Hemispheric brain injury and behavioral deficits induced by severe neonatal hypoxia-ischemia in rats are not attenuated by intravenous administration of human umbilical cord blood cells.
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.
de Paula
Simone
S
Laboratório de Neurociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Vitola
Affonso Santos
AS
Greggio
Samuel
S
de Paula
Davi
D
Mello
Pâmela Billig
PB
Lubianca
Jeremiah Mistrello
JM
Xavier
Léder Leal
LL
Fiori
Humberto Holmer
HH
Dacosta
Jaderson Costa
JC
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology*; D001930:Brain Injuries / Q000473:pathology / Q000628:therapy; D002469:Cell Separation; D005312:Fetal Blood / Q000166:cytology / Q000637:transplantation; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000628:therapy; D009043:Motor Activity / Q000502:physiology; D009483:Neuropsychological Tests; D011897:Random Allocation; D051381:Rats