Long-Lasting Paracrine Effects of Human Cord Blood Cells on Damaged Neocortex in an Animal Model of Cerebral Palsy

Abstract

Neonatal asphyxia is an important contributor to cerebral palsy (CP), for which there is no effective treatment to date. The administration of human cord blood cells (hUCBCs) is emerging as a therapeutic strategy for the treatment of neurological disorders. However, there are few studies on the application of hUCBCs to the treatment of neonatal ischemia as a model of CP. Experiments and behavioral tests (mainly motor tests) performed on neonatal hypoxia/ischemia have been limited to short-term effects of hUCBCs, but mechanisms of action have not been investigated. We performed a study on the use of hUCBCs in a rat model of neonatal hypoxia/ischemia and investigated the underlying mechanism for therapeutic benefits of hUCBC treatment. hUCBCs were intravenously transplanted into a rat model of neonatal hypoxia ischemia. hUCBCs increased microglia temporarily in the periventricular striatum in the early phase of disease, protected mature neurons in the neocortex from injury, paved the way for the near-normalization of brain damage in the subventricular zone (SVZ), and, in consequence, significantly improved performance in a battery of behavioral tests compared to the vehicle-treated group. Although the transplanted cells were rarely observed in the brain 3 weeks after transplantation, the effects of the improved behavioral functions persisted. Our preclinical findings suggest that the long-lasting positive influence of hUCBCs is derived from paracrine effects of hUCBCs that stimulate recovery in the injured brain and protect against further brain damage.