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Journal of Neurorestoratology  2015, Vol. 3 Issue (1): 57-62    doi: 10.2147/JN.S74486
Clinical neurorestorative progress in traumatic brain injury
Huiling Huang1, Lin Chen2,3, Hongyun Huang4-6
1Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin Neurosurgical Institute, Tianjin, People's Republic of China;
2Medical Center, Tsinghua University, Beijing, People's Republic of China;
3Tsinghua University Yuquan Hospital, Beijing, People's Republic of China;
4General Hospital of Chinese people's Armed Police Forces,
5Beijing Rehabilitation Hospital of Capital Medical University, Beijing, People's Republic of China;
6Beijing Hongtianji Neuroscience Academy, Beijing, People's Republic of China;
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Abstract  Traumatic brain injury (TBI) is a leading cause of death and disability from trauma to the central nervous system. Besides the surgical interventions and symptomatic management, the conventional therapies for TBI and its sequelae are still limited. Recently emerging evidence suggests that some neurorestorative treatments appear to have a potential therapeutic role for TBI and improving the patient's quality of life. The current clinical neurorestorative strategies available in TBI include pharmacological treatments (recombinant human interleukin-1 receptor antagonist, amantadine, lithium, and valproate), the neuromodulation treatments (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and low-level laser therapy), cell transplantation (bone marrow stromal cells and umbilical cord stromal cells), and combined neurorehabilitation. In this review, we summarize the recent clinical neurorestorative progress in the management of neurodegeneration as well as cognitive and motor deficits after TBI; indeed further clinical trials are required to provide more robust evidence.

Key wordsbrain trauma      neurorestorative treatment      cell transplantation      clinical study     
Published: 26 December 2015
Corresponding Authors: Huiling Huang, No 122 Qixiangtai Road, Hexi District, Tianjin, 300060, People's Republic of China Email;Lin Chen, No 5 Shijingshan Road, Shijingshan District, Beijing 100040, People's Republic of China, Email   
Cite this article:

Huiling Huang, Lin Chen, Hongyun Huang. Clinical neurorestorative progress in traumatic brain injury. Journal of Neurorestoratology, 2015, 3: 57-62.

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1. Werner C, Engelhard K.Pathophysiology of traumatic brain injury.Br J Anaesth. 2007;99(1):4-9.
2. Freire MA.Pathophysiology of neurodegeneration following traumatic brain injury.West Indian Med J. 2012;61(7):751-755.
3. Keightley ML, Sinopoli KJ, Davis KD, et al.Is there evidence for neurodegenerative change following traumatic brain injury in children and youth? A scoping review.Front Hum Neurosci. 2014;8:139.
4. Schoch KM, Madathil SK, Saatman KE.Genetic manipulation of cell death and neuroplasticity pathways in traumatic brain injury.Neurotherapeutics. 2012;9(2):323-337.
5. Xiong Y, Mahmood A, Meng Y, et al.Neuroprotective and neurorestorative effects of thymosin β4 treatment following experimental traumatic brain injury.Ann N Y Acad Sci. 2012;1270:51-58.
6. Xiong Y, Mahmood A, Chopp M.Neurorestorative treatments for traumatic brain injury.Discov Med. 2010;10(54):434-442.
7. Miller G.Neuroscience. New guidelines aim to improve studies of traumatic brain injury.Science. 2010;328(5976):297.
8. Helmy A, Guilfoyle MR, Carpenter KL, et al.Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial.J Cereb Blood Flow Metab. 2014;34(5):845-851.
9. Meythaler JM, Brunner RC, Johnson A, Novack TA.Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial.J Head Trauma Rehabil. 2002;17(4):300-313.
10. Giacino JT, Whyte J, Bagiella E, et al.Placebo-controlled trial of amantadine for severe traumatic brain injury.N Engl J Med. 2012;366(9):819-826.
11. Leeds PR, Yu F, Wang Z, et al.A new avenue for lithium: intervention in traumatic brain injury. ACS Chem Neurosci. Epub April 11, 2014.
12. Tai YT, Lee WY, Lee FP, et al.Low dose of valproate improves motor function after traumatic brain injury.Biomed Res Int. 2014;2014:980657.
13. Ma CY, Xue YJ, Li M, Zhang Y, Li GZ.Sodium valproate for prevention of early posttraumatic seizures.Chin J Traumatol. 2010;13(5):293-296.
14. Pape TL, Rosenow JM, Patil V, et al.rTMS Safety for Two Subjects With Disordered Consciousness After Traumatic Brain Injury.Brain Stimul. 2014;7(4):620-622.
15. Demirtas-Tatlidede A, Vahabzadeh-Hagh AM, Bernabeu M, Tormos JM, Pascual-Leone A.Noninvasive brain stimulation in traumatic brain injury.J Head Trauma Rehabil. 2012;27(4):274-292.
16. Yen HL, Wong JT.Rehabilitation for traumatic brain injury in children and adolescents.Ann Acad Med Singapore. 2007;36(1):62-66.
17. Peters DM, Jain S, Liuzzo DM, et al.Individuals with chronic traumatic brain injury improve walking speed and mobility with intensive mobility training.Arch Phys Med Rehabil. 2014;95(8):1454-1460.
18. Li Y, Chopp M.Marrow stromal cell transplantation in stroke and traumatic brain injury.Neurosci Lett. 2009;456(3):120-123.
19. Heile A, Brinker T.Clinical translation of stem cell therapy in traumatic brain injury: the potential of encapsulated mesenchymal cell biodelivery of glucagon-like peptide-1.Dialogues Clin Neurosci. 2011;13(3):279-286.
20. Tian C, Wang X, Wang X, et al.Autologous bone marrow mesenchymal stem cell therapy in the subacute stage of traumatic brain injury by lumbar puncture.Exp Clin Transplant. 2013;11(2):176-181.
21. Cox CS Jr, Baumgartner JE, Harting MT, et al.Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children.Neurosurgery. 2011;68(3):588-600.
22. Zhang ZX, Guan LX, Zhang K, Zhang Q, Dai LJ.A combined procedure to deliver autologous mesenchymal stromal cells to patients with traumatic brain injury.Cytotherapy. 2008;10(2):134-139.
23. Wang S, Cheng H, Dai G, et al.Umbilical cord mesenchymal stem cell transplantation significantly improves neurological function in patients with sequelae of traumatic brain injury.Brain Res. 2013;1532:76-84.
24. Dela Peña I, Sanberg P, Acosta S, et al.Stem cells and G-CSF for treating neuroinflammation in traumatic brain injury: aging as a co-morbidity factor.J Neurosurg Sci. 2014;58(3):145-149.
25. Emsley HC, Smith CJ, Georgiou RF, et al.A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients.J Neurol Neurosurg Psychiatry. 2005;76(10):1366-1372.
26. Huang EY, Tsui PF, Kuo TT, et al.Amantadine ameliorates dopamine-releasing deficits and behavioral deficits in rats after fluid percussion injury. PLoS One. 2014;9(1):e86354.
27. Wang T, Huang XJ, Van KC, et al.Amantadine improves cognitive outcome and increases neuronal survival after fluid percussion traumatic brain injury in rats.J Neurotrauma. 2014;31(4):370-377.
28. Yu F, Wang Z, Tchantchou F, et al.Lithium ameliorates neurodegeneration, suppresses neuroinflammation, and improves behavioral performance in a mouse model of traumatic brain injury.J Neurotrauma. 2012;29(2):362-374.
29. Chen S, Wu H, Klebe D, Hong Y, Zhang J.Valproic Acid: a new candidate of therapeutic application for the acute central nervous system injuries.Neurochem Res. 2014;39(9):1621-1633.
30. Dash PK, Orsi SA, Zhang M, et al.Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats.PLoS One. 2010;5(6):e11383.
31. Villamar MF, Santos Portilla A, Fregni F, Zafonte R.Noninvasive brain stimulation to modulate neuroplasticity in traumatic brain injury.Neuromodulation. 2012;15(4):326-338.
32. Opydo-Chanek M.Bone marrow stromal cells in traumatic brain injury (TBI) therapy: true perspective or false hope?Acta Neurobiol Exp (Wars). 2007;67(2):187-195.
33. Liu W, Jiang X, Fu X, et al.Bone marrow stromal cells can be delivered to the site of traumatic brain injury via intrathecal transplantation in rabbits.Neurosci Lett. 2008;434(2):160-164.
34. Mahmood A, Lu D, Qu C, Goussev A, Chopp M.Long-term recovery after bone marrow stromal cell treatment of traumatic brain injury in rats.J Neurosurg. 2006;104(2):272-277.
35. Qu C, Mahmood A, Lu D, et al.Treatment of traumatic brain injury in mice with marrow stromal cells.Brain Res. 2008;1208:234-239.
36. Mahmood A, Lu D, Chopp M.Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury.J Neurotrauma. 2004;21(1):33-39.
37. Lu D, Li Y, Mahmood A, et al.Neural and marrow-derived stromal cell sphere transplantation in a rat model of traumatic brain injury.J Neurosurg. 2002;97(4):935-940.
38. Mahmood A, Lu D, Chopp M.Marrow stromal cell transplantation after traumatic brain injury promotes cellular proliferation within the brain.Neurosurgery. 2004;55(5):1185-1193.
39. Chen Q, Long Y, Yuan X, et al.Protective effects of bone marrow stromal cell transplantation in injured rodent brain: synthesis of neurotrophic factors.J Neurosci Res. 2005;80(5):611-619.
40. Bonilla C, Zurita M, Otero L, Aguayo C, Vaquero J.Delayed intralesional transplantation of bone marrow stromal cells increases endogenous neurogenesis and promotes functional recovery after severe traumatic brain injury.Brain Inj. 2009;23(9):760-769.
41. Mahmood A, Lu D, Qu C, Goussev A, Chopp M.Human marrow stromal cell treatment provides long-lasting benefit after traumatic brain injury in rats.Neurosurgery. 2005;57(5):1026-1031.
42. Li L, Jiang Q, Qu CS, et al.Transplantation of marrow stromal cells restores cerebral blood flow and reduces cerebral atrophy in rats with traumatic brain injury: In vivo MRI study.J Neurotrauma. 2011;28(4):535-545.
43. Hetz RA, Bedi SS, Olson S, et al.Progenitor cells: therapeutic targets after traumatic brain injury.Transl Stroke Res. 2012;3(3):318-323.
44. Steiner B, Roch M, Holtkamp N, et al.Systemically administered human bone marrow-derived mesenchymal stem home into peripheral organs but do not induce neuroprotective effects in the MCAo-mouse model for cerebral ischemia.NeurosciLett. 2012;513(1):25-30.
45. Lu D, Sanberg PR, Mahmood A, et al.Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after traumatic brain injury.Cell Transplant. 2002;11(3):275-281.
46. Secco M, Zucconi E, Vieira NM, et al.Multipotent stem cells from umbilical cord: cord is richer then blood!Stem Cells. 2008;26(1):146-150.
47. Newcomb JD, Willing AE, Sanberg PR.Umbilical cord blood cells.Methods Mol Biol. 2009;549:119-136.
48. Zigova T, Song S, Willing AE, et al.Human umbilical cord blood cells express neural antigens after transplantation into the developing rat brain.Cell Transplant. 2002;11(3):265-274.
49. Zanier ER, Montinaro M, Vigano M, et al.Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma.Crit Care Med. 2011;39(11):2501-2510.
50. Kernie SG, Parent JM.Forebrain neurogenesis after focal Ischemic and traumatic brain injury.Neurobiol Dis. 2010;37(2):267-274.
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