The dose-response effect of acute intravenous transplantation of human umbilical cord blood cells on brain damage and spatial memory deficits in neonatal hypoxia-ischemia

Abstract Despite the beneficial effects of cell-based therapies on brain repair shown in most studies, there has not been a consensus regarding the optimal dose of human umbilical cord blood cells (HUCBC) for neonatal hypoxia-ischemia (HI). In this study, we compared the long-term effects of intrave...

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Bibliographic Details
Published in:Neuroscience 2012-05, Vol.210, p.431-441
Main Authors: de Paula, S, Greggio, S, Marinowic, D.R, Machado, D.C, DaCosta, J. Costa
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
asphyxia
Atrophy
Biological and medical sciences
Blood cells
Brain - pathology
Brain injury
Carotid artery
Cell migration
Cerebral blood flow
Cognitive ability
cord blood stem cell transplantation
Cord Blood Stem Cell Transplantation - methods
Disease Models, Animal
Dose-response effects
dose-response relationship
Fetal Blood - transplantation
Fluorescent Antibody Technique
Fundamental and applied biological sciences. Psychology
Humans
hypoxia-ischemia
Hypoxia-Ischemia, Brain - complications
Hypoxia-Ischemia, Brain - surgery
Immunofluorescence
Inhalation
Intravenous administration
Ischemia
Jugular vein
Long-term effects
Maze Learning
Memory
Memory Disorders - etiology
Memory Disorders - prevention & control
Microscopy, Confocal
Neonates
Neurology
Polymerase chain reaction
Rats
Rats, Wistar
spatial memory
stem cells
Transplantation
Umbilical cord
Vertebrates: nervous system and sense organs
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Summary:Abstract Despite the beneficial effects of cell-based therapies on brain repair shown in most studies, there has not been a consensus regarding the optimal dose of human umbilical cord blood cells (HUCBC) for neonatal hypoxia-ischemia (HI). In this study, we compared the long-term effects of intravenous administration of HUCBC at three different doses on spatial memory and brain morphological changes after HI in newborn Wistar rats. In addition, we tested whether the transplanted HUCBC migrate to the injured brain after transplantation. Seven-day-old animals underwent right carotid artery occlusion and were exposed to 8% O2 inhalation for 2 h. After 24 h, randomly selected animals were assigned to four different experimental groups: HI rats administered with vehicle (HI+vehicle), HI rats treated with 1×106 (HI+low-dose), 1×107 (HI+medium-dose), and 1×108 (HI+high-dose) HUCBC into the jugular vein. A control group (sham-operated) was also included in this study. After 8 weeks of transplantation, spatial memory performance was assessed using the Morris water maze (MWM), and subsequently, the animals were euthanized for brain morphological analysis using stereological methods. In addition, we performed immunofluorescence and polymerase chain reaction (PCR) analyses to identify HUCBC in the rat brain 7 days after transplantation. The MWM test showed a significant spatial memory recovery at the highest HUCBC dose compared with HI+vehicle rats ( P
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2012.03.009