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Functional outcome after diffuse traumatic axonal injury in mice is improved by post-injury neutralization of interleukin-1ß
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
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(English)Manuscript (preprint) (Other academic)
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-198738OAI: oai:DiVA.org:uu-198738DiVA: diva2:617607
Available from: 2013-04-23 Created: 2013-04-23 Last updated: 2014-01-02
In thesis
1. Cellular Reactions and Behavioral Changes in Focal and Diffuse Traumatic Brain Injury: A Study in the Rat and Mouse
Open this publication in new window or tab >>Cellular Reactions and Behavioral Changes in Focal and Diffuse Traumatic Brain Injury: A Study in the Rat and Mouse
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Traumatic brain injury (TBI) is a severe condition and a major cause of death and disability. There is no pharmacological treatment available in clinical practice today and knowledge of brain injury mechanisms is of importance for development of neuroprotective drugs. The aims of the thesis were to get a better understanding of astrocyte reactions and immune responses, as well as behavioral changes after focal unilateral cortical contusion injury and diffuse bilateral central fluid percussion injury in rats and mice.

In the focal injury models, the astrocyte reactions were generally restricted to the ipsilateral hemisphere. After diffuse TBI, vimentin and glial fibrillary acidic protein (GFAP) positive reactive astrocytes were bilaterally expressed in brain regions even distant from the injury site, including regions where axonal injury was seen. Early after diffuse TBI, there was a robust immune response, including activation of macrophages/microglia (Mac-2+) and infiltration of neutrophils (GR-1+) and T-cells (CD3+).

In order to measure functional outcome, the recently established Multivariate Concentric Square Field™ (MCSF) test for complex behaviors, including risk taking and explorative strategies was used. The Morris water maze (MWM) was applied for testing learning and memory. The MCSF test revealed alterations in risk taking, risk assessment and exploratory behavior, in the mice subjected to focal injury whereas mice subjected to the diffuse injury showed a deviant stereotyped behavior. After focal injury mice showed a decreased ability to adapt to the arena in the second trial, when tested repeatedly in the MCSF test. Mice subjected to diffuse injury had an impaired memory but not learning, in the MWM test. Post-injury treatment with the anti-inflammatory anti-interleukin-1β (IgG2 a/k) antibody showed a positive effect on functional outcome in the diffuse injury model. Altogether, the results demonstrate that focal and diffuse TBI models produce differences in cellular reactions and behavioral outcome and that the immune response plays a key role in the pathology after brain injury. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 83 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 909
Keyword
Traumatic brain injury, Astrocytes, Inflammatory response, Multivariate concentric square field test, Morris water maze, Exploratory behavior, Risk taking, Functional outcome.
National Category
Neurosciences
Research subject
Neurosurgery
Identifiers
urn:nbn:se:uu:diva-177083 (URN)978-91-554-8687-7 (ISBN)
Public defence
2013-06-14, Hedstrandsalen, Akademiska sjukhuset, 75185, Uppsala, 13:15 (Swedish)
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Supervisors
Available from: 2013-05-24 Created: 2012-07-03 Last updated: 2013-08-30

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Flygt, Johanna

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