{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:25:51Z","timestamp":1786973151270,"version":"build-2736575974"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Abdolreza Narouiepour"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite a great amount of effort, there is still a need for reliable treatments of traumatic brain injury (TBI). Recently, stem cell therapy has emerged as a new avenue to address neuronal regeneration after TBI. However, the environment of TBI lesions exerts negative effects on the stem cells efficacy. Therefore, to maximize the beneficial effects of stem cells in the course of TBI, we evaluated the effect of human neural stem\/progenitor cells (hNS\/PCs) and curcumin-loaded niosome nanoparticles (CM-NPs) on behavioral changes, brain edema, gliosis, and inflammatory responses in a rat model of TBI. After TBI, hNS\/PCs were transplanted within the injury site and CM-NPs were orally administered for 10\u00a0days. Finally, the effect of combination therapy was compared to several control groups. Our results indicated a significant improvement of general locomotor activity in the hNS\/PCs\u2009+\u2009CM-NPs treatment group compared to the control groups. We also observed a significant improvement in brain edema in the hNS\/PCs\u2009+\u2009CM-NPs treatment group compared to the other groups. Furthermore, a significant decrease in astrogliosis was seen in the combined treatment group. Moreover, TLR4-, NF-\u03baB-, and TNF-\u03b1- positive cells were significantly decreased in hNS\/PCs\u2009+\u2009CM-NPs group compared to the control groups. Taken together, this study indicated that combination therapy of stem cells with CM-NPs can be an effective therapy for TBI.<\/jats:p>","DOI":"10.1038\/s41598-022-07367-1","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T13:37:47Z","timestamp":1646401067000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Neural stem cell therapy in conjunction with curcumin loaded in niosomal nanoparticles enhanced recovery from traumatic brain injury"],"prefix":"10.1038","volume":"12","author":[{"given":"Abdolreza","family":"Narouiepour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Ebrahimzadeh-bideskan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghadir","family":"Rajabzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Gorji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2242-9794","authenticated-orcid":false,"given":"Sajad Sahab","family":"Negah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"7367_CR1","doi-asserted-by":"publisher","first-page":"3296","DOI":"10.1007\/s11064-017-2372-z","volume":"42","author":"Y Feng","year":"2017","unstructured":"Feng, Y. et al. Protective role of apocynin via suppression of neuronal autophagy and TLR4\/NF-\u03baB signaling pathway in a rat model of traumatic brain injury. Neurochem. Res. 42, 3296\u20133309 (2017).","journal-title":"Neurochem. Res."},{"key":"7367_CR2","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.brainresbull.2019.10.013","volume":"154","author":"S Evran","year":"2020","unstructured":"Evran, S. et al. The effect of high mobility group box-1 protein on cerebral edema, blood-brain barrier, oxidative stress and apoptosis in an experimental traumatic brain injury model. Brain Res. Bull. 154, 68\u201380 (2020).","journal-title":"Brain Res. Bull."},{"key":"7367_CR3","doi-asserted-by":"publisher","first-page":"45","DOI":"10.29252\/beat-060107","volume":"6","author":"M Saatian","year":"2018","unstructured":"Saatian, M., Ahmadpoor, J., Mohammadi, Y. & Mazloumi, E. Epidemiology and pattern of traumatic brain injury in a developing country regional trauma center. Bull. Emerg. Trauma 6, 45 (2018).","journal-title":"Bull. Emerg. Trauma"},{"key":"7367_CR4","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1097\/TA.0000000000002562","volume":"88","author":"RG Kumar","year":"2020","unstructured":"Kumar, R. G. et al. Effects of hospital-acquired pneumonia on long-term recovery and hospital resource utilization following moderate to severe traumatic brain injury. J. Trauma Acute Care Surg. 88, 491\u2013500 (2020).","journal-title":"J. Trauma Acute Care Surg."},{"key":"7367_CR5","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.neuropharm.2018.07.022","volume":"145","author":"H Shi","year":"2019","unstructured":"Shi, H., Hua, X., Kong, D., Stein, D. & Hua, F. Role of Toll-like receptor mediated signaling in traumatic brain injury. Neuropharmacology 145, 259\u2013267 (2019).","journal-title":"Neuropharmacology"},{"key":"7367_CR6","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1007\/s10571-016-0400-1","volume":"37","author":"ML Pearn","year":"2017","unstructured":"Pearn, M. L. et al. Pathophysiology associated with traumatic brain injury: Current treatments and potential novel therapeutics. Cell. Mol. Neurobiol. 37, 571\u2013585 (2017).","journal-title":"Cell. Mol. Neurobiol."},{"key":"7367_CR7","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1016\/j.neuron.2017.07.010","volume":"95","author":"YN Jassam","year":"2017","unstructured":"Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B. & El Khoury, J. Neuroimmunology of traumatic brain injury: Time for a paradigm shift. Neuron 95, 1246\u20131265 (2017).","journal-title":"Neuron"},{"key":"7367_CR8","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1007\/s12035-010-8098-4","volume":"41","author":"D Zhang","year":"2010","unstructured":"Zhang, D., Hu, X., Qian, L., O\u2019Callaghan, J. P. & Hong, J.-S. Astrogliosis in CNS pathologies: Is there a role for microglia?. Mol. Neurobiol. 41, 232\u2013241 (2010).","journal-title":"Mol. Neurobiol."},{"key":"7367_CR9","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/bph.13125","volume":"173","author":"IP Karve","year":"2016","unstructured":"Karve, I. P., Taylor, J. M. & Crack, P. J. The contribution of astrocytes and microglia to traumatic brain injury. Br. J. Pharmacol. 173, 692\u2013702 (2016).","journal-title":"Br. J. Pharmacol."},{"key":"7367_CR10","first-page":"376","volume":"7","author":"AJ Jahan-Abad","year":"2017","unstructured":"Jahan-Abad, A. J., Morteza-Zadeh, P., Negah, S. S. & Gorji, A. Curcumin attenuates harmful effects of arsenic on neural stem\/progenitor cells. Avicenna J. Phytomed. 7, 376 (2017).","journal-title":"Avicenna J. Phytomed."},{"key":"7367_CR11","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1080\/01616412.2020.1782079","volume":"42","author":"X Fan","year":"2020","unstructured":"Fan, X. et al. Schisandrin B improves cerebral ischemia and reduces reperfusion injury in rats through TLR4\/NF-\u03baB signaling pathway inhibition. Neurol. Res. 42, 693\u2013702 (2020).","journal-title":"Neurol. Res."},{"key":"7367_CR12","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.arr.2017.02.004","volume":"36","author":"M Rahimifard","year":"2017","unstructured":"Rahimifard, M. et al. Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation. Ageing Res. Rev. 36, 11\u201319 (2017).","journal-title":"Ageing Res. Rev."},{"key":"7367_CR13","doi-asserted-by":"crossref","unstructured":"Ntoufa, S., Vilia, M. G., Stamatopoulos, K., Ghia, P. & Muzio, M. In Seminars in Cancer Biology. 15\u201325 (2016).","DOI":"10.1016\/j.semcancer.2016.07.001"},{"key":"7367_CR14","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/1742-2094-11-59","volume":"11","author":"H-T Zhu","year":"2014","unstructured":"Zhu, H.-T. et al. Curcumin attenuates acute inflammatory injury by inhibiting the TLR4\/MyD88\/NF-\u03baB signaling pathway in experimental traumatic brain injury. J. Neuroinflamm. 11, 59 (2014).","journal-title":"J. Neuroinflamm."},{"key":"7367_CR15","doi-asserted-by":"publisher","first-page":"9122","DOI":"10.1007\/s12035-018-1050-8","volume":"55","author":"AJ Jahan-Abad","year":"2018","unstructured":"Jahan-Abad, A. J. et al. Human neural stem\/progenitor cells derived from epileptic human brain in a self-assembling peptide nanoscaffold improve traumatic brain injury in rats. Mol. Neurobiol. 55, 9122\u20139138 (2018).","journal-title":"Mol. Neurobiol."},{"key":"7367_CR16","doi-asserted-by":"publisher","first-page":"2765","DOI":"10.1007\/s11064-019-02897-z","volume":"44","author":"M-L Luo","year":"2019","unstructured":"Luo, M.-L. et al. Transplantation of NSCs promotes the recovery of cognitive functions by regulating neurotransmitters in rats with traumatic brain injury. Neurochem. Res. 44, 2765\u20132775 (2019).","journal-title":"Neurochem. Res."},{"key":"7367_CR17","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.biomaterials.2016.07.028","volume":"105","author":"P Moshayedi","year":"2016","unstructured":"Moshayedi, P. et al. Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain. Biomaterials 105, 145\u2013155 (2016).","journal-title":"Biomaterials"},{"key":"7367_CR18","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.expneurol.2014.11.014","volume":"264","author":"MO Blaya","year":"2015","unstructured":"Blaya, M. O., Tsoulfas, P., Bramlett, H. M. & Dietrich, W. D. Neural progenitor cell transplantation promotes neuroprotection, enhances hippocampal neurogenesis, and improves cognitive outcomes after traumatic brain injury. Exp. Neurol. 264, 67\u201381 (2015).","journal-title":"Exp. Neurol."},{"key":"7367_CR19","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.3727\/096368916X691150","volume":"25","author":"J Gao","year":"2016","unstructured":"Gao, J. et al. Human neural stem cell transplantation-mediated alteration of microglial\/macrophage phenotypes after traumatic brain injury. Cell Transplant. 25, 1863\u20131877 (2016).","journal-title":"Cell Transplant."},{"key":"7367_CR20","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.hest.2019.12.005","volume":"1","author":"S Corey","year":"2020","unstructured":"Corey, S. et al. Harnessing the anti-inflammatory properties of stem cells for transplant therapy in hemorrhagic stroke. Brain Hemorrhages 1, 24\u201333 (2020).","journal-title":"Brain Hemorrhages"},{"key":"7367_CR21","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.clineuro.2018.07.013","volume":"173","author":"C Grochowski","year":"2018","unstructured":"Grochowski, C., Radzikowska, E. & Maciejewski, R. Neural stem cell therapy\u2014brief review. Clin. Neurol. Neurosurg. 173, 8\u201314 (2018).","journal-title":"Clin. Neurol. Neurosurg."},{"key":"7367_CR22","doi-asserted-by":"publisher","first-page":"8050","DOI":"10.1007\/s12035-016-0295-3","volume":"54","author":"SS Negah","year":"2017","unstructured":"Negah, S. S. et al. Enhancement of neural stem cell survival, proliferation, migration, and differentiation in a novel self-assembly peptide nanofibber scaffold. Mol. Neurobiol. 54, 8050\u20138062 (2017).","journal-title":"Mol. Neurobiol."},{"key":"7367_CR23","first-page":"98","volume":"162","author":"AI Ahmed","year":"2016","unstructured":"Ahmed, A. I., Gajavelli, S., Spurlock, M., Chieng, L. & Bullock, M. Stem cells for therapy in TBI. BMJ Milit. Health 162, 98\u2013102 (2016).","journal-title":"BMJ Milit. Health"},{"key":"7367_CR24","first-page":"17","volume":"20","author":"L Huang","year":"2017","unstructured":"Huang, L. & Wang, G. The effects of different factors on the behavior of neural stem cells. Stem Cells Int. 20, 17 (2017).","journal-title":"Stem Cells Int."},{"key":"7367_CR25","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.ejpb.2012.10.019","volume":"83","author":"A Zanotto-Filho","year":"2013","unstructured":"Zanotto-Filho, A. et al. Curcumin-loaded lipid-core nanocapsules as a strategy to improve pharmacological efficacy of curcumin in glioma treatment. Eur. J. Pharm. Biopharm. 83, 156\u2013167 (2013).","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"7367_CR26","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ijpharm.2017.03.019","volume":"523","author":"GM Soliman","year":"2017","unstructured":"Soliman, G. M. Nanoparticles as safe and effective delivery systems of antifungal agents: Achievements and challenges. Int. J. Pharm. 523, 15\u201332 (2017).","journal-title":"Int. J. Pharm."},{"key":"7367_CR27","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1179\/2045772313Y.0000000179","volume":"38","author":"H Ni","year":"2015","unstructured":"Ni, H. et al. Curcumin modulates TLR4\/NF-\u03baB inflammatory signaling pathway following traumatic spinal cord injury in rats. J. Spinal Cord Med. 38, 199\u2013206 (2015).","journal-title":"J. Spinal Cord Med."},{"key":"7367_CR28","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1007\/s43440-020-00112-3","volume":"72","author":"S Eghbaliferiz","year":"2020","unstructured":"Eghbaliferiz, S., Farhadi, F., Barreto, G. E., Majeed, M. & Sahebkar, A. Effects of curcumin on neurological diseases: Focus on astrocytes. Pharmacol. Rep. 72, 769\u2013782 (2020).","journal-title":"Pharmacol. Rep."},{"key":"7367_CR29","doi-asserted-by":"publisher","first-page":"3391","DOI":"10.1007\/s12035-020-01922-5","volume":"57","author":"S Sahab-Negah","year":"2020","unstructured":"Sahab-Negah, S. et al. Curcumin loaded in niosomal nanoparticles improved the anti-tumor effects of free curcumin on glioblastoma stem-like cells: An in vitro study. Mol. Neurobiol. 57, 3391\u20133411 (2020).","journal-title":"Mol. Neurobiol."},{"key":"7367_CR30","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1097\/TA.0b013e3181f30fc9","volume":"71","author":"M Li","year":"2011","unstructured":"Li, M. et al. Immediate splenectomy decreases mortality and improves cognitive function of rats after severe traumatic brain injury. J. Trauma Acute Care Surg. 71, 141\u2013147 (2011).","journal-title":"J. Trauma Acute Care Surg."},{"key":"7367_CR31","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.brainres.2015.02.039","volume":"1608","author":"C-Z Chang","year":"2015","unstructured":"Chang, C.-Z., Wu, S.-C., Lin, C.-L. & Kwan, A.-L. Curcumin, encapsulated in nano-sized PLGA, down-regulates nuclear factor \u03baB (p65) and subarachnoid hemorrhage induced early brain injury in a rat model. Brain Res. 1608, 215\u2013224 (2015).","journal-title":"Brain Res."},{"key":"7367_CR32","doi-asserted-by":"publisher","first-page":"5670","DOI":"10.1007\/s12274-018-2104-y","volume":"11","author":"A Joseph","year":"2018","unstructured":"Joseph, A. et al. Curcumin-loaded polymeric nanoparticles for neuroprotection in neonatal rats with hypoxic-ischemic encephalopathy. Nano Res. 11, 5670\u20135688 (2018).","journal-title":"Nano Res."},{"key":"7367_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12035-015-9635-y","volume":"54","author":"Z-Y Zhang","year":"2017","unstructured":"Zhang, Z.-Y. et al. Enhanced therapeutic potential of nano-curcumin against subarachnoid hemorrhage-induced blood\u2013brain barrier disruption through inhibition of inflammatory response and oxidative stress. Mol. Neurobiol. 54, 1\u201314 (2017).","journal-title":"Mol. Neurobiol."},{"key":"7367_CR34","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1089\/neu.2015.4158","volume":"34","author":"J Haarbauer-Krupa","year":"2017","unstructured":"Haarbauer-Krupa, J. et al. Screening for post-traumatic stress disorder in a civilian emergency department population with traumatic brain injury. J. Neurotrauma 34, 50\u201358 (2017).","journal-title":"J. Neurotrauma"},{"key":"7367_CR35","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1089\/neu.2013.3169","volume":"31","author":"AR Jayakumar","year":"2014","unstructured":"Jayakumar, A. R. et al. Activation of NF-\u03baB mediates astrocyte swelling and brain edema in traumatic brain injury. J. Neurotrauma 31, 1249\u20131257 (2014).","journal-title":"J. Neurotrauma"},{"key":"7367_CR36","first-page":"1147","volume":"74","author":"JR Hay","year":"2015","unstructured":"Hay, J. R., Johnson, V. E., Young, A. M., Smith, D. H. & Stewart, W. Blood-brain barrier disruption is an early event that may persist for many years after traumatic brain injury in humans. J. Neuropathol. Exp. Neurol. 74, 1147\u20131157 (2015).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"7367_CR37","doi-asserted-by":"publisher","first-page":"e88916","DOI":"10.1371\/journal.pone.0088916","volume":"9","author":"DR Ormond","year":"2014","unstructured":"Ormond, D. R. et al. Stem cell therapy and curcumin synergistically enhance recovery from spinal cord injury. PLoS\u00a0One 9, e88916 (2014).","journal-title":"PLoS\u00a0One"},{"key":"7367_CR38","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1097\/CCM.0000000000004575","volume":"48","author":"DA Godoy","year":"2020","unstructured":"Godoy, D. A., Aguilera, S. & Rabinstein, A. A. Potentially severe (moderate) traumatic brain injury: A new categorization proposal. Crit. Care Med. 48, 1851\u20131854 (2020).","journal-title":"Crit. Care Med."},{"key":"7367_CR39","doi-asserted-by":"publisher","first-page":"e0214741","DOI":"10.1371\/journal.pone.0214741","volume":"14","author":"DR Boone","year":"2019","unstructured":"Boone, D. R. et al. Traumatic brain injury induces long-lasting changes in immune and regenerative signaling. PLoS\u00a0One 14, e0214741 (2019).","journal-title":"PLoS\u00a0One"},{"key":"7367_CR40","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.actbio.2019.05.010","volume":"92","author":"SS Negah","year":"2019","unstructured":"Negah, S. S. et al. Transplantation of human meningioma stem cells loaded on a self-assembling peptide nanoscaffold containing IKVAV improves traumatic brain injury in rats. Acta Biomater. 92, 132\u2013144 (2019).","journal-title":"Acta Biomater."},{"key":"7367_CR41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-018-1391-2","volume":"16","author":"TJ Kr\u00e4mer","year":"2019","unstructured":"Kr\u00e4mer, T. J. et al. Depletion of regulatory T cells increases T cell brain infiltration, reactive astrogliosis, and interferon-\u03b3 gene expression in acute experimental traumatic brain injury. J. Neuroinflamm. 16, 1\u201314 (2019).","journal-title":"J. Neuroinflamm."},{"key":"7367_CR42","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.neulet.2013.11.050","volume":"560","author":"Y-F Wang","year":"2014","unstructured":"Wang, Y.-F. et al. Curcumin promotes the spinal cord repair via inhibition of glial scar formation and inflammation. Neurosci. Lett. 560, 51\u201356 (2014).","journal-title":"Neurosci. Lett."},{"key":"7367_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1742-2094-8-125","volume":"8","author":"M Karlstetter","year":"2011","unstructured":"Karlstetter, M. et al. Curcumin is a potent modulator of microglial gene expression and migration. J. Neuroinflamm. 8, 1\u201312 (2011).","journal-title":"J. Neuroinflamm."},{"key":"7367_CR44","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.biomaterials.2016.10.032","volume":"113","author":"R Requejo-Aguilar","year":"2017","unstructured":"Requejo-Aguilar, R. et al. Combined polymer-curcumin conjugate and ependymal progenitor\/stem cell treatment enhances spinal cord injury functional recovery. Biomaterials 113, 18\u201330 (2017).","journal-title":"Biomaterials"},{"key":"7367_CR45","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1113\/EP088697","volume":"105","author":"F Attari","year":"2020","unstructured":"Attari, F., Ghadiri, T. & Hashemi, M. Combination of curcumin with autologous transplantation of adult neural stem\/progenitor cells leads to more efficient repair of damaged cerebral tissue of rat. Exp. Physiol. 105, 1610\u20131622 (2020).","journal-title":"Exp. Physiol."},{"key":"7367_CR46","first-page":"4284","volume":"20","author":"LM Kelso","year":"2014","unstructured":"Kelso, L. M. & Gendelman, E. H. Bridge between neuroimmunity and traumatic brain injury. Curr. Pharm. Des. 20, 4284\u20134298 (2014).","journal-title":"Curr. Pharm. Des."},{"key":"7367_CR47","doi-asserted-by":"publisher","first-page":"284","DOI":"10.12659\/MSM.894148","volume":"22","author":"X-E Meng","year":"2016","unstructured":"Meng, X.-E. et al. Hyperbaric oxygen alleviates secondary brain injury after trauma through inhibition of TLR4\/NF-\u03baB signaling pathway. Med. Sci. Monit. 22, 284 (2016).","journal-title":"Med. Sci. Monit."},{"key":"7367_CR48","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.bbi.2017.04.006","volume":"64","author":"F Corrigan","year":"2017","unstructured":"Corrigan, F., Arulsamy, A., Collins-Praino, L. E., Holmes, J. L. & Vink, R. Toll like receptor 4 activation can be either detrimental or beneficial following mild repetitive traumatic brain injury depending on timing of activation. Brain Behav. Immun. 64, 124\u2013139 (2017).","journal-title":"Brain Behav. Immun."},{"key":"7367_CR49","doi-asserted-by":"publisher","first-page":"3160","DOI":"10.1080\/15384101.2019.1670509","volume":"18","author":"Y Shang","year":"2019","unstructured":"Shang, Y., Dai, S., Chen, X., Wen, W. & Liu, X. MicroRNA-93 regulates the neurological function, cerebral edema and neuronal apoptosis of rats with intracerebral hemorrhage through TLR4\/NF-\u03baB signaling pathway. Cell Cycle 18, 3160\u20133176 (2019).","journal-title":"Cell Cycle"},{"key":"7367_CR50","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jneuroim.2017.06.006","volume":"310","author":"X Yao","year":"2017","unstructured":"Yao, X. et al. TLR4 signal ablation attenuated neurological deficits by regulating microglial M1\/M2 phenotype after traumatic brain injury in mice. J. Neuroimmunol. 310, 38\u201345 (2017).","journal-title":"J. Neuroimmunol."},{"key":"7367_CR51","doi-asserted-by":"publisher","first-page":"921","DOI":"10.3892\/ijmm.2016.2495","volume":"37","author":"Y Feng","year":"2016","unstructured":"Feng, Y. et al. Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4\/NF-\u03baB signaling pathway in experimental traumatic brain injury. Int. J. Mol. Med. 37, 921\u2013930 (2016).","journal-title":"Int. J. Mol. Med."},{"key":"7367_CR52","doi-asserted-by":"publisher","first-page":"e57208","DOI":"10.1371\/journal.pone.0057208","volume":"8","author":"A Ahmad","year":"2013","unstructured":"Ahmad, A. et al. Absence of TLR4 reduces neurovascular unit and secondary inflammatory process after traumatic brain injury in mice. PLoS\u00a0One 8, e57208 (2013).","journal-title":"PLoS\u00a0One"},{"key":"7367_CR53","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1016\/j.spinee.2019.07.013","volume":"19","author":"Y-S Lee","year":"2019","unstructured":"Lee, Y.-S. et al. Effect of curcumin on the inflammatory reaction and functional recovery after spinal cord injury in a hyperglycemic rat model. Spine J. 19, 2025\u20132039 (2019).","journal-title":"Spine J."},{"key":"7367_CR54","first-page":"096032712110033","volume":"20","author":"L Fan","year":"2021","unstructured":"Fan, L., Dong, J., He, X., Zhang, C. & Zhang, T. Bone marrow mesenchymal stem cells-derived exosomes reduce apoptosis and inflammatory response during spinal cord injury by inhibiting the TLR4\/MyD88\/NF-\u03baB signaling pathway. Human Exp. Toxicol. 20, 09603271211003311 (2021).","journal-title":"Human Exp. Toxicol."},{"key":"7367_CR55","doi-asserted-by":"publisher","first-page":"3763","DOI":"10.1021\/acsami.8b20594","volume":"11","author":"Y Wang","year":"2019","unstructured":"Wang, Y., Luo, J. & Li, S.-Y. Nano-curcumin simultaneously protects the blood-brain barrier and reduces M1 microglial activation during cerebral ischemia-reperfusion injury. ACS Appl. Mater. Interfaces 11, 3763\u20133770 (2019).","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"7367_CR56","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s00441-020-03247-0","volume":"382","author":"SS Negah","year":"2020","unstructured":"Negah, S. S. et al. Transplantation of R-GSIK scaffold with mesenchymal stem cells improves neuroinflammation in a traumatic brain injury model. Cell Tissue Res. 382, 575\u2013583 (2020).","journal-title":"Cell Tissue Res."},{"key":"7367_CR57","first-page":"20","volume":"20","author":"P Zamani Esmati","year":"2021","unstructured":"Zamani Esmati, P., Baharara, J., Sahab Negah, S. & Nejad Shahrokhabadi, K. Leukemia-derived exosomes activate migration and tumor-associated genes in astrocytes isolated from human brain tissue. Int. J. Pediatr. 20, 20 (2021).","journal-title":"Int. J. Pediatr."},{"key":"7367_CR58","doi-asserted-by":"publisher","first-page":"358","DOI":"10.21307\/ane-2018-035","volume":"78","author":"J Ruzicka","year":"2018","unstructured":"Ruzicka, J. et al. Anti-inflammatory compound curcumin and mesenchymal stem cells in the treatment of spinal cord injury in rats. Acta Neurobiol. Exp 78, 358\u2013374 (2018).","journal-title":"Acta Neurobiol. Exp"},{"key":"7367_CR59","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1161\/01.STR.32.4.1005","volume":"32","author":"J Chen","year":"2001","unstructured":"Chen, J. et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32, 1005\u20131011 (2001).","journal-title":"Stroke"},{"key":"7367_CR60","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jneumeth.2013.12.008","volume":"225","author":"H Aligholi","year":"2014","unstructured":"Aligholi, H. et al. A new and safe method for stereotactically harvesting neural stem\/progenitor cells from the adult rat subventricular zone. J. Neurosci. Methods 225, 81\u201389 (2014).","journal-title":"J. Neurosci. Methods"},{"key":"7367_CR61","first-page":"907","volume":"31","author":"SS Chiu","year":"2011","unstructured":"Chiu, S. S. et al. Differential distribution of intravenous curcumin formulations in the rat brain. Anticancer Res. 31, 907\u2013911 (2011).","journal-title":"Anticancer Res."},{"key":"7367_CR62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40360-017-0192-z","volume":"19","author":"RE Najafabadi","year":"2018","unstructured":"Najafabadi, R. E., Kazemipour, N., Esmaeili, A., Beheshti, S. & Nazifi, S. Using superparamagnetic iron oxide nanoparticles to enhance bioavailability of quercetin in the intact rat brain. BMC Pharmacol. Toxicol. 19, 1\u201312 (2018).","journal-title":"BMC Pharmacol. Toxicol."},{"key":"7367_CR63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1742-2094-10-106","volume":"10","author":"R Zhang","year":"2013","unstructured":"Zhang, R. et al. Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell transplantation in experimental traumatic brain injury. J. Neuroinflamm. 10, 1\u201312 (2013).","journal-title":"J. Neuroinflamm."},{"key":"7367_CR64","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3389\/fnana.2015.00022","volume":"9","author":"S Goto","year":"2015","unstructured":"Goto, S., Morigaki, R., Okita, S., Nagahiro, S. & Kaji, R. Development of a highly sensitive immunohistochemical method to detect neurochemical molecules in formalin-fixed and paraffin-embedded tissues from autopsied human brains. Front. Neuroanat. 9, 22 (2015).","journal-title":"Front. Neuroanat."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-07367-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-07367-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-07367-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T23:52:08Z","timestamp":1669333928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-07367-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,4]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["7367"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-07367-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,4]]},"assertion":[{"value":"2 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3572"}}