Differential responses to increasing numbers of mild traumatic brain injury in a rodent closed-head injury model

Brooke Fehily, Carole A Bartlett, Stephen Lydiard, Michael Archer, Hannah Milbourn, Maimuna Majimbi, Jan M Hemmi, Sarah A Dunlop, Nathanael J Yates, Melinda Fitzgerald

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. To compare chronic damage and deficits following increasing numbers of repeated mTBIs, a closed-head weight-drop model of repeated mTBI was used to deliver 1, 2 or 3 mTBIs to adult female rats at 24 h intervals. Outcomes were assessed at 3 months following the first mTBI. No gross motor, sensory or reflex deficits were identified (p > 0.05), consistent with current literature. Cognitive function assessed using a Morris water maze revealed chronic memory deficits following 1 and 2, but not 3 mTBI compared to shams (p ≤ 0.05). Oxidative damage to DNA was assessed immunohistochemically in the dentate hilus of the hippocampus and splenium of the corpus callosum; no changes were observed. IBA1 positive microglia were increased in size in the cortex following 1 mTBI and in the corpus callosum following 2 mTBI compared to shams (p ≤ 0.05); no changes were observed in the dentate hilus. GFAP positive astrocyte immunoreactivity was assessed in all three brain regions and no chronic changes were observed. Integrity of myelin ultrastructure in the corpus callosum was assessed using transmission electron microscopy. G ratio was decreased following 2 mTBIs compared to shams (p ≤ 0.05) at post-hoc level only. The changing patterns of damage and deficits following increasing numbers of mTBI may reflect dynamic responses to small numbers of mTBIs or a conditioning effect such that increasing numbers of mild traumatic brain injuries do not necessarily result in worsening pathology. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)660-678
JournalJournal of Neurochemistry
Volume149
Issue number5
Early online date31 Jan 2019
DOIs
Publication statusPublished - Jun 2019

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Brain Concussion
Closed Head Injuries
Rodentia
Brain
Corpus Callosum
Memory Disorders
Microglia
Myelin Sheath
Transmission Electron Microscopy
Astrocytes
Pathology
Cognition
DNA Damage
Reflex
Hippocampus
Dynamic response
Rats
Head
Weights and Measures
Transmission electron microscopy

Cite this

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title = "Differential responses to increasing numbers of mild traumatic brain injury in a rodent closed-head injury model",
abstract = "Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. To compare chronic damage and deficits following increasing numbers of repeated mTBIs, a closed-head weight-drop model of repeated mTBI was used to deliver 1, 2 or 3 mTBIs to adult female rats at 24 h intervals. Outcomes were assessed at 3 months following the first mTBI. No gross motor, sensory or reflex deficits were identified (p > 0.05), consistent with current literature. Cognitive function assessed using a Morris water maze revealed chronic memory deficits following 1 and 2, but not 3 mTBI compared to shams (p ≤ 0.05). Oxidative damage to DNA was assessed immunohistochemically in the dentate hilus of the hippocampus and splenium of the corpus callosum; no changes were observed. IBA1 positive microglia were increased in size in the cortex following 1 mTBI and in the corpus callosum following 2 mTBI compared to shams (p ≤ 0.05); no changes were observed in the dentate hilus. GFAP positive astrocyte immunoreactivity was assessed in all three brain regions and no chronic changes were observed. Integrity of myelin ultrastructure in the corpus callosum was assessed using transmission electron microscopy. G ratio was decreased following 2 mTBIs compared to shams (p ≤ 0.05) at post-hoc level only. The changing patterns of damage and deficits following increasing numbers of mTBI may reflect dynamic responses to small numbers of mTBIs or a conditioning effect such that increasing numbers of mild traumatic brain injuries do not necessarily result in worsening pathology. This article is protected by copyright. All rights reserved.",
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author = "Brooke Fehily and Bartlett, {Carole A} and Stephen Lydiard and Michael Archer and Hannah Milbourn and Maimuna Majimbi and Hemmi, {Jan M} and Dunlop, {Sarah A} and Yates, {Nathanael J} and Melinda Fitzgerald",
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Differential responses to increasing numbers of mild traumatic brain injury in a rodent closed-head injury model. / Fehily, Brooke; Bartlett, Carole A; Lydiard, Stephen; Archer, Michael; Milbourn, Hannah; Majimbi, Maimuna; Hemmi, Jan M; Dunlop, Sarah A; Yates, Nathanael J; Fitzgerald, Melinda.

In: Journal of Neurochemistry, Vol. 149, No. 5, 06.2019, p. 660-678.

Research output: Contribution to journalArticle

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AU - Fehily, Brooke

AU - Bartlett, Carole A

AU - Lydiard, Stephen

AU - Archer, Michael

AU - Milbourn, Hannah

AU - Majimbi, Maimuna

AU - Hemmi, Jan M

AU - Dunlop, Sarah A

AU - Yates, Nathanael J

AU - Fitzgerald, Melinda

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N2 - Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. To compare chronic damage and deficits following increasing numbers of repeated mTBIs, a closed-head weight-drop model of repeated mTBI was used to deliver 1, 2 or 3 mTBIs to adult female rats at 24 h intervals. Outcomes were assessed at 3 months following the first mTBI. No gross motor, sensory or reflex deficits were identified (p > 0.05), consistent with current literature. Cognitive function assessed using a Morris water maze revealed chronic memory deficits following 1 and 2, but not 3 mTBI compared to shams (p ≤ 0.05). Oxidative damage to DNA was assessed immunohistochemically in the dentate hilus of the hippocampus and splenium of the corpus callosum; no changes were observed. IBA1 positive microglia were increased in size in the cortex following 1 mTBI and in the corpus callosum following 2 mTBI compared to shams (p ≤ 0.05); no changes were observed in the dentate hilus. GFAP positive astrocyte immunoreactivity was assessed in all three brain regions and no chronic changes were observed. Integrity of myelin ultrastructure in the corpus callosum was assessed using transmission electron microscopy. G ratio was decreased following 2 mTBIs compared to shams (p ≤ 0.05) at post-hoc level only. The changing patterns of damage and deficits following increasing numbers of mTBI may reflect dynamic responses to small numbers of mTBIs or a conditioning effect such that increasing numbers of mild traumatic brain injuries do not necessarily result in worsening pathology. This article is protected by copyright. All rights reserved.

AB - Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. To compare chronic damage and deficits following increasing numbers of repeated mTBIs, a closed-head weight-drop model of repeated mTBI was used to deliver 1, 2 or 3 mTBIs to adult female rats at 24 h intervals. Outcomes were assessed at 3 months following the first mTBI. No gross motor, sensory or reflex deficits were identified (p > 0.05), consistent with current literature. Cognitive function assessed using a Morris water maze revealed chronic memory deficits following 1 and 2, but not 3 mTBI compared to shams (p ≤ 0.05). Oxidative damage to DNA was assessed immunohistochemically in the dentate hilus of the hippocampus and splenium of the corpus callosum; no changes were observed. IBA1 positive microglia were increased in size in the cortex following 1 mTBI and in the corpus callosum following 2 mTBI compared to shams (p ≤ 0.05); no changes were observed in the dentate hilus. GFAP positive astrocyte immunoreactivity was assessed in all three brain regions and no chronic changes were observed. Integrity of myelin ultrastructure in the corpus callosum was assessed using transmission electron microscopy. G ratio was decreased following 2 mTBIs compared to shams (p ≤ 0.05) at post-hoc level only. The changing patterns of damage and deficits following increasing numbers of mTBI may reflect dynamic responses to small numbers of mTBIs or a conditioning effect such that increasing numbers of mild traumatic brain injuries do not necessarily result in worsening pathology. This article is protected by copyright. All rights reserved.

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