Ligustilide Ameliorates Traumatic Brain Injury in Aged Mice by Attenuating Microglia-Mediated Neuroinflammation

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jianfei Wu, Binyou Wang, Youguo Tan, Kezhi Liu, Xin Liu, Shuang Liu, Duanfang Cai, Yu Liu
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Abstract

Traumatic brain injury (TBI) is common in the aged population and rapidly triggers a pro-inflammatory response in microglia, leading to severe secondary damage. Ligustilide (LIG), a natural compound with excellent blood-brain barrier (BBB) penetration, shows great potential in neuroprotection, primarily due to its anti-inflammatory, antioxidant, and pro-autophagic properties. However, the role of LIG in elderly TBI remains unclear. This study aims to investigate the effects of LIG on elderly TBI and explore its mechanisms of action. In vivo, we assessed the impact of LIG on behavioral outcomes in elderly TBI mice using the modified Neurological Severity Score (mNSS), open field test (OFT), and Morris water maze (MWM) experiment. We also measured the expression of microglial polarization-related proteins and pro-inflammatory cytokines, as well as the distribution and expression of neuronal marker NeuN and astrocytic marker GFAP. In vitro, we examined the effects of LIG on reactive oxygen species (ROS), mitochondrial membrane potential changes, and apoptosis rates in oxygen-glucose deprivation (OGD) BV-2 cells, as well as the expression of microglial polarization-related proteins. The results demonstrated that LIG promoted the polarization of microglia from the M1 to M2 phenotype in the brain injury side, reduced the release of inflammatory factors, enhanced autophagy, ensured neuronal survival, and improved neurological deficits and memory impairments in aged TBI mice. In conclusion, LIG attenuates TBI pathology in aged mice by driving microglial polarization from M1 to M2 phenotypes and enhancing autophagy. This provides a new therapeutic strategy for TBI in aged males.

藁本内酯通过减轻小胶质细胞介导的神经炎症改善老年小鼠创伤性脑损伤
创伤性脑损伤(TBI)在老年人群中很常见,并迅速触发小胶质细胞的促炎反应,导致严重的继发性损伤。liguslide (LIG)是一种具有良好血脑屏障(BBB)渗透性的天然化合物,主要由于其抗炎、抗氧化和促自噬的特性,在神经保护方面显示出巨大的潜力。然而,LIG在老年TBI中的作用尚不清楚。本研究旨在探讨LIG对老年TBI的影响,并探讨其作用机制。在体内,我们通过改良的神经严重程度评分(mNSS)、开放场测试(OFT)和Morris水迷宫(MWM)实验评估了LIG对老年TBI小鼠行为结局的影响。我们还测量了小胶质极化相关蛋白和促炎细胞因子的表达,以及神经元标记物NeuN和星形胶质细胞标记物GFAP的分布和表达。在体外,我们检测了LIG对氧-葡萄糖剥夺(OGD) BV-2细胞活性氧(ROS)、线粒体膜电位变化、凋亡率以及小胶质极化相关蛋白表达的影响。结果表明,LIG促进脑损伤侧小胶质细胞从M1表型向M2表型极化,减少炎症因子的释放,增强自噬,确保神经元存活,改善老年TBI小鼠神经功能缺损和记忆障碍。综上所述,LIG通过驱动小胶质细胞从M1表型到M2表型的极化和增强自噬来减轻老年小鼠TBI病理。这为老年男性创伤性脑损伤提供了一种新的治疗策略。
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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