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

Reactive changes in hippocampal astrocytes are frequently encountered in association with temporal lobe epilepsy in humans and with drug or kindling-induced seizures in animal models. These reactive changes generally involve increases in astrocyte size and number and often occur together with neuronal loss and synaptic rearrangements. In addition to producing astrocytic changes, seizure activity can also produce reactive changes in microglia, the resident macrophages of brain. In this study, we examined the effects of recurrent seizure activity on hippocampal neurons and glia in the epileptic EL mouse, a natural model of human multifactorial idiopathic epilepsy and complex partial seizures. Timm staining was used to evaluate infrapyramidal mossy fiber organization and the optical dissector method was used to count Nissl-stained neurons in hippocampus of adult (about one year of age) EL mice and nonepileptic C57BL/6J (B6) and DDY mice. Immunostaining for glial fibrillary acidic protein (GFAP) and Iba1, an actin cross-linking molecule restricted to macrophages and microglia, was used to evaluate astrocytes and microglia, respectively. The EL mice experienced about 25-30 complex partial seizures with secondary generalization during routine weekly cage changing. No significant differences were found among the mouse strains for Timm staining scores or for neuronal counts in the CA1 and CA3 pyramidal fields or in the hilus. However, the number of GFAP-positive astrocytes was significantly elevated in the stratum radiatum and hilus of EL mice, while microglia appeared hyper-ramified and were more intensely stained in EL mice than in the B6 or DDY mice in the hilus, parietal cortex, and pyriform cortex. The results indicate that recurrent seizure activity in EL mice is associated with abnormalities in hippocampal astrocytes and brain microglia, but is not associated with obvious neuronal loss or mossy fiber synaptic rearrangements. The EL mouse can be a useful model for evaluating neuron-glia interactions related to idiopathic epilepsy.
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PMID:Hippocampal neurons and glia in epileptic EL mice. 1450 Dec 7

The effect of hippocampal kindling on behavioral changes following 10 and 21 hippocampal afterdischarges (ADs) or electrographic seizures was examined in behaving rats. As compared to control, non-stimulated rats, 21 but not 10 hippocampal ADs resulted in a decrease in social contact, an increase in social isolation, and an increase in climbing and chasing behavior tested in an open field 3 days after cessation of kindling. Porsolt forced swimming test was not different among the control, 10- or 21-AD groups of rats. A deficit in sensorimotor gating, measured by prepulse inhibition of an acoustic startle, was observed in kindled as compared to control rats at 2 weeks after 21 ADs, but not after 10 ADs. Similarly, methamphetamine (1 mg/kg i.p.) induced higher locomotor activity in kindled rats, as compared to controls, after 21 ADs but not after 10 ADs. Spontaneous locomotor activity in a novel cage, without drug administration, was not different between kindled and control rats. These findings suggest that behavioral alterations after repeated hippocampal electrographic seizures may be mediated by increased dopaminergic functions, which may also mediate the psychiatric symptoms in human epileptic patients.
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PMID:Schizophrenia-like behavioral changes after partial hippocampal kindling. 1471 56

The effects of delta sleep-inducing peptide (DSIP) and its tetrapeptide analogue, DSIP(1-4), on metaphit-induced audiogenic seizures were studied. Five groups of adult male Wistar rats were intraperitoneally treated with (1) saline, (2) metaphit, (3) DSIP, (4) metaphit+DSIP and (5) metaphit+DSIP(1-4). To examine blocking effects of DSIP and its analogue on fully developed metaphit seizures, the last two groups were injected after the eight audiogenic testing. The rats were stimulated using electric bell (on the top of the cage, generating 100+/-3 dB and frequency 5-8 kHz, for 60 s) 1 h after metaphit and afterwards at hourly intervals during the experiment. For EEG recordings and power spectra, three gold-plated screws were implanted into the skull. In metaphit-treated animals, EEGs appeared as polyspikes and spike-wave complexes while the power spectra were increasing for 30-h period. The incidence and severity of metaphit-induced audiogenic seizures reached peak value 7-12 h after the injection. Both DSIP and DSIP(1-4) significantly increased power spectra of delta waves and decreased incidence of seizures, mean seizure grade and tonic component of metaphit-induced convulsions. Taken together, these results suggest that DSIP and its analogue DSIP(1-4) should be considered as potential antiepileptics.
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PMID:Delta sleep-inducing peptide and its tetrapeptide analogue alleviate severity of metaphit seizures. 1475 49

In conclusion, we have discussed a reverse genetics approach to studying seizure disorders in mice (Fig. 1), employing a targeted mutagenesis method to exploit the genetic defects identified in human epilepsy families. After detailed characterization of the nature of the human mutation and the mouse counterpart gene, a targeting vector containing the human disease allele is created. The endogenous mouse gene is replaced by the human disease allele through homologous recombination in ES cells, leading to the generation of chimeric animals. Mice carrying one copy or both copies of the human mutation can be bred to study the phenotypic effect of heterozygous and homozygous mutations. At this stage, one may want to split the newly created mice into two groups. One group will go through seizure phenotyping tests, while the other group will be used to generate disease allele-carrying mice on a different genetic background. Phenotypic characterization of mice on different inbred strains includes behavioral monitoring and EEG analysis looking for the occurrence of spontaneous seizures, as well as routine cage examination looking for handling-provoked seizure and ECT- and PTZ- induced seizure paradigms looking for sensitivity to these stimuli. A complete evaluation of the seizure phenotype at the whole-animal level establishes the relevance of the mouse model to the human condition. Further investigation including imaging, electrophysiology and AED response in these mouse models will shed light on the mechanistic basis of the convulsive disorder. Current epilepsy research in mouse genetics offers promise for understanding the molecular mechanisms that underlie epileptogenesis in humans. A large-scale forward genetic effort to create novel mouse mutants with seizure phenotypes by in vivo chemical mutagenesis with ethyl-nitroso urea (ENU) is underway at the Jackson Laboratory (http://www.jax.org/nmf/). Genetic mapping and isolation of the affected genes in these seizure-prone models will provide additional molecular pathways involved in seizures. The mutant mice generated through both forward and reverse genetic approaches will be a valuable resource for the biomedical community to study epilepsy at the molecular level and to characterize the pathological consequences of seizures in the whole organism.
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PMID:Genetic approaches to studying mouse models of human seizure disorders. 1525 May 82

Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching, neurogenesis, gene expression, and improved learning and memory. Moreover, in animal models of CNS insult (e.g., gene deletion), a more complex environment has attenuated or prevented the sequelae of the insult. Of relevance is the prevention of seizures and attenuation of their neuropathological sequelae as a consequence of exposure to a more complex environment. Relatively little attention, however, has been given to the issue of sensitive periods associated with such effects, the relative importance of social versus inanimate stimulation, or the unique contribution of exercise. Our studies have examined the effects of environmental complexity on the development of the restricted, repetitive behavior commonly observed in individuals with autism. In this model, a more complex environment substantially attenuates the development of the spontaneous and persistent stereotypies observed in deer mice reared in standard laboratory cages. Our findings support a sensitive period for such effects and suggest that early enrichment may have persistent neuroprotective effects after the animal is returned to a standard cage environment. Attenuation or prevention of repetitive behavior by environmental complexity was associated with increased neuronal metabolic activity, increased dendritic spine density, and elevated neurotrophin (BDNF) levels in brain regions that are part of cortical-basal ganglia circuitry. These effects were not observed in limbic areas such as the hippocampus.
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PMID:Environmental complexity and central nervous system development and function. 1536 62

Behavioral problems, school failure, and memory impairment are common among children with epilepsy. Currently, no effective treatment exists to promote recovery and neuron regeneration after seizures. To investigate the efficacy of environmental enrichment in reversing early-life seizure-induced changes in exploratory behavior and gene expression, we injected postnatal day 20 to 25 rats with kainic acid or saline and placed them either singly in a cage or as a group of eight in an enriched environment for 7 to 10 days. Exploratory behavior was quantified in an open field, and hippocampal gene analysis was performed on oligonucleotide microarrays. Exploratory behavior in kainic acid isolated rats were decreased in open field, whereas kainic acid rats exposed to an enriched environment behaved similarly to controls (n = 37, analysis of variance, P < .001). Correlated with an improvement in behavior, genes involved in synaptic plasticity and memory consolidation, such as Arc, Homer1a, and Egr1, were significantly increased in rats exposed to environmental enrichment. Real-time quantitative reverse transcriptase-polymerase chain reaction confirmed our microarray data on select genes. Our results provide an experimental basis for promoting enriching education programs for children with epilepsy.
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PMID:Environmental enrichment reverses the impaired exploratory behavior and altered gene expression induced by early-life seizures. 1641 73

This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD(50) dose of sarin (42 microg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD(50) of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD(50) of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD(50) sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD(50) sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD(50) sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD(50) sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD(50) doses of sarin failed to habituate to some aspects of neurobehavioral testing. Spectral analysis of EEG data suggested that repeated sarin exposure may disrupt normal sleeping patterns (i.e., lower frequency bandwidths). While these EEG changes returned to relative normalcy 6 days after the last injection in animals receiving 0.4 x LD(50) sarin, these changes were still observed in the animals that received 0.5 x LD(50) sarin. Ten to twelve days after the last sarin injection (in 0.4 x LD(50) group only), neurochemical data showed that striatal choline levels were reduced in comparison to the saline group. At this time, atropine sulfate (5 mg/kg, i.p.) challenge resulted in a transient elevation in striatal ACh levels in animals exposed to repeated 0.4 x LD(50) sarin as well as in control animals. No evidence of brain or heart pathology was found in any guinea pig that survived all 10 sarin injections.
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PMID:The effects of repeated low-dose sarin exposure. 1655 54

Both normal, non-epileptic as well as seizure-prone rodents exhibit a spectrum of anxiogenic-like behaviors in response to stressor exposure. Comparative analysis reveals that the same set of emotionality dependent measures is sensitive to both stress reactivity in normal rodents as well as stress hyperreactivity typically seen in seizure-prone rodents. A variety of unconditioned, exploratory tasks reflect global sensitivity to stressor exposure in the form of behavioral inhibition of locomotor output. Moreover, well chosen stressors can trigger de novo seizures with or without a history of seizure incidence. Seizures may be elicited in response to stressful environmental stimuli such as noxious noises, tail suspension handling, or home cage disturbance. Stress reactivity studies in rodents with a genetic predisposition to seizures have yielded important clues regarding brain substrates that mediate seizure ontogeny and modulate ictogenesis. Brains of seizure susceptible rodents reflect elevated content of the stress-related neuropeptide, corticotropin-releasing factor (CRF) in several nuclei relative to non-susceptible controls and neutralization of brain CRF attenuates seizure sensitivity. Findings outlined in this review support a diathesis-stress hypothesis in which behavioral- and neuro-pathologies of genetically seizure susceptible rodents arise in part due to multifaceted hyperreactivity to noxious environmental stimuli.
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PMID:Neurobehavioral consequences of stressor exposure in rodent models of epilepsy. 1991 90

We describe a new cable-free, non-telemetric method for synchronized electrophysiological and video recordings of seizure activity in freely moving mice. The electrophysiological recordings were made by a head-mounted 4-channel data-logging device, allowing the mouse to move freely in its cage, and even to be moved from cage to cage under ongoing recording. Seizures were studied in Synapsin I/II double knock-out (SynDKO) mice, a genetically engineered mouse line that shows seizures upon daily handling procedures such as tail lifting during cage changes, much in resemblance to the more studied El mouse. The ability to elicit seizures through daily handling in SynDKO mice undergoing electrophysiological recording is a significant improvement in comparison to the traditional cable-based set-up. Furthermore, with its four channels and a sample rate of up to 500Hz, the data-logging device opens for more varied electrophysiological studies than other available cable-free systems.
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PMID:Seizure logging: A new approach to synchronized cable-free EEG and video recordings of seizure activity in mice. 2070 34

The authors performed a pathological examination of a 5-year-old female laboratory Japanese monkey who developed cortical blindness and epileptic seizures. Generalized, tonic-clonic seizures started to occur during behavioral training to get the animal to enter a carrying cage for future psychological experiments. Blindness was suspected because of a lack of approaching behavior toward foods such as fruits. Although the monkey was extensively treated with anticonvulsants, the clinical signs did not improve. An increased serum creatine phosphokinase (CPK) level and bilateral occipital brain atrophy were detected. Histopathologically, a severe degree of cerebromalacia was detected bilaterally in the occipital lobe, and necrosis and gliosis were seen mainly in the temporal lobe. Focal inflammation was found in the meninges. No other changes were observed in other nervous tissues or organs, and no signs of a parasitic or viral infection were found in the systemic organs. Spontaneously occurring lesions in the central nervous system have been rarely reported in laboratory monkeys. In the present case, the cause of cerebromalacia could not be confirmed, but the relationship between symptoms such as abnormal vision and the presence of brain lesions was distinct. The authors believe that this case is a valuable historical control case for the laboratory Japanese macaque.
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PMID:Cerebromalacia with epilepsy and cortical blindness in a laboratory Japanese macaque (Macaca fuscata). 2088 16


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