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The Multivariate Concentric Square Field Test Reveals Behavioral Profiles of Risk Taking, Exploration, and Cognitive Impairment in Mice Subjected to Traumatic Brain Injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
2010 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 27, no 9, 1643-1655 p.Article in journal (Refereed) Published
Abstract [en]

There is a need for more efficient tests to evaluate functional outcome following experimental traumatic brain injury (TBI), reflecting deficits in cognitive, sensory, and motor functions that are seen in TBI patients. The Multivariate Concentric Square Field (TM) (MCSF) test is a relatively new behavioral model that measures exploration, risk taking, risk assessment, and shelter seeking, all of which are evolutionarily-conserved strategies for survival. The multivariate design enables scoring of different functional domains in a single test situation, with a free choice of optional environmental settings. Furthermore, repeated trials permits cognitive effects to be measured. In the present study, 11 anesthetized C57BL6 mice received controlled cortical injury (CCI) (0.5mm and 3.3 m/sec) over the right parietal cerebral cortex or sham surgery (n - 12). Naive mice (n 12) not subjected to any surgical procedure were also included. The animals were evaluated in the MCSF test at 2 and 7 days post-surgery, and behavioral profiles were analyzed. The results revealed differences in risk taking and explorative behavior between the sham animals and the animals subjected to trauma. Animals subjected to trauma were characterized by taking more risks and had a higher level of exploration activity, but they sought less shelter. Repeated exposure to the MCSF caused a general decrease in activity in the naive and sham group, while a more specific behavioral impairment was seen in injured mice, suggesting cognitive dysfunction. We submit that the MCSF test is a useful complementary tool for functional outcome evaluation in experimental TBI.

Place, publisher, year, edition, pages
2010. Vol. 27, no 9, 1643-1655 p.
Keyword [en]
cognition, functional outcome, mouse, Multivariate Concentric Square Field Test, traumatic brain injury
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-134829DOI: 10.1089/neu.2009.0953ISI: 000281796500011OAI: oai:DiVA.org:uu-134829DiVA: diva2:373927
Available from: 2010-12-02 Created: 2010-12-01 Last updated: 2017-12-12Bibliographically approved
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)
Opponent
Supervisors
Available from: 2013-05-24 Created: 2012-07-03 Last updated: 2013-08-30

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