Neuroprotective potential of erythropoietin and its derivative carbamylated erythropoietin in periventricular leukomalacia

Liu, Wei; Shen, Yan; Plane, Jennifer M.; Pleasure, David E; Deng, Wenbin

doi:10.1016/j.expneurol.2011.04.021

Cited by 63 publications

(58 citation statements)

References 67 publications

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“…Recent experimental34, 35 and clinical17, 36, 37, 38 studies indicate that rhEPO is a promising candidate for very preterm infants with brain injury and that it improves neurodevelopment and reduces the risk of neurodevelopmental disability. However, the safe dose range, timing, and duration of rhEPO administration still require careful exploration and consideration.…”

Section: Discussionmentioning

confidence: 99%

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

Shi

Sun

et al. 2016

Annals of Neurology

115

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ObjectiveTo evaluate the efficacy and safety of repeated low‐dose human recombinant erythropoietin (rhEPO) in the improvement of neurological outcomes in very preterm infants.MethodsA total of 800 infants of ≤32‐week gestational age who had been in an intensive care unit within 72 hours after birth were included in the trial between January 2009 and June 2013. Preterm infants were randomly assigned to receive rhEPO (500IU/kg; n = 366) or placebo (n = 377) intravenously within 72 hours after birth and then once every other day for 2 weeks. The primary outcome was death or moderate to severe neurological disability assessed at 18 months of corrected age.ResultsDeath and moderate/severe neurological disability occurred in 91 of 338 very preterm infants (26.9%) in the placebo group and in 43 of 330 very preterm infants (13.0%) in the rhEPO treatment group (relative risk [RR] = 0.40, 95% confidence interval [CI] = 0.27–0.59, p < 0.001) at 18 months of corrected age. The rate of moderate/severe neurological disability in the rhEPO group (22 of 309, 7.1%) was significantly lower compared to the placebo group (57 of 304, 18.8%; RR = 0.32, 95% CI = 0.19–0.55, p < 0.001), and no excess adverse events were observed.InterpretationRepeated low‐dose rhEPO treatment reduced the risk of long‐term neurological disability in very preterm infants with no obvious adverse effects. Ann Neurol 2016;80:24–34

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Section: Discussionmentioning

confidence: 99%

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

Shi

Sun

et al. 2016

Annals of Neurology

115

View full text Add to dashboard Cite

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“…Afterwards, CEPO caused the extensive concern in the treatment of neuropsychiatric diseases including memory and/or emotional associated disorders (17), depression and anxiety (18), which were ameliorated by increasing the NeuN/BrdU double-labeled cells in the dentate gyrus field of the hippocampus. Recently, accumulated researches have documented that CEPO was neuroprotective in many CNS diseases, including Alzheimer's disease (19), Parkinson's disease (20), periventricular leukomalacia (PVL) (21) and other hypoxic-ischemic/inflammatory white matter diseases.…”

Section: Cepo-mediated Neuroprotectionmentioning

confidence: 99%

Carbamylated Erythropoietin and Its Role of Tissue Protection

Li¹,

Diao²,

Ma³

et al. 2017

J Anesth Perioper Med

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Aim of review:We reviewed the study of carbamylated erythropoietin (CEPO) and its probable mechanism involved in the regulation of tissue-protection. Methods: Recent published literatures in this area were inclusive and reviewed. Recent findings: CEPO has equivalent tissue-protective properties as recombinant human erythropoietin (rhEPO) but with non-erythropoietic effects. It shows protective properties on nervous system, heart, kidney and some other organs, which are associated with inhibition of apoptosis, restoration of vascular autoregulation and attenuation of inflammatory responses. However, the underlying mechanism of CEPO responsible for its beneficial effects is still not well-known. Summary: CEPO gradually turned into a promising drug candidate at least for many diseases caused by ischemia reperfusion injury. The safety and efficacy of CEPO in clinical are warranted in the future.

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“…Microglial activation is a likely contributor to preOL injury in PVL. Anti-inflammatory compounds or agents that inhibit microglial activation, such as minocycline, have been reported to attenuate brain injury in models of excitotoxicity and hypoxia/ischemia [48,49] .…”

Section: Inflammatory Mechanismsmentioning

confidence: 99%

Vulnerability of premyelinating oligodendrocytes to white-matter damage in neonatal brain injury

et al. 2013

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Premature birth is a significant economic and public health burden, and its incidence is rising. Periventricular leukomalacia (PVL) is the predominant form of brain injury in premature infants and the leading cause of cerebral palsy. PVL is characterized by selective white-matter damage with prominent oligodendroglial injury. The maturation-dependent vulnerability of developing and premyelinating oligodendrocytes to excitotoxic, oxidative, and inflammatory forms of injury is a major factor in the pathogenesis of PVL. Recent studies using mouse models of PVL reveal that synapses between axons and developing oligodendrocytes are quickly and profoundly damaged in immature white matter. Axon-glia synapses are highly vulnerable to white-matter injury in the developing brain, and the loss of synapses between axons and premyelinating oligodendrocytes occurs before any cellular loss in the immature white matter. Microglial activation and astrogliosis play important roles in triggering white-matter injury. Impairment of white-matter development and function in the neonatal period contributes critically to functional and behavioral deficits. Preservation of the integrity of the white matter is likely key in the treatment of PVL and subsequent neurological consequences and disabilities.Keywords: prematurity; neonatal brain injury; white matter; oligodendrocyte; myelin; periventricular leukomalacia Types of Neonatal Brain InjuryBrain injury in the newborn leads to devastating neurological consequences and is the leading cause of neurological disabilities, including motor and cognitive deficits. Several forms of neonatal brain injury are associated with the development of cerebral palsy (CP) [1][2][3][4] ; these include periventricular leukomalacia (PVL), intraventricular hemorrhage, periventricular hemorrhagic infarction, neonatal stroke, hypoxic-ischemic encephalopathy, and combined gray and white matter injury (Table 1).The leading cause of CP is PVL in premature infants.PVL is traditionally classified as a white-matter disorder, and is the predominant form of brain injury. However, the white-matter damage underlying PVL is now recognized as the major component of a more generalized injury to the cerebrum that includes neuronal and axonal injury, and has been renamed "encephalopathy of prematurity" [5] . The classical lesion of PVL involves macroscopic cystic or non-cystic necrotic lesions with pan-cellular degeneration. Current data indicate that the incidence of cystic PVL is declining, whereas diffuse cerebral white-matter injury is emerging as the predominant lesion. Diffuse non-cystic lesions selectively trigger injury to premyelinating oligodendrocytes (OLs) and subsequent disturbances in myelination. Neuronal loss and axonal damage also occur in patients with PVL.

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Neuroprotective potential of erythropoietin and its derivative carbamylated erythropoietin in periventricular leukomalacia

Cited by 63 publications

References 67 publications

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

Carbamylated Erythropoietin and Its Role of Tissue Protection

Vulnerability of premyelinating oligodendrocytes to white-matter damage in neonatal brain injury

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