Background: Traumatic brain injury is the leading cause of acquired neurologic disability in children. In our model of pediatric traumatic brain injury, controlled cortical impact (CCI) in rat pups, docosahexaenoic acid (DHA) improved lesion volume and cognitive testing as late as postinjury day (PID) 50. Docosahexaenoic acid decreased proinflammatory messenger RNA (mRNA) in microglia and macrophages at PIDs 3 and 7, but not 30. We hypothesized that DHA affected inflammatory markers differentially relative to impact proximity, early and persistently after CCI. Methods: To provide a temporal snapshot of regional neuroinflammation, we measured 18-kDa translocator protein (TSPO) binding using whole brain autoradiography at PIDs 3, 7, 30, and 50. Guided by TSPO results, we measured mRNA levels in contused cortex and underlying hippocampus for genes associated with proinflammatory and inflammation-resolving states at PIDs 2 and 3. Results: Controlled cortical impact increased TSPO binding at all time points, most markedly at PID 3 and in regions closest to impact, not blunted by DHA. Controlled cortical impact increased cortical and hippocampal mRNA proinflammatory markers, blunted by DHA at PID 2 in hippocampus. Conclusion: Controlled cortical impact increased TSPO binding in the immature brain in a persistent manner more intensely with more severe injury, not altered by DHA. Controlled cortical impact increased PIDs 2 and 3 mRNA levels of proinflammatory and inflammation-resolving genes. Docosahexaenoic acid decreased proinflammatory markers associated with inflammasome activation at PID 2. We speculate that DHA's salutary effects on long-term outcomes result from early effects on the inflammasome. Future studies will examine functional effects of DHA on microglia both early and late after CCI.
|Number of pages||8|
|Journal||Journal of Trauma and Acute Care Surgery|
|State||Published - 2021|
Bibliographical noteFunding Information:
The authors declare no conflicts of interest. This work was supported by the NINDS grant number 5R21 NS090098-02, National Institutes of Health, and by Pediatric Critical Care Medicine at the University of Utah. Neither funding agency had any role in the study design; data collection, analysis, and interpretation; writing of the report; or decision to submit the article for publication.
© 2021 Wolters Kluwer Health, Inc. All rights reserved.
- Developing brain
- Polyunsaturated fatty acids
- Traumatic brain injury
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine