Mild closed-head injury in conscious rats causes transient neurobehavioral and glial disturbances

A novel experimental model of concussion

Louise Pham, Sandy R. Shultz, Hyun Ah Kim, Rhys Brady, Ryan Cristopher Wortman, Shannyn G. Genders, Matthew W. Hale, Ross O'Shea, Elvan Djouma, Maarten van den Buuse, Jarrod E. Church, Brian R. Christie, Grant Drummond, Christopher G Sobey, Stuart McDonald

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Rodent models can provide insights into the most pertinent issues surrounding concussion. Nonetheless, the relevance of some existing models to clinical concussion can be questioned, particularly with regard to the use of surgery and anesthesia and the mechanism and severity of injury. Accordingly, we have co-developed an awake closed-head injury (ACHI) model in rats. Here, we aimed to create a temporal profile of the neurobehavioral and neuropathological effects of a single ACHI. Adolescent male rats were placed in a restraint bag and a steel helmet was positioned over the head such that the impact target was centered over the left parietal cortex. Once positioned on a foam platform, a cortical impactor was used to strike the helmet. Sham animals underwent the same procedure without impact. When compared with sham rats, those given a single ACHI displayed evidence of sensorimotor deficits and reduced exploratory behavior within the first 20 min post-injury; however, these effects were resolved after 24 h. A single ACHI impaired spatial memory on the Y-maze task at both 5 min and 24 h post-ACHI; however, no deficits were apparent at 48 h. Immunostaining revealed region-specific increases in ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression at 3 days post-impact, with no differences found at either 1 or 14 days. Taken together, our findings indicate that a single ACHI results in transient neurobehavioral and glial disturbances and as such, this model may be a valuable tool for pre-clinical concussion research.

Original languageEnglish
Pages (from-to)2260-2271
Number of pages12
JournalJournal of Neurotrauma
Volume36
Issue number14
DOIs
Publication statusPublished - 15 Jul 2019

Keywords

  • anesthesia
  • astrocytes
  • behavior
  • microglia
  • mild traumatic brain injury
  • neuroinflammation

Cite this

Pham, Louise ; Shultz, Sandy R. ; Kim, Hyun Ah ; Brady, Rhys ; Wortman, Ryan Cristopher ; Genders, Shannyn G. ; Hale, Matthew W. ; O'Shea, Ross ; Djouma, Elvan ; van den Buuse, Maarten ; Church, Jarrod E. ; Christie, Brian R. ; Drummond, Grant ; Sobey, Christopher G ; McDonald, Stuart. / Mild closed-head injury in conscious rats causes transient neurobehavioral and glial disturbances : A novel experimental model of concussion. In: Journal of Neurotrauma. 2019 ; Vol. 36, No. 14. pp. 2260-2271.
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abstract = "Rodent models can provide insights into the most pertinent issues surrounding concussion. Nonetheless, the relevance of some existing models to clinical concussion can be questioned, particularly with regard to the use of surgery and anesthesia and the mechanism and severity of injury. Accordingly, we have co-developed an awake closed-head injury (ACHI) model in rats. Here, we aimed to create a temporal profile of the neurobehavioral and neuropathological effects of a single ACHI. Adolescent male rats were placed in a restraint bag and a steel helmet was positioned over the head such that the impact target was centered over the left parietal cortex. Once positioned on a foam platform, a cortical impactor was used to strike the helmet. Sham animals underwent the same procedure without impact. When compared with sham rats, those given a single ACHI displayed evidence of sensorimotor deficits and reduced exploratory behavior within the first 20 min post-injury; however, these effects were resolved after 24 h. A single ACHI impaired spatial memory on the Y-maze task at both 5 min and 24 h post-ACHI; however, no deficits were apparent at 48 h. Immunostaining revealed region-specific increases in ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression at 3 days post-impact, with no differences found at either 1 or 14 days. Taken together, our findings indicate that a single ACHI results in transient neurobehavioral and glial disturbances and as such, this model may be a valuable tool for pre-clinical concussion research.",
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author = "Louise Pham and Shultz, {Sandy R.} and Kim, {Hyun Ah} and Rhys Brady and Wortman, {Ryan Cristopher} and Genders, {Shannyn G.} and Hale, {Matthew W.} and Ross O'Shea and Elvan Djouma and {van den Buuse}, Maarten and Church, {Jarrod E.} and Christie, {Brian R.} and Grant Drummond and Sobey, {Christopher G} and Stuart McDonald",
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Mild closed-head injury in conscious rats causes transient neurobehavioral and glial disturbances : A novel experimental model of concussion. / Pham, Louise; Shultz, Sandy R.; Kim, Hyun Ah; Brady, Rhys; Wortman, Ryan Cristopher; Genders, Shannyn G. ; Hale, Matthew W.; O'Shea, Ross; Djouma, Elvan; van den Buuse, Maarten; Church, Jarrod E.; Christie, Brian R.; Drummond, Grant; Sobey, Christopher G; McDonald, Stuart.

In: Journal of Neurotrauma, Vol. 36, No. 14, 15.07.2019, p. 2260-2271.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Kim, Hyun Ah

AU - Brady, Rhys

AU - Wortman, Ryan Cristopher

AU - Genders, Shannyn G.

AU - Hale, Matthew W.

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AU - Djouma, Elvan

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AU - Church, Jarrod E.

AU - Christie, Brian R.

AU - Drummond, Grant

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AU - McDonald, Stuart

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