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

Long-term neuroplastic changes in dentate gyrus (DG) have been reported after seizure induction and were shown to contribute to epitogenesis of epilepsy. These changes include increased number of newborn granule cells, sprouted mossy fibers, granule cell layer dispersion, etc. The aim of current study is to determine the acute progression of neuroplastic changes involved newly generated granule cells after kainic acid (KA)-induced seizures. Doublecortion (DCX) analysis was used to examine the newly generated granule cells morphology 1-7 days after seizure induction. Quantitative analysis of DCX-labeled cells at different times shows that there are some rapid changes in the dentate gyrus. At day 7 epileptical mice induced an increase of the number of DCX-labeled cells in DG. At days 3 and 7 after epilepsy induction, the percentage of DCX-labeled cells per DG were significantly increased. These results show that seizures are capable to increase the number of new granule cell within a short time for function activation in post-seizure period. Therefore, the rapid changes in the DG might be having a potential for hippocampus neuroplastic function.
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PMID:Proliferation changes in dentate gyrus of hippocampus during the first week following kainic acid-induced seizures. 2113 3

Intellectual and developmental disabilities (IDDs) such as autistic spectrum disorders (ASDs) and epilepsies are heterogeneous disorders that have diverse etiologies and pathophysiologies. The high rate of co-occurrence of these disorders, however, suggests potentially shared underlying mechanisms. A number of well-known genetic disorders share epilepsy, intellectual disability, and autism as prominent phenotypic features, including tuberous sclerosis complex, Rett syndrome, and fragile X syndrome. In addition, mutations of several genes involved in neurodevelopment, including ARX, DCX, neuroligins, and neuropilin 2 have been identified in children with epilepsy, IDDs, ASDs, or a combination of thereof. Finally, in animal models, early life seizures can result in cellular and molecular changes that could contribute to learning and behavioral disabilities. Increased understanding of the common genetic, molecular, and cellular mechanisms of IDDs, ASDs, and epilepsy may provide insight into their underlying pathophysiology and elucidate new therapeutic approaches for these conditions.
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PMID:Molecular mechanisms of cognitive and behavioral comorbidities of epilepsy in children. 2121 35

Both evoked and spontaneous seizures have been reported to increase neurogenesis in animal models. Less is known about whether neurogenesis and markers thereof are aberrantly expressed in human temporal lobe epilepsy (TLE) with hippocampal sclerosis. In the present study we measured protein levels of multiple neurogenesis marker genes using Western blotting. Tissue homogenates from sclerotic hippocampus surgically resected from patients with pharmacoresistantTLE (n = 7) were compared to hippocampal samples from a group of age- and gender-matched autopsy controls (n = 6). Expression of the mature neuron marker NeuN was significantly lower in TLE samples compared to controls. In contrast, levels of neurogenesis-associated genes including TUC-4, doublecortin, Neu-roD and Numb, were all similarly expressed in TLE and control hippocampus samples. The present study suggests hippocampal expression levels of proteins associated with neurogenesis are not notably different in human TLE, implying the sclerotic hippocampus may retain neurogenic potential.
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PMID:Expression of neurogenesis genes in human temporal lobe epilepsy with hippocampal sclerosis. 2147 1

We present 2 cases of malformations of cortical development and early onset epilepsy. The first case is of a patient with left hemimegalencephaly who developed focal epilepsy at the age of 2 days and cluster spasms at 1.5 months. After left functional hemispherectomy, seizures originated from the contralateral hemisphere, which had shown normal signals in the preoperative magnetic resonance imaging study. The second case is of a patient with lissencephaly, caused by a missense mutation in the doublecortin gene, who developed West syndrome at the age of 5 months. In both the cases, (123)I-iomazenil single photon emission computed tomography performed during infancy showed significant hyperfixation in the dysplastic lesions. This finding indicates the immaturity of the affected neurons and a gamma-aminobutyric acidergic involvement in epileptogenesis associated with malformations of cortical development during infancy.
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PMID:Iomazenil hyperfixation in single photon emission computed tomography study of malformations of cortical development during infancy. 2150 62

Plannexin represents a NCAM-derived peptide mimicking trans-homophilic NCAM interaction, which proved to exert neuroprotective effects in vitro. The effect of plannexin was evaluated in a rat status epilepticus model. As expected, prolonged seizure activity resulted in a pronounced cell loss in hippocampal subregions. The comparison between the vehicle- and plannexin-treated animals with status epilepticus did not reveal neuroprotective effects of plannexin on mature neurons. However, treatment with plannexin partially prevented the reduction in the number of doublecortin-labeled neuronal progenitor cells, which was evident 48h following status epilepticus. In conclusion, the data might give first evidence that plannexin can protect immature neurons in vivo. Future studies are necessary to evaluate whether disease-modifying or preventive effects are observed in models of epileptogenesis.
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PMID:Impact of the NCAM derived mimetic peptide plannexin on the acute cellular consequences of a status epilepticus. 2178 39

Mice mutant for the presynaptic protein Bassoon develop epileptic seizures and an altered pattern of neuronal activity that is accompanied by abnormal enlargement of several brain structures, with the strongest size increase in hippocampus and cortex. Using manganese-enhanced magnetic resonance imaging, an abnormal brain enlargement was found, which is first detected in the hippocampus 1 month after birth and amounts to an almost 40% size increase of this structure after 3 months. Stereological quantification of cell numbers revealed that enlargement of the dentate gyrus and the hippocampus proper is associated with larger numbers of principal neurons and of astrocytes. In search for the underlying mechanisms, an approximately 3-fold higher proportion of proliferation and survival of new-born cells in the dentate gyrus was found to go hand in hand with similarly larger numbers of doublecortin-positive cells and reduced numbers of apoptotic cells in the dentate gyrus and the hippocampus proper. Enlargement of the hippocampus and of other forebrain structures was accompanied by increased levels of brain-derived neurotrophic factor (BDNF). These data show that hippocampal overgrowth in Bassoon-mutant mice arises from a dysregulation of neurogenesis and apoptosis that might be associated with unbalanced BDNF levels.
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PMID:Hippocampal enlargement in Bassoon-mutant mice is associated with enhanced neurogenesis, reduced apoptosis, and abnormal BDNF levels. 2193 77

The duration of sustained seizures (SS) plays a crucial role in the occurrence of spontaneous recurrent seizures (SRS) in experimental animals. We tested whether rats with varying durations of initial convulsive SS exhibited differential neurogenesis patterns in the hippocampal dentate gyrus that may be related to subsequent epileptogenesis. Sprague-Dawley rats with pilocarpine-induced convulsive SS were divided into short SS (30 min) and long SS (2 h) groups. Their behavior was monitored to identify convulsive SRS. From 1 to 28 days post-SS, cell proliferation was evaluated by 5'-bromo-2'-deoxyuridine (BrdU) labeling and immature neuroblasts in the dentate gyrus were identified by doublecortin immunohistochemistry. Convulsive SRS was detected in 8 out of the 9 long SS rats, but not in the 9 short SS rats. During day 1-3, proliferative cells were diffusely localized throughout the hippocampus in the long SS rats but were primarily confined within the subgranular zone in the short SS rats. Within the subgranular zone, a significant increase in the number of BrdU-positive cells was found at days 3 and 7 after the long SS and on day 1 after the short SS. Notably, abnormal dendritic outgrowth and hilar-ectopic localization of doublecortin-positive cells were present in the long SS rats. In conclusion, aberrant hippocampal neurogenesis following long SS may contribute to the development of SRS.
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PMID:The duration of sustained convulsive seizures determines the pattern of hippocampal neurogenesis and the development of spontaneous epilepsy in rats. 2201 48

Epileptic seizures can lead to various reactions in the brain, ranging from neuronal necrosis and glial cell activation to focal structural disorganization. Furthermore, increased hippocampal neurogenesis has been documented in rodent models of acute convulsions. This is a report of hippocampal neurogenesis in a dog with spontaneous epileptic seizures. A 16-week-old epileptic German Shepherd Dog had marked neuronal cell proliferation (up to 5 mitotic figures per high-power field and increased immunohistochemical expression of proliferative cell nuclear antigen) in the dentate gyrus accompanied by microglial and astroglial activation. Some granule cells expressed doublecortin, a marker of immature neurons; mitotically active cells expressed neuronal nuclear antigen. No mitotic figures were found in the brain of age-matched control dogs. Whether increased neurogenesis represents a general reaction pattern of young epileptic dogs should be investigated.
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PMID:Neurogenesis in a young dog with epileptic seizures. 2219 55

Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. Lissencephaly is characterized by a smooth cerebral surface, thick cortex and dilated lateral ventricles associated with mental retardation and seizures due to defective neuronal migration. Lissencephaly due to the heterozygous loss of the gene LIS1 is a good example of a haploinsufficiency disorder. LIS1 was deleted or mutated in a large proportion of patients with lissencephaly in a heterozygous fashion. A series of studies discovered that LIS1 is an essential regulator of cytoplasmic dynein. Notably, the role of LIS1 in regulating dynein activity is highly conserved among eukaryotes. In particular, we reported that LIS1 and NDEL1 are essential for dynein transport to the plus-end of microtubules by kinesin, which is essential to maintain the proper distribution of cytoplasmic dynein within the cell. In addition, we report that mNUDC (mammalian NUDC) interacts with kinesin-1 and is required for the anterograde transport of a cytoplasmic dynein complex by kinesin-1. A microtubule organization and motor proteins are further modulated by post-translational modifications, including phosphorylation and palmitoylation. These modifications share a common pathway with mitotic cell division. For example, Aurora-A is activated during neurite elongation, and phosphorylates NDEL1, which facilitates microtubule extension into neurite processes. Elucidations of molecular pathways involving neuronal migrations provide us a chance to design a novel strategy for neurological disorder due to defective neuronal migration. For example, inhibition of calpain protects LIS1 from proteolysis resulting in the augmentation of LIS1 levels, which leads to rescue of the phenotypes that are observed in Lis1+/- mice. Endeavoring to address the regulation of the microtubule network and motor proteins will help in understanding not only corticogenesis but neurodegenerative disorders.
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PMID:A unique role of dynein and nud family proteins in corticogenesis. 2239 75

Neurogenesis in the hippocampal dentate gyrus persists throughout the lifespan of mammals, however, the rate of neurogenesis decreases as the animal ages. Although seizures increase neurogenesis in young adult brains, this relationship has not been shown in aged animals. Using doublecortin (DCX) immunocytochemistry, the number of DCX-labeled cells in the dentate gyrus from aged rats (23 months of age) was assessed 30 days following pilocarpine-induced seizures and was compared to the number obtained from age-matched control rats. DCX-labeled cells were located in the subgranular zone, at the border between the hilus and the granule cell layer, and within the granule cell layer in both epileptic and control aged brains. When comparing the aged epileptic rats to age-matched controls, there was a significant increase in the number of DCX-labeled cells that was almost four and a half-fold. Therefore, aged rats also display an increase in adult neurogenesis following seizures.
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PMID:Seizure-induced Increased Neurogenesis Occurs in the Dentate Gyrus of Aged Sprague-Dawley Rats. 2239 80


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