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Ibuprofen attenuates the inflammatory response and allows formation of migratory neuroblasts from grafted stem cells after traumatic brain injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. 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, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
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2012 (English)In: Restorative Neurology and Neuroscience, ISSN 0922-6028, Vol. 30, no 1, 9-19 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: There is hope for neural stem and progenitor cells (NSPC) to enhance regeneration when transplanted to the injured brain after traumatic brain injury (TBI). So far, the therapeutic effects of NSPC transplantation have been hampered mainly by the notable death of the transplanted cells. Neuroinflammation may lead to additional cell death after TBI and we hypothesized that survival of grafted NSPC could be enhanced by anti-inflammatory treatment.

Methods: Mice that were subjected to controlled cortical impact TBI and grafted with NSPC, were treated with the non-steroidal anti-inflammatory drug ibuprofen.

Results: Ibuprofen was found to down-regulate the TBI-induced inflammatory response. In addition, migrating neuroblasts from transplanted cells were observed near the contusion and in the ipsilateral hippocampus in ibuprofen-treated animals only, suggesting that the anti-inflammatory treatment had beneficial effects on graft survival and/or differentiation. However, Morris Water Maze performance or TBI-induced tissue loss was not influenced by ibuprofen treatment.

Conclusions: Our data suggests that anti-inflammatory strategies may be a complement to enhance the outcome for the cell transplants following TBI.

Place, publisher, year, edition, pages
2012. Vol. 30, no 1, 9-19 p.
Keyword [en]
Neural stem cell, regeneration, transplantation, controlled cortical impact, eGFP
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-110094DOI: 10.3233/RNN-2011-0606ISI: 000300955300002OAI: oai:DiVA.org:uu-110094DiVA: diva2:275183
Available from: 2009-11-03 Created: 2009-11-03 Last updated: 2012-03-28Bibliographically approved
In thesis
1. Neural Stem and Progenitor Cells as a Tool for Tissue Regeneration
Open this publication in new window or tab >>Neural Stem and Progenitor Cells as a Tool for Tissue Regeneration
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neural stem and progenitor cells (NSPC) can differentiate to neurons and glial cells. NSPC are easily propagated in vitro and are therefore an attractive tool for tissue regeneration. Traumatic brain injury (TBI) is a common cause for death and disabilities. A fundamental problem following TBI is tissue loss. Animal studies aiming at cell replacement have encountered difficulties in achieving sufficient graft survival and differentiation. To improve outcome of grafted cells after experimental TBI (controlled cortical impact, CCI) in mice, we compared two transplantation settings. NSPC were transplanted either directly upon CCI to the injured parenchyma, or one week after injury to the contralateral ventricle. Enhanced survival of transplanted cells and differentiation were seen when cells were deposited in the ventricle. To further enhance cell survival, efforts were made to reduce the inflammatory response to TBI by administration of ibuprofen to mice that had been subjected to CCI. Inflammation was reduced, as monitored by a decrease in inflammatory markers. Cell survival as well as differentiation to early neuroblasts seemed to be improved.

To device a 3D system for future transplantation studies, NSPC from different ages were cultured in a hydrogel consisting of hyaluronan and collagen. Cells survived and proliferated in this culturing condition and the greatest neuronal differentiating ability was seen in cells from the newborn mouse brain.

NSPC were also used in a model of peripheral nervous system injury, and xeno-transplanted to rats where the dorsal root ganglion had been removed. Cells survived and differentiated to neurons and glia, furthermore demonstrating their usefulness as a tool for tissue regeneration.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 69 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 500
traumatic brain injury, neural stem cells, transplantation, CNS, PNS, progenitor cells, inflammation, CCI
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Neurosurgery; Medical Biochemistry
urn:nbn:se:uu:diva-110095 (URN)978-91-554-7658-8 (ISBN)
Public defence
2009-12-17, B42, Husargatan 3, BMC, 09:15 (Swedish)
Available from: 2009-11-26 Created: 2009-11-03 Last updated: 2009-11-26Bibliographically approved

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Wallenquist, UlrikaHånell, AndersMarklund, NiklasHillered, LarsForsberg-Nilsson, Karin
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