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

The present study was undertaken to evaluate the antiseizure activity spectrum of insulin against various behavioral seizure models in rats. Insulin was injected intraperitoneally (i.p.) at a test dose of 1 U/kg. Dextrose (3 g/kg) was administered simultaneously with insulin to counteract its hypoglycemic effect and induce a normoglycemic state. Insulin was found to significantly decrease the incidence, intensity and mortality rate and prolong the latency of generalized tonic-clonic convulsions induced by pentylenetetrazole (60 mg/kg i.p.) and significantly decrease the intensity and mortality rate and prolong the latency of generalized tonic-clonic convulsions induced by penicillin (2000 U/intracerebrocortical). Insulin was not only found to prolong the latency of all the seizure components but was found to reduce the incidence of focal myoclonic twitches and generalized tonic-clonic convulsions induced by kainic acid (12 mg/kg i.p.) as well. Insulin was shown to be ineffective to suppress ouabain (5 micrograms/intracerebroventricular) induced seizures. These findings indicate that insulin possesses a broad spectrum of antiseizure activity in rats. Interaction with brain Na(+)-K(+)-ATPase has been discussed as a possible mechanism of action.
 ...
PMID:Antiseizure activity of insulin: insulin inhibits pentylenetetrazole, penicillin and kainic acid-induced seizures in rats. 895 15

1. Phenytoin has been used with much clinical success against all types of epileptiform seizures, except petit mal epilepsy, for over 50 years. Its mechanism of action, however, is still open to interpretation. 2. Several potential targets for phenytoin action have been identified within the central nervous system. These include the Na-K-ATPase, the GABAA receptor complex, ionotropic glutamate receptors, calcium channels and sigma binding sites. 3. To date, though, the best evidence hinges on the inhibition of voltage-sensitive Na+ channels in the plasma membrane of neurons undergoing seizure activity. Quieter nerve cells are far less affected. Moreover, the fact that phenytoin also has important cardiac antiarrhythymic effects and can inhibit Na+ influx into cardiac cells supports the idea that the primary target of phenytoin is, indeed, the Na+ channel.
 ...
PMID:Basis of the antiseizure action of phenytoin. 898 Oct 53

Low Mg2+-induced epileptiform activity in the entorhinal cortex is characterized by an initial expression of seizure-like events followed by late recurrent discharges. Both these forms of activity as well as the transition between them were blocked by serotonin. In contrast, serotonin had little effect upon the epileptiform activity in areas CA3 and CA1 of the hippocampus. Both forms of epileptiform activity in the entorhinal cortex are sensitive to N-methyl-D-aspartate receptor antagonists and it is shown here that serotonin blocked both types of epileptiform activity through an effective concentration-dependent reduction of N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potentials in deep layer entorhinal cortex cells. Serotonin also prolonged or even prevented the transition between the two types of epileptiform activity and we suggest that this may be through activation of the Na+/K+-ATPase. The resistance of epileptiform activity in CA1 and CA3 to serotonin was most likely related to the inability of serotonin to reduce Schaffer collateral-evoked excitatory postsynaptic potentials. Given the strong serotonergic inputs to both the hippocampus and entorhinal cortex, the differential sensitivity of the two regions to serotonin suggests functional differences. In addition since the late recurrent discharges in the entorhinal cortex are resistant to all clinically used anticonvulsants, serotonin may open new avenues for the development of novel anticonvulsant compounds.
 ...
PMID:Serotonin blocks different patterns of low Mg2+-induced epileptiform activity in rat entorhinal cortex, but not hippocampus. 901 29

The aim of this study was to investigate the brain cortex Na(+)-K+ ATPase activity in rats made diabetic by streptozotocin and epileptic by pentylenetetrazol. Streptozotocin diabetic rats showed a significant decrease in brain cortex Na(+)-K+ ATPase activity whereas the pentylenetetrazol treatment caused no significant change in enzyme activity. On the other hand, no brain cortex Na(+)-K+ ATPase activity could be detected in all the diabetic rats treated with pentylenetetrazol. Our results concluded that reduced Na(+)-K+ ATPase activity in streptozotocin diabetic rats may contribute to the pathogenesis of metabolic complications of the central nervous system, and that the undetectable enzyme activity in diabetic convulsing rats may result from considerable damage or necrosis of brain tissue during pentylenetetrazol seizures.
 ...
PMID:Brain cortex Na(+)-K+ ATPase activities in streptozotocin-diabetic and pentylenetetrazol-epileptic rats. 936 17

A single cerebroventricular injection of ethacrynic acid (EA), a Cl(-)-ATPase inhibitor, induces generalized tonic-clonic convulsions in mice. To clarify whether such convulsive stimulus triggers a long-lasting rearrangement of the neural circuitry culminating in seizure susceptibility, we examined molecular, cellular and behavioral changes following the EA-induced seizure. The expression of immediate early gene c-fos mRNA as an index for cellular activation increased biphasically, with an early transient increase at 60 min and a late prolonged increase on the 10th to 14th day post-EA administration, most remarkably in the hippocampus and pyriform cortex. On the 14th day post-EA seizure, subconvulsive dose of kainic acid (5-17.5 mg/kg) caused severe (stage 5) seizure in 77% of the mice, with 70% mortality. In addition, the expression of nerve growth factor (NGF) also showed biphasic increases with close spatiotemporal correlation with c-fos expression. Moreover, the number of cell somata and the density of axon fibers of parvalbumin (PARV)-positive cells, a subpopulation of GABAergic interneurons, decreased in area dentata, CA1 and CA3 on the 7th and 14th day post-EA seizure. In area dentata and CA1, the density of glutamic acid decarboxylase (GAD)-positive cells also decreased on the 14th day. Thus, the transient EA-induced seizures appear to develop seizure susceptibility by causing damage of a subpopulation of inhibitory interneurons along with increases in the expression of c-fos and NGF in limbic structures.
 ...
PMID:Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure. 1040 97

Genetic linkage studies in rodents and humans have identified specific chromosomal regions harboring seizure susceptibility genes. We have identified a novel polymorphism in the human alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase (NaK-pump), a candidate gene for human temporal lobe epilepsy (TLE) based on its chromosomal location and function in ion homeostasis. The polymorphism consists of a four base pair insertion 12 base pairs upstream of the start of exon 2. We performed an association study between this polymorphism and TLE. Our study did not find a significant difference in the frequency of this polymorphism between TLE patients and controls, indicating that this variation is not a major susceptibility factor. However, since the number of patients studied so far is small and the functional consequence of the polymorphism is unknown, the variation may yet be found to play a minor role in increased risk for seizure susceptibility. In contrast to the findings in TLE patients and controls, we did find a significant difference in the frequency of the variation between African Americans and persons of European descent. This finding demonstrates the potential effect of population stratification on studies of this type and supports the growing use of parental and familial samples for controls in association studies. Further study of this polymorphism is warranted as it may be involved in other disease processes for which there are known ethnic-specific susceptibilities. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:79-83, 2000.
 ...
PMID:Lack of association between temporal lobe epilepsy and a novel polymorphism in the alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase. 1068 57

Spontaneous recurrent seizures (SRS) are the major clinical characteristic of epilepsy. In this study, using a SRS-behavior test combined with linker capture subtraction (LCS) to identify genes altered in their expression in response to a single kainic acid (KA)-induced SRS at 3 weeks in the rat hippocampal formation. Dot blot analysis of the differentially expressed cDNA fragments with LCS showed the down-regulation of one cDNA related to SRS, which was designated epilepsy-related gene 1 (ERG1). Northern blot analysis showed that ERG1 mRNA was reduced by KA administration with and without SRS, but more so with SRS. This differential expression had also been confirmed by in situ hybridization, which showed that ERG1 mRNA was down-regulated in the dorsal dentate granule cells (dDGCs) of the hippocampal formation, but remarkable up-regulated in the amygdalohippocampal area (AHi), posteromedial cortical amygdaloid nucleus (PMCo) and perirhinal cortex (PRh). The complete cDNA of ERG1 was cloned, sequenced (AF142097). It encodes a Rattus homologue of N-ethylmaleimide-sensitive fusion protein (NSF), which is an ATPase that plays a key role in mediating docking and/or fusion of transport vesicles in the multi-step pathways of vesicular transport. Sequence analysis revealed that ERG1 has high sequence similarity with the cDNA of the Mus musculus suppressor of K(+) transport growth defect (SKD2), N-ethylmaleimide(NEM)-sensitive fusion protein of Chinese hamster and human NEM-sensitive factor (HSU03985).
 ...
PMID:A spontaneous recurrent seizure-related Rattus NSF gene identified by linker capture subtraction. 1122 66

The effect of nantenine, an aporphine alkaloid, on ATPase K+-dependent dephosphorylation was evaluated using p-nitrophenylphosphate (p-NPP) as substrate. Basal K+-p-NPPase activity was significantly increased with 3 x 10(-4) M, remained unchanged with 3 x 10(-6) M, 3 x 10(-5) M but was reduced with 7.5 x 10(-4) M and 1 x 10(-3) M nantenine, whereas Mg2+-p-NPPase activity was not modified. Kinetic studies showed that K+-p-NPPase inhibition by nantenine is competitive to KCl but non-competitive to substrate p-NPP, whereas K+-p-NPPase stimulation by nantenine is non-competitive to KCl but competitive to p-NPP. These data suggest that there may be two acceptor sites for nantenine in p-NPPase, one eliciting stimulation and the other inhibition of K+-dependent p-NPP hydrolysis. Considering the biphasic action of nantenine on seizures and the correlation between decreased ATPase activity and seizure development, alkaloid anticonvulsant effect observed at low nantenine doses is attributable to the stimulation of phosphatase activity whereas the convulsant effect at high alkaloid doses seems related to Na+, K+-ATPase inhibition.
 ...
PMID:In vitro dose dependent inverse effect of nantenine on synaptosomal membrane K+-p-NPPase activity. 1131 51

NSF is a cytosolic ATPase implicated in a variety of cellular functions including synaptic vesicle exocytosis. Here we report a lethal mutation in the Drosophila homolog of NSF (dNSF1). Lethality staging and rescue experiments with the wild type dNSF1 transgene show that NSF1 is critically required during early larval stages and during late pupariation. Lethality in larval stages is associated with defects in neurogenesis as evidenced by an overall reduction in synapse size and synapse branching. Moreover, escaper adults, though showing abnormal seizure-like paralytic behavior, are normal in terms of synaptic transmission as assayed by electroretinograms. Taken together, these data indicate a role for NSF in neural growth and branching in addition to its documented role in synaptic transmission.
 ...
PMID:Lethal comatose mutation in Drosophila reveals possible role for NSF in neurogenesis. 1138 12

Cerebral perfusion single photon emission computed tomography (SPECT) has been used to confirm the localization of the epileptic focus and the evaluation of seizure. Recently, diffusion-weighted MR imaging (DWI) has been recognized for evaluation of seizure activity. We describe a case of transient seizure activity demonstrated by Tc-99m HMPAO SPECT and DWI. This patient was a 61-year-old woman with a 10-month history of right middle cerebral artery (MCA) infarction who had a generalized seizure during MRI. DWI immediately after seizure showed transient hyperintensity in the right frontal gray matter and the white matter, and these apparent diffusion coefficients (ADC) were transiently decreased. This transient hyperintensity on DWI corresponded to transient hyperperfusion identifying the epileptic focus on interictal Tc-99m HMPAO SPECT. Transient sustained seizure activity might cause these changes on DWI and SPECT. It was considered that interictal Tc-99m HMPAO SPECT showed the delayed hyperperfusion caused by excitatory neuronal overaction and DWI showed cytotoxic edema seizure-induced by energy failure of the membrane-bound Na/K-ATPase pump.
 ...
PMID:Transient seizure activity demonstrated by Tc-99m HMPAO SPECT and diffusion-weighted MR imaging. 1154


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>