Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine is thought to act as an endogenous anticonvulsant and neuroprotective substance in the brain. In the present study we compared neuronal death following status epilepticus (SE) induced in the presence of 8-cyclopentyl-1,3-dimethylxanthine (8-CPT), an A1-adenosine receptor antagonist, with that following SE induced by continuous hippocampal stimulation. Hippocampal damage was characterized using selective nerve and nonnerve cell markers. Six days after SE, both models produced similar patterns of CA1 and CA3 cell loss and selective loss of parvalbumin and hilar somatostatin-immunoreactive interneurons. Calbindin D28K-immunoreactive interneuron numbers and calbindin D28K immunoreactivity in dentate granule cells remained unchanged although calbindin D28K staining was lost in damaged CA1 neurons. Neuronal injury in these areas was also accompanied by reactive gliosis and microglial proliferation, as well as the production of basic fibroblast growth factor and insulin-like growth factor-1 by astrocytes. Although hippocampal damage appeared to be more severe after SE induced in the presence of 8-CPT, this may be due to the increased severity of SE generated in this model.
 ...
PMID:Neuronal injury following electrically induced status epilepticus with and without adenosine receptor antagonism. 764 19

Adenosine is an endogenous neuromodulator that suppresses excitatory neurotransmission. We postulated that adenosine-mediated mechanisms resist status epilepticus (SE) entry and limit SE severity. In the first experiment rats were given an adenosine agonist (2-chloroadenosine), an adenosine antagonist (aminophylline), or saline vehicle, prior to SE induction with pulsed-train current delivered to amygdala in successive 5-min current-on sessions. Saline-treated animals entered limbic SE, with predominantly exploratory behavior, after 6.0 +/- 0.9 current-on sessions. Aminophylline increased major convulsive activity during stimulation and resulted in entry into convulsive SE after only 2.1 +/- 0.1 sessions. 2-Chloroadenosine, in contrast, suppressed major convulsive activity during stimulation, and blocked (in 3/7) or delayed (4/7) SE entry, with successes requiring 12.8 +/- 0.9 stimulation sessions. In a second experiment, animals already in exploratory SE were administered a single injection of saline vehicle, aminophylline, or 2-chloroadenosine. Aminophylline converted exploratory SE into lethally severe convulsive SE. 2-Chloroadenosine suppressed SE behaviorally and electrographically, and protected recipients from the seizure-associated cerebral damage seen in saline-administered SE controls. These results support the hypothesis that endogenous adenosine mechanisms resist SE entry, modulate the severity of ongoing SE, and limit the anatomic spread of seizure activity.
 ...
PMID:Effect of an adenosine antagonist and an adenosine agonist on status entry and severity in a model of limbic status epilepticus. 808 55

Adenosine has been proposed as an endogenous anticonvulsant which can play an important role in seizure initiation, propagation and arrest. Besides the release of adenosine per se, the ectonucleotidase pathway is an important metabolic source of extracellular adenosine. Here we evaluated ATP diphosphohydrolase and 5'-nucleotidase activities in synaptosomes from hippocampus and cerebral cortex at different periods after induction of status epilepticus (SE) by intraperitoneal administration of pilocarpine or kainate. Ectonucleotidase activities from synaptosomes of hippocampus and cerebral cortex of rats were significantly increased at 48-52 h, 7-9 days and 45-50 days after induction of SE by pilocarpine. In relation to kainate model, both hippocampal enzymes were enhanced at 7-9 days and 45-50 days, but only 5'-nucleotidase remained elevated at 100-110 days after the treatment. In cerebral cortex, an increase in ATP diphosphohydrolase was observed at 48-52 h, 7-9 days and 45-50 days after induction of SE by kainate. However, 5'-nucleotidase activity only presented significant changes at 45-50 and 100-110 days. Our results suggest that SE can induce late and prolonged changes in ectonucleotidases activities. The regulation of the ectonucleotidase pathway may play a modulatory role during the evolution of behavioral and pathophysiological changes related to temporal lobe epilepsy.
 ...
PMID:Changes in synaptosomal ectonucleotidase activities in two rat models of temporal lobe epilepsy. 1077 Dec 49

Adenosine is an endogenous modulator that has an inhibitory effect on neuronal activity. The aim of this work was to investigate the role of aminophylline, an adenosine receptor antagonist, on the long-term effects of status epilepticus (SE) in the developing brain. Four groups of rats at the postnatal age of 12 days were intraperitoneally administered with saline, aminophylline (50 mg/kg), lithium-pilocarpine (Li-PC) (3 mEq/kg-60 mg/kg), and Li-PC plus aminophylline, respectively. The four groups were tested for spatial memory using the Morris water maze task at P80 and motor performance by the Rotarod test at P100. The brains were then analyzed with cresyl violet stain for histological lesions and evaluated for mossy fiber sprouting with the Timm stain. At the acute stage, all rats subjected to Li-PC developed SE and no seizures were elicited in the saline-treated or aminophylline-treated rats. The seizure duration was longer in the Li-PC plus aminophylline group (346.9+/-32.7 min) as compared with that in the Li-PC group (265.2+/-9.8 min). The difference of mortality was not significant. Rats without seizures exhibited no motor imbalance, spatial deficits, or morphological changes. The rats with Li-PC-induced SE demonstrated spatial memory deficits without motor incoordination or morphological changes. However, the rats subjected to Li-PC plus aminophylline exhibited motor impairment and morphological changes, including neuronal cell loss in CA1 area and increased mossy fiber sprouting in CA3 area. In addition, the rats of Li-PC plus aminophylline had greater spatial memory deficits than that seen in rats with Li-PC. We concluded that an adenosine receptor antagonist, such as aminophylline, had synergistic effects on the SE-induced long-term deficit of cognition and motor performance in the developing brain. The present study may provide experimental evidence and lead to novel therapeutic interventions.
 ...
PMID:Aminophylline exacerbates status epilepticus-induced neuronal damages in immature rats: a morphological, motor and behavioral study. 1207 43

Adenosine has powerful inhibitory effects in the central nervous system. In this study, we aim to understand how adenosine controls the progression of seizure-like events (SLEs) in a seizure-prone region of the brain, the entorhinal cortex. We chose to use a low Mg(2+) model of epilepsy in an in vitro slice preparation where, in the entorhinal cortex, SLEs progress into a type of epileptiform activity called late recurrent discharges (LRDs) that bear resemblance to status epilepticus. Adenosine, acting via its A1 receptor, exerted powerful inhibitory effects to prevent the spontaneous progression to LRDs while the potent A1 receptor antagonist, DPCPX, accelerated the progression in a concentration dependent manner. The spontaneous progression from SLEs to LRDs was associated with a decline in total cellular ATP levels and studies with metabolic inhibitors indicated a key role for the production of endogenous adenosine from ATP. We therefore hypothesise that when ATP becomes rate limiting, extracellular adenosine levels fall, the normal inhibitory brake is removed and the progression from SLEs to LRDs or status epilepticus-like activity can ensue. Moreover, under these conditions, inhibition of the adenine nucleotide salvage pathways reversed the status epilepticus-like activity. Our findings suggest a powerful role for adenosine for the control of the progression to status epilepticus-like activity in an epilepsy model that is refractory to most anti-epileptic drugs. On this basis, manipulation of adenine nucleotide metabolism may represent a potential therapeutic approach for the treatment of status epilepticus.
 ...
PMID:Adenosine acting via A1 receptors, controls the transition to status epilepticus-like behaviour in an in vitro model of epilepsy. 1527 32

Adenosine, acting at A1 receptors, exhibits anticonvulsant effects in experimental epilepsy--and inhibits progression to status epilepticus (SE). Seizures after traumatic brain injury (TBI) may contribute to pathophysiology. Thus, we hypothesized that endogenous adenosine, acting via A1 receptors, mediates antiepileptic benefit after experimental TBI. We subjected A1-receptor knockout (ko) mice, heterozygotes, and wild-type (wt) littermates (n=115) to controlled cortical impact (CCI). We used four outcome protocols in male mice: (1) observation for seizures, SE, and mortality in the initial 2 h, (2) assessment of seizure score (electroencephalogram (EEG)) in the initial 2 h, (3) assessment of mortality at 24 h across injury levels, and (4) serial assessment of arterial blood pressure, heart rate, blood gases, and hematocrit. Lastly, to assess the influence of gender on this observation, we observed female mice for seizures, SE, and mortality in the initial 2 h. Seizure activity was noted in 83% of male ko mice in the initial 2 h, but was seen in no heterozygotes and only 33% of wt (P<0.05). Seizures in wt were brief (1 to 2 secs). In contrast, SE involving lethal sustained (>1 h) tonic clonic activity was uniquely seen in ko mice after CCI (50% incidence in males), (P<0.05). Seizure score was twofold higher in ko mice after CCI versus either heterozygote or wt (P<0.05). An injury-intensity dose-response for 24 h mortality was seen in ko mice (P<0.05). Physiologic parameters were similar between genotypes. Seizures were seen in 100% of female ko mice after CCI versus 14% of heterozygotes and 25% wt (P<0.05) and SE was restricted to the ko mice (83% incidence). Our data suggest a critical endogenous anticonvulsant action of adenosine at A1 receptors early after experimental TBI.
 ...
PMID:Adenosine A1 receptor knockout mice develop lethal status epilepticus after experimental traumatic brain injury. 1612 Nov 25

Adenosine, a well-known neuromodulator, can act as an endogenous anticonvulsant via the activation of adenosine A1 receptors. This adenine nucleoside can be produced in the synaptic cleft by the ectonucleotidase cascade, which includes the nucleoside triphosphate diphosphohydrolase (NTPDase) family and ecto-5'-nucleotidase. It has been previously reported that ectonucleotidase activities are increased in female adult rats submitted to the pilocarpine model of epilepsy. Several studies have suggested that the immature brain is less vulnerable to morphologic and physiologic alterations after status epilepticus (SE). Here, we evaluate the ectonucleotidase activities of synaptosomes from the hippocampus and cerebral cortex of male and female rats at different ages (7-9, 14-16 and 27-30-day old) submitted to the pilocarpine model of epilepsy. Our results show that ATP and ADP hydrolysis in the hippocampus and cerebral cortex were not altered by the pilocarpine treatment in female and male rats at 7-9, 14-16 and 27-30 days. There were no changes in AMP hydrolysis in female and male rats submitted to the model at different ages, but a significant increase in AMP hydrolysis (71%) was observed in synaptosomes from the cerebral cortex of male rats at 27-30 days. Pilocarpine-treated male rats (60-70-day old) presented an enhancement in ectonucleotidase activities in the synaptosomes of the cerebral cortex (33, 40 and 64% for ATP, ADP and AMP hydrolysis, respectively) and hippocampus (55, 98 and 101% for ATP, ADP and AMP hydrolysis, respectively). These findings highlight differences between the purinergic system of young and adult rats submitted to the pilocarpine model of epilepsy.
 ...
PMID:Ontogenetic profile of ectonucleotidase activities from brain synaptosomes of pilocarpine-treated rats. 1627 51

Adenosine is an endogenous neuromodulator with anticonvulsant and neuroprotective properties presumably mediated by activation of adenosine A1 receptors (A1Rs). To study the involvement of A1Rs in neuroprotection during epileptogenesis, we induced status epilepticus by a unilateral intrahippocampal kainic acid (KA) injection (1 nmol) in wild-type C57BL/6 and homozygous adenosine A1R knock out (A1R-KO) mice of the same genetic background. Whereas the KA injection caused non-convulsive status epilepticus in wild-type mice, in A1R-KO mice KA induced status epilepticus with severe convulsions and subsequent death of the animals within 5 days. 24 h after KA injection, brains from wild-type C57BL/6 mice were characterized by slight neuronal cell loss confined to the immediate location of the KA injection. In contrast, KA-injected A1R-KO mice displayed massive neuronal cell loss in the ipsilateral hippocampus, and, importantly, the contralateral hippocampus was also affected with significant cell loss in the hilus and in the CA1 region of the pyramidal cell layer. We conclude that activation of A1 receptors by ambient adenosine is crucial in keeping epileptic foci localized. These results open up a new dimension of the A1 receptor's role in controlling excitotoxic cell death and further demonstrate its importance in preventing the progression of status epilepticus to lethal consequences.
 ...
PMID:Adenosine A1 receptors are crucial in keeping an epileptic focus localized. 1675 Jan 95

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.
 ...
PMID:Effects of progesterone on total brain tissue adenosine deaminase activity in experimental epilepsy. 1912 74

The homeostatic bioenergetic network regulator adenosine is an endogenous anticonvulsant of the brain that plays critical roles in seizure termination and postictal refractoriness. Adenosine homeostasis in the adult brain is largely under the control of metabolic clearance through adenosine kinase (ADK), expressed predominantly in astrocytes. The role of adenosine in status epilepticus (SE) appears to be a double-edged sword. We demonstrated that the severity of an SE clearly depends on the expression levels of ADK. A genetic knockdown of ADK prevented SE in a mouse model, whereas transgenic overexpression of the enzyme aggravated the SE. Therefore, ADK inhibition or adenosine augmentation might be a therapeutic strategy to terminate or attenuate an SE. On the other hand, SE triggers a surge of endogenous adenosine, which may initiate secondary events leading to epileptogenesis. Two new findings point into this direction: (1) Elevated adenosine triggers changes in the epigenome; and (2) SE triggers transient changes in ADK expression, which have been linked to neurogenesis. Although the ADK/adenosine system is an attractive target for the attenuation of an SE, the same system may also trigger downstream events related to epileptogenesis.
...
PMID:Role of adenosine in status epilepticus: a potential new target? 2400 Oct 64


1 2 Next >>