Growth Hormone and Visual Stimulation Restore Normal Vision in Children with Cerebral Palsy
Main Article Content
Abstract
A common problem in children affected by cerebral palsy, independently of its etiology, is the existence of visual impairment. In this retrospective study we analyzed the effects of Growth hormone (GH) administration (0,04 mg/kg/day, 5 days/week) together with visual stimulation with a tachistoscope in 42 children with cerebral palsy (22 boys, 20 girls, aged 2,48 ± 1,5 years [mean ± SD) in whom there was an evident lesion of the visual pathway. In 17 of these cases, prematurity was the responsible factor, while in the other 25 children, ischemic encephalopathy due to pre/perinatal problems was the origin of visual impairment. In addition, we analyzed three other children (1, 2 months and 1 year of age) in whom multicystic encephalopathy (due to severe hypoxia-ischemia at delivery) mainly affecting the occipital lobes was the responsible factor. Visual evoked potentials were recorded before beginning and after treatment, assessing the latency in ms of the N75, P100 and N140 waves, as well as the amplitude of the waves (µV). Treatment duration (mean ± SD) was 5.20 + 2.05 months. Completion of treatment was established by clinical criteria. The statistical significance of the data was carried out using the Wilcoxon test.
The treatment induced a significant decrease in the latency of N75, P100 and N140 (p < 0.001), as well as a clear tendency to increase the amplitude of the waves (p < 0.05). Of special interest is the case of a child affected by Multicystic Encephalopathy in which the cystic cavities in the occipital lobes detected by MRI before starting treatment (15 days of age) completely disappeared in a new MRI performed 1 year later. That child is now totally independent for activities of daily living. GH treatment did not produce any adverse effects. In summary, from our results we can conclude that the administration of GH added to visual stimulation with a tachistoscope is an effective and safe method for the repair of visual deficiencies in children with cerebral palsy, regardless of the existence or not of GH deficiency.
Keywords:
Cerebral palsy, Visual impairment, GH, tachistoscope, Myelination
Article Details
How to Cite
MYRADOVA, Selbi et al.
Growth Hormone and Visual Stimulation Restore Normal Vision in Children with Cerebral Palsy.
Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3069>. Date accessed: 05 nov. 2024.
doi: https://doi.org/10.18103/mra.v10i9.3069.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Krageloh-Mann I, Cans C. Cerebral palsy update. Brain Dev. 2009;31(7):537–544.
2. Kerem Gunel M. Rehabilitation of children with cerebral palsy from a physiotherapist’s perspective. Acta Orthop Traumatol Turc. 2009; 43(2):173–180.
3. Odding E, Roebroeck ME, Stam HJ. The epidemiology of cerebral palsy: incidence, impairments and risk factors. Disabil Rehabil. 2006; 28:183–191.
4. Rutherford MA, Supramaniam V, Ederies A, et al. Magnetic resonance imaging of white matter diseases of prematurity. Neuroradiology. 2010; 52(6)505-21.
5. Rong G, Weijian H, Yafeng D, Zhiyong Y, Stites J, Weiner CP. Brain injury caused by chronic fetal hypoxemia is mediated by inflammatory cascade activation. Reprod Sci. 2010;17:540–548.
6. Wong VCN. Cortical blindness in children: a study of etiology and prognosis. Pediatr Neurol. 1991;7:178–85.
7. Rogers M. Visual impairment in Liverpool: prevalence and morbidity. Arch Dis Child. 1996;74:299–303.
8. Ahmed M, Dutton GN. Cognitive visual dysfunction in a child with cerebral damage. Dev Med Child Neurol. 1996; 38(8):736-9.
9. Schenk-Rootlieb A J, van Nieuwenhuizen O, van Waes P F, van der Graaf Y. Cerebral visual impairment in cerebral palsy: Relation to structural abnormalities of the cerebrum. Neuropediatrics. 1994; 25(2): 68–72.
10. Uggetti C, Egitto MG, Fazzi E, et al. Cerebral visual impairment in periventricular leukomalacia: MR correlation. AJNR Am J Neuroradiol. 1996; 17(5): 979–985.
11. Philip SS, Dutton GN. Identifying and characterising cerebral visual impairment in children: A review. Clin Exp Optom. 2014; 97(3):196–208.
12. Striber N, Vulin K, Đaković I, et al. Visual impairment in children with cerebral palsy: Croatian population-based study for birth years 2003-2006. Croat Med J. 2019; 60(5):414-420.
13. Devesa P, Reimunde P, Gallego R, Devesa J, Arce VM.. Growth Hormone (GH) treatment may cooperate with locally-produced GH in increasing the proliferative response of hippocampal progenitors to kainate-induced injury. Brain Inj. 2011; 25(5): 503-10.
14. Reimunde P, Quintana A, Castañón B, et al. Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury. Brain Inj. 2011; 25(1)65-73.
15. Devesa J, Devesa P, Reimunde P. [Growth hormone revisited]. Med Clin (Barc). 2010; 135(14):665-70.
16. Arce VM, Devesa P, Devesa J. Role of growth hormone (GH) in the treatment on neural diseases: from neuroprotection to neural repair. Neurosci Res. 2013;76(4):179-86.
17. Devesa J, Reimunde P, Devesa P, Barberá M, Arce V. Growth hormone a(GH) and brain trauma. Horm Behav. 2013;63(2):331-44.
18. Devesa J, Díaz-Getino G, Rey P, et al. Brain Recovery after a Plane Crash: Treatment with Growth Hormone (GH) and Neurorehabilitation: A Case Report. Int J Mol Sci. 2015; 16(12):30470-82.
19. Devesa J, Lema H, Zas E, Munín B, Taboada P, Devesa P. Learning and Memory Recoveries in a Young Girl Treated with Growth Hormone and Neurorehabilitation. J Clin Med. 2016; 26;5(2):14.
20. Devesa J, Casteleiro N, Rodicio C, López N, Reimunde P. Growth hormone deficiency and cerebral palsy. Ther Clin Risk Manag. 2010; 6:413-8.
21. Reimunde P, Rodicio C, López N, Alonso A, Devesa P, Devesa J. Effects of recombinant growth hormone replacement and physical rehabilitation in recovery of gross motor function in children with cerebral palsy. Ther Clin Risk Manag. 2010; 6:585-92.
22. Devesa J, Alonso B, Casteleiro N, et al. Effects of recombinant growth hormone (GH) replacement and psychomotor and cognitive stimulation in the neurodevelopment of GH-deficient (GHD) children with cerebral palsy: a pilot study. Ther Clin Risk Manag. 2011;7:199-206.
23. Odom JV, Bach M, Brigell B, Holder GH, McCulloch DI, Tormene AP, et al. ISCEV standard for clinical visual evoked potentials (2009 update). Doc Ophtalmol. 2010; 120(1):111-9.
24. Jansen BH, Zouridakis G, Brandt ME. A neurophysiologically-based mathematical mode of flash visual evoked potentials. Biol Cybern. 1993; 68(3):275-83.
25. Good WV. Development of a quantitative method to measure vision in children with chronic cortical visual impairment. Trans Am Ophthalmol Soc. 2001;99:253-69.
26. Pleger B, Foerster AF, Widdig W. et al. Functional magnetic resonance imaging mirrors recovery of visual perception after repetitive tachistoscopic stimulation in patients with partial cortical blindness. Neurosci Lett. 2003;335:192-6.
27. Hoyt, CS. Visual function in the brain-damaged child. Eye (Lond). 2003;17(3):369–384.
28. Good WV, Jan JE, Burden SK, Skoczenski A, Candy R. Recent advances in cortical visual impairment. Dev Med Child Neurol. 2001;43:56–60.
29. Huo R, Burden SK, Hoyt CS, Good WV. Chronic cortical visual impairment in children: aetiology, prognosis, and associated neurological deficits. Br J Ophthalmol. 1999;83:670-5.
30. Aldrich MS, Alessi AG, Beck VX, Gilman S. Cortical blindness: etiology, diagnosis, and prognosis. Ann Neurol. 1987;21:149–158.
31. Zihl J. Recovery of visual functions in patients with cerebral blindness. Effect of specific practice with saccadic localization. Exp Brain Res. 1981;44:159–169.
32. Widdig W, Pleger B, Rommel O, Malin JP, Tegenthoff M. Repetitive visual stimulation: a neuropsychological approach to the treatment of cortical blindness. NeuroRehabilitation. 2003, 18(3):227-37.
33. Malkowicz DE, Myers G, Leisman G. Rehabilitation of cortical visual impairment in children. Int J Neurosci. 2006;116(9):1015–1033.
34. Kaas JH, Merzenich MM, Killackey HP. The reorganization of somatosensory cortex following peripheral nerve damage in adult and developing mammals. Annu Rev Neurosci. 1983;6:325-56.
35. Jenkins WM, Merzenich MM. Reorganization of neocortical representations after brain injury: a neurophysiological model of the bases of recovery from stroke. Prog Brain Res. 1987;71:249–66.
36. Johansson BB. Brain plasticity in health and disease. Keio J Med. 2004;53:231–46.
37. Kaas JH, Florence SL, Jain N. Subcortical contribution to massive cortical reorganization. Neuron. 1999;22:657–60.
38. Pascual-Leone A, Amedi A, Fregni F, Merabet LB. The plastic human brain cortex. Annu Rev Neurosci. 2005;28:377–401.
39. Floel A, Cohen LG. Translational studies in neurorehabilitation: from bench to bedside. Cogn Behav Neurol. 2006;16:1–10.
40. Nudo RJ. Mechanisms for recovery of motor function following cortical damage. Curr Opin Neurobiol. 2006;16:1–7.
41. Johansson BB. Regeneration and plasticity in the brain and spinal cord. J Cereb Blood Flow Metab. 2007; 27: 1417–1430.
42. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992; 255:1707-10.
43. Richards LJ, Kilpatrick TJ, Bartlett PF. De novo generation of neuronal cells from the adult mouse brain. Proc Natl Acad Sci U S A. 1992;89:8591–8595.
44. Eriksson PS, Perfilieva E, Björk-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4:1313–1317.
45. Roy NS, Wang S, Jiang L, et al. In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med. 2000; 6(3):271-7.
46. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell. 1999;97:703–16.
47. García AD, Doan NB, Imura T, Bush TG, Sofroniew MW. GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat Neurosci. 2004; 7:1233–41.
48. Dayer AG, Cleaver KM, Abouantoun T, Cameron HA. New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J Cell Biol. 2005;168:415-27.
49. Levison SW, Young GM, Goldman JE. Cycling cells in the adult rat neocortex preferentially generate oligodendroglia. J Neurosci Res. 1999;57:435–446.
50. Kokoeva MV, Yin H, Flier JS. Neurogenesis in the Hypothalamus of Adult Mice: Potential Role in Energy Balance. Science. 2005;310: 679-683.
51. Jin K, Minami M, Lan JQ, et al. Neurogenesis in dentate subgranular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci U S A. 2001;98:4710-5.
52. Zhang RL, Zhang ZG, Zhang L, Chopp M. Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience. 2001;105:33–41.
53. Kolb B, Morshead C, Gonzalez C, et al. Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats. J Cereb Blood Flow Metab. 2007;27:983-97.
54. Aberg ND, Brywe KG, Isgaard J. Aspects of Growth Hormone and Insulin-Like Growth Factor-I Related to Neuroprotection, Regeneration, and Functional Plasticity in the Adult Brain. ScientificWorldJournal. 2006;6:53–80.
55. Lobie PE, García-Aragón J, Lincoln DT, Barnard R, Wilcox JN, Waters MJ. Localization and ontogeny of growth hormone receptor gene expression in the central nervous system. Brain Res Dev Brain Res.1993;74(2):225-33.
56. Åberg MA, Åberg ND, Palmer TD, et al. IGF-I has a direct proliferative effect in adult hippocampal progenitor cells. Mol Cell Neurosci. 2003;24:23–40.
57. Christophidis LJ, Gorba T, Gustavsson M, et al. Growth hormone receptor immunoreactivity is increased in the subventricular zone of juvenile rat brain after focal ischemia: a potential role for growth hormone in injury-induced neurogenesis. Growth Horm IGF Res. 2009; 19(6):497-506.
58. Aberg ND, Johansson I, Aberg MI, et l. Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats. J Endocrinol. 2009; 201(1):141-50.
59. Aberg MA, Aberg ND, Hedbäcker H, Oscarsson J, Eriksson PS. Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci. 2000; 20(8):2896-903.
60. Beilharz EJ, Russo VC, Butler G, et al. Co-ordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic-ischemic injury. Brain Res Mol Brain Res. 1998; 59(2):119-34.
61. Gustafson K, Hagberg H, Bengtsson BA, Brantsing C, Isgaard J. Possible protective role of growth hormone in hypoxia-ischemia in neonatal rats. Pediatr Res. 1999; 45(3):318-23.
62. Hua K, Forbes ME, Lichtenwalner RG, Sonntag WE, Riddle DR. Adult-Onset Deficiency in Growth Hormone and Insulin-Like Growth Factor-I Alters Oligodendrocyte Turnover in the Corpus Callosum. Glia. 2009;57(10):1062-71.
63. Liu X, Yao DL, Bondy CA, Brenner M, Hudson LD, Zhou J, Webster HD. Astrocytes express insulin like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis. Mol Cell Neurosci. 1994; 5:418–430.
64. Hinks GL, Franklin RJ. Distinctive patterns of PDGF-A, FGF-2, IGF-I, and TGF-beta1 gene expression during remyelination of experimentally-induced spinal cord demyelination. Mol Cell Neurosci. 1999; 14:153–168.
65. Fushimi S, Shirabe T. Expression of insulin-like growth factors in remyelination following ethidium bromide-induced demyelination in the mouse spinal cord. Neuropathology. 2004; 24:208–218.
66. McMorris FA, McKinnon RD. Regulation of oligodendrocyte development and CNS myelination by growth factors: prospects for therapy of demyelinating disease. Brain Pathol. 1996; 6(3):313–329.
67. Mason JL, Ye P, Suzuki K, D'Ercole AJ, Matsushima GK. Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. J Neurosci. 2000; 20:5703–5708.
68. Kumar S, Biancotti JC, Yamaguchi M, de Vellis J. Combination of growth factors enhances remyelination in a cuprizone-induced demyelination mouse model. Neurochem Res. 2007; 32:783–797.
69. Hinks GL, Franklin RJ. Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats. Mol Cell Neurosci. 2000; 16:542–556.
70. Sim FJ, Zhao C, Penderis J, Franklin RJ. The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci. 2002; 22:2451–2459.
71. Chari DM, Crang AJ, Blakemore WF. Decline in rate of colonization of oligodendrocyte progenitor cell (OPC)-depleted tissue by adult OPCs with age. J Neuropathol Exp Neurol. 2003; 62:908– 916.
72. Devesa J, Lima L, Tresguerres JA. Neuroendocrine control of growth hormone secretion in humans. Trends Endocrinol Metab. 1992; 3(5):175-83.
73. Devesa P, Gelabert M, González-Mosquera T, et al. Growth hormone treatment enhances the functional recovery of sciatic nerves after transection and repair. Muscle Nerve. 2012; 45(3):385-92
2. Kerem Gunel M. Rehabilitation of children with cerebral palsy from a physiotherapist’s perspective. Acta Orthop Traumatol Turc. 2009; 43(2):173–180.
3. Odding E, Roebroeck ME, Stam HJ. The epidemiology of cerebral palsy: incidence, impairments and risk factors. Disabil Rehabil. 2006; 28:183–191.
4. Rutherford MA, Supramaniam V, Ederies A, et al. Magnetic resonance imaging of white matter diseases of prematurity. Neuroradiology. 2010; 52(6)505-21.
5. Rong G, Weijian H, Yafeng D, Zhiyong Y, Stites J, Weiner CP. Brain injury caused by chronic fetal hypoxemia is mediated by inflammatory cascade activation. Reprod Sci. 2010;17:540–548.
6. Wong VCN. Cortical blindness in children: a study of etiology and prognosis. Pediatr Neurol. 1991;7:178–85.
7. Rogers M. Visual impairment in Liverpool: prevalence and morbidity. Arch Dis Child. 1996;74:299–303.
8. Ahmed M, Dutton GN. Cognitive visual dysfunction in a child with cerebral damage. Dev Med Child Neurol. 1996; 38(8):736-9.
9. Schenk-Rootlieb A J, van Nieuwenhuizen O, van Waes P F, van der Graaf Y. Cerebral visual impairment in cerebral palsy: Relation to structural abnormalities of the cerebrum. Neuropediatrics. 1994; 25(2): 68–72.
10. Uggetti C, Egitto MG, Fazzi E, et al. Cerebral visual impairment in periventricular leukomalacia: MR correlation. AJNR Am J Neuroradiol. 1996; 17(5): 979–985.
11. Philip SS, Dutton GN. Identifying and characterising cerebral visual impairment in children: A review. Clin Exp Optom. 2014; 97(3):196–208.
12. Striber N, Vulin K, Đaković I, et al. Visual impairment in children with cerebral palsy: Croatian population-based study for birth years 2003-2006. Croat Med J. 2019; 60(5):414-420.
13. Devesa P, Reimunde P, Gallego R, Devesa J, Arce VM.. Growth Hormone (GH) treatment may cooperate with locally-produced GH in increasing the proliferative response of hippocampal progenitors to kainate-induced injury. Brain Inj. 2011; 25(5): 503-10.
14. Reimunde P, Quintana A, Castañón B, et al. Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury. Brain Inj. 2011; 25(1)65-73.
15. Devesa J, Devesa P, Reimunde P. [Growth hormone revisited]. Med Clin (Barc). 2010; 135(14):665-70.
16. Arce VM, Devesa P, Devesa J. Role of growth hormone (GH) in the treatment on neural diseases: from neuroprotection to neural repair. Neurosci Res. 2013;76(4):179-86.
17. Devesa J, Reimunde P, Devesa P, Barberá M, Arce V. Growth hormone a(GH) and brain trauma. Horm Behav. 2013;63(2):331-44.
18. Devesa J, Díaz-Getino G, Rey P, et al. Brain Recovery after a Plane Crash: Treatment with Growth Hormone (GH) and Neurorehabilitation: A Case Report. Int J Mol Sci. 2015; 16(12):30470-82.
19. Devesa J, Lema H, Zas E, Munín B, Taboada P, Devesa P. Learning and Memory Recoveries in a Young Girl Treated with Growth Hormone and Neurorehabilitation. J Clin Med. 2016; 26;5(2):14.
20. Devesa J, Casteleiro N, Rodicio C, López N, Reimunde P. Growth hormone deficiency and cerebral palsy. Ther Clin Risk Manag. 2010; 6:413-8.
21. Reimunde P, Rodicio C, López N, Alonso A, Devesa P, Devesa J. Effects of recombinant growth hormone replacement and physical rehabilitation in recovery of gross motor function in children with cerebral palsy. Ther Clin Risk Manag. 2010; 6:585-92.
22. Devesa J, Alonso B, Casteleiro N, et al. Effects of recombinant growth hormone (GH) replacement and psychomotor and cognitive stimulation in the neurodevelopment of GH-deficient (GHD) children with cerebral palsy: a pilot study. Ther Clin Risk Manag. 2011;7:199-206.
23. Odom JV, Bach M, Brigell B, Holder GH, McCulloch DI, Tormene AP, et al. ISCEV standard for clinical visual evoked potentials (2009 update). Doc Ophtalmol. 2010; 120(1):111-9.
24. Jansen BH, Zouridakis G, Brandt ME. A neurophysiologically-based mathematical mode of flash visual evoked potentials. Biol Cybern. 1993; 68(3):275-83.
25. Good WV. Development of a quantitative method to measure vision in children with chronic cortical visual impairment. Trans Am Ophthalmol Soc. 2001;99:253-69.
26. Pleger B, Foerster AF, Widdig W. et al. Functional magnetic resonance imaging mirrors recovery of visual perception after repetitive tachistoscopic stimulation in patients with partial cortical blindness. Neurosci Lett. 2003;335:192-6.
27. Hoyt, CS. Visual function in the brain-damaged child. Eye (Lond). 2003;17(3):369–384.
28. Good WV, Jan JE, Burden SK, Skoczenski A, Candy R. Recent advances in cortical visual impairment. Dev Med Child Neurol. 2001;43:56–60.
29. Huo R, Burden SK, Hoyt CS, Good WV. Chronic cortical visual impairment in children: aetiology, prognosis, and associated neurological deficits. Br J Ophthalmol. 1999;83:670-5.
30. Aldrich MS, Alessi AG, Beck VX, Gilman S. Cortical blindness: etiology, diagnosis, and prognosis. Ann Neurol. 1987;21:149–158.
31. Zihl J. Recovery of visual functions in patients with cerebral blindness. Effect of specific practice with saccadic localization. Exp Brain Res. 1981;44:159–169.
32. Widdig W, Pleger B, Rommel O, Malin JP, Tegenthoff M. Repetitive visual stimulation: a neuropsychological approach to the treatment of cortical blindness. NeuroRehabilitation. 2003, 18(3):227-37.
33. Malkowicz DE, Myers G, Leisman G. Rehabilitation of cortical visual impairment in children. Int J Neurosci. 2006;116(9):1015–1033.
34. Kaas JH, Merzenich MM, Killackey HP. The reorganization of somatosensory cortex following peripheral nerve damage in adult and developing mammals. Annu Rev Neurosci. 1983;6:325-56.
35. Jenkins WM, Merzenich MM. Reorganization of neocortical representations after brain injury: a neurophysiological model of the bases of recovery from stroke. Prog Brain Res. 1987;71:249–66.
36. Johansson BB. Brain plasticity in health and disease. Keio J Med. 2004;53:231–46.
37. Kaas JH, Florence SL, Jain N. Subcortical contribution to massive cortical reorganization. Neuron. 1999;22:657–60.
38. Pascual-Leone A, Amedi A, Fregni F, Merabet LB. The plastic human brain cortex. Annu Rev Neurosci. 2005;28:377–401.
39. Floel A, Cohen LG. Translational studies in neurorehabilitation: from bench to bedside. Cogn Behav Neurol. 2006;16:1–10.
40. Nudo RJ. Mechanisms for recovery of motor function following cortical damage. Curr Opin Neurobiol. 2006;16:1–7.
41. Johansson BB. Regeneration and plasticity in the brain and spinal cord. J Cereb Blood Flow Metab. 2007; 27: 1417–1430.
42. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992; 255:1707-10.
43. Richards LJ, Kilpatrick TJ, Bartlett PF. De novo generation of neuronal cells from the adult mouse brain. Proc Natl Acad Sci U S A. 1992;89:8591–8595.
44. Eriksson PS, Perfilieva E, Björk-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4:1313–1317.
45. Roy NS, Wang S, Jiang L, et al. In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med. 2000; 6(3):271-7.
46. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell. 1999;97:703–16.
47. García AD, Doan NB, Imura T, Bush TG, Sofroniew MW. GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat Neurosci. 2004; 7:1233–41.
48. Dayer AG, Cleaver KM, Abouantoun T, Cameron HA. New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J Cell Biol. 2005;168:415-27.
49. Levison SW, Young GM, Goldman JE. Cycling cells in the adult rat neocortex preferentially generate oligodendroglia. J Neurosci Res. 1999;57:435–446.
50. Kokoeva MV, Yin H, Flier JS. Neurogenesis in the Hypothalamus of Adult Mice: Potential Role in Energy Balance. Science. 2005;310: 679-683.
51. Jin K, Minami M, Lan JQ, et al. Neurogenesis in dentate subgranular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci U S A. 2001;98:4710-5.
52. Zhang RL, Zhang ZG, Zhang L, Chopp M. Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience. 2001;105:33–41.
53. Kolb B, Morshead C, Gonzalez C, et al. Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats. J Cereb Blood Flow Metab. 2007;27:983-97.
54. Aberg ND, Brywe KG, Isgaard J. Aspects of Growth Hormone and Insulin-Like Growth Factor-I Related to Neuroprotection, Regeneration, and Functional Plasticity in the Adult Brain. ScientificWorldJournal. 2006;6:53–80.
55. Lobie PE, García-Aragón J, Lincoln DT, Barnard R, Wilcox JN, Waters MJ. Localization and ontogeny of growth hormone receptor gene expression in the central nervous system. Brain Res Dev Brain Res.1993;74(2):225-33.
56. Åberg MA, Åberg ND, Palmer TD, et al. IGF-I has a direct proliferative effect in adult hippocampal progenitor cells. Mol Cell Neurosci. 2003;24:23–40.
57. Christophidis LJ, Gorba T, Gustavsson M, et al. Growth hormone receptor immunoreactivity is increased in the subventricular zone of juvenile rat brain after focal ischemia: a potential role for growth hormone in injury-induced neurogenesis. Growth Horm IGF Res. 2009; 19(6):497-506.
58. Aberg ND, Johansson I, Aberg MI, et l. Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats. J Endocrinol. 2009; 201(1):141-50.
59. Aberg MA, Aberg ND, Hedbäcker H, Oscarsson J, Eriksson PS. Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci. 2000; 20(8):2896-903.
60. Beilharz EJ, Russo VC, Butler G, et al. Co-ordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic-ischemic injury. Brain Res Mol Brain Res. 1998; 59(2):119-34.
61. Gustafson K, Hagberg H, Bengtsson BA, Brantsing C, Isgaard J. Possible protective role of growth hormone in hypoxia-ischemia in neonatal rats. Pediatr Res. 1999; 45(3):318-23.
62. Hua K, Forbes ME, Lichtenwalner RG, Sonntag WE, Riddle DR. Adult-Onset Deficiency in Growth Hormone and Insulin-Like Growth Factor-I Alters Oligodendrocyte Turnover in the Corpus Callosum. Glia. 2009;57(10):1062-71.
63. Liu X, Yao DL, Bondy CA, Brenner M, Hudson LD, Zhou J, Webster HD. Astrocytes express insulin like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis. Mol Cell Neurosci. 1994; 5:418–430.
64. Hinks GL, Franklin RJ. Distinctive patterns of PDGF-A, FGF-2, IGF-I, and TGF-beta1 gene expression during remyelination of experimentally-induced spinal cord demyelination. Mol Cell Neurosci. 1999; 14:153–168.
65. Fushimi S, Shirabe T. Expression of insulin-like growth factors in remyelination following ethidium bromide-induced demyelination in the mouse spinal cord. Neuropathology. 2004; 24:208–218.
66. McMorris FA, McKinnon RD. Regulation of oligodendrocyte development and CNS myelination by growth factors: prospects for therapy of demyelinating disease. Brain Pathol. 1996; 6(3):313–329.
67. Mason JL, Ye P, Suzuki K, D'Ercole AJ, Matsushima GK. Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. J Neurosci. 2000; 20:5703–5708.
68. Kumar S, Biancotti JC, Yamaguchi M, de Vellis J. Combination of growth factors enhances remyelination in a cuprizone-induced demyelination mouse model. Neurochem Res. 2007; 32:783–797.
69. Hinks GL, Franklin RJ. Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats. Mol Cell Neurosci. 2000; 16:542–556.
70. Sim FJ, Zhao C, Penderis J, Franklin RJ. The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci. 2002; 22:2451–2459.
71. Chari DM, Crang AJ, Blakemore WF. Decline in rate of colonization of oligodendrocyte progenitor cell (OPC)-depleted tissue by adult OPCs with age. J Neuropathol Exp Neurol. 2003; 62:908– 916.
72. Devesa J, Lima L, Tresguerres JA. Neuroendocrine control of growth hormone secretion in humans. Trends Endocrinol Metab. 1992; 3(5):175-83.
73. Devesa P, Gelabert M, González-Mosquera T, et al. Growth hormone treatment enhances the functional recovery of sciatic nerves after transection and repair. Muscle Nerve. 2012; 45(3):385-92