Neuroprotective effect of oligodendrocyte precursor cell transplantation in a long-term model of periventricular leukomalacia.
Perinatal white matter injury, or periventricular leukomalacia (PVL), is the most common cause of brain injury in premature infants and is the leading cause of cerebral palsy. Despite increasing numbers of surviving extreme premature infants and associated long-term neurological morbidity, our understanding and treatment of PVL remains incomplete. Inflammation- or ischemia/hypoxia-based rodent models, although immensely valuable, are largely restricted to reproducing short-term features of up to 3 weeks after injury. Given the long-term sequelae of PVL, there is a need for subchronic models that will enable testing of putative neuroprotective therapies. Here, we report long term characterization of a neonatal inflammation-induced rat model of PVL. We show bilateral ventriculomegaly, inflammation, reactive astrogliosis, injury to pre-oligodendrocytes, and neuronal loss 8 weeks after injury. We demonstrate neuroprotective effects of oligodendrocyte precursor cell transplantation. Our findings present a subchronic model of PVL and highlight the tissue protective effects of oligodendrocyte precursor cell transplants that demonstrate the potential of cell-based therapy for PVL.
Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge, United Kingdom.
Daniel J
DJ
Webber
Marka
M
van Blitterswijk
Siddharthan
S
Chandran
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000473:pathology* / Q000628:therapy*; D009836:Oligodendroglia / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation