Closed head injury in a mouse model results in molecular changes indicating inflammatory responses

Charlotte Israelsson, Yun Wang, Annika Kylberg, Chaim G. Pick, Barry J. Hoffer, Ted Ebendal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Cerebral gene expression changes in response to traumatic brain injury will provide useful information in the search for future trauma treatment. In order to characterize the outcome of mild brain injury, we studied C57BL/6J mice in a weight-drop, closed head injury model. At various times post-injury, mRNA was isolated from neocortex and hippocampus and transcriptional alterations were studied using quantitative reverse transcriptase PCR and gene array analysis. At three days post-injury, the results showed unilateral injury responses, both in neocortex and hippocampus, with the main effect seen on the side of the skull hit by the dropping weight. Upregulated transcripts encoded products characterizing reactive astrocytes, phagocytes, microglia, and immune-reactive cells. Markers for oligodendrocytes and T-cells were not altered. Notably, strong differences in the responses among individual mice were seen (e.g., for the Gfap transcript expressed by reactive astrocytes and the chemokine Ccl3 transcript expressed by activated microglial cells). In conclusion, mild TBI chiefly activates transcripts leading to tissue signaling, inflammatory processes, and chemokine signaling, as in focal brain injury, suggesting putative targets for drug development.

Original languageEnglish
Pages (from-to)1307-1314
Number of pages8
JournalJournal of Neurotrauma
Volume26
Issue number8
DOIs
StatePublished - 1 Aug 2009

Funding

FundersFunder number
National Institute on Drug AbuseZIADA000429

    Keywords

    • Closed head injury
    • GeneChip array
    • Inflammation
    • Mild trauma
    • Quantitative RT-PCR
    • Weight drop impact

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