nach oben

Child's Nervous System

Erschienen in:

01.01.2014 | Review Paper

Stem cells for brain repair in neonatal hypoxia–ischemia

verfasst von: L. Chicha, T. Smith, R. Guzman

Erschienen in: Child's Nervous System | Ausgabe 1/2014

Einloggen, um Zugang zu erhalten

Abstract

Neonatal hypoxic–ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain’s plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic–ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

Andres RH, Choi R, Pendharkar AV, Gaeta X, Wang N, Nathan JK, Chua JY, Lee SW, Palmer TD, Steinberg GK, Guzman R (2011) The CCR2/CCL2 interaction mediates the transendothelial recruitment of intravascularly delivered neural stem cells to the ischemic brain. Stroke 42(10):2923–2931. doi:10.1161/STROKEAHA.110.606368 PubMedCentralPubMedCrossRef

Andres RH, Horie N, Slikker W, Keren-Gill H, Zhan K, Sun G, Manley NC, Pereira MP, Sheikh LA, McMillan EL, Schaar BT, Svendsen CN, Bliss TM, Steinberg GK (2011) Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain. Brain 134(Pt 6):1777–1789. doi:10.1093/brain/awr094 PubMedCrossRef

Ayuso-Sacido A, Roy NS, Schwartz TH, Greenfield JP, Boockvar JA (2008) Long-term expansion of adult human brain subventricular zone precursors. Neurosurgery 62(1):223–229. doi:10.1227/01.NEU.0000311081.50648.4C, discussion 229-231PubMedCrossRef

Back SA, Han BH, Luo NL, Chricton CA, Xanthoudakis S, Tam J, Arvin KL, Holtzman DM (2002) Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. J Neurosci 22(2):455–463PubMed

Ban H, Nishishita N, Fusaki N, Tabata T, Saeki K, Shikamura M, Takada N, Inoue M, Hasegawa M, Kawamata S, Nishikawa S (2011) Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors. Proc Natl Acad Sci U S A 108(34):14234–14239. doi:10.1073/pnas.1103509108 PubMedCentralPubMedCrossRef

Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA (2008) An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40(5):499–507. doi:10.1038/ng.127 PubMedCentralPubMedCrossRef

Brederlau A, Correia AS, Anisimov SV, Elmi M, Paul G, Roybon L, Morizane A, Bergquist F, Riebe I, Nannmark U, Carta M, Hanse E, Takahashi J, Sasai Y, Funa K, Brundin P, Eriksson PS, Li JY (2006) Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson’s disease: effect of in vitro differentiation on graft survival and teratoma formation. Stem Cells 24(6):1433–1440. doi:10.1634/stemcells.2005-0393 PubMedCrossRef

Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98(5):1076–1084. doi:10.1002/jcb.20886 PubMedCrossRef

Chaichana K, Zamora-Berridi G, Camara-Quintana J, Quinones-Hinojosa A (2006) Neurosphere assays: growth factors and hormone differences in tumor and nontumor studies. Stem Cells 24(12):2851–2857. doi:10.1634/stemcells.2006-0399 PubMedCrossRef

10.

Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27(3):275–280. doi:10.1038/nbt.1529 PubMedCentralPubMedCrossRef

11.

Chang DJ, Lee N, Park IH, Choi C, Jeon I, Kwon J, Oh SH, Shin DA, Do JT, Lee DR, Lee H, Moon H, Hong KS, Daley GQ, Song J (2012) Therapeutic potential of human induced pluripotent stem cells in experimental stroke. Cell Transplant. doi:10.3727/096368912X657314

12.

Chua JY, Pendharkar AV, Wang N, Choi R, Andres RH, Gaeta X, Zhang J, Moseley ME, Guzman R (2011) Intra-arterial injection of neural stem cells using a microneedle technique does not cause microembolic strokes. J Cereb Blood Flow Metab 31(5):1263–1271. doi:10.1038/jcbfm.2010.213 PubMedCrossRef

13.

Daadi MM, Davis AS, Arac A, Li Z, Maag AL, Bhatnagar R, Jiang K, Sun G, Wu JC, Steinberg GK (2010) Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury. Stroke 41(3):516–523. doi:10.1161/STROKEAHA.109.573691 PubMedCrossRef

14.

Dammann O (2007) Persistent neuro-inflammation in cerebral palsy: a therapeutic window of opportunity? Acta Paediatr 96(1):6–7. doi:10.1111/j.1651-2227.2007.00097.x PubMedCrossRef

15.

Dammann O, Leviton A (1997) Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res 42(1):1–8. doi:10.1203/00006450-199707000-00001 PubMedCrossRef

16.

De Feo D, Merlini A, Laterza C, Martino G (2012) Neural stem cell transplantation in central nervous system disorders: from cell replacement to neuroprotection. Curr Opin Neurol 25(3):322–333. doi:10.1097/WCO.0b013e328352ec45 PubMedCrossRef

17.

de Vries LS, Jongmans MJ (2010) Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 95(3):F220–F224. doi:10.1136/adc.2008.148205 PubMedCrossRef

18.

Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SB, Guyenet PG, Kipnis J (2012) Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484(7392):105–109. doi:10.1038/nature10907 PubMedCentralPubMedCrossRef

19.

Ding DC, Shyu WC, Chiang MF, Lin SZ, Chang YC, Wang HJ, Su CY, Li H (2007) Enhancement of neuroplasticity through upregulation of beta1-integrin in human umbilical cord-derived stromal cell implanted stroke model. Neurobiol Dis 27(3):339–353. doi:10.1016/j.nbd.2007.06.010 PubMedCrossRef

20.

Einstein O, Friedman-Levi Y, Grigoriadis N, Ben-Hur T (2009) Transplanted neural precursors enhance host brain-derived myelin regeneration. J Neurosci 29(50):15694–15702. doi:10.1523/JNEUROSCI.3364-09.2009 PubMedCrossRef

21.

Elbers J, Viero S, MacGregor D, DeVeber G, Moore AM (2011) Placental pathology in neonatal stroke. Pediatrics 127(3):e722–e729. doi:10.1542/peds.2010-1490 PubMedCrossRef

22.

Elsayed MH, Hogan TP, Shaw PL, Castro AJ (1996) Use of fetal cortical grafts in hypoxic-ischemic brain injury in neonatal rats. Exp Neurol 137(1):127–141. doi:10.1006/exnr.1996.0013 PubMedCrossRef

23.

Erblich B, Zhu L, Etgen AM, Dobrenis K, Pollard JW (2011) Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS One 6(10):e26317. doi:10.1371/journal.pone.0026317 PubMedCentralPubMedCrossRef

24.

Erceg S, Ronaghi M, Stojkovic M (2009) Human embryonic stem cell differentiation toward regional specific neural precursors. Stem Cells 27(1):78–87. doi:10.1634/stemcells.2008-0543 PubMedCentralPubMedCrossRef

25.

Flax JD, Aurora S, Yang C, Simonin C, Wills AM, Billinghurst LL, Jendoubi M, Sidman RL, Wolfe JH, Kim SU, Snyder EY (1998) Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes. Nat Biotechnol 16(11):1033–1039. doi:10.1038/3473 PubMedCrossRef

26.

Fleiss B, Gressens P (2012) Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy? Lancet Neurol 11(6):556–566. doi:10.1016/S1474-4422(12)70058-3 PubMedCrossRef

27.

Fruttiger M, Karlsson L, Hall AC, Abramsson A, Calver AR, Bostrom H, Willetts K, Bertold CH, Heath JK, Betsholtz C, Richardson WD (1999) Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice. Development 126(3):457–467PubMed

28.

Fu YS, Shih YT, Cheng YC, Min MY (2004) Transformation of human umbilical mesenchymal cells into neurons in vitro. J Biomed Sci 11(5):652–660. doi:10.1159/000079678 PubMedCrossRef

29.

Gera A, Steinberg GK, Guzman R (2010) In vivo neural stem cell imaging: current modalities and future directions. Regen Med 5(1):73–86. doi:10.2217/rme.09.79 PubMedCrossRef

30.

Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330(6005):841–845. doi:10.1126/science.1194637 PubMedCentralPubMedCrossRef

31.

Grad I, Hibaoui Y, Jaconi M, Chicha L, Bergstrom-Tengzelius R, Sailani MR, Pelte MF, Dahoun S, Mitsiadis TA, Tohonen V, Bouillaguet S, Antonarakis SE, Kere J, Zucchelli M, Hovatta O, Feki A (2011) NANOG priming before full reprogramming may generate germ cell tumours. Eur Cell Mater 22:258–274, discussio 274PubMed

32.

Greenfield JP, Ayuso-Sacido A, Schwartz TH, Pannullo S, Souweidane M, Stieg PE, Boockvar JA (2008) Use of human neural tissue for the generation of progenitors. Neurosurgery 62(1):21–37. doi:10.1227/01.NEU.0000311059.87873.46, discussion 27-30PubMedCrossRef

33.

Grether JK, Nelson KB (1997) Maternal infection and cerebral palsy in infants of normal birth weight. JAMA 278(3):207–211PubMedCrossRef

34.

Gunther G, Junker R, Strater R, Schobess R, Kurnik K, Heller C, Kosch A, Nowak-Gottl U (2000) Symptomatic ischemic stroke in full-term neonates : role of acquired and genetic prothrombotic risk factors. Stroke 31(10):2437–2441PubMedCrossRef

35.

Guzman R, Choi R, Gera A, De Los Angeles A, Andres RH, Steinberg GK (2008) Intravascular cell replacement therapy for stroke. Neurosurg Focus 24(3–4):E15. doi:10.3171/FOC/2008/24/3-4/E14 PubMedCrossRef

36.

Guzman R, De Los Angeles A, Cheshier S, Choi R, Hoang S, Liauw J, Schaar B, Steinberg G (2008) Intracarotid injection of fluorescence activated cell-sorted CD49d-positive neural stem cells improves targeted cell delivery and behavior after stroke in a mouse stroke model. Stroke 39(4):1300–1306. doi:10.1161/STROKEAHA.107.500470 PubMedCrossRef

37.

Guzman R, Uchida N, Bliss TM, He D, Christopherson KK, Stellwagen D, Capela A, Greve J, Malenka RC, Moseley ME, Palmer TD, Steinberg GK (2007) Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI. Proc Natl Acad Sci U S A 104(24):10211–10216. doi:10.1073/pnas.0608519104 PubMedCentralPubMedCrossRef

38.

Hochedlinger K, Yamada Y, Beard C, Jaenisch R (2005) Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121(3):465–477. doi:10.1016/j.cell.2005.02.018 PubMedCrossRef

39.

Huang H, Zhang J, Wakana S, Zhang W, Ren T, Richards LJ, Yarowsky P, Donohue P, Graham E, van Zijl PC, Mori S (2006) White and gray matter development in human fetal, newborn and pediatric brains. Neuroimaging 33(1):27–38. doi:10.1016/j.neuroimage.2006.06.009 CrossRef

40.

Hung SC, Pochampally RR, Hsu SC, Sanchez C, Chen SC, Spees J, Prockop DJ (2007) Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. PLoS One 2(5):e416. doi:10.1371/journal.pone.0000416 PubMedCentralPubMedCrossRef

41.

Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J, Sidman RL, Walsh CA, Snyder EY, Khoury SJ (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A 101(52):18117–18122. doi:10.1073/pnas.0408258102 PubMedCentralPubMedCrossRef

42.

Issa R, AlQteishat A, Mitsios N, Saka M, Krupinski J, Tarkowski E, Gaffney J, Slevin M, Kumar S, Kumar P (2005) Expression of basic fibroblast growth factor mRNA and protein in the human brain following ischaemic stroke. Angiogenesis 8(1):53–62. doi:10.1007/s10456-005-5613-8 PubMedCrossRef

43.

Jansen EM, Solberg L, Underhill S, Wilson S, Cozzari C, Hartman BK, Faris PL, Low WC (1997) Transplantation of fetal neocortex ameliorates sensorimotor and locomotor deficits following neonatal ischemic-hypoxic brain injury in rats. Exp Neurol 147(2):487–497. doi:10.1006/exnr.1997.6596 PubMedCrossRef

44.

Johnston MV, Hagberg H (2007) Sex and the pathogenesis of cerebral palsy. Dev Med Child Neurol 49(1):74–78. doi:10.1111/j.1469-8749.2007.0199a.x PubMedCrossRef

45.

Khwaja O, Volpe JJ (2008) Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child Fetal Neonatal Ed 93(2):F153–F161. doi:10.1136/adc.2006.108837 PubMedCentralPubMedCrossRef

46.

Kim H, Walczak P, Kerr C, Galpoththawela C, Gilad AA, Muja N, Bulte JW (2012) Immunomodulation by Transplanted Human Embryonic Stem Cell- Derived Oligodendroglial Progenitors in Experimental Autoimmune Encephalomyelitis. Stem Cells. doi:10.1002/stem.1218

47.

Kirby RS (2012) Cerebral palsy and birth defects: what is the frame of reference? Dev Med Child Neurol 54(8):677–678. doi:10.1111/j.1469-8749.2012.04331.x PubMedCrossRef

48.

Kokaia Z, Martino G, Schwartz M, Lindvall O (2012) Cross-talk between neural stem cells and immune cells: the key to better brain repair? Nat Neurosci 15(8):1078–1087. doi:10.1038/nn.3163 PubMedCrossRef

49.

Kotter MR, Li WW, Zhao C, Franklin RJ (2006) Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. J Neurosci 26(1):328–332. doi:10.1523/JNEUROSCI.2615-05.2006 PubMedCrossRef

50.

Kuhl NM, De Keyser J, De Vries H, Hoekstra D (2002) Insulin-like growth factor binding proteins-1 and -2 differentially inhibit rat oligodendrocyte precursor cell survival and differentiation in vitro. J Neurosci Res 69(2):207–216. doi:10.1002/jnr.10293 PubMedCrossRef

51.

Kurinczuk JJ, White-Koning M, Badawi N (2010) Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 86(6):329–338. doi:10.1016/j.earlhumdev.2010.05.010 PubMedCrossRef

52.

Lacaud G, Robertson S, Palis J, Kennedy M, Keller G (2001) Regulation of hemangioblast development. Ann N Y Acad Sci 938:96–107, discussion 108PubMedCrossRef

53.

Larouche A, Roy M, Kadhim H, Tsanaclis AM, Fortin D, Sebire G (2005) Neuronal injuries induced by perinatal hypoxic-ischemic insults are potentiated by prenatal exposure to lipopolysaccharide: animal model for perinatally acquired encephalopathy. Dev Neurosci 27(2–4):134–142. doi:10.1159/000085985 PubMedCrossRef

54.

Levine S (1960) Anoxic-ischemic encephalopathy in rats. Am J Pathol 36:1–17PubMed

55.

Lim JY, Park SI, Kim SM, Jun JA, Oh JH, Ryu CH, Jeong CH, Park SH, Park SA, Oh W, Chang JW, Jeun SS (2011) Neural differentiation of brain-derived neurotrophic factor-expressing human umbilical cord blood-derived mesenchymal stem cells in culture via TrkB-mediated ERK and beta-catenin phosphorylation and following transplantation into the developing brain. Cell Transplant. doi:10.3727/096368910X557236

56.

Lu P, Jones LL, Snyder EY, Tuszynski MH (2003) Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp Neurol 181(2):115–129PubMedCrossRef

57.

Lu Z, Elliott MR, Chen Y, Walsh JT, Klibanov AL, Ravichandran KS, Kipnis J (2011) Phagocytic activity of neuronal progenitors regulates adult neurogenesis. Nat Cell Biol 13(9):1076–1083. doi:10.1038/ncb2299 PubMedCentralPubMedCrossRef

58.

Mahmood A, Lu D, Chopp M (2004) Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury. J Neurotrauma 21(1):33–39. doi:10.1089/089771504772695922 PubMedCrossRef

59.

Marchetto MC, Winner B, Gage FH (2010) Pluripotent stem cells in neurodegenerative and neurodevelopmental diseases. Hum Mol Genet 19(R1):R71–R76. doi:10.1093/hmg/ddq159 PubMedCrossRef

60.

Martino G, Bacigaluppi M, Peruzzotti-Jametti L (2011) Therapeutic stem cell plasticity orchestrates tissue plasticity. Brain 134(Pt 6):1585–1587. doi:10.1093/brain/awr115 PubMedCrossRef

61.

Mercuri E, Cowan F, Gupte G, Manning R, Laffan M, Rutherford M, Edwards AD, Dubowitz L, Roberts I (2001) Prothrombotic disorders and abnormal neurodevelopmental outcome in infants with neonatal cerebral infarction. Pediatrics 107(6):1400–1404PubMedCrossRef

62.

Mosher KI, Andres RH, Fukuhara T, Bieri G, Hasegawa-Moriyama M, He Y, Guzman R, Wyss-Coray T (2012) Neural progenitor cells regulate microglia functions and activity. Nat Neurosci 15(11):1485–1487. doi:10.1038/nn.3233 PubMedCentralPubMedCrossRef

63.

Muotri AR, Nakashima K, Toni N, Sandler VM, Gage FH (2005) Development of functional human embryonic stem cell-derived neurons in mouse brain. Proc Natl Acad Sci U S A 102(51):18644–18648. doi:10.1073/pnas.0509315102 PubMedCentralPubMedCrossRef

64.

Murohara T (2001) Therapeutic vasculogenesis using human cord blood-derived endothelial progenitors. Trends Cardiovasc Med 11(8):303–307PubMedCrossRef

65.

Nagae LM, Hoon AH Jr, Stashinko E, Lin D, Zhang W, Levey E, Wakana S, Jiang H, Leite CC, Lucato LT, van Zijl PC, Johnston MV, Mori S (2007) Diffusion tensor imaging in children with periventricular leukomalacia: variability of injuries to white matter tracts. AJNR Am J Neuroradiol 28(7):1213–1222. doi:10.3174/ajnr.A0534 PubMedCrossRef

66.

Nguyen HT, Geens M, Spits C (2013) Genetic and epigenetic instability in human pluripotent stem cells. Hum Reprod Update 19(2):187–205. doi:10.1093/humupd/dms048 PubMedCrossRef

67.

Obenaus A, Dilmac N, Tone B, Tian HR, Hartman R, Digicaylioglu M, Snyder EY, Ashwal S (2011) Long-term magnetic resonance imaging of stem cells in neonatal ischemic injury. Ann Neurol 69(2):282–291. doi:10.1002/ana.22168 PubMedCentralPubMedCrossRef

68.

Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448(7151):313–317. doi:10.1038/nature05934 PubMedCrossRef

69.

Oliff HS, Coyle P, Weber E (1997) Rat strain and vendor differences in collateral anastomoses. J Cereb Blood Flow Metab 17(5):571–576. doi:10.1097/00004647-199705000-00012 PubMedCrossRef

70.

Palmer TD, Schwartz PH, Taupin P, Kaspar B, Stein SA, Gage FH (2001) Cell culture. Progenitor cells from human brain after death. Nature 411(6833):42–43. doi:10.1038/35075141 PubMedCrossRef

71.

Park KI, Teng YD, Snyder EY (2002) The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue. Nat Biotechnol 20(11):1111–1117. doi:10.1038/nbt751 PubMedCrossRef

72.

Patrick LA, Smith GN (2002) Proinflammatory cytokines: a link between chorioamnionitis and fetal brain injury. J Obstet Gynaecol Can 24(9):705–709PubMed

73.

Paus T, Collins DL, Evans AC, Leonard G, Pike B, Zijdenbos A (2001) Maturation of white matter in the human brain: a review of magnetic resonance studies. Brain Res Bull 54(3):255–266PubMedCrossRef

74.

Peitz M, Jungverdorben J, Brustle O (2013) Disease-specific iPS cell models in neuroscience. Curr Mol Med 13(5):832–841PubMedCrossRef

75.

Pendharkar AV, Chua JY, Andres RH, Wang N, Gaeta X, Wang H, De A, Choi R, Chen S, Rutt BK, Gambhir SS, Guzman R (2010) Biodistribution of neural stem cells after intravascular therapy for hypoxic-ischemia. Stroke 41(9):2064–2070. doi:10.1161/STROKEAHA.109.575993 PubMedCrossRef

76.

Pimentel-Coelho PM, Rosado-de-Castro PH, da Fonseca LM, Mendez-Otero R (2012) Umbilical cord blood mononuclear cell transplantation for neonatal hypoxic-ischemic encephalopathy. Pediatr Res 71(4 Pt 2):464–473. doi:10.1038/pr.2011.59 PubMedCrossRef

77.

Pluchino S, Zanotti L, Rossi B, Brambilla E, Ottoboni L, Salani G, Martinello M, Cattalini A, Bergami A, Furlan R, Comi G, Constantin G, Martino G (2005) Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature 436(7048):266–271. doi:10.1038/nature03889 PubMedCrossRef

78.

Rice JE 3rd, Vannucci RC, Brierley JB (1981) The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 9(2):131–141. doi:10.1002/ana.410090206 PubMedCrossRef

79.

Rickhag M, Teilum M, Wieloch T (2007) Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain. Brain Res 1151:203–210. doi:10.1016/j.brainres.2007.03.005 PubMedCrossRef

80.

Righini A, Doneda C, Parazzini C, Arrigoni F, Matta U, Triulzi F (2010) Diffusion tensor imaging of early changes in corpus callosum after acute cerebral hemisphere lesions in newborns. Neuroradiology 52(11):1025–1035. doi:10.1007/s00234-010-0745-y PubMedCrossRef

81.

Rosenblum S, Wang N, Smith TN, Pendharkar AV, Chua JY, Birk H, Guzman R (2012) Timing of intra-arterial neural stem cell transplantation after hypoxia-ischemia influences cell engraftment, survival, and differentiation. Stroke 43(6):1624–1631. doi:10.1161/STROKEAHA.111.637884 PubMedCrossRef

82.

Ruckh JM, Zhao JW, Shadrach JL, van Wijngaarden P, Rao TN, Wagers AJ, Franklin RJ (2012) Rejuvenation of regeneration in the aging central nervous system. Cell Stem Cell 10(1):96–103. doi:10.1016/j.stem.2011.11.019 PubMedCentralPubMedCrossRef

83.

Santilli G, Lamorte G, Carlessi L, Ferrari D, Rota Nodari L, Binda E, Delia D, Vescovi AL, De Filippis L (2010) Mild hypoxia enhances proliferation and multipotency of human neural stem cells. PLoS One 5(1):e8575. doi:10.1371/journal.pone.0008575 PubMedCentralPubMedCrossRef

84.

Schwarting S, Litwak S, Hao W, Bahr M, Weise J, Neumann H (2008) Hematopoietic stem cells reduce postischemic inflammation and ameliorate ischemic brain injury. Stroke 39(10):2867–2875. doi:10.1161/STROKEAHA.108.513978 PubMedCrossRef

85.

Segovia KN, McClure M, Moravec M, Luo NL, Wan Y, Gong X, Riddle A, Craig A, Struve J, Sherman LS, Back SA (2008) Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury. Ann Neurol 63(4):520–530. doi:10.1002/ana.21359 PubMedCentralPubMedCrossRef

86.

Seminatore C, Polentes J, Ellman D, Kozubenko N, Itier V, Tine S, Tritschler L, Brenot M, Guidou E, Blondeau J, Lhuillier M, Bugi A, Aubry L, Jendelova P, Sykova E, Perrier AL, Finsen B, Onteniente B (2010) The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors. Stroke 41(1):153–159. doi:10.1161/STROKEAHA.109.563015 PubMedCrossRef

87.

Shah PS, Perlman M (2009) Time courses of intrapartum asphyxia: neonatal characteristics and outcomes. Am J Perinatol 26(1):39–44. doi:10.1055/s-0028-1095185 PubMedCrossRef

88.

Shechter R, London A, Varol C, Raposo C, Cusimano M, Yovel G, Rolls A, Mack M, Pluchino S, Martino G, Jung S, Schwartz M (2009) Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med 6(7):e1000113. doi:10.1371/journal.pmed.1000113 PubMedCentralPubMedCrossRef

89.

Sizonenko SV, Camm EJ, Dayer A, Kiss JZ (2008) Glial responses to neonatal hypoxic-ischemic injury in the rat cerebral cortex. Int J Dev Neurosci 26(1):37–45. doi:10.1016/j.ijdevneu.2007.08.014 PubMedCrossRef

90.

Sotak CH (2002) The role of diffusion tensor imaging in the evaluation of ischemic brain injury—a review. NMR Biomed 15(7–8):561–569. doi:10.1002/nbm.786 PubMedCrossRef

91.

Stewart MH (2013) Pluripotency and targeted reprogramming: strategies, disease modeling and drug screening. Curr Drug Deliv

92.

Svendsen CN, Caldwell MA, Ostenfeld T (1999) Human neural stem cells: isolation, expansion and transplantation. Brain Pathol 9(3):499–513PubMedCrossRef

93.

Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM, Naritomi H, Matsuyama T (2004) Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest 114(3):330–338. doi:10.1172/JCI20622 PubMedCentralPubMed

94.

Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. doi:10.1016/j.cell.2006.07.024 PubMedCrossRef

95.

Tamaki S, Eckert K, He D, Sutton R, Doshe M, Jain G, Tushinski R, Reitsma M, Harris B, Tsukamoto A, Gage F, Weissman I, Uchida N (2002) Engraftment of sorted/expanded human central nervous system stem cells from fetal brain. J Neurosci Res 69(6):976–986. doi:10.1002/jnr.10412 PubMedCrossRef

96.

Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147PubMedCrossRef

97.

Thornton C, Rousset CI, Kichev A, Miyakuni Y, Vontell R, Baburamani AA, Fleiss B, Gressens P, Hagberg H (2012) Molecular mechanisms of neonatal brain injury. Neurol Res Int 2012:506320. doi:10.1155/2012/506320 PubMedCentralPubMed

98.

Tipnis S, Viswanathan C, Majumdar AS (2010) Immunosuppressive properties of human umbilical cord-derived mesenchymal stem cells: role of B7-H1 and IDO. Immunol Cell Biol 88(8):795–806. doi:10.1038/icb.2010.47 PubMedCrossRef

99.

Titomanlio L, Kavelaars A, Dalous J, Mani S, El Ghouzzi V, Heijnen C, Baud O, Gressens P (2011) Stem cell therapy for neonatal brain injury: perspectives and challenges. Ann Neurol 70(5):698–712. doi:10.1002/ana.22518 PubMedCrossRef

100.

Tso GH, Law HK, Tu W, Chan GC, Lau YL (2010) Phagocytosis of apoptotic cells modulates mesenchymal stem cells osteogenic differentiation to enhance IL-17 and RANKL expression on CD4+ T cells. Stem Cells 28(5):939–954. doi:10.1002/stem.406 PubMed

101.

van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ (2010) Mesenchymal stem cell treatment after neonatal hypoxic-ischemic brain injury improves behavioral outcome and induces neuronal and oligodendrocyte regeneration. Brain Behav Immun 24(3):387–393. doi:10.1016/j.bbi.2009.10.017 PubMedCrossRef

102.

Van’t Veer A, Du Y, Fischer TZ, Boetig DR, Wood MR, Dreyfus CF (2009) Brain-derived neurotrophic factor effects on oligodendrocyte progenitors of the basal forebrain are mediated through trkB and the MAP kinase pathway. J Neurosci Res 87(1):69–78. doi:10.1002/jnr.21841 CrossRef

103.

Vannucci RC (1993) Experimental models of perinatal hypoxic-ischemic brain damage. APMIS Suppl 40:89–95PubMed

104.

Vannucci RC, Perlman JM (1997) Interventions for perinatal hypoxic-ischemic encephalopathy. Pediatrics 100(6):1004–1014PubMedCrossRef

105.

Vannucci SJ, Hagberg H (2004) Hypoxia-ischemia in the immature brain. J Exp Biol 207(Pt 18):3149–3154. doi:10.1242/jeb.01064 PubMedCrossRef

106.

Vendrame M, Gemma C, Pennypacker KR, Bickford PC, Davis Sanberg C, Sanberg PR, Willing AE (2006) Cord blood rescues stroke-induced changes in splenocyte phenotype and function. Exp Neurol 199(1):191–200. doi:10.1016/j.expneurol.2006.03.017 PubMedCrossRef

107.

Vescovi AL, Gritti A, Galli R, Parati EA (1999) Isolation and intracerebral grafting of nontransformed multipotential embryonic human CNS stem cells. J Neurotrauma 16(8):689–693PubMedCrossRef

108.

Vescovi AL, Parati EA, Gritti A, Poulin P, Ferrario M, Wanke E, Frolichsthal-Schoeller P, Cova L, Arcellana-Panlilio M, Colombo A, Galli R (1999) Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Exp Neurol 156(1):71–83. doi:10.1006/exnr.1998.6998 PubMedCrossRef

109.

Volpe JJ (2008) Neonatal encephalitis and white matter injury: more than just inflammation? Ann Neurol 64(3):232–236. doi:10.1002/ana.21466 PubMedCentralPubMedCrossRef

110.

Volpe JJ (2008) Postnatal sepsis, necrotizing entercolitis, and the critical role of systemic inflammation in white matter injury in premature infants. J Pediatr 153(2):160–163. doi:10.1016/j.jpeds.2008.04.057 PubMedCentralPubMedCrossRef

111.

Walker PA, Shah SK, Jimenez F, Gerber MH, Xue H, Cutrone R, Hamilton JA, Mays RW, Deans R, Pati S, Dash PK, Cox CS Jr (2010) Intravenous multipotent adult progenitor cell therapy for traumatic brain injury: preserving the blood brain barrier via an interaction with splenocytes. Exp Neurol 225(2):341–352. doi:10.1016/j.expneurol.2010.07.005 PubMedCentralPubMedCrossRef

112.

Wang M, Yang Y, Yang D, Luo F, Liang W, Guo S, Xu J (2009) The immunomodulatory activity of human umbilical cord blood-derived mesenchymal stem cells in vitro. Immunology 126(2):220–232. doi:10.1111/j.1365-2567.2008.02891.x PubMedCrossRef

113.

Wei Y, Yemisci M, Kim HH, Yung LM, Shin HK, Hwang SK, Guo S, Qin T, Alsharif N, Brinkmann V, Liao JK, Lo EH, Waeber C (2011) Fingolimod provides long-term protection in rodent models of cerebral ischemia. Ann Neurol 69(1):119–129. doi:10.1002/ana.22186 PubMedCentralPubMedCrossRef

114.

Wu YW, Hamrick SE, Miller SP, Haward MF, Lai MC, Callen PW, Barkovich AJ, Ferriero DM (2003) Intraventricular hemorrhage in term neonates caused by sinovenous thrombosis. Ann Neurol 54(1):123–126. doi:10.1002/ana.10619 PubMedCrossRef

115.

Wu YW, March WM, Croen LA, Grether JK, Escobar GJ, Newman TB (2004) Perinatal stroke in children with motor impairment: a population-based study. Pediatrics 114(3):612–619. doi:10.1542/peds.2004-0385 PubMedCrossRef

116.

Xia G, Hong X, Chen X, Lan F, Zhang G, Liao L (2010) Intracerebral transplantation of mesenchymal stem cells derived from human umbilical cord blood alleviates hypoxic ischemic brain injury in rat neonates. J Perinat Med 38(2):215–221. doi:10.1515/JPM.2010.021 PubMedCrossRef

117.

Zhang J, Li Y, Cui Y, Chen J, Lu M, Elias SB, Chopp M (2005) Erythropoietin treatment improves neurological functional recovery in EAE mice. Brain Res 1034(1–2):34–39. doi:10.1016/j.brainres.2004.11.036 PubMedCrossRef

Titel: Stem cells for brain repair in neonatal hypoxia–ischemia
verfasst von: L. Chicha
T. Smith
R. Guzman
Publikationsdatum: 01.01.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Child's Nervous System / Ausgabe 1/2014
Print ISSN: 0256-7040
Elektronische ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-013-2304-4

Neu im Fachgebiet Chirurgie

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 Ablationstherapie Nachrichten

Nach der Katheterablation von Vorhofflimmern kommt es bei etwa einem Drittel der Patienten zu Rezidiven, meist binnen eines Jahres. Wie sich spätere Rückfälle auf die Erfolgschancen einer erneuten Ablation auswirken, haben Schweizer Kardiologen erforscht.

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 Appendizitis Nachrichten

Schmerzen im Unterbauch, aber sonst nicht viel, was auf eine Appendizitis hindeutete: Ein junger Mann hatte Glück, dass trotzdem eine Laparoskopie mit Appendektomie durchgeführt und der Wurmfortsatz histologisch untersucht wurde.

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

23.04.2024 Operationsvorbereitung Nachrichten

Derzeit wird empfohlen, eine Therapie mit GLP-1-Rezeptoragonisten präoperativ zu unterbrechen. Eine neue Studie nährt jedoch Zweifel an der Notwendigkeit der Maßnahme.

Ureterstriktur: Innovative OP-Technik bewährt sich

19.04.2024 EAU 2024 Kongressbericht

Die Ureterstriktur ist eine relativ seltene Komplikation, trotzdem bedarf sie einer differenzierten Versorgung. In komplexen Fällen wird dies durch die roboterassistierte OP-Technik gewährleistet. Erste Resultate ermutigen.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Aktuelle BDC Leitlinien-Webinare

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare

CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare

CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske

Dr. med. Benjamin Meyknecht

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare

CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2014

Rhabdoid meningioma: analysis of one case

Are pediatric brain tumors on the rise in the USA? Significant incidence and survival findings from the SEER database analysis

The assessment of relationship between the skull base development and the severity of frontal plagiocephaly after bilateral fronto-orbital advancement in the early life

Clinical manifestation and neurosurgical intervention of encephalocraniocutaneous lipomatosis—a case report and review of the literature

Radiological findings in relation to the neurodevelopmental outcome in hydrocephalic children treated with shunt insertion or endoscopic third ventriculostomy

Normative data for fetal cisterna magna length measurement between 18 and 24 weeks of pregnancy

Update Chirurgie