Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium binding proteins are well known to be expressed by different groups of hippocampal interneurons; however, whether voltage-dependent calcium channels (Ca(v)) are also localized in these neurons, changed during and after status epilepticus (SE), and involved in epileptic activity have not been reported. In the present study, we showed the colocalization of three subtypes of voltage-gated calcium channels (Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1) with different calcium binding proteins such as calbindin (CB), calretinin (CR), and parvalbumin (PV). At early stages during and after pilocarpine-induced status epilepticus (PISE), significant changes of expression of Ca(v)1.2, Ca(v)1.3 (L-type), and Ca(v)2.1 (P/Q-type) were found in different groups of hippocampal neurons. Induced expression of Ca(v)1.3 or Ca(v)2.1 in reactive astrocytes was shown at 1 week and 2 months after PISE. At the latter time point, higher percentages of colocalization of PV and Ca(v)1.2, CB, or PV and Ca(v)1.3 or Ca(v)2.1, lower percentages of CR and Ca(v)1.3 or Ca(v)2.1 immunoposivie neurons were observed in gliotic CA1 area. We therefore conclude that voltage-gated calcium channels are expressed by different groups of hippocampal interneurons in the mouse. At acute stages during and after PISE, up- or down-regulation of Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1 in functionally different groups of interneurons in CA1 area may be related to the changes of their plasticity. Up-regulation of Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1 in granule cells may be directly related to the occurrence of SE. The induced expression of Ca(v)1.3 or Ca(v)2.1 in reactive astrocytes at 1 week and 2 months after PISE suggests that Ca(v)1.3 or Ca(v)2.1-related calcium signaling in reactive astrocytes may be involved in initiation, maintenance or spread of seizure activity. In gliotic CA1 area at chronic stage (i.e., 2 months after PISE), the occurrence of higher percentages of colocalization of PV and Ca(v)1.2, CB, or PV and Ca(v)1.3 or Ca(v)2.1, lower percentages of CR and Ca(v)1.3 or Ca(v)2.1 immunopositive neurons may suggest that such colocalizations may be linked to the survival or loss of particular group of hippocampal neurons.
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PMID:Ca(v)1.2, Ca(v)1.3, and Ca(v)2.1 in the mouse hippocampus during and after pilocarpine-induced status epilepticus. 1726 61

Granule cell neurogenesis increases following seizures, and some newly born granule cells develop at abnormal locations within the hilus. These ectopic granule cells (EGCs) demonstrate regular bursts of action potentials that are synchronized with CA3 pyramidal cell burst discharges and the bursts of hilar neurons, including mossy cells. Such findings suggest that mossy cells may participate in circuits that activate EGCs. Electron microscopic immunolabeling was therefore used to determine if mossy cell axon terminals form synapses with hilar EGC dendrites, using animals that underwent pilocarpine-induced status epilepticus. Pilocarpine was administered to adult male rats, and those which developed status epilepticus were perfused 5-7 months later, after the period of EGC genesis. Hippocampal sections were processed for dual electron microscopic immunolabeling (using calcitonin gene-related peptide (CGRP) as a marker for mossy cells and calbindin (CaBP) as a marker for EGCs). Light microscopic analysis revealed large CGRP-immunoreactive cells in the hilus, with the appearance and distribution of mossy cells. Electron microscopic analysis revealed numerous CaBP-immunoreactive dendrites in the hilus, some of which were innervated by CGRP-immunoreactive terminals. The results suggest that mossy cells participate in the excitatory circuits which activate EGCs, providing further insight into the network rearrangements that accompany seizure-induced neurogenesis in this animal model of epilepsy.
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PMID:Mossy cell axon synaptic contacts on ectopic granule cells that are born following pilocarpine-induced seizures. 1761 Oct 32

With the mouse pilocarpine model of temporal lobe epilepsy (TLE), we showed a progressive loss of both principal cells and calbindin (CB)-, calretinin (CR)-, and parvalbumin (PV)-immunopositive interneurons in layers II-III of lateral entorhinal cortex (LEnt) from 2 months to 1 year after pilocarpine-induced status epilepticus (PISE). In the efferent pathway of LEnt, more Phaseolus vulgaris leucoagglutinin (PHA-L)-labelled en passant and terminal boutons with larger diameters were shown in the hippocampus and subiculum; in the prefrontal, piriform, and perirhinal cortices; and in the amygdaloid complex in experimental mice at the two time points compared with the control after iontophoretical injection of an anterograde tracer PHA-L into the LEnt. Furthermore, the numbers of CB- or CR-immunopositive neurons contacted by PHA-L-labelled en passant and terminal boutons decreased in most of these areas at 2 months or 1 year after PISE. In the afferent pathway of LEnt, the numbers of retrogradely labelled neurons were reduced significantly in the ipsilateral piriform cortex and endopiriform nucleus at 2 months and 1 year and in the reuniens thalamic nucleus only at 1 year after injection of a retrograde tracer cholera toxin B subunit (CTB) into the LEnt. The percentages of the number of CTB and CB or CR double-labelled neurons of all the retrogradely labelled neurons were also decreased in the reunions thalamic nucleus at 1 year after PISE. It is concluded that both cytoarchitectonic change and reorganization of afferent and efferent pathways in LEnt may be involved in the occurrence of TLE.
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PMID:Cytoarchitectonics and afferent/efferent reorganization of neurons in layers II and III of the lateral entorhinal cortex in the mouse pilocarpine model of temporal lobe epilepsy. 1805 44

Acquired epilepsy (AE) is characterized by spontaneous recurrent seizures and long-term changes that occur in surviving neurons following an injury such as status epilepticus (SE). Long-lasting alterations in hippocampal Ca(2+) homeostasis have been observed in both in vivo and in vitro models of AE. One major regulator of Ca(2+) homeostasis is the neuronal calcium binding protein, calbindin-D28k that serves to buffer and transport Ca(2+) ions. This study evaluated the expression of hippocampal calbindin levels in the rat pilocarpine model of AE. Calbindin protein expression was reduced over 50% in the hippocampus in epileptic animals. This decrease was observed in the pyramidal layer of CA1, stratum lucidum of CA3, hilus, and stratum granulosum and stratum moleculare of the dentate gyrus when corrected for cell loss. Furthermore, calbindin levels in individual neurons were also significantly reduced. In addition, the expression of calbindin mRNA was decreased in epileptic animals. Time course studies demonstrated that decreased calbindin expression was initially present 1 month following pilocarpine-induced SE and lasted for up to 2 years after the initial episode of SE. The results indicate that calbindin is essentially permanently decreased in the hippocampus in AE. This decrease in hippocampal calbindin may be a major contributing factor underlying some of the plasticity changes that occur in epileptogenesis and contribute to the alterations in Ca(2+) homeostasis associated with AE.
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PMID:Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus. 1839 65

Status epilepticus (SE) typically progresses into temporal lobe epilepsy (TLE) typified by complex partial seizures. Because sizable fraction of patients with TLE exhibit chronic seizures that are resistant to antiepileptic drugs, alternative therapies that are efficient for diminishing SE-induced chronic epilepsy have great significance. We hypothesize that bilateral grafting of appropriately treated striatal precursor cells into hippocampi shortly after SE is efficacious for diminishing SE-induced chronic epilepsy through long-term survival and differentiation into GABA-ergic neurons. We induced SE in adult rats via graded intraperitoneal injections of kainic acid, bilaterally placed grafts of striatal precursors (pre-treated with fibroblast growth factor-2 and caspase inhibitor) into hippocampi at 4 days post-SE, and examined long-term effects of grafting on spontaneous recurrent motor seizures (SRMS). Analyses at 9-12 months post-grafting revealed that, the overall frequency of SRMS was 67-89% less than that observed in SE-rats that underwent sham-grafting surgery and epilepsy-only controls. Graft cell survival was approximately 33% of injected cells and approximately 69% of surviving cells differentiated into GABA-ergic neurons, which comprised subclasses expressing calbindin, parvalbumin, calretinin and neuropeptide Y. Grafting considerably preserved hippocampal calbindin but had no effects on aberrant mossy fiber sprouting. The results provide novel evidence that bilateral grafting of appropriately treated striatal precursor cells into hippocampi shortly after SE is proficient for greatly reducing the frequency of SRMS on a long-term basis in the chronic epilepsy period. Presence of a large number of GABA-ergic neurons in grafts further suggests that strengthening of the inhibitory control in host hippocampi likely underlies the beneficial effects mediated by grafts.
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PMID:Grafting of striatal precursor cells into hippocampus shortly after status epilepticus restrains chronic temporal lobe epilepsy. 1857 33

The patterns of hippocampal neuronal loss and rewiring of the dentate gyrus (DG) were studied in the mouse model of temporal lobe epilepsy at 2 months after pilocarpine-induced status epilepticus (PISE). NeuN immunocytochemistry showed two patterns of neuronal damage, i.e., type 1 with partial loss of pyramidal neurons in CA3 area and type 2 with almost compete loss of CA3 pyramidal neurons. Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) demonstrated that, at different rostrocaudal segments of the hippocampus, associational and commissural connections in the DG changed differently between mice with type 1 vs. type 2 neuronal loss. Calretinin (CR)-immunopositive mossy cells in ventral hilus and its fibers in inner molecular layer of bilateral DG remained in mice with type 1 but almost disappeared in mice with type 2 neuronal loss, which was further supported by retrograde labeling with cholera toxin subunit B (CTB) showing colocalization of CTB with CR in the ventral hilus of bilateral DG in mice with type 1 neuronal loss, which was lost in those with type 2 neuronal loss. Furthermore, the sprouted PHA-L-immunopositive en passant and terminal boutons from the DG were found in CA1 area to contact with surviving calbindin-, CR-, and parvalbumin-immunopositive neurons. The present study therefore suggests that different patterns of neuronal loss in CA3 area may be linked to different axon reorganizations in the DG.
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PMID:Patterns of hippocampal neuronal loss and axon reorganization of the dentate gyrus in the mouse pilocarpine model of temporal lobe epilepsy. 1902 71

The goal of this study was to examine the morpho-physiologic changes in the dorsal subiculum network in the mouse model of temporal lobe epilepsy using extracellular recording, juxtacellular and immunofluorescence double labeling, and anterograde tracing methods. A significant loss of total dorsal subicular neurons, particularly calbindin, parvalbumin (PV) and immunopositive interneurons, was found at 2 months after pilocarpine-induced status epilepticus (SE). However, the sprouting of axons from lateral entorhinal cortex (LEnt) was observed to contact with surviving subicular neurons. These neurons had two predominant discharge patterns: bursting and fast irregular discharges. The bursting neurons were mainly pyramidal cells, and their dendritic spine density and bursting discharge rates were increased significantly in SE mice compared with the control group. Fast irregular discharge neurons were PV-immunopositive interneurons and had less dendritic spines in SE mice when compared with the control mice. When LEnt was stimulated, bursting and fast irregular discharge neurons had much shorter latency and stronger excitatory response in SE mice compared with the control group. Our results illustrate that morpho-physiologic changes in the dorsal subiculum could be part of a multilevel pathologic network that occurs simultaneously in many brain areas to contribute to the generation of epileptiform activity.
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PMID:Morpho-physiologic characteristics of dorsal subicular network in mice after pilocarpine-induced status epilepticus. 1929 97

Traumatic brain injury (TBI) produces several cellular changes, such as gliosis, axonal and dendritic plasticity, and inhibition-excitation imbalance, as well as cell death, which can initiate epileptogenesis. It has been demonstrated that dysfunction of the inhibitory components of the cerebral cortex after injury may cause status epilepticus in experimental models; we proposed to analyze the response of cortical interneurons and astrocytes after TBI in humans. Twelve contusion samples were evaluated, identifying the expression of glial fibrillary acidic protein (GFAP) and calcium-binding proteins (CaBPs). The study was made in sectors with and without preserved cytoarchitecture evaluated with NeuN immunoreactivity (IR). In sectors with total loss of NeuN-IR the results showed a remarkable loss of CaBP-IR both in neuropil and somata. In sectors with conserved cytoarchitecture less drastic changes in CaBP-IR were detected. These changes include a decrease in the amount of parvalbumin (PV-IR) neurons in layer II, an increase of calbindin (CB-IR) neurons in layers III and V, and an increase in calretinin (CR-IR) neurons in layer II. We also observed glial fibrillary acidic protein immunoreactivity (GFAP-IR) in the white matter, in the gray-white matter transition, and around the sectors with NeuN-IR total loss. These findings may reflect dynamic activity as a consequence of the lesion that is associated with changes in the excitatory circuits of neighboring hyperactivated glutamatergic neurons, possibly due to the primary impact, or secondary events such as hypoxia-ischemia. Temporal evolution of these changes may be the substrate linking severe cortical contusion and the resulting epileptogenic activity observed in some patients.
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PMID:Changes in calcium-binding protein expression in human cortical contusion tissue. 1964 26

The mechanism of status epilepticus-induced neuronal death in the immature brain is not fully understood. In the present study, we examined the contribution of caspases in our lithium-pilocarpine model of status epilepticus in 14 days old rat pups. In CA1, upregulation of caspase-8, but not caspase-9, preceded caspase-3 activation in morphologically necrotic cells. Pretreatment with a pan-caspase inhibitor provided neuroprotection, showing that caspase activation was not an epiphenomenon but contributed to neuronal necrosis. By contrast, upregulation of active caspase-9 and caspase-3, but not caspase-8, was detected in apoptotic dentate gyrus neurons, which were immunoreactive for doublecortin and calbindin-negative, two features of immature neurons. These results suggest that, in cells which are aligned in series as parts of the same excitatory hippocampal circuit, the same seizures induce neuronal death through different mechanisms. The regional level of neuronal maturity may be a determining factor in the execution of a specific death program.
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PMID:Vulnerability of postnatal hippocampal neurons to seizures varies regionally with their maturational stage. 1987 60

Status epilepticus occurring in early postnatal development protects CA1 hippocampal neurons, the region most sensitive to seizure-induced injury in the developing brain. Here, we developed a "two hit" model in dissociated cultures of the rat hippocampus to test whether pre-exposure of immature neurons to high concentrations of glutamate, N-methyl-D-aspartic acid (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) during a relatively resistant period prevents neurons from dying following a second exposure to the same chemicals after neurons mature and become highly vulnerable to excitatory amino acids (EAAs). Cultures were exposed to varied doses of glutamate, NMDA, or AMPA for 48 h at 5 DIV and again at 14 DIV for 5, 15, or 30 min. NeuN immunohistochemistry showed early exposure to glutamate (500 microM) killed approximately half of the neurons (52+/-8.6%) compared to the marked depletion that occurs after one exposure at 14 DIV (98+/-0.79%). When cultures were first challenged with moderate doses of glutamate (200 microM) followed by the high dose 7 days later, a significant population of neurons was spared (35.3+/-1.2%). Similarly, pre-exposure to maximal doses of NMDA (100 microM) increased the proportion of surviving cells following the second challenge. In contrast, AMPA (100 microM) was equally toxic after early or late applications and did not protect from the second exposure. GluR1 subunit expression was markedly decreased at 48 h after one or two exposures to 200 microM glutamate (by 44.57+/-3.6%, 45.07+/-3.69%) whereas GluR2 subunit expression was reduced by a lesser amount (25.7 57+/-3.8%). Confocal microscopy showed that one or two exposures to NMDA caused GluR2 protein to downregulate even further whereas parvalbumin (PV) was dramatically increased in the same neurons by over four-fold. On the other hand, calbindin (CB) immunoreactivity was nearly absent after the first exposure to 500 microM glutamate. These data indicate that early, transient exposure to certain EAAs at high doses can induce long-lasting neuroprotection. Alterations in the GluR1/GluR2 ratio as well as differential expression of specific calcium binding proteins may contribute to this neuroprotection.
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PMID:Early exposure of cultured hippocampal neurons to excitatory amino acids protects from later excitotoxicity. 1991 87


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