Distinct cellular patterns of upregulated chemokine expression supporting a prominent inflammatory role in traumatic brain injury
2008 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 25, no 8, 959-974 p.Article in journal (Refereed) Published
Cerebral gene expressions change in response to traumatic brain injury (TBI), and future trauma treatment may improve with increased knowledge about these regulations. We subjected C57BL/6J mice to injury by controlled cortical impact (CCI). At various time points post-injury, mRNA from neocortex and hippocampus was isolated, and transcriptional alterations studied using quantitative real-time polymerase chain reaction (PCR) and gene array analysis. Spatial distribution of enhanced expression was characterized by in situ hybridization. Products of the upregulated transcripts serve functions in a range of cellular mechanisms, including stress, inflammation and immune responses, and tissue remodeling. We also identified increased transcript levels characterizing reactive astrocytes, oligodendrocytes, and microglia, and furthermore, we demonstrated a novel pattern of scattered cell clusters expressing the chemokine Cxcl10. Notably, a sustained increase in integrin alpha X (Itgax), characterizing antigen-presenting dendritic cells, was found with the transcript located to similar cell clusters. In contrast, T-cell receptor alpha transcript showed only a modest increase. The induced P-selectin (Selp) expression level in endothelial cells, and chemokines from microglia, may guide perivascular accumulation of extravasating inflammatory monocytes differentiating into dendritic cells. In conclusion, our study shows that following TBI, secondary injury chiefly involves inflammatory processes and chemokine signaling, which comprise putative targets for pharmaceutical neuroprotection.
Place, publisher, year, edition, pages
2008. Vol. 25, no 8, 959-974 p.
Cxcl10, dendritic cells, inflammatory monocytes, integrin alpha X, TBI
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-102572DOI: 10.1089/neu.2008.0562ISI: 000258895700002PubMedID: 18665806OAI: oai:DiVA.org:uu-102572DiVA: diva2:216406