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Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice

The weight-drop model is used widely to replicate closed-head injuries in mice; however, the histopathological and functional outcomes may vary significantly between laboratories. Because skull fractures are reported to occur in this model, we aimed to evaluate whether these breaks may influence the...

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Autores principales: Zvejniece, Liga, Stelfa, Gundega, Vavers, Edijs, Kupats, Einars, Kuka, Janis, Svalbe, Baiba, Zvejniece, Baiba, Albert-Weissenberger, Christiane, Sirén, Anna-Leena, Plesnila, Nikolaus, Dambrova, Maija
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964812/
https://www.ncbi.nlm.nih.gov/pubmed/31441378
http://dx.doi.org/10.1089/neu.2019.6524
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author Zvejniece, Liga
Stelfa, Gundega
Vavers, Edijs
Kupats, Einars
Kuka, Janis
Svalbe, Baiba
Zvejniece, Baiba
Albert-Weissenberger, Christiane
Sirén, Anna-Leena
Plesnila, Nikolaus
Dambrova, Maija
author_facet Zvejniece, Liga
Stelfa, Gundega
Vavers, Edijs
Kupats, Einars
Kuka, Janis
Svalbe, Baiba
Zvejniece, Baiba
Albert-Weissenberger, Christiane
Sirén, Anna-Leena
Plesnila, Nikolaus
Dambrova, Maija
author_sort Zvejniece, Liga
collection PubMed
description The weight-drop model is used widely to replicate closed-head injuries in mice; however, the histopathological and functional outcomes may vary significantly between laboratories. Because skull fractures are reported to occur in this model, we aimed to evaluate whether these breaks may influence the variability of the weight-drop (WD) model. Male Swiss Webster mice underwent WD injury with either a 2 or 5 mm cone tip, and behavior was assessed at 2 h and 24 h thereafter using the neurological severity score. The expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 genes was measured at 12 h and 1, 3, and 14 days after injury. Before the injury, micro-computed tomography (micro-CT) was performed to quantify skull thickness at the impact site. With a conventional tip diameter of 2 mm, 33% of mice showed fractures of the parietal bone; the 5 mm tip produced only 10% fractures. Compared with mice without fractures, mice with fractures had a severity-dependent worse functional outcome and a more pronounced upregulation of inflammatory genes in the brain. Older mice were associated with thicker parietal bones and were less prone to skull fractures. In addition, mice that underwent traumatic brain injury (TBI) with skull fracture had macroscopic brain damage because of skull depression. Skull fractures explain a considerable proportion of the variability observed in the WD model in mice—i.e., mice with skull fractures have a much stronger inflammatory response than do mice without fractures. Using older mice with thicker skull bones and an impact cone with a larger diameter reduces the rate of skull fractures and the variability in this very useful closed-head TBI model.
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spelling pubmed-69648122020-02-10 Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice Zvejniece, Liga Stelfa, Gundega Vavers, Edijs Kupats, Einars Kuka, Janis Svalbe, Baiba Zvejniece, Baiba Albert-Weissenberger, Christiane Sirén, Anna-Leena Plesnila, Nikolaus Dambrova, Maija J Neurotrauma Original Articles The weight-drop model is used widely to replicate closed-head injuries in mice; however, the histopathological and functional outcomes may vary significantly between laboratories. Because skull fractures are reported to occur in this model, we aimed to evaluate whether these breaks may influence the variability of the weight-drop (WD) model. Male Swiss Webster mice underwent WD injury with either a 2 or 5 mm cone tip, and behavior was assessed at 2 h and 24 h thereafter using the neurological severity score. The expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 genes was measured at 12 h and 1, 3, and 14 days after injury. Before the injury, micro-computed tomography (micro-CT) was performed to quantify skull thickness at the impact site. With a conventional tip diameter of 2 mm, 33% of mice showed fractures of the parietal bone; the 5 mm tip produced only 10% fractures. Compared with mice without fractures, mice with fractures had a severity-dependent worse functional outcome and a more pronounced upregulation of inflammatory genes in the brain. Older mice were associated with thicker parietal bones and were less prone to skull fractures. In addition, mice that underwent traumatic brain injury (TBI) with skull fracture had macroscopic brain damage because of skull depression. Skull fractures explain a considerable proportion of the variability observed in the WD model in mice—i.e., mice with skull fractures have a much stronger inflammatory response than do mice without fractures. Using older mice with thicker skull bones and an impact cone with a larger diameter reduces the rate of skull fractures and the variability in this very useful closed-head TBI model. Mary Ann Liebert, Inc., publishers 2020-01-15 2019-12-20 /pmc/articles/PMC6964812/ /pubmed/31441378 http://dx.doi.org/10.1089/neu.2019.6524 Text en © Liga Zvejniece et al., 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Original Articles
Zvejniece, Liga
Stelfa, Gundega
Vavers, Edijs
Kupats, Einars
Kuka, Janis
Svalbe, Baiba
Zvejniece, Baiba
Albert-Weissenberger, Christiane
Sirén, Anna-Leena
Plesnila, Nikolaus
Dambrova, Maija
Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice
title Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice
title_full Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice
title_fullStr Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice
title_full_unstemmed Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice
title_short Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice
title_sort skull fractures induce neuroinflammation and worsen outcomes after closed head injury in mice
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964812/
https://www.ncbi.nlm.nih.gov/pubmed/31441378
http://dx.doi.org/10.1089/neu.2019.6524
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