Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus
The pathophysiological mechanisms that cause spontaneous seizures following status epilepticus are largely unknown. Erosion of inhibition is regarded as an important pathophysiological hallmark of ongoing status epilepticus. Therefore, we investigated if loss of inhibitory functions also plays an im...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-06-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999610400289X |
| _version_ | 1819119436357959680 |
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| author | M. Holtkamp J. Matzen F. van Landeghem K. Buchheim H. Meierkord |
| author_facet | M. Holtkamp J. Matzen F. van Landeghem K. Buchheim H. Meierkord |
| author_sort | M. Holtkamp |
| collection | DOAJ |
| description | The pathophysiological mechanisms that cause spontaneous seizures following status epilepticus are largely unknown. Erosion of inhibition is regarded as an important pathophysiological hallmark of ongoing status epilepticus. Therefore, we investigated if loss of inhibitory functions also plays an important role in the development of spontaneous seizures after status epilepticus. Furthermore, we analyzed possible changes in excitation that might contribute to epileptogenesis. Finally, neuronal cell loss in the dentate gyrus granule cell layer was analyzed. In rats, inhibition and excitation in the dentate gyrus were monitored 1, 4, and 8 weeks after electrically induced self-sustaining status epilepticus (SSSE). Control animals had electrodes implanted either without subsequent stimulation or with stimulation but under barbiturate anesthesia, neither of which resulted in subsequent spontaneous seizures or impairment of inhibition. Following SSSE 80% of animals developed seizures after 8 weeks. A pronounced impairment of inhibition 1 week after SSSE was followed by gradual recovery over 8 weeks. In the dentate gyrus, cell damage was highly variable most likely explaining the heterogeneity of changes in excitatory parameters. Loss of GABAergic inhibition in the dentate gyrus may facilitate initiation of epileptogenesis but impaired inhibition is not required for the process of epileptogenesis to be maintained. |
| first_indexed | 2024-12-22T06:04:44Z |
| format | Article |
| id | doaj.art-98a253171bec4b18839d55af077bd33b |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T06:04:44Z |
| publishDate | 2005-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-98a253171bec4b18839d55af077bd33b2022-12-21T18:36:26ZengElsevierNeurobiology of Disease1095-953X2005-06-01191162170Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticusM. Holtkamp0J. Matzen1F. van Landeghem2K. Buchheim3H. Meierkord4Department of Neurology, Charité-Universitätsmedizin Berlin (Campus Mitte), Schumannstr. 20/21, 10117 Berlin, Germany; Corresponding author. Fax: +49 30 450 56 09 32.Department of Neurology, Charité-Universitätsmedizin Berlin (Campus Mitte), Schumannstr. 20/21, 10117 Berlin, GermanyInstitute of Neuropathology, Charité-Universitätsmedizin Berlin (Campus Virchow-Klinikum), Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Neurology, Charité-Universitätsmedizin Berlin (Campus Mitte), Schumannstr. 20/21, 10117 Berlin, GermanyDepartment of Neurology, Charité-Universitätsmedizin Berlin (Campus Mitte), Schumannstr. 20/21, 10117 Berlin, GermanyThe pathophysiological mechanisms that cause spontaneous seizures following status epilepticus are largely unknown. Erosion of inhibition is regarded as an important pathophysiological hallmark of ongoing status epilepticus. Therefore, we investigated if loss of inhibitory functions also plays an important role in the development of spontaneous seizures after status epilepticus. Furthermore, we analyzed possible changes in excitation that might contribute to epileptogenesis. Finally, neuronal cell loss in the dentate gyrus granule cell layer was analyzed. In rats, inhibition and excitation in the dentate gyrus were monitored 1, 4, and 8 weeks after electrically induced self-sustaining status epilepticus (SSSE). Control animals had electrodes implanted either without subsequent stimulation or with stimulation but under barbiturate anesthesia, neither of which resulted in subsequent spontaneous seizures or impairment of inhibition. Following SSSE 80% of animals developed seizures after 8 weeks. A pronounced impairment of inhibition 1 week after SSSE was followed by gradual recovery over 8 weeks. In the dentate gyrus, cell damage was highly variable most likely explaining the heterogeneity of changes in excitatory parameters. Loss of GABAergic inhibition in the dentate gyrus may facilitate initiation of epileptogenesis but impaired inhibition is not required for the process of epileptogenesis to be maintained.http://www.sciencedirect.com/science/article/pii/S096999610400289XSelf-sustaining status epilepticusDentate gyrusGABAergic inhibitionSpontaneous seizures |
| spellingShingle | M. Holtkamp J. Matzen F. van Landeghem K. Buchheim H. Meierkord Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus Neurobiology of Disease Self-sustaining status epilepticus Dentate gyrus GABAergic inhibition Spontaneous seizures |
| title | Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus |
| title_full | Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus |
| title_fullStr | Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus |
| title_full_unstemmed | Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus |
| title_short | Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus |
| title_sort | transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus |
| topic | Self-sustaining status epilepticus Dentate gyrus GABAergic inhibition Spontaneous seizures |
| url | http://www.sciencedirect.com/science/article/pii/S096999610400289X |
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