Docosahexaenoic acid decreased inflammatory gene expression, but not 18-kDa translocator protein binding, in rat pup brain after controlled cortical impact.
Docosahexaenoic acid decreased inflammatory gene expression, but not 18-kDa translocator protein binding, in rat pup brain after controlled cortical impact.
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DOI：
10.1097/ta.0000000000003084
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发表时间：
2021-05-01
期刊：
影响因子：
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通讯作者：
Pauly JR
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文献类型：
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作者：
Schober ME;Requena DF;Ohde JW;Maves S;Pauly JR
创伤性脑损伤（TBI）是儿童获得性神经功能障碍的主要原因。在我们的儿科TBI模型中，在大鼠幼仔中控制皮质撞击（CCI），二十二碳六烯酸（DHA）改善了损伤体积和认知测试，最晚至损伤后第50天（PID）。DHA在PID 3和7时降低小胶质细胞和巨噬细胞中的促炎mRNA，但在PID 30时不降低。我们假设，DHA影响炎症标志物差异相对于影响接近，早期和持续后CCI。为了提供局部神经炎症的时间快照，我们使用全脑放射自显影术在PID 3、7、30和50测量TSPO（18-kDa转运蛋白）结合。在TSPO结果的指导下，我们在PID 2和3测量了挫伤皮层和底层海马中与促炎和炎症消退状态相关的基因的mRNA水平。CCI在所有时间点增加TSPO结合，在PID 3和最接近影响的区域最明显，而不是被DHA钝化。CCI增加皮质和海马mRNA促炎标记物，在海马中PID 2被DHA钝化。CCI以持续的方式增加未成熟大脑中TSPO的结合，随着损伤的加重而增加，而不受DHA的影响。CCI增加促炎基因和炎症消退基因的PID 2和3 mRNA水平。DHA降低了PID 2时与炎性小体激活相关的促炎标志物。我们推测，DHA对长期结果的有益作用来自于对炎性小体的早期作用。未来的研究将检查DHA对CCI后早期和晚期小胶质细胞的功能影响。N/A.这不是一项临床研究，而是一篇使用大鼠随机对照的基础科学文章。根据临床研究的证据等级外推，证据等级为II级，研究类型为治疗性。
Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. In our model of pediatric TBI, controlled cortical impact (CCI) in rat pups, Docosahexaenoic Acid (DHA) improved lesion volume and cognitive testing as late as Post Injury Day (PID) 50. DHA decreased pro-inflammatory mRNA in microglia and macrophages at PID 3 and 7, but not 30. We hypothesized that DHA affected inflammatory markers differentially relative to impact proximity, early and persistently after CCI. To provide a temporal snapshot of regional neuroinflammation, we measured TSPO (18-kDa Translocator Protein) binding using whole brain autoradiography at PID 3, 7, 30 and 50. Guided by TSPO results, we measured mRNA levels in contused cortex and underlying hippocampus for genes associated with pro-inflammatory and inflammation-resolving states at PID2 and 3. CCI increased TSPO binding at all time points, most markedly at PID3 and in regions closest to impact, not blunted by DHA. CCI increased cortical and hippocampal mRNA pro-inflammatory markers, blunted by DHA at PID2 in hippocampus. CCI increased TSPO binding in the immature brain in a persistent manner more intensely with more severe injury, not altered by DHA. CCI increased PID2 and 3 mRNA levels of pro-inflammatory and inflammation-resolving genes. DHA decreased pro-inflammatory markers associated with inflammasome activation at PID2. 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. N/A. This is a not a clinical study but a basic science article that is randomized and controlled using rats. Extrapolating from Evidence Levels for clinical studies, the level of evidence would be II and the study type would be therapeutic.