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Vimentin and GFAP responses in astrocytes after contusion trauma to the murine brain
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2010 (English)In: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627, Vol. 28, no 3, 311-321 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: Astroglial responses after traumatic brain injury are difficult to detect with routine morphological methods. The aims for this study were to compare the temporal and spatial expression pattern of vimentin-and glial fibrillary acidic protein (GFAP) in a weight drop model of mild cerebral contusion injury in the rat. We also wanted to study the vimentin response with immunohistochemistry and vimentin mRNA RT-PCR analysis in severe cortical contusion injury produced by the controlled cortical impact in the mouse. Methods: Vimentin and GFAP immunohistochemistry (1day, 3 days and 7 days) combined with vimentin mRNA RT-PCR analysis (1 h, 4 h, 22 h, 3 days and 7 days) were used after experimental traumatic brain injury in the rat and mouse. Results: Increases in post-traumatic vimentin mRNA levels in the cortex and in the hippocampus appeared together with vimentin immunoreactivity in astrocytes in the perimeter of the cortical lesion, in the subcortical white matter and in the hippocampus starting at one day after severe trauma. GFAP immunostaining revealed hypertrophic astrocytes peaking at day 3 in the perifocal cortical region. There was no significant increase in GFAP immunoreactivity in the white matter in the rat. However, in the mouse there was a slight increase in the number of GFAP positive cells in this region, 3 days after trauma. Overall the pattern of vimentin immunoreactivity was very similar in the rat and mouse. Conclusions: Vimentin immunoreactivity was more sensitive than the GFAP staining method to demonstrate the distribution and time course of astrocyte reactions after a contusion injury, especially in the white matter distant from the cortical lesion.

Place, publisher, year, edition, pages
2010. Vol. 28, no 3, 311-321 p.
Keyword [en]
Traumatic brain injury, rat, mouse, astrocytes, gliosis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-136066DOI: 10.3233/RNN-2010-0529ISI: 000278442500002OAI: oai:DiVA.org:uu-136066DiVA: diva2:376136
Available from: 2010-12-10 Created: 2010-12-09 Last updated: 2017-12-11Bibliographically 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)
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Available from: 2013-05-24 Created: 2012-07-03 Last updated: 2013-08-30

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