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)

We report a 23-year-old woman who slowly developed progressive tremulous myoclonus and rare convulsive seizures beginning at the age of 9 and 11 years, respectively. She also showed a mild degree of ataxia and cognitive dysfunction. Convulsive seizures were well suppressed by valproic acid since the age of 17 years, but tremulous myoclonus gradually progressed and became rather intractable in spite of treatment by clonazepam and piracetam. Her cognitive dysfunction was mild (total IQ score in Wechsler Adult Intelligence Scale Revised being 85 points). In addition, she had a fear of walking which disabled her in the daily life although she could actually walk without assistance. The brain MRI showed a mild cerebellar atrophy, and FDG-PET showed a mild hypometabolism in the cerebellar hemispheres. Somatosensory evoked potentials (SEPs) showed enlarged P25 and N33 amplitudes (giant SEPs). A Cystatin B gene analysis exhibited a homozygous expansion of the dodecamer repeat, and thus we made a diagnosis of Unverricht-Lundborg disease (ULD). We also did gene analysis and SEP study to her parents after written informed consents were obtained. They had heterozygous expansion of the dodecamer repeat. The mother also showed enlarged P25 and N33 amplitudes, whereas the father showed normal amplitudes. It is known that degree of clinical symptoms varies among patients with ULD diagnosed by gene analysis. Gene analysis was helpful for a diagnosis of ULD in this patient because the ataxia and cognitive dysfunction were much milder than those commonly seen in patients with ULD.
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PMID:[Unverricht-Lundborg disease manifesting tremulous myoclonus with rare convulsive seizures: a case report]. 1922 96

Frequently repetitive febrile seizures (FRFS) in immature brain could impair long-term memory without obvious pathological alteration. Although astrocyte activation has been implicated in many seizure models, it has never been examined in febrile seizure models. We investigated astrocyte activation states after FRFS in postnatal-10-day (P10) rats by western blot and immunohistochemical analysis of GFAP and S100beta, two protein markers for activated astrocytes, at three time points (P25, P35, P45). The levels of GFAP and S100beta increased significantly at all the time examined. Furthermore, we administered propentofylline, an astrocyte modulator, to verify the relationship between the activated astrocytes and memory injury. After propentofylline treatment for 10 consecutive days following P10 frequently repetitive FS, rats exhibited improved performances in Morris water maze at P36 and inhibitory avoidance task at P45, along with markedly suppressed overexpression of GFAP and S100beta. This research suggests that modulation of astrocyte activation might be a potential therapeutic target to improve memory outcomes after frequently repetitive febrile seizures.
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PMID:Astrocyte activation and memory impairment in the repetitive febrile seizures model. 1964 77

In immature rats, N-methyl-D-aspartate (NMDA) induces several seizure types: flexion seizures (FS; in rats younger than 3 weeks), clonic seizures (in animals older than 3 weeks), and clonic-tonic seizures (CTS; in rats of all ages). FS represent a model of human infantile spasms. Effects of vigabatrin and valproate against all types of NMDA-induced seizures were studied in rats at postnatal days 12 (P12) and 25 (P25). NMDA (60 or 300 mg/kg) was injected to animals pretreated with vigabatrin (300-1,200 mg/kg; 24 h before NMDA) or valproate (100-400 mg/kg; 15 min before NMDA). Vigabatrin suppressed FS in P12 rats, but was ineffective against CTS in both age groups. Valproate suppressed CTS in P12, but not in P25 rats. Clonic seizures were rare in NMDA-treated P25 rats, but valproate pretreatment increased their incidence significantly. Neither drug decreased NMDA-induced mortality, which occurred within approximately 15 min after NMDA administration and reached almost 100% in all groups.
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PMID:Vigabatrin but not valproate prevents development of age-specific flexion seizures induced by N-methyl-D-aspartate (NMDA) in immature rats. 1978 Jul 95

Recently, we have found that postnatal caffeine treatment results in a dose-dependent pro- or anticonvulsant effect during brain maturation which effect is transient and disappears in adult rats. The aim of the present study was to determine whether the developmental period of chronic caffeine treatment and the age of testing are crucial for the effects of acute caffeine on cortical epileptic afterdischarges (ADs) in rats. Rhythmic electrical stimulation of somatosensory cortex was applied to elicit EEG and motor phenomena in 18- and 25-day-old rats, respectively. Acute injection of caffeine (10 and 20mg/kg s.c.) decreased the threshold for stimulation-bound movements in both age groups while it increased the thresholds for spike-and-wave ADs and clonic seizures accompanying them at P25. Acute caffeine had a similar effect on thresholds for spike-and-wave ADs and clonic seizures in 25-day-old rats exposed to the methylxanthine at P7-P11 and P13-17, respectively. Though caffeine administration per se did not change the duration of ADs at P18 it produced either a pro- or anticonvulsant effect after postnatal treatment (P7-P11 and P13-P17, respectively). However, acute caffeine exerted a prolongation of ADs at P25 which effect was alleviated after both developmental periods of treatment. Taken together, acute caffeine effects on cortical epileptic ADs in rats can be modulated by the postnatal period of treatment and age of testing.
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PMID:Postnatal period of caffeine treatment and time of testing modulate the effect of acute caffeine on cortical epileptic afterdischarges in rats. 2069 37

More than half of neonatal stroke survivors have long-term sequelae, including seizures and neurological deficits. Although the immature brain has tremendous potential for recovery, mechanisms governing repair are essentially unexplored. We investigated whether magnetic resonance imaging (MRI) early or late after transient middle cerebral arterial occlusion in postnatal day (P) 10 rats can serve as an intermediate endpoint for long-term studies. Injured animals selected by diffusion-weighted MRI during middle cerebral arterial occlusion were scanned using T2-weighted MRI at P18 and P25 (injury volumes on MRI and histology were compared) or were subjected to contrast-enhanced MRI at P13 to characterize cerebral microcirculatory disturbances and blood-brain barrier leakage. Injury volume during middle cerebral artery occlusion did not predict histological outcome at 2 weeks. Major reductions in injury volume occurred by P18, with no further changes by P25 and correlated with histological injury. Cerebral perfusion was significantly reduced in the injured caudate but blood-brain barrier leakage was small. Therefore, conventional T2-weighted MRI performed during a subchronic injury phase predicts a long-term histological outcome after experimental neonatal focal stroke.
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PMID:Magnetic resonance imaging (MRI) as a translational tool for the study of neonatal stroke. 2167 Mar 90

Innate immunity mediated by microglia appears to play a crucial role in initiating and propagating seizure-induced inflammatory responses. To address the role of activated microglia in the pathogenesis of childhood epilepsy, we first examined the time course of microglia activation following kainic acid-induced status epilepticus (KA-SE) in Cx3cr1(GFP/+) transgenic mice whose microglia are fluorescently labeled. We then determined whether this seizure-induced microglia activation primes the central immune response to overreact and to increase the susceptibility to a second seizure later in life. We used an inhibitor of microglia activation, minocycline, to block the seizure-induced inflammation to determine whether innate immunity plays a causal role in mediating the long-term epileptogenic effects of early-life seizure. First status epilepticus was induced at postnatal day (P) 25 and a second status at P39. KA-SE at P25 caused nearly a two-fold increase in microglia activation within 24h. Significant seizure-induced activation persisted for 7 days and returned to baseline by 14 days. P39 animals with prior exposure to KA-SE not only responded with greater microglial activation in response to "second hit" of KA, but shorter latency to express seizures. Inhibition of seizure-induced inflammation by 7 day minocycline post-treatment abrogated both the exaggerated microglia activation and the increased susceptibility to the second seizure later in life. The priming effect of early-life seizures is accompanied by modified and rapidly reactivated microglia. Our results suggest that anti-inflammatory therapy after SE may be useful to block the epileptogenic process and mitigate the long-term damaging effects of early-life seizures.
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PMID:Minocycline attenuates microglia activation and blocks the long-term epileptogenic effects of early-life seizures. 2236 82

Retigabine is a new-generation antiepileptic drug that exerts therapeutic action through the activation of KCNQ channel dependent M-type potassium currents. While retigabine has been extensively studied in adult animals using a wide variety of seizure models, its effects in developing animals have not been examined. There has only been one previous report of retigabine efficacy in juvenile rats (Mazarati et al., 2008), which examined efficacy against kindled seizures and did not examine ages younger than postnatal day (P) 14. To determine the efficacy of retigabine during brain development we pretreated rats with retigabine (0-30 mg/kg) at three ages corresponding to the neonatal period through late childhood/early adolescence (i.e., P7, P14, or P25). Seizures were induced 30 min later using a chemoconvulsant (pentylenetetrazol, PTZ) model, which has been widely used to determine anticonvulsant efficacy of many other antiepileptic drugs in neonatal animals. In a dose and age-dependent manner, retigabine reduced the severity of PTZ evoked seizures, increased the latency to seizure onset, and decreased the incidence of full maximal seizures. The minimum effective dose was found to be 5mg/kg for P7 animals, 2.5mg/kg for P14 animals, and 1mg/kg for P25 animals. These findings allow a direct comparison between retigabine and previously studied antiepileptic drugs against PTZ seizures during development, and provide the first report of the effective dose range of retigabine in neonatal animals.
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PMID:Anticonvulsant effect of retigabine during postnatal development in rats. 2248 39

Opioids show both pro- and anti-epileptogenic effects in different experimental models of epilepsy. In the present study, the pentylentetrazole (PTZ)-induced seizure model was used to test the hypothesis that neonatal morphine administration affects seizure susceptibility in prepubertal rats. Female rats were subcutaneously injected with either morphine or saline on postnatal days 8-14 (P8-P14). To verify the long-term effect of morphine (or saline), the animals were treated second time with morphine (21 mg/kg; or saline) on either P25 or P32. Morphine administration decreased latency of myoclonic jerks and time to onset and increased tonic-clonic seizure rate at P25, but these findings were inversed at P32. Results showed a significant age difference in seizure behaviors between P25 and P32 animals. Blood corticosterone (COS) levels were significantly higher in P32 rats than in P25 rats. These findings show that neonatal morphine exposure plays an important role in increasing seizure vulnerability in P25 prepubertal rats but not in P32 rats. We conclude that early exposure to chronic morphine in infant rats might change their susceptibility to PTZ-induced seizure in an age-dependent manner.
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PMID:Morphine exposure induces age-dependent alterations in pentylenetetrazole-induced epileptic behaviors in prepubertal rats. 2297 85

The activation of metabotropic glutamate receptors subtype 4 (mGluR4) potentiates models of absence seizures in adult rats. These seizures are age-dependent, but data concerning the role of mGluR4 in immature brain is insufficient. N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1acarboxamide (PHCCC), which is a positive allosteric modulator of these receptors, was used in three different models of seizures in immature rats: 1) convulsions induced by high doses of pentetrazol (PTZ; a model of generalised tonic-clonic seizures); 2) rhythmic electro-encephalographic (EEG) activity induced by low doses of PTZ (a model of absence seizures); and 3) electrically elicited cortical afterdischarges (ADs, a model of myoclonic seizures). We administered four doses of PHCCC (1, 3, 10 and 20 mg/kg) in PTZ-induced convulsions and two doses (3 and 10 mg/kg) in the two electrophysiological models of freely moving rats with implanted electrodes. Every dose and age group consisted from 8 to 10 rats. PTZ-elicited convulsions were not significantly influenced by PHCCC. In contrast, PHCCC potentiated the effect of a subconvulsant dose (60 mg/kg) of PTZ. The 10-mg/kg dose of PHCCC significantly prolonged the duration of PTZ-induced rhythmic activity episodes and shortened the intervals between individual episodes in 25-day-old rats (P25). In contrast, this potentiation was not seen in P18 rats. Cortical ADs were significantly prolonged with repeated stimulations by both doses of PHCCC in P12 and P18 animals. P25 rats exhibited only slightly longer AD durations. In conclusion, we did not find any anticonvulsant effect of PHCCC. On the contrary, proconvulsant action was demonstrated in all three models in immature rats.
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PMID:Positive allosteric modulator of mGluR4 PHCCC exhibits proconvulsant action in three models of epileptic seizures in immature rats. 2309 51

The present study examined whether status epilepticus (SE) induced by LiCl-pilocarpine in immature rats (postnatal day [P]12) interferes with normal development; leads to progressive epileptogenesis, or cognitive decline and to pathology similar to that seen in human temporal lobe epilepsy. We correlated the extent of pathologic changes with the severity of functional alterations or epilepsy. SE-induced changes were compared with those of rats with SE induced at P25. Animals of both ages were exposed to a battery of behavioral tests for up to 3months after SE. Rats with SE at P12 showed mild retardation of psychomotor development and delayed habituation, whereas rats with SE at P25 showed no habituation. Assessment in adulthood using the Morris water maze test revealed that SE at both P12 and P25 led to cognitive impairment and that the severity of the impairment increased with age. A handling test revealed increased aggression in rats with SE at P25, but not in rats with SE at P12. Epilepsy was diagnosed with continuous video-electroencephalographic (EEG) monitoring for up to 7d. P25 rats were monitored at 5months after SE and seizures were detected in 83.3% of animals. P12 animals were divided into two groups and monitored at 5 or 7months after SE. Both the severity and incidence of spontaneous recurrent seizures tended to progress with time, and their incidence increased from 50% to 87.5% at 5 and 7months, respectively. Morphometric analysis and stereologic assessment of hilar neurons performed after video-EEG monitoring revealed atrophy of temporal brain structures, enlargement of lateral ventricles, and loss of hilar neurons in both age groups. In P12 rats, morphologic damage also tended to progress over time. Performance of animals in the Morris water maze correlated with the severity of damage, but not with seizure parameters.
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PMID:Are morphologic and functional consequences of status epilepticus in infant rats progressive? 2330 65


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