Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal Sclerosis
Mesial temporal lobe epilepsy (MTLE) is the most frequent focal epileptic syndrome in adults, and the majority of seizures originate primarily from the hippocampus. The resected hippocampal tissue often shows severe neuronal loss, a condition referred to as hippocampal sclerosis (HS). In order to un...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-03-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418300677 |
| _version_ | 1818945060647993344 |
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| author | Hiroki Kitaura Hiroshi Shirozu Hiroshi Masuda Masafumi Fukuda Yukihiko Fujii Akiyoshi Kakita |
| author_facet | Hiroki Kitaura Hiroshi Shirozu Hiroshi Masuda Masafumi Fukuda Yukihiko Fujii Akiyoshi Kakita |
| author_sort | Hiroki Kitaura |
| collection | DOAJ |
| description | Mesial temporal lobe epilepsy (MTLE) is the most frequent focal epileptic syndrome in adults, and the majority of seizures originate primarily from the hippocampus. The resected hippocampal tissue often shows severe neuronal loss, a condition referred to as hippocampal sclerosis (HS). In order to understand hippocampal epileptogenesis in MTLE, it seems important to clarify any discrepancies between the clinical and pathological features of affected patients. Here we investigated epileptiform activities ex vivo using living hippocampal tissue taken from patients with MTLE. Flavoprotein fluorescence imaging and local field potential recordings revealed that epileptiform activities developed from the subiculum. Moreover, physiological and morphological experiments revealed possible impairment of K+ clearance in the subiculum affected by HS. Stimulation of mossy fibers induced recurrent trans-synaptic activity in the granule cell layer of the dentate gyrus, suggesting that mossy fiber sprouting in HS also contributes to the epileptogenic mechanism. These results indicate that pathophysiological alterations involving the subiculum and dentate gyrus could be responsible for epileptogenesis in patients with MTLE. Keywords: Epilepsy, Hippocampal sclerosis, Subiculum, Kir4.1, Mossy fiber sprouting |
| first_indexed | 2024-12-20T07:53:07Z |
| format | Article |
| id | doaj.art-ea1137f9348a4bb6a5dd4612be052b63 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-20T07:53:07Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-ea1137f9348a4bb6a5dd4612be052b632022-12-21T19:47:48ZengElsevierEBioMedicine2352-39642018-03-01293846Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal SclerosisHiroki Kitaura0Hiroshi Shirozu1Hiroshi Masuda2Masafumi Fukuda3Yukihiko Fujii4Akiyoshi Kakita5Department of Pathology, Brain Research Institute, Niigata University, 1 Asahimachi, Chuo-ku, Niigata 951-8585, Japan; Corresponding author.Department of Neurosurgery, Nishi-Niigata Chuo National Hospital, 1 Masago, Nishi-ku, Niigata 950-2085, JapanDepartment of Neurosurgery, Nishi-Niigata Chuo National Hospital, 1 Masago, Nishi-ku, Niigata 950-2085, JapanDepartment of Neurosurgery, Nishi-Niigata Chuo National Hospital, 1 Masago, Nishi-ku, Niigata 950-2085, JapanDepartment of Neurosurgery, Brain Research Institute, Niigata University, 1 Asahimachi, Chuo-ku, Niigata 951-8585, JapanDepartment of Pathology, Brain Research Institute, Niigata University, 1 Asahimachi, Chuo-ku, Niigata 951-8585, JapanMesial temporal lobe epilepsy (MTLE) is the most frequent focal epileptic syndrome in adults, and the majority of seizures originate primarily from the hippocampus. The resected hippocampal tissue often shows severe neuronal loss, a condition referred to as hippocampal sclerosis (HS). In order to understand hippocampal epileptogenesis in MTLE, it seems important to clarify any discrepancies between the clinical and pathological features of affected patients. Here we investigated epileptiform activities ex vivo using living hippocampal tissue taken from patients with MTLE. Flavoprotein fluorescence imaging and local field potential recordings revealed that epileptiform activities developed from the subiculum. Moreover, physiological and morphological experiments revealed possible impairment of K+ clearance in the subiculum affected by HS. Stimulation of mossy fibers induced recurrent trans-synaptic activity in the granule cell layer of the dentate gyrus, suggesting that mossy fiber sprouting in HS also contributes to the epileptogenic mechanism. These results indicate that pathophysiological alterations involving the subiculum and dentate gyrus could be responsible for epileptogenesis in patients with MTLE. Keywords: Epilepsy, Hippocampal sclerosis, Subiculum, Kir4.1, Mossy fiber sproutinghttp://www.sciencedirect.com/science/article/pii/S2352396418300677 |
| spellingShingle | Hiroki Kitaura Hiroshi Shirozu Hiroshi Masuda Masafumi Fukuda Yukihiko Fujii Akiyoshi Kakita Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal Sclerosis EBioMedicine |
| title | Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal Sclerosis |
| title_full | Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal Sclerosis |
| title_fullStr | Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal Sclerosis |
| title_full_unstemmed | Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal Sclerosis |
| title_short | Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal Sclerosis |
| title_sort | pathophysiological characteristics associated with epileptogenesis in human hippocampal sclerosis |
| url | http://www.sciencedirect.com/science/article/pii/S2352396418300677 |
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