DID YOU KNOW? DTIC has over 3.5 million final reports on DoD funded research, development, test, and evaluation activities available to our registered users. Click
HERE to register or log in.
Accession Number:
ADA581397
Title:
The Role of Microglial Subsets in Regulating Traumatic Brain Injury
Descriptive Note:
Annual rept. 1 Jul 2011-30 Jun 2012
Corporate Author:
NORTHERN CALIFORNIA INST FOR RESEARCH AND EDUCATION SAN FRANCISCO
Report Date:
2012-07-01
Pagination or Media Count:
20.0
Abstract:
Following brain injury, there is an influx of inflammatory cells, especially macrophages, and there is reportedly widespread activation of microglia. Microglia have been divided into two major subgroups i classical or M1 macrophages, which promote inflammation and secrete IL-12, and ii alternatively activated or M2 macriophages, which phagocytose apoptotic cells, promote wound repair, and in mice express arginase 1. We originally proposed that micriglial might also reflect these functional subsets whtih differential effects on TBI. To test this, we are studying TBI in reporter mice that express the fluor YFP undeer control of the promoter for either IL-12 or arginase 1. To date, we have not found activation of either IL-12, or arginase 1 in microglia following TBI, but we do find that TBI induces the CCR2- dependent influx of macrophages that express arginase-1, and that in the first day after injury about 20 of macrophages express arginase-1 at very high levels. We have not seen an effect of PPAR agonists on levels of this subset, but we have recently performed expression arrays on the post-TBI macrophages. The arrays demonstrate that these two cell populations differ from each other not only in the level of expression of arginase-1 but also in multiple other genes, especially chemokines. Neither cell population has the expression profile of M1or M2 cells. Instead, they represent novel macrophage cell populations. We are also performing microarray studies of microglia, following TBI. Our studies to date have not found evidence for microglial subsets, but by using a TBI model with greater impact than before, and by improving sensitivity of analysis, we do find that TBI induces widespread activation of microglia, as demonstrated by up-regulation of surface CD86.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
