Transplantation of Fetal Neocortex Ameliorates Sensorimotor and Locomotor Deficits Following Neonatal Ischemic–Hypoxic Brain Injury in Rats

Jansen, Elizabeth M.; Solberg, Leah C.; Underhill, Suzanne M.; Wilson, Spencer; Cozzari, Costantino; Hartman, Boyd K.; Faris, Patricia L.; Low, Walter C.

doi:10.1006/exnr.1997.6596

Cited by 41 publications

(21 citation statements)

References 30 publications

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“…Using these same approaches, endogenous precursors can be activated in situ, undergo similarly directed migration, neuronal differentiation, long-distance axonal projection, and even behaviorally functional circuit restoration in adult songbirds and mice (Magavi et al, 2000;Scharff et al, 2000). Although other studies have explored neuronal differentiation Yirmiya et al, 1988;Valouskova and Galik, 1995) and expression of some phenotypic markers (Gonzalez and Sharp, 1987;Jansen et al, 1997) by transplanted cortical tissue, none of these studies has investigated in detail the fidelity and precision with which transplanted neuroblasts undergo phenotypic differentiation required for high-level functionality. The development of a mature CPN phenotype in the studies reported here is also indicative of functional maturity, i.e., the ability of newly incorporated neurons to integrate and communicate in an appropriate manner with other neurons in the complex cortical circuitry.…”

Section: Neuroblasts Transplanted To Regions Of Targeted Neuronal Degmentioning

confidence: 99%

Transplanted Neuroblasts Differentiate Appropriately into Projection Neurons with Correct Neurotransmitter and Receptor Phenotype in Neocortex Undergoing Targeted Projection Neuron Degeneration

et al. 2000

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Reconstruction of complex neocortical and other CNS circuitry may be possible via transplantation of appropriate neural precursors, guided by cellular and molecular controls. Although cellular repopulation and complex circuitry repair may make possible new avenues of treatment for degenerative, developmental, or acquired CNS diseases, functional integration may depend critically on specificity of neuronal synaptic integration and appropriate neurotransmitter/receptor phenotype.The current study investigated neurotransmitter and receptor phenotypes of newly incorporated neurons after transplantation in regions of targeted neuronal degeneration of cortical callosal projection neurons (CPNs). Donor neuroblasts were compared to the population of normal endogenous CPNs in their expression of appropriate neurotransmitters (glutamate, aspartate, and GABA) and receptors (kainate-R, AMPA-R, NMDA-R. and GABA-R), and the time course over which this phenotype developed after transplantation.Transplanted immature neuroblasts from embryonic day 17 (E17) primary somatosensory (S1) cortex migrated to cortical layers undergoing degeneration, differentiated to a mature CPN phenotype, and received synaptic input from other neurons. In addition, 23.1 Ϯ 13.6% of the donor-derived neurons extended appropriate long-distance callosal projections to the contralateral S1 cortex. The percentage of donor-derived neurons expressing appropriate neurotransmitters and receptors showed a steady increase with time, reaching numbers equivalent to adult endogenous CPNs by 4-16 weeks after transplantation.These results suggest that previously demonstrated changes in gene expression induced by synchronous apoptotic degeneration of adult CPNs create a cellular and molecular environment that is both permissive and instructive for the specific and appropriate maturation of transplanted neuroblasts. These experiments demonstrate, for the first time, that newly repopulating neurons can undergo directed differentiation with high fidelity of their neurotransmitter and receptor phenotype, toward reconstruction of complex CNS circuitry.

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Section: Neuroblasts Transplanted To Regions Of Targeted Neuronal Degmentioning

confidence: 99%

Transplanted Neuroblasts Differentiate Appropriately into Projection Neurons with Correct Neurotransmitter and Receptor Phenotype in Neocortex Undergoing Targeted Projection Neuron Degeneration

et al. 2000

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“…Fetal neural stem cells can reduce behavioral deficits in damaged and compromised brain in animals and in humans. 1,2 However, transplantation of embryonic grafts is plagued with logistical and ethical considerations. Thus, it is reasonable to seek alternative sources or an equivalent of stem cells.…”

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confidence: 99%

Intravenous Administration of Human Umbilical Cord Blood Reduces Behavioral Deficits After Stroke in Rats

Chen¹,

Sanberg

et al. 2001

Stroke

1,175

825

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Background and Purpose-Human umbilical cord blood cells (HUCBC) are rich in stem and progenitor cells. In this study we tested whether intravenously infused HUCBC enter brain, survive, differentiate, and improve neurological functional recovery after stroke in rats. In addition, we tested whether ischemic brain tissue extract selectively induces chemotaxis of HUCBC in vitro. Methods-Adult male Wistar rats were subjected to transient (2-hour) middle cerebral artery occlusion (MCAO).Experimental groups were as follows: group 1, MCAO alone (nϭ5); group 2, 3ϫ10 6 HUCBC injected into tail vein at 24 hours after MCAO (nϭ6) (animals of groups 1 and 2 were killed at 14 days after MCAO); group 3, MCAO alone (nϭ5); group 4, MCAO injected with PBS at 1 day after stroke (nϭ8); and group 5, 3ϫ10 6 HUCBC injected into tail vein at 7 days after MCAO (nϭ5). Rats of groups 3, 4, and 5 were killed at 35 days after MCAO.

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“…Adicionalmente, o respectivo trabalho não realizou uma avaliação funcional dos animais transplantados. Outro grupo de pesquisa também realizou transplante intracerebral de tecido neocortical fetal 3 dias após a indução da HI 16 . Em vez de usar um bloco tecidual, os autores utilizaram uma suspensão celular a fim de facilitar o procedimento de transplante.…”

Section: Transplante De Tecido Neocortical Fetalunclassified

“…Elsayed et al 15 Jansen et al 16 Park et al 27 Imitola et al 23 Katsuragi et al 32 Katsuragi et al 33 Zheng et al 21 Meier et al 36 58 Park et al 22 Park et al 29 Ma et al 24 Dayer et al 30 BDNF = fator neurotrófico derivado do cérebro; BHK-GDNF = células renais de filhotes de hamster (BHK) transfectadas com DNA complementar de fator neurotrófico derivado de linhagem celular glial (GDNF); CPAM = células progenitoras adultas multipotentes; ChABC = condroitinase ABC; CTCUH = células-tronco de cordão umbilical humano; CTM = células-tronco mesenquimais; CTN = células-tronco neurais; CXCR4 = receptor de quimiocina CXC 4; FGF-2 = fator de crescimento de fibroblasto 2; GDNF = fator neurotrófico derivado de linhagem celular glial; HI = hipóxia-isquemia; ic = via intracerebral; ica = via intracardíaca; icv = via intracerebroventricular; ip = via intraperitoneal; iv = via intravenosa; NA = não avaliado; NGF = fator de crescimento neural; NT3 = neurotrofina -3; P = dia pós-natal; PGA = ácido poliglicólico; pT = pós-transplante; SDF-1 = fator derivado do estroma 1; T-PX = transplante no dia pós-natal X; SI = sem imunossupressão; TC = transplante contralateral; TI = transplante ipsilateral; VEH = veículo. * Animais tratados versus animais controle.…”

Section: Referênciaunclassified

Use of stem cells in perinatal asphyxia: from bench to bedside

Paula¹,

Greggio²,

Costa³

2010

J Pediatr (Rio J)

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Objectives: To present recent scientific evidence on the effects of stem cell transplantation in animal models of neonatal hypoxic-ischemic brain injury and address the translational relevance of cell therapy for clinical application in this context. Sources:The PubMed and Scopus databases were used to select articles. The selection criterion was the specificity of articles regarding the subject studied, preferably articles published from 2000 onward. We also reviewed classic articles from previous years that were applicable to this review. Summary of the findings:Stem cells from different exogenous sources may exhibit neuroprotective properties in experimental models of neonatal hypoxia-ischemia. In most animal experiments, the morphological and functional benefits observed were independent of neural differentiation, suggesting associated mechanisms of action, such as the release of trophic factors and inflammatory modulation. Conclusions:Based on the experimental studies analyzed, cell therapy may become a promising therapeutic approach in the treatment of children with hypoxic-ischemic encephalopathy. However, further studies are warranted to elucidate potential mechanisms of action of these cells and to define safe and effective clinical strategies.J Pediatr (Rio J). 2010;86(6):451-464: Hypoxic-ischemic encephalopathy, stem cells, asphyxia, cell therapy. ResumoObjetivos: Apresentar evidências científicas recentes sobre os efeitos do transplante com células-tronco em modelos animais de lesão cerebral hipóxico-isquêmica neonatal e abordar os aspectos translacionais relevantes à aplicação clínica da terapia celular nesse contexto. Fonte dos dados:Para a seleção dos artigos, utilizou-se a base de dados PubMed e Scopus. O critério de seleção de artigos foi a especificidade em relação ao tema estudado, preferencialmente a partir do ano de 2000. Também foram revisados artigos clássicos de anos anteriores que se aplicavam ao propósito desta revisão. Síntese dos dados:Células-tronco de diferentes fontes exógenas podem exibir propriedades neuroprotetoras em modelos experimentais de hipóxia-isquemia neonatal. Na maioria dos experimentos animais, os benefícios morfológicos e funcionais observados foram independentes da diferenciação neural, sugerindo mecanismos de ação associados, tais como a liberação de fatores tróficos e a modulação inflamatória. Conclusões:Baseado nos estudos experimentais analisados, a terapia celular pode tornar-se uma promissora abordagem terapêutica no tratamento de crianças com encefalopatia hipóxico-isquêmica. No entanto, estudos adicionais necessitam ser realizados a fim de elucidar os possíveis mecanismos de ação dessas células e definir estratégias clínicas seguras e efetivas.J Pediatr (Rio J). 2010;86(6):451-464: Encefalopatia hipóxico-isquêmica, células-tronco, asfixia, terapia celular.

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Transplantation of Fetal Neocortex Ameliorates Sensorimotor and Locomotor Deficits Following Neonatal Ischemic–Hypoxic Brain Injury in Rats

Cited by 41 publications

References 30 publications

Transplanted Neuroblasts Differentiate Appropriately into Projection Neurons with Correct Neurotransmitter and Receptor Phenotype in Neocortex Undergoing Targeted Projection Neuron Degeneration

Transplanted Neuroblasts Differentiate Appropriately into Projection Neurons with Correct Neurotransmitter and Receptor Phenotype in Neocortex Undergoing Targeted Projection Neuron Degeneration

Intravenous Administration of Human Umbilical Cord Blood Reduces Behavioral Deficits After Stroke in Rats

Use of stem cells in perinatal asphyxia: from bench to bedside

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