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  • 2000-2004  (3)
  • 2001  (3)
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  • 2000-2004  (3)
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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cystatin C (CSTC), a cysteine protease inhibitor, has been implicated in the processes of neuronal degeneration and repair of the nervous system. Using serial analysis of gene expression (SAGE), we recently identified CSTC as one of the genes that are overexpressed after electrically induced status epilepticus (SE). In the present study, Western blot analysis extended the SAGE results, showing increased CSTC protein in the hippocampus and entorhinal cortex. Immunocytochemistry revealed an increase in CSTC expression in glial cells, which was first apparent 24 h after onset of SE, and persisted for at least 3 months. Double immunolabelling confirmed that both reactive astrocytes, and activated microglia were CSTC immunopositive. Within the hippocampus, up-regulation was also observed in neuronal cells within one day after SE. Up-regulation was still present in hippocampal pyramidal cells and surviving interneurons of chronic epileptic rats (3–8 months post-SE). This study demonstrates that status epilepticus leads to a widespread and persistent up-regulation of CSTC in the hippocampus and entorhinal cortex, which may represent an intrinsic neuroprotective mechanism in the course of epileptogenesis that may counteract progression of the disease.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sodium channels (NaChs) regulate neuronal excitability in both physiological and pathological conditions, including epilepsy and are therefore an important target for antiepileptic drugs. In the present study, we examined the distribution of mRNAs encoding neonatal NaChs II and III α-isoforms in control rat hippocampus and after electrically-induced status epilepticus (SE), using nonradioactive in situ hybridization (ISH). Only weak expression of neonatal NaCh II and III mRNAs was observed in control hippocampus. By contrast, increased expression of neonatal NaCh II and III mRNAs was observed 4 h after the induction of SE in neurons of CA1–CA3 and the dentate granule cell layer. These changes were detected only in rats in which SE was successfully induced and persisted, although less intense, for up to 3 months, when rats display spontaneous seizures. Strong expression of neonatal NaCh α-isoforms was observed 1 week after SE in microglial cells, as confirmed by double labelling, combining ISH with immunocytochemistry for microglia markers. The increased expression of neonatal isoforms of the NaCh in both neurons and microglial cells may represent a critical mechanism for modulation of neuronal excitability, glial function and pharmacological response to antiepileptic drugs in the course of epileptogenesis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Neuronal loss, gliosis and axonal sprouting in the hippocampal formation are characteristics of the syndrome of mesial temporal sclerosis (MTS). In the post-status epilepticus (SE) rat model of spontaneous seizures these features of the MTS syndrome can be reproduced. To get a global view of the changes in gene expression in the hippocampus we applied serial analysis of gene expression (SAGE) during the early phase of epileptogenesis (latent period), prior to the onset of the first spontaneous seizure. A total of 10 000 SAGE tags were analyzed per experimental group, resulting in 5053 (SE) and 5918 (control group) unique tags (genes), each representing a specific mRNA transcript. Of these, 92 genes were differentially expressed in the hippocampus of post-SE rats in comparison to controls. These genes appeared to be mainly associated with ribosomal proteins, protein processing, axonal growth and glial proliferation proteins. Verification of two of the differentially expressed genes by in situ hybridization confirmed the changes found by SAGE. Histological analysis of hippocampal sections obtained 8 days after SE showed extensive cell loss, mossy fibre sprouting and gliosis in hippocampal sub regions. This study identifies new high-abundant genes that may play an important role in post-SE epileptogenesis.
    Type of Medium: Electronic Resource
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