{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T13:00:28Z","timestamp":1781614828533,"version":"3.54.5"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004761","name":"the Natural Science Foundation of Hunan Province","doi-asserted-by":"crossref","award":["2023JJ60458, 2023JJ30367"],"award-info":[{"award-number":["2023JJ60458, 2023JJ30367"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Scientific Research Project of Hunan Provincial Health Commission","award":["D202319019427"],"award-info":[{"award-number":["D202319019427"]}]},{"name":"the Natural Science Foundation Project of Changsha City","award":["kq2208144"],"award-info":[{"award-number":["kq2208144"]}]},{"name":"the Clinical Medical Technology Innovation Guidance Project of Hunan Province","award":["2021SK51010"],"award-info":[{"award-number":["2021SK51010"]}]},{"name":"the Scientific Research Project of Hunan Provincial Administration of Traditional Chinese Medicine","award":["C2022011"],"award-info":[{"award-number":["C2022011"]}]},{"name":"the Academic inheritance and communication project of China Academy of Chinese Medical Sciences","award":["CI2022E014XB"],"award-info":[{"award-number":["CI2022E014XB"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Promoting nerve regeneration is a crucial approach in treating ischemic stroke, with neural stem cells (NSCs) playing a vital role in this process. Qixian Tongluo Formula (QXTLF) has shown effectiveness in treating ischemic stroke, yet its impact on regulating the directional differentiation of NSCs during ischemic stroke remains unclear. A middle cerebral artery occlusion (MCAO) model was induced in Sprague-Dawley rats, and primary NSCs were isolated from these rats. By gavage QXTLF (7.83\u00a0g\/kg\/d or 31.32\u00a0g\/kg\/d) was administered intragastrically to the MCAO rats. In vitro experiments confirmed the successful isolation of NSCs from rats, capable of differentiating into immature neurons, mature neurons and astrocytes. In vitro, NSCs were exposed to fibrinogen (Fg) and induced by low glucose-oxygen (LGO) conditions to simulate the NSC niche in ischemic stroke. Various assessments were conducted, including neurological score evaluation in MCAO rats, analysis of infarct size using 2,3,5-triphenyltetrazolium chloride (TTC) staining, and examination of the expression of markers like bromodeoxyuridine (BrdU), doublecortin (DCX), microtubule-associated protein 2 (MAP-2), glial fibrillary acidic protein (GFAP), and bone morphogenetic protein type I receptor (BMPRI)\/inhibitor of DNA binding 3 (ID3) by immunofluorescence and western blot analysis. The Fg content was quantified by enzyme-linked immunosorbent assay. Results demonstrated that QXTLF reduced cerebral infarction and decreased the neurological score of MCAO rat in a dose-dependent manner. Additionally, QXTLF promoted the directional differentiation of NSCs into neurons within ipsilateral hippocampus following cerebral ischemia. Furthermore, the study revealed that QXTLF facilitated the directional differentiation of LGO-induced NSCs into neurons and implicated Fg in mediating this effect. QXTLF was found to regulate the directional differentiation of LGO-induced NSCs through the Fg-mediated BMPRI\/ID3 signal axis, highlighting its role in promoting the differentiation of NSCs into neurons post-ischemic stroke.<\/jats:p>","DOI":"10.1186\/s13023-025-04080-w","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T10:04:10Z","timestamp":1761818650000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Qixian Tongluo Formula promotes the directional differentiation of neural stem cells into neurons via fibrinogen-mediated BMPRI\/ID3 signal axis after ischemic stroke"],"prefix":"10.1186","volume":"20","author":[{"given":"Shengqiang","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjuan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"issue":"3","key":"4080_CR1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.gendis.2018.06.001","volume":"5","author":"Y Hou","year":"2018","unstructured":"Hou Y, Wang K, Wan W, Cheng Y, Pu X, Ye X. Resveratrol provides neuroprotection by regulating the JAK2\/STAT3\/PI3K\/AKT\/mTOR pathway after stroke in rats. Genes Dis. 2018;5(3):245\u201355.","journal-title":"Genes Dis"},{"issue":"Suppl 2","key":"4080_CR2","first-page":"S140","volume":"23","author":"C Chugh","year":"2019","unstructured":"Chugh C. Acute ischemic stroke: management Approach. Indian journal of critical care medicine: peer-reviewed. Official Publication Indian Soc Crit Care Med. 2019;23(Suppl 2):S140\u20136.","journal-title":"Official Publication Indian Soc Crit Care Med"},{"key":"4080_CR3","doi-asserted-by":"publisher","first-page":"105171","DOI":"10.1016\/j.neuint.2021.105171","volume":"150","author":"H Xiao","year":"2021","unstructured":"Xiao H, Jiang Q, Qiu H, Wu K, Ma X, Yang J, et al. Gastrodin promotes hippocampal neurogenesis via PDE9-cGMP-PKG pathway in mice following cerebral ischemia. Neurochem Int. 2021;150:105171.","journal-title":"Neurochem Int"},{"issue":"1","key":"4080_CR4","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s13287-021-02187-y","volume":"12","author":"B Yang","year":"2021","unstructured":"Yang B, Zang L, Cui J, Wei L, Circular. RNA TTC3 regulates cerebral ischemia-reperfusion injury and neural stem cells by miR-372-3p\/TLR4 axis in cerebral infarction. Stem Cell Res Ther. 2021;12(1):125.","journal-title":"Stem Cell Res Ther"},{"issue":"10","key":"4080_CR5","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.1007\/s11064-020-03092-1","volume":"45","author":"W Li","year":"2020","unstructured":"Li W, Ye A, Ao L, Zhou L, Yan Y, Hu Y, et al. Protective mechanism and treatment of neurogenesis in cerebral ischemia. Neurochem Res. 2020;45(10):2258\u201377.","journal-title":"Neurochem Res"},{"issue":"5","key":"4080_CR6","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1111\/j.1471-4159.2010.06849.x","volume":"114","author":"E Molina-Holgado","year":"2010","unstructured":"Molina-Holgado E, Molina-Holgado F. Mending the broken brain: neuroimmune interactions in neurogenesis. J Neurochem. 2010;114(5):1277\u201390.","journal-title":"J Neurochem"},{"issue":"1","key":"4080_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12975-020-00841-w","volume":"12","author":"AA Rahman","year":"2021","unstructured":"Rahman AA, Amruta N. Neurogenesis after stroke: A therapeutic perspective. Translational Stroke Res. 2021;12(1):1\u201314.","journal-title":"Translational Stroke Res"},{"issue":"5","key":"4080_CR8","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s12975-022-00984-y","volume":"13","author":"T Zhao","year":"2022","unstructured":"Zhao T, Zhu T, Xie L, Li Y, Xie R, Xu F, et al. Neural stem cells therapy for ischemic stroke: progress and challenges. Translational Stroke Res. 2022;13(5):665\u201375.","journal-title":"Translational Stroke Res"},{"issue":"10","key":"4080_CR9","doi-asserted-by":"publisher","first-page":"817","DOI":"10.4252\/wjsc.v11.i10.817","volume":"11","author":"GL Zhang","year":"2019","unstructured":"Zhang GL, Zhu ZH, Wang YZ. Neural stem cell transplantation therapy for brain ischemic stroke: review and perspectives. World J Stem Cells. 2019;11(10):817\u201330.","journal-title":"World J Stem Cells"},{"issue":"4","key":"4080_CR10","first-page":"405","volume":"74","author":"A Lebreton","year":"2016","unstructured":"Lebreton A, Casini A. Diagnosis of congenital fibrinogen disorders. Ann Biol Clin. 2016;74(4):405\u201312.","journal-title":"Ann Biol Clin"},{"issue":"10","key":"4080_CR11","doi-asserted-by":"publisher","first-page":"e01425","DOI":"10.1002\/brb3.1425","volume":"9","author":"P Guo","year":"2019","unstructured":"Guo P, Jin Z, Wu H, Li X, Ke J, Zhang Z, et al. Effects of Irisin on the dysfunction of blood-brain barrier in rats after focal cerebral ischemia\/reperfusion. Brain Behav. 2019;9(10):e01425.","journal-title":"Brain Behav"},{"issue":"5","key":"4080_CR12","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/nrn.2018.13","volume":"19","author":"MA Petersen","year":"2018","unstructured":"Petersen MA, Ryu JK, Akassoglou K. Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics. Nat Rev Neurosci. 2018;19(5):283\u2013301.","journal-title":"Nat Rev Neurosci"},{"key":"4080_CR13","doi-asserted-by":"crossref","unstructured":"McLarnon JG. A leaky blood-brain barrier to fibrinogen contributes to oxidative damage in Alzheimer\u2019s disease. Antioxid (Basel Switzerland). 2021;11(1).","DOI":"10.3390\/antiox11010102"},{"issue":"31","key":"4080_CR14","doi-asserted-by":"publisher","first-page":"e2323050121","DOI":"10.1073\/pnas.2323050121","volume":"121","author":"O Weaver","year":"2024","unstructured":"Weaver O, Gano D, Zhou Y, Kim H, Tognatta R, Yan Z, et al. Fibrinogen inhibits Sonic Hedgehog signaling and impairs neonatal cerebellar development after blood-brain barrier disruption. Proc Natl Acad Sci USA. 2024;121(31):e2323050121.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"4080_CR15","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s11357-023-00988-y","volume":"46","author":"PK Chandra","year":"2024","unstructured":"Chandra PK, Panner Selvam MK, Castorena-Gonzalez JA, Rutkai I, Sikka SC, Mostany R, et al. Fibrinogen in mice cerebral microvessels induces blood-brain barrier dysregulation with aging via a dynamin-related protein 1-dependent pathway. GeroScience. 2024;46(1):395\u2013415.","journal-title":"GeroScience"},{"issue":"6","key":"4080_CR16","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.4103\/1673-5374.300436","volume":"16","author":"JD Lin","year":"2021","unstructured":"Lin JD, Chu YH, Nath S, Schachtrup C. Fibrinogen triggered signaling pathways modify stem cell behavior in central nervous system disease. Neural Regeneration Res. 2021;16(6):1196\u20137.","journal-title":"Neural Regeneration Res"},{"issue":"105","key":"4080_CR17","first-page":"311","volume":"19","author":"Y Hai","year":"2015","unstructured":"Hai Y, Sun M, Niu M, Yuan Q, Guo Y, Li Z, et al. BMP4 promotes human Sertoli cell proliferation via Smad1\/5 and ID2\/3 pathway and its abnormality is associated with azoospermia. Discov Med. 2015;19(105):311\u201325.","journal-title":"Discov Med"},{"issue":"19","key":"4080_CR18","doi-asserted-by":"publisher","first-page":"3465","DOI":"10.1242\/dev.152520","volume":"144","author":"M Boareto","year":"2017","unstructured":"Boareto M, Iber D, Taylor V. Differential interactions between Notch and ID factors control neurogenesis by modulating Hes factor autoregulation. Development. 2017;144(19):3465\u201374.","journal-title":"Development"},{"issue":"05","key":"4080_CR19","doi-asserted-by":"publisher","first-page":"543","DOI":"10.3760\/cma.j.cn115398-20220429-00462","volume":"45","author":"YH Qi","year":"2023","unstructured":"Qi YH, Xin X, Zhang Y, Yang AR. Effect of Qixian Tongluo formula fumigation adjuvant therapy on neurological function and rehabilitation efficacy in patients with hemiplegia due to cerebral infarction presenting with Qi deficiency and blood stasis syndrome. Int J Traditional Chin Med. 2023;45(05):543\u20137. https:\/\/doi.org\/10.3760\/cma.j.cn115398-20220429-00462. [Article in Chinese].","journal-title":"Int J Traditional Chin Med"},{"issue":"10","key":"4080_CR20","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.3969\/j.issn.1674-070X.2020.10.022","volume":"40","author":"SQ Zhou","year":"2020","unstructured":"Zhou SQ, Liu F, Deng YH, Li B, Zeng CC, Wu ZR, et al. Retrospective study on Qixian Tongluo formula in the treatment of cerebral infarction recovery and sequelae of kidney deficiency and blood stasis syndrome. J Hunan Univ Chin Med. 2020;40(10):1283\u20139. https:\/\/doi.org\/10.3969\/j.issn.1674-070X.2020.10.022. [Article in Chinese].","journal-title":"J Hunan Univ Chin Med"},{"issue":"24","key":"4080_CR21","doi-asserted-by":"publisher","first-page":"141","DOI":"10.13422\/j.cnki.syfjx.2017240141","volume":"23","author":"X Lin","year":"2017","unstructured":"Lin X, Zhou C, Ma K, Liu F, Liu Z. Effect and mechanism of Qixian Tongluo Decoction on regeneration of endogenous neural stem cells after cerebral ischemia in rats. Chin J Experimental Traditional Med Formulae. 2017;23(24):141\u20137. https:\/\/doi.org\/10.13422\/j.cnki.syfjx.2017240141. [Article in Chinese].","journal-title":"Chin J Experimental Traditional Med Formulae"},{"issue":"5","key":"4080_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.16705\/j.cnki.1004-1850.2023.05.001","volume":"32","author":"W Zeng","year":"2023","unstructured":"Zeng W, Tan LG, Zhou SQ, Liu F. Fibrinogen inhibits axonal regeneration of neurons subjected to in vitro low-glucose and low-oxygen damage by activating the EGFR signaling pathway. Chin J Histochem Cytochemistry. 2023;32(5):1\u20138. https:\/\/doi.org\/10.16705\/j.cnki.1004-1850.2023.05.001. [Article in Chinese].","journal-title":"Chin J Histochem Cytochemistry"},{"key":"4080_CR23","first-page":"101","volume":"1717","author":"MS Lopez","year":"2018","unstructured":"Lopez MS, Vemuganti R. Modeling transient focal ischemic stroke in rodents by intraluminal filament method of middle cerebral artery occlusion. (Clifton NJ). 2018;1717:101\u201313. Methods in molecular biology.","journal-title":"(Clifton NJ)"},{"key":"4080_CR24","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.cbi.2019.06.008","volume":"308","author":"Y Zhang","year":"2019","unstructured":"Zhang Y, Shan Z, Zhao Y, Ai Y. Sevoflurane prevents miR-181a-induced cerebral ischemia\/reperfusion injury. Chemico-Biol Interact. 2019;308:332\u20138.","journal-title":"Chemico-Biol Interact"},{"key":"4080_CR25","doi-asserted-by":"publisher","first-page":"107335","DOI":"10.1016\/j.intimp.2020.107335","volume":"92","author":"L Li","year":"2021","unstructured":"Li L, Gan H, Jin H, Fang Y, Yang Y, Zhang J, et al. Astragaloside IV promotes microglia\/macrophages M2 polarization and enhances neurogenesis and angiogenesis through PPAR\u03b3 pathway after cerebral ischemia\/reperfusion injury in rats. Int Immunopharmacol. 2021;92:107335.","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"4080_CR26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s12974-024-03026-6","volume":"21","author":"Y Qian","year":"2024","unstructured":"Qian Y, Yang L, Chen J, Zhou C, Zong N, Geng Y, et al. SRGN amplifies microglia-mediated neuroinflammation and exacerbates ischemic brain injury. J Neuroinflamm. 2024;21(1):35.","journal-title":"J Neuroinflamm"},{"issue":"2","key":"4080_CR27","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1136\/svn-2023-002320","volume":"9","author":"W Li","year":"2024","unstructured":"Li W, Shen N, Kong L, Huang H, Wang X, Zhang Y, et al. STING mediates microglial pyroptosis via interaction with NLRP3 in cerebral ischaemic stroke. Stroke Vascular Neurol. 2024;9(2):153\u201364.","journal-title":"Stroke Vascular Neurol"},{"issue":"1","key":"4080_CR28","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/S0006-8993(03)02224-8","volume":"968","author":"S Lou","year":"2003","unstructured":"Lou S, Gu P, Chen F, He C, Wang M, Lu C. The effect of bone marrow stromal cells on neuronal differentiation of mesencephalic neural stem cells in Sprague-Dawley rats. Brain Res. 2003;968(1):114\u201321.","journal-title":"Brain Res"},{"issue":"9","key":"4080_CR29","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.19378\/j.issn.1003-9783.2024.09.005","volume":"35","author":"SQ Zhou","year":"2024","unstructured":"Zhou SQ, Wu DH, Li B, Chen YJ, Huang J, Wang Q, et al. The effect and mechanism of Qixian Tongluo formula on the remodeling of healthy corticospinal tract and motor function recovery in rats with cerebral infarction. Traditional Chin Drug Res Clin Pharmacol. 2024;35(9):1319\u201328. https:\/\/doi.org\/10.19378\/j.issn.1003-9783.2024.09.005. [Article in Chinese].","journal-title":"Traditional Chin Drug Res Clin Pharmacol"},{"issue":"1","key":"4080_CR30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s12975-016-0460-z","volume":"8","author":"SH Koh","year":"2017","unstructured":"Koh SH, Park HH. Neurogenesis in stroke recovery. Translational Stroke Res. 2017;8(1):3\u201313.","journal-title":"Translational Stroke Res"},{"issue":"1","key":"4080_CR31","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/s41420-023-01532-9","volume":"9","author":"L Nie","year":"2023","unstructured":"Nie L, Yao D, Chen S, Wang J, Pan C, Wu D, et al. Directional induction of neural stem cells, a new therapy for neurodegenerative diseases and ischemic stroke. Cell Death Discovery. 2023;9(1):215.","journal-title":"Cell Death Discovery"},{"key":"4080_CR32","doi-asserted-by":"crossref","unstructured":"Hamblin MH, Lee JP. Neural stem cells for early ischemic stroke. Int J Mol Sci. 2021;22(14).","DOI":"10.3390\/ijms22147703"},{"issue":"1","key":"4080_CR33","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/s13287-018-0913-2","volume":"9","author":"AC Boese","year":"2018","unstructured":"Boese AC, Le QE, Pham D, Hamblin MH, Lee JP. Neural stem cell therapy for subacute and chronic ischemic stroke. Stem Cell Res Ther. 2018;9(1):154.","journal-title":"Stem Cell Res Ther"},{"key":"4080_CR34","doi-asserted-by":"crossref","unstructured":"Zhang R, Mao W, Niu L, Bao W, Wang Y, Wang Y, et al. NSC-derived exosomes enhance therapeutic effects of NSC transplantation on cerebral ischemia in mice. eLife. 2023;12.","DOI":"10.7554\/eLife.84493"},{"issue":"7","key":"4080_CR35","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.02.034","volume":"26","author":"JD Zhu","year":"2017","unstructured":"Zhu JD, Wang JJ, Ge G, Kang CS. Effects of Noggin-Transfected neural stem cells on neural functional recovery and underlying mechanism in rats with cerebral ischemia reperfusion injury. J Stroke Cerebrovasc Diseases: Official J Natl Stroke Association. 2017;26(7):1547\u201359.","journal-title":"J Stroke Cerebrovasc Diseases: Official J Natl Stroke Association"},{"key":"4080_CR36","doi-asserted-by":"publisher","first-page":"628115","DOI":"10.3389\/fncel.2021.628115","volume":"15","author":"J Wang","year":"2021","unstructured":"Wang J, Hu J, Chen X, Lei X, Feng H, Wan F, et al. Traditional Chinese medicine monomers: novel strategy for endogenous neural stem cells activation after stroke. Front Cell Neurosci. 2021;15:628115.","journal-title":"Front Cell Neurosci"},{"key":"4080_CR37","doi-asserted-by":"publisher","first-page":"115684","DOI":"10.1016\/j.jep.2022.115684","volume":"299","author":"L Hong","year":"2022","unstructured":"Hong L, Jiang H, Liu M, Zhao G, Shi X, Tan H, et al. Investigation of naoluoxintong on the neural stem cells by facilitating proliferation and differentiation in vitro and on protecting neurons by up-regulating the expression of Nestin in MCAO rats. J Ethnopharmacol. 2022;299:115684.","journal-title":"J Ethnopharmacol"},{"issue":"007","key":"4080_CR38","doi-asserted-by":"publisher","first-page":"912","DOI":"10.19378\/j.issn.1003-9783.2021.07.002","volume":"32","author":"S Zhou","year":"2021","unstructured":"Zhou S, Shou Y, Wang Q, Li B, Liu F, Deng Y. Effect and mechanism of Qixian Tongluo formula on synaptic plasticity and functional recovery in rats with cerebral infarction. Traditional Chin Drug Res Clin Pharmacol. 2021;32(007):912\u20139. https:\/\/doi.org\/10.19378\/j.issn.1003-9783.2021.07.002. [Article in Chinese].","journal-title":"Traditional Chin Drug Res Clin Pharmacol"},{"key":"4080_CR39","doi-asserted-by":"publisher","first-page":"9974625","DOI":"10.1155\/2021\/9974625","volume":"2021","author":"D Ma","year":"2021","unstructured":"Ma D, Zhao L, Zhang L, Li Y, Zhang L, Li L. Icariin promotes Survival, Proliferation, and differentiation of neural stem cells in vitro and in a rat model of Alzheimer\u2019s disease. Stem Cells Int. 2021;2021:9974625.","journal-title":"Stem Cells Int"},{"issue":"10","key":"4080_CR40","doi-asserted-by":"publisher","first-page":"8163","DOI":"10.1007\/s11033-023-08707-8","volume":"50","author":"A Ebrahimi","year":"2023","unstructured":"Ebrahimi A, Parivar K, Roodbari NH, Eidi A. Treatment with Quercetin increases Nrf2 expression and neuronal differentiation of sub ventricular zone derived neural progenitor stem cells in adult rats. Mol Biol Rep. 2023;50(10):8163\u201375.","journal-title":"Mol Biol Rep"},{"issue":"1","key":"4080_CR41","doi-asserted-by":"publisher","first-page":"2746","DOI":"10.1080\/21691401.2019.1628040","volume":"47","author":"B Wang","year":"2019","unstructured":"Wang B, Ma W, Yang H. Puerarin attenuates hypoxia-resulted damages in neural stem cells by up-regulating microRNA-214. Artif Cells Nanomed Biotechnol. 2019;47(1):2746\u201353.","journal-title":"Artif Cells Nanomed Biotechnol"},{"issue":"3","key":"4080_CR42","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1055\/s-0037-1613020","volume":"87","author":"IA Baker","year":"2002","unstructured":"Baker IA, Pickering J, Elwood PC, Bayer A, Ebrahim S. Fibrinogen, viscosity and white blood cell count predict myocardial, but not cerebral infarction: evidence from the caerphilly and speedwell cohort. Thromb Haemost. 2002;87(3):421\u20135.","journal-title":"Thromb Haemost"},{"issue":"3","key":"4080_CR43","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S0049-3848(01)00350-4","volume":"104","author":"M Yamazaki","year":"2001","unstructured":"Yamazaki M, Uchiyama S, Iwata M. Measurement of platelet fibrinogen binding and p-selectin expression by flow cytometry in patients with cerebral infarction. Thromb Res. 2001;104(3):197\u2013205.","journal-title":"Thromb Res"},{"issue":"19","key":"4080_CR44","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1089\/neu.2017.5291","volume":"35","author":"DR Jenkins","year":"2018","unstructured":"Jenkins DR, Craner MJ, Esiri MM, DeLuca GC. Contribution of fibrinogen to inflammation and neuronal density in human traumatic brain injury. J Neurotrauma. 2018;35(19):2259\u201371.","journal-title":"J Neurotrauma"},{"issue":"5","key":"4080_CR45","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1111\/cns.14113","volume":"29","author":"H Hou","year":"2023","unstructured":"Hou H, Wang Y, Yang L, Wang Y, Exosomal. miR-128-3p reversed fibrinogen-mediated Inhibition of oligodendrocyte progenitor cell differentiation and remyelination after cerebral ischemia. CNS Neurosci Ther. 2023;29(5):1405\u201322.","journal-title":"CNS Neurosci Ther"},{"issue":"2","key":"4080_CR46","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1167\/iovs.16-20472","volume":"58","author":"AA Mody","year":"2017","unstructured":"Mody AA, Wordinger RJ, Clark AF. Role of ID proteins in BMP4 Inhibition of profibrotic effects of TGF-\u03b22 in human TM cells. Investig Ophthalmol Vis Sci. 2017;58(2):849\u201359.","journal-title":"Investig Ophthalmol Vis Sci"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04080-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-025-04080-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04080-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:35:49Z","timestamp":1781613349000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13023-025-04080-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4080"],"URL":"https:\/\/doi.org\/10.1186\/s13023-025-04080-w","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]},"assertion":[{"value":"5 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 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 experiment has obtained approval from the Experimental Animal Ethics Committee of Hunan Academy of Chinese Medicine (NO. 2022-0083).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declared no competing interest in this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"549"}}