An Immune-Deficient Prkdc Knockout Rat Model of Perinatal Hypoxic-Ischemic Brain Injury for Future Xenograft Studies

Perinatal hypoxia ischemia (HI) is a significant cause of brain damage leading to motor and cognitive impairments. There are no treatments that can repair the damage and improve outcomes, though preclinical research using neural precursor cell (NPC) transplantation as a therapy has shown promise. To promote clinical translation, it is essential that human-derived NPCs also be tested in animal models. To reduce the risk of xenograft rejection, we characterized a model of HI injury in immune-deficient Prkdc knockout rats. Knockout HI rats displayed sensorimotor deficits on the cylinder and pasta-handling tests, and reductions in size of and cellular loss in the hippocampus, cortex, and corpus callosum. Ventriculomegaly and grey matter gliosis were also prominent. Interestingly, knockout rats displayed overall more severe injuries than wildtype littermates. This model characterization will allow for future studies of human-derived NPCs in the rodent brain, paving the way for the clinical translation of this therapy.M.Sc