Cargando…

The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy

BACKGROUND: An animal model of chronic traumatic encephalopathy (CTE) is essential for further understanding the pathophysiological link between repetitive head injury and the development of chronic neurodegenerative disease. We previously described a model of repetitive mild traumatic brain injury...

Descripción completa

Detalles Bibliográficos
Autores principales: Petraglia, Anthony L., Plog, Benjamin A., Dayawansa, Samantha, Dashnaw, Matthew L., Czerniecka, Katarzyna, Walker, Corey T., Chen, Michael, Hyrien, Ollivier, Iliff, Jeffrey J., Deane, Rashid, Huang, Jason H., Nedergaard, Maiken
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287910/
https://www.ncbi.nlm.nih.gov/pubmed/25593768
http://dx.doi.org/10.4103/2152-7806.147566
_version_ 1782351880928624640
author Petraglia, Anthony L.
Plog, Benjamin A.
Dayawansa, Samantha
Dashnaw, Matthew L.
Czerniecka, Katarzyna
Walker, Corey T.
Chen, Michael
Hyrien, Ollivier
Iliff, Jeffrey J.
Deane, Rashid
Huang, Jason H.
Nedergaard, Maiken
author_facet Petraglia, Anthony L.
Plog, Benjamin A.
Dayawansa, Samantha
Dashnaw, Matthew L.
Czerniecka, Katarzyna
Walker, Corey T.
Chen, Michael
Hyrien, Ollivier
Iliff, Jeffrey J.
Deane, Rashid
Huang, Jason H.
Nedergaard, Maiken
author_sort Petraglia, Anthony L.
collection PubMed
description BACKGROUND: An animal model of chronic traumatic encephalopathy (CTE) is essential for further understanding the pathophysiological link between repetitive head injury and the development of chronic neurodegenerative disease. We previously described a model of repetitive mild traumatic brain injury (mTBI) in mice that encapsulates the neurobehavioral spectrum characteristic of patients with CTE. We aimed to study the pathophysiological mechanisms underlying this animal model. METHODS: Our previously described model allows for controlled, closed head impacts to unanesthetized mice. Briefly, 12-week-old mice were divided into three groups: Control, single, and repetitive mTBI. Repetitive mTBI mice received six concussive impacts daily, for 7 days. Mice were then subsequently sacrificed for macro- and micro-histopathologic analysis at 7 days, 1 month, and 6 months after the last TBI received. Brain sections were immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, CD68 for activated microglia, and AT8 for phosphorylated tau protein. RESULTS: Brains from single and repetitive mTBI mice lacked macroscopic tissue damage at all time-points. Single mTBI resulted in an acute rea ctive astrocytosis at 7 days and increased phospho-tau immunoreactivity that was present acutely and at 1 month, but was not persistent at 6 months. Repetitive mTBI resulted in a more marked neuroinflammatory response, with persistent and widespread astrogliosis and microglial activation, as well as significantly elevated phospho-tau immunoreactivity to 6-months. CONCLUSIONS: The neuropathological findings in this new model of repetitive mTBI resemble some of the histopathological hallmarks of CTE, including increased astrogliosis, microglial activation, and hyperphosphorylated tau protein accumulation.
format Online
Article
Text
id pubmed-4287910
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Medknow Publications & Media Pvt Ltd
record_format MEDLINE/PubMed
spelling pubmed-42879102015-01-15 The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy Petraglia, Anthony L. Plog, Benjamin A. Dayawansa, Samantha Dashnaw, Matthew L. Czerniecka, Katarzyna Walker, Corey T. Chen, Michael Hyrien, Ollivier Iliff, Jeffrey J. Deane, Rashid Huang, Jason H. Nedergaard, Maiken Surg Neurol Int Original Article BACKGROUND: An animal model of chronic traumatic encephalopathy (CTE) is essential for further understanding the pathophysiological link between repetitive head injury and the development of chronic neurodegenerative disease. We previously described a model of repetitive mild traumatic brain injury (mTBI) in mice that encapsulates the neurobehavioral spectrum characteristic of patients with CTE. We aimed to study the pathophysiological mechanisms underlying this animal model. METHODS: Our previously described model allows for controlled, closed head impacts to unanesthetized mice. Briefly, 12-week-old mice were divided into three groups: Control, single, and repetitive mTBI. Repetitive mTBI mice received six concussive impacts daily, for 7 days. Mice were then subsequently sacrificed for macro- and micro-histopathologic analysis at 7 days, 1 month, and 6 months after the last TBI received. Brain sections were immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, CD68 for activated microglia, and AT8 for phosphorylated tau protein. RESULTS: Brains from single and repetitive mTBI mice lacked macroscopic tissue damage at all time-points. Single mTBI resulted in an acute rea ctive astrocytosis at 7 days and increased phospho-tau immunoreactivity that was present acutely and at 1 month, but was not persistent at 6 months. Repetitive mTBI resulted in a more marked neuroinflammatory response, with persistent and widespread astrogliosis and microglial activation, as well as significantly elevated phospho-tau immunoreactivity to 6-months. CONCLUSIONS: The neuropathological findings in this new model of repetitive mTBI resemble some of the histopathological hallmarks of CTE, including increased astrogliosis, microglial activation, and hyperphosphorylated tau protein accumulation. Medknow Publications & Media Pvt Ltd 2014-12-23 /pmc/articles/PMC4287910/ /pubmed/25593768 http://dx.doi.org/10.4103/2152-7806.147566 Text en Copyright: © 2014 Petraglia AL. http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Original Article
Petraglia, Anthony L.
Plog, Benjamin A.
Dayawansa, Samantha
Dashnaw, Matthew L.
Czerniecka, Katarzyna
Walker, Corey T.
Chen, Michael
Hyrien, Ollivier
Iliff, Jeffrey J.
Deane, Rashid
Huang, Jason H.
Nedergaard, Maiken
The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy
title The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy
title_full The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy
title_fullStr The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy
title_full_unstemmed The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy
title_short The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy
title_sort pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287910/
https://www.ncbi.nlm.nih.gov/pubmed/25593768
http://dx.doi.org/10.4103/2152-7806.147566
work_keys_str_mv AT petragliaanthonyl thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT plogbenjamina thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT dayawansasamantha thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT dashnawmatthewl thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT czernieckakatarzyna thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT walkercoreyt thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT chenmichael thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT hyrienollivier thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT iliffjeffreyj thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT deanerashid thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT huangjasonh thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT nedergaardmaiken thepathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT petragliaanthonyl pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT plogbenjamina pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT dayawansasamantha pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT dashnawmatthewl pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT czernieckakatarzyna pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT walkercoreyt pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT chenmichael pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT hyrienollivier pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT iliffjeffreyj pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT deanerashid pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT huangjasonh pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy
AT nedergaardmaiken pathophysiologyunderlyingrepetitivemildtraumaticbraininjuryinanovelmousemodelofchronictraumaticencephalopathy