Neuroinflammation is a major pathophysiological feature of traumatic brain injury (TBI). Early and persistent activation of innate immune response signaling pathways by primary injuries is associated with secondary cellular injuries that cause TBI outcomes to change over time. We used a Drosophila melanogaster model to investigate the role of antimicrobial peptides (AMPs) in acute and chronic outcomes of closed-head TBI. AMPs are effectors of pathogen and stress defense mechanisms mediated by the evolutionarily conserved Toll and Immune-deficiency (Imd) innate immune response pathways that activate Nuclear Factor kappa B (NF-B) transcription factors. Here, we analyzed the effect of null mutations in 10 of the 14 known Drosophila AMP genes on TBI outcomes. We found that mutation of Metchnikowin (Mtk) was unique in protecting flies from mortality within the 24 h following TBI under two diet conditions that produce different levels of mortality. In addition, Mtk mutants had reduced behavioral deficits at 24 h following TBI and increased lifespan either in the absence or presence of TBI. Using a transcriptional reporter of gene expression, we found that TBI increased Mtk expression in the brain. Quantitative analysis of mRNA in whole flies revealed that expression of other AMPs in the Toll and Imd pathways as well as NF-B transcription factors were not altered in Mtk mutants. Overall, these results demonstrate that Mtk plays an infection-independent role in the fly nervous system, and TBI-induced expression of Mtk in the brain activates acute and chronic secondary injury pathways that are also activated during normal aging.

神经炎症是创伤性脑损伤（TBI）的主要病理生理学特征。原发性损伤对先天免疫反应信号通路的早期和持续激活与继发性细胞损伤相关，继发性细胞损伤导致 TBI 结果随时间变化。我们使用果蝇模型来研究抗菌肽 (AMP) 在闭头 TBI 急性和慢性结局中的作用。 AMP 是病原体和应激防御机制的效应器，由进化上保守的 Toll 和免疫缺陷 (Imd) 先天免疫反应途径介导，可激活核因子 kappa B (NF-B) 转录因子。在这里，我们分析了 14 个已知果蝇AMP 基因中 10 个的无效突变对 TBI 结局的影响。我们发现，在两种产生不同死亡率水平的饮食条件下， Metchnikowin ( Mtk ) 的突变在 TBI 后 24 小时内保护果蝇免于死亡方面具有独特的作用。此外， Mtk突变体在 TBI 后 24 小时减少了行为缺陷，并且在没有或存在 TBI 的情况下延长了寿命。使用基因表达转录报告基因，我们发现 TBI 增加了大脑中Mtk的表达。对整个果蝇 mRNA 的定量分析表明，Toll 和 Imd 通路中的其他 AMP 以及 NF-B 转录因子的表达在Mtk突变体中没有改变。总的来说，这些结果表明Mtk在果蝇神经系统中发挥着独立于感染的作用，并且 TBI 诱导的Mtk在大脑中的表达激活了急性和慢性继发性损伤途径，这些途径在正常衰老过程中也会被激活。