Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.

Posttraumatic epilepsy is a major source of disability following traumatic brain injury (TBI) and a common cause of medically-intractable epilepsy. Previous attempts to prevent the development of posttraumatic epilepsy with treatments administered immediately following TBI have failed. Recently, the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Dongjun Guo, Linghui Zeng, David L Brody, Michael Wong
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9148b105b8f44b3d9b0bb8a2b0783f67
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9148b105b8f44b3d9b0bb8a2b0783f67
record_format	dspace
spelling	oai:doaj.org-article:9148b105b8f44b3d9b0bb8a2b0783f672021-11-18T07:45:47ZRapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.1932-620310.1371/journal.pone.0064078https://doaj.org/article/9148b105b8f44b3d9b0bb8a2b0783f672013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23691153/?tool=EBIhttps://doaj.org/toc/1932-6203Posttraumatic epilepsy is a major source of disability following traumatic brain injury (TBI) and a common cause of medically-intractable epilepsy. Previous attempts to prevent the development of posttraumatic epilepsy with treatments administered immediately following TBI have failed. Recently, the mammalian target of rapamycin complex 1 (mTORC1) pathway has been implicated in mechanisms of epileptogenesis and the mTORC1 inhibitor, rapamycin, has been proposed to have antiepileptogenic effects in preventing some types of epilepsy. In this study, we have tested the hypothesis that rapamycin has antiepileptogenic actions in preventing the development of posttraumatic epilepsy in an animal model of TBI. A detailed characterization of posttraumatic epilepsy in the mouse controlled cortical impact model was first performed using continuous video-EEG monitoring for 16 weeks following TBI. Controlled cortical impact injury caused immediate hyperactivation of the mTORC1 pathway lasting at least one week, which was reversed by rapamycin treatment. Rapamycin decreased neuronal degeneration and mossy fiber sprouting, although the effect on mossy fiber sprouting was reversible after stopping rapamycin and did not directly correlate with inhibition of epileptogenesis. Most posttraumatic seizures occurred greater than 10 weeks after TBI, and rapamycin treatment for one month after TBI decreased the seizure frequency and rate of developing posttraumatic epilepsy during the entire 16 week monitoring session. These results suggest that rapamycin may represent a rational treatment for preventing posttraumatic epilepsy in patients with TBI.Dongjun GuoLinghui ZengDavid L BrodyMichael WongPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e64078 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dongjun Guo Linghui Zeng David L Brody Michael Wong Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.
description	Posttraumatic epilepsy is a major source of disability following traumatic brain injury (TBI) and a common cause of medically-intractable epilepsy. Previous attempts to prevent the development of posttraumatic epilepsy with treatments administered immediately following TBI have failed. Recently, the mammalian target of rapamycin complex 1 (mTORC1) pathway has been implicated in mechanisms of epileptogenesis and the mTORC1 inhibitor, rapamycin, has been proposed to have antiepileptogenic effects in preventing some types of epilepsy. In this study, we have tested the hypothesis that rapamycin has antiepileptogenic actions in preventing the development of posttraumatic epilepsy in an animal model of TBI. A detailed characterization of posttraumatic epilepsy in the mouse controlled cortical impact model was first performed using continuous video-EEG monitoring for 16 weeks following TBI. Controlled cortical impact injury caused immediate hyperactivation of the mTORC1 pathway lasting at least one week, which was reversed by rapamycin treatment. Rapamycin decreased neuronal degeneration and mossy fiber sprouting, although the effect on mossy fiber sprouting was reversible after stopping rapamycin and did not directly correlate with inhibition of epileptogenesis. Most posttraumatic seizures occurred greater than 10 weeks after TBI, and rapamycin treatment for one month after TBI decreased the seizure frequency and rate of developing posttraumatic epilepsy during the entire 16 week monitoring session. These results suggest that rapamycin may represent a rational treatment for preventing posttraumatic epilepsy in patients with TBI.
format	article
author	Dongjun Guo Linghui Zeng David L Brody Michael Wong
author_facet	Dongjun Guo Linghui Zeng David L Brody Michael Wong
author_sort	Dongjun Guo
title	Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.
title_short	Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.
title_full	Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.
title_fullStr	Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.
title_full_unstemmed	Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.
title_sort	rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9148b105b8f44b3d9b0bb8a2b0783f67
work_keys_str_mv	AT dongjunguo rapamycinattenuatesthedevelopmentofposttraumaticepilepsyinamousemodeloftraumaticbraininjury AT linghuizeng rapamycinattenuatesthedevelopmentofposttraumaticepilepsyinamousemodeloftraumaticbraininjury AT davidlbrody rapamycinattenuatesthedevelopmentofposttraumaticepilepsyinamousemodeloftraumaticbraininjury AT michaelwong rapamycinattenuatesthedevelopmentofposttraumaticepilepsyinamousemodeloftraumaticbraininjury
_version_	1718422987349164032

Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury.

Ejemplares similares