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

Uridine, like adenosine, is released under sustained depolarization and it can inhibit hippocampal neuronal activity, suggesting that uridine may be released during seizures and can be involved in epileptic mechanisms. In an in vivo microdialysis study, we measured the extracellular changes of nucleoside and amino acid levels and recorded cortical EEG during 3-aminopyridine-induced epilepsy. Applying silver impregnation and immunohistochemistry, we examined the degree of hippocampal cell loss. We found that extracellular concentration of uridine, adenosine, inosine, and glutamate increased significantly, while glutamine level decreased during seizures. The release of uridine correlated with seizure activity. Systemic and local uridine application was ineffective. The number of parvalbumin- and calretinin-containing interneurons of dorsal hippocampi decreased. We conclude that uridine is released during epileptic activity, and suggest that as a neuromodulator, uridine may contribute to epilepsy-related neuronal activity changes, but uridine analogues having slower turnover would be needed for further investigation of physiological role of uridine.
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PMID:Uridine release during aminopyridine-induced epilepsy. 1526 60

Although there is evidence that astrocytes support neuronal function, the contribution of astrocytes to seizure onset and termination is not known. To determine whether there are changes in seizure susceptibility or neuronal damage when the ability of astrocytes to generate ATP is reduced, 0.5 nmol of fluorocitrate (FC) was injected into the right ventricle. Injection of FC alone did not produce electrographic or behavioral seizures and did not stress or injure neurons or astrocytes, as measured with silver stain and immunohistochemistry for HSP32 or HSP72. However, in animals pretreated with FC, administration of kainic acid, at a dose that does not initiate seizures in control animals (7 mg/kg), caused wet dog shakes and neuronal damage in the hilus. Wet dog shakes did not cause any neuronal damage in control animals. If the dose of FC was increased to 0.75 nmol, then subsequent administration of the same dose of kainic acid (7 mg/kg) caused stage 3-5 seizures. Injection of FC also reduced the dose of pilocarpine needed to produce seizures. Given simultaneously with FC, isocitrate, which bypasses the biochemical inhibition of aconitase, blocked the effects of FC in both kainic acid and pilocarpine treated animals. The data demonstrate that inhibition of aconitase in astrocytes lowers the doses of both kainic acid and pilocarpine that will cause behavioral seizures and may increase neuronal vulnerability to seizures.
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PMID:Inhibition of aconitase in astrocytes increases the sensitivity to chemical convulsants. 1527 69

Sensitive indices of neural injury were used to evaluate the time course of kainic acid (KA)-induced hippocampal damage in adult C57BL/6J mice (4 months), a strain previously reported to be resistant to kainate-induced neurotoxicity. Mice were injected systemically with saline or kainate, scored for seizure severity (Racine scale), and allowed to survive 12 h, one, three, or seven days following which they were evaluated for neuropathological changes using histological or biochemical endpoints. Most kainate-treated mice exhibited limited seizure activity (stage 1); however, cupric-silver and Fluoro-Jade B stains revealed significant damage by 12 h post-treatment. Immunohistochemistry and immunoassay of glial fibrillary acidic protein and lectin staining revealed a strong treatment-induced reactive gliosis and microglial activation. Immunostaining for immunoglobulin G revealed a kainate-induced breach in the blood-brain barrier. Nissl and hematoxylin stains provided little information regarding neuronal damage, but revealed the identity of non-resident cells which infiltrated the pyramidal layer. Our data suggest sensitive indicators of neural injury evaluated over a time course, both proximal and distal to treatment, are necessary to reveal the full extent of neuropathological changes which may be underestimated by traditional histological stains. The battery of neuropathological indices reported here reveals the C57BL/6J mouse is sensitive to excitotoxic neural damage caused by kainic acid, in the absence of tonic-clonic seizures.
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PMID:Sensitive indicators of injury reveal hippocampal damage in C57BL/6J mice treated with kainic acid in the absence of tonic-clonic seizures. 1545 67

Domoic acid and its potent excitotoxic analogues glutamic acid and kainic acid, are synthesized by marine algae such as seaweed and phytoplankton. During an algal bloom, domoic acid may enter the food web through its consumption by a variety of marine organisms held in high regard as seafoods by both animals and humans. These seafoods include clams, mussels, oysters, anchovies, sardines, crabs, and scallops, among others. Animals, such as pelicans, cormorants, loons, grebes, sea otters, dolphins, and sea lions, which consume seafood contaminated with domoic acid, suffer disorientation and often death. Humans consuming contaminated seafood may suffer seizures, amnesia and also sometimes death. In addition to analytical measurement of domoic acid exposure levels in algae and/or seafood, it is useful to be able to identify the mode of toxicity through post-mortem evaluation of the intoxicated animal. In the present study, using the rat as an animal model of domoic acid intoxication, we compared histochemical staining of the limbic system and especially the hippocampus with degeneration-selective techniques (Fluoro-Jade and silver), a conventional Nissl stain for cytoplasm (Cresyl violet), a myelin-selective stain (Black-Gold), an astrocyte-specific stain (glial fibrillary acidic protein), early/immediate gene responses (c-Fos and c-Jun), as well as for heat shock protein (HSP-72) and blood-brain barrier integrity (rat IgG). The results demonstrate that the degeneration-selective stains are the biomarkers of domoic acid neurotoxicity that are the most useful and easy to discern when screening brain sections at low magnification. We also observed that an impairment of blood-brain barrier integrity within the piriform cortex accompanied the onset of domoic acid neurotoxicity.
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PMID:Neurohistochemical biomarkers of the marine neurotoxicant, domoic acid. 1620 21

Neonatal seizures may increase neuronal vulnerability later in life. Therefore, status epilepticus was induced with kainate (KA) during the first and second postnatal (P) weeks to determine whether early seizures shift the window of neuronal vulnerability to a younger age. KA was injected (i.p.) once (1x KA) on P13, P20 or P30 or three times (3 x KA), once on P6 and P9, and then either on P13, P20 or P30. After 1x KA, onset to behavioral seizures increased with age. Electroencephalography (EEG) showed interictal events appeared with maturation. After 3 x KA, spike number, frequency, spike amplitude, and high-frequency synchronous events and duration were increased at P13 when compared to age-matched controls. In contrast, P20 and P30 rats had decreases in EEG parameters relative to P20 and P30 rats with 1x KA despite that these animals had the same history of perinatal seizures on P6 and P9. In P13 rats with 1x KA, silver impregnation, hematoxylin/eosin and TUNEL methods showed no significant hippocampal injury and damage was minimal with 3 x KA. In contrast, P20 and P30 rats with 1x KA had robust eosinophilic or TUNEL positive labeling and preferential accumulation of silver ions within inner layer CA1 neurons. After 3 x KA, the CA1 but not CA3 of P20 and P30 rats was preferentially protected following 3 or 6 days. Although paradoxical changes occur in the EEG with maturation, the results indicate that early perinatal seizures do not significantly shift the window of hippocampal vulnerability to an earlier age but induce a tolerance that leads to long-term neuroprotection that differentially affects endogenous properties of CA1 versus CA3 neurons.
Seizure 2006 Jan
PMID:Perinatal seizures preferentially protect CA1 neurons from seizure-induced damage in prepubescent rats. 1630 25

Intracerebral injection of hamster neurotropic (HNT) measles virus in weanling Balb/C mice leads to an encephalitis, which is characterized by glial activation, behavioral seizures, selective neurodegeneration, and, after approximately 7 days, death. To provide a better understanding of the underlying molecular pathology, we studied seizure evolution by continuously monitoring electroencephalographic (EEG) activity, examined neuroglia and neurons histologically, and measured the brain content of glia-derived neuroactive metabolites of the kynurenine pathway of tryptophan degradation. Microglia and astrocytes were activated as early as postinoculation day (PID) 1, with reactive microglia lining the extent of the alveus. This was followed by a more extensive microglial activation that specifically outlined hippocampal pyramidal neurons in areas CA1-CA3 and by increases in the hippocampal levels of the neurotoxins 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN). These changes preceded the onset of EEG seizures, which had a mean onset of 108 h after inoculation. Prominent hippocampal cell loss, demonstrated by Nissl- and silver staining, was apparent by PID 5. Thus, we speculate that early glial reactions to HNT inoculation result in the excess formation of 3-HK and QUIN, which in turn causes subclinical seizure activity, behavioral seizures, and, eventually, neurodegeneration. In addition to its conceptual implications, our study indicates that timely interventions modulating glial activation or 3-HK/QUIN synthesis may be of benefit in preventing or arresting seizure-induced neuronal damage.
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PMID:Glial activation precedes seizures and hippocampal neurodegeneration in measles virus-infected mice. 1822 68

Previous studies have shown that VEGF expression in forebrain increases after experimental manipulations that increase neuronal activity. One question is whether this also occurs in motor neurons. If so, it could be potentially advantageous from a therapeutic perspective, because VEGF prevents motor neuron degeneration. Therefore, we asked whether endogenous VEGF expression in motor neurons could be modulated. We also asked how VEGF exposure would influence motor neurons using electrophysiology. Immunocytochemistry showed that motor neuron VEGF expression increased after a stimulus that increases neuronal and motor activity, i.e., convulsive seizures. The increase in VEGF immunoreactivity occurred in all motor neuron populations that were examined 24h later. This effect was unlikely to be due to seizure-induced toxicity, because silver degeneration stain did not show the typical appearance of a dying or dead neuron. To address the effects of VEGF on motor neuron function, VEGF was applied directly to motor neurons while recording intracellularly, using a brainstem slice preparation. Exposure to exogenous VEGF (200 ng/ml) in normal conditions depressed stimulus-evoked depolarization of hypoglossal motor neurons. There was no detectable effect of VEGF on membrane properties or firing behavior. We suggest that VEGF is upregulated in neurons when they are strongly activated, and VEGF depresses neuronal excitation as a compensatory mechanism. Failure of this mechanism may contribute to diseases that involve a dysregulation of VEGF, excessive excitation of motor neurons, and motor neuron loss, such as amyotrophic lateral sclerosis (ALS).
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PMID:Modulation of vascular endothelial growth factor (VEGF) expression in motor neurons and its electrophysiological effects. 1839 8

Distribution and time course of the occurrence of "dark" neurons were compared with the EEG activity and behavior of rats during 4-aminopyridine (4-AP) induced epileptic seizures. A crystal of the K(+) channel blocker 4-AP (0.5 mg/kg) was placed onto the exposed parieto-occipital cortex of Halothane-anesthetized rats for 40 min. Thereafter, the anesthesia was discontinued and the behavioral signs of the epileptic seizure activity were observed. The presence of "dark" neurons was demonstrated by the sensitive silver method of Gallyas in rats sacrificed at 0, 3 and 6 h after the end of the 4-AP crystal application. The EEG activity was recorded in the rats with longer survival times. The EEG analysis revealed the generalization of the epileptic seizures. We found that the formation of "dark" neurons in the hippocampus and the pontine reticular formation paralleled the generalization of the seizures.
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PMID:Generalization of seizures parallels the formation of "dark" neurons in the hippocampus and pontine reticular formation after focal-cortical application of 4-aminopyridine (4-AP) in the rat. 1860

Elevated Ca(2+) concentrations have been implicated in cell death mechanisms following seizures, however, the age and brain region of intracellular Ca(2+) accumulations [Ca(2+)](i), may influence whether or not they are toxic. Therefore, we examined regional accumulations of (45)Ca(2+) by autoradiography from rats of several developmental stages (P14, P21, P30 and P60) at 5, 14, and 24h after status epilepticus. To determine whether the uptake was intracellular, Ca(2+) was also assessed in hippocampal slices with the dye indicator, Fura 2AM at P14. Control animals accumulated low homogeneous levels of (45)Ca(2+); however, highly specific and age-dependent patterns of (45)Ca(2+) uptake were observed at 5h. (45)Ca(2+) accumulations were predominant in dorsal hippocampal regions, CA1/CA2/CA3a, in P14 and P21 rats and in CA3a and CA3c neurons of P30 and P60 rats. Selective midline and amygdala nuclei were marked at P14 but not at P21 and limbic accumulations recurred with maturation that were extensive at P30 and even more so at P60. At 14 h, P14 and P21 rats had no persistent accumulations whereas P30 and P60 rats showed persistent uptake patterns within selective amygdala, thalamic and hypothalamic nuclei, and other limbic cortical regions that continued to differ at these ages. For example, piriform cortex accumulation was highest at P60. Fura 2AM imaging at P14 confirmed that Ca(2+) rises were intracellular and occurred in both vulnerable and invulnerable regions of the hippocampus, such as CA2 pyramidal and dentate granule cells. Silver impregnation showed predominant CA1 injury at P20 and P30 but CA3 injury at P60 whereas little or no injury was found in extrahippocampal structures at P14 and P20 but was modest at P30 and maximal at P60. Thus, at young ages there was an apparent dissociation between high (45)Ca(2+) accumulations and neurotoxicity whereas in adults a closer relationship was observed, particularly in the extrahippocampal structures.
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PMID:Age- and region-dependent patterns of Ca2+ accumulations following status epilepticus. 1868 97

Fibroblast growth factor 2 (FGF-2) has multiple, pleiotropic effects on the nervous system that include neurogenesis, neuroprotection and neuroplasticity. Thus, alteration in FGF-2 expression patterns may have a profound impact in brain function, both in normal physiology and in pathology. Here, we used FGF-2 transgenic mice (TgFGF2) to study the effects of endogenous FGF-2 overexpression on susceptibility to seizures and to the pathological consequences of seizures. TgFGF2 mice display increased FGF-2 expression in hippocampal pyramidal neurons and dentate granule cells. Increased density of glutamatergic synaptic vesicles was observed in the hippocampus of TgFGF2 mice, and electrophysiological data (input/output curves and patch-clamp recordings in CA1) confirmed an increase in excitatory inputs in CA1, suggesting the presence of a latent hyperexcitability. Indeed, TgFGF2 mice displayed increased susceptibility to kainate-induced seizures compared with wild-type (WT) littermates, in that latency to generalized seizure onset was reduced, whereas behavioral seizure scores and lethality were increased. Finally, WT and TgFGF2 mice with similar seizure scores were used for examining seizure-induced cellular consequences. Neurogenesis and mossy fiber sprouting were not significantly different between the two groups. In contrast, cell damage (assessed with Fluoro-Jade B, silver impregnation and anti-caspase 3 immunohistochemistry) was significantly lower in TgFGF2 mice, especially in the areas of overexpression (CA1 and CA3), indicating reduction of seizure-induced necrosis and apoptosis. These data suggest that FGF-2 may be implicated in seizure susceptibility and in seizure-induced plasticity, exerting different, and apparently contrasting effects: favoring ictogenesis but reducing seizure-induced cell death.
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PMID:Fgf-2 overexpression increases excitability and seizure susceptibility but decreases seizure-induced cell loss. 1905 2


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