Closed head injury in a mouse model results in molecular changes indicating inflammatory responses - PubMed (original) (raw)

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

Charlotte Israelsson et al. J Neurotrauma. 2009 Aug.

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.

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Figures

FIG. 1.

FIG. 1.

Transcriptional changes three days after mTBI in neocortex (CTX) and hippocampus (HC) ipsilaterally and contralaterally analyzed by qRT-PCR. Individual samples from five mice were measured at least twice in duplicate reactions. (A) Gfap expression showed increases on the injured side that did not reach significance. (B) Lyz2 expression showed an increase on the ipsilateral side in both neocortex and hippocampus. (C) Ccl3 expression showed a significant response in hippocampus on both sides and a marked increase in the ipsilateral neocortex. (D) Cxcl10 expression increased but did not reach significant levels. Mean value ± SEM is indicated. Statistical differences to samples from uninjured mice are shown (*p < 0.05; **p < 0.01).

FIG. 2.

FIG. 2.

Ipsilateral gene expression at different time points after mTBI shown by qRT-PCR (uninjured, 4 h, 22 h, 3 days, 7 days). The same mice show elevated levels with both markers. Individual samples from five mice were measured at least twice in duplicate reactions. (A) Gfap levels peak after three days. (B) Ccl3 levels show the largest individual result after seven days. SEM is indicated.

FIG. 3.

FIG. 3.

Neocortical changes using qRT-PCR in several different markers indicating a large variety in response to mTBI. Mean and SEM of samples from five mice were measured individually at least twice in duplicate reactions.

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