{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:43:01Z","timestamp":1791916981310,"version":"4.3.4"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Collaborative Innovation Project of Zigong Medical Big Data and Artificial Intelligence Research Institute","award":["2024-YGY-02-04"],"award-info":[{"award-number":["2024-YGY-02-04"]}]},{"name":"Zigong Science and Technology Program","award":["2023YKY11"],"award-info":[{"award-number":["2023YKY11"]}]},{"name":"Scientific Research Project of Zigong Health Commission","award":["24zd008"],"award-info":[{"award-number":["24zd008"]}]},{"name":"Key Science and Technology Plan Projects in Zigong","award":["2023-NKY-01-02"],"award-info":[{"award-number":["2023-NKY-01-02"]}]},{"name":"Key Science and Technology Plan Projects in Zigong","award":["2023-NKY-02-13"],"award-info":[{"award-number":["2023-NKY-02-13"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2009900"],"award-info":[{"award-number":["2022YFC2009900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurochem Res"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1007\/s11064-025-04560-2","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T08:20:28Z","timestamp":1758961228000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ligustilide Ameliorates Traumatic Brain Injury in Aged Mice by Attenuating Microglia-Mediated Neuroinflammation"],"prefix":"10.1007","volume":"50","author":[{"given":"Jianfei","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binyou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youguo","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kezhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duanfang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"4560_CR1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1001\/jamaneurol.2022.0114","volume":"79","author":"D Waltzman","year":"2022","unstructured":"Waltzman D, Haarbauer-Krupa J, Womack LS (2022) Traumatic brain injury in older adults\u2014a public health perspective. JAMA Neurol 79:437\u2013438. https:\/\/doi.org\/10.1001\/jamaneurol.2022.0114","journal-title":"JAMA Neurol"},{"key":"4560_CR2","doi-asserted-by":"publisher","first-page":"3065","DOI":"10.1002\/alz.12934","volume":"19","author":"NSN Graham","year":"2023","unstructured":"Graham NSN, Cole JH, Bourke NJ, Schott JM, Sharp DJ (2023) Distinct patterns of neurodegeneration after TBI and in Alzheimer\u2019s disease. Alzheimers Dement 19:3065\u20133077. https:\/\/doi.org\/10.1002\/alz.12934","journal-title":"Alzheimers Dement"},{"key":"4560_CR3","doi-asserted-by":"publisher","first-page":"4430","DOI":"10.1007\/s00415-024-12386-1","volume":"271","author":"C Barbiellini Amidei","year":"2024","unstructured":"Barbiellini Amidei C, Salmaso L, Fedeli U, Saia M (2024) Traumatic brain injury incidence and mortality: a large population-based study. J Neurol 271:4430\u20134440. https:\/\/doi.org\/10.1007\/s00415-024-12386-1","journal-title":"J Neurol"},{"key":"4560_CR4","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1111\/j.1532-5415.2010.03011.x","volume":"58","author":"N Zeevi","year":"2010","unstructured":"Zeevi N, Pachter J, McCullough LD, Wolfson L, Kuchel GA (2010) The blood-brain barrier: geriatric relevance of a critical brain-body interface. J Am Geriatr Soc 58:1749\u20131757. https:\/\/doi.org\/10.1111\/j.1532-5415.2010.03011.x","journal-title":"J Am Geriatr Soc"},{"key":"4560_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101955","volume":"88","author":"Y Guo","year":"2023","unstructured":"Guo Y, Guan T, Shafiq K, Yu Q, Jiao X, Na D, Li M, Zhang G, Kong J (2023) Mitochondrial dysfunction in aging. Ageing Res Rev 88:101955. https:\/\/doi.org\/10.1016\/j.arr.2023.101955","journal-title":"Ageing Res Rev"},{"key":"4560_CR6","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.neurobiolaging.2019.02.010","volume":"77","author":"RM Ritzel","year":"2019","unstructured":"Ritzel RM, Doran SJ, Glaser EP, Meadows VE, Faden AI, Stoica BA, Loane DJ (2019) Old age increases microglial senescence, exacerbates secondary neuroinflammation, and worsens neurological outcomes after acute traumatic brain injury in mice. Neurobiol Aging 77:194\u2013206. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2019.02.010","journal-title":"Neurobiol Aging"},{"key":"4560_CR7","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s40035-017-0088-2","volume":"6","author":"M Cruz-Haces","year":"2017","unstructured":"Cruz-Haces M, Tang J, Acosta G, Fernandez J, Shi R (2017) Pathological correlations between traumatic brain injury and chronic neurodegenerative diseases. Transl Neurodegener 6:20. https:\/\/doi.org\/10.1186\/s40035-017-0088-2","journal-title":"Transl Neurodegener"},{"key":"4560_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02309-6","volume":"18","author":"SC Woodburn","year":"2021","unstructured":"Woodburn SC, Bollinger JL, Wohleb ES (2021) The semantics of microglia activation: neuroinflammation, homeostasis, and stress. J Neuroinflamm 18:258. https:\/\/doi.org\/10.1186\/s12974-021-02309-6","journal-title":"J Neuroinflamm"},{"key":"4560_CR9","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202105442","volume":"9","author":"Z Yu","year":"2022","unstructured":"Yu Z, Fang X, Liu W, Sun R, Zhou J, Pu Y, Zhao M, Sun D, Xiang Z, Liu P, Ding Y, Cao L, He C (2022) Microglia regulate blood-brain barrier integrity via MiR-126a-5p\/MMP9 axis during inflammatory demyelination. Adv Sci 9:e2105442. https:\/\/doi.org\/10.1002\/advs.202105442","journal-title":"Adv Sci"},{"key":"4560_CR10","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s12974-020-01778-5","volume":"17","author":"WT O\u2019Brien","year":"2020","unstructured":"O\u2019Brien WT, Pham L, Symons GF, Monif M, Shultz SR, McDonald SJ (2020) The NLRP3 inflammasome in traumatic brain injury: potential as a biomarker and therapeutic target. J Neuroinflamm 17:104. https:\/\/doi.org\/10.1186\/s12974-020-01778-5","journal-title":"J Neuroinflamm"},{"key":"4560_CR11","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1016\/j.neurobiolaging.2012.11.013","volume":"34","author":"A Kumar","year":"2013","unstructured":"Kumar A, Stoica BA, Sabirzhanov B, Burns MP, Faden AI, Loane DJ (2013) Traumatic brain injury in aged animals increases lesion size and chronically alters microglial\/macrophage classical and alternative activation states. Neurobiol Aging 34:1397\u20131411. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2012.11.013","journal-title":"Neurobiol Aging"},{"key":"4560_CR12","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1002\/glia.20412","volume":"54","author":"K F\u00e4rber","year":"2006","unstructured":"F\u00e4rber K, Kettenmann H (2006) Functional role of calcium signals for microglial function. Glia 54:656\u2013665. https:\/\/doi.org\/10.1002\/glia.20412","journal-title":"Glia"},{"key":"4560_CR13","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1111\/bph.13426","volume":"174","author":"F Vilhardt","year":"2017","unstructured":"Vilhardt F, Haslund-Vinding J, Jaquet V, McBean G (2017) Microglia antioxidant systems and redox signalling. Br J Pharmacol 174:1719\u20131732. https:\/\/doi.org\/10.1111\/bph.13426","journal-title":"Br J Pharmacol"},{"key":"4560_CR14","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1038\/s41593-020-0672-0","volume":"23","author":"Q Cong","year":"2020","unstructured":"Cong Q, Soteros BM, Wollet M, Kim JH, Sia GM (2020) The endogenous neuronal complement inhibitor SRPX2 protects against complement-mediated synapse elimination during development. Nat Neurosci 23:1067\u20131078. https:\/\/doi.org\/10.1038\/s41593-020-0672-0","journal-title":"Nat Neurosci"},{"key":"4560_CR15","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s11064-024-04316-4","volume":"50","author":"ACS Kursancew","year":"2024","unstructured":"Kursancew ACS, Faller CJ, Bortoluzzi DP, Niero LB, Brand\u00e3o B, Danielski LG, Petronilho F, Generoso JS (2024) Neuroinflammatory response in the traumatic brain injury: an update. Neurochem Res 50:64. https:\/\/doi.org\/10.1007\/s11064-024-04316-4","journal-title":"Neurochem Res"},{"key":"4560_CR16","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1016\/j.jep.2016.10.012","volume":"194","author":"PO Donkor","year":"2016","unstructured":"Donkor PO, Chen Y, Ding L, Qiu F (2016) Locally and traditionally used ligusticum species\u2014a review of their phytochemistry, pharmacology and pharmacokinetics. J Ethnopharmacol 194:530\u2013548. https:\/\/doi.org\/10.1016\/j.jep.2016.10.012","journal-title":"J Ethnopharmacol"},{"key":"4560_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.hest.2025.01.003","author":"Q Xu","year":"2025","unstructured":"Xu Q, Mei W, Tang Z (2025) Advancing brain injury treatment and neuroprotection with ligustilide: mechanisms and therapeutic potential. Brain Hemorrhages. https:\/\/doi.org\/10.1016\/j.hest.2025.01.003","journal-title":"Brain Hemorrhages"},{"key":"4560_CR18","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1021\/acs.jafc.6b04979","volume":"65","author":"J Li","year":"2017","unstructured":"Li J, Yu J, Ma H, Yang N, Li L, Zheng DD, Wu MX, Zhao ZL, Qi HY (2017) Intranasal pretreatment with Z-ligustilide, the main volatile component of Rhizoma Chuanxiong, confers prophylaxis against cerebral ischemia via Nrf2 and HSP70 signaling pathways. J Agric Food Chem 65:1533\u20131542. https:\/\/doi.org\/10.1021\/acs.jafc.6b04979","journal-title":"J Agric Food Chem"},{"key":"4560_CR19","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1002\/ptr.6925","volume":"35","author":"LJ Gao","year":"2021","unstructured":"Gao LJ, Li P, Ma T, Zhong ZQ, Xu SJ (2021) Ligustilide alleviates neurotoxicity in SH-SY5Y cells induced by A\u03b2(25\u201335) via regulating endoplasmic reticulum stress and autophagy. Phytother Res 35:1572\u20131584. https:\/\/doi.org\/10.1002\/ptr.6925","journal-title":"Phytother Res"},{"key":"4560_CR20","doi-asserted-by":"publisher","first-page":"979","DOI":"10.3389\/fphar.2020.00979","volume":"11","author":"Q Wu","year":"2020","unstructured":"Wu Q, Mao Z, Liu J, Huang J, Wang N (2020) Ligustilide attenuates ischemia reperfusion-induced hippocampal neuronal apoptosis via activating the PI3K\/Akt pathway. Front Pharmacol 11:979. https:\/\/doi.org\/10.3389\/fphar.2020.00979","journal-title":"Front Pharmacol"},{"key":"4560_CR21","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.brainres.2006.04.110","volume":"1102","author":"X Kuang","year":"2006","unstructured":"Kuang X, Yao Y, Du JR, Liu YX, Wang CY, Qian ZM (2006) Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR mice. Brain Res 1102:145\u2013153. https:\/\/doi.org\/10.1016\/j.brainres.2006.04.110","journal-title":"Brain Res"},{"key":"4560_CR22","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.freeradbiomed.2014.03.028","volume":"71","author":"X Kuang","year":"2014","unstructured":"Kuang X, Wang LF, Yu L, Li YJ, Wang YN, He Q, Chen C, Du JR (2014) Ligustilide ameliorates neuroinflammation and brain injury in focal cerebral ischemia\/reperfusion rats: involvement of inhibition of TLR4\/peroxiredoxin 6 signaling. Free Radic Biol Med 71:165\u2013175. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2014.03.028","journal-title":"Free Radic Biol Med"},{"key":"4560_CR23","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1007\/s11357-022-00562-y","volume":"44","author":"RM Ritzel","year":"2022","unstructured":"Ritzel RM, Li Y, Lei Z, Carter J, He J, Choi HMC, Khan N, Li H, Allen S, Lipinski MM, Faden AI, Wu J (2022) Functional and transcriptional profiling of microglial activation during the chronic phase of TBI identifies an age-related driver of poor outcome in old mice. GeroScience 44:1407\u20131440. https:\/\/doi.org\/10.1007\/s11357-022-00562-y","journal-title":"Geroscience"},{"key":"4560_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103324","volume":"76","author":"S Peng","year":"2024","unstructured":"Peng S, Chen Y, Wang R, Zhang J (2024) Z-ligustilide provides a neuroprotective effect by regulating the phenotypic polarization of microglia via activating Nrf2-TrxR axis in the Parkinson\u2019s disease mouse model. Redox Biol 76:103324. https:\/\/doi.org\/10.1016\/j.redox.2024.103324","journal-title":"Redox Biol"},{"key":"4560_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155975","volume":"134","author":"K Xia","year":"2024","unstructured":"Xia K, Jin Z, Qiu Q, Zhou Y, Lu Y, Qiu T, Zhou J, Chen Z (2024) Ligustilide alleviates oxidative stress during renal ischemia-reperfusion injury through maintaining Sirt3-dependent mitochondrial homeostasis. Phytomed Int J Phytother Phytopharmacol 134:155975. https:\/\/doi.org\/10.1016\/j.phymed.2024.155975","journal-title":"Phytomedicine: Int J Phytotherapy Phytopharmacology"},{"key":"4560_CR26","doi-asserted-by":"publisher","first-page":"4382","DOI":"10.7150\/ijbs.98051","volume":"20","author":"H Yao","year":"2024","unstructured":"Yao H, Cai C, Huang W, Zhong C, Zhao T, Di J, Tang J, Wu D, Pang M, He L, Rong L, Liu B (2024) Enhancing mitophagy by ligustilide through BNIP3-LC3 interaction attenuates oxidative stress-induced neuronal apoptosis in spinal cord injury. Int J Biol Sci 20:4382\u20134406. https:\/\/doi.org\/10.7150\/ijbs.98051","journal-title":"Int J Biol Sci"},{"key":"4560_CR27","doi-asserted-by":"publisher","unstructured":"Wu J, Liu Y, Wang B, Wang Y, Liu B, Tan Y, Cai D, Liu K, Wei D (2025) A potential strategy for improving offspring behavior in maternal immune activation: amantadine-mediated suppression of neuroinflammation. Anim Models Exp Med. https:\/\/doi.org\/10.1002\/ame2.70059","DOI":"10.1002\/ame2.70059"},{"key":"4560_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2023.101934","volume":"51","author":"L Yan","year":"2023","unstructured":"Yan L, Zhao C, Wang Y, Qin Q, Liu Z, Hu Y, Xu Z, Wang K, Jiang X, Han LJNT (2023) Adhesive and conductive hydrogel-based therapy simultaneously targeting neuroinflammation and neurofunctional damage after brain injury. Nano Today 51:101934","journal-title":"Nano Today"},{"key":"4560_CR29","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1007\/s11064-023-04021-8","volume":"49","author":"K Zhao","year":"2024","unstructured":"Zhao K, Zhou X, Chen M, Gou L, Mei D, Gao C, Zhao S, Luo S, Wang X, Tan T, Zhang Y (2024) Neuroprotective effects of CXCR2 antagonist SB332235 on traumatic brain injury through suppressing NLRP3 inflammasome. Neurochem Res 49:184\u2013198. https:\/\/doi.org\/10.1007\/s11064-023-04021-8","journal-title":"Neurochem Res"},{"key":"4560_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02678-6","volume":"19","author":"J Xu","year":"2022","unstructured":"Xu J, Ji T, Li G, Zhang H, Zheng Y, Li M, Ma J, Li Y, Chi G (2022) Lactate attenuates astrocytic inflammation by inhibiting ubiquitination and degradation of NDRG2 under oxygen-glucose deprivation conditions. J Neuroinflamm 19:314. https:\/\/doi.org\/10.1186\/s12974-022-02678-6","journal-title":"J Neuroinflamm"},{"key":"4560_CR31","doi-asserted-by":"publisher","first-page":"120675","DOI":"10.1016\/j.biomaterials.2021.120675","volume":"270","author":"F Qian","year":"2021","unstructured":"Qian F, Han Y, Han Z, Zhang D, Zhang L, Zhao G, Li S, Jin G, Yu R, Liu H (2021) In situ implantable, post-trauma microenvironment-responsive, ROS depletion hydrogels for the treatment of traumatic brain injury. Biomaterials 270:120675. https:\/\/doi.org\/10.1016\/j.biomaterials.2021.120675","journal-title":"Biomaterials"},{"key":"4560_CR32","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s11064-024-04270-1","volume":"50","author":"D Lao","year":"2024","unstructured":"Lao D, Gong Z, Li T, Mo X, Huang W (2024) The P38MAPK pathway mediates the destruction of the Blood-Brain barrier in Anti-NMDAR encephalitis mice. Neurochem Res 50:21. https:\/\/doi.org\/10.1007\/s11064-024-04270-1","journal-title":"Neurochem Res"},{"key":"4560_CR33","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1007\/s11064-013-1033-0","volume":"38","author":"K Liu","year":"2013","unstructured":"Liu K, Sun Y, Gu Z, Shi N, Zhang T, Sun X (2013) Mitophagy in ischaemia\/reperfusion induced cerebral injury. Neurochem Res 38:1295\u20131300. https:\/\/doi.org\/10.1007\/s11064-013-1033-0","journal-title":"Neurochem Res"},{"key":"4560_CR34","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1002\/ame2.12369","volume":"7","author":"H Zhang","year":"2024","unstructured":"Zhang H, Cai W, Dong L, Yang Q, Li Q, Ran Q, Liu L, Wang Y, Li Y, Weng X, Zhu X, Chen Y (2024) Jiaohong pills attenuate neuroinflammation and amyloid-\u03b2 protein-induced cognitive deficits by modulating the mitogen-activated protein kinase\/nuclear factor kappa-B pathway. Anim Models Exp Med 7:222\u2013233. https:\/\/doi.org\/10.1002\/ame2.12369","journal-title":"Anim Models Exp Med"},{"key":"4560_CR35","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1080\/15548627.2023.2167689","volume":"19","author":"N Hegdekar","year":"2023","unstructured":"Hegdekar N, Sarkar C, Bustos S, Ritzel RM, Hanscom M, Ravishankar P, Philkana D, Wu J, Loane DJ, Lipinski MM (2023) Inhibition of autophagy in microglia and macrophages exacerbates innate immune responses and worsens brain injury outcomes. Autophagy 19:2026\u20132044. https:\/\/doi.org\/10.1080\/15548627.2023.2167689","journal-title":"Autophagy"},{"key":"4560_CR36","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1089\/neu.2022.0360","volume":"40","author":"MJ Lennon","year":"2023","unstructured":"Lennon MJ, Brooker H, Creese B, Thayanandan T, Rigney G, Aarsland D, Hampshire A, Ballard C, Corbett A, Raymont V (2023) Lifetime traumatic brain injury and cognitive domain deficits in late life: the PROTECT-TBI cohort study. J Neurotrauma 40:1423\u20131435. https:\/\/doi.org\/10.1089\/neu.2022.0360","journal-title":"J Neurotrauma"},{"key":"4560_CR37","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1665","volume":"14","author":"Z Li","year":"2024","unstructured":"Li Z, Yu S, Li L, Zhou C, Wang L, Tang S, Gu N, Zhang Z, Huang Z, Chen H, Tang W, Wang Y, Yang X, Sun X, Yan J (2024) TREM2 alleviates white matter injury after traumatic brain injury in mice might be mediated by regulation of DHCR24\/LXR pathway in microglia. Clin Transl Med 14:e1665. https:\/\/doi.org\/10.1002\/ctm2.1665","journal-title":"Clin Transl Med"},{"key":"4560_CR38","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/nrneurol.2010.74","volume":"6","author":"D Shlosberg","year":"2010","unstructured":"Shlosberg D, Benifla M, Kaufer D, Friedman A (2010) Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol 6:393\u2013403. https:\/\/doi.org\/10.1038\/nrneurol.2010.74","journal-title":"Nat Rev Neurol"},{"key":"4560_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02923-6","volume":"20","author":"S Meng","year":"2023","unstructured":"Meng S, Cao H, Huang Y, Shi Z, Li J, Wang Y, Zhang Y, Chen S, Shi H, Gao Y (2023) ASK1-K716R reduces neuroinflammation and white matter injury via preserving blood-brain barrier integrity after traumatic brain injury. J Neuroinflamm 20:244. https:\/\/doi.org\/10.1186\/s12974-023-02923-6","journal-title":"J Neuroinflamm"},{"key":"4560_CR40","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41420-025-02350-x","volume":"11","author":"XB Zheng","year":"2025","unstructured":"Zheng XB, Wang X, Gao SQ, Gao CC, Li T, Han YL, Zhao R, Sun Y, Miao SH, Qiu JY, Jin WX, Zhou ML (2025) NINJ1-mediated plasma membrane rupture of pyroptotic endothelial cells exacerbates blood-brain barrier destruction caused by neutrophil extracellular traps in traumatic brain injury. Cell Death Discov 11:69. https:\/\/doi.org\/10.1038\/s41420-025-02350-x","journal-title":"Cell Death Discov"},{"key":"4560_CR41","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1038\/s41586-023-06737-7","volume":"623","author":"R Hussain","year":"2023","unstructured":"Hussain R, Tithof J, Wang W, Cheetham-West A, Song W, Peng W, Sigurdsson B, Kim D, Sun Q, Peng S, Pl\u00e1 V, Kelley DH, Hirase H, Castorena-Gonzalez JA, Weikop P, Goldman SA, Davis MJ, Nedergaard M (2023) Potentiating glymphatic drainage minimizes post-traumatic cerebral oedema. Nature 623:992\u20131000. https:\/\/doi.org\/10.1038\/s41586-023-06737-7","journal-title":"Nature"},{"key":"4560_CR42","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1089\/neu.2013.3169","volume":"31","author":"AR Jayakumar","year":"2014","unstructured":"Jayakumar AR, Tong XY, Ruiz-Cordero R, Bregy A, Bethea JR, Bramlett HM, Norenberg MD (2014) Activation of NF-\u03baB mediates astrocyte swelling and brain edema in traumatic brain injury. J Neurotrauma 31:1249\u20131257. https:\/\/doi.org\/10.1089\/neu.2013.3169","journal-title":"J Neurotrauma"},{"key":"4560_CR43","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.nec.2016.05.008","volume":"27","author":"EA Winkler","year":"2016","unstructured":"Winkler EA, Minter D, Yue JK, Manley GT (2016) Cerebral edema in traumatic brain injury: pathophysiology and prospective therapeutic targets. Neurosurg Clin N Am 27:473\u2013488. https:\/\/doi.org\/10.1016\/j.nec.2016.05.008","journal-title":"Neurosurg Clin North Am"},{"key":"4560_CR44","doi-asserted-by":"publisher","first-page":"2932","DOI":"10.1161\/hs1201.099820","volume":"32","author":"G Xi","year":"2001","unstructured":"Xi G, Hua Y, Bhasin RR, Ennis SR, Keep RF, Hoff JT (2001) Mechanisms of edema formation after intracerebral hemorrhage: effects of extravasated red blood cells on blood flow and blood-brain barrier integrity. Stroke 32:2932\u20132938. https:\/\/doi.org\/10.1161\/hs1201.099820","journal-title":"Stroke"},{"key":"4560_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/biom14121623","author":"L Shen","year":"2024","unstructured":"Shen L, Tian Q, Ran Q, Gan Q, Hu Y, Du D, Qin Z, Duan X, Zhu X, Huang W (2024) Z-ligustilide: a potential therapeutic agent for atherosclerosis complicating cerebrovascular disease. Biomolecules. https:\/\/doi.org\/10.3390\/biom14121623","journal-title":"Biomolecules"},{"key":"4560_CR46","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1007\/s00401-018-1944-6","volume":"137","author":"MC Morganti-Kossmann","year":"2019","unstructured":"Morganti-Kossmann MC, Semple BD, Hellewell SC, Bye N, Ziebell JM (2019) The complexity of neuroinflammation consequent to traumatic brain injury: from research evidence to potential treatments. Acta Neuropathol 137:731\u2013755. https:\/\/doi.org\/10.1007\/s00401-018-1944-6","journal-title":"Acta Neuropathol"},{"key":"4560_CR47","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.expneurol.2015.08.018","volume":"275","author":"DJ Loane","year":"2016","unstructured":"Loane DJ, Kumar A (2016) Microglia in the TBI brain: the good, the bad, and the dysregulated. Exp Neurol 275:316\u2013327. https:\/\/doi.org\/10.1016\/j.expneurol.2015.08.018","journal-title":"Exp Neurol"},{"key":"4560_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-02041-7","volume":"18","author":"H Wu","year":"2021","unstructured":"Wu H, Zheng J, Xu S, Fang Y, Wu Y, Zeng J, Shao A, Shi L, Lu J, Mei S, Wang X, Guo X, Wang Y, Zhao Z, Zhang J (2021) Mer regulates microglial\/macrophage M1\/M2 polarization and alleviates neuroinflammation following traumatic brain injury. J Neuroinflamm 18:2. https:\/\/doi.org\/10.1186\/s12974-020-02041-7","journal-title":"J Neuroinflamm"},{"key":"4560_CR49","doi-asserted-by":"publisher","first-page":"e0164586","DOI":"10.1371\/journal.pone.0164586","volume":"11","author":"LX Zhao","year":"2016","unstructured":"Zhao LX, Du JR, Zhou HJ, Liu DL, Gu MX, Long FY (2016) Differences in proinflammatory property of six subtypes of peroxiredoxins and anti-inflammatory effect of ligustilide in macrophages. PLoS ONE 11:e0164586. https:\/\/doi.org\/10.1371\/journal.pone.0164586","journal-title":"PLoS ONE"},{"key":"4560_CR50","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.3389\/fphar.2020.01126","volume":"11","author":"L Zhou","year":"2020","unstructured":"Zhou L, Wang D, Qiu X, Zhang W, Gong Z, Wang Y, Xu X (2020) DHZCP modulates microglial M1\/M2 polarization via the p38 and TLR4\/NF-\u03baB signaling pathways in LPS-stimulated microglial cells. Front Pharmacol 11:1126. https:\/\/doi.org\/10.3389\/fphar.2020.01126","journal-title":"Front Pharmacol"},{"key":"4560_CR51","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/aps.2010.71","volume":"31","author":"J Wang","year":"2010","unstructured":"Wang J, Du JR, Wang Y, Kuang X, Wang CY (2010) Z-ligustilide attenuates lipopolysaccharide-induced proinflammatory response via inhibiting NF-kappaB pathway in primary rat microglia. Acta Pharmacol Sin 31:791\u2013797. https:\/\/doi.org\/10.1038\/aps.2010.71","journal-title":"Acta Pharmacol Sin"},{"key":"4560_CR52","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.neuropharm.2010.12.002","volume":"60","author":"TC Or","year":"2011","unstructured":"Or TC, Yang CL, Law AH, Li JC, Lau AS (2011) Isolation and identification of anti-inflammatory constituents from Ligusticum chuanxiong and their underlying mechanisms of action on microglia. Neuropharmacology 60:823\u2013831. https:\/\/doi.org\/10.1016\/j.neuropharm.2010.12.002","journal-title":"Neuropharmacology"},{"key":"4560_CR53","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.brainresbull.2014.10.002","volume":"109","author":"MD Zhu","year":"2014","unstructured":"Zhu MD, Zhao LX, Wang XT, Gao YJ, Zhang ZJ (2014) Ligustilide inhibits microglia-mediated proinflammatory cytokines production and inflammatory pain. Brain Res Bull 109:54\u201360. https:\/\/doi.org\/10.1016\/j.brainresbull.2014.10.002","journal-title":"Brain Res Bull"},{"issue":"789","key":"4560_CR54","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adn2635","volume":"17","author":"N Liu","year":"2025","unstructured":"Liu N, Jiang Y, Xiu Y, Tortelote GG, Xia W, Wang Y, Li Y, Shi S, Han J, Vidoudez C, Niamnud A, Kilgore MD, Zhou D, Shi M, Graziose SA, Fan J, Katakam PVG, Dumont AS, Wang X (2025) Itaconate restrains acute proinflammatory activation of microglia MG after traumatic brain injury in mice. Sci Transl Med 17(789):eadn2635. https:\/\/doi.org\/10.1126\/scitranslmed.adn2635","journal-title":"Sci Transl Med"},{"key":"4560_CR55","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1038\/s41593-022-01199-y","volume":"25","author":"A Zambusi","year":"2022","unstructured":"Zambusi A, Novoselc KT, Hutten S, Kalpazidou S, Koupourtidou C, Schieweck R, Aschenbroich S, Silva L, Yazgili AS, van Bebber F, Schmid B, M\u00f6ller G, Tritscher C, Stigloher C, Delbridge C, Sirko S, G\u00fcnes ZI, Liebscher S, Schlegel J, Aliee H, Theis F, Meiners S, Kiebler M, Dormann D, Ninkovic J (2022) TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury. Nat Neurosci 25:1608\u20131625. https:\/\/doi.org\/10.1038\/s41593-022-01199-y","journal-title":"Nat Neurosci"},{"key":"4560_CR56","doi-asserted-by":"publisher","first-page":"1231706","DOI":"10.3389\/fragi.2023.1231706","volume":"4","author":"SF Darwish","year":"2023","unstructured":"Darwish SF, Elbadry AMM, Elbokhomy AS, Salama GA, Salama RM (2023) The dual face of microglia (M1\/M2) as a potential target in the protective effect of nutraceuticals against neurodegenerative diseases. Front Aging 4:1231706. https:\/\/doi.org\/10.3389\/fragi.2023.1231706","journal-title":"Front Aging"},{"key":"4560_CR57","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1093\/jpp\/rgae024","volume":"76","author":"M Sadeghi","year":"2024","unstructured":"Sadeghi M, Khayati S, Dehnavi S, Almahmeed W, Sukhorukovi VN, Sahebkar A (2024) Regulatory impact of statins on macrophage polarization: mechanistic and therapeutic implications. J Pharm Pharmacol 76:763\u2013775. https:\/\/doi.org\/10.1093\/jpp\/rgae024","journal-title":"J Pharm Pharmacol"},{"key":"4560_CR58","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14352","volume":"30","author":"X Yang","year":"2024","unstructured":"Yang X, Li T, Liu J, Sun H, Cheng L, Song X, Han Z, Luo H, Han W, Xie L, Jiang L (2024) Effects of minocycline on dendrites, dendritic spines, and microglia in immature mouse brains after kainic acid-induced status epilepticus. CNS Neurosci Ther 30:e14352. https:\/\/doi.org\/10.1111\/cns.14352","journal-title":"CNS Neurosci Ther"},{"key":"4560_CR59","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s40001-025-02344-6","volume":"30","author":"Z Chen","year":"2025","unstructured":"Chen Z, Zhang C, Fang Y, Zhang H, Luo J, Miao C, Li J, Peng J, Qiu Y, Xia Y, Luo Q (2025) Olfactory mucosa-mesenchymal stem cells with overexpressed Nrf2 modulate angiogenesis and exert anti-inflammation effect in an in vitro traumatic brain injury model. Eur J Med Res 30:80. https:\/\/doi.org\/10.1186\/s40001-025-02344-6","journal-title":"Eur J Med Res"},{"key":"4560_CR60","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-58","volume":"11","author":"A Vilalta","year":"2014","unstructured":"Vilalta A, Brown GC (2014) Deoxyglucose prevents neurodegeneration in culture by eliminating microglia. J Neuroinflamm 11:58. https:\/\/doi.org\/10.1186\/1742-2094-11-58","journal-title":"J Neuroinflamm"},{"key":"4560_CR61","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1016\/j.neuropharm.2011.11.012","volume":"62","author":"H Qi","year":"2012","unstructured":"Qi H, Han Y, Rong J (2012) Potential roles of PI3K\/Akt and Nrf2-Keap1 pathways in regulating hormesis of Z-ligustilide in PC12 cells against oxygen and glucose deprivation. Neuropharmacology 62:1659\u20131670. https:\/\/doi.org\/10.1016\/j.neuropharm.2011.11.012","journal-title":"Neuropharmacology"},{"key":"4560_CR62","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/978-981-15-4272-5_46","volume":"1207","author":"C Luo","year":"2020","unstructured":"Luo C, Tao L (2020) The function and mechanisms of autophagy in traumatic brain injury. Adv Exp Med Biol 1207:635\u2013648. https:\/\/doi.org\/10.1007\/978-981-15-4272-5_46","journal-title":"Adv Exp Med Biol"},{"key":"4560_CR63","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/s41418-024-01408-0","volume":"32","author":"W Weng","year":"2025","unstructured":"Weng W, He Z, Ma Z, Huang J, Han Y, Feng Q, Qi W, Peng Y, Wang J, Gu J, Wang W, Lin Y, Jiang G, Jiang J, Feng J (2025) Tufm lactylation regulates neuronal apoptosis by modulating mitophagy in traumatic brain injury. Cell Death Differ 32:530\u2013545. https:\/\/doi.org\/10.1038\/s41418-024-01408-0","journal-title":"Cell Death Differ"},{"key":"4560_CR64","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00862-y","volume":"20","author":"L Cai","year":"2022","unstructured":"Cai L, Gong Q, Qi L, Xu T, Suo Q, Li X, Wang W, Jing Y, Yang D, Xu Z, Yuan F, Tang Y, Yang G, Ding J, Chen H, Tian H (2022) ACT001 attenuates microglia-mediated neuroinflammation after traumatic brain injury via inhibiting AKT\/NF\u03baB\/NLRP3 pathway. Cell Commun Signal 20:56. https:\/\/doi.org\/10.1186\/s12964-022-00862-y","journal-title":"Cell Commun Signal"},{"key":"4560_CR65","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s40001-023-01631-4","volume":"29","author":"X Zheng","year":"2024","unstructured":"Zheng X, Yang J, Hou Y, Shi X, Liu K (2024) Prediction of clinical progression in nervous system diseases: plasma glial fibrillary acidic protein (GFAP). Eur J Med Res 29:51. https:\/\/doi.org\/10.1186\/s40001-023-01631-4","journal-title":"Eur J Med Res"}],"container-title":["Neurochemical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-025-04560-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11064-025-04560-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-025-04560-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:10:33Z","timestamp":1761541833000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11064-025-04560-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,27]]},"references-count":65,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["4560"],"URL":"https:\/\/doi.org\/10.1007\/s11064-025-04560-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7005217\/v1","asserted-by":"object"}]},"ISSN":["0364-3190","1573-6903"],"issn-type":[{"value":"0364-3190","type":"print"},{"value":"1573-6903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,27]]},"assertion":[{"value":"30 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}}],"article-number":"309"}}