{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:57:02Z","timestamp":1786982222098,"version":"build-2736575974"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82202721"],"award-info":[{"award-number":["82202721"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 82302689"],"award-info":[{"award-number":["No. 82302689"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"crossref","award":["LY23H060006"],"award-info":[{"award-number":["LY23H060006"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"crossref","award":["LY23H060005"],"award-info":[{"award-number":["LY23H060005"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"crossref","award":["LY19H060003"],"award-info":[{"award-number":["LY19H060003"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"crossref","award":["2020KY183"],"award-info":[{"award-number":["2020KY183"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1007\/s12035-025-04793-w","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T01:28:18Z","timestamp":1740619698000},"page":"8587-8602","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pectolinarin Promotes Functional Recovery after Spinal Cord Injury by Regulating Microglia Polarization Through the PI3K\/AKT Signaling Pathway"],"prefix":"10.1007","volume":"62","author":[{"given":"Chenggui","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouwei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichen","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juntao","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fancheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunren","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzeng","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"4793_CR1","doi-asserted-by":"publisher","first-page":"17018","DOI":"10.1038\/nrdp.2017.18","volume":"3","author":"CS Ahuja","year":"2017","unstructured":"Ahuja CS, Wilson JR, Nori S, Kotter MRN, Druschel C, Curt A, Fehlings MG (2017) Traumatic spinal cord injury. Nat Rev Dis Primers 3:17018. https:\/\/doi.org\/10.1038\/nrdp.2017.18","journal-title":"Nat Rev Dis Primers"},{"key":"4793_CR2","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1093\/neuros\/nyw080","volume":"80","author":"CS Ahuja","year":"2017","unstructured":"Ahuja CS, Nori S, Tetreault L, Wilson J, Kwon B, Harrop J, Choi D, Fehlings MG (2017) Traumatic spinal cord injury-repair and regeneration. Neurosurgery 80:S9-s22. https:\/\/doi.org\/10.1093\/neuros\/nyw080","journal-title":"Neurosurgery"},{"key":"4793_CR3","doi-asserted-by":"publisher","first-page":"914","DOI":"10.5966\/sctm.2015-0381","volume":"5","author":"CS Ahuja","year":"2016","unstructured":"Ahuja CS, Fehlings M (2016) Concise review: bridging the gap: novel neuroregenerative and neuroprotective strategies in spinal cord injury. Stem Cells Transl Med 5:914\u2013924. https:\/\/doi.org\/10.5966\/sctm.2015-0381","journal-title":"Stem Cells Transl Med"},{"key":"4793_CR4","doi-asserted-by":"publisher","first-page":"2933","DOI":"10.1093\/brain\/awab250","volume":"144","author":"J Van Broeckhoven","year":"2021","unstructured":"Van Broeckhoven J, Sommer D, Dooley D, Hendrix S, Franssen A (2021) Macrophage phagocytosis after spinal cord injury: when friends become foes. Brain 144:2933\u20132945. https:\/\/doi.org\/10.1093\/brain\/awab250","journal-title":"Brain"},{"key":"4793_CR5","doi-asserted-by":"publisher","first-page":"4096","DOI":"10.1038\/s41467-022-31797-0","volume":"13","author":"FH Brennan","year":"2022","unstructured":"Brennan FH, Li Y, Wang C, Ma A, Guo Q, Li Y, Pukos N, Campbell WA et al (2022) Microglia coordinate cellular interactions during spinal cord repair in mice. Nat Commun 13:4096. https:\/\/doi.org\/10.1038\/s41467-022-31797-0","journal-title":"Nat Commun"},{"key":"4793_CR6","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1186\/s12974-021-02337-2","volume":"18","author":"DJ Hellenbrand","year":"2021","unstructured":"Hellenbrand DJ, Quinn CM, Piper ZJ, Morehouse CN, Fixel JA, Hanna AS (2021) Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration. J Neuroinflammation 18:284. https:\/\/doi.org\/10.1186\/s12974-021-02337-2","journal-title":"J Neuroinflammation"},{"key":"4793_CR7","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s13311-018-0631-6","volume":"15","author":"MB Orr","year":"2018","unstructured":"Orr MB, Gensel JC (2018) Spinal cord injury scarring and inflammation: therapies targeting glial and inflammatory responses. Neurotherapeutics 15:541\u2013553. https:\/\/doi.org\/10.1007\/s13311-018-0631-6","journal-title":"Neurotherapeutics"},{"key":"4793_CR8","doi-asserted-by":"publisher","first-page":"7016","DOI":"10.7150\/thno.37601","volume":"9","author":"C Wang","year":"2019","unstructured":"Wang C, Gong Z, Huang X, Wang J, Xia K, Ying L, Shu J, Yu C et al (2019) An injectable heparin-Laponite hydrogel bridge FGF4 for spinal cord injury by stabilizing microtubule and improving mitochondrial function. Theranostics 9:7016\u20137032. https:\/\/doi.org\/10.7150\/thno.37601","journal-title":"Theranostics"},{"key":"4793_CR9","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/s41593-020-0597-7","volume":"23","author":"X Zhou","year":"2020","unstructured":"Zhou X, Wahane S, Friedl MS, Kluge M, Friedel CC, Avrampou K, Zachariou V, Guo L et al (2020) Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2. Nat Neurosci 23:337\u2013350. https:\/\/doi.org\/10.1038\/s41593-020-0597-7","journal-title":"Nat Neurosci"},{"key":"4793_CR10","doi-asserted-by":"publisher","first-page":"113310","DOI":"10.1016\/j.expneurol.2020.113310","volume":"329","author":"NA Devanney","year":"2020","unstructured":"Devanney NA, Stewart AN, Gensel JC (2020) Microglia and macrophage metabolism in CNS injury and disease: the role of immunometabolism in neurodegeneration and neurotrauma. Exp Neurol 329:113310. https:\/\/doi.org\/10.1016\/j.expneurol.2020.113310","journal-title":"Exp Neurol"},{"key":"4793_CR11","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/nrn3053","volume":"12","author":"S David","year":"2011","unstructured":"David S, Kroner A (2011) Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 12:388\u2013399. https:\/\/doi.org\/10.1038\/nrn3053","journal-title":"Nat Rev Neurosci"},{"key":"4793_CR12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1084\/jem.20151570","volume":"213","author":"LA O'Neill","year":"2016","unstructured":"O\u2019Neill LA, Pearce EJ (2016) Immunometabolism governs dendritic cell and macrophage function. J Exp Med 213:15\u201323. https:\/\/doi.org\/10.1084\/jem.20151570","journal-title":"J Exp Med"},{"key":"4793_CR13","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/nri.2016.70","volume":"16","author":"LA O'Neill","year":"2016","unstructured":"O\u2019Neill LA, Kishton RJ, Rathmell J (2016) A guide to immunometabolism for immunologists. Nat Rev Immunol 16:553\u2013565. https:\/\/doi.org\/10.1038\/nri.2016.70","journal-title":"Nat Rev Immunol"},{"key":"4793_CR14","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1073\/pnas.1518000113","volume":"113","author":"L Liu","year":"2016","unstructured":"Liu L, Lu Y, Martinez J, Bi Y, Lian G, Wang T, Milasta S, Wang J et al (2016) Proinflammatory signal suppresses proliferation and shifts macrophage metabolism from Myc-dependent to HIF1\u03b1-dependent. Proc Natl Acad Sci U S A 113:1564\u20131569. https:\/\/doi.org\/10.1073\/pnas.1518000113","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4793_CR15","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/s0140-6736(02)07603-1","volume":"359","author":"JW McDonald","year":"2002","unstructured":"McDonald JW, Sadowsky C (2002) Spinal-cord injury. Lancet 359:417\u2013425. https:\/\/doi.org\/10.1016\/s0140-6736(02)07603-1","journal-title":"Lancet"},{"key":"4793_CR16","doi-asserted-by":"publisher","first-page":"e2105586","DOI":"10.1002\/advs.202105586","volume":"9","author":"L Fan","year":"2022","unstructured":"Fan L, Liu C, Chen X, Zheng L, Zou Y, Wen H, Guan P, Lu F et al (2022) Exosomes-loaded electroconductive hydrogel synergistically promotes tissue repair after spinal cord injury via immunoregulation and enhancement of myelinated axon growth. Adv Sci (Weinh) 9:e2105586. https:\/\/doi.org\/10.1002\/advs.202105586","journal-title":"Adv Sci (Weinh)"},{"key":"4793_CR17","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.bioactmat.2021.10.005","volume":"11","author":"BQ Lai","year":"2022","unstructured":"Lai BQ, Bai YR, Han WT, Zhang B, Liu S, Sun JH, Liu JL, Li G et al (2022) Construction of a niche-specific spinal white matter-like tissue to promote directional axon regeneration and myelination for rat spinal cord injury repair. Bioact Mater 11:15\u201331. https:\/\/doi.org\/10.1016\/j.bioactmat.2021.10.005","journal-title":"Bioact Mater"},{"key":"4793_CR18","doi-asserted-by":"publisher","first-page":"15095","DOI":"10.1523\/jneurosci.0278-13.2013","volume":"33","author":"MJ Kwon","year":"2013","unstructured":"Kwon MJ, Kim J, Shin H, Jeong SR, Kang YM, Choi JY, Hwang DH, Kim BG (2013) Contribution of macrophages to enhanced regenerative capacity of dorsal root ganglia sensory neurons by conditioning injury. J Neurosci 33:15095\u201315108. https:\/\/doi.org\/10.1523\/jneurosci.0278-13.2013","journal-title":"J Neurosci"},{"key":"4793_CR19","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1038\/nn.3469","volume":"16","author":"VE Miron","year":"2013","unstructured":"Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ et al (2013) M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci 16:1211\u20131218. https:\/\/doi.org\/10.1038\/nn.3469","journal-title":"Nat Neurosci"},{"key":"4793_CR20","doi-asserted-by":"publisher","first-page":"e2107838","DOI":"10.1002\/smll.202107838","volume":"18","author":"GY Xu","year":"2022","unstructured":"Xu GY, Xu S, Zhang YX, Yu ZY, Zou F, Ma XS, Xia XL, Zhang WJ et al (2022) Cell-free extracts from human fat tissue with a hyaluronan-based hydrogel attenuate inflammation in a spinal cord injury model through M2 microglia\/microphage polarization. Small 18:e2107838. https:\/\/doi.org\/10.1002\/smll.202107838","journal-title":"Small"},{"key":"4793_CR21","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.actbio.2021.03.018","volume":"126","author":"ZS Gao","year":"2021","unstructured":"Gao ZS, Zhang CJ, Xia N, Tian H, Li DY, Lin JQ, Mei XF, Wu C (2021) Berberine-loaded M2 macrophage-derived exosomes for spinal cord injury therapy. Acta Biomater 126:211\u2013223. https:\/\/doi.org\/10.1016\/j.actbio.2021.03.018","journal-title":"Acta Biomater"},{"key":"4793_CR22","unstructured":"LM M, CB R and JK L (2019) The origin, fate, and contribution of macrophages to spinal cord injury pathology. Acta Neuropathologica Undefined:Undefined"},{"key":"4793_CR23","doi-asserted-by":"publisher","first-page":"13435","DOI":"10.1523\/jneurosci.3257-09.2009","volume":"29","author":"KA Kigerl","year":"2009","unstructured":"Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG (2009) Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 29:13435\u201313444. https:\/\/doi.org\/10.1523\/jneurosci.3257-09.2009","journal-title":"J Neurosci"},{"key":"4793_CR24","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1016\/j.neuron.2014.07.027","volume":"83","author":"A Kroner","year":"2014","unstructured":"Kroner A, Greenhalgh AD, Zarruk JG, dos Santos RP, Gaestel M, David S (2014) TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. Neuron 83:1098\u20131116","journal-title":"Neuron"},{"key":"4793_CR25","doi-asserted-by":"publisher","DOI":"10.23736\/s0031-0808.20.03974-9","author":"X Lv","year":"2020","unstructured":"Lv X, Liang J, Wang Z (2020) MiR-21-5p reduces apoptosis and inflammation in rats with spinal cord injury through PI3K\/AKT pathway. Panminerva Med. https:\/\/doi.org\/10.23736\/s0031-0808.20.03974-9","journal-title":"Panminerva Med"},{"key":"4793_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2014.12.045","volume":"1619","author":"JC Gensel","year":"2015","unstructured":"Gensel JC, Zhang B (2015) Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res 1619:1\u201311. https:\/\/doi.org\/10.1016\/j.brainres.2014.12.045","journal-title":"Brain Res"},{"key":"4793_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcot.2022.101760","volume":"25","author":"P Cheng","year":"2022","unstructured":"Cheng P, Liao HY, Zhang HH (2022) The role of Wnt\/mTOR signaling in spinal cord injury. J Clin Orthop Trauma 25:101760. https:\/\/doi.org\/10.1016\/j.jcot.2022.101760","journal-title":"J Clin Orthop Trauma"},{"key":"4793_CR28","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1159\/000490829","volume":"47","author":"Y Zhou","year":"2018","unstructured":"Zhou Y, Xia L, Liu Q, Wang H, Lin J, Oyang L, Chen X, Luo X et al (2018) Induction of pro-inflammatory response via activated macrophage-mediated NF-\u03baB and STAT3 pathways in gastric cancer cells. Cell Physiol Biochem 47:1399\u20131410. https:\/\/doi.org\/10.1159\/000490829","journal-title":"Cell Physiol Biochem"},{"key":"4793_CR29","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.3892\/ijmm.2018.3786","volume":"42","author":"N Wang","year":"2018","unstructured":"Wang N, Feng Z, Zhao W, Zhang Z, Zhang L (2018) Ultrashortwave radiation promotes the recovery of spinal cord injury by inhibiting inflammation via suppression of the MK2\/TNF-\u03b1 pathway. Int J Mol Med 42:1909\u20131916. https:\/\/doi.org\/10.3892\/ijmm.2018.3786","journal-title":"Int J Mol Med"},{"key":"4793_CR30","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.tcb.2019.01.001","volume":"29","author":"F Gulluni","year":"2019","unstructured":"Gulluni F, De Santis MC, Margaria JP, Martini M, Hirsch E (2019) Class II PI3K functions in cell biology and disease. Trends Cell Biol 29:339\u2013359. https:\/\/doi.org\/10.1016\/j.tcb.2019.01.001","journal-title":"Trends Cell Biol"},{"key":"4793_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00582-5","author":"JE Burke","year":"2022","unstructured":"Burke JE, Triscott J, Emerling BM, Hammond GRV (2022) Beyond PI3Ks: targeting phosphoinositide kinases in disease. Nat Rev Drug Discov. https:\/\/doi.org\/10.1038\/s41573-022-00582-5","journal-title":"Nat Rev Drug Discov"},{"key":"4793_CR32","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/sji.12148","volume":"79","author":"M Zhu","year":"2014","unstructured":"Zhu M, Li D, Wu Y, Huang X, Wu M (2014) TREM-2 promotes macrophage-mediated eradication of Pseudomonas aeruginosa via a PI3K\/Akt pathway. Scand J Immunol 79:187\u2013196. https:\/\/doi.org\/10.1111\/sji.12148","journal-title":"Scand J Immunol"},{"key":"4793_CR33","doi-asserted-by":"publisher","first-page":"2779","DOI":"10.1007\/s11064-016-1994-x","volume":"41","author":"XK Tu","year":"2016","unstructured":"Tu XK, Zhang HB, Shi SS, Liang RS, Wang CH, Chen CM, Yang WZ (2016) 5-LOX inhibitor zileuton reduces inflammatory reaction and ischemic brain damage through the activation of PI3K\/Akt signaling pathway. Neurochem Res 41:2779\u20132787. https:\/\/doi.org\/10.1007\/s11064-016-1994-x","journal-title":"Neurochem Res"},{"key":"4793_CR34","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1007\/s12975-018-0665-4","volume":"9","author":"J Pang","year":"2018","unstructured":"Pang J, Peng J, Matei N, Yang P, Kuai L, Wu Y, Chen L, Vitek MP et al (2018) Apolipoprotein E exerts a whole-brain protective property by promoting M1? Microglia quiescence after experimental subarachnoid hemorrhage in mice. Transl Stroke Res 9:654\u2013668. https:\/\/doi.org\/10.1007\/s12975-018-0665-4","journal-title":"Transl Stroke Res"},{"key":"4793_CR35","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1007\/s12035-017-0400-2","volume":"55","author":"A Zendedel","year":"2018","unstructured":"Zendedel A, Monnink F, Hassanzadeh G, Zaminy A, Ansar MM, Habib P, Slowik A, Kipp M et al (2018) Estrogen attenuates local inflammasome expression and activation after spinal cord injury. Mol Neurobiol 55:1364\u20131375. https:\/\/doi.org\/10.1007\/s12035-017-0400-2","journal-title":"Mol Neurobiol"},{"key":"4793_CR36","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1248\/cpb.35.861","volume":"35","author":"H Ishida","year":"1987","unstructured":"Ishida H, Umino T, Tsuji K, Kosuge T (1987) Studies on antihemorrhagic substances in herbs classified as hemostatics in Chinese medicine. VII. On the antihemorrhagic principle in Cirsium japonicum DC. Chem Pharm Bull (Tokyo) 35:861\u2013864. https:\/\/doi.org\/10.1248\/cpb.35.861","journal-title":"Chem Pharm Bull (Tokyo)"},{"key":"4793_CR37","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/ptr.1299","volume":"18","author":"JC Park","year":"2004","unstructured":"Park JC, Hur JM, Park JG, Kim SC, Park JR, Choi SH, Choi JW (2004) Effects of methanol extract of Cirsium japonicum var. ussuriense and its principle, hispidulin-7-O-neohesperidoside on hepatic alcohol-metabolizing enzymes and lipid peroxidation in ethanol-treated rats. Phytother Res 18:19\u201324. https:\/\/doi.org\/10.1002\/ptr.1299","journal-title":"Phytother Res"},{"key":"4793_CR38","doi-asserted-by":"publisher","first-page":"247","DOI":"10.4162\/nrp.2008.2.4.247","volume":"2","author":"J Yin","year":"2008","unstructured":"Yin J, Heo SI, Wang MH (2008) Antioxidant and antidiabetic activities of extracts from Cirsium japonicum roots. Nutr Res Pract 2:247\u2013251. https:\/\/doi.org\/10.4162\/nrp.2008.2.4.247","journal-title":"Nutr Res Pract"},{"key":"4793_CR39","doi-asserted-by":"publisher","first-page":"15202","DOI":"10.1002\/jcb.28784","volume":"120","author":"L Wang","year":"2019","unstructured":"Wang L, Wang N, Zhao Q, Zhang B, Ding Y (2019) Pectolinarin inhibits proliferation, induces apoptosis, and suppresses inflammation in rheumatoid arthritis fibroblast-like synoviocytes by inactivating the phosphatidylinositol 3 kinase\/protein kinase B pathway. J Cell Biochem 120:15202\u201315210. https:\/\/doi.org\/10.1002\/jcb.28784","journal-title":"J Cell Biochem"},{"key":"4793_CR40","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1111\/jcmm.13368","volume":"22","author":"C Wang","year":"2018","unstructured":"Wang C, Wang Q, Lou Y, Xu J, Feng Z, Chen Y, Tang Q, Zheng G et al (2018) Salidroside attenuates neuroinflammation and improves functional recovery after spinal cord injury through microglia polarization regulation. J Cell Mol Med 22:1148\u20131166. https:\/\/doi.org\/10.1111\/jcmm.13368","journal-title":"J Cell Mol Med"},{"key":"4793_CR41","doi-asserted-by":"publisher","first-page":"2523","DOI":"10.1016\/j.bioactmat.2021.01.029","volume":"6","author":"C Wang","year":"2021","unstructured":"Wang C, Wang M, Xia K, Wang J, Cheng F, Shi K, Ying L, Yu C et al (2021) A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury. Bioact Mater 6:2523\u20132534. https:\/\/doi.org\/10.1016\/j.bioactmat.2021.01.029","journal-title":"Bioact Mater"},{"key":"4793_CR42","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/sc.2011.109","volume":"50","author":"V Noonan","year":"2012","unstructured":"Noonan V, Kwon B, Soril L, Fehlings M, Hurlbert R, Townson A, Johnson M, Dvorak M (2012) The Rick Hansen Spinal Cord Injury Registry (RHSCIR): a national patient-registry. Spinal Cord 50:22\u201327","journal-title":"Spinal Cord"},{"key":"4793_CR43","doi-asserted-by":"publisher","first-page":"309","DOI":"10.2147\/clep.s68889","volume":"6","author":"A Singh","year":"2014","unstructured":"Singh A, Tetreault L, Kalsi-Ryan S, Nouri A, Fehlings MG (2014) Global prevalence and incidence of traumatic spinal cord injury. Clin Epidemiol 6:309\u2013331. https:\/\/doi.org\/10.2147\/clep.s68889","journal-title":"Clin Epidemiol"},{"key":"4793_CR44","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.14336\/ad.2023.0505","volume":"14","author":"H Ma","year":"2023","unstructured":"Ma H, Li H, Zhang Y, Zhou Y, Liu H, Xu H, Zhu L, Zhang G et al (2023) Microglia exhibit distinct heterogeneity rather than M1\/M2 polarization within the early stage of acute ischemic stroke. Aging Dis 14:2284\u20132302. https:\/\/doi.org\/10.14336\/ad.2023.0505","journal-title":"Aging Dis"},{"key":"4793_CR45","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.ymthe.2019.09.004","volume":"28","author":"S Kobashi","year":"2020","unstructured":"Kobashi S, Terashima T, Katagi M, Nakae Y, Okano J, Suzuki Y, Urushitani M, Kojima H (2020) Transplantation of M2-deviated microglia promotes recovery of motor function after spinal cord injury in mice. Mol Ther 28:254\u2013265. https:\/\/doi.org\/10.1016\/j.ymthe.2019.09.004","journal-title":"Mol Ther"},{"key":"4793_CR46","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.actbio.2021.09.026","volume":"136","author":"Z Luo","year":"2021","unstructured":"Luo Z, Peng W, Xu Y, Xie Y, Liu Y, Lu H, Cao Y, Hu J (2021) Exosomal OTULIN from M2 macrophages promotes the recovery of spinal cord injuries via stimulating Wnt\/\u03b2-catenin pathway-mediated vascular regeneration. Acta Biomater 136:519\u2013532. https:\/\/doi.org\/10.1016\/j.actbio.2021.09.026","journal-title":"Acta Biomater"},{"key":"4793_CR47","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/nri3073","volume":"11","author":"PJ Murray","year":"2011","unstructured":"Murray PJ, Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11:723\u2013737. https:\/\/doi.org\/10.1038\/nri3073","journal-title":"Nat Rev Immunol"},{"key":"4793_CR48","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/nri978","volume":"3","author":"S Gordon","year":"2003","unstructured":"Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23\u201335. https:\/\/doi.org\/10.1038\/nri978","journal-title":"Nat Rev Immunol"},{"key":"4793_CR49","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","volume":"25","author":"A Mantovani","year":"2004","unstructured":"Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677\u2013686. https:\/\/doi.org\/10.1016\/j.it.2004.09.015","journal-title":"Trends Immunol"},{"key":"4793_CR50","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s12974-020-01853-x","volume":"17","author":"S Chen","year":"2020","unstructured":"Chen S, Peng J, Sherchan P, Ma Y, Xiang S, Yan F, Zhao H, Jiang Y et al (2020) TREM2 activation attenuates neuroinflammation and neuronal apoptosis via PI3K\/Akt pathway after intracerebral hemorrhage in mice. J Neuroinflammation 17:168. https:\/\/doi.org\/10.1186\/s12974-020-01853-x","journal-title":"J Neuroinflammation"},{"key":"4793_CR51","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","volume":"170","author":"DA Fruman","year":"2017","unstructured":"Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT (2017) The PI3K pathway in human disease. Cell 170:605\u2013635. https:\/\/doi.org\/10.1016\/j.cell.2017.07.029","journal-title":"Cell"},{"key":"4793_CR52","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1126\/science.296.5573.1655","volume":"296","author":"LC Cantley","year":"2002","unstructured":"Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296:1655\u20131657. https:\/\/doi.org\/10.1126\/science.296.5573.1655","journal-title":"Science"},{"key":"4793_CR53","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.cell.2015.12.042","volume":"164","author":"H Hu","year":"2016","unstructured":"Hu H, Juvekar A, Lyssiotis CA, Lien EC, Albeck JG, Oh D, Varma G, Hung YP et al (2016) Phosphoinositide 3-kinase regulates glycolysis through mobilization of aldolase from the actin cytoskeleton. Cell 164:433\u2013446. https:\/\/doi.org\/10.1016\/j.cell.2015.12.042","journal-title":"Cell"},{"key":"4793_CR54","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.4049\/jimmunol.1601515","volume":"198","author":"E Vergadi","year":"2017","unstructured":"Vergadi E, Ieronymaki E, Lyroni K, Vaporidi K, Tsatsanis C (2017) Akt signaling pathway in macrophage activation and M1\/M2 polarization. J Immunol 198:1006\u20131014. https:\/\/doi.org\/10.4049\/jimmunol.1601515","journal-title":"J Immunol"},{"key":"4793_CR55","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41392-021-00627-y","volume":"6","author":"HY Zhao","year":"2021","unstructured":"Zhao HY, Zhang YY, Xing T, Tang SQ, Wen Q, Lyu ZS, Lv M, Wang Y et al (2021) M2 macrophages, but not M1 macrophages, support megakaryopoiesis by upregulating PI3K-AKT pathway activity. Signal Transduct Target Ther 6:234. https:\/\/doi.org\/10.1038\/s41392-021-00627-y","journal-title":"Signal Transduct Target Ther"},{"key":"4793_CR56","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1007\/s10753-023-01825-2","volume":"46","author":"L Pan","year":"2023","unstructured":"Pan L, Cheng Y, Yang W, Wu X, Zhu H, Hu M, Zhang Y, Zhang M (2023) Nintedanib ameliorates bleomycin-induced pulmonary fibrosis, inflammation, apoptosis, and oxidative stress by modulating PI3K\/Akt\/mTOR pathway in mice. Inflammation 46:1531\u20131542. https:\/\/doi.org\/10.1007\/s10753-023-01825-2","journal-title":"Inflammation"},{"key":"4793_CR57","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1186\/s12967-023-04771-7","volume":"21","author":"L Wang","year":"2023","unstructured":"Wang L, Xu H, Li X, Chen H, Zhang H, Zhu X, Lin Z, Guo S et al (2023) Cucurbitacin E reduces IL-1\u03b2-induced inflammation and cartilage degeneration by inhibiting the PI3K\/Akt pathway in osteoarthritic chondrocytes. J Transl Med 21:880. https:\/\/doi.org\/10.1186\/s12967-023-04771-7","journal-title":"J Transl Med"},{"key":"4793_CR58","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1007\/s10753-022-01777-z","volume":"46","author":"T Tian","year":"2023","unstructured":"Tian T, Chen L, Wang Z, Zhu M, Xu W, Wu B (2023) Sema3A drives alternative macrophage activation in the resolution of periodontitis via PI3K\/AKT\/mTOR signaling. Inflammation 46:876\u2013891. https:\/\/doi.org\/10.1007\/s10753-022-01777-z","journal-title":"Inflammation"},{"key":"4793_CR59","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.freeradbiomed.2023.10.380","volume":"209","author":"X Chen","year":"2023","unstructured":"Chen X, Song QL, Wang JY, Ji R, Cao ML, Guo DY, Zhang Y, Yang J (2023) FKBP5 regulates trophoblast-macrophage crosstalk in recurrent spontaneous abortion through PI3K\/AKT and NF-\u03baB signaling pathways. Free Radic Biol Med 209:55\u201369. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2023.10.380","journal-title":"Free Radic Biol Med"},{"key":"4793_CR60","doi-asserted-by":"publisher","first-page":"113881","DOI":"10.1016\/j.biopha.2022.113881","volume":"156","author":"CL Xiao","year":"2022","unstructured":"Xiao CL, Yin WC, Zhong YC, Luo JQ, Liu LL, Liu WY, Zhao K (2022) The role of PI3K\/Akt signalling pathway in spinal cord injury. Biomed Pharmacother 156:113881. https:\/\/doi.org\/10.1016\/j.biopha.2022.113881","journal-title":"Biomed Pharmacother"},{"key":"4793_CR61","doi-asserted-by":"publisher","first-page":"839796","DOI":"10.3389\/fimmu.2022.839796","volume":"13","author":"Y Tian","year":"2022","unstructured":"Tian Y, Liu B, Li Y, Zhang Y, Shao J, Wu P, Xu C, Chen G et al (2022) Activation of RAR\u03b1 receptor attenuates neuroinflammation after SAH via promoting M1-to-M2 phenotypic polarization of microglia and regulating Mafb\/Msr1\/PI3K-Akt\/NF-\u03baB pathway. Front Immunol 13:839796. https:\/\/doi.org\/10.3389\/fimmu.2022.839796","journal-title":"Front Immunol"},{"key":"4793_CR62","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1126\/science.1227901","volume":"339","author":"A Aguzzi","year":"2013","unstructured":"Aguzzi A, Barres BA, Bennett ML (2013) Microglia: scapegoat, saboteur, or something else? Science 339:156\u2013161. https:\/\/doi.org\/10.1126\/science.1227901","journal-title":"Science"},{"key":"4793_CR63","doi-asserted-by":"publisher","first-page":"4670","DOI":"10.1038\/s41467-018-07036-w","volume":"9","author":"TM Tsarouchas","year":"2018","unstructured":"Tsarouchas TM, Wehner D, Cavone L, Munir T, Keatinge M, Lambertus M, Underhill A, Barrett T et al (2018) Dynamic control of proinflammatory cytokines Il-1\u03b2 and Tnf-\u03b1 by macrophages in zebrafish spinal cord regeneration. Nat Commun 9:4670. https:\/\/doi.org\/10.1038\/s41467-018-07036-w","journal-title":"Nat Commun"},{"key":"4793_CR64","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","volume":"23","author":"J Marschallinger","year":"2020","unstructured":"Marschallinger J, Iram T, Zardeneta M, Lee SE, Lehallier B, Haney MS, Pluvinage JV, Mathur V et al (2020) Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain. Nat Neurosci 23:194\u2013208. https:\/\/doi.org\/10.1038\/s41593-019-0566-1","journal-title":"Nat Neurosci"},{"key":"4793_CR65","doi-asserted-by":"publisher","first-page":"101932","DOI":"10.1016\/j.redox.2021.101932","volume":"41","author":"X Ge","year":"2021","unstructured":"Ge X, Tang P, Rong Y, Jiang D, Lu X, Ji C, Wang J, Huang C et al (2021) Exosomal miR-155 from M1-polarized macrophages promotes EndoMT and impairs mitochondrial function via activating NF-\u03baB signaling pathway in vascular endothelial cells after traumatic spinal cord injury. Redox Biol 41:101932. https:\/\/doi.org\/10.1016\/j.redox.2021.101932","journal-title":"Redox Biol"},{"key":"4793_CR66","doi-asserted-by":"publisher","unstructured":"Ma D, Shen H, Chen F, Liu W, Zhao Y, Xiao Z, Wu X, Chen B, Lu J, Shao D and Dai J (2022) Inflammatory microenvironment-responsive nanomaterials promote spinal cord injury repair by targeting IRF5. Adv Healthc Mater. e2201319. https:\/\/doi.org\/10.1002\/adhm.202201319","DOI":"10.1002\/adhm.202201319"},{"key":"4793_CR67","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.bioactmat.2022.05.026","volume":"18","author":"X Gao","year":"2022","unstructured":"Gao X, Han Z, Huang C, Lei H, Li G, Chen L, Feng D, Zhou Z et al (2022) An anti-inflammatory and neuroprotective biomimetic nanoplatform for repairing spinal cord injury. Bioact Mater 18:569\u2013582. https:\/\/doi.org\/10.1016\/j.bioactmat.2022.05.026","journal-title":"Bioact Mater"},{"key":"4793_CR68","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12974-020-1726-7","volume":"17","author":"W Liu","year":"2020","unstructured":"Liu W, Rong Y, Wang J, Zhou Z, Ge X, Ji C, Jiang D, Gong F et al (2020) Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1\/M2 polarization. J Neuroinflammation 17:47. https:\/\/doi.org\/10.1186\/s12974-020-1726-7","journal-title":"J Neuroinflammation"},{"key":"4793_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00562-y","author":"B Zheng","year":"2023","unstructured":"Zheng B, Tuszynski MH (2023) Regulation of axonal regeneration after mammalian spinal cord injury. Nat Rev Mol Cell Biol. https:\/\/doi.org\/10.1038\/s41580-022-00562-y","journal-title":"Nat Rev Mol Cell Biol"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-04793-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-025-04793-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-04793-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T10:03:24Z","timestamp":1751364204000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-025-04793-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":69,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["4793"],"URL":"https:\/\/doi.org\/10.1007\/s12035-025-04793-w","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,27]]},"assertion":[{"value":"19 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal experiments were performed following approval from the ethics committee of Wenzhou Medical University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}