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Neonatal hypoxia-ischemia (HI) is an important cause of mortality and morbidity in infants. Human umbilical cord blood (HUCB) is a potential source of cellular therapy in perinatology. We investigated the effects of HUCB cells on spatial memory, motor performance, and brain morphologic changes in neonate rats submitted to HI. Seven-day-old rats underwent right carotid artery occlusion followed by exposure to 8% O 2 inhalation for 2 h. Twenty-four hours after HI, rats received either saline solution or HUCB cells i.v. After 3 wk, rats were assessed using a Morris Water Maze and four motor tests. Subsequently, rats were killed for histologic, immunohistochemical, and polymerase chain reaction (PCR) analyses. HI rats showed significant spatial memory deficits and a volumetric decrease in the hemisphere ipsilateral to arterial occlusion. These deficits and decreases were not significantly attenuated by the injection of HUCB cells. Moreover, immunofluorescence and PCR analysis revealed few HUCB cells located in rat brain. Intravenous administration of HUCB cells requires optimization to achieve improved therapeutic outcomes in neonatal hypoxic-ischemic injury. (Pediatr Res 65: 631-635, 2009) N eonatal hypoxia-ischemia (HI) is a major cause of mortality and morbidity in infants and occurs in approximately 2-4 per 1000 full-term births. Between 20 and 50% of asphyxiated newborns with hypoxic-ischemic encephalopathy die within the neonatal period, and up to 25% of the survivors will exhibit neurodevelopment morbidity, such as cerebral palsy, mental retardation, and epilepsy. The most widely used and accepted animal model of neonatal HI is the Levine method as modified by Rice et al. (1), which represents a useful tool to study long-term effects of neuroprotective strategies in behavioral changes, especially in learning and memory tasks (2). Although promising neuroprotective strategies have been studied in animal models and clinical trials, current management techniques have reached only limited success (3).Human umbilical cord blood (HUCB), is rich in adult stem cells and seems to be a potential source for transplantation, especially for perinatal neuronal repair. Studies have shown behavioral and neurologic recovery in stroke (4 -7) and HIinsulted animals (8,9) that received i.v. injection of HUCB, indicating that cells migrate toward ischemic regions and cross the blood brain barrier (BBB), especially in acute periods postischemia (10). The i.v. route is less invasive and a safer access to clinical applications when compared with intracerebral delivery. However, very few transplanted cells are found in the brain when delivered intravascularly. Therefore, evidence suggests that these cells increase endogenous mechanisms of brain repair by trophic factor secretion rather than by replacing the damaged tissue (11,12).The aim of this study was to assess the effects of HUCB cells on spatial memory, motor performance, and brain morphologic changes in 30-d-old rats after neonatal HI on postnatal d 7. In addition, w...

Our findings contribute to the translational knowledge of cell based-therapy in neonatal HI and demonstrate for the first time that IA transplantation into rat pups is a feasible route for cellular delivery and prevents long-term cognitive deficits induced by experimental neonatal HI.

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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.