TY - JOUR
T1 - Neuroprotective Effect of Oligodendrocyte Precursor Cell Transplantation in a Long-Term Model of Periventricular Leukomalacia
AU - Webber, Daniel J.
AU - van Blitterswijk, Marka
AU - Chandran, Siddharthan
PY - 2009/12
Y1 - 2009/12
N2 - 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, inflammnation, reactive astrogliosts, 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 of oligodendrocyte precursor cell transplants that demonstrate the potential of cell-based therapy for PVL. (Am J Pathol 2009, 175:2332-2342; DOI: 10.2353/ajpath.2009.090051)
AB - 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, inflammnation, reactive astrogliosts, 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 of oligodendrocyte precursor cell transplants that demonstrate the potential of cell-based therapy for PVL. (Am J Pathol 2009, 175:2332-2342; DOI: 10.2353/ajpath.2009.090051)
U2 - 10.2353/ajpath.2009.090051
DO - 10.2353/ajpath.2009.090051
M3 - Article
SN - 0002-9440
VL - 175
SP - 2332
EP - 2342
JO - The American Journal of Pathology
JF - The American Journal of Pathology
IS - 6
ER -