Hippocampal Programmed Cell Death after Status Epilepticus

Summary:  Purpose: Status epilepticus (SE) can result in acute neuronal injury with subsequent long-term age-dependent behavioral and histologic sequelae. To investigate potential mechanisms that may underlie SE-related neuronal injury, we studied the occurrence of programmed cell death (PCD) in the...

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Main Author: Abi-Habib, Ralph J. (author)
Other Authors: Kobbeissi, Mohamad (author), Farhat, Firas (author), Dbaibo, Ghassan S. (author), Kurdi, Rana M. (author), Mikati, Mohamad A. (author), El Sabban, Marwan E. (author), Asaad, Wissal (author)
Format: article
Published: 2003
Online Access:http://hdl.handle.net/10725/2734
http://dx.doi.org/10.1046/j.1528-1157.2003.22502.x
http://onlinelibrary.wiley.com/doi/10.1046/j.1528-1157.2003.22502.x/full
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_version_ 1864513459122601984
author Abi-Habib, Ralph J.
author2 Kobbeissi, Mohamad
Farhat, Firas
Dbaibo, Ghassan S.
Kurdi, Rana M.
Mikati, Mohamad A.
El Sabban, Marwan E.
Asaad, Wissal
author2_role author
author
author
author
author
author
author
author_facet Abi-Habib, Ralph J.
Kobbeissi, Mohamad
Farhat, Firas
Dbaibo, Ghassan S.
Kurdi, Rana M.
Mikati, Mohamad A.
El Sabban, Marwan E.
Asaad, Wissal
author_role author
dc.creator.none.fl_str_mv Abi-Habib, Ralph J.
Kobbeissi, Mohamad
Farhat, Firas
Dbaibo, Ghassan S.
Kurdi, Rana M.
Mikati, Mohamad A.
El Sabban, Marwan E.
Asaad, Wissal
dc.date.none.fl_str_mv 2003
2015-11-30T09:46:42Z
2015-11-30T09:46:42Z
2015-11-30
dc.identifier.none.fl_str_mv 0013-9580
http://hdl.handle.net/10725/2734
http://dx.doi.org/10.1046/j.1528-1157.2003.22502.x
Mikati, M. A., Abi‐Habib, R. J., El Sabban, M. E., Dbaibo, G. S., Kurdi, R. M., Kobeissi, M., ... & Asaad, W. (2003). Hippocampal Programmed Cell Death after Status Epilepticus: Evidence for NMDA‐Receptor and Ceramide‐Mediated Mechanisms. Epilepsia, 44(3), 282-291.
http://onlinelibrary.wiley.com/doi/10.1046/j.1528-1157.2003.22502.x/full
dc.language.none.fl_str_mv en
dc.relation.none.fl_str_mv Epilepsia
dc.rights.*.fl_str_mv info:eu-repo/semantics/openAccess
dc.title.none.fl_str_mv Hippocampal Programmed Cell Death after Status Epilepticus
Evidence for NMDA-Receptor and Ceramide-Mediated Mechanisms
dc.type.none.fl_str_mv Article
info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/article
description Summary:  Purpose: Status epilepticus (SE) can result in acute neuronal injury with subsequent long-term age-dependent behavioral and histologic sequelae. To investigate potential mechanisms that may underlie SE-related neuronal injury, we studied the occurrence of programmed cell death (PCD) in the hippocampus in the kainic acid (KA) model. Methods: In adult rats, KA-induced SE resulted in DNA fragmentation documented at 30 h after KA injection. Ceramide, a known mediator of PCD in multiple neural and nonneural tissues, increased at 2–3 h after KA intraperitoneal injection, and then decreased to control levels before increasing again from 12 to 30 h after injection. MK801 pretreatment prevented KA-induced increases in ceramide levels and DNA fragmentation, whether there was reduction in seizure severity or not (achieved with 5 mg/kg and 1 mg/kg of MK801, respectively). Results: Both ceramide increases and DNA fragmentation were observed after KA-induced SE in adult and in P35 rats. Ceramide did not increase after KA-induced SE in P7 pups, which also did not manifest any DNA fragmentation. Intrahippocampal injection of the active ceramide analogue C2-ceramide produced widespread DNA fragmentation, whereas the inactive ceramide analogue C2-dihydroceramide did not. Conclusions: Our data support the hypotheses that (a) N-methyl-d-aspartate–receptor activation results in ceramide increases and in DNA fragmentation; (b) ceramide is a mediator of PCD after SE; and (c) there are age-related differences in PCD and in the ceramide response after SE. Differences in the ceramide response could, potentially, be responsible for observed age-related differences in the response to SE.
eu_rights_str_mv openAccess
format article
id LAURepo_bdde51c4e6b294696190b723cc267ff2
identifier_str_mv 0013-9580
Mikati, M. A., Abi‐Habib, R. J., El Sabban, M. E., Dbaibo, G. S., Kurdi, R. M., Kobeissi, M., ... & Asaad, W. (2003). Hippocampal Programmed Cell Death after Status Epilepticus: Evidence for NMDA‐Receptor and Ceramide‐Mediated Mechanisms. Epilepsia, 44(3), 282-291.
language_invalid_str_mv en
network_acronym_str LAURepo
network_name_str Lebanese American University repository
oai_identifier_str oai:laur.lau.edu.lb:10725/2734
publishDate 2003
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repository.name.fl_str_mv
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spelling Hippocampal Programmed Cell Death after Status EpilepticusEvidence for NMDA-Receptor and Ceramide-Mediated MechanismsAbi-Habib, Ralph J.Kobbeissi, MohamadFarhat, FirasDbaibo, Ghassan S.Kurdi, Rana M.Mikati, Mohamad A.El Sabban, Marwan E.Asaad, WissalSummary:  Purpose: Status epilepticus (SE) can result in acute neuronal injury with subsequent long-term age-dependent behavioral and histologic sequelae. To investigate potential mechanisms that may underlie SE-related neuronal injury, we studied the occurrence of programmed cell death (PCD) in the hippocampus in the kainic acid (KA) model. Methods: In adult rats, KA-induced SE resulted in DNA fragmentation documented at 30 h after KA injection. Ceramide, a known mediator of PCD in multiple neural and nonneural tissues, increased at 2–3 h after KA intraperitoneal injection, and then decreased to control levels before increasing again from 12 to 30 h after injection. MK801 pretreatment prevented KA-induced increases in ceramide levels and DNA fragmentation, whether there was reduction in seizure severity or not (achieved with 5 mg/kg and 1 mg/kg of MK801, respectively). Results: Both ceramide increases and DNA fragmentation were observed after KA-induced SE in adult and in P35 rats. Ceramide did not increase after KA-induced SE in P7 pups, which also did not manifest any DNA fragmentation. Intrahippocampal injection of the active ceramide analogue C2-ceramide produced widespread DNA fragmentation, whereas the inactive ceramide analogue C2-dihydroceramide did not. Conclusions: Our data support the hypotheses that (a) N-methyl-d-aspartate–receptor activation results in ceramide increases and in DNA fragmentation; (b) ceramide is a mediator of PCD after SE; and (c) there are age-related differences in PCD and in the ceramide response after SE. Differences in the ceramide response could, potentially, be responsible for observed age-related differences in the response to SE.PublishedN/A2015-11-30T09:46:42Z2015-11-30T09:46:42Z20032015-11-30Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0013-9580http://hdl.handle.net/10725/2734http://dx.doi.org/10.1046/j.1528-1157.2003.22502.xMikati, M. A., Abi‐Habib, R. J., El Sabban, M. E., Dbaibo, G. S., Kurdi, R. M., Kobeissi, M., ... & Asaad, W. (2003). Hippocampal Programmed Cell Death after Status Epilepticus: Evidence for NMDA‐Receptor and Ceramide‐Mediated Mechanisms. Epilepsia, 44(3), 282-291.http://onlinelibrary.wiley.com/doi/10.1046/j.1528-1157.2003.22502.x/fullenEpilepsiainfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/27342016-08-26T09:30:01Z
spellingShingle Hippocampal Programmed Cell Death after Status Epilepticus
Abi-Habib, Ralph J.
status_str publishedVersion
title Hippocampal Programmed Cell Death after Status Epilepticus
title_full Hippocampal Programmed Cell Death after Status Epilepticus
title_fullStr Hippocampal Programmed Cell Death after Status Epilepticus
title_full_unstemmed Hippocampal Programmed Cell Death after Status Epilepticus
title_short Hippocampal Programmed Cell Death after Status Epilepticus
title_sort Hippocampal Programmed Cell Death after Status Epilepticus
url http://hdl.handle.net/10725/2734
http://dx.doi.org/10.1046/j.1528-1157.2003.22502.x
http://onlinelibrary.wiley.com/doi/10.1046/j.1528-1157.2003.22502.x/full