{"title":"Ligustilide Ameliorates Traumatic Brain Injury in Aged Mice by Attenuating Microglia-Mediated Neuroinflammation","authors":"Jianfei Wu, Binyou Wang, Youguo Tan, Kezhi Liu, Xin Liu, Shuang Liu, Duanfang Cai, Yu Liu","doi":"10.1007/s11064-025-04560-2","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s11064-025-04560-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.