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

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dc.contributor.authorZvejniece, Liga
dc.contributor.authorStelfa, Gundega
dc.contributor.authorVavers, Edijs
dc.contributor.authorKupats, Einars
dc.contributor.authorKuka, Janis
dc.contributor.authorSvalbe, Baiba
dc.contributor.authorZvejniece, Baiba
dc.contributor.authorAlbert-Weissenberger, Christiane
dc.contributor.authorSirén, Anna Leena
dc.contributor.authorPlesnila, Nikolaus
dc.contributor.authorDambrova, Maija
dc.contributor.institutionRīga Stradiņš University
dc.date.accessioned2022-01-05T09:55:01Z
dc.date.available2022-01-05T09:55:01Z
dc.date.issued2020-01-15
dc.descriptionPublisher Copyright: © Liga Zvejniece et al., 2020; Published by Mary Ann Liebert, Inc. 2020. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
dc.description.abstractThe 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.en
dc.description.statusPeer reviewed
dc.format.extent10
dc.format.extent418794
dc.identifier.citationZvejniece, L, Stelfa, G, Vavers, E, Kupats, E, Kuka, J, Svalbe, B, Zvejniece, B, Albert-Weissenberger, C, Sirén, A L, Plesnila, N & Dambrova, M 2020, 'Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice', Journal of Neurotrauma, vol. 37, no. 2, pp. 295-304. https://doi.org/10.1089/neu.2019.6524
dc.identifier.doi10.1089/neu.2019.6524
dc.identifier.issn0897-7151
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/7174
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85074992129&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofJournal of Neurotrauma
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectneuroinflammation
dc.subjectskull fracture
dc.subjecttraumatic brain injury
dc.subjectweight-drop model
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectClinical Neurology
dc.titleSkull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Miceen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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