TY - JOUR
T1 - Time to reconsider extended erythropoietin treatment for infantile traumatic brain injury?
AU - Jantzie, Lauren
AU - El Demerdash, Nagat
AU - Newville, Jessie C.
AU - Robinson, Shenandoah
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/8
Y1 - 2019/8
N2 - Pediatric traumatic brain injury (TBI) remains a leading cause of childhood morbidity and mortality worldwide. Most efforts to reduce the chronic impact of pediatric TBI involve prevention and minimization of secondary injury. Currently, no treatments are used in routine clinical care during the acute and subacute phases to actively repair injury to the developing brain. The endogenous pluripotent cytokine erythropoietin (EPO) holds promise as an emerging neuroreparative agent in perinatal brain injury (PBI). EPO signaling in the central nervous system (CNS) is essential for multiple stages of neurodevelopment, including the genesis, survival and differentiation of multiple lineages of neural cells. Postnatally, EPO signaling decreases markedly as the CNS matures. Importantly, high-dose, extended EPO regimens have shown efficacy in preclinical controlled cortical impact (CCI) models of infant TBI at two different, early ages by independent research groups. Specifically, extended high-dose EPO treatment after infantile CCI prevents long-term cognitive deficits in adult rats. Because of the striking differences in the molecular and cellular responses to both injury and recovery in the developing and mature CNS, and the excellent safety profile of EPO in infants and children, extended courses of EPO are currently in Phase III trials for neonates with PBI. Extended, high-dose EPO may also warrant testing for infants and young children with TBI.
AB - Pediatric traumatic brain injury (TBI) remains a leading cause of childhood morbidity and mortality worldwide. Most efforts to reduce the chronic impact of pediatric TBI involve prevention and minimization of secondary injury. Currently, no treatments are used in routine clinical care during the acute and subacute phases to actively repair injury to the developing brain. The endogenous pluripotent cytokine erythropoietin (EPO) holds promise as an emerging neuroreparative agent in perinatal brain injury (PBI). EPO signaling in the central nervous system (CNS) is essential for multiple stages of neurodevelopment, including the genesis, survival and differentiation of multiple lineages of neural cells. Postnatally, EPO signaling decreases markedly as the CNS matures. Importantly, high-dose, extended EPO regimens have shown efficacy in preclinical controlled cortical impact (CCI) models of infant TBI at two different, early ages by independent research groups. Specifically, extended high-dose EPO treatment after infantile CCI prevents long-term cognitive deficits in adult rats. Because of the striking differences in the molecular and cellular responses to both injury and recovery in the developing and mature CNS, and the excellent safety profile of EPO in infants and children, extended courses of EPO are currently in Phase III trials for neonates with PBI. Extended, high-dose EPO may also warrant testing for infants and young children with TBI.
KW - Biomarkers
KW - Cognition
KW - Controlled cortical impact
KW - Diffusion tensor imaging
KW - Neurorepair
KW - Pediatric
KW - Perinatal brain injury
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U2 - 10.1016/j.expneurol.2019.05.004
DO - 10.1016/j.expneurol.2019.05.004
M3 - Review article
C2 - 31082389
AN - SCOPUS:85065718776
SN - 0014-4886
VL - 318
SP - 205
EP - 215
JO - Experimental Neurology
JF - Experimental Neurology
ER -