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)

Zinc induces in cultured cortical neurons both p75(NTR) and p75(NTR)-associated death executor (NADE), which together contribute to caspase-dependent neuronal apoptosis. Since zinc neurotoxicity may contribute to neuronal death following seizures, we examined whether p75(NTR) and NADE are co-induced also in rat hippocampal neurons degenerating after seizures. Staining of brain sections with a zinc-specific fluorescent dye (N-(6-methoxy-8-quinolyl)-p-carboxybenzoylsulphonamide) and acid fuchsin revealed zinc accumulation in degenerating neuronal cell bodies in CA1 and CA3 of hippocampus 24 h after kainate injection. Both anti-p75(NTR) and anti-NADE immunoreactivities appeared in zinc-accumulating/degenerating neurons in both areas. Intraventricular injection of CaEDTA, without altering the severity or time course of kainate-induced seizures, markedly attenuated the induction of p75(NTR)/NADE in hippocampus, which correlated with the decrease of caspase-3 activation and zinc accumulation/cell death. The present study has demonstrated that p75(NTR) and NADE are co-induced in neurons degenerating after kainate-induced seizures in rats, likely in a zinc-dependent manner.
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PMID:Co-induction of p75(NTR) and the associated death executor NADE in degenerating hippocampal neurons after kainate-induced seizures in the rat. 1287 43

Status epilepticus (SE) increases neurogenesis in the subgranular zone (SGZ) of the adult dentate gyrus, but many of the newborn cells die, partly through caspase-induced apoptosis. Here we provide immunohistochemical evidence indicating that the caspase-evoked death of the new neurons involves the mitochondrial but not the death-receptor-mediated pathway. Cytochrome c released from mitochondria was found in a subset of progenitor cell progeny, while Fas ligand and tumor necrosis factor 1 receptor-associated domain as well as the mitochondria-related, caspase-independent apoptosis-inducing factor were not detected. We also show that additional seizures, induced at different stages during neuronal differentiation of progenitor cell progeny following SE, neither potentiate cell death mechanisms in the SGZ nor compromise the survival of the new cells. Thus, we found similar expression of cytochrome c, active caspase-3, caspase-cleaved PARP, and TUNEL/Hoechst-positive DNA fragmentation, as well as numbers of new cells in the SGZ in rats exposed to additional seizures at days 6 and 7 or days 33 and 34 following SE as in control animals only subjected to SE. We propose that the degree of survival of newly generated neurons is determined primarily by the initial SE insult and the ensuing pathology in the tissue environment, whereas spontaneous seizures play a minor role.
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PMID:Death mechanisms in status epilepticus-generated neurons and effects of additional seizures on their survival. 1467 67

Several Bcl-2 family members, including Bim, may contribute to programmed cell death by inducing mitochondrial cytochrome c release, which activates caspase-9 and then caspase-3, the "executioner" of the cell. In this issue of the JCI, Shinoda and collaborators show the key role of Bim in epileptic seizure-induced neuronal injury and identify the contribution of transcription factors responsible for seizure-induced Bim upregulation.
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PMID:Bim, Bad, and Bax: a deadly combination in epileptic seizures. 1505 13

Relations between seizures induced by repeated electroshock (ES) and structural changes in the hippocampus were investigated in Balb/C mice. Brain sections of the animals 2 or 7 days after the last ES were stained for Nissl or TUNEL (apoptotic nuclei). Direct measurement of caspase-3 activity (a key enzyme of apoptosis) in brain regions was performed immediately after the last ES. Statistically significant, albeit moderate cell loss was demonstrated in the CA1 field and dentate gyrus, but not in the CA3 field of the hippocampus. The number of neurons in these fields inversely correlated with seizure severity. No apoptotic nuclei could be revealed either in hippocampus or in other brain regions. Caspase-3 in the hippocampus decreased after ES. The data obtained support the results from other groups showing prominent functional changes in neurons induced by repeated ES and extend this concept directly testifying for a moderate (within 10%), albeit statistically significant neuronal death in selected hippocampal fields. The inverse correlation of cell number with severity of seizures suggest that these are seizures inducing neuronal death.
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PMID:[Electroconvulsive shock causes neuronal death in the mouse hippocampus: correlation of neurodegeneration and convulsive activity]. 1515 63

The levels of zinc in the brain are directly affected by dietary zinc and deficiency has been associated with alcohol withdrawal seizures, excitotoxicity, impaired learning and memory and an accelerated rate of dysfunction in aged brain. Although zinc is essential for a healthy nervous system, high concentrations of zinc are neurotoxic, thus it is important to identify the most effective forms of zinc for treatment of conditions of the central nervous system. Accumulating evidence suggests that zinc-histidine complex (Zn(His)(2)) has greater biological potency and enhanced bioavailability compared with other zinc salts and also has antioxidant potential. Therefore, in this study we investigated the ability of zinc-histidine to protect cultured cortical neurons against hydrogen peroxide-induced damage. Pre-treating neurons for 18 h with subtoxic concentrations of zinc-histidine (5-25 microM) improved neuronal viability and strongly inhibited hydrogen peroxide-induced (75 microM, 30 min) cell damage as assessed by MTT turnover and morphological analysis 24h later. Low concentrations of zinc-histidine were more neuroprotective than zinc chloride. There was evidence of an anti-apoptotic mechanism of action as zinc-histidine inhibited hydrogen peroxide-induced caspase-3 activation and c-jun-N-terminal kinase phosphorylation. In summary, zinc supplementation with zinc-histidine protects cultured neurons against oxidative insults and inhibits apoptosis which suggests that zinc-histidine may be beneficial in the treatment of diseases of the CNS associated with zinc deficiency.
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PMID:Zinc-histidine complex protects cultured cortical neurons against oxidative stress-induced damage. 1551 38

We examined metallothionein (MT)-induced neuroprotection during kainic acid (KA)-induced excitotoxicity by studying transgenic mice with MT-I overexpression (TgMT mice). KA induces epileptic seizures and hippocampal excitotoxicity, followed by inflammation and delayed brain damage. We show for the first time that even though TgMT mice were more susceptible to KA, the cerebral MT-I overexpression decreases the hippocampal inflammation and delayed neuronal degeneration and cell death as measured 3 days after KA administration. Hence, the proinflammatory responses of microglia/macrophages and lymphocytes and their expression of interleukin (IL)-1, IL-6, IL-12, tumor necrosis factor-alpha and matrix metalloproteinases (MMP-3, MMP-9) were significantly reduced in hippocampi of TgMT mice relative to wild-type mice. Also by 3 days after KA, the TgMT mice showed significantly less delayed damage, such as oxidative stress (formation of nitrotyrosine, malondialdehyde, and 8-oxoguanine), neurodegeneration (neuronal accumulation of abnormal proteins), and apoptotic cell death (judged by TUNEL and activated caspase-3). This reduced bystander damage in TgMT mice could be due to antiinflammatory and antioxidant actions of MT-I but also to direct MT-I effects on the neurons, in that significant extracellular MT presence was detected. Furthermore, MT-I overexpression stimulated astroglia and increased immunostaining of antiinflammatory IL-10, growth factors, and neurotrophins (basic fibroblastic growth factor, transforming growth factor-beta, nerve growth factor, brain-derived neurotrophic factor, glial-derived neurotrophic factor) in hippocampus. Accordingly, MT-I has different functions that likely contribute to the increased neuron survival and improved CNS condition of TgMT mice. The data presented here add new insight into MT-induced neuroprotection and indicate that MT-I therapy could be used against neurological disorders.
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PMID:Metallothionein reduces central nervous system inflammation, neurodegeneration, and cell death following kainic acid-induced epileptic seizures. 1561 85

Brain injury due to seizures results in transiently increased cell proliferation and neurogenesis in the subgranular zone of the adult dentate gyrus. In contrast, the immature postnatal brain appears to be more resistant to cell death after seizure-induced brain injury and paradoxically reacts to seizures by reducing SGZ proliferation. Organotypic hippocampal slice cultures are a useful paradigm for modelling the early postnatal hippocampus. We have investigated the temporal relationship between cell death and cell proliferation after kainate in the granule cell layer of rat organotypic hippocampal slice cultures equivalent to post natal day 11 animals. We found stable numbers and densities of mature thionine stained cells in the granule cell layer over 72 h in control cultures grown in defined medium. We also found a slowly declining cell proliferation rate over the same time period under control conditions. We report evidence of early cell death in the granule cell layer after just 2 h exposure to 5 microM kainate, followed by a significant decrease in cell proliferation in the granule cell layer at 24 h. In contrast to control conditions, cell proliferation rose significantly in the kainate exposed cultures by 72 h back to levels seen at 2 h. There were no significant changes in cell labelling with antibody to activated caspase-3 between kainate treated and control cultures at any time point examined. Our results suggest that kainate-induced injury in the early postnatal hippocampus damages precursor cells contributing to a reduction in granule layer cell proliferation.
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PMID:Kainic acid induces rapid cell death followed by transiently reduced cell proliferation in the immature granule cell layer of rat organotypic hippocampal slice cultures. 1572 51

Ribonucleotide reductase (RNR), an enzyme for DNA synthesis, was recently used as a marker of proliferating cells in the dentate gyrus and subventricular zone in normal adult mammalian brains. However, the duration of RNR expression in normal adult brain and the expression pattern of RNR in the adult dentate gyrus following brain injury have not been explored. In this study, we examined the duration of the RNR expression in newborn cells in the normal adult rat brain by analysis of RNR and BrdU double-labeled specimens at different time intervals after BrdU application. Secondly, we induced, in adult rats, seizures by kainic acid and investigated the changes in expression of RNR following seizures, and characterized the phenotype of RNR-positive cells using a variety of other markers. Our results revealed that RNR was detectable in proliferating cells from 2 h to at least 1 day. At 7 and 28 days after seizures, there was a fivefold increase in number of clusters of RNR-positive cells in the dentate gyrus, and a doubling of the number of BrdU-labeled cells in each cluster. Proliferating astrocytes and neuronal precursors were recognized in each RNR-positive cell cluster, and both types increased in number after seizures. Colocalization of RNR and activated caspase-3 was observed at 7 days, indicating that proliferating cells were susceptible to status epilepticus induced damage. RNR immunohistochemistry provides a useful approach in experiments investigating a change in cell proliferation, revealing the location, number, morphology and fate of newly formed cells after, e.g., brain injury.
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PMID:Characterization of cell proliferation in the adult dentate under normal conditions and after kainate induced seizures using ribonucleotide reductase and BrdU. 1572 96

Pilocarpine-induced status epilepticus (PCSE) is a widely used model to study neurodegeneration in limbic structures after prolonged epileptic seizures. However, mechanisms mediating neuronal cell death in this model require further characterization. Examining the expression time course and spatial distribution of activated caspase-3, we sought to determine the role of apoptosis in PCSE-mediated neuronal cell death. Expression of activated caspase-3, predominantly located in neurons, was detected 24 h (amygdala; piriform and temporal cortex) and 7 days (hippocampus; amygdala; piriform, temporal and parietal cortex; thalamus) after PCSE with strongest induction being observed in the amygdala, the piriform cortex, and the hippocampus. Further analysis revealed TUNEL positivity (24 h and 7 days after SE) and a significant, progressive neuronal cell loss in all brain regions displaying caspase-3 activation. Corresponding to high levels of activated caspase-3 expression, neuronal cell loss was most pronounced in the amygdala, piriform cortex, and dorsal CA-1 hippocampus. These results demonstrate that apoptosis contributes significantly to PCSE-induced neuronal cell death.
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PMID:Expression time course and spatial distribution of activated caspase-3 after experimental status epilepticus: contribution of delayed neuronal cell death to seizure-induced neuronal injury. 1575 84

We investigated the effect of ketogenic diet (KD) on clusterin accumulation in the kainic acid (KA)-induced seizure model. Two days after KA administration, strong clusterin-like immunoreactivity (IR) was detected in the hippocampus in the normal diet (ND)-fed mice. But in the KD-fed mice, few clusterin-like IR was detected. These results indicate that KD has neuroprotective effects throughout diminishing nuclear clusterin accumulation that is involved in caspase-3 independent cell death mechanism.
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PMID:Ketogenic diet prevents clusterin accumulation induced by kainic acid in the hippocampus of male ICR mice. 1582 60


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