance by 50% and small vessel resistance by 85%. Pial arterial pressure, which depends on the ratio of large and small vessel resistance, increased during infusion of acetylcholine and adenosine, but decreased during seizures. We conclude that both large and small cerebral vessels are responsive to acetylcholine and adenosine, and seizures produce preferential reduction in resistance of small vessels.
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PMID:Effects of vasodilator stimuli on resistance of large and small cerebral vessels. 378 70


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