TY - JOUR
T1 - Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy
AU - Barkhuizen, Melinda
AU - van Mechelen, Ralph
AU - Vermeer, Marijne
AU - Chedraui, Peter
AU - Paes, Dean
AU - van den Hove, Daniel L A
AU - Vaes, Bart
AU - Mays, Robert W
AU - Steinbusch, Harry W M
AU - Robertson, Nicola J
AU - Kramer, Boris W
AU - Gavilanes, Antonio W D
N1 - Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.
PY - 2019/4/19
Y1 - 2019/4/19
N2 - There is an urgent need for therapies that could reduce the disease burden of preterm hypoxic-ischemic encephalopathy. Here, we evaluate the long-term effects of multipotent adult progenitor cells (MAPC) on long-term behavioral outcomes in a preterm rat model of perinatal asphyxia. Rats of both sexes were treated with two doses of MAPCs within 24 h after the insult. Locomotor, cognitive and psychiatric impairments were evaluated starting at 1.5 (juvenile) and 6 months (adult). Hypoxia-ischemia affected locomotion, cognition, and anxiety in a sex-dependent manner, with higher vulnerability observed in males. The MAPC therapy partially attenuated deficits in object recognition memory in females of all tested ages, and in the adult males. The hypoxic insult caused delayed hyperactivity in adult males, which was corrected by MAPC therapy. These results suggest that MAPCs may have long-term benefits for neurodevelopmental outcome after preterm birth and global hypoxia-ischemia, which warrants further preclinical exploration.
AB - There is an urgent need for therapies that could reduce the disease burden of preterm hypoxic-ischemic encephalopathy. Here, we evaluate the long-term effects of multipotent adult progenitor cells (MAPC) on long-term behavioral outcomes in a preterm rat model of perinatal asphyxia. Rats of both sexes were treated with two doses of MAPCs within 24 h after the insult. Locomotor, cognitive and psychiatric impairments were evaluated starting at 1.5 (juvenile) and 6 months (adult). Hypoxia-ischemia affected locomotion, cognition, and anxiety in a sex-dependent manner, with higher vulnerability observed in males. The MAPC therapy partially attenuated deficits in object recognition memory in females of all tested ages, and in the adult males. The hypoxic insult caused delayed hyperactivity in adult males, which was corrected by MAPC therapy. These results suggest that MAPCs may have long-term benefits for neurodevelopmental outcome after preterm birth and global hypoxia-ischemia, which warrants further preclinical exploration.
KW - Animals
KW - Animals, Newborn
KW - Asphyxia Neonatorum/physiopathology
KW - Brain/physiopathology
KW - Disease Models, Animal
KW - Female
KW - Hypoxia/drug therapy
KW - Hypoxia-Ischemia, Brain/physiopathology
KW - Male
KW - Multipotent Stem Cells/cytology
KW - Rats, Sprague-Dawley
U2 - 10.1016/j.bbr.2019.01.016
DO - 10.1016/j.bbr.2019.01.016
M3 - Article
C2 - 30639607
SN - 0166-4328
VL - 362
SP - 77
EP - 81
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -