title: Intra-arterial transplantation of human umbilical cord blood mononuclear cells in neonatal hypoxic-ischemic rats.
abstract: Based on preclinical findings, cellular therapy has become a promising therapeutic approach for neonatal hypoxia-ischemia (HI). However, before translation into the clinical setting, new and effective routes of cell delivery must be determined. Intra-arterial (IA) delivery is an attractive route of cellular administration but has never been used in neonatal HI rats.
  
  
  OBJECTIVE
  In this study, we investigated the feasibility of IA transplantation of human umbilical cord blood (HUCB) mononuclear cells for the treatment of long-term behavior dysfunction and brain lesion after neonatal HI.
  
  
  METHODS
  Seven-day-old rats were subjected to a HI model and the animals received HUCB mononuclear cells into the left common carotid artery 24 h after HI insult.
  
  
  RESULTS
  At 9 weeks post-HI, intra-arterially transplanted HUCB mononuclear cells significantly improved learning and long-term spatial memory impairments when evaluated by the Morris water maze paradigm. There was no effect of neonatal HI insult or IA procedure on body weight and on motor coordination and balance when evaluated by the accelerating rotarod test. Cellular transplantation by the IA route did not restore neonatal HI-induced brain damage according to stereological volume assessment. Furthermore, HUCB mononuclear cells were tracked in the injured brain and peripheral organs of HI transplanted-rats by nested polymerase chain reaction analysis at different time points.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centro de Pesquisa Pré-Clínica, Instituto do Cérebro do Rio Grande do Sul (InsCer), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Pediatria e Saúde da Criança, Laboratório de Neurociências e Sinalização Celular, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: Samuel
authors.initials: S
authors.lastname: Greggio
authors.affiliation: Programa de Pós-Graduação em Pediatria e Saúde da Criança, Laboratório de Neurociências e Sinalização Celular, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: de Paula
authors.affiliation: Programa de Pós-Graduação em Medicina e Ciências da Saúde, Laboratório de Neurociências e Sinalização Celular, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: Pâmella Nunes
authors.initials: PN
authors.lastname: Azevedo
authors.affiliation: Centro de Pesquisa Pré-Clínica, Instituto do Cérebro do Rio Grande do Sul (InsCer), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, Laboratório de Neurociências e Sinalização Celular, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: Gianina Teribele
authors.initials: GT
authors.lastname: Venturin
authors.affiliation: Programa de Pós-Graduação em Pediatria e Saúde da Criança, Laboratório de Neurociências e Sinalização Celular, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, Laboratório de Neurociências e Sinalização Celular, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil. Electronic address: jcc@pucrs.br.
authors.forename: Jaderson Costa
authors.initials: JC
authors.lastname: Dacosta
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000473:pathology* / Q000601:surgery*; D007261:Infusions, Intra-Arterial; D008297:Male; D051381:Rats; D017208:Rats, Wistar
keywords: Brain lesion; Human umbilical cord blood mononuclear cells; Intra-arterial transplantation; Memory; Motor function; Neonatal hypoxia–ischemia; Rodent model