关键词: Autophagy Mild traumatic brain injury Neuro-inflammation Triptolide

来  源:   DOI:10.1016/j.ibneur.2024.05.007   PDF(Pubmed)

Abstract:
Concussions sustained while playing sports are a prominent cause of mild traumatic brain injury (mTBI), which is prevalent among teenagers. The early and intermediate stages of mild traumatic brain injury (mTBI) can be characterized by inflammation, neurodegeneration, and brain tissue edema, which can lead to permanent brain damage. The present study investigated the therapeutic effects of triptolide in mTBI and brain damage recovery. After building mTBI model in male rat, triptolide administrated daily for 1 week in the treated group. On day 3 and day 7 of administration, hippocampus tissues were collected to evaluate inflammation and autophagy in the brain. The expressions of inflammatory factors interleukin (IL)-1β and tumor necrosis factor-alpha in serum were downregulated, while IL-10 expression was upregulated when compared with the mTBI group on day 3 and day 7. The expression of IL-10 on day 7 was higher than on day 3. Quantitative polymerase chain reaction (qPCR) analysis of inflammatory-related factors (i.e., Il-1β and nuclear factor-κB (Nf-κb), and western blot as well as immunofluorescence staining of autophagy-related proteins (i.e., LC3B) and aquaporin (AQP 4) showed lower expression on day 3 and day 7 in the triptolide-treated group. Moreover, NeuN immunostaining, and hematoxylin and eosin (HE) staining for hippocampus region revealed that the triptolide-treated group showed a decrease in damaged cells. Our findings emphasize the effectiveness of triptolide therapy after mild traumatic brain injury via modulating autophagy, attenuating inflammation and reduces edema by decreasing AQP 4 expression.
摘要:
运动时持续的脑震荡是轻度创伤性脑损伤(mTBI)的主要原因,这在青少年中很普遍。轻度创伤性脑损伤(mTBI)的早期和中期阶段可以以炎症为特征,神经变性,和脑组织水肿,会导致永久性脑损伤.本研究调查了雷公藤甲素在mTBI和脑损伤恢复中的治疗作用。在雄性大鼠建立mTBI模型后,治疗组每日给予雷公藤甲素,持续1周。在给药的第3天和第7天,收集海马组织以评估大脑中的炎症和自噬。血清炎症因子白细胞介素(IL)-1β和肿瘤坏死因子-α表达下调,而与mTBI组相比,IL-10表达在第3天和第7天上调。第7天的IL-10表达高于第3天。定量聚合酶链反应(qPCR)分析炎症相关因子(即,IL-1β和核因子-κB(NF-κb),和蛋白质印迹以及自噬相关蛋白的免疫荧光染色(即,LC3B)和水通道蛋白(AQP4)在雷公藤甲素治疗组的第3天和第7天显示较低的表达。此外,NeuN免疫染色,海马区苏木精和伊红(HE)染色显示雷公藤甲素治疗组受损细胞减少。我们的研究结果强调了雷公藤甲素通过调节自噬治疗轻度创伤性脑损伤后的有效性,通过降低AQP4表达减轻炎症和减轻水肿。
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