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)

Protein kinase C (PKC) comprises a family of kinases consisting of nine subspecies that are differentially distributed in the central nervous system. This implies distinct functions. Its involvement is suggested in cellular and molecular mechanisms by which the hippocampus exerts influence on information processing. In this study, it was questioned whether abnormal activity in the neuronal substrate, particularly the hippocampal formation, induced by amygdala kindling indeed impairs spatial memory performance and correlated alpha, beta I/II, and gamma PKC subspecies expression. Rats were trained in a spatial discrimination task (SDT) and simultaneously kindled in the amygdala to induce abnormal, epileptiform activity. Control rats were only trained in the holeboard, a "free choice" maze, in which working (WM) and reference memory (RM) were simultaneously examined. Halfway through and at the end of the experiments the influence of kindling and SDT training on the immunoreactivity for PKC subspecies alpha, beta I/II, and gamma was evaluated in the hippocampal formation. Kindling resulted in a gradual increase in afterdischarge duration and motor seizure (MS) severity. Repeated SDT training ultimately resulted in an asymptotic level of WM and RM performance. As soon as generalized MSs developed, kindled rats failed to improve RM, whereas WM was not influenced. Compared to untrained rats, in trained controls PKC gamma but not PKC alpha beta I/II immunoreactivity was elevated in CA1 pyramidal and dentate gyrus granular cells. Generalized but not partial MSs abolished these alterations in PKC gamma immunoreactivity. The present data indicate that repeated training in a SDT affects the expression of PKC subspecies gamma but not of alpha or beta in the rat hippocampus. Generalized epileptiform activity impair both acquisition of new spatial RM information and PKC gamma expression. It is argued that PKC gamma plays a role in cellular mechanisms through which pathological brain activity impairs certain aspects of spatial memory.
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PMID:Amygdala kindling-induced seizures selectively impair spatial memory. 1. Behavioral characteristics and effects on hippocampal neuronal protein kinase C isoforms. 130 96

We describe a syndrome of rhythmic coma in children that consists of an invariant, nonreactive, diffuse cortical activity of a specific frequency, such as alpha, beta, spindle, or theta, recorded from a comatose child. We report 11 cases of children who were found to be in rhythmic coma during their acute illnesses. Their ages ranged from 2 to 15 years, and their diagnoses included encephalitis, head trauma, seizures, near drowning, brain tumors, stroke, and metabolic derangements. The specific frequency of the electroencephalographic pattern, ie, alpha, beta, spindle, or theta, did not influence the outcome. The clinical outcome appeared to depend on the primary disease process rather than the electroencephalographic finding. The prognosis of alpha-frequency rhythmic coma as well as of rhythmic coma in general was better in children than in adults. The pathophysiology in children may be similar, ie, the interruption of reticulothalamocortical pathways by metabolic or structural abnormalities, but the expression of this deafferentation may be more varied in the developing brain. Thus, we propose the term rhythmic coma as a unified concept for alpha, beta, spindle, and theta coma in children.
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PMID:Rhythmic coma in children. 239 39

The effects of three isomers (alpha, beta, gamma) of hexachlorocyclohexane on the acquisition and expression of kindled amygdaloid seizures were compared. Treatment with corn oil (vehicle) was compared with daily 5 mg/kg doses of the isomers for 15 days during kindling procedures. The results confirmed the proconvulsant action previously described for the gamma-HCH isomer (lindane). Alpha-HCH did not produce significant effects. Rats treated with beta-HCH exhibited delayed rates of kindling acquisition and less severe seizures. Exposure to beta-HCH (5, 10 and 20 mg/kg) daily produced a dose-dependent decrease in the rate of kindling acquisition, seizure severity and afterdischarge duration. The differences were still manifest during an additional 20 kindling trials after beta-HCH administration had stopped. It is concluded that significant differences exist among the isomers of HCH with respect to their effects on the mammalian central nervous system and their effect in the kindling model of epilepsy. The availability of stereoisomers possessing different actions on kindling should make these compounds useful for discriminating between non-specific changes induced in membranes or at binding sites and specific changes correlated with proconvulsant or anticonvulsant effects in the kindling model.
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PMID:Effects of hexachlorocyclohexane isomers on the acquisition of kindled seizures. 243 33

Protein kinase C (PKC) activity, Western blot analysis of PKC alpha, beta, gamma, epsilon and zeta with isozyme-specific antibodies, endogenous substrate protein phosphorylation, and Western blot analysis of neuromodulin, were studied in mouse brain after repeated electroconvulsive shock. The PKC isozymes and endogenous substrates in the crude cytosolic and membrane fractions were partially purified on DE-52 columns eluted with buffer containing 100 or 200 mM KCl. The kinase activity assayed by phosphorylation of exogenous histone was increased in the 200 mM KCl eluates of both the cytosol and membrane fractions from electroshocked mice. Further analysis by immunoblotting demonstrated that this increased activity was due to an increase in the PKC gamma isozyme. The level of the novel type isozymes, epsilon and zeta, was not altered in electroshocked mice. An in vitro phosphorylation study showed that the endogenous substrate, 17 kDa neurogranin, was mostly eluted by 100 mM KCl. In contrast, the 43 kDa neuromodulin only appeared in the 200 mM KCl eluate, according to autoradiography, SDS-PAGE and Western blot analysis; its level was found to be increased in the membrane fraction of electroshocked mice, as demonstrated by in vitro phosphorylation studies. Therefore, an increase in both PKC gamma and neuromodulin contributed to the increased phosphorylation of neuromodulin during electroshock seizure.
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PMID:Alterations of protein kinase C isozyme and substrate proteins in mouse brain after electroconvulsive seizures. 792 28

A1 adenosine receptors in the rat prepiriform cortex play an important role in the inhibition of bicuculline methiodide-induced convulsions. In the present study we evaluated manipulation of endogenous adenosine in this brain area as a strategy to effect seizure suppression. All compounds evaluated were unilaterally microinjected into the rat prepiriform cortex. Administration of exogenous adenosine afforded a dose-dependent protection (ED50 = 48.1 +/- 8.4 nmol) against bicuculline methiodide-induced seizures, and these anticonvulsant effects were significantly potentiated by treatment with an adenosine kinase inhibitor, 5'-amino-5'-deoxyadenosine; by the adenosine transport blockers, dilazep or nitrobenzylthioinosine 5'-monophosphate; and by an adenosine deaminase inhibitor, 2'-deoxycoformycin. When administered alone, 5'-amino-5'-deoxyadenosine, 5'-iodotubercidin and dilazep were found to be highly efficacious as anticonvulsants with respective ED50 values of 2.6 +/- 0.8, 4.0 +/- 2.7 and 5.6 +/- 1.5 nmol. In contrast, 2'-deoxycoformycin was both less potent and less efficacious. These results suggest that accumulation of endogenous adenosine may contribute to seizure suppression, and that adenosine kinase and adenosine transport may play a pivotal role in the regulation of extracellular levels of adenosine in the central nervous system. The adenosine antagonist, 8-(p-sulfophenyl)theophylline, increased markedly the severity of bicuculline methiodide-induced seizures. Moreover, reduction of extracellular adenosine formation by a focal injection of an ecto-5'-nucleotidase inhibitor, alpha, beta-methyleneadenosine diphosphate, produced generalized seizures (ED50 = 37.3 +/- 22.7 nmol). Together the proconvulsant effect of an adenosine receptor antagonist and the convulsant action of an ecto-5'-nucleotidase inhibitor further support the role of endogenous adenosine as a tonically active antiepileptogenic substance in the rat prepiriform cortex.
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PMID:Manipulation of endogenous adenosine in the rat prepiriform cortex modulates seizure susceptibility. 845 Apr 75

Tramadol, an analgesic with mean potency one tenth that of morphine is used regularly for the treatment of chronic and postoperative pain. Previous reports have indicated that tramadol may induce seizure activity when given together with a selective serotonin reuptake inhibitor (SSRI). Therefore, its major mode of action may be questioned which purportedly is due to binding with the opioid receptor and partly due to the inhibition of monoamine reuptake. We therefore set out to study its potential in inducing seizure activity and to quantify its effect on EEG-power spectra and on the central modulation of sensory afferents in awake and trained dogs (n=7). In order to demonstrate if opioid receptors mediated these effects, incremental doses of tramadol were given which was followed by naloxone for possible reversal. After a wash-out period the same animals were exposed to graded doses of alfentanil, a pure mu-receptor agonist. Again this was followed by the opioid antagonist naloxone for reversal.The electroencephalogram (EEG) and the event-related evoked potentials (SEP) were used to demonstrate possible excitatory effects. In order to derive the SEP the front paw was stimulated electrically (Digi Stim II trade mark ) while the evoked potentials were picked up contralaterally from the somatosensory cortex using stick-on electrodes. 256 sweeps were averaged (Lifescan) and the peak-to-peak amplitude was measured to demonstrate CNS excitation compared to control (%). Additionally, the raw electroencephalogram was viewed for epileptogenic changes and its power computed into the various power bands alpha, beta, delta und theta using FFT over a time epoch of 60 s. Following control, graded doses of either tramadol (2-5-10 mg/kg i.v.) or alfentanil (10-30-60 microg/kg i.v.) were given every 15 min while the EEG and the SEP were recorded. Thereafter naloxone (20 microg/kg i.v.) was injected for reversal. Tramadol did not suppress the amplitude of the SEP at any dose. High doses (>5 mg/kg i.v.) resulted in an increase (+100%) of the amplitude of the evoked potential. This was accompanied by short-term muscle fibrillations, and a short-term spike-and-wave activity in the EEG followed by a long-lasting theta-dominance. These effects could not be reversed by naloxone. In contrast to tramadol, alfentanil induced a dose-related depression of amplitude in the SEP with a maximum of 82% suggesting a depressive effect of modulation of afferents in the sensory cortex. This effect was fully naloxone reversible and was followed by a rebound in amplitude of the SEP together with an increase in fast beta-waves in the EEG. Tramadol very little mediates its central action via the mu-opioid receptor as the present effects were not naloxone reversible. Consistent with the results is the very low affinity of tramadol to the opioid receptor which is several thousand times less than that of morphine. Most likely, inhibition of central norepinephrine and serotonin reuptake as well as the reduction in 5-HT-turnover may contribute to the effects of tramadol. Due to the monoamine reuptake inhibition an increase in transmission may result, triggering off excitatory phenomena with spike-and-wave activity in the CNS. Such excitatory effects, however, may only be seen when tramadol is used in doses exceeding the therapeutic range.
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PMID:[The opioid tramadol demonstrates excitatory properties of non-opioid character--a preclinical study using alfentanil as a comparison]. 1279 88

Myristoylated alanine-rich C kinase substrate (MARCKS) is a widely distributed protein kinase C (PKC) substrate and has been implicated in actin cytoskeletal rearrangement in response to extracellular stimuli. Although MARCKS was extensively examined in various cell culture systems, the physiological function of MARCKS in the central nervous system has not been clearly understood. We investigated alterations of cellular distribution and phosphorylation of MARCKS in the hippocampus following kainic acid (KA)-induced seizures. KA (25 mg/kg, i.p.) was administered to eight to nine week-old C57BL/6 mice. Behavioral seizure activity was observed for 2 h after the onset of seizures and was terminated with diazepam (8 mg/kg, i.p.). The animals were sacrificed and analyzed at various points in time after the initiation of seizure activity. Using double-labeling immunofluorescence analysis, we demonstrated that the expression and phosphorylation of MARCKS was dramatically upregulated specifically in microglial cells after KA-induced seizures, but not in other types of glial cells. PKC alpha, beta I, beta II and delta, from various PKC isoforms examined, also were markedly upregulated, specifically in microglial cells. Moreover, immunoreactivities of phosphorylated MARCKS were co-localized in the activated microglia with those of the above isoforms of PKC. Taken together, our in vivo data suggest that MARCKS is closely linked to microglial activation processes, which are important in pathological conditions, such as neuroinflammation and neurodegeneration.
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PMID:Cell type-specific upregulation of myristoylated alanine-rich C kinase substrate and protein kinase C-alpha, -beta I, -beta II, and -delta in microglia following kainic acid-induced seizures. 1681 90

A wavelet-chaos methodology is presented for analysis of EEGs and delta, theta, alpha, beta, and gamma subbands of EEGs for detection of seizure and epilepsy. The nonlinear dynamics of the original EEGs are quantified in the form of the correlation dimension (CD, representing system complexity) and the largest Lyapunov exponent (LLE, representing system chaoticity). The new wavelet-based methodology isolates the changes in CD and LLE in specific subbands of the EEG. The methodology is applied to three different groups of EEG signals: 1) healthy subjects; 2) epileptic subjects during a seizure-free interval (interictal EEG); 3) epileptic subjects during a seizure (ictal EEG). The effectiveness of CD and LLE in differentiating between the three groups is investigated based on statistical significance of the differences. It is observed that while there may not be significant differences in the values of the parameters obtained from the original EEG, differences may be identified when the parameters are employed in conjunction with specific EEG subbands. Moreover, it is concluded that for the higher frequency beta and gamma subbands, the CD differentiates between the three groups, whereas for the lower frequency alpha subband, the LLE differentiates between the three groups.
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PMID:A wavelet-chaos methodology for analysis of EEGs and EEG subbands to detect seizure and epilepsy. 1727 77

Epileptic seizures can cause a variety of temporary changes in perception and behavior. In the human EEG they are reflected by multiple ictal patterns, where epileptic seizures typically become apparent as characteristic, usually rhythmic signals, often coinciding with or even preceding the earliest observable changes in behavior. Their detection at the earliest observable onset of ictal patterns in the EEG can, thus, be used to start more-detailed diagnostic procedures during seizures and to differentiate epileptic seizures from other conditions with seizure-like symptoms. Recently, warning and intervention systems triggered by the detection of ictal EEG patterns have attracted increasing interest. Since the workload involved in the detection of seizures by human experts is quite formidable, several attempts have been made to develop automatic seizure detection systems. So far, however, none of these found widespread application. Here, we present a novel procedure for generic, online, and real-time automatic detection of multimorphologic ictal-patterns in the human long-term EEG and its validation in continuous, routine clinical EEG recordings from 57 patients with a duration of approximately 43 hours and additional 1,360 hours of seizure-free EEG data for the estimation of the false alarm rates. We analyzed 91 seizures (37 focal, 54 secondarily generalized) representing the six most common ictal morphologies (alpha, beta, theta, and delta- rhythmic activity, amplitude depression, and polyspikes). We found that taking the seizure morphology into account plays a crucial role in increasing the detection performance of the system. Moreover, besides enabling a reliable (mean false alarm rate<0.5/h, for specific ictal morphologies<0.25/h), early and accurate detection (average correct detection rate>96%) within the first few seconds of ictal patterns in the EEG, this procedure facilitates the automatic categorization of the prevalent seizure morphologies without the necessity to adapt the proposed system to specific patients.
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PMID:Detecting epileptic seizures in long-term human EEG: a new approach to automatic online and real-time detection and classification of polymorphic seizure patterns. 1846 27

Heterotrimeric G-protein signaling, involving alpha, beta and gamma subunits, plays a number of roles in differentiation and development. Individual gamma subunits interact with a beta subunit and as a heterodimer, is responsible for modulating many G protein-mediated cellular responses. The 12 gamma subunits in mammals have highly variable distribution and expression patterns in adult tissues. gamma3 is abundantly and widely expressed in the brain and when its expression is knocked-out, the mice show increased susceptibility to seizures, reduced body weights and decreased adiposity compared to the wild-type littermates (Schwindinger et al., 2004). Recent evidence has shown the Gng3 gene being strongly induced in activated CD4+ T-cells (Dubeykovskiy et al., 2006) and its involvement in the developing mammalian enteric nervous system (Heanue and Pachnis, 2006). Given this diversity in expression and interest in finding models of human disease, and to extend our previous investigation with zebrafish gamma3 (Kelly et al., 2001), we undertook an analysis to report the temporal and spatial expression patterns of gamma3 mRNA during mouse embryogenesis. Analysis reveals that gamma3 transcripts were first expressed in mid-late embryonic stages. Specifically, signals were predominant in the CNS and in neural crest cell derivatives including but not limited to the trigeminal and dorsal root (spinal) ganglia, and in cells of the adrenal medulla. These data indicate that G protein coupled signaling involving gamma3 participates in a number of physiological roles, not only in the CNS, but also in numerous cells derived from the neural crest.
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PMID:Mouse G-protein gamma3 expression in the developing CNS and neural crest cell derivatives. 1895 48


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