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Journal of Neurorestoratology  2017, Vol. 5 Issue (1): 51-57    doi: 10.2147/JN.S99014
Clinical neurorestorative progresses in cerebral palsy
Alok Sharma1, Tongchao Geng2, Hemangi Sane3, Pooja Kulkarni3
1 Department of Medical Services & Clinical Research, NeuroGen Brain and Spine Institute, Mumbai, India;
2 Department of Neurology, Yuquan Hospital, Tsinghua University, Beijing, People’s Republic of China;
3 Department of Research and Development, Neurogen Brain and Spine Institute, Mumbai, India
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Abstract  Cerebral palsy (CP), group of permanent nonprogressive clinical disorders in children, is caused by damage to the immature brain. Conventionally available treatments for CP are mainly targeted toward management of its symptoms. With the upcoming field of neurorestorative strategies, we are now able to repair the core brain damage in CP. There are various drugs, stem cells, etc, which have been implicated to have neurorestorative properties. Autologous bone marrow stem cells, umbilical cord stem cells, neural stem cells, and olfactory ensheathing cells have shown the safety and efficacy in preliminary studies. Here, we review the different medicines and cell types that have shown beneficial effects in clinical studies. We propose that combination strategies may be the future of neurorestoration.

Key wordsstem cell therapy      bone marrow      umbilical cord      neural cells      regenerative medicine      brain     
Received: 23 October 2015      Published: 26 December 2017
Corresponding Authors: Alok Sharma, NeuroGen Brain & Spine Institute, Stem Asia Hospital and Research Centre Plot No 19, Sector 40, Opp Rail Vihar, Next to Seawood Station (W), Navi Mumbai-400706, India Tel +91 22 2528 3706 Email   
Cite this article:

Alok Sharma, Tongchao Geng, Hemangi Sane, Pooja Kulkarni. Clinical neurorestorative progresses in cerebral palsy. Journal of Neurorestoratology, 2017, 5: 51-57.

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1. Carroll JE, Robert WM.Update on stem cell therapy for cerebral palsy.Expert Opin Biol Ther. 2011;11(4):463-471.
2. Novak I, Hines M, Goldsmith S, Barclay R.Clinical prognostic messages from a systematic review on cerebral palsy.Pediatrics. 2012;130(5):e1285-e1312.
3. Irazábal M, Marsà F, García M, et al.Family burden related to clinical and functional variables of people with intellectual disability with and without a mental disorder.Res Dev Disabil. 2012;33(3):796-803.
4. Rosenbaum P, Paneth N, Leviton A, et al.A report: the definition and classification of cerebral palsy.Dev Med Child Neurol Suppl. 2007;109:8-14.
5. Lynn AK, Turner M, Chambers HG.Surgical management of spasticity in persons with cerebral palsy.PM R. 2009, 1(9):834-838.
6. Cajal SRY.Degeneration and Regeneration of the Nervous System (translated by RM May). London: Oxford University Press; 1928.
7. Wang Y, Gao B, Yang W.Clinical effect of oxiracetam capsules in the children suffering from cerebral palsy.Chin J Neuromed. 2007;4:409-411.
8. Izhbuldina GI.Changes in the hemostasis system and free-radical lipid oxidation in the acute stage of ischemic stroke in patients on neuroprotection treatment.Zh Nevrol Psikhiatr Im S S Korsakova. 2012;112(3 Pt 2):31-37.
9. Zhang C, Chopp M, Cui Y, et al.Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke.J Neurosci Res. 2010;88:3275-3281.
10. Hassanein SM, Deifalla SM, El-Houssinie M, Mokbel SA.Safety and efficacy of cerebrolysin in infants with communication defects due to severe perinatal brain insult: a randomized controlled clinical trial.J Clin Neurol. 2016;12(1):79-84.
11. Xiaoming L.Point injection of cerebrolysin in treatment of child cerebral palsy.Acta Acad Medicin Bengbu. 2004;29(4):331-332.
12. Rong X, Zhou W, Chen XW, Tao L, Tang J.Ganglioside GM1 reduces white matter damage in neonatal rats.Acta Neurobiol Exp. 2013;73:379-386.
13. Lee HS, Song J, Min K, et al.Short-term effects of erythropoietin on neurodevelopment in infants with cerebral palsy: a pilot study.Brain Dev. 2014;36(9):764-769.
14. Jantzie LL, Miller RH, Robinson S.Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic-ischemic brain injury.Pediatr Res. 2013;74(6):658-667.
15. Ohls RK, Kamath-Rayne BD, Christensen RD, et al.Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo.Pediatrics. 2014;133(6):1023-1030.
16. Kinney HC, Haynes RL, Xu G, et al.Neuron deficit in the white matter and subplate in periventricular leukomalacia.Ann Neurol. 2012;71(3):397-406.
17. Khwaja O, Volpe JJ.Pathogenesis of cerebral white matter injury of prematurity.Arch Dis Child Fetal Neonatal Ed. 2008;93(2):F153-F161.
18. Alvarez P, Carrillo E, Vélez C, et al.Regulatory systems in bone marrow for hematopoietic stem/progenitor cells mobilization and homing.Biomed Res Int. 2013;2013:312656.
19. Gnecchi M, Zhang Z, Ni A, Dzau, VJ.Paracrine mechanisms in adult stem cell signaling and therapy.Circ Res. 2008;103(11):1204-1219.
20. Daadi MM, Davis AS, Arac A, et al.Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury.Stroke. 2010;41(3):516-523.
21. Sharma S, Yang B, Strong R, et al.Bone marrow mononuclear cells protect neurons and modulate microglia in cell culture models of ischemic stroke.J Neurosci Res. 2010;88(13):2869-2876.
22. Brenneman M, Sharma S, Harting M, et al.Autologous bone marrow mononuclear cells enhance recovery after acute ischemic stroke in young and middle-aged rats.J Cereb Blood Flow Metab. 2010;30(1):140-149.
23. Bianco P, Riminucci M, Gronthos S, Robey PG.Bone marrow stromal stem cells: nature, biology, and potential applications.Stem Cells. 2001;19(3):180-192.
24. Sharma A, Gokulchandran N, Chopra G, et al.Administration of autologous bone marrow derived mononuclear cells in children with incurable neurological disorders and injury is safe and improves their quality of life.Cell Transplant. 2012;21(Suppl 1):S1-S12.
25. Sharma A.Stem Cell Therapy in Neurological Disorders. Mumbai: NeuroGen Brain and Spine Institute; 2014.
26. Sharma A, Kulkarni P, Sane H, et al.Positron emission tomography-computed tomography scan captures the effects of cellular therapy in a case of cerebral palsy.J Clin Case Rep. 2012;2:195.
27. Sharma A, Sane H, Paranjape A, et al.Positron emission tomography - computer tomography scan used as a monitoring tool following cellular therapy in cerebral palsy and mental retardation - a case report.Case Rep Neurol Med. 2013;2013:141983.
28. Purandare C, Shitole DG, Belle V, Kedari A, Bora N, Joshi M.Therapeutic potential of autologous stem cell transplantation for cerebral palsy.Case Rep Transplant. 2012;2012:825289.
29. Mancías-Guerra C, Marroquín-Escamilla AR, González-Llano O, et al.Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial. Cytotherapy. 2014;16(6):810-820.
30. Chen G, Wang Y, Xu Z, et al.Neural stem cell-like cells derived from autologous bone mesenchymal stem cells for the treatment of patients with cerebral palsy.J Transl Med. 2013;11:21.
31. Wang X, Cheng H, Hua R, et al.Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study.Cytotherapy. 2013;15(12):1549-1562.
32. Newcomb JD, Willing AE, Sanberg PR.Umbilical cord blood cells.Methods Mol Biol. 2009;549:119-136.
33. Moise KJ.Umbilical cord stem cells.Obstet Gynecol. 2005;106(6):1393-1407.
34. Chik KW, Chan PK, Li CK, et al.Human herpes virus-6 encephalitis after unrelated umbilical cord blood transplant in children.Bone Marrow Transplant. 2002;99:991-994.
35. El-Cheikh J, Fürst S, Casalonga F, et al.JC virus leuko-encephalopathy in reduced intensity conditioning cord blood transplant recipient with a review of the literature.Mediterr J Hematol Infect Dis. 2012;4(1):e2012043.
36. Papadopoulos KI, Low SS, Aw TC, Chantarojanasiri T.Safety and feasibility of autologous umbilical cord blood transfusion in 2 toddlers with cerebral palsy and the role of low dose granulocyte-colony stimulating factor injections.Restor Neurol Neurosci. 2011;29(1):17-22.
37. Jensen A, Hamelmann E.First autologous cell therapy of cerebral palsy caused by hypoxic-ischemic brain damage in a child after cardiac arrest-individual treatment with cord blood.Case Rep Transplant. 2013;2013:951827.
38. Wang L, Ji H, Zhou J, et al.Therapeutic potential of umbilical cord mesenchymal stromal cells transplantation for cerebral palsy: a case report.Case Rep Transplant. 2013;2013:146347.
39. Luan Z, Liu W, Qu S, et al.Effects of neural progenitor cell transplantation in children with severe cerebral palsy.Cell Transplant. 2012;21(Suppl 1):S91-S98.
40. Min K, Song J, Kang JY, et al.Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial.Stem Cells. 2013;31(3):581-591.
41. Huang H, Chen L, Xi H, et al.Olfactory ensheathing cells transplantation for central nervous system diseases in 1,255 patients.Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009;23(1):14-20.
42. Fischer UM., Harting MT, Jimenez F, et al.Pulmonary passage is a major obstacle for intravenous stem cell delivery: The pulmonary first-pass effect.Stem Cells Dev. 2009;18(5):683-691.
43. Lim JY, Jeong CH, Jun JA, et al.Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia.Stem Cell Res Ther. 2011;2(5):38.
44. Kondziolka D, Steinberg G, Wechsler L, et al.Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial.J Neurosurg. 2005;103:38-45.
45. Shankaran S, Laptook AR, Ehrenkranz RA, et al.Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy.N Engl J Med. 2005;353:1574-1584.
46. Rutherford MA, Azzopardi D, Whitelaw A, et al.Mild hypothermia and the distribution of cerebral lesions in neonates with hypoxic-ischemic encephalopathy.Pediatrics. 2005;116:1001-1006.
47. Lei B, Tan X, Cai H, Xu Q, Guo Q.Effect of moderate hypothermia on lipid peroxidation in canine brain tissue after cardiac arrest and resuscitation.Stroke. 1994;25:147-152.
48. Thoresen M, Penrice J, Lorek A, et al.Mild hypothermia after severe transient hypoxia-ischemia ameliorates delayed cerebral energy failure in the newborn piglet.Pediatr Res. 1995;37:667-670.
49. Azzopardi DV, Strohm B, Edwards AD, et al.Moderate hypothermia to treat perinatal asphyxial encephalopathy.N Engl J Med. 2009;361:1349-1358.
50. Gluckman PD, Wyatt JS, Azzopardi D, et al.Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial.Lancet. 2005;365:663-670.
51. Gonzalez-Ibarra FP, Varon J, Lopez-Meza EG.Therapeutic hypothermia: critical review of the molecular mechanism of action.Front Neurol. 2011;2:4.
52. Gonzales-Portillo GS, Reyes S, Aguirre D, Pabon MM, Borlongan CV.Stem cell therapy for neonatal hypoxic-ischemic encephalopathy.Front Neurol. 2014;5:147.
53. Mukherjee A, Raison M, Sahni T, et al.Intensive rehabilitation combined with HBO2 therapy in children with cerebral palsy: a controlled longitudinal study.Undersea Hyperb Med. 2014;41(2):77-85.
54. Lacey DJ, Stolfi A, Pilati LE.Effects of hyperbaric oxygen on motor function in children with cerebral palsy.Ann Neurol. 2012;72(5):695-703.
55. Pérez-Gaxiola G.Hyperbaric oxygen did not improve symptoms in children with cerebral palsy.Arch Dis Child Educ Pract Ed. 2013;98(5):198.
56. Sharma A, Sane H, Paranjape A, Gokulchandran N, Takle M, Badhe P.Seizures as an adverse event of cellular therapy in pediatric neurological disorders and its prevention.J Neurol Disord. 2014;2:164.
57. Debuse D, Brace H.Outcome measures of activity for children with cerebral palsy: a systematic review.Pediatr Phys Ther. 2011;23(3):221-231.
58. Bax M, Tydeman C, Flodmark O.Clinical and MRI correlates of cerebral palsy: The European Cerebral Palsy Study.JAMA. 2006;296(13):1602-1608.
59. Li DK, Li MJ, Traboulsee A, Zhao G, Riddehough A, Paty D.The use of MRI as an outcome measure in clinical trials.Adv Neurol. 2006;98:203-226.
60. Spiriev T, Sandu N, Schaller B.Molecular imaging and tracking stem cells in neurosciences.Methods Mol Biol. 2013;1052:195-201.
61. Sandu N, Momen-Heravi F, Sadr-Eshkevari P, Schaller B.Molecular imaging for stem cell transplantation in neuroregenerative medicine.Neurodegener Dis. 2012;9(2):60-67.
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