Traumatic brain injury: basic cellular mechanisms and new approaches to therapy
- Authors: Sudina A.K.1,2, Grinchevskaia L.R.1,2, Goldstein D.V.1,2, Fatkhudinov T.H.1,2, Salikhova D.I.1,2
-
Affiliations:
- RUDN University
- Federal State Budgetary Institution Research Centre for Medical Genetics
- Issue: Vol 28, No 2 (2024): CARDIOLOGY
- Pages: 246-255
- Section: CYTOLOGY
- URL: https://journal-vniispk.ru/2313-0245/article/view/319764
- DOI: https://doi.org/10.22363/2313-0245-2024-28-1-246-255
- EDN: https://elibrary.ru/ZUTIHV
- ID: 319764
Cite item
Full Text
Abstract
Relevance. Traumatic brain injury (TBI) is a serious medical problem and one of the leading causes of disability and mortality among military personnel and civilians. It is known that about 1.5 million people in the world die from TBI every year, while about 2.5–3 million lose work capacity. In Russia, one million people are diagnosed with TBI every year, among which one in five gets group I or II disability. Despite significant efforts in research, effective TBI treatment methods are still limited, as TBI leads to a wide range of pathological changes in brain tissues. Primary brain damage is an acute and irreversible mechanical damage to the parenchyma of the nervous tissue. Among subsequent secondary processes are excitotoxicity, mitochondrial dysfunction, oxidative stress, axon degeneration, and neuroinflammation. These processes are often long and can take from several days to several years. Recent advances in cell therapy are opening up new perspectives for the treatment of this condition. The current review examines the main cellular mechanisms of TBI acute and chronic phases, as well as the treatment prospects for the use of stem cells for. Analysis of recent studies on the use of cell therapy in TBI is presented. Various types of stem cells such as neural stem cells, mesenchymal stromal cells and others are considered in the context of their potential to repair damaged brain tissues. Special attention is paid to the cells action mechanisms in the regeneration process, including their effect on inflammation, neurogenesis, and synaptic plasticity. The issue of using paracrine factors secreted by stem cells as a potential drug for traumatic brain injuries treatment is addressed. Conclusion. Сell therapy, as well as the use of products secreted by cells, is one of the new and promising ways of treating TBI.
About the authors
Anastasiia K. Sudina
RUDN University; Federal State Budgetary Institution Research Centre for Medical Genetics
Author for correspondence.
Email: sudyina-ak@rudn.ru
ORCID iD: 0000-0003-3531-7684
SPIN-code: 5225-7878
Moscow, Russian Federation
Lidiia R. Grinchevskaia
RUDN University; Federal State Budgetary Institution Research Centre for Medical Genetics
Email: sudyina-ak@rudn.ru
ORCID iD: 0009-0008-5850-8460
Moscow, Russian Federation
Dmitry V. Goldstein
RUDN University; Federal State Budgetary Institution Research Centre for Medical Genetics
Email: sudyina-ak@rudn.ru
ORCID iD: 0000-0003-2438-1605
SPIN-code: 7714-9099
Moscow, Russian Federation
Timur H. Fatkhudinov
RUDN University; Federal State Budgetary Institution Research Centre for Medical Genetics
Email: sudyina-ak@rudn.ru
ORCID iD: 0000-0002-6498-5764
SPIN-code: 7919-8430
Moscow, Russian Federation
Diana I. Salikhova
RUDN University; Federal State Budgetary Institution Research Centre for Medical Genetics
Email: sudyina-ak@rudn.ru
ORCID iD: 0000-0001-7842-7635
SPIN-code: 1436-5027
Moscow, Russian Federation
References
- Burton D, Aisen M. Traumatic Brain Injury. Handbook of Secondary Dementials. 2006;26(7): 83-118. doi: 10.1177/0963689717714102
- Burda JE, Sofroniew MV. Reactive gliosis and the multicellular response to CNS damage and disease. Neuron. 2014;81(2):229-248. doi: 10.1016/j.neuron.2013.12.034
- Humble SS, Wilson LD, Wang L, Long DA, Smith MA, Siktberg JC, Mirhoseini MF, Bhatia A, Pruthi S, Day MA, Muehlschlegel S, Patel MB. Prognosis of diffuse axonal injury with traumatic brain injury. The journal of trauma and acute care surgery. 2018;85(1):155-159. doi: 10.1097/TA.0000000000001852
- Sulhan S, Lyon KA, Shapiro LA, Huang JH. Neuroinflammation and blood-brain barrier disruption following traumatic brain injury: Pathophysiology and potential therapeutic targets. Journal of neuroscience research. 2020;98(1):19-28. doi: 10.1002/jnr.24331
- Lu J, Goh SJ, Lei Tng YL, Deng YY, Ling EA, Moochhala S. Systemic inflammatory response following acute traumatic brain injury. Frontiers in bioscience (Landmark edition). 2009;14(10):3795-3813. doi: 10.2741/3489
- Beschorner R, Nguyen TD, Gözalan F, Pedal I, Mattern R, Schluesener HJ, Meyermann R, Schwab JM. CD14 expression by activated parenchymal microglia/macrophages and infiltrating monocytes following human traumatic brain injury. Acta neuropathologica. 2002;103(6)541-549. doi: 10.1007/s00401-001-0503-7
- Xiong Y, Mahmood A, Chopp M. Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities. Chinese journal of traumatology. 2018;21(3):137-151. doi: 10.1016/j.cjtee.2018.02.003
- Bergold PJ. Treatment of traumatic brain injury with anti-inflammatory drugs. Experimental neurology. 2016;275(3):367-380. doi: 10.1016/j.expneurol.2015.05.024
- Wu H, Zheng J, Shenbin X, Fang Y, Wu Y, Zeng J, Shao A, Shi L, Lu J, Mei S, Wang X, Guo X, Wang Y, Zhao Z, Zhang J. Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury. Journal of neuroinflammation. 2021;18(1):1-20. doi: 10.1186/s12974-020-02041-7
- Chiu CC, Liao YE, Yang LY, Wang JY, Tweedie D, Karnati HK, Greig NH, Wang JY. Neuroinflammation in animal models of traumatic brain injury. Journal of neuroscience methods. 2016;272:38-49. doi: 10.1016/j.jneumeth.2016.06.018
- Brenner M. Role of GFAP in CNS injuries. Neuroscence. Letters. 2014;565:7-13. doi: 10.1016/j.neulet.2014.01.055
- Engelmann C, Weih F, Haenold R. Role of nuclear factor kappa B in central nervous system regeneration. Neural regeneration research. 2014;9(7):707-711. doi: 10.4103/1673-5374.131572
- Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541(7638):481-487. doi: 10.1038/nature21029
- Rhodes J. Peripheral immune cells in the pathology of traumatic brain injury? Current opinion in critical care. 2011;17(2):122-130. doi: 10.1097/MCC.0b013e3283447948
- Weston NM, Sun D. The Potential of Stem Cells in Treatment of Traumatic Brain Injury. Current neurology and neuroscience reports. 2018;18(1):1. doi: 10.1007/s11910-018-0812-z
- Li X, Sundström. Stem Cell Therapies for Central Nervous System Trauma: The 4 Ws-What, When, Where, and Why. Stem cells translational medicine. 2022;11(1):14-25. doi: 10.1093/stcltm/szab006
- Bonilla C, Zurita M. Cell-based therapies for traumatic brain injury: Therapeutic treatments and clinical trials. Biomedicines. 2021;9(6)1-34. doi: 10.3390/biomedicines9060669
- Pang AL, Xiong LL, Xia QJ, Liu F, Wang YC, Liu F, Zhang P, Meng BL, Tan S, Wang TH. Neural stem cell transplantation is associated with inhibition of apoptosis, Bcl-xL upregulation, and recovery of neurological function in a rat model of traumatic brain injury. Cell transplantation. 2017;26(7):1262-1275. doi: 10.1177/0963689717715168
- Hentze H, Graichen R, Colman A. Cell therapy and the safety of embryonic stem cell-derived grafts. Trends in biotechnology. 2007;25(1):24-32. doi: 10.1016/j.tibtech.2006.10.010
- Narouiepour A, Ebrahimzadeh-Bideskan A, Rajabzadeh G, Gorji A, Negah SS. Neural stem cell therapy in conjunction with curcumin loaded in niosomal nanoparticles enhanced recovery from traumatic brain injury. Scietific reports. 2022;12(1):1-13. doi: 10.1038/s41598-022-07367-1
- Haus DL, López-Velázquez L, Gold EM, Cunningham KM, Perez H, Anderson AJ, Cummings BJ. Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury. Experimental neurology. 2016;281:1-16. doi: 10.1016/j.expneurol.2016.04.008
- Takahashi K, Yamanaka S. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell. 2006;126(4):663-676. doi: 10.1016/j.cell.2006.07.024
- Dunkerson J, Moritz KE, Young J, Pionk T, Fink K, Rossignol J, Dunbar G, Smith JS. Combining enriched environment and induced pluripotent stem cell therapy results in improved cognitive and motor function following traumatic brain injury. Restorative neurology and neuroscience. 2014;32(5):675-687. doi: 10.3233/RNN-140408
- Wei ZZ, Lee JH, Zhang Y, Zhu YB, Deveau TC, Gu X, Winter MM, Li J, Wei L, Yu SP. Intracranial Transplantation of Hypoxia-Preconditioned iPSC-Derived Neural Progenitor Cells Alleviates Neuropsychiatric Defects after Traumatic Brain Injury in Juvenile Rats. Cell transplantation. 2016;25(5):797-809. doi: 10.3727/096368916X690403
- Zhang K, Jiang Y, Wang B, Li T, Shang D, Zhang X. Mesenchymal Stem Cell Therapy: A Potential Treatment Targeting Pathological Manifestations of Traumatic Brain Injury. Oxidative medicine and cellular longevity. 2022;2022. doi: 10.1155/2022/4645021
- Silachev DN, Plotnikov EYu, Babenko VA, Danilina TI, Zorova LD, Pevzner IB, Zorov DB, Sukhikh GT. Intra-Arterial Administration of Multipotent Mesenchymal Stromal Cells Promotes Functional Recovery of the Brain After Traumatic Brain Injury. Bulletin of experimental biology and medicine. 2015;159(4):528-533. doi: 10.1007/s10517-015-3009-3 (In Russian)
- Cox CS, Hetz RA, Liao GP, Aertker BM, Ewing-Cobbs L, Juranek J, Savitz SI, Jackson ML, Romanowska-Pawliczek AM, Triolo F, Dash PK, Pedroza C, Lee DA, Worth L, Aisiku IP, Choi HA, Holcomb JB, Kitagawa RS. Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells. Stem Cells. 2017;35(4):1065-1079. doi: 10.1002/stem.2538
- Tian C, Wang X, Wang X, Wang L, Wang X, Wu S, Wan Z. Autologous Bone Marrow Mesenchymal Stem Cell Therapy in the Subacute Stage of Traumatic Brain Injury by Lumbar Puncture. Experimental and clinical transplantation: official journal of the Middle East Society for Organ Transplantation. 2013;11(2):176-181. doi: 10.6002/ect.2012.0053
- Argibay B. Trekker J, Himmelreich U, Beiras A, Topete A, Taboada P, Pérez-Mato M, Vieites-Prado A, Iglesias-Rey R, Rivas J, Planas AM, Sobrino T, Castillo J, Campo F. Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia. Scietific reports. 2017;7(1):40758. doi: 10.1038/srep40758
- Pinho AG, Cibrão JR, Silva NA, Monteiro S, Salgado AJ. Cell secretome: Basic insights and therapeutic opportunities for CNS disorders. Pharmaceuticals. 2020;13(2):1-18. doi: 10.3390/ph13020031
- Yang HN, Wang C, Chen H, Li L, Ma S, Wang H, Fu YR, Qu T. Neural stem cell-conditioned medium ameliorated cerebral ischemia-reperfusion injury in rats. Stem Cells Internetional. 2018;2018:4659159. doi: 10.1155/2018/4659159
- Roura S, Monguió-Tortajada M, Munizaga-Larroudé M, Clos-Sansalvador M, Franquesa M, Rosell A, Borràs FE. Potential of extracellular vesicle-associated TSG-6 from adipose mesenchymal stromal cells in traumatic brain injury. International journal of molecular sciences. 2020;21(18):1-21. doi: 10.3390/ijms21186761
- Zhang Y, Zhang Y, Chopp M, Pang H, Zhang ZG, Mahmood A, Xiong Y. MiR-17-92 Cluster-Enriched Exosomes Derived from Human Bone Marrow Mesenchymal Stromal Cells Improve Tissue and Functional Recovery in Rats after Traumatic Brain Injury. Journal of neurotrauma. 2021;38(11):1535-1550. doi: 10.1089/neu.2020.7575
- Zhang Y, Chopp M, Meng Y, Katakowski M, Xin H, Mahmood A, Xiong Y. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. Journal of neurosurgery. 2015;122(4):856-867. doi: 10.3171/2014.11.JNS14770
- Liu YY, Li Y, Wang L, Zhao Y, Yuan R, Yang MM, Chen Y, Zhang H, Zhou FH, Qian ZR, Kang HJ. Mesenchymal stem cell-derived exosomes regulate microglia phenotypes: a promising treatment for acute central nervous system injury. Neural regeneration research. 2022;18(8):1657-1665. doi: 10.4103/1673-5374.363819
- Pischiutta F, Caruso E, Cavaleiro H, Salgado AJ, Loane DJ, Zanier ER. Mesenchymal stromal cell secretome for traumatic brain injury: Focus on immunomodulatory action. Experimental neurology. 2022;357:114199. doi: 10.1016/j.expneurol.2022.114199
- Sun MK, Passaro AP, Latchoumane CF, Spellicy SE, Bowler M, Goeden M, Martin WJ, Holmes PV, Stice SL, Karumbaiah L. Extracellular Vesicles Mediate Neuroprotection and Functional Recovery after Traumatic Brain Injury. Journal of neurotrauma. 2020;37(11):1358-1369. doi: 10.1089/neu.2019.6443
- Hering C, Shetty AK. Extracellular Vesicles Derived From Neural Stem Cells, Astrocytes, and Microglia as Therapeutics for Easing TBI-Induced Brain Dysfunction. Stem cells translational medicine. 2023;12(3):140-153. doi: 10.1093/stcltm/szad004
- Zhong L, Wang J, Wang P, Liu X, Liu P, Cheng X, Cao L, Wu H, Chen J, Zhou L. Neural stem cell-derived exosomes and regeneration: cell-free therapeutic strategies for traumatic brain injury. Stem cell research & therapy. 2023;14(1):198.
- Zhang Y, Liao JM, Zeng SX, Lu H. p53 downregulates Down syndrome-associated DYRK1A through miR-1246. EMBO Reports. 2011;12(8):811-817. doi: 10.1038/embor.2011.98
- Ma Y, Li C, Huang Y, Wang Y, Xia X, Zheng JC. Exosomes released from neural progenitor cells and induced neural progenitor cells regulate neurogenesis through miR-21a. Cell communication and signaling: CCS. 2019;17(1):96. doi: 10.1186/s12964-019-0418-3
Supplementary files
