Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy

Melinda Barkhuizen, Ralph van Mechelen, Marijne Vermeer, Peter Chedraui, Dean Paes, Daniel L A van den Hove, Bart Vaes, Robert W Mays, Harry W M Steinbusch, Nicola J Robertson, Boris W Kramer, Antonio W D Gavilanes

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)77-81
Number of pages5
JournalBehavioural Brain Research
Volume362
DOIs
Publication statusPublished - 19 Apr 2019

Keywords

  • Animals
  • Animals, Newborn
  • Asphyxia Neonatorum/physiopathology
  • Brain/physiopathology
  • Disease Models, Animal
  • Female
  • Hypoxia/drug therapy
  • Hypoxia-Ischemia, Brain/physiopathology
  • Male
  • Multipotent Stem Cells/cytology
  • Rats, Sprague-Dawley

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