Histological Characterisation of a Sheep Model of Mild Traumatic Brain Injury: A Pilot Study

Large animal models of mild traumatic brain injury (mTBI) are needed to elucidate the pathophysiology of mechanical insult to a gyrencephalic brain. Sheep (ovis aries) are an attractive model for mTBI because of their neuroanatomical similarity to humans; however, few histological studies of sheep m...

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Main Authors: Sheryl Tan, Danica Hamlin, Eryn Kwon, Miriam Scadeng, Vickie Shim, Samantha Holdsworth, Sarah-Jane Guild, Helen Murray
Format: Article
Language:English
Published: Mary Ann Liebert 2024-03-01
Series:Neurotrauma Reports
Subjects:
Online Access:https://www.liebertpub.com/doi/full/10.1089/NEUR.2023.0105
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author Sheryl Tan
Danica Hamlin
Eryn Kwon
Miriam Scadeng
Vickie Shim
Samantha Holdsworth
Sarah-Jane Guild
Helen Murray
author_facet Sheryl Tan
Danica Hamlin
Eryn Kwon
Miriam Scadeng
Vickie Shim
Samantha Holdsworth
Sarah-Jane Guild
Helen Murray
author_sort Sheryl Tan
collection DOAJ
description Large animal models of mild traumatic brain injury (mTBI) are needed to elucidate the pathophysiology of mechanical insult to a gyrencephalic brain. Sheep (ovis aries) are an attractive model for mTBI because of their neuroanatomical similarity to humans; however, few histological studies of sheep mTBI models have been conducted. We previously developed a sheep mTBI model to pilot methods for investigating the mechanical properties of brain tissue after injury. Here, we sought to histologically characterize the cortex under the impact site in this model. Three animals received a closed skull mTBI with unconstrained head motion, delivered with an impact stunner, and 3 sham animals were anesthetized but did not receive an impact. Magnetic resonance imaging (MRI) of the brain was performed before and after the impact and revealed variable degrees of damage to the skull and brain. Fluorescent immunohistochemistry revealed regions of hemorrhage in the cortex underlying the impact site in 2 of 3 mTBI sheep, the amount of which correlated with the degree of damage observed on the post-impact MRI scans. Labeling for microtubule-associated protein 2 and neuronal nuclear protein revealed changes in cellular anatomy, but, unexpectedly, glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 labeling were relatively unchanged compared to sham animals. Our findings provide preliminary evidence of vascular and neuronal damage with limited glial reactivity and highlight the need for further in-depth histological assessment of large animal mTBI models.
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spelling doaj.art-1cf78b79b8074039baeb2100ba41c9e42024-03-08T04:00:47ZengMary Ann LiebertNeurotrauma Reports2689-288X2024-03-015119420210.1089/NEUR.2023.0105Histological Characterisation of a Sheep Model of Mild Traumatic Brain Injury: A Pilot StudySheryl TanDanica HamlinEryn KwonMiriam ScadengVickie ShimSamantha HoldsworthSarah-Jane GuildHelen MurrayLarge animal models of mild traumatic brain injury (mTBI) are needed to elucidate the pathophysiology of mechanical insult to a gyrencephalic brain. Sheep (ovis aries) are an attractive model for mTBI because of their neuroanatomical similarity to humans; however, few histological studies of sheep mTBI models have been conducted. We previously developed a sheep mTBI model to pilot methods for investigating the mechanical properties of brain tissue after injury. Here, we sought to histologically characterize the cortex under the impact site in this model. Three animals received a closed skull mTBI with unconstrained head motion, delivered with an impact stunner, and 3 sham animals were anesthetized but did not receive an impact. Magnetic resonance imaging (MRI) of the brain was performed before and after the impact and revealed variable degrees of damage to the skull and brain. Fluorescent immunohistochemistry revealed regions of hemorrhage in the cortex underlying the impact site in 2 of 3 mTBI sheep, the amount of which correlated with the degree of damage observed on the post-impact MRI scans. Labeling for microtubule-associated protein 2 and neuronal nuclear protein revealed changes in cellular anatomy, but, unexpectedly, glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 labeling were relatively unchanged compared to sham animals. Our findings provide preliminary evidence of vascular and neuronal damage with limited glial reactivity and highlight the need for further in-depth histological assessment of large animal mTBI models.https://www.liebertpub.com/doi/full/10.1089/NEUR.2023.0105hemorrhageimmunohistochemistrymild traumatic brain injurysheepneuroinflammation
spellingShingle Sheryl Tan
Danica Hamlin
Eryn Kwon
Miriam Scadeng
Vickie Shim
Samantha Holdsworth
Sarah-Jane Guild
Helen Murray
Histological Characterisation of a Sheep Model of Mild Traumatic Brain Injury: A Pilot Study
Neurotrauma Reports
hemorrhage
immunohistochemistry
mild traumatic brain injury
sheep
neuroinflammation
title Histological Characterisation of a Sheep Model of Mild Traumatic Brain Injury: A Pilot Study
title_full Histological Characterisation of a Sheep Model of Mild Traumatic Brain Injury: A Pilot Study
title_fullStr Histological Characterisation of a Sheep Model of Mild Traumatic Brain Injury: A Pilot Study
title_full_unstemmed Histological Characterisation of a Sheep Model of Mild Traumatic Brain Injury: A Pilot Study
title_short Histological Characterisation of a Sheep Model of Mild Traumatic Brain Injury: A Pilot Study
title_sort histological characterisation of a sheep model of mild traumatic brain injury a pilot study
topic hemorrhage
immunohistochemistry
mild traumatic brain injury
sheep
neuroinflammation
url https://www.liebertpub.com/doi/full/10.1089/NEUR.2023.0105
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AT miriamscadeng histologicalcharacterisationofasheepmodelofmildtraumaticbraininjuryapilotstudy
AT vickieshim histologicalcharacterisationofasheepmodelofmildtraumaticbraininjuryapilotstudy
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